Peter Fitzgerald, MD, PhD

All Publications

• INTRAVASCULAR ULTRASOUND PREDICTORS OF 4-YEAR CLINICAL OUTCOMES FOLLOWING ABSORB BIORESORBABLE SCAFFOLD IMPLANTATION: INSIGHTS FROM THE ABSORB JAPAN TRIAL Nishi, T., Okada, K., Kitahara, H., Kameda, R., Ikutomi, M., Hollak, B., Yock, P., Popma, J., Kusano, H., Cheong, W., Sudhir, K., Fitzgerald, P., Honda, Y., Kimura, T. ELSEVIER SCIENCE INC. 2019: 1305

  View details for Web of Science ID 000460565901318

• PERIARTERIAL NEOVASCULARIZATION AND ATTENUATED-SIGNAL PLAQUE PREDICT LONG-TERM MORTALITY AFTER HEART TRANSPLANTATION: RISK STRATIFICATION WITH IVUS-DETERMINED CORONARY INFLAMMATORY FINDINGS Kashiyama, K., Okada, K., Kitahara, H., Kameda, R., Hollak, M., Luikart, H., Yock, P., Yeung, A., Fitzgerald, P., Khush, K., Fearon, W., Honda, Y. ELSEVIER SCIENCE INC. 2019: 1428

  View details for Web of Science ID 000460565901440

• A FIRST-IN-HUMAN STUDY OF THE SECOND-GENERATION, THIN-STRUT, EVEROLIMUS-ELUTING BIORESORBABLE SCAFFOLD: 6-MONTH IVUS AND OCT RESULTS FROM THE FAST CLINICAL TRIAL Kameda, R., Okada, K., Ikutomi, M., Hollak, M., Yock, P., Popma, J., Seneviratne, S., Erglis, A., Walters, D., Whitbourn, R., Layland, J., Stewart, J., El-Jack, S., Christen, T., Meredith, I., Fitzgerald, P., Honda, Y. ELSEVIER SCIENCE INC. 2019: 1111

  View details for Web of Science ID 000460565901124

• Cardiac function response to stenting in atherosclerotic renal artery disease with and without heart failure: results from the Carmel study. ESC heart failure Kawarada, O. n., Kume, T. n., Zen, K. n., Nakamura, S. n., Hozawa, K. n., Akimitsu, T. n., Asano, H. n., Ando, H. n., Yamamoto, Y. n., Yamashita, T. n., Shinozaki, N. n., Odashiro, K. n., Sato, T. n., Yuba, K. n., Sakanoue, Y. n., Uzu, T. n., Okada, K. n., Fitzgerald, P. J., Honda, Y. n., Yasuda, S. n. 2019

  Abstract

  Consensus-derived guidelines recommend renal stenting for patients with atherosclerotic renal artery disease (ARAD) and heart failure (HF). The aim of this prospective multi-centre observational study was to verify our hypothesis that changes in E/e', an echocardiographic correlate of left ventricular (LV) filling pressure, following renal stenting may differ between ARAD patients with and without HF.This study enrolled de novo ARAD patients undergoing renal stenting at 14 institutions. The primary endpoint was the difference in E/e' change between ARAD patients with and without HF. Clinical and echocardiographic data were prospectively collected at baseline, the day following renal stenting, and 1 month and 6 months afterwards. ARAD patients with HF were defined as patients with New York Heart Association (NYHA) Class 2 and more, or a history of HF hospitalization. A total of 76 patients were included, and 39% were ARAD patients with HF. ARAD patients with HF had significantly lower estimated glomerular filtration rate (P = 0.028) and higher NYHA functional class (P < 0.001) and Minnesota Living with Heart Failure Questionnaire (MLHFQ) score (P = 0.001) than ARAD patients without HF. Also, ARAD patients with HF had significantly lower LV ejection fraction (P = 0.003) and e'-velocity (P = 0.003) and higher E/e' ratio (P = 0.001), left atrial volume index (LAVI) (P = 0.046), LV end-diastolic volume (LVEDV) (P = 0.001), LV end-systolic volume (LVESV) (P = 0.001), and LV mass index (P = 0.009) than ARAD patients without HF. All procedures were successful. In contrast to blood pressure and renal function, there was a significant interaction in E/e' (Pinteraction  < 0.001) between time and HF, and ARAD patients with HF showed a significant (P < 0.001) decrease in E/e' albeit those without HF. By the same token, there was a significant interaction in NYHA class (Pinteraction  < 0.001), MLHFQ score (Pinteraction  = 0.018), E-velocity (Pinteraction  = 0.002), LAVI (Pinteraction  = 0.001), LVEDV (Pinteraction  = 0.003), and LVESV (Pinteraction  = 0.001) between time and HF with a significant improvement in all these variables in ARAD patients with HF (NYHA class, P = 0.001; MLHFQ score, P = 0.002; E-velocity, P = 0.005; LAVI, P = 0.001; LVEDV, P = 0.017; and LVESV, P = 0.011).Change in LV filling pressure after renal stenting differed between ARAD patients with and without HF, with a significant improvement in LV filling pressure in patients with HF-ARAD. These unique findings might support clinical cardiac benefits of renal artery stenting in ARAD patients with HF.

  View details for PubMedID 30614643

• Comparison between instantaneous wave-free ratio versus morphometric assessments by intracoronary imaging. Heart and vessels Matsushita, K., Hibi, K., Okada, K., Sakamaki, K., Akiyama, E., Kimura, Y., Matsuzawa, Y., Maejima, N., Iwahashi, N., Tsukahara, K., Kosuge, M., Ebina, T., Fitzgerald, P. J., Honda, Y., Tamura, K., Kimura, K. 2018

  Abstract

  Anatomical measurements obtained by intracoronary imaging devices are reported to correlate significantly with fractional flow reserve (FFR). Instantaneous wave-free ratio (iFR) is a nonhyperemic index of stenosis severity with discordant reports regarding its accuracy in relation to FFR. There is no information on the correlation of iFR with measurements derived from intracoronary imaging devices. The purpose of this study was to assess the relationship among iFR, intravascular ultrasound (IVUS), and optical frequency domain imaging (OFDI) parameters. Eighty lesions in 72 patients who underwent elective angiography and had intermediate lesions were enrolled. All lesions were assessed by iFR, FFR, IVUS, and OFDI. iFR was ≤0.89 in 21 (26%) lesions and FFR was ≤0.80 in 41 (51%) lesions. iFR correlated significantly with both IVUS-derived minimum lumen area (MLA) (r=0.375, p=0.003) and OFDI-derived MLA (r=0.357, p=0.005). FFR also correlated significantly with both IVUS-derived MLA (r=0.472, p<0.001) and OFDI-derived MLA (r=0.445, p<0.001). Among the lesions with FFR ≤0.80, iFR>0.89 (mismatch) was observed in 20 lesions. There was no lesion with iFR ≤0.89 (reverse mismatch) among the lesions with FFR>0.80. The lesion location among three major coronary vessels was related with the discrepancy between iFR and FFR (p=0.007). In conclusion, iFR and FFR showed a significant correlation with IVUS and OFDI measurements. The discrepancy of iFR and FFR was associated with the lesion locations.

  View details for PubMedID 30535756

• Bioresorbable Scaffold for Treatment of Coronary Artery Lesions Intravascular Ultrasound Results From the ABSORB Japan Trial JACC-CARDIOVASCULAR INTERVENTIONS Okada, K., Honda, Y., Kitahara, H., Otagiri, K., Tanaka, S., Hollak, M., Yock, P. G., Popma, J. J., Kusano, H., Cheong, W., Sudhir, K., Fitzgerald, P. J., Kimura, T., ABSORB Japan Investigators 2018; 11 (7): 648–61

  Abstract

  The aim of this study was to characterize post-procedural intravascular ultrasound (IVUS) findings in the ABSORB Japan trial, specifically stratified by the size of target coronary arteries.Despite overall noninferiority confirmed in recent randomized trials comparing bioresorbable vascular scaffolds (BVS) (Absorb BVS) and cobalt-chromium everolimus-eluting metallic stents (CoCr-EES), higher event rates of Absorb BVS have been reported with suboptimal deployment, especially in small coronary arteries.In the ABSORB Japan trial, 150 patients (2:1 randomization) were scheduled in the IVUS cohort. Small vessel was defined as mean reference lumen diameter <2.75 mm. Tapered-vessel lesions were defined as tapering index (proximal/distal reference lumen diameter) ≥1.2.Overall, IVUS revealed that the Absorb BVS arm had smaller device expansion than the CoCr-EES arm did, which was particularly prominent in small- and tapered-vessel lesions. Higher tapering index was also associated with higher rates of incomplete strut apposition in Absorb BVS, but not in CoCr-EES. With respect to procedural techniques, small-vessel lesions were treated more frequently with noncompliant balloons at post-dilatation but using significantly lower pressure in the Absorb BVS arm. In contrast, tapered-vessel lesions were post-dilated at equivalent pressure but with significantly smaller balloon catheters in the Absorb BVS arm, compared with the CoCr-EES arm.The significantly smaller device expansion especially in small vessels may account for the poorer outcomes of Absorb BVS in this lesion type. Appropriate optimization strategy, possibly different between polymeric and metallic devices, needs to be established for bioresorbable scaffold technology. (AVJ-301 Clinical Trial: A Clinical Evaluation of AVJ-301 Absorb™ BVS) in Japanese Population [ABSORB JAPAN]; NCT01844284).

  View details for PubMedID 29622143

• BIORESORBABLE SCAFFOLD FOR TREATMENT OF CORONARY ARTERY LESIONS: FINAL INTRAVASCULAR ULTRASOUND RESULTS FROM THE ABSORB JAPAN TRIAL Okada, K., Honda, Y., Kitahara, H., Ikutomi, M., Kameda, R., Hollak, M., Yock, P., Kusano, H., Cheong, W., Sudhir, K., Fitzgerald, P., Kimura, T. ELSEVIER SCIENCE INC. 2018: 1020

  View details for DOI 10.1016/S0735-1097(18)31561-4

  View details for Web of Science ID 000429659702270

• Association Between Scaffold Under-Expansion and Late Lumen Loss after Bioresorbable Scaffold Implantation: IVUS and Angiographic Insights from the ABSORB Japan Trial Okada, K., Honda, Y., Kitahara, H., Hollak, M., Yock, P. G., Popma, J. J., Kusano, H., Cheong, W., Sudhir, K., Fitzgerald, P. J., Kimura, T. ELSEVIER SCIENCE INC. 2017: B5

  View details for Web of Science ID 000413459200012

• Differential Late Stent Enlargement and Vascular Response Following New-Generation Self-Expanding Stent Implantation in Tapered Peripheral Arteries: Insights from Serial Optical Coherence Tomography Ikutomi, M., Okada, K., Miki, K., Kameda, R., Otsuka, F., Yock, P. G., Fitzgerald, P. J., Kawarada, O., Honda, Y. ELSEVIER SCIENCE INC. 2017: B165–B166

  View details for Web of Science ID 000413459200401

• Comparison of Bioresorbable Scaffold Measurements between Intravascular Ultrasound and Quantitative Coronary Angiography in the ABSORB Japan Trial Okada, K., Honda, Y., Kitahara, H., Hollak, M., Yock, P. G., Popma, J. J., Kusano, H., Cheong, W., Sudhir, K., Fitzgerald, P. J., Kimura, T. ELSEVIER SCIENCE INC. 2017: B57–B58

  View details for Web of Science ID 000413459200131

• Bioresorbable Scaffold for the Treatment of Calcified Coronary Lesions: IVUS Insights from the ABSORB Japan Trial Okada, K., Honda, Y., Kitahara, H., Hollak, M., Yock, P. G., Kusano, H., Cheong, W., Sudhir, K., Fitzgerald, P. J., Kimura, T. ELSEVIER SCIENCE INC. 2017: B19

  View details for Web of Science ID 000413459200044

• Impact of attenuated-signal plaque observed by intravascular ultrasound on vessel response after drug-eluting stent implantation ATHEROSCLEROSIS Kitahara, H., Waseda, K., Sakamoto, K., Yamada, R., Huang, C., Nakatani, D., Sakata, K., Kawarada, O., Yock, P. G., Matsuyama, Y., Yokoi, H., Nakamura, M., Muramatsu, T., Nanto, S., Fitzgerald, P. J., Honda, Y. 2017; 259: 68-74

  Abstract

  The aim of this study was to investigate the impact of attenuated-signal plaque (ASP) observed by intravascular ultrasound (IVUS) on vessel response after drug-eluting stent implantation.Data were derived from the IVUS cohort of the J-DESsERT trial comparing paclitaxel- and sirolimus-eluting stents. Serial IVUS analysis (pre- and post-intervention, and 8-month follow-up) was performed in 136 non-AMI lesions. ASP was defined as hypoechoic plaque with ultrasound attenuation without calcification. Calcified plaque (CP) was defined as brightly echoreflective plaque with acoustic shadowing. ASP and CP scores were calculated by grading their measured angle as 0 to 4 for 0°, <90°, 90-180°, 180-270° and >270°, respectively. The entire stented segment was analyzed at 1-mm intervals.At pre-intervention, ASP was observed in 40.4% of lesions, and this group had greater % neointimal volume (%NIV) at follow-up than the no-ASP group (p = 0.011). ASP score at pre-intervention positively correlated with %NIV (p = 0.023). During the follow-up, ASP score significantly decreased (p < 0.001), and CP score significantly increased (p < 0.001), with a negative correlation between them (p < 0.001). A decrease in the ASP score was associated with less %NIV in PES (p = 0.031), but not in SES (p = 0.229).The greater extent of plaque with IVUS-signal attenuation at pre-intervention and its persistence during follow-up were associated with neointimal proliferation, possibly representing sustained inflammatory status, depending on the type of DES used.

  View details for DOI 10.1016/j.atherosclerosis.2017.02.009

  View details for Web of Science ID 000397736900011

  View details for PubMedID 28327450

• Impact of Stent Size Selection on Acute and Long-Term Outcomes After Drug-Eluting Stent Implantation in De Novo Coronary Lesions. Circulation. Cardiovascular interventions Kitahara, H. n., Okada, K. n., Kimura, T. n., Yock, P. G., Lansky, A. J., Popma, J. J., Yeung, A. C., Fitzgerald, P. J., Honda, Y. n. 2017; 10 (10)

  Abstract

  Although significant undersizing often results in incomplete stent apposition or underexpansion, the possible impact of oversized stent implantation on arterial wall injury has not been systematically investigated with drug-eluting stents. The aim of this study was to investigate the impact of stent oversizing on acute and long-term outcomes after drug-eluting stents implantation in de novo coronary lesions.Serial (baseline and 6-12 months) coronary angiography and intravascular ultrasound were performed in 2931 lesions treated with drug-eluting stents (355 sirolimus, 846 paclitaxel, 1387 zotarolimus, and 343 everolimus). The percentage of stent oversizing to angiographic reference vessel diameter (RVD) was calculated as (nominal stent diameter-RVD)/RVD×100 (%). Clinical outcomes, including target lesion revascularization and stent thrombosis, were followed for 1 year. Overall, smaller preintervention RVD was associated with higher percentage of stent oversizing (P<0.001). The significant oversizing group underwent less post-dilatation (P=0.002) but achieved greater stent expansion (P<0.001) and less incomplete stent apposition (P<0.001) without increase of edge dissection after procedure. When stratified by vessel size and stent oversizing, progressive decreases of restenosis (P=0.002) and target lesion revascularization rates (P=0.007) were found in favor of larger vessel size and oversized stents. Stent thrombosis was observed the most in small RVD with low percentage of stent oversizing group among the subgroups (P=0.040).The positive impact of stent oversizing was documented on procedural and clinical outcomes. In particular, small vessels treated with smaller stents were associated with greater adverse events, suggesting that aggressive selection of larger stents, with appropriate attention to edge effects, may optimize long-term outcomes, even in drug-eluting stents implantation.

  View details for PubMedID 28951394

• Assessment of bioresorbable scaffold with a novel high-definition 60 MHz IVUS imaging system: Comparison with 40-MHz IVUS referenced to optical coherence tomography. Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions Okada, K. n., Kitahara, H. n., Mitsutake, Y. n., Tanaka, S. n., Kimura, T. n., Yock, P. G., Fitzgerald, P. J., Ikeno, F. n., Honda, Y. n. 2017

  Abstract

  In vivo assessment of bioresorbable scaffold (BRS) is of growing clinical interest. The novel 60MHz high-definition intravascular ultrasound (HD-IVUS) has been developed to overcome the limitations of conventional 40 MHz IVUS. This study aimed to evaluate the performance and limitations of 60 MHz HD-IVUS compared with 40 MHz IVUS with respect to polymeric-strut visualization, quantitative and qualitative analysis, and feasibility of high-speed pullback in the assessment of BRS.In a bench-test model, 361 struts were analyzed to evaluate the influence of ultrasound-beam angles and proximity of adjacent struts on IVUS visualization of BRS struts. Various settings were created by deforming the BRS and positioning the transducer offcenter. In an in vivo swine coronary model, scaffold and lumen areas, degree of visible external elastic membrane, incomplete strut apposition, and strut fracture were evaluated in 59 matched cross-sections obtained at conventional (0.5 mm/sec) and high speed (10 mm/sec) pullbacks. Both studies utilized optical coherence tomography (OCT) as reference. Overall, 60 MHz HD-IVUS demonstrated significantly improved visualization of polymeric struts compared with 40 MHz IVUS (well-visualized: 84.5% vs 62.3%, not visible: 4.4% vs 13.9%, respectively. P < 0.001), which was less affected by the beam angle and adjacent strut proximity. In the in vivo model, 60-MHz HD-IVUS showed better agreement of area measurements and strut abnormalities with OCT than 40 MHz IVUS. These findings were also confirmed on high-speed pullback images of 60 MHz HD-IVUS.As referenced to OCT, this study showed superiority of 60 MHz HD-IVUS over 40 MHz IVUS in the assessment of BRS with feasibility of high-speed pullback imaging.

  View details for PubMedID 28707349

• Comparative analysis method of permanent metallic stents (XIENCE) and bioresorbable poly-L-lactic (PLLA) scaffolds (Absorb) on optical coherence tomography at baseline and follow-up EUROINTERVENTION Nakatani, S., Sotomi, Y., Ishibashi, Y., Grundeken, M. J., Tateishi, H., Tenekecioglu, E., Zeng, Y., Suwannasom, P., Regar, E., Radu, M. D., Raber, L., Bezerra, H., Costa, M. A., Fitzgerald, P., Prati, F., Costa, R. A., Dijkstra, J., Kimura, T., Kozuma, K., Tanabe, K., Akasaka, T., Di Mario, C., Serruys, P. W., Onuma, Y. 2016; 12 (12): 1498-1509

  Abstract

  Fully bioresorbable Absorb poly-L-lactic-acid (PLLA) scaffolds (Abbott Vascular, Santa Clara, CA, USA) are a novel approach for the treatment of coronary narrowing. Due to the translucency of the material (PLLA), the optical coherence tomography (OCT) measurement methods used in the ABSORB trials were unique but not applicable for permanent metallic stents. When the Absorb scaffold and metallic stents are compared in the context of randomised trials, it is challenging to compare the two devices using the conventional methods. The primary purpose of this report is to explain the biases in conventional methodologies applied for metallic stents and for PLLA scaffolds at baseline and follow-up, and to propose a new standard methodology that enables us to compare two different devices using an almost identical and methodological language.A consensus amongst multiple core labs and expert researchers of OCT was reached on a new standard OCT measurement methodology that enables us to compare these two different devices. In brief, the proposed OCT methods are summarised as follows. 1) Both endoluminal and abluminal scaffold/stent contours should be traced. 2) Consistently, endoluminal and abluminal incomplete stent apposition areas should be measured. 3) The area occupied by scaffold/stent struts should be quantified directly or virtually. 4) The strut area should be systematically excluded from the flow area as well as the neointimal area. 5) Additional information on the degree of embedment could be reported using the interpolated lumen contour. Interobserver variability of the proposed method was excellent (intraclass correlation 0.89-100).A standardised OCT measurement methodology is proposed. This should be implemented in ongoing and future trials comparing the Absorb scaffolds and metallic stents.

  View details for DOI 10.4244/EIJY15M10_03

  View details for Web of Science ID 000392688700012

  View details for PubMedID 26448577

• DESyne novolimus-eluting coronary stent is superior to Endeavor zotarolimus-eluting coronary stent at five-year follow-up: final results of the multicentre EXCELLA II randomised controlled trial EUROINTERVENTION Iqbal, J., Verheye, S., Abizaid, A., Ormiston, J., de Vries, T., Morrison, L., Toyloy, S., Fitzgerald, P., Windecker, S., Serruys, P. W. 2016; 12 (11): E1336-E1342

  Abstract

  Newer-generation drug-eluting stents (DES) have been shown to be superior to first-generation DES. Current-generation DES have zotarolimus, everolimus or biolimus as antiproliferative drugs. Novolimus, a metabolite of sirolimus, has been specifically developed to provide efficacy similar to currently available agents at a lower dose and thus requires a lower polymer load. We report the final five-year outcomes of the EXCELLA II trial comparing a zotarolimus-eluting stent (ZES) with a novolimus-eluting stent (NES).EXCELLA II is a prospective, multicentre, single-blind, non-inferiority clinical trial. Patients (n=210) with a maximum of two de novo lesions in two different epicardial vessels were randomised (2:1) to treatment with either NES (n=139) or ZES (n=71). At five-year follow-up, patients in the NES group had a significantly lower incidence of the patient-oriented (HR 0.53, 95% CI: 0.32-0.87, p=0.013) and device-oriented (HR 0.38, 95% CI: 0.17-0.83, p=0.011) composite endpoints. There was no difference in cardiac death and definite/probable stent thrombosis between the two groups; however, there was a trend towards reduction in myocardial infarction and repeat revascularisation in the NES group at five-year follow-up.At five-year follow-up, the incidence of device- and patient-oriented events was significantly lower in the NES group. Further studies, adequately powered for clinical outcomes, are warranted.

  View details for Web of Science ID 000400778800006

  View details for PubMedID 26465374

• Characteristics of Late-Acquired Incomplete Stent Apposition: A Comparison With First-Generation and Second-Generation Drug-Eluting Stents. journal of invasive cardiology Waseda, K., Ako, J., Kume, T., Fitzgerald, P. J., Honda, Y. 2016; 28 (8): 323-329

  Abstract

  This study aim was to investigate the morphometric parameters of late-acquired incomplete stent apposition (ISA) following use of Cypher sirolimus-eluting stent (SES; Cordis), Taxus paclitaxel-eluting stent (PES; Boston Scientific), and Resolute zotarolimus-eluting stent (ZES; Medtronic).Characteristics of late-acquired ISA between first-generation and second-generation drug-eluting stents (DESs) have not been systematically examined.Late-acquired ISA was defined as separation of at least 1 stent strut from the vessel wall with evidence of blood speckle behind the strut, where poststent implantation intravascular ultrasound (IVUS) revealed complete apposition. A total of 30 late-acquired ISA cases (12 SES, 10 PES, 8 ZES) were included in this IVUS analysis. Corresponding cross-sections at post procedure were selected for comparison. Vessel, lumen, peristent tissue, and stent area were measured in the late-acquired ISA arc as referenced to stent center.Late-acquired ISA area was 2.4 ± 1.5 mm² in SES, 2.2 ± 2.7 mm² in PES, and 0.9 ± 0.6 mm² in ZES (P=.02 for SES vs ZES). Vessel area increased from post procedure to follow-up in SES (4.6 ± 1.7 mm² to 7.0 ± 2.5 mm²; P<.01) and PES (3.6 ± 1.7 mm² to 5.7 ± 3.8 mm²; P=.06), but not in ZES. Vessel expansion was the main mechanism in SES and PES groups; however, tissue regression and stent recoil, as well as vessel expansion, also contributed to late-acquired ISA in ZES. Per-patient analyses demonstrated that vessel expansion was the predominant mechanism of late-acquired ISA in 83% of SES, 60% in PES, and 50% of ZES cases.The magnitude and mechanism of late-acquired ISA appear to be different between first-generation and second-generation DESs, possibly due to varying vessel response to different stent component types.

  View details for PubMedID 26689416

• Attenuated-Signal Plaque Progression Predicts Long-Term Mortality After Heart Transplantation: IVUS Assessment of Cardiac Allograft Vasculopathy. Journal of the American College of Cardiology Okada, K., Fearon, W. F., Luikart, H., Kitahara, H., Otagiri, K., Tanaka, S., Kimura, T., Yock, P. G., Fitzgerald, P. J., Yeung, A. C., Valantine, H. A., Khush, K. K., Honda, Y. 2016; 68 (4): 382-392

  Abstract

  Although cardiac allograft vasculopathy (CAV) is typically characterized by diffuse coronary intimal thickening with pathological vessel remodeling, plaque instability may also play an important role in CAV. Previous studies of native coronary atherosclerosis have demonstrated associations between attenuated-signal plaque (ASP), plaque instability, and adverse clinical events.This study's aim was to characterize the association between ASP and long-term mortality post-heart transplantation.In 105 heart transplant recipients, serial (baseline and 1-year post-transplant) intravascular ultrasound was performed in the first 50 mm of the left anterior descending artery. The ASP score was calculated by grading the measured angle of attenuation from grades 0 to 4 (specifically, 0°, 1° to 90°, 91° to 180°, 181° to 270°, and >270°) at 1-mm intervals. The primary endpoint was all-cause death or retransplantation.At 1-year post-transplant, 10.5% of patients demonstrated ASP progression (newly developed or increased ASP). Patients with ASP progression had a higher incidence of acute cellular rejection during the first year (63.6% vs. 22.3%; p = 0.006) and tendency for greater intimal growth (percent intimal volume: 9.2 ± 9.3% vs. 4.4 ± 5.3%; p = 0.07) than those without. Over a median follow-up of 4.6 years, there was a significantly lower event-free survival rate in patients with ASP progression at 1-year post-transplant compared with those without. In contrast, maximum intimal thickness did not predict long-term mortality.ASP progression appears to reflect chronic inflammation related to acute cellular rejection and is an independent predictor of long-term mortality after heart transplantation. Serial assessments of plaque instability may enhance identification of high-risk patients who may benefit from closer follow-up and targeted medical therapies.

  View details for DOI 10.1016/j.jacc.2016.05.028

  View details for PubMedID 27443435

• Acute stent recoil and optimal balloon inflation strategy: an experimental study using real-time optical coherence tomography. EuroIntervention Kitahara, H., Waseda, K., Yamada, R., Otagiri, K., Tanaka, S., Kobayashi, Y., Okada, K., Kume, T., Nakagawa, K., Teramoto, T., Ikeno, F., Yock, P. G., Fitzgerald, P. J., Honda, Y. 2016; 12 (2): e190-8

  Abstract

  Our aim was to evaluate stent expansion and acute recoil at deployment and post-dilatation, and the impact of post-dilatation strategies on final stent dimensions.Optical coherence tomography (OCT) was performed on eight bare metal platforms of drug-eluting stents (3.0 mm diameter, n=6 for each) during and after balloon inflation in a silicone mock vessel. After nominal-pressure deployment, a single long (30 sec) vs. multiple short (10 sec x3) post-dilatations were performed using a non-compliant balloon (3.25 mm, 20 atm). Stent areas during deployment with original delivery systems were smaller in stainless steel stents than in cobalt-chromium and platinum-chromium stents (p<0.001), whereas subsequent acute recoil was comparable among the three materials. At post-dilatation, acute recoil was greater in cobalt-chromium and platinum-chromium stents than in stainless steel stents (p<0.001), resulting in smaller final stent areas in cobalt-chromium and platinum-chromium stents than in stainless steel stents (p<0.001). In comparison between conventional and latest-generation cobalt-chromium stents, stent areas were not significantly different after both deployment and post-dilatation. With multiple short post-dilatations, acute recoil was significantly improved from first to third short inflation (p<0.001), achieving larger final area than a single long inflation, despite stent materials/designs (p<0.001).Real-time OCT revealed significant acute recoil in all stent types. Both stent materials/designs and post-dilatation strategies showed a significant impact on final stent expansion.

  View details for DOI 10.4244/EIJV12I2A32

  View details for PubMedID 27290678

• Association of periarterial neovascularization with progression of cardiac allograft vasculopathy and long-term clinical outcomes in heart transplant recipients JOURNAL OF HEART AND LUNG TRANSPLANTATION Kitahara, H., Okada, K., Tanaka, S., Yang, H., Miki, K., Kobayashi, Y., Kimura, T., Luikart, H., Yock, P. G., Yeung, A. C., Fitzgerald, P. J., Khush, K. K., Fearon, W. F., Honda, Y. 2016; 35 (6): 752-759

  Abstract

  This study investigated the relationship between periarterial neovascularization, development of cardiac allograft vasculopathy (CAV), and long-term clinical outcomes after heart transplantation. Proliferation of the vasa vasorum is associated with arterial inflammation. The contribution of angiogenesis to the development of CAV has been suggested.Serial (baseline and 1-year post-transplant) intravascular ultrasound was performed in 102 heart transplant recipients. Periarterial small vessels (PSV) were defined as echolucent luminal structures <1 mm in diameter, located ≤2 mm outside of the external elastic membrane. The signal void structures were excluded when they connected to the coronary lumen (considered as side branches) or could not be followed in ≥3 contiguous frames. The number of PSV was counted at 1-mm intervals throughout the first 50 mm of the left anterior descending artery, and the PSV score was calculated as the sum of cross-sectional values. Patients with a PSV score increase of ≥ 4 between baseline and 1-year post-transplant were classified as the "proliferative" group. Maximum intimal thickness was measured for the entire analysis segment.During the first year post-transplant, the proliferative group showed a greater increase in maximum intimal thickness (0.33 ± 0.36 mm vs 0.10 ± 0.28 mm, p < 0.001) and had a higher incidence of acute cellular rejection (50.0% vs 23.9%, p = 0.025) than the non-proliferative group. On Kaplan-Meier analysis, cardiac death-free survival rate over a median of 4.7 years was significantly lower in the proliferative group than in the non-proliferative group (hazard ratio, 3.10; p = 0.036).The increase in PSV, potentially representing an angioproliferative response around the coronary arteries, was associated with early CAV progression and reduced survival after heart transplantation.

  View details for DOI 10.1016/j.healun.2016.02.002

  View details for PubMedID 27068036

• Intravascular Ultrasound-Derived Stent Dimensions as Predictors of Angiographic Restenosis Following Nitinol Stent Implantation in the Superficial Femoral Artery JOURNAL OF ENDOVASCULAR THERAPY Miki, K., Fujii, K., Kawasaki, D., Shibuya, M., Fukunaga, M., Imanaka, T., Tamaru, H., Sumiyoshi, A., Nishimura, M., Horimatsu, T., Saita, T., Okada, K., Kimura, T., Honda, Y., Fitzgerald, P. J., Masuyama, T., Ishihara, M. 2016; 23 (3): 424-432

  Abstract

  To identify intravascular ultrasound (IVUS) measurements that can predict angiographic in-stent restenosis (ISR) following nitinol stent implantation in superficial femoral artery (SFA) lesions.A retrospective review was conducted of 97 patients (mean age 72.9±8.9 years; 63 men) who underwent IVUS examination during endovascular treatment of 112 de novo SFA lesions between July 2012 and December 2014. Self-expanding bare stents were implanted in 46 lesions and paclitaxel-eluting stents in 39 lesions. Six months after stenting, follow-up angiography was conducted to assess stent patency. The primary endpoint was angiographic ISR determined by quantitative vascular angiography analysis at the 6-month follow-up. Variables associated with restenosis were sought in multivariate analysis; the results are presented as the odds ratio (OR) and 95% confidence interval (CI).At follow-up, 27 (31.8%) angiographic ISR lesions were recorded. The lesions treated with uncoated stents were more prevalent in the ISR group compared with the no restenosis group (74.1% vs 44.8%, p=0.02). Lesion length was longer (154.4±79.5 vs 109.0±89.3 mm, p=0.03) and postprocedure minimum stent area (MSA) measured by IVUS was smaller (13.9±2.8 vs 16.3±1.6 mm(2), p<0.001) in the ISR group. Multivariate analysis revealed that bare stent use (OR 7.11, 95% CI 1.70 to 29.80, p<0.01) and longer lesion length (OR 1.08, 95% CI 1.01 to 1.16, p=0.04) were predictors of ISR, while increasing postprocedure MSA (OR 0.58, 95% CI 0.41 to 0.82, p<0.01) was associated with lower risk of ISR. Receiver operating characteristic analysis identified a MSA of 15.5 mm(2) as the optimal cutpoint below which the incidence of restenosis increased (area under the curve 0.769).Postprocedure MSA can predict ISR in SFA lesions, which suggests that adequate stent enlargement during angioplasty might be required for superior patency.

  View details for DOI 10.1177/1526602816641669

  View details for Web of Science ID 000376287000003

  View details for PubMedID 27044270

• Quantitative precision of optical frequency domain imaging: direct comparison with frequency domain optical coherence tomography and intravascular ultrasound. Cardiovascular intervention and therapeutics Kobayashi, Y., Kitahara, H., Tanaka, S., Okada, K., Kimura, T., Ikeno, F., Yock, P. G., Fitzgerald, P. J., Honda, Y. 2016; 31 (2): 79-88

  Abstract

  No systematic validation study is available with optical frequency domain imaging (OFDI), directly compared with frequency domain optical coherence tomography (FD-OCT) and intravascular ultrasound (IVUS). Controversy also remains about the impact of different stent contour tracing methods by OFDI/FD-OCT. In vitro: coronary phantom models (1.51-5.04 mm) were imaged with OFDI, FD-OCT, and IVUS, demonstrating excellent quantitative precision with a slight overestimation of mean lumen diameter (difference 0.01-0.02 mm). In vivo: corresponding 64 OFDI/IVUS images of stented coronary segments from 20 swines were analyzed. Minimum lumen area by OFDI was larger than IVUS at baseline (P < 0.001), whereas it was smaller than IVUS at follow-up. When stent was traced at leading edges of struts by OFDI, minimum stent area was similar between OFDI and IVUS (P = 0.60). When traced at the highest intensity points of struts by OFDI, it was significantly larger in OFDI than in IVUS (P < 0.001). Three modalities have clinically acceptable precision across the wide range of lumen diameters. In vivo measurements by OFDI and IVUS could slightly be discrepant depending on the parameters and time points. In stent assessment by OFDI, the 2 methods led to a small but systematic difference; therefore, consistency in methodology is advised for comparative studies.

  View details for DOI 10.1007/s12928-015-0349-x

  View details for PubMedID 26271203

• Functional Versus Anatomic Assessment of Myocardial Bridging by Intravascular Ultrasound: Impact of Arterial Compression on Proximal Atherosclerotic Plaque. Journal of the American Heart Association Yamada, R., Tremmel, J. A., Tanaka, S., Lin, S., Kobayashi, Y., Hollak, M. B., Yock, P. G., Fitzgerald, P. J., Schnittger, I., Honda, Y. 2016; 5 (4)

  Abstract

  The presence of a myocardial bridge (MB) has been shown to promote atherosclerotic plaque formation proximal to the MB, presumably because of hemodynamic disturbances provoked by retrograde blood flow toward this segment in cardiac systole. We aimed to determine the anatomic and functional properties of an MB related to the extent of atherosclerosis assessed by intravascular ultrasound.We enrolled 100 patients with angina but no significant obstructive coronary artery disease who had an intravascular ultrasound-detected MB in the left anterior descending artery (median age 54 years, 36% male). The MB was identified with intravascular ultrasound by the presence of an echolucent band (halo). Anatomically, the MB length was 22±13 mm, and halo thickness was 0.7±0.6 mm. Functionally, systolic arterial compression was 23±12%. The maximum plaque burden up to 20 mm proximal to the MB entrance was significantly greater than the maximum plaque burden within the MB segment. Among the intravascular ultrasound-defined MB properties, arterial compression was the sole MB parameter that demonstrated a significant positive correlation with maximum plaque burden up to 20 mm proximal to the MB entrance (r=0.254, P=0.011 overall; r=0.545, P<0.001 low coronary risk). In multivariate analysis, adjusting for clinical characteristics and coronary risk factors, arterial compression was independently associated with maximum plaque burden up to 20 mm proximal to the MB entrance.In patients with an MB in the left anterior descending artery, the percentage of arterial compression is related directly to the burden of atherosclerotic plaque located proximally to the MB, particularly in patients who otherwise have low coronary risk. This may prove helpful in identifying high-risk MB patients.

  View details for DOI 10.1161/JAHA.114.001735

  View details for PubMedID 27098967

• Relative dose and vascular response after drug-eluting stent implantation: A dosimetric 3D-intravascular ultrasound study INTERNATIONAL JOURNAL OF CARDIOLOGY Kitahara, H., Waseda, K., Yamada, R., Sakamoto, K., Yock, P. G., Fitzgerald, P. J., Honda, Y. 2016; 204: 211-217

  Abstract

  In drug-eluting stents (DESs), the theoretical drug dose exposed to the vessel wall per stent surface area may vary due to the fixed loading dose and differences in the stent surface area once expanded in varying vessel sizes. The aim of this study was to evaluate the potential effects of different dose intensities, as estimated by 3D-IVUS dosimetry, on vascular response after DES implantation.Follow-up (6-9 months) 3D-IVUS was performed in 840 coronary lesions treated with a single DES of the following types: sirolimus (SES, n=148), paclitaxel (PES, n=162), Endeavor zotarolimus (E-ZES, n=233), Resolute zotarolimus (R-ZES, n=147), and everolimus (EES, n=150). Volume index (volume/length, mm(3)/mm) was obtained for vessel, lumen, plaque, stent, and neointima. In each lesion, exposed dose intensity was calculated as known loading dose divided by measured luminal surface area of the stented segment. Lesions were divided into tertiles based on the exposed dose intensity: high, medium, and low dose groups.The exposed dose intensity ranged 0.74-1.76 μg/mm(2) for SES, 0.41-1.18 μg/mm(2) for PES, 0.71-1.57 μg/mm(2) for E-ZES, 0.72-1.63 μg/mm(2) for R-ZES, and 0.40-0.99 μg/mm(2) for EES. All types of DES showed no significant difference in neointimal hyperplasia among the 3 groups, except that E-ZES showed significantly less neointimal hyperplasia in the high dose group.Detailed 3D-IVUS revealed significant lesion-to-lesion variability in dose intensity exposed to the vessel wall following DES implantation. However, the major types of DES appear to yield equally effective neointimal suppression, despite the varying dose intensity, except for E-ZES.

  View details for DOI 10.1016/j.ijcard.2015.11.130

  View details for Web of Science ID 000367008200059

  View details for PubMedID 26681540

• Paradoxical Vessel Remodeling of the Proximal Segment of the Left Anterior Descending Artery Predicts Long-Term Mortality After Heart Transplantation JACC-HEART FAILURE Okada, K., Kitahara, H., Yang, H., Tanaka, S., Kobayashi, Y., Kimura, T., Luikart, H., Yock, P. G., Yeung, A. C., Valantine, H. A., Fitzgerald, P. J., Khush, K. K., Honda, Y., Fearon, W. F. 2015; 3 (12): 942-952

  Abstract

  This study investigated the association between arterial remodeling and geographic distribution of cardiac allograft vasculopathy (CAV), and outcomes after heart transplantation.CAV is characterized by a combination of coronary intimal thickening and pathological vessel remodeling, which varies at different locations in coronary arteries.In 100 transplant recipients, serial volumetric intravascular ultrasonography (IVUS) was performed at baseline and 1 year post-transplantation in the first 50 mm of the left anterior descending artery (LAD). IVUS indices were evaluated in the entire segment and 3 equally divided LAD segments. Paradoxical vessel remodeling was defined as [Δvessel volume/Δintimal volume <0].After 1 year, death or re-transplantation occurred in 20 patients over a median follow-up period of 4.7 years. Paradoxical vessel remodeling was observed in 57%, 41%, 50%, and 40% for the entire vessel, proximal, middle, and distal LAD segments, respectively. Kaplan-Meier analysis revealed a significantly lower event-free rate of survival in patients with paradoxical vessel remodeling involving the proximal LAD segment, which was not present when involving the entire LAD or mid and distal LAD segments. In multivariate analysis, paradoxical vessel remodeling of the proximal LAD segment was independently associated with death or re-transplantation (hazard ratio [HR]: 11.18; 95% confidence interval [CI]: 2.39 to 83.23; p = 0.0015).Despite the diffuse nature of CAV, paradoxical vessel remodeling of the proximal LAD segment at 1 year was the primary determinant of long-term mortality or re-transplantation. Assessment of arterial remodeling combined with coronary intimal thickening may enhance identification of high-risk patients who may benefit from closer follow-up and targeted medical therapies.

  View details for DOI 10.1016/j.jchf.2015.07.013

  View details for Web of Science ID 000366949300002

• Evaluation of a fully bioresorbable vascular scaffold in patients with coronary artery disease: Design of and rationale for the ABSORB III randomized trial AMERICAN HEART JOURNAL Kereiakes, D. J., Ellis, S. G., Popma, J. J., Fitzgerald, P. J., Samady, H., Jones-McMeans, J., Zhang, Z., Cheong, W., Su, X., Ben-Yehuda, O., Stone, G. W. 2015; 170 (4): 641-?

  Abstract

  Randomized trials have demonstrated progressive improvements in clinical and angiographic measures of restenosis with technologic iterations from balloon angioplasty to bare-metal stents and subsequently to drug-eluting stents (DES). However, the permanent presence of a metal stent prevents coronary vasomotion, autoregulation, and adaptive coronary remodeling. The limitations imposed by a permanent metal implant may be overcome with a bioresorbable scaffold. ABSORB III is a large-scale, multicenter, randomized trial designed to support US premarket approval of the ABSORB BVS platform and is the first study with sufficient size to allow valid examination of the relative clinical outcomes between metallic DES and bioresorbable scaffold.ABSORB III (ClincalTrials.gov NCT01751906) will register approximately 2,262 patients and includes a lead-in phase (n = 50), the primary randomized analysis group (n = 2,000), an imaging cohort (n = 200), and a pharmacokinetic substudy (n = 12). In the primary analysis group, approximately 2,000 patients with up to 2 de novo native coronary artery lesions in separate epicardial vessels will be prospectively assigned in a 2:1 ratio to ABSORB BVS versus XIENCE everolimus-eluting stents (EES). The primary end point is target lesion failure (the composite of cardiac death, target vessel-related myocardial infarction, or ischemia-driven target lesion revascularization) at 1 year, powered for noninferiority of ABSORB BVS compared to XIENCE EES. Clinical follow-up will continue for 5 years. Enrollment has been completed, and the principal results will be available in the fall of 2015.The large-scale ABSORB III randomized trial will evaluate the safety and effectiveness of ABSORB BVS compared to XIENCE EES in the treatment of patients with coronary artery disease.

  View details for DOI 10.1016/j.ahj.2015.07.013

  View details for Web of Science ID 000361575200005

  View details for PubMedID 26386787

• Effect of Sex Differences on Invasive Measures of Coronary Microvascular Dysfunction in Patients With Angina in the Absence of Obstructive Coronary Artery Disease JACC-CARDIOVASCULAR INTERVENTIONS Kobayashi, Y., Fearon, W. F., Honda, Y., Tanaka, S., Pargaonkar, V., Fitzgerald, P. J., Lee, D. P., Stefanick, M., Yeung, A. C., Tremmel, J. A. 2015; 8 (11): 1433-1441

  Abstract

  This study investigated sex differences in coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) in patients with angina in the absence of obstructive coronary artery disease.Coronary microvascular dysfunction is associated with worse long-term outcomes, especially in women. Coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) are 2 methods of assessing the coronary microcirculation.We prospectively enrolled 117 women and 40 men with angina in the absence of obstructive coronary artery disease. We performed CFR, IMR, fractional flow reserve, and quantitative coronary angiography in the left anterior descending artery. Coronary flow was assessed with a thermodilution method by obtaining mean transit time (Tmn) (an inverse correlate to absolute flow) at rest and hyperemia.All patients had minimal atherosclerosis by quantitative coronary angiography (% diameter stenosis: 23.2 ± 12.3%), and epicardial disease was milder in women (fractional flow reserve: 0.88 ± 0.04 vs. 0.87 ± 0.04; p = 0.04). IMR was similar between the sexes (20.7 ± 9.8 vs. 19.1 ± 8.0; p = 0.45), but CFR was lower in women (3.8 ± 1.6 vs. 4.8 ± 1.9; p = 0.004). This was primarily due to a shorter resting Tmn in women (p = 0.005), suggesting increased resting coronary flow, whereas hyperemic Tmn was identical (p = 0.79). In multivariable analysis, female sex was an independent predictor of lower CFR and shorter resting Tmn.Despite similar microvascular function in women and men by IMR, CFR is lower in women. This discrepancy appears to be due to differences in resting coronary flow between the sexes. The effect of sex differences should be considered in interpretation of physiological indexes using resting coronary flow.

  View details for DOI 10.1016/j.jcin.2015.03.045

  View details for Web of Science ID 000361757600013

• Association between blood glucose variability and coronary plaque instability in patients with acute coronary syndromes CARDIOVASCULAR DIABETOLOGY Okada, K., Hibi, K., Gohbara, M., Kataoka, S., Takano, K., Akiyama, E., matsuzawa, Y., Saka, K., Maejima, N., Endo, M., Iwahashi, N., Tsukahara, K., Kosuge, M., Ebina, T., Fitzgerald, P. J., Honda, Y., Umemura, S., Kimura, K. 2015; 14

  Abstract

  Blood glucose variability is receiving considerable attention as a new risk factor for coronary artery disease. This study aimed to investigate the association between blood glucose variability and coronary plaque tissue characteristics.In 57 patients with acute coronary syndrome, integrated backscatter intravascular ultrasound (IB-IVUS) and gray-scale IVUS were performed before balloon dilatation or stent implantation in the culprit vessels. Standard IVUS indices were evaluated for volume index (volume/length), and plaque components were measured by IB-IVUS for percent tissue volume. In addition to conventional glucose indicators, blood glucose variability in a stable state was determined by calculating the mean amplitude of glycemic excursions (MAGE) using a continuous glucose monitoring system.Higher MAGE values were significantly correlated with larger percent plaque volumes (r = 0.32, p = 0.015), and increased lipid (r = 0.44, p = 0.0006) and decreased fibrous (r = -0.45, p = 0.0005) plaque components. In contrast, HbA1c or fasting plasma glucose values were not significantly correlated with plaque volumes and percent plaque components. Homeostasis model assessment of insulin resistance values were positively correlated with vessel (r = 0.35, p = 0.007) and plaque (r = 0.27, p = 0.046) volumes, but not with percent plaque components. In multiple regression analysis, higher MAGE values were independently associated with increased lipid (β = 0.80, p = 0.0035) and decreased fibrous (β = -0.79, p = 0.0034) contents in coronary plaques.Among all glucose indicators studied, only higher blood glucose variability was an independent determinant of increased lipid and decreased fibrous contents with larger plaque burden, suggesting blood glucose variability as one of the important factors related to coronary plaque vulnerability.

  View details for DOI 10.1186/s12933-015-0275-3

  View details for Web of Science ID 000359704400001

  View details for PubMedCentralID PMC4546046

• A Y-shaped bifurcation-dedicated stent for the treatment of de novo coronary bifurcation lesions: an IVUS analysis from the BRANCH trial. EuroIntervention Sakata, K., Koo, B., Waseda, K., Nakatani, D., Yock, P. G., Whitbourn, R., Worthley, S. G., Ormiston, J., Webster, M., Wilkins, G. T., Honda, Y., Meredith, I. T., Fitzgerald, P. J. 2015; 10 (11): e1-8

  Abstract

  Aims: The aim of this IVUS substudy was to assess the efficacy of the Y-shaped Medtronic bifurcation-dedicated stent (BDS) for the treatment of de novo coronary bifurcated lesions. Methods and results: In the BRANCH trial, post-procedure IVUS was performed in 45 patients. IVUS was available in both branches in 19 lesions and only the main branch (MB) in 26 lesions. IVUS analysis included four distinct locations: proximal MB, bifurcation site, distal MB, and side branch (SB). Lumen symmetry was calculated as minimum/maximum lumen diameters. The quantity of isolated stent struts across the SB ostium was used to assess inadequate strut apposition to the carina resulting in partial jailing of the SB orifice. A minimum stent area (MSA) <4 mm2 was found in 0% of proximal and distal MB, and in 15.4% of SB. In SB, MSA was located mainly at mid or distal segments (84.6%), rather than at the SB ostium. Eccentric stent expansion and edge dissection were seen primarily at proximal MB. Isolated struts were seen in only 20.9% of SB ostia with a minimum length of 0.7±0.4 mm. Conclusions: Implantation of BDS resulted in adequate stent dimensions and strut apposition at the carina and SB ostium. ClinicalTrials.gov Identifier: NCT0060732.

  View details for DOI 10.4244/EIJY14M08_16

  View details for PubMedID 25169593

• Baseline and 9 Months IVUS Analysis of the Bifurcation-Dedicated Biolimus A9-Eluting Axxess Stent System: The DIVERGE IVUS Substudy CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Buysschaert, I., Sanidas, E., Hasegawa, T., Koo, B., Honda, Y., Fitzgerald, P. J., Verheye, S. 2014; 84 (7): 1062-1070

  Abstract

  Percutaneous treatment of complex coronary bifurcation lesions remains challenging, even in the drug-eluting stent era. We sought to evaluate the baseline and 9 months intravascular ultrasound (IVUS) analysis of the Axxess™ stent, a self-expanding, Biolimus A9™-eluting, and dedicated bifurcation stent.We enrolled the first 76 patients from selected sites of the 302 patients large DIVERGE trial (a prospective, single-arm, multicenter trial evaluating the safety and efficacy of the Axxess stent). Both baseline and 9 months IVUS images were collected for serial two-dimensional (2D) and 3D analysis. A minimal amount and a low percentage of neointimal volume index were seen in the Axxess stent at 9 months (0.4 ± 0.6 mm(3) /mm and 4.3 ± 5.2%, respectively). Vessel, lumen, and stent volume indices increased significantly (respectively, 17.0 ± 3.6 to 18.9 ± 3.7 mm(3) /mm, P < 0.0001; 7.3 ± 2.0 to 9.2 ± 2.5 mm(3) /mm, P < 0.0001; and 7.4 ± 2.0 to 9.6 ± 2.6 mm(3) /mm, P < 0.0001). This resulted in minimum lumen area (MLA) enlargement (6.1 ± 1.9 to 7.2 ± 2.3 mm(2) , P < 0.0001), whereas peristent plaque area decreased (8.7 ± 2.5 to 8.5 ± 2.1 mm(3) /mm, P = 0.016). At 9 months, 16 (26%) incomplete stent apposition (ISA) persisted from baseline, while six resolved (9.7%). Only one (2%) ISA was late acquired. In the additional distal sirolimus-eluting stents, MLA decreased from 4.3 ± 1.1 to 4.1 ± 1.2 mm(2) (P = 0.04) at 9 months for the main branch, and from 3.4 ± 1.2 to 3.2 ± 1.2 mm(2) (P = 0.09) for the side branch.The dedicated bifurcation Axxess stent system demonstrates significant stent volume increase with minimal neointimal formation and a low incidence of late-acquired ISA at 9 months. © 2014 Wiley Periodicals, Inc.

  View details for DOI 10.1002/ccd.25414

  View details for Web of Science ID 000345514400009

• First-in-Man Study of the Low-Dose Paclitaxel Using the COBRA-P Drug-Eluting Coronary Stent System With a Novel Biodegradable Coating in De Novo Coronary Lesions: IVUS Results From the PLUS-ONE Trial CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Nakatani, D., Waseda, K., Ako, J., Calderas, C., Condado, J. A., Condado, J. F., Honda, Y., Fitzgerald, P. J. 2014; 84 (7): 1101-1109

  View details for DOI 10.1002/ccd.25351

  View details for Web of Science ID 000345514400016

• Intravascular Ultrasound Analysis of Small Vessel Lesions Treated with the Sparrow Coronary Stent System: Results of the CARE II Trial CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Kume, T., Waseda, K., Koo, B., Yock, P. G., Botelho, R., Verheye, S., Whitbourn, R., Meredith, I., Worthley, S., Hai, K. T., Honda, Y., Abizaid, A., Fitzgerald, P. J. 2014; 83 (1): 19-24

  Abstract

  OBJECTIVES: The aim of this study was to evaluate the Sparrow sirolimus-eluting stent (Sparrow-SES) against the Sparrow bare-metal stent (Sparrow-BMS) and conventional balloon-expandable bare-metal stent (BMS: Driver/Micro-Driver(®) stent, Medtronic Vascular, Santa Rosa, CA). BACKGROUND: The Sparrow(®) stent (Biosensors International, Singapore) consists of a guide wire-based, self-expandable, ultra-thin nitinol stent. The performance of this device with sirolimus in a fully biodegradable polymer has not been determined. METHODS: A total of 74 patients were included in this intravascular ultrasound (IVUS) sub-study of the CARE II trial, which was a prospective, randomized, multicenter trial in the treatment of single de novo native coronary artery lesions in vessels ranging from 2.0 mm to 2.75 mm in diameter (Sparrow-SES: n = 31, Sparrow-BMS: n = 22, BMS: n = 21). RESULTS: Stent volume index (VI) was significantly increased 8-month later in Sparrow-SES and Sparrow-BMS, but not in BMS (4.0±1.0 to 4.6±1.0 mm(3) /mm, p<0.0001, 4.0±0.6 to 4.4±0.8 mm(3) /mm, p<0.05, and 5.2±1.0 to 5.1±0.9 mm(3) /mm, p=0.421, respectively). % neointimal obstruction in Sparrow-SES was significantly smaller than those in Sparrow-BMS and BMS at follow-up (17.6±9.4 vs. 36.2±13.8 and 39.9±11.1%, p<0.001). Sparrow-SES showed a mean 15% stent expansion and good suppression of neointimal proliferation, resulting in a significantly lower percentage of change in lumen VI during follow-up period (Sparrow-SES: -6.2±16.2%, Sparrow-BMS: -30.4±11.6%, BMS: -40.4±10.0%, p<0.001). CONCLUSIONS: The self-expanding Sparrow-SES demonstrated chronic stent expansion, good suppression of neointimal proliferation and resulted in a more preserved lumen in stented small vessels compared with the Sparrow-BMS and conventional balloon expandable BMS. © 2013 Wiley Periodicals, Inc.

  View details for DOI 10.1002/ccd.24867

  View details for Web of Science ID 000328631400007

  View details for PubMedID 23413202

• Contemporary infrapopliteal intervention for limb salvage and wound healing: harmonization of revascularization and wound management. Circulation journal Kawarada, O., Yasuda, S., Huang, J., Honda, Y., Fitzgerald, P. J., Ishihara, M., Ogawa, H. 2014; 78 (7): 1540-1549

  Abstract

  Infrapopliteal arterial disease is a significant cause of critical limb ischemia (CLI), whether single-segment or multisegment disease. The collaboration between the tremendous advancements in endovascular technology and the refinement of endovascular techniques has renewed the classic infrapopliteal interventions during the past decade. With this paradigm shift in the treatment of CLI, the role of a comprehensive approach of different disciplines for tissue loss is becoming greater. Given the increasing global burden of CLI, we review the cutting-edge diagnostic and endovascular approaches to infrapopliteal artery disease, and the importance of wound management in optimizing clinical outcomes.

  View details for PubMedID 24964979

• First-in-Human Evaluation of a Bioabsorbable Polymer-Coated Sirolimus-Eluting Stent Imaging and Clinical Results of the DESSOLVE I Trial (DES With Sirolimus and a Bioabsorbable Polymer for the Treatment of Patients With De Novo Lesion in the Native Coronary Arteries) JACC-CARDIOVASCULAR INTERVENTIONS Ormiston, J., Webster, M., Stewart, J., Vrolix, M., Whitbourn, R., Donohoe, D., Knape, C., Lansky, A., Attizzani, G. F., Fitzgerald, P., Kandzari, D. E., Wijns, W. 2013; 6 (10): 1026-1034

  Abstract

  This first-in-human multicenter study sought to examine prospectively the safety and efficacy of a new, cobalt chromium thin-strut, coronary absorbable polymer-coated, sirolimus-eluting stent.Bioabsorbable polymers on drug-eluting stents may lower the long-term risks of inflammation, delayed healing, and adverse events.We enrolled patients with symptomatic coronary artery disease with stable or unstable angina pectoris and >50% diameter stenosis, amenable to coverage with a ≤23-mm long stent in a vessel 2.5 to 3.5 mm in diameter. All patients received dual antiplatelet therapy after implantation. Patients, in groups of 10, underwent repeat angiography, intravascular ultrasound, and optical coherence tomography at 4, 6, or 8 months, and all patients were seen or contacted at 18 months of follow-up.The median (range) in-stent late lumen loss (LLL) was 0.03 mm (-0.22 to 0.21 mm), 0.10 mm (-0.03 to 1.2 mm), and 0.08 mm (-0.01 to 0.28 mm), at 4, 6, and 8 months, respectively. At 18 months, the median in-stent LLL was 0.08 mm (-0.30 to 0.46 mm). On optical coherence tomography, the proportion of uncovered stent struts decreased from a median of 7.3% (range 0.4% to 46.3%) at 4 months to 0% (range: 0% to 3.4%) at 18 months. The percentage of neointimal volume obstruction by intravascular ultrasound increased from a median of 5.3% to 9.1% between 4 and 6 months and remained nearly unchanged thereafter through 18 months of follow-up. The only recorded major adverse cardiac event was a myocardial infarction.At 18 months of follow-up, this absorbable polymer-coated, cobalt chromium sirolimus-eluting stent was associated with a low and stable in-stent LLL, complete strut coverage, and no stent thrombosis. (First-In-Human Trial of the MiStent Drug-Eluting Stent [DES] in Coronary Artery Disease [DESSOLVE-I]; NCT01247428).

  View details for DOI 10.1016/j.jcin.2013.05.013

  View details for Web of Science ID 000327101600006

  View details for PubMedID 24055443

• Variability in quantitative and qualitative analysis of intravascular ultrasound and frequency domain optical coherence tomography. Catheterization and cardiovascular interventions Abnousi, F., Waseda, K., Kume, T., Otake, H., Kawarada, O., Yong, C. M., Fitzgerald, P. J., Honda, Y., Yeung, A. C., Fearon, W. F. 2013; 82 (3): E192-9

  Abstract

  BACKGROUND: Frequency-domain optical coherence tomography (FD-OCT) is an intravascular imaging technique now available in the United States. However, the importance of level of training required for analysis using intravascular ultrasound (IVUS) and FD-OCT is unclear. The aim of this study was to evaluate inter- and intra-observer variability between expert and beginner analysts interpreting IVUS and FD-OCT images. METHODS AND RESULTS: Two independent expert analysts and two independent beginner analysts evaluated a total of 226 ± 2 stent cross-sections with IVUS and 232 ± 2 stent cross-sections with FD-OCT in 14 patients after stenting. Inter- and intra-observer variability for determining stent volume index (VI), as well as identifying incomplete stent apposition and dissection were assessed. The inter- and intra-observer variability of stent VI was minimal for both beginner and expert analysts regardless of imaging technology (random variability: 0.38 vs. 0.05 mm(3) /mm for IVUS, 0.26 vs. 0.08 mm(3) /mm for FD-OCT). Although qualitative IVUS analysis at the patient level revealed no significant difference between beginners and experts, this was not the case for FD-OCT. The number of overall qualitative findings noted by beginner and expert analysts were more variable (overestimated or underestimated) with FD-OCT. CONCLUSION: Despite varying levels of training, the increased resolution of FD-OCT compared to IVUS provides better detection and less variability in quantitative image analysis. On the contrary, this increased resolution not only increases the rate but also the variability of detection of qualitative image analysis, especially for beginner analysts. © 2013 Wiley Periodicals, Inc.

  View details for DOI 10.1002/ccd.24871

  View details for PubMedID 23412754

• Variability in quantitative and qualitative analysis of intravascular ultrasound and frequency domain optical coherence tomography CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Abnousi, F., Waseda, K., Kume, T., Otake, H., Kawarada, O., Yong, C. M., Fitzgerald, P. J., Honda, Y., Yeung, A. C., Fearon, W. F. 2013; 82 (3): E192-E199

  Abstract

  BACKGROUND: Frequency-domain optical coherence tomography (FD-OCT) is an intravascular imaging technique now available in the United States. However, the importance of level of training required for analysis using intravascular ultrasound (IVUS) and FD-OCT is unclear. The aim of this study was to evaluate inter- and intra-observer variability between expert and beginner analysts interpreting IVUS and FD-OCT images. METHODS AND RESULTS: Two independent expert analysts and two independent beginner analysts evaluated a total of 226 ± 2 stent cross-sections with IVUS and 232 ± 2 stent cross-sections with FD-OCT in 14 patients after stenting. Inter- and intra-observer variability for determining stent volume index (VI), as well as identifying incomplete stent apposition and dissection were assessed. The inter- and intra-observer variability of stent VI was minimal for both beginner and expert analysts regardless of imaging technology (random variability: 0.38 vs. 0.05 mm(3) /mm for IVUS, 0.26 vs. 0.08 mm(3) /mm for FD-OCT). Although qualitative IVUS analysis at the patient level revealed no significant difference between beginners and experts, this was not the case for FD-OCT. The number of overall qualitative findings noted by beginner and expert analysts were more variable (overestimated or underestimated) with FD-OCT. CONCLUSION: Despite varying levels of training, the increased resolution of FD-OCT compared to IVUS provides better detection and less variability in quantitative image analysis. On the contrary, this increased resolution not only increases the rate but also the variability of detection of qualitative image analysis, especially for beginner analysts. © 2013 Wiley Periodicals, Inc.

  View details for DOI 10.1002/ccd.24871

  View details for Web of Science ID 000323454100008

• Duplex criteria for in-stent restenosis in the superficial femoral artery CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Kawarada, O., Higashimori, A., Noguchi, M., Waratani, N., Yoshida, M., Fujihara, M., Yokoi, Y., Honda, Y., Fitzgerald, P. J. 2013; 81 (4): E199-E205

  Abstract

  To elucidate the optimal cutoff and accuracy of duplex ultrasonography (DUS) parameters for in-stent restenosis (ISR) after nitinol stenting in the superficial femoral artery (SFA).Few data are available regarding the performance of DUS for binary ISR based on quantitative vessel analysis (QVA) in the era of SFA nitinol stenting.This retrospective study included 74 in-stent stenoses of SFA who underwent DUS before follow-up angiography. DUS parameters, such as peak systolic velocity (PSV) and the peak systolic velocity ratio (PSVR), were compared with percent diameter stenosis (%DS) from a QVA basis.There was a statistically significant correlation (P < 0.001) between "%DS and PSV" and "%DS and PSVR," and the correlation with %DS proved to be stronger in PSVR (R = 0.720) than in PSV (R = 0.672). The best performing parameter for ISR (50% or greater stenosis) was revealed PSVR, as the areas under the receiver operator characteristics curves using PSVR and PSV were 0.908 and 0.832, respectively. A PSVR cut off value of 2.85 yielded the best predictive value with sensitivity of 88%, specificity of 84%, and accuracy of 86%. The positive predictive value was 85% and the negative predictive value was 88%.A PSVR of 2.85 is the optimal threshold for ISR after nitinol stenting in the SFA. Further large prospective studies are required for the validation and establishment of uniform criteria for DUS parameters.

  View details for DOI 10.1002/ccd.24509

  View details for Web of Science ID 000315416600004

  View details for PubMedID 22639187

• Improved automated lumen contour detection by novel multifrequency processing algorithm with current intravascular ultrasound system CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Kume, T., Kim, B., Waseda, K., Sathyanarayana, S., Li, W., Teo, T., Yock, P. G., Fitzgerald, P. J., Honda, Y. 2013; 81 (3): E173-E177

  Abstract

  The aim of this study was to evaluate a new fully automated lumen border tracing system based on a novel multifrequency processing algorithm.We developed the multifrequency processing method to enhance arterial lumen detection by exploiting the differential scattering characteristics of blood and arterial tissue. The implementation of the method can be integrated into current intravascular ultrasound (IVUS) hardware.This study was performed in vivo with conventional 40-MHz IVUS catheters (Atlantis SR Pro™, Boston Scientific Corp, Natick, MA) in 43 clinical patients with coronary artery disease. A total of 522 frames were randomly selected, and lumen areas were measured after automatically tracing lumen borders with the new tracing system and a commercially available tracing system (TraceAssist™) referred to as the "conventional tracing system." The data assessed by the two automated systems were compared with the results of manual tracings by experienced IVUS analysts.New automated lumen measurements showed better agreement with manual lumen area tracings compared with those of the conventional tracing system (correlation coefficient: 0.819 vs. 0.509). When compared against manual tracings, the new algorithm also demonstrated improved systematic error (mean difference: 0.13 vs. -1.02 mm(2) ) and random variability (standard deviation of difference: 2.21 vs. 4.02 mm(2) ) compared with the conventional tracing system.This preliminary study showed that the novel fully automated tracing system based on the multifrequency processing algorithm can provide more accurate lumen border detection than current automated tracing systems and thus, offer a more reliable quantitative evaluation of lumen geometry.

  View details for DOI 10.1002/ccd.23274

  View details for Web of Science ID 000315339400004

  View details for PubMedID 21805600

• Impact of Diabetes Mellitus on Vessel Response in the Drug-Eluting Stent Era Pooled Volumetric Intravascular Ultrasound Analyses CIRCULATION-CARDIOVASCULAR INTERVENTIONS Sakata, K., Waseda, K., Kume, T., Otake, H., Nakatani, D., Yock, P. G., Fitzgerald, P. J., Honda, Y. 2012; 5 (6): 763-771

  Abstract

  Exaggerated neointimal hyperplasia is considered as the primary mechanism for increased restenosis in patients with diabetes mellitus (DM) treated with bare-metal stent. However, the vessel response in DM and non-DM treated with different drug-eluting stents (DES) has not been systematically evaluated.We investigated 3D intravascular ultrasound (postprocedure and 6 to 9 months) in 971 patients (267 with DM and 704 without DM) treated with sirolimus- (n=104), paclitaxel- (n=303), zotarolimus- (n=391), or everolimus- (n=173) eluting stents. Volumetric data were standardized by length as volume index (VI). At postprocedure, lumen VI at the stented segment was significantly smaller in DM than in non-DM, whereas vessel VI was similar between the 2 groups. At follow-up, neointimal obstruction and maximum cross-sectional narrowing (neointimal area/stent area) were not significantly different between the 2 groups with no interaction for the DES type. Consequently, lumen VI was smaller in DM than in non-DM at follow-up. In the reference segments, residual plaque burden at postprocedure was significantly greater in DM than in non-DM, although change in lumen VI was similar between the 2 groups. The arterial responses at the reference segments also showed no interaction for the DES type.DM and non-DM lesions showed similar vessel response in both in-stent and reference segments regardless of the DES type. In the DES era, the follow-up lumen in DM patients seems to be determined primarily by the smaller lumen at postprocedure rather than exaggerated neointima within the stent or plaque proliferation at the reference segments.

  View details for DOI 10.1161/CIRCINTERVENTIONS.111.962878

  View details for Web of Science ID 000313576500014

  View details for PubMedID 23149332

• Predictors of adverse clinical outcomes after successful infrapopliteal intervention CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Kawarada, O., Fujihara, M., Higashimori, A., Yokoi, Y., Honda, Y., Fitzgerald, P. J. 2012; 80 (5): 861-871

  Abstract

  To clarify the clinical and angiographical variables related to delayed wound healing, major amputation and death after successful infrapopliteal intervention in critical limb ischemia patients with tissue loss.There is an underappreciation of adverse clinical outcomes after successful infrapopliteal intervention.Stent-assisted infrapopliteal angioplasty was successful in 106 limbs in 85 patients. Successful intervention was defined as revascularization of at least one straight-line flow to the foot.At 6 months and 1, 2, and 5 years, the repeat intervention-free rates were 55.0, 49.6, 44.4, and 36.1%, respectively; the amputation-free survival rates were 85.7, 68.0, 54.5, and 39.8%, respectively; and the limb salvage rates were 96.0, 92.4, 86.3, and 86.3%, respectively. An infectious wound was an independent predictor of major amputation after successful intervention. The complete wound healing rates were 36.8, 57.5, 67.9, and 73.6% at 3, 6, 9, and 12 months, respectively. In stepwise multivariate Cox analysis, diabetes mellitus, an infectious wound, and the pedal arch classification were identified as independent predictors of wound healing. The long-term survival rates at 6 months and 1, 2, and 5 years were 89.5, 73.8, 62.0, and 43.4%, respectively. Stepwise multivariate Cox analysis indentified end-stage renal disease (ESRD) on hemodialysis to be an independent predictor of death.An infectious wound, comorbidities of diabetes mellitus and ESRD on hemodialysis and classification of pedal arch can be predictors of adverse clinical outcomes after successful infrapopliteal intervention.

  View details for DOI 10.1002/ccd.24370

  View details for Web of Science ID 000310472300029

  View details for PubMedID 22431493

• Intravascular Ultrasound Comparison of Small Coronary Lesions Between Novel Guidewire-Based Sirolimus-Eluting Stents and Conventional Sirolimus-Eluting Stents JOURNAL OF INVASIVE CARDIOLOGY Kume, T., Waseda, K., Koo, B., Botelho, R., Verheye, S., Whitbourn, R., Meredith, I., Worthley, S., Hai, K. T., Yock, P. G., Azevedo de Oliveira, F. R., Abizaid, A., Fitzgerald, P. J., Honda, Y. 2012; 24 (10): 489-493

  Abstract

  The Sparrow stent system (Biosensors International) consists of a self-expanding, ultra-thin nitinol stent mounted within a 0.014″ guidewire designed for small or tortuous coronary lesions. We compared the intravascular ultrasound (IVUS) findings between the novel self-expanding sirolimus-eluting stent (Sparrow-SES) and a conventional balloon-expandable sirolimus-eluting stent (Cypher-SES) in patients with small coronary disease.We examined 14 lesions treated with the Sparrow-SES from CARE II, compared with 22 small vessel lesions treated with Cypher-SES. IVUS examination was performed post-procedure and 8 months later. Volumetric data were standardized by length as volume index (VI; mm³/mm).While baseline stent VI trended smaller in Sparrow-SES, follow-up stent VI became similar between the 2 groups due to a significant increase of stent VI in self-expanding Sparrow-SES during the follow-up period. At 8 months, Sparrow-SES showed greater neointima than Cypher-SES (0.8 ± 0.6 mm³/mm vs 0.2 ± 0.2 mm³/mm; P<.001). However, the decrease in lumen VI was only 0.3 ± 0.7 mm³/mm in Sparrow-SES, as compared to 0.1 ± 0.3 mm³/mm in Cypher-SES (P=.259), since the late loss due to neointimal hyperplasia was partly counterbalanced by the chronic stent expansion in Sparrow-SES.While 8-month follow-up of Sparrow-SES revealed greater amounts of neointimal hyperplasia compared with conventional Cypher-SES, chronic stent expansion preserved the lumen by increasing stent volume. This novel, guidewire-based, self-expanding stent system designed to be delivered through complex anatomies may be useful to treat patients with small-caliber coronary lesions by offering sufficient lumen preservation at follow-up.

  View details for Web of Science ID 000311028600014

  View details for PubMedID 23043031

• Comparison of vascular response to the everolimus-eluting stent versus the paclitaxel-eluting stent: intravascular ultrasound results from the SPIRIT III trial EUROINTERVENTION Yamasaki, M., Tsujino, I., Lima-Filho, M. O., Ako, J., Shimohama, T., Hasegawa, T., Sakurai, R., Sudhir, K., Stone, G. W., Waseda, K., Honda, Y., Fitzgerald, P. J. 2012; 8 (6): 724-731

  Abstract

  The purpose of this study was to investigate the vascular response of the everolimus-eluting stent (EES) compared with the paclitaxel-eluting stent (PES) using serial intravascular ultrasound (IVUS).Data were obtained from the SPIRIT III trial, a multicentre, 2:1 randomised, controlled study comparing EES and PES in de novo native coronary artery lesions. IVUS images were eligible for volumetric analysis at eight-month follow-up in 158 lesions (EES: 113, PES: 45). At eight months, EES had a smaller neointimal volume index (VI: mm3/mm) (EES: 0.4±0.4 vs. PES: 0.8±0.8 mm3/mm, p=0.002) and also a smaller % neointimal obstruction (EES: 7.1±6.7% vs. PES: 11.1±10.5%, p=0.005) compared with PES. While there was no significant change in vessel VI with EES, there was a significant increase in vessel VI in PES during eight-month follow-up (EES: 0.1±1.2 vs. PES: 1.2±0.8 mm3/mm, p=0.001). There were no statistical differences in the frequency of edge dissection or incomplete stent apposition between the two groups.Detailed IVUS analysis confirmed significantly less neointimal hyperplasia with EES compared with PES. While there was no increase in vessel volume with EES during the eight-month follow-up period, vessel enlargement was seen at the stented segment in PES.

  View details for DOI 10.4244/EIJV8I6A112

  View details for Web of Science ID 000312043500014

  View details for PubMedID 23086791

• Mid-Term Results of Everolimus-Eluting Stent in a Japanese Population Compared With a US Randomized Cohort: SPIRIT III Japan Registry With Harmonization by Doing JOURNAL OF INVASIVE CARDIOLOGY Saito, S., Nakamura, S., Fujii, K., Nakamura, M., Isshiki, T., Hirayama, H., Kikuchi, T., Fujita, H., Nonogi, H., Mitsudo, K., Kimura, T., Igarashi, K., Saito, K., Lansky, A. J., Stone, G. W., Honda, Y., Waseda, K., Fitzgerald, P. J., Sudhir, K. 2012; 24 (9): 444-450

  Abstract

  To address safety concerns with first-generation drug-eluting stents (DESs), the everolimus-eluting stent (EES) has been developed as a second-generation DES. The study aim was to: (1) demonstrate that use of the EES in Japanese patients is non-inferior to use of the paclitaxel-eluting stent (PES) in US patients; and (2) compare vessel response to the EES in Japanese vs US patients.The SPIRIT III Japan Registry, a prospective single-arm multicenter study was a part of the SPIRIT III global clinical program using harmonization by doing. The primary endpoint was in-segment late loss at 8 months, compared to US PES.A total of 88 subjects were enrolled in the Japan EES group. Angiographic in-segment late loss was significantly less in Japan EES vs US PES (0.15 ± 0.34 mm vs 0.28 ± 0.48 mm, respectively; P=.0185; Pnon-inferio r<.0001), while target vessel failure (TVF; 8.0% vs 9.9%) and major adverse cardiac events (MACE) at 9 months (5.7% vs 8.8%) were not significantly different between the 2 groups. No differences were observed between Japan and US EES populations in terms of late loss, TVF, or MACE. Neointimal volume and postprocedural incomplete stent apposition rate were lower in Japan EES vs US EES/PES.The SPIRIT III Japan Registry met the primary endpoint of lower late loss in the Japan EES group vs the US PES group, with comparable results for EES between the Japanese and US patients.

  View details for Web of Science ID 000310543300016

  View details for PubMedID 22954564

• Evaluation of the peri-strut low intensity area following sirolimus- and paclitaxel-eluting stents implantation: Insights from an optical coherence tomography study in humans INTERNATIONAL JOURNAL OF CARDIOLOGY Otake, H., Shite, J., Ikeno, F., Shinke, T., Teramoto, T., Miyoshi, N., Ako, J., Honda, Y., Fitzgerald, P. J., Hirata, K. 2012; 157 (1): 38-42

  Abstract

  Recent pathological studies have demonstrated that peri-strut low intensity area (PLIA) seen on optical coherence tomography (OCT) imaging represents the presence of fibrinogen and/or extracellular matrix. We sought to assess the clinical prevalence of PLIA and its relation to neointimal proliferation after the implantation of sirolimus- (SES) and paclitaxel-eluting stents (PES) in humans.Seventy patients underwent 6-months follow-up OCT after SES (43 stents) or PES (37 stents) implantation. PLIA was defined as a region around stent struts with homogenous lower intensity than surrounding tissue on OCT images without signal attenuation. The incidence of stent struts with PLIA (+PLIA struts) was calculated as the number of +PLIA struts/number of all struts (%).PES showed a higher incidence of stents with PLIA than SES (86% vs. 58%; p=0.005) with a higher prevalence of +PLIA struts (27.8±21.9% vs. 10.9±11.0%; p=0.0008). SES with PLIA showed a significantly greater neointimal thickness (NIT) than SES without PLIA (p=0.02), while PES showed a similar tendency (p=0.19). In a detailed strut basis analysis, average NIT on +PLIA struts were significantly greater than that on -PLIA struts in both SES and PES. In addition, average NIT was positively correlated with the prevalence of +PLIA struts (SES: Rho=0.73; p<0.0001, PES: Rho=0.58, p=0.0005) in both stents.The prevalence of PLIA was significantly higher in PES than in SES. The presence and extent of PLIA might be associated with intimal thickening after 1st-generation DES implantation.

  View details for DOI 10.1016/j.ijcard.2010.11.006

  View details for Web of Science ID 000303206800015

  View details for PubMedID 21168926

• A randomized, controlled, multi-center trial comparing the safety and efficacy of zotarolimus-eluting and paclitaxel-eluting stents in de novo lesions in coronary arteries: Final results of the ZoMaxx II trial Conference of the Paris Course on Revascularization Gray, W. A., Yeung, A. C., Cutlip, D. E., Popma, J. J., Fitzgerald, P. J., Williams, D. O., Heuer, H., O'Shaughnessy, C. D., Overlie, P. A., Mann, J. T., Cannon, L. A., Hermiller, J. B., Henry, T. D., Whitbourn, R., Stuckey, T. D., Midei, M. G., Coe, J., Schwartz, L. B. ELSEVIER IRELAND LTD. 2012: 96–101

  Abstract

  The purpose of this prospective, randomized, single-blind controlled clinical trial was to compare the effectiveness of a zotarolimus-eluting stent (ZoMaxx™) with a paclitaxel-eluting coronary stent (Taxus™ Express(2)™) in patients with angina pectoris and a single native coronary artery lesion between 10-28 mm in length and 2.5-3.75mm in diameter.Patients were enrolled at 75 international institutions between June 2005 and November 2006.1099 (1672 originally planned) patients received 557 ZoMaxx and 542 Taxus stents: cohorts were well-matched for diabetes (27% vs. 27%), reference vessel diameter (2.73 ± 0.46mm vs. 2.74 ± 0.45mm) and lesion length (14.8 ± 6.7mm vs. 14.3 ± 6.4mm). Nine month clinical and angiographic follow-up was available in 1052/1099 (96%) and 649/836 (78%) patients, respectively. The safety profiles for the two stents (myocardial infarction (MI), cardiac death and/or target vessel revascularization (TVR)) were similar (ZoMaxx 8.7% vs. Taxus 6.9%, p=NS). The primary endpoint of 9-month TVR occurred more frequently after treatment with ZoMaxx (6.8%) as compared with Taxus (4.2%), therefore the primary clinical endpoint was not met. However, the 9-month in-segment late lumen loss for ZoMaxx (0.29 ± 0.47mm) and Taxus (0.22 ± 0.41mm, p=NS) were similar, thus satisfying the primary angiographic endpoint. Secondary endpoints of the rates of in-segment and in-stent binary restenosis were also similar (5.9% vs. 5.8%, 7.8% vs. 7.9%, respectively).At 9months, the ZoMaxx stent failed to achieve the primary endpoint of non-inferiority in TVR to the Taxus stent, but safety endpoints were equal between the two stent systems.

  View details for DOI 10.1016/j.ijcard.2011.05.061

  View details for Web of Science ID 000303206800026

  View details for PubMedID 21658783

• Consensus Standards for Acquisition, Measurement, and Reporting of Intravascular Optical Coherence Tomography Studies A Report From the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Tearney, G. J., Regar, E., Akasaka, T., Adriaenssens, T., Barlis, P., Bezerra, H. G., Bouma, B., Bruining, N., Cho, J., Chowdhary, S., Costa, M. A., de Silva, R., Dijkstra, J., Di Mario, C., Dudeck, D., Falk, E., Feldman, M. D., Fitzgerald, P., Garcia, H., Gonzalo, N., Granada, J. F., Guagliumi, G., Holm, N. R., Honda, Y., Ikeno, F., Kawasaki, M., Kochman, J., Koltowski, L., Kubo, T., Kume, T., Kyono, H., Lam, C. C., Lamouche, G., Lee, D. P., Leon, M. B., Maehara, A., Manfrini, O., Mintz, G. S., Mizuno, K., Morel, M., Nadkarni, S., Okura, H., Otake, H., Pietrasik, A., Prati, F., Raeber, L., Radu, M. D., Rieber, J., Riga, M., Rollins, A., Rosenberg, M., Sirbu, V., Serruys, P. W., Shimada, K., Shinke, T., Shite, J., Siegel, E., Sonada, S., Suter, M., Takarada, S., Tanaka, A., Terashima, M., Troels, T., Uemura, S., Ughi, G. J., van Beusekom, H. M., van der Steen, A. F., van Es, G., Van Soest, G., Virmani, R., Waxman, S., Weissman, N. J., Weisz, G. 2012; 59 (12): 1058-1072

  Abstract

  The purpose of this document is to make the output of the International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT) Standardization and Validation available to medical and scientific communities, through a peer-reviewed publication, in the interest of improving the diagnosis and treatment of patients with atherosclerosis, including coronary artery disease.Intravascular optical coherence tomography (IVOCT) is a catheter-based modality that acquires images at a resolution of ~10 μm, enabling visualization of blood vessel wall microstructure in vivo at an unprecedented level of detail. IVOCT devices are now commercially available worldwide, there is an active user base, and the interest in using this technology is growing. Incorporation of IVOCT in research and daily clinical practice can be facilitated by the development of uniform terminology and consensus-based standards on use of the technology, interpretation of the images, and reporting of IVOCT results.The IWG-IVOCT, comprising more than 260 academic and industry members from Asia, Europe, and the United States, formed in 2008 and convened on the topic of IVOCT standardization through a series of 9 national and international meetings.Knowledge and recommendations from this group on key areas within the IVOCT field were assembled to generate this consensus document, authored by the Writing Committee, composed of academicians who have participated in meetings and/or writing of the text.This document may be broadly used as a standard reference regarding the current state of the IVOCT imaging modality, intended for researchers and clinicians who use IVOCT and analyze IVOCT data.

  View details for DOI 10.1016/j.jacc.2011.09.079

  View details for Web of Science ID 000301443000003

  View details for PubMedID 22421299

• Intravascular ultrasound insights from the Cobalt Chromium Stent With Antiproliferative for Restenosis II (COSTAR II) trial comparing CoStar and Taxus paclitaxel-eluting stents. Cardiovascular revascularization medicine : including molecular interventions Tsujino, I., Koizumi, T., Shimohama, T., Ako, J., Waseda, K., Krucoff, M., Honda, Y., Fitzgerald, P. J. 2012; 13 (2): 111-118

  Abstract

  Dedicated IVUS analyses of the second CObalt chromium STent with Antiproliferative for Restenosis (COSTAR II) trial have not been documented. We aim to compare IVUS findings between CoStar paclitaxel-eluting stent (PES) and Taxus PES in patients enrolled in the COSTAR II trial. We also attempted to examine the possible regional impact of multiple stenting.Among the 1700 patients enrolled, 238 were assigned to an IVUS cohort including 168 patients treated by provisional multiple stenting. At 9 months, qualitative and quantitative IVUS observations including incomplete stent apposition (ISA) and neointimal proliferation (neointimal obstruction: neointimal volume/stent volume ×100) were compared between CoStar and Taxus PESs.In qualitative analysis, late-acquired ISA was observed in 1 patient treated by Taxus PES. Impaired strut continuity suggestive of stent fracture was observed in 2 out of 33 patients treated by multiple CoStar, and 4 out of 21 patients treated by multiple Taxus (P=.14). No such findings were found in single-stented patients in either stent subset. Quantitative analysis showed greater neointimal obstruction in CoStar (19.7%±13.4%, n=52) than in Taxus (10.7%±9.9%, n=38), whereas no significant difference in neointimal obstruction was found between single and multiple stenting in either CoStar or Taxus PES.The CoStar PES exhibits greater neointimal proliferation compared with Taxus PES at 9 months but with similar qualitative outcomes including late-acquired ISA. IVUS findings suggestive of stent fracture were found only in multiple-stenting cases irrespective of the stent used.

  View details for DOI 10.1016/j.carrev.2012.01.010

  View details for PubMedID 22406056

• Intravascular Ultrasound Assessment of Postprocedural Incomplete Stent Apposition JOURNAL OF INVASIVE CARDIOLOGY Kume, T., Waseda, K., Ako, J., Sakata, K., Yamasaki, M., Shimohama, T., Tsujino, I., Hasegawa, T., Fitzgerald, P. J., Honda, Y. 2012; 24 (1): 13-16

  Abstract

  There has been no detailed intravascular ultrasound (IVUS) analysis to evaluate the degree to which stent underexpansion or reference vessel/stent size mismatch contributes to the occurrence of post-procedural incomplete stent apposition (post-ISA).We evaluated 238 lesions treated with everolimus-eluting stents (n = 110) or paclitaxel-eluting stents (n = 128). Reference lumen/stent area ratio was defined as the ratio of lumen area adjacent to the stent edge in the reference segment to stent area at the stent edge or at stent body ISA site.Post-ISA was observed in 36 of the 238 cases (15%) at the proximal stent edge, 15 of the 238 cases (6%) at the distal stent edge and 14 of the 238 cases (6%) at stent body. Reference lumen/stent area ratio was significantly greater in the ISA group compared with non-ISA in proximal edge (127 ± 20 vs. 99 ± 10%; P<.001), and greater reference lumen/stent area ratio (118 ± 18 vs. 94 ± 11%; P<.001) and higher presence of calcification (60 vs. 29%; P<0.001) were observed in distal edge ISA group compared with non-ISA. At the stent body, presence of calcification was more frequently observed in the ISA compared with the non-ISA group (86 vs. 42%; P=.002).Post-ISA at the stent edge was significantly associated with vessel/stent mismatch rather than stent underexpansion. IVUS-guided appropriate stent or balloon sizing might be useful to prevent post-ISA and optimize initial stent deployment.

  View details for Web of Science ID 000299082000011

  View details for PubMedID 22210583

• Assessment of macro- and microcirculation in contemporary critical limb ischemia CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Kawarada, O., Yokoi, Y., Higashimori, A., Waratani, N., Fujihara, M., Kume, T., Sakata, K., Honda, Y., Fitzgerald, P. J. 2011; 78 (7): 1051-1058

  Abstract

  A paucity of data exists regarding manifestations of macro- and microcirculation in contemporary critical limb ischemia (CLI). The aim of this study was (1) to evaluate the differences in foot circulation based on angiographic findings, (2) to clarify the relationship between macro- and microcirculation, and (3) to investigate the effects of postural changes on micro as well as macrocirculation between the supine position to the dependent position.A total of 40 critically ischemic limbs in 29 patients were included in this study. Noninvasive evaluation of macrocirculation, based on the ankle brachial index (ABI) and ankle pressure, and microcirculation, using skin perfusion pressure (SPP), was performed in both the supine and dependent positions.There was no significant difference in macro- and microcirculations between any angiographical involvements. In the supine position, dorsal SPP correlated significantly with ABI (P = 0.021, r = 0.363) and ankle-pressure (P = 0.001, r = 0.495), whereas plantar SPP failed to correlate with ABI (P = 0.198, r = 0.208) or ankle-pressure (P = 0.185, r = 0.214). In the dependent position, however, SPP showed no significant correlation with ABI and ankle pressure. Postural change from the supine to dependent position yielded a significant increase in SPP (dorsal: 37.2 ± 16.2 to 77.9 ± 17.7 mm Hg, P < 0.001; plantar: 33.6 ± 17.3 to 75.7 ± 18.3 mm Hg, P < 0.001) as well as ABI and ankle-pressure (ABI: 0.70 ± 0.35 to 0.78 ± 0.42, P = 0.003; ankle-pressure; 108 ± 61 to 111 ± 60 mm Hg, P = 0.038). The effect of postural change on SPP showed no difference between patients with and without any clinical and angiographical complications.Of microcirculation assessed, only dorsal SPP correlated significantly with macrocirculation in the supine position. Furthermore, postural change from the supine to dependent position produced a dramatic improvement in microcirculation due to the effects of gravity.

  View details for DOI 10.1002/ccd.23086

  View details for Web of Science ID 000297203000015

  View details for PubMedID 21805568

• Arterial Response to Sirolimus Eluting Stents with Bioabsorbable Polymer: First IVUS Report from the DESSOLVE-I FIM Trial 23rd Annual Scientific Symposium of Transcatheter Cardiovascular Therapeutics (TCT) Sakamoto, K., Waseda, K., Yock, P. G., Honda, Y., Wijns, W., Ormiston, J., Fitzgerald, P. J. ELSEVIER SCIENCE INC. 2011: B32–B32

  View details for Web of Science ID 000296891900131

• Discrepancy in the Assessment of Jailed Side Branch Lesions by Visual Estimation and Quantitative Coronary Angiographic Analysis: Comparison With Fractional Flow Reserve CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Shin, D., Koo, B., Waseda, K., Park, K. W., Kim, H., Corral, M., Lansky, A., Honda, Y., Fearon, W. F., Fitzgerald, P. J. 2011; 78 (5): 720-726

  Abstract

  We sought to evaluate the variability in the assessment of jailed side branch (SB) lesions by visual estimation and quantitative coronary angiography (QCA) and to compare those results with fractional flow reserve (FFR).Twenty jailed SB lesions with available FFR (median 0.76; range, 0.39-0.94) were selected from the PRESSURE trial. Lesions were assessed by three independent QCA core laboratories with different QCA systems and by three different cardiologist groups (five European bifurcation club members, five Korean experts, and five trainees). Agreements of the continuous measurements were expressed as the intraclass correlation coefficient (ICC) and average coefficient of variance (CV), and those of the categorical values as kappa.Mean minimum lumen diameter (MLD) and % diameter stenosis differed among the three QCA systems up to 0.30 mm and 9.65%, respectively (P < 0.001). Three QCA systems showed fair agreement for the measurements of reference diameter, % diameter stenosis, MLD, and lesion length (ICC 0.346-0.686, CV 8.7-29.5%), and a poor agreement on stenosis of 75% or more (Fleiss κ 0.14 and mean κ 0.18). Agreements of visual estimation among the three groups were poor to fair (Fleiss κ 0.167-0.367). Sensitivity and specificity for predicting ischemia-inducible lesion (FFR < 0.75) were 64.7% and 48.0% for visual estimation and 56.6% and 56.6% by QCA, respectively. Visual estimation overestimated the % diameter stenosis and functional significance of the lesions compared with QCA (P < 0.001) and FFR (P = 0.036).Angiographic assessment of jailed SB lesions by both QCA and visual estimation showed variability. Visual estimation tended to overestimate the severity of jailed SB lesions compared to FFR and QCA.

  View details for DOI 10.1002/ccd.23049

  View details for Web of Science ID 000296412800012

  View details for PubMedID 22025472

• Sex Differences in Neointimal Hyperplasia Following Endeavor Zotarolimus-Eluting Stent Implantation AMERICAN JOURNAL OF CARDIOLOGY Nakatani, D., Ako, J., Tremmel, J. A., Waseda, K., Otake, H., Koo, B., Miyazawa, A., Hongo, Y., Hur, S., Sakurai, R., Yock, P. G., Honda, Y., Fitzgerald, P. J. 2011; 108 (7): 912-917

  Abstract

  Inconsistent results in outcomes have been observed between the genders after drug-eluting stent implantation. The aim of this study was to investigate gender differences in neointimal proliferation for the Endeavor zotarolimus-eluting stent (ZES) and the Driver bare-metal stent (BMS). A total of 476 (n = 391 ZES, n = 85 BMS) patients whose volumetric intravascular ultrasound analyses were available at 8-month follow-up were studied. At 8 months, neointimal obstruction and maximum cross-sectional narrowing (CSN) were significantly lower in women than in men receiving ZES (neointimal obstruction 15.5 ± 9.5% vs 18.2 ± 10.9%, p = 0.025; maximum CSN 30.3 ± 13.2% vs 34.8 ± 15.0%, p = 0.007). Conversely, these parameters tended to be higher in women than in men receiving BMS (neointimal obstruction 36.3 ± 15.9% vs 27.5 ± 17.2%, p = 0.053; maximum CSN 54.3 ± 18.6% vs 45.6 ± 18.3%, p = 0.080). There was a significant interaction between stent type and gender regarding neointimal obstruction (p = 0.001) and maximum CSN (p = 0.003). Multivariate linear regression analysis revealed that female gender was independently associated with lower neointimal obstruction (p = 0.027) and maximum CSN (p = 0.004) for ZES but not for BMS. Compared to BMS, ZES were independently associated with a reduced risk for binary restenosis in both genders (odds ratio for women 0.003, p = 0.001; odds ratio for men 0.191, p <0.001), but the magnitude of this risk reduction with ZES was significantly greater in women than men (p = 0.015). In conclusion, female gender is independently associated with decreased neointimal hyperplasia in patients treated with ZES. The magnitude of risk reduction for binary restenosis with ZES is significantly greater in women than in men.

  View details for DOI 10.1016/j.amjcard.2011.05.019

  View details for Web of Science ID 000295863200002

  View details for PubMedID 21784390

• First-in-human experience with the Medtronic Bifurcation Stent System EUROINTERVENTION Meredith, I. T., Worthley, S., Whitbourn, R., Webster, M., Fitzgerald, P. J., Ormiston, J. 2011; 7 (6): 662-669

  Abstract

  The BRANCH study was a prospective, multicentre, non-randomised, single arm trial to investigate the feasibility, safety, efficacy, and performance of the bare metal Medtronic Bifurcation Stent System for the treatment of de novo bifurcation lesions.Sixty patients were enrolled in the study. After a learning curve of one case at seven centres, 53 patients from six centres were prospectively treated. The primary endpoint was target vessel failure (TVF) at 30 days. Secondary endpoints included acute device, lesion, and procedure success and TVF at 12 months. Medina complex bifurcation lesions (1,1,1; 1,1,0; 1,0,1; 0,1,1) were treated in 71.7%. The stent was successfully implanted in 86.8% of cases. Acute device, lesion, and procedure success rates were 83.0%, 92.5%, and 88.7%, respectively. TVF occurred in 2/52 patients (3.8%) at 30 days. No other major adverse cardiac adverse events (MACE) occurred through 30 days follow-up. At 12 months, TVF occurred in 6/47 (12.8%) patients, and MACE occurred in 5/47 (10.6%) patients.Results from the BRANCH study demonstrate that the Medtronic Bifurcation Stent System is safe and can be successfully and effectively deployed in a variety of bifurcation lesions with good clinical outcomes.

  View details for DOI 10.4244/EIJV7I6A108

  View details for Web of Science ID 000297898200005

  View details for PubMedID 21959379

• Impact of Donor-Transmitted Atherosclerosis on Early Cardiac Allograft Vasculopathy: New Findings by Three-Dimensional Intravascular Ultrasound Analysis TRANSPLANTATION Yamasaki, M., Sakurai, R., Hirohata, A., Honda, Y., Bonneau, H. N., Luikart, H., Yock, P. G., Fitzgerald, P. J., Yeung, A. C., Valantine, H. A., Fearon, W. F. 2011; 91 (12): 1406-1411

  Abstract

  The influence of donor-transmitted coronary atherosclerosis (DA) on plaque progression during the first year after cardiac transplantation (Tx) is unknown.Serial 3-dimensional intravascular ultrasound (IVUS) studies were performed within 8 weeks (baseline; BL) and at 1 year after Tx in 38 recipients. On the basis of maximum intimal thickness (MIT) at BL, recipients were divided into DA group (DA+; MIT≥0.5 mm, n=23) or non-DA group (DA-; MIT<0.5 mm, n=15). Plaque, lumen, and vessel volume indexes were calculated by volume/measured length (mm/mm) in the left anterior descending artery. Univariate and multivariate regression analyses were attempted to reveal clinical predictors of change in coronary dimensions.During the first year after Tx, plaque volume index increased significantly in DA+ group, but did not change in DA- Group (DA+, 3.0±1.5 to 4.1±1.5 mm/mm, P<0.0001: DA-, 1.2±0.4 to 1.3±0.5 mm/mm, P=0.53). In both groups vessel volume index decreased significantly (DA+, 16.3±3.6 to 14.6±3.3 mm/mm, P=0.003: DA-, 13.5±4.1 to 12.0±3.3 mm/mm, P=0.01), as did lumen volume index (DA+, 13.2±3.1 to 10.5±2.7 mm/mm, P<0.0001: DA-, 12.2±3.7 to 10.7±3.0 mm/mm, P=0.004). Univariate and multivariate regression analyses revealed that DA was one of the strongest predictors for plaque progression.DA was associated with significant plaque progression during the first year after Tx, and in conjunction with negative remodeling, may be an important determinant of cardiac allograft vasculopathy.

  View details for DOI 10.1097/TP.0b013e31821ab91b

  View details for PubMedID 21512436

• Impact of Polymer Formulations on Neointimal Proliferation After Zotarolimus-Eluting Stent With Different Polymers Insights From the RESOLUTE Trial CIRCULATION-CARDIOVASCULAR INTERVENTIONS Waseda, K., Ako, J., Yamasaki, M., Koizumi, T., Sakurai, R., Hongo, Y., Koo, B., Ormiston, J., Worthley, S. G., Whitbourn, R. J., Walters, D. L., Meredith, I. T., Fitzgerald, P. J., Honda, Y. 2011; 4 (3): 248-255

  Abstract

  Polymer formulation may affect the efficacy of drug-eluting stents. Resolute, Endeavor, and ZoMaxx are zotarolimus-eluting stents with different stent platforms and different polymer coatings and have been tested in clinical trials. The aim of this analysis was to compare the efficacy of zotarolimus-eluting stents with different polymers.Data were obtained from the first-in man trial or first randomized trials of each stent, The Clinical RESpOnse EvaLUation of the MedTronic Endeavor CR ABT-578 Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions (RESOLUTE), Randomized Controlled Trial to Evaluate the Safety and Efficacy of the Medtronic AVE ABT-578 Eluting Driver Coronary Stent in De Novo Native Coronary Artery Lesions (ENDEAVOR II), and ZoMaxx I trials. Follow-up intravascular ultrasound analyses (8 to 9 months of follow-up) were possible in 353 patients (Resolute: 88, Endeavor: 98, ZoMaxx: 82, Driver: 85). Volume index (volume/stent length) was obtained for vessel, stent, lumen, peristent plaque, and neointima. Cross-sectional narrowing was defined as neointimal area divided by stent area (%). Neointima-free frame ratio was calculated as the number of frames without intravascular ultrasound-detectable neointima divided by the total number of frames within the stent. At baseline, vessel, lumen, and peristent plaque volume index were not significantly different among the 4 stent groups. At follow-up, percent neointimal obstruction was significantly lower in Resolute compared with Endeavor, ZoMaxx, and Driver (Resolute: 3.7±4.0, Endeavor: 17.5±10.1, ZoMaxx: 14.6±8.1, Driver: 29.4±17.2%; P<0.001). Greater maximum cross-sectional narrowing and higher neointima-free frame ratio, suggesting less neointimal coverage, were observed in Resolute compared with other stent groups. Multiple regression analysis confirmed that the biodurable polymer used in Resolute independently correlated with neointimal suppression among 3 zotarolimus-eluting stents.The different polymer formulations significantly affect the relative amount of neointima for zotarolimus-eluting stents.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00248079.

  View details for DOI 10.1161/CIRCINTERVENTIONS.110.957548

  View details for Web of Science ID 000291592000012

  View details for PubMedID 21586691

• Late-Term Clinical Outcomes With Zotarolimus- and Sirolimus-Eluting Stents 5-Year Follow-Up of the ENDEAVOR III (A Randomized Controlled Trial of the Medtronic Endeavor Drug [ABT-578] Eluting Coronary Stent System Versus the Cypher Sirolimus-Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions) JACC-CARDIOVASCULAR INTERVENTIONS Kandzari, D. E., Mauri, L., Popma, J. J., Turco, M. A., Gurbel, P. A., Fitzgerald, P. J., Leon, M. B. 2011; 4 (5): 543-550

  Abstract

  This study sought to compare late safety and efficacy outcomes following percutaneous coronary revascularization with zotarolimus-eluting stents (ZES) and sirolimus-eluting stents (SES).Despite higher late lumen loss and binary restenosis with ZES compared with SES, it is uncertain whether differences in early angiographic measures translate into more disparate late clinical events.Clinical outcomes were prospectively evaluated through 5 years in the ENDEAVOR III (A Randomized Controlled Trial of the Medtronic Endeavor Drug [ABT-578] Eluting Coronary Stent System Versus the Cypher Sirolimus-Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions) that randomized 436 patients of relatively low anatomic and clinical risk to treatment with ZES (n = 323) or SES (n = 113) and evaluated a primary endpoint of 8-month angiographic late lumen loss.At 5 years (completeness of follow-up: 95.2%), pre-specified endpoints of all-cause mortality (5.2% vs. 13.0%, p = 0.02), myocardial infarction (1.0% vs. 4.6%, p = 0.03), and the composite event rates of cardiac death/myocardial infarction (1.3% vs. 6.5%, p = 0.009) and major adverse cardiac events (14.0% vs. 22.2%, p = 0.05) were significantly lower among patients treated with ZES. Rates of target lesion (8.1% ZES vs. 6.5% SES, p = 0.68) and target vessel revascularization were similar between treatment groups. Stent thrombosis was infrequent and similar in both groups (0.7% ZES vs. 0.9% SES, p = 1.0). Between 9 months and 5 years, progression of major adverse cardiac events was significantly more common with SES than with ZES (16.7% vs. 7.8%, p = 0.015).Despite initially higher angiographic late lumen loss, rates of clinical restenosis beyond the protocol-specified angiographic follow-up period remain stable with ZES compared with the rates for SES, resulting in similar late-term efficacy. Over 5 years, significant differences in death, myocardial infarction, and composite endpoints favored treatment with ZES. (The Medtronic Endeavor III Drug Eluting Coronary Stent System Clinical Trial [ENDEAVOR III]; NCT00217256).

  View details for DOI 10.1016/j.jcin.2010.12.014

  View details for Web of Science ID 000291012500010

  View details for PubMedID 21596327

• Clinical Evaluation of the Resolute Zotarolimus-Eluting Coronary Stent System in the Treatment of De Novo Lesions in Native Coronary Arteries The RESOLUTE US Clinical Trial JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Yeung, A. C., Leon, M. B., Jain, A., Tolleson, T. R., Spriggs, D. J., Laurin, B. T., Popma, J. J., Fitzgerald, P. J., Cutlip, D. E., Massaro, J. M., Mauri, L. 2011; 57 (17): 1778-1783

  Abstract

  The RESOLUTE US (R-US) trial is a prospective, observational study designed to evaluate the clinical effectiveness of the Resolute zotarolimus-eluting stent (R-ZES) in a U.S. population.The R-ZES releases zotarolimus over a 6-month period in order to achieve optimal clinical effectiveness and safety.The R-US trial recruited patients with de novo native coronary lesions suitable for 1- or 2-vessel treatment with stents from 2.25 to 4.0 mm in diameter. In the main analysis cohort (2.5- to 3.5-mm stents and single-lesion treatment), the primary endpoint was 12-month target lesion failure (TLF) defined as the composite of cardiac death, myocardial infarction (MI), and clinically-driven target lesion revascularization (TLR), compared with data from Endeavor zotarolimus-eluting stent (E-ZES) trials, adjusting for baseline covariates through propensity scores.Overall, 1,402 patients were enrolled with a mean reference vessel diameter of 2.59 ± 0.47 mm and diabetes prevalence of 34.4%. In the main analysis cohort, TLF was 3.7% at 12 months compared with historical E-ZES results (TLF = 6.5%). The R-ZES met the 3.3% margin of noninferiority (rate difference = -2.8%, upper 1-sided 95% confidence interval: -1.3%, p < 0.001). The overall TLF rate was 4.7%, and rates of cardiac death, MI, and TLR were 0.7%, 1.4%, and 2.8%, respectively. The 12-month rate of stent thrombosis was 0.1%.The R-ZES achieved a very low rate of clinical restenosis while maintaining low rates of important clinical safety events such as death, MI, and stent thrombosis at 1-year follow-up. (The Medtronic RESOLUTE US Clinical Trial [R-US]; NCT00726453).

  View details for DOI 10.1016/j.jacc.2011.03.005

  View details for Web of Science ID 000289715600009

  View details for PubMedID 21470813

• GENDER-ASSOCIATED DIFFERENCES IN NEOINTIMAL VOLUME AFTER CORONARY ZOTAROLIMUS-ELUTING STENT IMPLANTATION: RELATIONSHIP TO RENAL FUNCTION 60th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) / I2 Summit / ACCF/Herman K. Gold Young Investigator's Award in Molecular and Cellular Cardiology Kawarada, O., Waseda, K., Kume, T., Sakata, K., Yock, P. G., Honda, Y., Fitzgerald, P. J. ELSEVIER SCIENCE INC. 2011: E1902–E1902

  View details for Web of Science ID 000291695101905

• Intravascular Ultrasound Results From the NEVO ResElution-I Trial A Randomized, Blinded Comparison of Sirolimus-Eluting NEVO Stents With Paclitaxel-Eluting Taxus Liberte Stents in De Novo Native Coronary Artery Lesions CIRCULATION-CARDIOVASCULAR INTERVENTIONS Otake, H., Honda, Y., Courtney, B. K., Shimohama, T., Ako, J., Waseda, K., Macours, N., Rogers, C., Popma, J. J., Abizaid, A., Ormiston, J. A., Spaulding, C., Cohen, S. A., Fitzgerald, P. J. 2011; 4 (2): 146-U69

  Abstract

  The NEVO sirolimus-eluting stent (NEVO SES) is a novel cobalt-chromium stent combining sirolimus release from reservoirs with bioabsorbable polymer to reduce spatial and temporal polymer exposure. The aim of this study was to assess the arterial response to the NEVO SES in a randomized, blinded comparison versus the surface-coated TAXUS Liberte paclitaxel-eluting stent (TAXUS Liberté PES) in human native coronary lesions using intravascular ultrasound (IVUS).The NEVO ResElution-I IVUS substudy enrolled 100 patients (1:1 randomization). In addition to standard IVUS variables, uniformity of neointimal distribution within stents was evaluated in 3 dimensions by computing mean neointimal thickness within 12 equally spaced radial sectors on every 1-mm cross section along the stented segment. The NEVO SES showed significantly less neointimal proliferation (neointimal obstruction: 5.5±11.0% versus 11.5±9.7%, P=0.02), resulting in less late lumen area loss and smaller maximum cross-sectional narrowing at 6 months. The absolute variability of neointima distribution, assessed by the standard deviation of neointimal thickness within each stent, was significantly reduced with the NEVO SES compared with the TAXUS Liberté PES(0.04±0.04 mm versus 0.10±0.07 mm, P<0.0001). TAXUS Liberté PES showed significantly greater positive vessel remodeling than the NEVO SES (Δvessel volume index: 1.30±1.36 mm(3)/mm versus 0.36±0.63 mm(3)/mm, respectively, P=0.003).The NEVO SES with focal release of sirolimus from reservoirs achieved significantly greater and more consistent suppression of neointimal hyperplasia than the surface-coated TAXUS Liberté PES. This was associated with less positive remodeling and no increased morphological or morphometric abnormalities surrounding the stent or at the stent margins.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00714883.

  View details for DOI 10.1161/CIRCINTERVENTIONS.110.957175

  View details for PubMedID 21386089

• Stent-Assisted Below-the-Ankle Angioplasty for Limb Salvage JOURNAL OF ENDOVASCULAR THERAPY Kawarada, O., Yokoi, Y., Higashimori, A., Waratani, N., Waseda, K., Honda, Y., Fitzgerald, P. J. 2011; 18 (1): 32-42

  Abstract

  To report the clinical outcome of stent-assisted below-the-ankle angioplasty for limb salvage in the setting of critical limb ischemia (CLI).A retrospective single-center study was conducted of 40 critical ischemic limbs in 31 patients (mean age 67 ± 8 years, range 46-94) undergoing below-the-ankle stent-assisted angioplasty between April 2006 and April 2009. Coronary bare metal stents were implanted in cases of failed balloon angioplasty due to significant recoil, flow-limiting dissection, abrupt closure, or repeat early reocclusion.Technical success was 93% (37 limbs), with 3 failures to cross the occlusive lesions. Acute or subacute occlusion was evident in 9 (23%) limbs. The number of runoff vessels increased significantly (p < 0.001) from 0.6 ± 0.8 to 1.8 ± 0.8. During a clinical follow-up of 19.3 ± 11.4 months (range 1-48), the number of repeat interventions for limb salvage was 2.2 ± 1.6 (range 1-9), and a total of 1.6 ± 0.9 stents (range 1-3) were implanted in 8 dorsalis pedis arteries. Acute or subacute stent thrombosis after stenting was observed in 2 of these, and symptomatic in-stent restenosis was detected in 4, which were all treated by repeat intervention. At 6, 12, and 24 months, the freedom from repeat intervention was 39.6%, 39.6%, and 35.2%, respectively. Amputation-free survival was 80.0%, 69.7%, and 62.7%, and limb salvage was 94.7%, 91.4%, and 82.1% at the same time points. Patient survival rates were 77.4%, 71.0%, and 71.0%, respectively. During a mean follow-up of 13.4 ± 12.7 months (range 1-31 months) in 7 of the 8 stented arteries, all examined stents were deformed: stent compression was evident in 5 and stent fracture in 5. However, 7 limbs undergoing dorsalis pedis artery stenting showed complete wound healing; 1 limb had a resistant wound in the heel.Stent-assisted below-the-ankle angioplasty produced a satisfactory clinical outcome but with the need for repeat intervention. Thus, further refinement in endovascular technology is mandatory to reduce the need for repeat interventions and to resolve stent deformity issues.

  View details for Web of Science ID 000287071700005

  View details for PubMedID 21314346

• Six-Month Results of the NEVO RES-ELUTION I (NEVO RES-I) Trial A Randomized, Multicenter Comparison of the NEVO Sirolimus-Eluting Coronary Stent With the TAXUS Liberte Paclitaxel-Eluting Stent in De Novo Native Coronary Artery Lesions CIRCULATION-CARDIOVASCULAR INTERVENTIONS Ormiston, J. A., Abizaid, A., Spertus, J., Fajadet, J., Mauri, L., Schofer, J., Verheye, S., Dens, J., Thuesen, L., Dubois, C., Hoffmann, R., Wijns, W., Fitzgerald, P. J., Popma, J. J., Macours, N., Cebrian, A., Stoll, H., Rogers, C., Spaulding, C. 2010; 3 (6): 556-564

  Abstract

  Drug-eluting stents reduce restenosis and reintervention rates but are complicated by stent thrombosis, which may be related to polymer coating. The NEVO sirolimus-eluting coronary stent (NEVO SES) is designed to improve long-term percutaneous coronary intervention safety by combining sirolimus release from reservoirs with bioabsorbable polymer to reduce spatial and temporal polymer exposure.NEVO ResElution-I was a prospective randomized study in 394 patients with coronary artery disease comparing the NEVO SES with the TAXUS Liberté paclitaxel-eluting coronary stent (TAXUS Liberté PES) stent. The primary end point was in-stent angiographic late loss at 6 months. Six months after percutaneous coronary intervention (PCI), the primary end point favored NEVO SES (0.13±0.31 mm versus 0.36±0.48 mm, P<0.001 for noninferiority and superiority). The study was not powered for clinical end points and showed no significant difference for NEVO SES versus TAXUS Liberté PES: death: 0.5 versus 1.6%, P=0.36; myocardial infarction: 2.0 versus 2.6%, P=0.75; target lesion revascularization: 1.5 versus 3.2%, P=0.33; major adverse cardiac events: 4.0 versus 7.4%, P=0.19. No stent thrombosis was observed with NEVO SES, whereas 2 cases occurred in TAXUS Liberté PES. Intravascular ultrasound showed lower percent volume obstruction for NEVO SES (5.5±11% versus 11.5±9.7%, P=0.016).This trial proved the superiority of NEVO SES over TAXUS Liberté PES for the primary angiographic end point of in-stent late loss. No stent thrombosis occurred in the NEVO SES group.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00606333.

  View details for DOI 10.1161/CIRCINTERVENTIONS.110.946426

  View details for Web of Science ID 000285296100009

  View details for PubMedID 21062998

• Impact of Diabetes Mellitus on Vessel Response in the Drug-Eluting Stent Era: Pooled Volumetric Intravascular Ultrasound Analysis Sakata, K., Waseda, K., Otake, H., Nakatani, D., Kume, T., Yock, P. G., Fitzgerald, P. J., Honda, Y. LIPPINCOTT WILLIAMS & WILKINS. 2010

  View details for Web of Science ID 000208231600752

• Intravascular Ultrasound Comparison of Small Coronary Lesions Between the CardioMind Coronary Stent and Conventional Sirolimus-Eluting Stent Kume, T., Waseda, K., Koo, B., Botelho, R., Verheye, S., Whitbourn, R., Meredith, I., Worthley, S., Hai, K. T., Yock, P. G., Honda, Y., Abizaid, A., Fitzgerald, P. J. LIPPINCOTT WILLIAMS & WILKINS. 2010

  View details for Web of Science ID 000208231601636

• Impact of Mechanical Factor and Biologic Response on Severe In-Stent Lumen Narrowing in Currently Approved Drug-Eluting Stents Sakata, K., Waseda, K., Otake, H., Nakatani, D., Kume, T., Yock, P. G., Fitzgerald, P. J., Honda, Y. LIPPINCOTT WILLIAMS & WILKINS. 2010

  View details for Web of Science ID 000208231602056

• Awareness of Anatomical Variations for Infrapopliteral Intervention CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Kawarada, O., Yokoi, Y., Honda, Y., Fitzgerald, P. J. 2010; 76 (6): 888-894

  Abstract

  With the tremendous advancement and accumulated expertise of endovascular techniques, infrapopliteal intervention is emerging as an alternative therapeutic option to distal bypass surgery for limb salvage in the setting of critical limb ischemia (CLI). However, though much attention has been given to infrapopliteal intervention, the importance of identifying preprocedural infrapopliteal variants remains underappreciated. Becoming more aware of these anatomical variants will translate to increased clinical effectiveness for the patient with infrapopliteal artery disease. Therefore, this review will highlight the fundamental aspects of infrapopliteal variant anatomy for the catheter-based treatment of CLI patients with symptomatic infrapopliteal artery disease.

  View details for DOI 10.1002/ccd.22673

  View details for Web of Science ID 000284676100022

  View details for PubMedID 20578165

• Neointimal hyperplasia in a thin-strut cobalt-chromium stent: Insights from detailed 3-D intravascular ultrasound analysis INTERNATIONAL JOURNAL OF CARDIOLOGY Otake, H., Ako, J., Waseda, K., Sakurai, R., Hirohata, A., Kaneda, H., Hasegawa, T., Honda, Y., Fitzgerald, P. J. 2010; 145 (1): 125-126

  Abstract

  The effect of current generation cobalt-chromium stents on neointimal proliferation has not been fully elucidated. IVUS images of 137 patients treated with a single thin-strut cobalt-chromium stent (Driver: DRI, n=74) or stainless steel stent (Multilink plus: ML, n=63) were selected. Although % neointima volume (neointimal volume divided by stent volume) were comparable, DRI showed significantly smaller maximum %cross-sectional narrowing (%CSN: neointimal area divided by stent area) (P=0.006) with significantly less %CSN>60 (percent stent length with %CSN>60%) than ML (P=0.04). In conclusion, the amount of neointimal hyperplasia after DRI implantation was comparable to that after ML. However, current generation cobalt-chromium DRI may show less and shorter severe narrowing than the stainless steel ML.

  View details for DOI 10.1016/j.ijcard.2009.06.038

  View details for Web of Science ID 000283727000070

  View details for PubMedID 19619904

• Comparison of Vascular Response to Zotarolimus-Eluting Stent vs Paclitaxel-Eluting Stent Implantation - Pooled IVUS Results From the ZoMaxx I and II Trials CIRCULATION JOURNAL Waseda, K., Hasegawa, T., Ako, J., Honda, Y., Grube, E., Whitbourn, R., Ormiston, J., O'Shaughnessy, C. D., Henry, T. D., Overlie, P., Schwartz, L. B., Sudhir, K., Chevalier, B., Gray, W. A., Yeung, A. C., Fitzgerald, P. J. 2010; 74 (11): 2334-2339

  Abstract

  The ZoMaxx I and II trials were randomized controlled studies of the zotarolimus-eluting, phosphorylcholine-coated, TriMaxx stent for the treatment of de novo coronary lesions. The aim of this study was to compare the vessel response between zotarolimus- (ZES) and paclitaxel-eluting stents (PES) using intravascular ultrasound (IVUS).Data were obtained from the ZoMaxx I and II trials, in which a standard IVUS parameter was available in 263 cases (baseline and 9-months follow up). Neointima-free frame ratio was calculated as the number of frames without IVUS-detectable neointima divided by the total number of frames within the stent. While an increase in vessel and plaque was observed in PES from baseline to follow up, there was no significant change in ZES. At follow up, % neointimal obstruction was significantly higher (15.4 ± 8.8% vs 11.3 ± 9.7%), and minimum lumen area at follow up was significantly smaller in ZES compared to PES. However, the incidence of IVUS-defined restenosis (maximum cross-sectional narrowing >60%) was similar in the 2 groups (3.2% vs 6.7%). Neointima-free frame ratio was significantly lower in ZES. There were 5 cases of late incomplete stent apposition in PES and none in ZES.These IVUS results demonstrate a similar incidence of severe narrowing between these 2 DES. There was a moderate increase in neointimal hyperplasia that was associated with a greater extent of neointimal coverage in ZES compared with PES.

  View details for DOI 10.1253/circj.CJ-09-0850

  View details for PubMedID 20890052

• Short- and Mid-Term Intravascular Ultrasound Analysis of the New Zotarolimus-Eluting Stent With Durable Polymer - Results From the RESOLUTE Trial - CIRCULATION JOURNAL Waseda, K., Ako, J., Yamasaki, M., Koizumi, T., Ormiston, J., Worthley, S. G., Whitbourn, R. J., Walters, D. L., Honda, Y., Meredith, I. T., Fitzgerald, P. J. 2010; 74 (10): 2097-2102

  Abstract

  The Resolute stent is a newly developed system with a bio-histocompatible polymer that allows programmed drug delivery up to 180 days. The aim of this intravascular ultrasound (IVUS) analysis was to evaluate the short- (4 months) and mid-term (9 months) efficacy using the Resolute stent.Data were derived from the RESOLUTE trial, a prospective, multicenter, non-randomized, single-arm study to treat de novo native coronary artery lesions. This trial included 2 cohorts with different follow-up periods, and all enrollment patients in this trial received IVUS study. Follow-up IVUS was available in 24 patients (4-month group) and 88 patients (9-month group). Neointimal obstruction (%) was defined as neointimal volume divided by stent volume. Cross-sectional narrowing (CSN, %) was defined as neointimal area divided by stent area. No significant differences in vessel, lumen and stent volume at post-procedure were observed within stented segments between the 4- and 9-month follow-up groups. Although neointimal volume and % neointimal obstruction showed no significant difference between the 2 groups (% neointimal obstruction: 2.2 ± 2.5 vs 3.7 ± 4.0%, P=0.09), maximum CSN was significantly larger in the 9-month group. There were 7 cases of late incomplete stent apposition.These IVUS results showed minimum growth of neointimal proliferation by the Resolute stent throughout the stented segment up to 9 months follow up. 

  View details for DOI 10.1253/circj.CJ-10-0063

  View details for Web of Science ID 000282562300015

  View details for PubMedID 20689221

• Incidence of diffuse and focal chronic stent recoil after implantation of current generation bare-metal and drug-eluting stents INTERNATIONAL JOURNAL OF CARDIOLOGY Koo, B., Waseda, K., Ako, J., Hasegawa, T., Shimohama, T., Nakatani, D., Otake, H., Yamasaki, M., Sakurai, R., Tsujino, I., Honda, Y., Fitzgerald, P. J. 2010; 144 (1): 132-134

  View details for DOI 10.1016/j.ijcard.2008.12.117

  View details for Web of Science ID 000282679000054

  View details for PubMedID 19171393

• Comparison of Everolimus- Versus Paclitaxel-Eluting Stents Implanted in Patients With Diabetes Mellitus as Evaluated by Three-Dimensional Intravascular Ultrasound Analysis AMERICAN JOURNAL OF CARDIOLOGY Otake, H., Ako, J., Yamasaki, M., Tsujino, I., Shimohama, T., Hasegawa, T., Sakurai, R., Waseda, K., Honda, Y., Sood, P., Sudhir, K., Stone, G. W., Fitzgerald, P. J. 2010; 106 (4): 492-497

  Abstract

  Previous reports have shown the advantage of paclitaxel compared to limus-derivative drugs for the treatment of diabetics. A total of 109 diabetics (115 lesions) treated with everolimus-eluting stents (EESs, n = 58) or paclitaxel-eluting stents (PESs, n = 55) undergoing 8 to 9 months of follow-up 3-dimensional intravascular ultrasound examinations were enrolled. In addition to the standard intravascular ultrasound parameters, the percentage of neointimal volume (neointimal volume/stent volume) and maximum percentage of cross-sectional narrowing (neointimal area/stent area) was calculated. EESs showed a lower percentage of neointimal volume (7.2 +/- 7.1% vs 11.7 +/- 11.0%; p = 0.01) and maximum percentage of cross-sectional narrowing (22.5 +/- 16.3% vs 29.4 +/- 19.2%; p = 0.04) than PESs. One case of severe narrowing (lesions with maximum percentage of cross-sectional narrowing >60%) in the EES group developed and 6 cases in the PESs group (p = 0.05). The EESs showed no serial changes for vessel or peri-stent plaque during the follow-up period, and PESs showed significant increases in vessel and peri-stent plaque. PESs showed significantly greater peri-stent plaque increase, with a tendency toward greater vessel enlargement than EESs. Late acquired incomplete stent apposition was observed in 2 PES cases. The major adverse cardiac event rate was comparable < or =2 years. In conclusion, EESs showed greater neointimal suppression without significant vessel expansion than PESs in diabetic patients. In this small cohort, no significant differences were observed in the major adverse cardiac event rate < or =2 years.

  View details for DOI 10.1016/j.amjcard.2010.03.059

  View details for Web of Science ID 000281174500007

  View details for PubMedID 20691306

• Local hemodynamic changes caused by main branch stent implantation and subsequent virtual side branch balloon angioplasty in a representative coronary bifurcation JOURNAL OF APPLIED PHYSIOLOGY Williams, A. R., Koo, B., Gundert, T. J., Fitzgerald, P. J., LaDisa, J. F. 2010; 109 (2): 532-540

  Abstract

  Abnormal blood flow patterns promoting inflammation, cellular proliferation, and thrombosis may be established by local changes in vessel geometry after stent implantation in bifurcation lesions. Our objective was to quantify altered hemodynamics due to main vessel (MV) stenting and subsequent virtual side branch (SB) angioplasty in a coronary bifurcation by using computational fluid dynamics (CFD) analysis. CFD models were generated from representative vascular dimensions and intravascular ultrasound images. Time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and fractional flow reserve (FFR) were quantified. None of the luminal surface was exposed to low TAWSS (<4 dyn/cm(2)) in the nondiseased bifurcation model. MV stenting introduced eccentric areas of low TAWSS along the lateral wall of the MV. Virtual SB angioplasty resulted in a more concentric region of low TAWSS in the MV distal to the carina and along the lateral wall of the SB. The luminal surface exposed to low TAWSS was similar before and after virtual SB angioplasty (rest: 43% vs. 41%; hyperemia: 18% vs. 21%) and primarily due to stent-induced flow alterations. Sites of elevated OSI (>0.1) were minimal but more impacted by general vessel geometry established after MV stenting. FFR measured at a jailed SB was within the normal range despite angiographic stenosis of 54%. These findings indicate that the most commonly used percutaneous interventional strategy for a bifurcation lesion causes abnormal local hemodynamic conditions. These results may partially explain the high clinical event rates in bifurcation lesions.

  View details for DOI 10.1152/japplphysiol.00086.2010

  View details for Web of Science ID 000280758800035

  View details for PubMedID 20507966

• Vascular responses to the multiple overlapped paclitaxel-eluting stents for the treatment of bare-metal in-stent restenotic lesions: angiographic and intravascular ultrasound analysis from the TAXUS-V ISR trial. Cardiovascular revascularization medicine : including molecular interventions Koizumi, T., Fitzgerald, P. J., Honda, Y., Ellis, S. G., Kent, K., Martin, S. L., Brown, C. L., Masud, A. R., Patterson, J. B., Greenberg, J., Friedman, M., Uchida, T., Stone, G. W. 2010; 11 (3): 140-148

  Abstract

  Although effective coverage of coronary diffuse in-stent restenosis (ISR) lesions has warranted the use of multiple drug-eluting stents, the vessel response to paclitaxel-eluting stent (PES) overlap is not fully understood.In the TAXUS-V ISR, i.e., comparing PES versus brachytherapy for the treatment of bare-metal ISR, angiographic analyses at 9-month follow-up were available in 184 ISR lesions treated with PES.In-stent late loss in entire stented segment of multiple PES (n=50) was 0.45+/-0.48 mm, whereas that of single PES (n=134) was 0.3+/-0.47 mm, P=.06. No aneurysm was observed at overlapping PES segments at 9 months. Stent thrombosis up to 9 months was observed in one in each group (single PES, 0.7% vs. multiple PES, 1.8%; P=.47). In a subset of 30 patients, volumetric intravascular ultrasound analysis demonstrated that in-stent net volume obstruction was 12.3+/-12.4 in single PES (n=20) and 14.9+/-9.8 in multiple PES (n=10), P=.60. The changes of vessel and lumen at the overlapping PES segment were similar to those of the adjacent 5-mm segments (Deltaminimum lumen area, mm(2): -1.2+/-1.0, -1.1+/-1.1, -0.8+/-0.9, P=.48; Deltavessel volume, mm(3)/mm: -0.2+/-1.4, 0.1+/-1.7, 0.3+/-1.3, P=.37; proximal, overlap, distal segment, respectively). There was no late incomplete stent apposition at overlapping PES segments.No in vivo evidence of adverse local vessel response at the site of overlapping PES for the treatment of bare-metal ISR has been demonstrated.

  View details for DOI 10.1016/j.carrev.2009.07.004

  View details for PubMedID 20599163

• SPIRIT III JAPAN Versus SPIRIT III USA: A Comparative Intravascular Ultrasound Analysis of the Everolimus-Eluting Stent AMERICAN JOURNAL OF CARDIOLOGY Shimohama, T., Ako, J., Yamasaki, M., Otake, H., Tsujino, I., Hasegawa, T., Nakatani, D., Sakurai, R., Chang, H., Kusano, H., Waseda, K., Honda, Y., Stone, G. W., Saito, S., Fitzgerald, P. J., Sudhir, K. 2010; 106 (1): 13-17

  Abstract

  The aim of this study was to evaluate the vascular response after everolimus-eluting stent (EES) implantation in the SPIRIT III Japan Registry (JAPAN) compared to EES implantation in the SPIRIT III United States (USA) trial using serial intravascular ultrasound (IVUS) analysis. Data were obtained from the JAPAN and the randomized EES arm of the USA trial. Serial (postprocedure and 8-month follow-up) IVUS analysis was available in 199 lesions (JAPAN 82, USA 117) of 183 patients (JAPAN 73, USA 110). Although no difference was observed in vessel size in the reference segment between the 2 groups, postprocedure minimum lumen area and stent volume index were significantly greater in the JAPAN arm (minimum lumen area 5.8 +/- 2.2 vs 5.1 +/- 1.5 mm(2), p = 0.03; stent volume index 7.0 +/- 2.4 vs 6.3 +/- 1.7 mm(3)/mm, p = 0.03). Postprocedure incomplete stent apposition (ISA) was less frequently observed in the JAPAN arm (15.9% vs 33.3%, p = 0.006), possibly related to higher maximum balloon pressure and/or more postdilatation without excess tissue prolapse or edge dissection. In the JAPAN arm, percent neointimal obstruction and maximum percent cross-sectional narrowing were significantly lower at 8-month follow-up (percent neointimal obstruction 3.5 +/- 4.2% vs 6.8 +/- 6.4%, p = 0.0004). Late acquired ISA was infrequent in the 2 arms. In conclusion, comparative IVUS analysis between the JAPAN and USA arms showed more optimal stent deployment in the JAPAN arm as evidenced by the lower incidence of postprocedure ISA and larger minimum lumen area after the procedure. Moreover, there was less neointimal hyperplasia in patients with EES implants from the JAPAN arm compared to the USA arm.

  View details for DOI 10.1016/j.amjcard.2010.02.008

  View details for PubMedID 20609640

• Mechanism of lumen gain with a novel rotational aspiration atherectomy system for peripheral arterial disease: examination by intravascular ultrasound. Cardiovascular revascularization medicine : including molecular interventions Hassan, A. H., Ako, J., Waseda, K., Honda, Y., Zeller, T., Leon, M. B., Fitzgerald, P. J. 2010; 11 (3): 155-158

  Abstract

  The purpose of this study was to evaluate the mechanism of luminal gain with a novel atheroablation system (Pathway PV) for the treatment of peripheral artery disease using intravascular ultrasound (IVUS).The atherectomy system is a rotational atherectomy device, which employs expandable rotating blades with ports that allow flushing and aspiration of the plaque material or thrombus. In this first-in-man clinical study, IVUS analysis was available in 6 patients with lower limb ischemia treated with this device. The treatment results were assessed using IVUS at pre and post atherectomy. Lumen beyond burr size (LBB) was defined as lumen gain divided by the estimated burr area determined by the burr-size.IVUS analysis was available in six patients (superficial femoral artery n=3, popliteal artery n=2, posterior tibial artery n=1). Atheroablation achieved a significant increase in lumen area (LA) (preintervention 3.9+/-0.4, postatheroablation 8.0+/-1.7 mm(2), P<.05), and significant reduction in plaque area (27.5+/-4.0, 23.7+/-3.1 mm(2), P=.001), while there was no change in the vessel area (31.3+/-4.2, 32.1+/-2.8 mm(2), P=.4). LBB was 57.4+/-51.3%.This novel rotational aspiration atherectomy device achieved significant luminal gain by debulking in the absence of vessel stretching. The LA was greater than burr-sized lumen expectancy at cross-sections along the treated segments, suggesting a complimentary role of aspiration in luminal gain in atherosclerotic peripheral artery lesions.

  View details for DOI 10.1016/j.carrev.2009.05.001

  View details for PubMedID 20599165

• A First-in-Man, Randomized, Placebo-Controlled Study to Evaluate the Safety and Feasibility of Autologous Delipidated High-Density Lipoprotein Plasma Infusions in Patients With Acute Coronary Syndrome JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Waksman, R., Torguson, R., Kent, K. M., Pichard, A. D., Suddath, W. O., Satler, L. F., Martin, B. D., Perlman, T. J., Maltais, J. B., Weissman, N. J., Fitzgerald, P. J., Brewer, H. B. 2010; 55 (24): 2727-2735

  Abstract

  This study aimed to determine whether serial autologous infusions of selective high-density lipoprotein (HDL) delipidated plasma are feasible and well tolerated in patients with acute coronary syndrome (ACS).Low HDL is associated with increased risk of cardiovascular disease. Plasma selective delipidation converts alphaHDL to prebeta-like HDL, the most effective form of HDL for lipid removal from arterial plaques.ACS patients undergoing cardiac catheterization with >or=1 nonobstructive native coronary artery atheroma were randomized to either 7 weekly HDL selective delipidated or control plasma apheresis/reinfusions. Patients underwent intravascular ultrasound (IVUS) evaluation of the target vessel during the catheterization for ACS and up to 14 days following the final apheresis/reinfusion session. 2-D gel electrophoresis of delipidated plasmas established successful conversion of alphaHDL to prebeta-like HDL. The trial was complete with 28 patients randomized.All reinfusion sessions were tolerated well by all patients. The levels of prebeta-like HDL and alphaHDL in the delipidated plasma converted from 5.6% to 79.1% and 92.8% to 20.9%, respectively. The IVUS data demonstrated a numeric trend toward regression in the total atheroma volume of -12.18 +/- 36.75 mm(3) in the delipidated group versus an increase of total atheroma volume of 2.80 +/- 21.25 mm(3) in the control group (p = 0.268).In ACS patients, serial autologous infusions of selective HDL delipidated plasma are clinically feasible and well tolerated. This therapy may offer a novel adjunct treatment for patients presenting with ACS. Further study will be needed to determine its ability to reduce clinical cardiovascular events.

  View details for DOI 10.1016/j.jacc.2009.12.067

  View details for Web of Science ID 000278565200005

  View details for PubMedID 20538165

• A randomised comparison of novolimus-eluting and zotarolimus-eluting coronary stents: 9-month follow-up results of the EXCELLA II study EUROINTERVENTION Serruys, P. W., Garg, S., Abizaid, A., Ormiston, J., Windecker, S., Verheye, S., Dubois, C., Stewart, J., Hauptmann, K. E., Schafer, J., Stangl, K., Witzenbichler, B., Wiemer, M., Barbato, E., de Vries, T., den Drijver, A., Otake, H., Meredith, L., Tayloy, S., Fitzgerald, P. 2010; 6 (2): 195-205

  Abstract

  Novolimus, a macrocyclic lactone with anti-proliferative properties, has a similar efficacy to currently available agents; however it requires a lower dose, and less polymer, and is therefore conceivably safer.The EXCELLA II study was a prospective, multicentre, single-blind, non-inferiority clinical trial which randomised 210 patients with a maximum of two de novo coronary artery lesions in two different epicardial vessels in a ratio of 2:1 to treatment with either the Elixir DESyne Novolimus Eluting Coronary Stent System (NES n=139, Elixir Medical, Sunnyvale, CA, USA) or the Endeavor zotarolimus eluting stent (ZES n=71, Medtronic, Santa Rosa, CA, USA). The primary endpoint was in-stent mean late lumen loss (LLL) at 9-months follow-up. In-stent percent volume obstruction (%VO) was measured in a?sub-group of 65 patients having 9-month intravascular ultrasound (IVUS) follow-up. Clinical secondary endpoints included a device orientated composite of cardiac death, target vessel myocardial infarction (MI), and clinically indicated target lesion revascularisation (CI-TLR) assessed at 9-months follow-up. At 9-months, the in-stent LLL was 0.11+/-0.32 mm in the NES arm, as compared to 0.63+/-0.42 mm in the ZES (p<0.0001 non-inferiority, p<0.0001 superiority). In-stent%VO was 4.5+/-5.1% and 20.9+/-11.3% for NES and ZES, respectively (p<0.001). There was no significant difference between stent groups in the device orientated composite endpoint (NES 2.9% vs. ZES 5.6%, -2.8% [-8.8%, 3.3%], p=0.45) or its individual components of cardiac death, target vessel MI and CI-TLR.This non-inferiority randomised study not only met its primary endpoint, but also demonstrated superiority of NES compared to the ZES in terms of in-stent LLL.

  View details for Web of Science ID 000294134200007

  View details for PubMedID 20562069

• Vascular Response to Overlapping Everolimus-Eluting Stents - Comparison With Paclitaxel-Eluting Stents CIRCULATION JOURNAL Otake, H., Honda, Y., Yamasaki, M., Tsujino, I., Shimohama, T., Sakurai, R., Hasegawa, T., Waseda, K., Ako, J., Fitzgerald, P. J. 2010; 74 (5): 1023-1025

  Abstract

  Overlapping drug-eluting stents might be associated with an adverse vessel response because of increased drug/polymer toxicity and lesion rigidity.Lesions treated with overlapping everolimus- (EES=36) or paclitaxel-eluting stents (PES=38) were analyzed for 8-9-months by 3-dimensional intravascular ultrasound. EES were associated with significantly greater neointimal suppression in the single-strut regions than PES, with a similar trend in the overlap region. PES had significant vessel expansion in all regions, whereas there were no changes with EES. Neither stent fracture nor late incomplete stent apposition (LISA) in the overlap region was observed.Overlapping EES appears to be effective without vessel expansion, stent fracture or LISA for up to 8-9 months.

  View details for DOI 10.1253/circj.CJ-10-0052

  View details for Web of Science ID 000277226100033

  View details for PubMedID 20424338

• Anatomic and Functional Evaluation of Bifurcation Lesions Undergoing Percutaneous Coronary Intervention CIRCULATION-CARDIOVASCULAR INTERVENTIONS Koo, B., Waseda, K., Kang, H., Kim, H., Nam, C., Hur, S., Kim, J., Choi, D., Jang, Y., Hahn, J., Gwon, H., Yoon, M., Tahk, S., Chung, W., Cho, Y., Choi, D., Hasegawa, T., Kataoka, T., Oh, S. J., Honda, Y., Fitzgerald, P. J., Fearon, W. F. 2010; 3 (2): 113-119

  Abstract

  We sought to investigate the mechanism of geometric changes after main branch (MB) stent implantation and to identify the predictors of functionally significant "jailed" side branch (SB) lesions.Seventy-seven patients with bifurcation lesions were prospectively enrolled from 8 centers. MB intravascular ultrasound was performed before and after MB stent implantation, and fractional flow reserve was measured in the jailed SB. The vessel volume index of both the proximal and distal MB was increased after stent implantation. The plaque volume index decreased in the proximal MB (9.1+/-3.0 to 8.4+/-2.4 mm(3)/mm, P=0.001), implicating plaque shift, but not in the distal MB (5.4+/-1.8 to 5.3+/-1.7 mm(3)/mm, P=0.227), implicating carina shifting to account for the change in vessel size (N=56). The mean SB fractional flow reserve was 0.71+/-0.20 (N=68) and 43% of the lesions were functionally significant. Binary logistic-regression analysis revealed that preintervention % diameter stenosis of the SB (odds ratio=1.05; 95% CI, 1.01 to 1.09) and the MB minimum lumen diameter located distal to the SB ostium (odds ratio=3.86; 95% CI, 1.03 to 14.43) were independent predictors of functionally significant SB jailing. In patients with > or =75% stenosis and Thrombolysis In Myocardial Infarction grade 3 flow in the SB, no difference in post-stent angiographic and intravascular ultrasound parameters was found between SB lesions with and without functional significance.Both plaque shift from the MB and carina shift contribute to the creation/aggravation of an SB ostial lesion after MB stent implantation. Anatomic evaluation does not reliably predict the functional significance of a jailed SB stenosis.

  View details for DOI 10.1161/CIRCINTERVENTIONS.109.887406

  View details for PubMedID 20407111

• Endovascular detection and removal of radiographic contrast. Cardiovascular revascularization medicine : including molecular interventions Hassan, A. H., Luna, J., Davidson, C. J., Fitzgerald, P. J. 2010; 11 (2): 114-115

  View details for DOI 10.1016/j.carrev.2009.03.003

  View details for PubMedID 20347803

• A Randomized Comparison of the Endeavor Zotarolimus-Eluting Stent Versus the TAXUS Paclitaxel-Eluting Stent in De Novo Native Coronary Lesions 12-Month Outcomes From the ENDEAVOR IV Trial JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Leon, M. B., Mauri, L., Popma, J. J., Cutlip, D. E., Nikolsky, E., O'Shaughnessy, C., Overlie, P. A., McLaurin, B. T., Solomon, S. L., Douglas, J. S., Ball, M. W., Caputo, R. P., Jain, A., Tolleson, T. R., Reen, B. M., Kirtane, A. J., Fitzgerald, P. J., Thompson, K., Kandzari, D. E. 2010; 55 (6): 543-554

  Abstract

  The ENDEAVOR IV (Randomized Comparison of Zotarolimus-Eluting and Paclitaxel-Eluting Stents in Patients with Coronary Artery Disease) trial evaluated the safety and efficacy of the zotarolimus-eluting stent (ZES) compared with the paclitaxel-eluting stent (PES).First-generation drug-eluting stents have reduced angiographic and clinical restenosis, but long-term safety remains controversial. A second-generation drug-eluting stent, which delivers zotarolimus, a potent antiproliferative agent, via a biocompatible phosphorylcholine polymer on a cobalt alloy thin-strut stent has shown promising experimental and early clinical results.This is a prospective, randomized (1:1), single-blind, controlled trial comparing outcomes of patients with single de novo coronary lesions treated with ZES or PES. The primary end point was noninferiority of 9-month target vessel failure defined as cardiac death, myocardial infarction, or target vessel revascularization.Among a total of 1,548 patients assigned to ZES (n = 773) or PES (n = 775), at 9 months, ZES was noninferior to PES with rates of target vessel failure 6.6% versus 7.1%, respectively (p(noninferiority) < or = 0.001). There were fewer periprocedural myocardial infarctions with ZES (0.5% vs. 2.2%; p = 0.007), whereas at 12 months, there were no significant differences between groups in rates of cardiac death, myocardial infarction, target vessel revascularization, or stent thrombosis. Although incidence of 8-month binary angiographic in-segment restenosis was higher in patients treated with ZES versus PES (15.3% vs. 10.4%; p = 0.284), rates of 12-month target lesion revascularization were similar (4.5% vs. 3.2%; p = 0.228), especially in patients without planned angiographic follow-up (3.6% vs. 3.2%; p = 0.756).These findings demonstrate that ZES has similar clinical safety and efficacy compared with PES in simple and medium complexity single de novo coronary lesions. (ENDEAVOR IV Clinical Trial; NCT00217269).

  View details for DOI 10.1016/j.jacc.2009.08.067

  View details for Web of Science ID 000274232000004

  View details for PubMedID 20152559

• Serial Angiography and Intravascular Ultrasound: Results of the SISC Registry (Stents In Small Coronaries) JACC-CARDIOVASCULAR INTERVENTIONS Chamie, D., Costa, J. R., Abizaid, A., Feres, F., Staico, R., Devito, F., Costa, R. A., Abizaid, A., Tanajura, L. F., Sousa, A. G., Fitzgerald, P. J., Whitbourn, R. J., Sousa, J. E. 2010; 3 (2): 191-202

  Abstract

  The aim of this study was to evaluate the novel CardioMind Sparrow (CMS) stent (CardioMind, Inc., Sunnyvale, California) against the Multi-Link Pixel (MLP) stent (Guidant Corp., Santa Clara, California) for small vessel percutaneous coronary intervention (PCI).The CMS consists of a guidewire-based, self-expandable, ultra-thin nitinol stent with smaller profile and improved flexibility and deliverability. The performance of this novel device against a standard balloon-expandable stent for small vessel PCI has not been determined.Twenty-one patients were treated with the CMS and compared with 30 patients treated with MLP. Only single de novo lesions <14 mm in length, in native vessels of 2.0 to 2.5 mm were included. The primary goal was the comparison of quantitative coronary angiography lumen loss and intravascular ultrasound intimal hyperplasia (IH) formation between groups at 6 months.Clinical characteristics were similar between groups. The CMS cohort had smaller vessels (2.20 +/- 0.20 mm vs. 2.43 +/- 0.16 mm, p < 0.0001) and shorter lesions (10.86 +/- 3.19 mm vs. 13.12 +/- 2.79 mm, p = 0.0091). Six-month late loss was significantly lower among CMS cohort (0.73 +/- 0.57 mm vs. 1.11 +/- 0.72 mm, p = 0.038). By intravascular ultrasound, 6-month IH volume was similar between groups (1.45 +/- 0.46 mm(3)/mm vs. 1.65 +/- 1.02 mm(3)/mm, p = 0.50). However, CMS presented a mean 13.39% expansion of its volumes, resulting in a significantly lower percentage of IH volumetric obstruction (31.94 +/- 8.19% vs. 39.90 +/- 4.72%, p = 0.0005).Despite producing similar amounts of IH volume, the self-expanding CMS stent presented chronic expansion of its volumes, better accommodating the neoformed tissue and resulting in significantly lower late loss and percent of IH volumetric obstruction in comparison with the MLP stent.

  View details for DOI 10.1016/j.jcin.2009.11.014

  View details for Web of Science ID 000278972000009

  View details for PubMedID 20170877

• Sirolimus-eluting stent implantation in small coronary arteries: A three dimensional intravascular ultrasound study from the SIRIUS trial INTERNATIONAL JOURNAL OF CARDIOLOGY Kaneda, H., Ako, J., Terashima, M., Morino, Y., Honda, Y., Yock, P. G., Leon, M. B., Moses, J. W., Fitzgerald, P. J. 2010; 138 (2): 126-130

  Abstract

  To assess the efficacy of the sirolimus-eluting stent when implanted in smaller caliber vessels using three-dimensional intravascular ultrasound (IVUS) analysis.One hundred and twenty-three patients (69 sirolimus-coated Bx Velocity and 54 control) who underwent successful three-dimensional IVUS at follow up comprised this IVUS substudy from the SIRIUS (SIRolImUS-coated Bx Velocity stent in the treatment of patients with de novo coronary artery lesions) population. To evaluate the impact of vessel size, 2 groups were created using QCA reference vessel diameter (RVD; large vessel group: RVD>/=2.75 mm and small vessel group: RVD<2.75 mm).Sirolimus-eluting stents significantly reduced neointimal hyperplasia by the same relative magnitude within the stent in small vessels as well as in large vessels. Although sirolimus-eluting stents had favorable effects on lumen area at stent edges in larger vessels, the effect was less in smaller vessels, especially at the proximal edge. IVUS-detected adverse vessel response, such as late-acquired incomplete apposition, did not increase in smaller vessels even with relatively higher dose exposure.Sirolimus-eluting stents showed inhibition of neointimal hyperplasia in small vessels compared to bare metal stents with no increase of vascular complications.

  View details for DOI 10.1016/j.ijcard.2008.08.006

  View details for Web of Science ID 000273613300004

  View details for PubMedID 18804877

• Stent Expansion as a Mechanical Parameter to Predict Late Stent Patency Back to the Basics JACC-CARDIOVASCULAR INTERVENTIONS Honda, Y., Fitzgerald, P. J. 2009; 2 (12): 1276-1278

  View details for DOI 10.1016/j.jcin.2009.10.013

  View details for Web of Science ID 000275914400015

  View details for PubMedID 20129556

• Preprocedural Inflammation Does Not Affect Neointimal Hyperplasia following Everolimus-Eluting Stent Implantation JOURNAL OF INVASIVE CARDIOLOGY Nakatani, D., Ako, J., Yamasaki, M., Shimohama, T., Hasegawa, T., Otake, H., Waseda, K., Tsujino, I., Sakurai, R., Koo, B., Chang, H., Yock, P. G., Sudhir, K., Pierson, W., Stone, G. W., Saito, S., Honda, Y., Fitzgerald, P. J. 2009; 21 (12): 613-617

  Abstract

  Preprocedual C-reactive protein (CRP) has been reported to correlate with in-stent restenosis following bare-metal stent implantation. The aim of this study was to investigate the impact of preprocedural inflammation on neointimal hyperplasia assessed by intravascular ultrasound (IVUS) following everolimus-eluting stent (EES) implantation.We identified 134 patients meeting the following criteria: 1) patients treated with EES; 2) those with stable or unstable angina; and 3) patients available for high-sensitivity (hs)-CRP before the procedure and volumetric IVUS analysis at follow up. We divided the patients into two groups on the basis of hs-CRP levels (< 3 or > or = 3 mg/L) before the procedure and compared IVUS parameters. Volume index (volume/length) was calculated for vessel (VVI), plaque (PVI), neointima (NIV), stent (SVI), and lumen (LVI). Percent neointimal volume (%NIV) was calculated as (NIV/SVI) x 100. Cross-sectional narrowing (CSN) was defined as neointimal area divided by stent area (%).There was no significant difference in VVI, PVI, or LVI at either baseline or 8-month follow up between the two groups. At 8-month follow up, there was also no significant difference in %NIV (4.93 +/- 5.66% vs. 4.98 +/- 5.25% p = 0.959) and maximum %CSN (16.81 +/- 13.62% vs. 18.14 +/- 13.91%; p = 0.608) as well as VVI, PVI, and LVI between the two groups. Furthermore, hs-CRP did not correlate with %NIV (r = 0.044; p = 0.610) and maximum %CSN (r = 0.086, p = 0.321) at follow up. There was no significant difference in incidence of late-acquired incomplete stent apposition between the two groups (1.2% vs. 0%; p = 0.512).Our results suggest that preprocedural inflammation does not affect neointimal hyperplasia following EES implantation.

  View details for PubMedID 19966361

• Late-acquired incomplete stent apposition: morphologic characterization. Cardiovascular revascularization medicine : including molecular interventions Hur, S., Ako, J., Honda, Y., Sudhir, K., Fitzgerald, P. J. 2009; 10 (4): 236-246

  Abstract

  Incomplete stent apposition (ISA) is a lack of contact between stents and the underlying vessel wall, best described by intravascular ultrasound (IVUS). Late acquired incomplete apposition, defined as complete stent apposition at the time of procedure but ISA at follow-up, is an unusual IVUS finding reported in intracoronary brachytherapy, bare-metal stent (BMS), and drug-eluting stent (DES) implantation. Late-acquired ISA is observed relatively more frequently with DES implantation compared with BMS implantation. Possible mechanisms of this phenomenon include focal/extensive vascular remodeling and dissolution of thrombus. While there are conflicting reports regarding the possible impact of this IVUS finding on clinical outcomes, recent reports of DES have suggested its possible association with late adverse cardiac events including late stent thrombosis. In this paper, we review the incidence, location, underlying pathology, and possible clinical sequelae of late-acquired ISA, primarily focusing on that of DES.

  View details for DOI 10.1016/j.carrev.2009.02.002

  View details for PubMedID 19815171

• Clinical and Angiographic Results With the Next-Generation Resolute Stent System A Prospective, Multicenter, First-in-Human Trial JACC-CARDIOVASCULAR INTERVENTIONS Meredith, I. T., Worthley, S., Whitbourn, R., Walters, D. L., McClean, D., Horrigan, M., Popma, J. J., Cutlip, D. E., DePaoli, A., Negoita, M., Fitzgerald, P. J. 2009; 2 (10): 977-985

  Abstract

  The RESOLUTE trial examined the safety and efficacy of a next-generation zotarolimus-eluting coronary stent, Resolute (Medtronic CardioVascular Inc., Santa Rosa, California).Revascularization benefits associated with current drug-eluting stents are often diminished in the presence of complex coronary lesions and in certain patient cohorts. Resolute uses a new proprietary polymer coating that extends the duration of drug delivery to match the longer healing duration often experienced in more complex cases.The RESOLUTE trial was a prospective, nonrandomized, multicenter study of the Resolute stent in 139 patients with de novo coronary lesions with reference vessel diameters > or =2.5 and < or =3.5 mm and lesion length > or =14 and < or =27 mm. The primary end point was 9-month in-stent late lumen loss by quantitative coronary angiography. Secondary end points included major adverse cardiac events (MACE) at 30 days, 6, 9, and 12 months; acute device, lesion, and procedure success; and 9-month target vessel failure (TVF), target lesion revascularization (TLR), stent thrombosis, neointimal hyperplastic (NIH) volume, and percent NIH volume obstruction.The 9-month in-stent late lumen loss was 0.22 +/- 0.27 mm. Cumulative MACE were 4.3%, 4.3%, 7.2%, and 8.7% at 30 days, 6, 9, and 12 months, respectively. Acute lesion, procedure, and device success rates were 100.0%, 95.7%, and 99.3%, respectively. At 9 months, TLR was 0.0%, TVF was 6.5%, stent thrombosis was 0.0%, NIH volume was 6.55 +/- 7.83 mm(3), and percent NIH volume obstruction was 3.73 +/- 4.05%.In this feasibility study, the Resolute stent demonstrated low in-stent late lumen loss, minimal neointimal hyperplastic ingrowth, low TLR, no stent thrombosis, and acceptable TVF and MACE. (The RESOLUTE Clinical Trial; NCT00248079).

  View details for DOI 10.1016/j.jcin.2009.07.007

  View details for Web of Science ID 000278971800012

  View details for PubMedID 19850258

• Clinical and Angiographic Outcomes in Diabetics From the ENDEAVOR IV Trial Randomized Comparison of Zotarolimus- and Paclitaxel-Eluting Stents in Patients With Coronary Artery Disease JACC-CARDIOVASCULAR INTERVENTIONS Kirtane, A. J., Patel, R., O'Shaughnessy, C., Overlie, P., McLaurin, B., Solomon, S., Mauri, L., Fitzgerald, P., Popma, J. J., Kandzari, D. E., Leon, M. B. 2009; 2 (10): 967-976

  Abstract

  The aim of this study was to examine outcomes related to the use of the Endeavor zotarolimus-eluting stent (ZES) (Medtronic CardioVascular, Santa Rosa, California) compared with the TAXUS paclitaxel-eluting stent (PES) (Boston Scientific Corp., Natick, Massachusetts) in the 477 patients with diabetes mellitus (DM) enrolled in the randomized ENDEAVOR IV (Randomized Comparison of Zotarolimus- and Paclitaxel-Eluting Stents in Patients with Coronary Artery Disease) trial.Percutaneous coronary intervention (PCI) in diabetic patients is associated with increased rates of restenosis-related end points compared with PCI in nondiabetic patients. Although ZES has been associated with similar clinical efficacy compared with PES in the overall trial population of the ENDEAVOR IV trial, whether these results are maintained in the higher-risk restenosis subgroup of patients with DM has not been determined.Clinical and angiographic outcomes were compared according to randomized treatment assignment to either ZES or PES.Baseline characteristics were similar among ZES (n = 241) and PES (n = 236) diabetic patients, with slightly longer lesion lengths in PES-treated patients (12.9 mm vs. 14.0 mm, p = 0.041). Among the 86 DM patients assigned to routine angiographic follow-up (18% of the overall DM cohort), in-stent percent diameter stenosis at 8 months was greater among ZES-treated patients (32.9 vs. 21.1, p = 0.023), with a trend toward higher in-stent late loss. One-year clinical outcomes were similar among DM patients treated with either ZES or PES (target vessel failure: 8.6% vs. 10.8%, p = 0.53; target lesion revascularization: 6.9% vs. 5.8%, p = 0.70; target vessel revascularization: 8.6% vs. 9.4%, p = 0.87). There were no significant interactions between DM status and stent type with respect to the outcomes measured, and the relative efficacy/safety of ZES and PES were similar among insulin- and noninsulin-requiring subgroups.One-year clinical outcomes were similar among DM patients treated with ZES and PES in the ENDEAVOR IV trial. These findings parallel the overall trial results, which demonstrated similar efficacy and safety of ZES and PES for single de novo coronary lesions.

  View details for DOI 10.1016/j.jcin.2009.08.008

  View details for Web of Science ID 000278971800011

  View details for PubMedID 19850257

• Impact of Lumen Narrowing Within Everolimus-Eluting Stents on Downstream Vessel Segments 21st Annual Transcatheter Cardiovascular Therapeutics Conference Sakata, K., Ako, J., Waseda, K., Yamasaki, M., Tsujino, I., Shimohama, T., Otake, H., Hasegawa, T., Sakurai, R., Yock, P. G., Sudhir, K., Kusano, H., Stone, G. W., Fitzgerald, P. J., Honda, Y. EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2009: 18D–18D

  View details for Web of Science ID 000269981600063

• Six-Month Volumetric IVUS Analysis in Diabetic and non-Diabetic Patients Treated with The Custom NX Biolimus-A9 Eluting stent: A Pooled Analysis of CUSTOM II and III Trials 21st Annual Transcatheter Cardiovascular Therapeutics Conference Shimohama, T., Ako, J., Nakatani, D., Waseda, K., Chang, H., Yock, P. G., Honda, Y., DeBruyne, B., Grube, E., Fitzgerald, P. J. EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2009: 63D–63D

  View details for Web of Science ID 000269981600179

• Intravascular Ultrasound Results From the ENDEAVOR IV Trial Randomized Comparison Between Zotarolimus- and Paclitaxel-Eluting Stents in Patients With Coronary Artery Disease JACC-CARDIOVASCULAR INTERVENTIONS Waseda, K., Miyazawa, A., Ako, J., Hasegawa, T., Tsujino, I., Sakurai, R., Yock, P. G., Honda, Y., Kandzari, D. E., Leon, M. B., Fitzgerald, P. J. 2009; 2 (8): 779-784

  Abstract

  The aim of this study was to compare the vessel response between zotarolimus-eluting stents (ZES) and paclitaxel-eluting stents (PES) using intravascular ultrasound.The ENDEAVOR IV (Randomized Comparison of Zotarolimus- and Paclitaxel-Eluting Stents in Patients With Coronary Artery Disease) trial was a randomized controlled study of zotarolimus-eluting, phosphorylcholine-coated, cobalt-alloy stents for the treatment of de novo coronary lesions compared with using PES for the same treatment.Data were obtained from patients with serial (baseline and 8-months follow-up) intravascular ultrasound analysis available (n = 198). Volumetric analysis was performed for vessel, lumen, plaque, stent, and neointima. Cross-sectional narrowing (given as percentage) was defined as neointimal area divided by stent area. Neointima-free frame ratio was calculated as the number of frames without intravascular ultrasound-detectable neointima divided by the total number of frames within the stent. Subsegment analysis was performed at every matched 1-mm subsegment throughout the stent.At follow-up, the ZES group showed significantly greater percentage of neointimal obstruction (16.6 +/- 12.0% vs. 9.9 +/- 8.9%, p < 0.01) and maximum cross-sectional narrowing (31.8 +/- 16.1% vs. 25.2 +/- 14.9%, p < 0.01) with smaller minimum lumen area than the PES group did. However, the incidence of maximum cross-sectional narrowing >50% was similar in the 2 groups. Neointima-free frame ratio was significantly lower in the ZES group. In overall analysis, whereas the PES group showed positive remodeling during follow-up (13.7 +/- 4.2 mm(3)/mm to 14.3 +/- 4.3 mm(3)/mm), the ZES group showed no significant difference (12.7 +/- 3.6 mm(3)/mm to 12.9 +/- 3.5 mm(3)/mm). In subsegment analysis, significant focal positive vessel remodeling was observed in 5% of ZES and 25% of PES cases (p < 0.05).There were different global and focal vessel responses for ZES and PES. Both drug-eluting stents showed a similar incidence of lesions with severe narrowing despite ZES having a moderate increase in neointimal hyperplasia compared with neointimal hyperplasia in PES. There was a relatively lower neointima-free frame ratio in ZES, suggesting a greater extent of neointimal coverage. (The ENDEAVOR IV Clinical Trial: A Trial of a Coronary Stent System in Coronary Artery Lesions; NCT00217269).

  View details for DOI 10.1016/j.jcin.2009.05.015

  View details for Web of Science ID 000278971500011

  View details for PubMedID 19695548

• A Novel Technique for Endovascular Detection and Removal of Radiographic Contrast during Angiography JOURNAL OF INVASIVE CARDIOLOGY Chang, H., Hassan, A. H., Kim, Y. L., Lloyd, L. J., Koo, B., Ako, J., Honda, Y., Davidson, C. J., Fitzgerald, P. J. 2009; 21 (7): 314-318

  Abstract

  This study aims at in-vitro validation of the principles of endovascular detection of contrast medium and assessing the feasibility of in-vivo detection and removal of contrast during angiography.Contrast-induced nephropathy is a growing concern in current percutaneous interventions with increasing lesion complexity and patient comorbidity. To address this clinical problem, a novel method of endovascular detection and automatic removal of contrast has been developed, and is comprised of a catheter-based system with a reflectance-type optical sensor.Blood samples were obtained from ovine subjects to characterize the optical response of blood by measuring the reflectance spectrum at varying levels of hematocrit diluted by a contrast agent. The results from the in-vitro test were implemented into an in-vivo system. An aspiration catheter equipped with a fiberoptic sensor was inserted into the coronary sinus (CS) of 5 canines. Contrast was administered through the coronary artery and reflectance signals were recorded at the CS. The removal rate was analyzed through 20 specimen collections.A proportional relationship was found between hematocrit and reflectance intensity in in-vitro test. Upon in-vivo detection of contrast, the sensor signal showed a 79.5 +/- 9.9% (n = 33) drop from the pre-injection baseline. This was highly reproducible and beyond the noise level of baseline, (2.5 +/- 0.9%), enabling automatic activation of the aspiration system. The signal duration was 12.2 +/- 3.7 seconds. The removal rate of contrast was 59.3 +/- 11%.The present study validated the principles of endovascular contrast detection and demonstrated the feasibility of an in-vivo, catheter-based removal of contrast using reflectance technology.

  View details for PubMedID 19571339

• Distribution pattern of neointimal hyperplasia following sirolimus-eluting stent implantation assessed by 3-dimensional intravascular ultrasound INTERNATIONAL JOURNAL OF CARDIOLOGY Kaneda, H., Ako, J., Terashima, M., Waseda, K., Yock, P. G., Fitzgerald, P. J. 2009; 135 (2): 243-245

  Abstract

  Sirolimus-eluting stents (SES) have been shown to reduce intimal hyperplasia (IH) within the stent. Although angiographic studies have suggested focal distribution of IH, these data are limited by its spatial resolution and the minimal amount of IH. Therefore, the exact distribution pattern of SES IH remains unclear. Ninety-six SIRIUS trial patients who underwent SES (51) or bare metal stent (45) implantation and three-dimensional IVUS at 8 months follow-up were enrolled. Neointimal area (stent-lumen area) was obtained at every 0.5-mm interval throughout the stented segment. The length of each stent with IVUS-detectable neointima was determined and divided by the stented length in each case to normalize the data. Even with IVUS, IH was detectable in very limited SES stented segments (median 8% of total stented length) compared to the diffuse nature of IH within BMS with only 5 stented lesions having segments free from IH. In 25% (13 of 51) of patients, no IH was detectable within whole SES stented segments. In conclusion, SES has reduced not only the total amount of IH, but also limited the distribution. These data suggest that local conditions (heterogeneity of biological responses of particular plaques, pharmacokinetics, or their combination) may play a role in IH following SES implantation.

  View details for DOI 10.1016/j.ijcard.2008.01.054

  View details for Web of Science ID 000266884600020

  View details for PubMedID 18571251

• A Prospective, Multicenter, Randomized Trial to Assess Efficacy of Pioglitazone on In-Stent Neointimal Suppression in Type 2 Diabetes POPPS (Prevention of In-Stent Neointimal Proliferation by Pioglitazone Study) JACC-CARDIOVASCULAR INTERVENTIONS Takagi, T., Okura, H., Kobayashi, Y., Kataoka, T., Taguchi, H., Toda, I., Tamita, K., Yamamuro, A., Sakanoue, Y., Ito, A., Yanagi, S., Shimeno, K., Waseda, K., Yamasaki, M., Fitzgerald, P. J., Ikeno, F., Honda, Y., Yoshiyama, M., Yoshikawa, J. 2009; 2 (6): 524-531

  Abstract

  The aim of this study was to clarify whether pioglitazone suppresses in-stent neointimal proliferation and reduces restenosis and target lesion revascularization (TLR) after percutaneous coronary intervention (PCI).Previous single-center studies have demonstrated the anti-restenotic effect of a peroxisome proliferator-activated receptor gamma agonist, pioglitazone, after PCI.A total of 97 patients with type 2 diabetes mellitus (T2DM) undergoing PCI (bare-metal stents only) were enrolled. After PCI, patients were randomly assigned to either the pioglitazone group (n = 48) or the control group (n = 49). Angiographical and intravascular ultrasound (IVUS) imaging were performed at baseline and repeated at 6-month follow-up. Primary end points included angiographical restenosis and TLR at 6 months follow-up. Secondary end point was in-stent neointimal volume by IVUS.Baseline glucose level and glycosylated hemoglobin (HbA1c) level were similar between the pioglitazone group and the control group. Angiographical restenosis rate was 17% in the pioglitazone group and 35% in control group (p = 0.06). The TLR was significantly lower in pioglitazone group than in control group (12.5% vs. 29.8%, p = 0.04). By IVUS (n = 56), in-stent neointimal volume at 6 months showed a trend toward smaller in the pioglitazone group than in the control group (48.0 +/- 30.2 mm(3) vs. 62.7 +/- 29.0 mm(3), p = 0.07). Neointimal index (neointimal volume/stent volume x 100) was significantly smaller in the pioglitazone group than in the control group (31.1 +/- 14.3% vs. 40.5 +/- 12.9%, p = 0.01).Pioglitazone treatment might suppress in-stent neointimal proliferation and reduce incidence of TLR after PCI in patients with T2DM.

  View details for DOI 10.1016/j.jcin.2009.04.007

  View details for Web of Science ID 000278971200008

  View details for PubMedID 19539256

• Intraoperative Fluorescence Imaging System for On-Site Assessment of Off-Pump Coronary Artery Bypass Graft JACC-CARDIOVASCULAR IMAGING Waseda, K., Ako, J., Hasegawa, T., Shimada, Y., Ikeno, F., Ishikawa, T., Demura, Y., Hatada, K., Yock, P. G., Honda, Y., Fitzgerald, P. J., Takahashi, M. 2009; 2 (5): 604-612

  Abstract

  The aim of this study was to evaluate the intraoperative fluorescence imaging (IFI) system in the real-time assessment of graft patency during off-pump coronary artery bypass graft.Intraoperative fluorescence imaging is an intraoperative angiography-like imaging modality using fluorescent indocyanine green excited with laser light. Recently, assessment of graft patency using the IFI system was introduced into clinical use. The feasibility and efficacy of IFI technology in off-pump coronary artery bypass graft has not been systematically compared with other conventional diagnostic modalities.Patients undergoing off-pump coronary artery bypass graft received IFI analysis, intraoperative transit time flowmetry, and postoperative X-ray angiography. In off-line IFI analysis, the graft washout was classified based on the number of heartbeats required for indocyanine green washout: fast washout (15 beats).A total of 507 grafts in 137 patients received IFI analysis. Of all the IFI analyses, 379 (75%) grafts were visualized clearly up to the distal anastomosis. With regard to anastomosis location, anterior location was associated with a higher percentage of fully analyzable images (90%). More than 80% of images were analyzable, irrespective of graft type. Six grafts with acceptable transit time flowmetry results were diagnosed with graft failure by IFI, which required on-site graft revision. All revised grafts' patency was confirmed by post-operative X-ray angiography. Conversely, 21 grafts with unsatisfactory transit time flowmetry results demonstrated acceptable patency with IFI. Graft revision was considered unnecessary in these grafts, and 20 grafts (95%) were patent by post-operative X-ray angiography. Compared with slow washout, fast washout was associated with a higher preoperative ejection fraction, use of internal mammary artery grafts, and anterior anastomosis location.The IFI system enables on-site assessment of graft patency, providing both morphologic and functional information. This technique may help reduce procedure-related, early graft failures in off-pump bypass patients.

  View details for DOI 10.1016/j.jcmg.2008.12.028

  View details for Web of Science ID 000287653200013

  View details for PubMedID 19442948

• Local Determinants of Thrombus Formation Following Sirolimus-Eluting Stent Implantation Assessed by Optical Coherence Tomography JACC-CARDIOVASCULAR INTERVENTIONS Otake, H., Shite, J., Ako, J., Shinke, T., Tanino, Y., Ogasawara, D., Sawada, T., Miyoshi, N., Kato, H., Koo, B., Honda, Y., Fitzgerald, P. J., Hirata, K. 2009; 2 (5): 459-466

  Abstract

  We conducted this study to assess the prevalence and determinants of subclinical thrombus after sirolimus-eluting stent (SES) implantation.Angioscopic analyses have demonstrated the presence of thrombus is more common than the clinical incidence of SES thrombosis.Fifty-three patients (53 lesions) underwent 6-month follow-up optical coherence tomography. A stent eccentricity index ([SEI] minimum/maximum stent diameter) was determined in each cross section. To evaluate unevenness of neointimal thickness, a neointimal unevenness score ([NUS] maximum neointimal thickness in the cross section/average neointimal thickness of the same cross section) was calculated for each cross section. Average SEI and NUS were calculated for each stent. Major adverse cardiac events were defined as a composite of death, myocardial infarction, and target vessel revascularization.Fourteen cases of thrombus (26%) were detected by optical coherence tomography (thrombus: n = 14 vs. nonthrombus: n = 39). The percentage of thrombus was associated with longer stents (36.4 +/- 20.2 mm vs. 25.1 +/- 9.8 mm; p = 0.008), a larger number of uncovered struts (17 +/- 16 vs. 8 +/- 11; p = 0.03), smaller average SEI (0.89 +/- 0.04 vs. 0.92 +/- 0.03; p = 0.001), and greater average NUS (2.22 +/- 0.24 vs. 2.00 +/- 0.33; p = 0.03). A significant relationship existed between average SEI and average NUS (p < 0.0001, R = 0.68), and between average SEI and the number of uncovered struts (p < 0.0006, R = 0.46). There was no significant difference in major adverse cardiac events during follow-up (median: 485 days, 7.1% vs. 12.8%; p > 0.99).Longer stents and greater asymmetric stent expansion may be important determinants of thrombus formation after SES implantation. In this small cohort, the presence of thrombus did not increase the risk of major adverse cardiac events.

  View details for DOI 10.1016/j.jcin.2009.03.003

  View details for Web of Science ID 000278971000014

  View details for PubMedID 19463471

• Whole blood reflectance for assessment of hematologic condition and detection of angiographic contrast media APPLIED OPTICS Chang, H., Kim, Y. L., Hassan, A., Fitzgerald, P. J. 2009; 48 (13): 2435-2443

  Abstract

  We present simple whole blood reflectance analyses in the range 500-900 nm, using intact whole blood to simultaneously quantify hematocrit and oxygen saturation from a single spectral reading. We applied these results for the development of an intravascular catheter-based reflectance sensing system to detect and remove contrast media injected during angiography so as to reduce the risk of complications associated with the injected contrast media. We further tested the practicality of the optical detection of angiographic contrast media in a pilot animal study in vivo. We successfully demonstrated the feasibility of real-time in vivo contrast detection and removal during angiography. Our simple method for the detection and removal of angiographic contrast media will facilitate the development of intravascular optical sensing systems.

  View details for PubMedID 19412200

• A Randomized Controlled Trial of Angiography Versus Intravascular Ultrasound-Directed Bare-Metal Coronary Stent Placement (The AVID Trial) CIRCULATION-CARDIOVASCULAR INTERVENTIONS Russo, R. J., Silva, P. D., Teirstein, P. S., Attubato, M. J., Davidson, C. J., DeFranco, A. C., Fitzgerald, P. J., Goldberg, S. L., Hermiller, J. B., Leon, M. B., Ling, F. S., Lucisano, J. E., Schatz, R. A., Wong, S. C., Weissman, N. J., Zientek, D. M. 2009; 2 (2): 113-U56

  Abstract

  AVID (Angiography Versus Intravascular ultrasound-Directed stent placement) is a multicenter, randomized controlled trial designed to assess the effect of intravascular ultrasound (IVUS)-directed stent placement on the 12-month rate of target lesion revascularization (TLR).After elective coronary stent placement and an optimal angiographic result (<10% stenosis), 800 patients were randomized to Angiography- or IVUS-directed therapy. Blinded IVUS was performed in the Angiography group without further therapy. In the IVUS group, IVUS criteria for optimal stent placement (<10% area stenosis, apposition, and absence of dissection) were applied. Final minimum stent area was 6.90+/-2.43 mm(2) in the Angiography group and 7.55+/-2.82 mm(2) in the IVUS group (P=0.001). In the IVUS group, only 37% with inadequate expansion (<90%) received further therapy. The 12-month TLR rate was 12.0% in the Angiography group and 8.1% in the IVUS group (P=0.08, 95% confidence level [CI], [-8.3% to 0.5%]). When vessels with a distal reference diameter <2.5 mm by core laboratory angiography measurement were excluded from analysis, the 12-month TLR rate was 10.1% in the Angiography group and 4.3% in the IVUS group (P=0.01, 95% CI, [-10.6% to -1.2%]). With a pre-stent angiographic stenosis of > or =70%, the TLR rate was lower in the IVUS group compared with the Angiography group (3.1% versus 14.2%; P=0.002; 95% CI, [-18.4% to -4.2%]).IVUS-directed bare-metal stent placement results in larger acute stent dimensions without an increase in complications and a significantly lower 12-month TLR rate for vessels > or =2.5 mm by angiography and for vessels with high-grade pre-stent stenosis. However, for the entire sample analyzed on an intention-to-treat basis, IVUS-directed bare-metal stent placement does not significantly reduce the 12-month TLR rate when compared with stent placement guided by angiography alone. In addition, IVUS evaluation of adequate stent expansion is underutilized by experienced operators.

  View details for DOI 10.1161/CIRCINTERVENTIONS.108.778647

  View details for Web of Science ID 000276051600006

  View details for PubMedID 20031704

• 9-Month Clinical, Angiographic, and Intravascular Ultrasound Results of a Prospective Evaluation of the Axxess Self-Expanding Biolimus A9-Eluting Stent in Coronary Bifurcation Lesions JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Verheye, S., Agostoni, P., Dubois, C. L., Dens, J., Ormiston, J., Worthley, S., Trauthen, B., Hasegawa, T., Koo, B., Fitzgerald, P. J., Mehran, R., Lansky, A. J. 2009; 53 (12): 1031-1039

  Abstract

  This study sought to assess the safety and performance of the Axxess (Devax Inc., Lake Forest, California) self-expanding drug-eluting stent in coronary bifurcation lesions.Percutaneous treatment of coronary bifurcations is a predictor of adverse late outcomes, in part because of the lack of dedicated devices.Patients with de novo bifurcation lesions were prospectively enrolled in a multicenter study. The Axxess stent was deployed at the level of the carina followed by additional sirolimus-eluting stents in the distal parent vessel (PV) and/or side branch (SB). All patients underwent clinical follow-up at 9 months; 150 were to receive control angiography and 76 were to receive intravascular ultrasound. The primary end point was the rate of major adverse cardiac events (MACE): a composite of death, myocardial infarction (MI), and target lesion revascularization (TLR). Secondary end points included in-segment restenosis, late loss, and percent neointimal volume obstruction.Overall, 302 patients were treated with 299 Axxess stents (99%). Additional stenting of 1 branch was performed in 21.7% of patients (17.7% PV, 4% SB), and of both branches in 64.7%. At 9 months, 99.3% of patients returned for clinical follow-up; from the angiographic and IVUS substudies, 93.3% and 89.4% returned. The cumulative 9-month MACE rate was 7.7% (0.7% death, 3.3% non-Q-wave MI, 1.0% Q-wave MI, 4.3% TLR). Subacute and late stent thrombosis occurred in 0.7% and 0.3% of patients. Total restenosis was 6.4% (3.6% PV, 4.3% SB), late loss was 0.20 +/- 0.41 mm in the PV and 0.17 +/- 0.34 mm in the SB. In the Axxess stent segment, percent neointimal volume obstruction was 4.3 +/- 5.2%.This prospective multicenter study confirms the safety and performance of the Axxess stent in bifurcation lesions. (Drug-Eluting Stent Intervention for Treating Side Branches Effectively; ACTRN12606000259549).

  View details for DOI 10.1016/j.jacc.2008.12.012

  View details for Web of Science ID 000264316900003

  View details for PubMedID 19298915

• Relative Dose and Vascular Response After Drug-Eluting Stent Implantation: A Dosimetric 3D-Intravascular Ultrasound Study 58th Annual Scientific Session of the American-College-of-Cardiology Waseda, K., Hasegawa, T., Nakatani, D., Koo, B., Otake, H., Shimohama, T., Chang, H., Ako, J., Yock, P. G., Fitzgerald, P. J., Honda, Y. ELSEVIER SCIENCE INC. 2009: A9–A9

  View details for Web of Science ID 000263864200036

• Comparison of Vessel Response Between Zotarolimus- and Paclitaxel-eluting Stents: Global and Focal Vessel Responses as Assessed by Serial Intravascular Ultrasound 58th Annual Scientific Session of the American-College-of-Cardiology Waseda, K., Miyazawa, A., Hasegawa, T., Tsujino, I., Sakurai, R., Ako, J., Yock, P. G., Kandzari, D. E., Leon, M. B., Fitzgerald, P. J., Honda, Y. ELSEVIER SCIENCE INC. 2009: A12–A12

  View details for Web of Science ID 000263864200048

• The GENESIS (Randomized, Multicenter Study of the Pimecrolimus-Eluting and Pimecrolimus/Paclitaxel-Eluting Coronary Stent System in Patients with De Novo Lesions of the Native Coronary Arteries) Trial JACC-CARDIOVASCULAR INTERVENTIONS Verheye, S., Agostoni, P., Dawkins, K. D., Dens, J., Rutsch, W., Carrie, D., Schofer, J., Lotan, C., Dubois, C. L., Cohen, S. A., Fitzgerald, P. J., Lansky, A. J. 2009; 2 (3): 205-214

  Abstract

  The aim of this study was to compare, in a randomized multicenter trial, paclitaxel-eluting stents (CoStar, Conor Medsystems, Menlo Park, California) versus pimecrolimus-eluting stents (Corio, Conor Medsystems) versus stents with dual elution of both drugs (SymBio, Conor Medsystems) in native coronary arteries.The CoStar cobalt-chromium reservoir-based stent platform, eluting paclitaxel in a controlled way via a bioresorbable polymer, reduces restenosis versus its respective bare-metal stent. The reservoir system allows the use of other drugs targeted to different mechanisms involved in the process of vascular restenosis and simultaneous loading of multiple, synergistic drugs.Patients with single de novo lesions were asymmetrically randomized to 1 of the 3 types of stent (1:2:2). Six-month coronary angiography was planned in all. The primary analysis was a noninferiority test for the primary end point of 6-month angiographic in-stent late lumen loss of Corio versus CoStar and SymBio versus CoStar. Secondary end points included binary angiographic restenosis and major adverse clinical events (cardiac death, myocardial infarction, target vessel revascularization).The trial was prematurely suspended after 246 patients were enrolled (planned enrollment: 375 patients): 49 patients received CoStar, 97 received SymBio, and 100 received Corio. In-stent late loss was significantly reduced with CoStar versus either SymBio or Corio (0.58 +/- 0.58 mm vs. 0.96 +/- 0.73 mm and 0.58 +/- 0.58 mm vs. 1.40 +/- 0.67 mm, p < 0.001 for both comparisons). Binary in-stent restenosis rates were, 7.1%, 20%, and 40.9%, respectively (p < 0.001 for both comparisons); 6-month major adverse cardiac event rates were, 2.0%, 14.4%, and 39.0%, respectively (p < 0.001 for both comparisons).Stents eluting pimecrolimus or the dual combination of pimecrolimus and paclitaxel failed to show angiographic noninferiority when compared with paclitaxel-eluting stents. (A Randomized, Multi-Center Study of the Pimecrolimus-Eluting and Pimecrolimus/Paclitaxel-Eluting Coronary Stent Systems; NCT00322569).

  View details for DOI 10.1016/j.jcin.2008.12.011

  View details for Web of Science ID 000278970500007

  View details for PubMedID 19463427

• Intraoperative assessment of coronary grafts with fluorescent angiography. BMJ case reports Waseda, K., Fitzgerald, P. J., Takahashi, M. 2009; 2009: bcr2006109421-?

  View details for DOI 10.1136/bcr.2006.109421

  View details for PubMedID 21687223

• Analysis of Left Main Coronary Artery Bifurcation Lesions Treated With Biolimus-Eluting DEVAX AXXESS Plus Nitinol Self-Expanding Stent: Intravascular Ultrasound Results of the AXXENT Trial CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Hasegawa, T., Ako, J., Koo, B., Miyazawa, A., Sakurai, R., Chang, H., Dens, J., Verheye, S., Grube, E., Honda, Y., Fitzgerald, P. J. 2009; 73 (1): 34-41

  Abstract

  To assess the efficacy of the AXXESS stent on the treatment of left main coronary artery (LMCA) bifurcation lesions using IVUS.The treatment of LMCA bifurcation lesions remains challenging even with the use of drug-eluting stents. The AXXESS system is a biolimus A9-eluting self-expanding stent, dedicated to the treatment of bifurcation lesions.Data were obtained from the AXXENT trial, a prospective, single-arm, multicenter study designed to evaluate the efficacy of the AXXESS stent on the treatment of LMCA bifurcation lesions. IVUS was available in 26 cases at 6-months follow-up. Volumetric and cross-sectional analyses within the AXXESS stent, and cross-sectional analyses at the ostia of left anterior descending (LAD) and left circumflex coronary arteries (LCX) were performed.Within the AXXESS stent, percent neointimal volume obstruction was (3.0 +/- 4.1)% with a minimal lumen area of 10.3 +/- 2.6 mm(2). AXXESS stent volume showed an 12.4% increase at follow-up compared with postprocedure (P = 0.04). Lumen area was significantly smaller in the LCX ostium compared with the LAD ostium at follow-up (3.6 +/- 1.3 mm(2) vs. 5.5 +/- 2.0 mm(2), P = 0.0112). There was greater neointimal formation in the LCX ostium compared with the LAD ostium (1.37 +/- 1.20 mm(2) vs. 0.30 +/- 0.36 mm(2), P = 0.0003).The AXXESS stent in the LMCA showed enlargement through 6-months follow-up and significant neointimal suppression. Greater neointimal formation and relatively inadequate stent expansion may contribute to luminal narrowing in the LCX ostium.

  View details for DOI 10.1002/ccd.21765

  View details for PubMedID 19089934

• Intravascular Ultrasound Analysis of Small-Vessel Lesions Treated with Novel Ultra-Low Profile, Guidewire-Based Self-Expanding Stent System JOURNAL OF INVASIVE CARDIOLOGY Koo, B., Yamasaki, M., Ako, J., Waseda, K., Honda, Y., Fitzgerald, P. J., Abizaid, A., Whitbourn, R. J. 2008; 20 (12): 647-650

  Abstract

  This study was performed to evaluate the long-term vascular response of the first series of patients treated by a novel ultra-low profile, guidewire-based self-expanding stent system (Sparrow stent) using serial intravascular ultrasound (IVUS).The long-term vascular response and stent geometry change after self-expanding stent implantation are not known.The CARE 1 trial was a single-arm feasibility study of the Sparrow stent in patients with small-vessel disease. Twenty patients were included in this prospective IVUS study, and serial volumetric IVUS analysis was performed after stent implantation and at 6- and 12-months follow up.Serial volumetric IVUS analysis was available in 13 cases between post-procedure and 6- month follow up and in 6 cases between 6- and 12-month follow up. At 6-month follow up, % neointimal volume was 34 +/- 9%. Stent volume index was increased by 13% , negating part of the luminal loss due to neointimal hyperplasia. There was no correlation between % neointimal volume index and % change in stent volume index (p = 0.7). No additional change occurred in any IVUS parameter between 6 and 12 months after stent implantation.In this small feasibility study, the use of a novel guidewire-based self-expanding stent was associated with the same degree of neointimal response as that seen with conventional bare-metal stents. Through serial analyses, the IVUS parameters of both the stent and the vessel remained unchanged beyond 6 months after stent implantation.

  View details for Web of Science ID 000207739500007

  View details for PubMedID 19057028

• Serial angiographic and intravascular ultrasound analysis of late stent strut fracture of sirolimus-eluting stents in native coronary arteries INTERNATIONAL JOURNAL OF CARDIOLOGY Yamada, K. P., Koizumi, T., Yamaguchi, H., Kaneda, H., Bonneau, H. N., Honda, Y., Fitzgerald, P. J. 2008; 130 (2): 255-259

  Abstract

  Stent fracture in sirolimus-eluting stents (SES) has been reported to be associated with late adverse events. However, a suitable method to diagnose stent fracture is not fully elucidated.One hundred and two consecutive SES implantations were performed in 83 lesions in 56 patients and underwent serial angiography with intravascular ultrasound (IVUS) at baseline and at 6 months follow-up. Angiographic stent strut fracture was defined as stent bending with separation of stent struts. Angiographic hinge movement was defined as stent shaft deviation without separation of stent struts. IVUS stent strut dissociation was defined as the disappearance of stent struts in more than one cross-sectional image which were previously visualized at baseline.By angiography, no cases of stent fracture were detected at 6 months. One case of angiographic hinge movement was found at 12 months. However, three instances of stent fracture were detected by IVUS at 6 months. One case of stent fracture showed a patent lumen area at 6 months but subsequently developed late stent restenosis at 12 months. The other two cases were associated with in-stent restenosis at 6 months.Compared to angiography, IVUS can more reliably detect stent fracture during follow-up evaluation.

  View details for DOI 10.1016/j.ijcard.2007.08.082

  View details for Web of Science ID 000260757600021

  View details for PubMedID 18096257

• Impact of Additional Ballooning on Plaque Prolapse After Stent Implantation in Patients With Acute Myocardial Infarction JACC-CARDIOVASCULAR IMAGING Kaneda, H., Honda, Y., Fitzgerald, P. J. 2008; 1 (6): 815-815

  View details for DOI 10.1016/j.jcmg.2008.09.003

  View details for Web of Science ID 000207650100017

  View details for PubMedID 19356522

• SPIRIT III Japan: Eight-Month IVUS Analysis of Everolimus-Elurting Stent Compared to the US Arm 81st Annual Scientific Session of the American-Heart-Association Shimohama, T., Otake, H., Ako, J., Yamasaki, M., Tsujino, I., Waseda, K., Hasegawa, T., Sakurai, R., Nakatani, D., Chang, H., Yock, P. G., Honda, Y., Kusano, H., Sudhir, K., Saito, S., Stone, G. W., Fitzgerald, P. J. LIPPINCOTT WILLIAMS & WILKINS. 2008: S1044–S1044

  View details for Web of Science ID 000262104504150

• Six-Month IVUS Analysis of Pimecrolimus and Dual Pimecrolimus/Paclitaxel Eluting Stents: Results of the GENESIS Trial 20th Annual Transcatheter Cardiovascular Therapeutics Conference Shimohama, T., Tsujino, I., Ako, J., Hasegawa, T., Chang, H., Yock, P. G., Honda, Y., Dawkins, K. D., Verheye, S., Fitzgerald, P. J. EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2008: 139I–140I

  View details for Web of Science ID 000260094700336

• Comparison of Vascular Response to Zotarolimus-Eluting Stent Versus Paclitaxel-Eluting Stent Implantation: IVUS Results From the ENDEAVOR IV Trial 20th Annual Transcatheter Cardiovascular Therapeutics Conference Waseda, K., Miyazawa, A., Hasegawa, T., Tsujino, I., Sakurai, R., Ako, J., Yock, P. G., Honda, Y., Kandzari, D. E., Leon, M. B., Fitzgerald, P. J. EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2008: 146I–146I

  View details for Web of Science ID 000260094700353

• IVUS Analysis in the SPIRIT III Japan Treated with XIENCE (TM) V Everolimus-Eluting Stent Compared to the SPIRIT III US Arm 20th Annual Transcatheter Cardiovascular Therapeutics Conference Shimohama, T., Otake, H., Ako, J., Yamasaki, M., Tsujino, I., Waseda, K., Hasegawa, T., Sakurai, R., Nakatani, D., Chang, H., Yock, P. G., Honda, Y., Kusano, H., Sudhir, K., Saito, S., Stone, G. W., Fitzgerald, P. J. EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2008: 138I–138I

  View details for Web of Science ID 000260094700332

• Evaluation of vessel response to percutaneous coronary intervention REVISTA ESPANOLA DE CARDIOLOGIA Fitzgerald, P. J., Otake, H. 2008; 61 (10): 1001-1006

  View details for Web of Science ID 000259574100001

  View details for PubMedID 18817674

• A Randomized, Controlled, Multicenter Trial to Evaluate the Safety and Efficacy of Zotarolimus-Versus Paclitaxel-Eluting Stents in De Novo Occlusive Lesions in Coronary Arteries The ZoMaxx I Trial JACC-CARDIOVASCULAR INTERVENTIONS Chevalier, B., Di Mario, C., Neumann, F., Ribichini, F., Urban, P., Popma, J. J., Fitzgerald, P. J., Cutlip, D. E., Williams, D. O., Ormiston, J., Grube, E., Whitbourn, R., Schwartz, L. B. 2008; 1 (5): 524-532

  Abstract

  A novel zotarolimus-eluting coronary stent system (ZoMaxx, Abbott Laboratories, Abbott Park, Illinois) was compared with a paclitaxel-eluting coronary stent (Taxus Express2) in a randomized trial of percutaneous intervention for de novo coronary artery stenosis. The primary end point was defined as noninferiority of in-segment late lumen loss after 9 months.The ZoMaxx stent system elutes 10 microg/mm zotarolimus using a phosphorylcholine polymer loaded onto a novel stainless steel stent platform containing a 0.0007-inch inner layer of tantalum.Twenty-nine investigative sites in Europe, Australia, and New Zealand enrolled 401 patients, 396 of whom received a study stent.After 9 months, late lumen loss was significantly greater in the ZoMaxx group (in-stent 0.67 +/- 0.57 mm vs. 0.45 +/- 0.48 mm; p < 0.001; in-segment 0.43 +/- 0.60 mm vs. 0.25 +/- 0. 45 mm; p = 0.003), resulting in significantly higher rates of >50% angiographic restenosis (in-stent 12.9% vs. 5.7%; p = 0.03; in-segment 16.5% vs. 6.9%; p = 0.007). The upper bound of the 95% confidence interval on the difference in in-segment late lumen loss between the 2 treatment groups (0.27 mm) exceeded the 0.25 mm value pre-specified for noninferiority. There were no significant differences between ZoMaxx and Taxus-treated groups with respect to target lesion revascularization (8.0% vs. 4.1%; p = 0.14), major adverse cardiac events (12.6% vs. 9.6%; p = 0.43), or stent thrombosis (0.5% in both groups).After 9 months, the ZoMaxx stent showed less neointimal inhibition than the Taxus stent, as shown by higher in-stent late loss and restenosis by qualitative coronary angiography.

  View details for DOI 10.1016/j.jcin.2008.08.010

  View details for Web of Science ID 000207586300010

  View details for PubMedID 19463354

• Two-Year Intravascular Ultrasound Observations in Diabetic Patients Treated with Single and Double Dose Sirolimus-Eluting Stents: Results of the Double Dose Diabetes (3D) Study JOURNAL OF INVASIVE CARDIOLOGY Hur, S., Ako, J., Shimada, Y., Tsujino, I., Hassan, A. H., Abizaid, A., Shiran, A., Lewis, B. S., Guagliumi, G., Cohen, S. A., Honda, Y., Fitzgerald, P. J., Eduardo Sousa, J. 2008; 20 (8): 411-416

  Abstract

  Diabetes has been reported as an independent predictor of restenosis after drug-eluting stent implantation. The purpose of this study was to assess the long-term impact of increased drug dose in sirolimus-eluting stents (SES) on neointimal hyperplasia (NIH) in diabetic patients using volumetric intravascular ultrasound analysis.The 3D trial is a multicenter, prospective, randomized, feasibility study of double-dose (280 microg/cm2) or conventional single-dose (140 microg/cm2) SES for the treatment of de novo coronary lesions in diabetic patients. To evaluate long-term efficacy, complete serial volumetric analyses (baseline, 6-month and 2-year follow up) were performed in 39 diabetic patients (17 single-dose, 22 double-dose). Each volume was divided by stent length to acquire volume index, expressed as mm3/mm. Percent neointimal volume was calculated as (neointimal volume/stent volume) x 100 at follow up.Volumetric analysis showed similar results over time between the 2 stent groups (p = NS for all). At 2-year follow up, minimal increases in NIH area and percent NIH were observed in both groups, which translated into a decrease in lumen volume index compared to baseline (p < 0.05 for all). No late-acquired incomplete stent apposition was observed in either group.The current single dose of sirolimus in SES is effective in inhibiting NIH in diabetic patients up to 2 years. In this patient subset, double-dose SES did not confer additional NIH suppression at 2-year follow up compared to conventional single-dose SES.

  View details for Web of Science ID 000207739100009

  View details for PubMedID 18688066

• Thoracoscopic ligation versus coil occlusion for patent ductus arteriosus: A matched cohort study of outcomes and cost SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES Dutta, S., Mihailovic, A., Benson, L., Kantor, P. F., Fitzgerald, P. G., Walton, J. M., Langer, J. C., Cameron, B. H. 2008; 22 (7): 1643-1648

  Abstract

  Coil occlusion (CO) and video-assisted thoracoscopic surgery (VATS) have both emerged as minimal access therapies for patent ductus arteriosus (PDA). These techniques have not previously been statistically compared.Twenty-four consecutive children undergoing VATS for PDA were each retrospectively matched by PDA diameter and child weight to two children undergoing CO (total 48) during the same time period. The two modalities were compared with respect to outcome and cost. Statistical analysis was performed using a Student's t-test and Mantel-Haenszel relative risk. Cost analysis from an institutional perspective was used to compare resource consumption.Mean PDA diameter was 3.6 +/- 1.2 mm in both groups. Mean age and weight for VATS and CO children were 2.7 and 2.9 yrs and 13.2 and 13.1 kg, respectively. Mean surgical times were 94 +/- 34 min for VATS and 50 +/- 23 min for CO (p < 0.0001). Mean length of stay was 1.6 +/- 0.2 days for VATS and 0.6 +/- 0.2 days for CO (Mantel-Haenszel RR (95% CI) = 0.15 [0.07, 0.29], p < 0.0001). Mean fluoroscopy time with CO was 13 +/- 7 min. No VATS or CO children required conversion to open surgical ligation. Two children in each arm (8% VATS, 4% CO) required indefinite antibiotic endarteritis prophylaxis for a persistent shunt. The cost per child was C$ 4282.80 (Canadian dollars) for VATS and C$ 3958.08 for CO.VATS is as efficacious for PDA closure as CO but requires longer surgical times and lengths of stay. Costs for each procedure are similar.

  View details for DOI 10.1007/s00464-007-9674-1

  View details for Web of Science ID 000256530000019

  View details for PubMedID 18027029

• Clinical and Angiographic Outcomes in Diabetic Patients following Single or Multivessel Stenting in the COSTAR II Randomized Trial JOURNAL OF INVASIVE CARDIOLOGY Kereiakes, D. J., Petersen, J. L., Batchelor, W. B., Fitzgerald, P. J., Mehran, R., Lansky, A., Tsujino, I., Schofer, J., Dubois, C., Verheye, S., Cristea, E., Garg, J., Wijns, W., Krucoff, M. W. 2008; 20 (7): 335-341

  Abstract

  Percutaneous coronary intervention (PCI) is associated with increased clinical and angiographic restenosis in diabetic patients. Stent-based elution of paclitaxel from a biostable polymer reduces restenosis and major adverse cardiovascular events (MACE) when compared with bare-metal stent deployment. The safety and efficacy of paclitaxel elution from a bioresorbable polymer has not been studied in diabetic patients.Patients (n = 1700) with single- or multivessel coronary disease were randomized (3:2) to receive the CoStar or Taxus stent. All patients had glycolated hemoglobin (HbA1c) obtained at enrollment.Medically-treated diabetes was present in 469 patients (117 insulin-treated) and 77 patients had elevated HbA1c > 6.5% in the absence of previously diagnosed diabetes. MACE were increased in diabetics and were greatest in those requiring insulin. Elevated HbA1c, in the absence of diagnosed diabetes, was not associated with adverse outcomes. MACE (8 months) in the diabetic cohort trended lower with Taxus versus CoStar (10.9 vs. 14.4%, respectively; p = 0.271) due to a reduction in target vessel revascularization. Late lumen loss in-segment (9 months) was reduced by Taxus compared to CoStar (0.20 vs. 0.52 mm, respectively; p < 0.05).Diabetes is associated with adverse outcomes following stent deployment. Taxus stents improved angiographic outcomes with a trend toward improved clinical outcomes when compared with CoStar stents following PCI in diabetic patients. As a measure of preprocedural glycemic control, the HbA1c level was weakly correlated with outcomes.

  View details for Web of Science ID 000207739000006

  View details for PubMedID 18599890

• Novel guidewire-based stent-delivery system: Examination by intravascular ultrasound CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Yamasaki, M., Ako, J., Honda, Y., Hassan, A., Koo, B., Abizaid, A., Fitzgerald, P., Whitbourn, R. 2008; 72 (1): 47-51

  Abstract

  This report describes the first-in-man experience with a novel 0.014-in. guidewire-based, self-expanding stent delivery system designed for small or tortuous coronary arteries that may be difficult to access with conventional stent-delivery systems.

  View details for DOI 10.1002/ccd.21562

  View details for Web of Science ID 000257306300010

  View details for PubMedID 18412249

• Comparison of an everolimus-eluting stent and a paclitaxel-eluting stent in patients with coronary artery disease - A randomized trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Stone, G. W., Midei, M., Newman, W., Sanz, M., Hermiller, J. B., Williams, J., Farhat, N., Mahaffey, K. W., Cutlip, D. E., Fitzgerald, P. J., Sood, P., Su, X., Lansky, A. J. 2008; 299 (16): 1903-1913

  Abstract

  A thin, cobalt-chromium stent eluting the antiproliferative agent everolimus from a nonadhesive, durable fluoropolymer has shown promise in preliminary studies in improving clinical and angiographic outcomes in patients with coronary artery disease.To evaluate the safety and efficacy of an everolimus-eluting stent compared with a widely used paclitaxel-eluting stent. Design, Setting, andThe SPIRIT III trial, a prospective, randomized, single-blind, controlled trial enrolling patients at 65 academic and community-based US institutions between June 22, 2005, and March 15, 2006. Patients were 1002 men and women undergoing percutaneous coronary intervention in lesions 28 mm or less in length and with reference vessel diameter between 2.5 and 3.75 mm. Angiographic follow-up was prespecified at 8 months in 564 patients and completed in 436 patients. Clinical follow-up was performed at 1, 6, 9, and 12 months.Patients were randomized 2:1 to receive the everolimus-eluting stent (n = 669) or the paclitaxel-eluting stent (n = 333).The primary end point was noninferiority or superiority of angiographic in-segment late loss. The major secondary end point was noninferiority assessment of target vessel failure events (cardiac death, myocardial infarction, or target vessel revascularization) at 9 months. An additional secondary end point was evaluation of major adverse cardiac events (cardiac death, myocardial infarction, or target lesion revascularization) at 9 and 12 months.Angiographic in-segment late loss was significantly less in the everolimus-eluting stent group compared with the paclitaxel group (mean, 0.14 [SD, 0.41] mm vs 0.28 [SD, 0.48] mm; difference, -0.14 [95% CI, -0.23 to -0.05]; P < or = .004). The everolimus stent was noninferior to the paclitaxel stent for target vessel failure at 9 months (7.2% vs 9.0%, respectively; difference, -1.9% [95% CI, -5.6% to 1.8%]; relative risk, 0.79 [95% CI, 0.51 to 1.23]; P < .001). The everolimus stent compared with the paclitaxel stent resulted in significant reductions in composite major adverse cardiac events both at 9 months (4.6% vs 8.1%; relative risk, 0.56 [95% CI, 0.34 to 0.94]; P = .03) and at 1 year (6.0% vs 10.3%; relative risk, 0.58 [95% CI, 0.37 to 0.90]; P = .02), due to fewer myocardial infarctions and target lesion revascularization procedures.In this large-scale, prospective randomized trial, an everolimus-eluting stent compared with a paclitaxel-eluting stent resulted in reduced angiographic late loss, noninferior rates of target vessel failure, and fewer major adverse cardiac events during 1 year of follow-up.clinicaltrials.gov Identifier: NCT00180479.

  View details for Web of Science ID 000255163800024

  View details for PubMedID 18430909

• A novel bioresorbable polymer paclitaxel-eluting stent for the treatment of single and multivessel coronary disease JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Krucoff, M. W., Kereiakes, D. J., Petersen, J. L., Mehran, R., Hasselblad, V., Lansky, A. J., Fitzgerald, P. J., Garg, J., Turco, M. A., Simonton, C. A., Verheye, S., Dubois, C. L., Gammon, R., Batchelor, W. B., O'Shaughnessy, C. D., Hermiller, J. B., Schofer, J., Buchbinder, M., Wijns, W. 2008; 51 (16): 1543-1552

  Abstract

  The aim was to compare safety and effectiveness of the CoStar drug-eluting stent (DES) (Conor MedSystems, Menlo Park, California) with those of the Taxus DES (Boston Scientific, Maple Grove, Minnesota) in de novo single- and multivessel percutaneous coronary intervention (PCI).Paclitaxel elution from a stent coated with biostable polymer (Taxus) reduces restenosis after PCI. The CoStar DES is a novel stent with laser-cut reservoirs containing bioresorbable polymer loaded to elute 10 microg paclitaxel/30 days.Patients undergoing PCI for a single target lesion per vessel in up to 3 native epicardial vessels were randomly assigned 3:2 to CoStar or Taxus. Primary end point was 8-month major adverse cardiac events (MACE), defined as adjudicated death, myocardial infarction (MI), or clinically driven target vessel revascularization (TVR). Protocol-specified 9-month angiographic follow-up included 457 vessels in 286 patients.Of the 1,700 patients enrolled, 1,675 (98.5%) were evaluable (CoStar = 989; Taxus = 686), including 1,330 (79%) single-vessel and 345 (21%) multivessel PCI. The MACE rate at 8 months was 11.0% for CoStar versus 6.9% for Taxus (p < 0.005), including adjudicated death (0.5% vs. 0.7%, respectively), MI (3.4% vs. 2.4%, respectively), and TVR (8.1% vs. 4.3%, respectively). Per-vessel 9-month in-segment late loss was 0.49 mm with CoStar and 0.18 mm with Taxus (p < 0.0001). Findings were consistent across pre-specified subgroups.The CoStar DES is not noninferior to the Taxus DES based on per-patient clinical and per-vessel angiographic analyses. The relative benefit of Taxus is primarily attributable to reduction in TVR. Follow-up to 9 months showed no apparent difference in death, MI, or stent thrombosis rates.

  View details for DOI 10.1016/j.jacc.2008.01.020

  View details for Web of Science ID 000255353200003

  View details for PubMedID 18420096

• Frontiers in intravascular Imaging technologies CIRCULATION Honda, Y., Fitzgerald, P. J. 2008; 117 (15): 2024-2037

  View details for DOI 10.1161/CIRCULATIONAHA.105.551804

  View details for Web of Science ID 000254966200014

  View details for PubMedID 18413510

• In Vivo Comparison Between Optical Coherence Tomography and Intravascular Ultrasound for Detecting Small Degrees of In-Stent Neointima After Stent Implantation JACC-CARDIOVASCULAR INTERVENTIONS Suzuki, Y., Ikeno, F., Koizumi, T., Tio, F., Yeung, A. C., Yock, P. G., Fitzgerald, P. J., Fearon, W. F. 2008; 1 (2): 168-173

  Abstract

  The purpose of this study was to evaluate optical coherence tomography (OCT) for detecting small degrees of in-stent neointima (ISN) after stent implantation compared with intravascular ultrasound (IVUS).The importance of detecting neointimal coverage of stent struts has grown with the appreciation of the increased risk for late stent thrombosis after drug-eluting stent (DES) implantation. Intravascular ultrasound, the current standard for evaluating the status of DES, lacks the resolution to detect the initial neointimal coverage. Optical coherence tomography has greater resolution but has not yet been compared with IVUS in vivo with histological correlation for validation.Intravascular ultrasound and OCT were performed with motorized pullback imaging in 6 pigs across 33 stents, 1 month after implantation. Each pig was euthanized, and histological measurements of vessel, stent, and lumen dimensions were performed in 3 sections of each stent. A small degree of ISN was defined as occupying <30% of the stent area measured with histology. The IVUS, OCT, and histological assessment of ISN were compared in matched cross-sections of the stents with a small degree of ISN.Eleven stents had a small degree of ISN (average ISN area: 1.26 +/- 0.46 mm(2), and percent area obstruction: 21.4 +/- 5.2%). Compared with histology, the diagnostic accuracy of OCT (area under the receiver operating characteristic curve [AUC] = 0.967, 95% confidence interval [CI] 0.914 to 1.019) was higher than that of IVUS (AUC = 0.781, 95% CI 0.621 to 0.838).Optical coherence tomography detects smaller degrees of ISN more accurately than IVUS and might be a useful method for identifying neointimal coverage of stent struts after DES implantation.

  View details for DOI 10.1016/j.jcin.2007.12.007

  View details for PubMedID 19463295

• Effect of lumen narrowing within sirolimus-eluting stents on proximal and distal vessel segments CIRCULATION JOURNAL Waseda, K., Ako, J., Kaneda, H., Miyazawa, A., Shimada, Y., Morino, Y., Honda, Y., Fitzgerald, P. J. 2008; 72 (4): 534-537

  Abstract

  Flow dynamics and shear stress may influence downstream vessel segments. The aim of this study was to investigate the potential impact of lumen narrowing within sirolimus-eluting stents (SES) on vessel response at adjacent reference sites.In 135 patients after SES implantation, minimal lumen area (MLA) within the stent and average lumen area at distal or proximal adjacent reference segments (5 mm) were obtained at baseline and follow up. In the smaller in-stent MLA group (MLA <3 mm(2)), lumen area decreased significantly at the distal reference compared with the larger in-stent MLA group (MLA >or=3 mm(2)), although no significant difference was seen at the proximal reference.In-stent lumen patency may influence vascular responses at adjacent reference segments after SES implantation.

  View details for Web of Science ID 000254468800005

  View details for PubMedID 18362421

• Overlapping drug-eluting stents: Intravascular ultrasound insights from cobalt chromium stent with antiproliferative for restenosis II (COSTAR II) trial 57th Annual Scientific Session of the American-College-of-Cardiology Ako, J., Tsujino, I., Koizumi, T., Waseda, K., Honda, Y., Yock, P. G., Kereiakes, D. J., Krucoff, M. W., Fitzgerald, P. J. ELSEVIER SCIENCE INC. 2008: B41–B41

  View details for Web of Science ID 000253997200167

• Impact of late incomplete stent apposition after sirolimus-eluting stent implantation on 4-year clinical events: intravascular ultrasound analysis from the multicentre, randomised, RAVEL, E-SIRIUS and SIRIUS trials 79th Annual Scientific Session of the American-Heart-Association Hoffmann, R., Morice, M., Moses, J. W., Fitzgerald, P. J., Mauri, L., Breithardt, G., Schofer, J., Serruys, P. W., Stoll, H., Leon, M. B. BMJ PUBLISHING GROUP. 2008: 322–28

  Abstract

  The impact of incomplete stent apposition (ISA) after drug-eluting stent implantation determined by intravascular ultrasound (IVUS) on late clinical events is not well defined.To evaluate the clinical impact of ISA after sirolimus-eluting stent (SES) placement during a follow-up period of 4 years.Pooled analysis from the RAVEL, E-SIRIUS and SIRIUS trials, three randomised, multicentre studies comparing SES and bare-metal stents (BMS).IVUS at angiographic follow-up was available in 325 patients (SES: n = 180, BMS: n = 145). IVUS images were reviewed for the presence of ISA defined as one or more unapposed stent struts. Clinical follow-up was available for a 4-year period in all patients. Frequency, predictors and clinical sequel of ISA at follow-up after SES and BMS implantation were determined.ISA at follow-up was more common after SES (n = 45 (25%)) than after BMS (n = 12 (8.3%), p<0.001). Canadian Cardiology Society class III or IV angina at stent implantation (odds ratio (OR) = 4.69, 95% CI 2.15 to 10.23, p<0.001) and absence of diabetes (OR = 3.42, 95% CI 1.05 to 11.1, p = 0.041) were predictors of ISA at follow-up after SES placement. Rate of myocardial infarction tended to be slightly higher for ISA than for non-ISA patients. When SES patients only were considered, major adverse cardiac event free survival at 4 years was identical for those with and without ISA at follow-up (11.1% vs 16.3%, p = 0.48).ISA at follow-up is more common after SES implantation than after BMS implantation. Considering the current very sensitive IVUS definition, ISA appears to be an IVUS finding without significant impact on the incidence of major adverse cardiac events even during long-term follow-up.

  View details for DOI 10.1136/hrt.2007.120154

  View details for Web of Science ID 000253193700017

  View details for PubMedID 17761505

• Coronary risk factors and coronary atheroma burden at severely narrowing segments INTERNATIONAL JOURNAL OF CARDIOLOGY Kaneda, H., Kataoka, T., Ako, J., Honda, Y., Yock, P. G., Fitzgerald, P. J. 2008; 124 (1): 124-126

  Abstract

  While only few data exist correlating cardiovascular risk factors with volumetric measurements of coronary atheroma burden in patients with coronary artery disease, a recent report using intravascular ultrasound (IVUS) demonstrated independent predictors of atherosclerotic burden in a native coronary artery with relatively mild narrowing (20-50% diameter stenosis by visual estimation). The purpose of this study was to examine whether cardiovascular risk factors can predict atherosclerotic burden at severely narrowing segments (>50% diameter stenosis).Patients who met the criteria (high-quality, automated pull-back IVUS images of severely narrowing segments prior to intervention) were identified from the IVUS database of the Cardiovascular Core Analysis Laboratory at Stanford University. Using commercially available planimetry software, lumen and vessel inside external elastic membrane areas were manually traced at every 0.5-mm interval in diseased segments. Using Simpson's method, vessel, lumen, and plaque (vessel minus lumen) volumes were calculated, and average area was calculated as volume data divided by length. Percent plaque volume was computed as plaque volume divided by vessel volume. Multiple linear regression analysis with backward selection was used to determine the risk factors for atherosclerotic burden.For percent plaque volume, diabetes or hypertension were predictors of more severe disease. For average plaque area, male gender or diabetes were predictors of more severe disease. These variables were also independent predictors in multivariate regression models.Male gender, hypertension, and diabetes are also strong independent predictors of atherosclerotic burden in coronary disease patients, though analyzed segments and disease severity were different.

  View details for DOI 10.1016/j.ijcard.2006.11.194

  View details for Web of Science ID 000253546900022

  View details for PubMedID 17350700

• Predictive value of the index of microcirculatory resistance in patients with ST-segment elevation myocardial infarction JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Fearon, W. F., Shah, M., Ng, M., Brinton, T., Wilson, A., Trernmel, J. A., Schnittger, I., Lee, D. P., Vagelos, R. H., Fitzgerald, P. J., Yock, P. G., Yeung, A. C. 2008; 51 (5): 560-565

  Abstract

  The objective of this study is to evaluate the predictive value of the index of microcirculatory resistance (IMR) in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI).Despite adequate epicardial artery reperfusion, a number of patients with STEMI have a poor prognosis because of microvascular damage. Assessing the status of the microvasculature in this setting remains challenging.In 29 patients after primary PCI for STEMI, IMR was measured with a pressure sensor/thermistor-tipped guidewire. The Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grade, TIMI frame count, coronary flow reserve, and ST-segment resolution were also recorded.The IMR correlated significantly with the peak creatinine kinase (CK) (R = 0.61, p = 0.0005) while the other measures of microvascular dysfunction did not. In patients with an IMR greater than the median value of 32 U, the peak CK was significantly higher compared with those having values 32 U compared with

  View details for DOI 10.1016/j.jacc.2007.08.062

  View details for PubMedID 18237685

• Intraoperative assessment of coronary grafts with fluorescent angiography. Heart Waseda, K., Fitzgerald, P. J., Takahashi, M. 2008; 94 (1): 64-?

  View details for PubMedID 18083950

• Comparison of vascular response to zotarolimus-eluting stent versus sirolimus-eluting stent: Intravascular ultrasound results from ENDEAVOR III AMERICAN HEART JOURNAL Miyazawa, A., Ako, J., Hongo, Y., Hur, S., Tsujino, I., Courtney, B. K., Hassan, A. H., Kandzari, D. E., Honda, Y., Fitzgerald, P. J. 2008; 155 (1): 108-113

  Abstract

  The purpose of this study was to investigate the vascular response of zotarolimus-eluting stent (ZES) and sirolimus-eluting stent (SES) using serial intravascular ultrasound (IVUS).Data were obtained from the Endeavor Drug-Eluting Coronary Stent System Versus the Center Siromlimus-Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions (ENDEAVOR) III trial, a randomized study comparing ZES and SES for the treatment of de novo native coronary artery lesions. Serial (baseline and 8-month follow-up) IVUS was available in 258 patients (190 ZES, 68 SES).At 8 months, ZES had greater percentage of neointimal volume index (ZES 1.1 +/- 0.8 mm3/mm vs SES 0.2 +/- 0.1 mm3/mm, P < .01), resulting in smaller lumen volume index (6.0 +/- 2.0 mm3/mm vs 7.0 +/- 2.1 mm3/mm, P < .05). Zotarolimus-eluting stents showed larger IVUS-detectable neointimal coverage over stent surface (50.2% vs 10.5%, P < .01) and greater mean neointimal thickness (0.19 +/- 0.07 mm vs 0.10 +/- 0.06 mm, P < .01). Zotarolimus-eluting stents had a significantly lower incidence of late-acquired incomplete stent apposition.Zotarolimus-eluting stent is associated with a significantly greater amount of neointimal hyperplasia compared with SES. This amount of hyperplasia in ZES is distributed throughout the stent at 8-month follow-up.

  View details for DOI 10.1016/j.ahj.2007.08.008

  View details for PubMedID 18082499

• Characterization of late incomplete stent apposition: a comparison among bare-metal stents, intracoronary radiation and sirolimus-eluting stents. journal of invasive cardiology Miyazawa, A., Tsujino, I., Ako, J., Shimada, Y., Courtney, B. K., Sakurai, R., Nakamura, M., Okura, H., Waseda, K., Honda, Y., Fitzgerald, P. J. 2007; 19 (12): 515-518

  Abstract

  Late incomplete stent apposition (LISA) develops following implantation of conventional bare-metal stents (BMS) or drug-eluting stents, or after adjunctive intracoronary radiation (IR). However, no study has systematically compared the morphology of LISA seen with various treatment modalities.To compare the morphometric features of LISA accompanying BMS, IR or sirolimus-eluting stents (SES) using serial intravascular ultrasound (IVUS).A query of Stanford University's IVUS database of the Cardiovascular Core Analysis Laboratory was performed to identify LISA cases. Dedicated software programs were used for volumetric IVUS analyses.In 30 LISA cases (12 BMS, 6 IR and 12 SES), there was no intertreatment difference in the degree of LISA (lumen area minus stent area at follow up). Serial analyses of LISA segments showed that vessel area of SES and IR showed significant increase at follow up as compared with post procedure, while there was no significant change in plaque area. In contrast, the BMS group showed no increase in vessel area, whereas plaque area revealed significant reduction. Eight of 12 BMS cases were treated by directional atherectomy before stenting; however, there was no difference in the area change between patients with or without pre-stent atherectomy. Post-procedure plaque thickness beneath the stent struts of LISA was thinner for SES as compared with BMS.Plaque reduction primarily contributes to LISA after BMS, whereas vessel expansion is the predominant factor in LISA development for IR and SES. Thus, the mechanism of LISA may vary among different interventional treatments.

  View details for PubMedID 18180522

• Efficacy of reduced-dose sirofimus-eluting stems on the human coronary artery: Serial IVUS analysis of neointimal hyperplasia and luminal dimension CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Nakamura, M., Abizaid, A., Hirohata, A., Honda, Y., Sousa, E., Fitzgerald, P. J. 2007; 70 (7): 946-951

  Abstract

  Using serial intravascular ultrasound (IVUS), the efficacy of reduced-dose sirolimus-eluting stents (SESs) in the prevention of neointimal hyperplasia (NH) and maintenance of luminal patency in human coronary arteries was evaluated.In the animal model, a broad therapeutic window regarding sirolimus doses in suppressing NH has been reported.Serial cross-sectional and volumetric IVUS analyses were performed in 44 patients treated with SES that contained lower sirolimus doses (either 45% or 70%) than standard SES. For cross-sectional analysis, minimum lumen area (MLA) was measured. Percent (%) NH volumetric obstruction was calculated as 100 x NH volume/stent volume.IVUS measurements were similar between the two drug-dose groups. At 12 months follow-up, only one case developed late incomplete stent apposition. Between 4 and 12 months, a slight increase of in-stent % area loss and % NH obstruction was noted (3.5% +/- 10.4% to 6.7% +/- 10.7% and 1.9% +/- 5.0% to 4.4% +/- 8.0%, respectively). The majority of studied cases, however, sustained less than a 10% volumetric (93% of studied cases) and area loss (75% of studied cases) in the stented segment up to 12 months. At 12 months, % area loss within the stented segments and 5-mm reference segments were comparable (7.0% +/- 19.6% versus 6.7% +/- 10.7%).Although slight increases of NH were noted, SESs, delivering two reduced drug doses, appeared to be effective for maintaining luminal patency during 12 months follow-up.

  View details for DOI 10.1002/ccd.21272

  View details for Web of Science ID 000251442900008

  View details for PubMedID 17621671

• Analysis of bifurcation lesions treated with novel drug-eluting dedicated bifurcation stent system: Intravascular ultrasound results of the AXXESS PLUS trial CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Miyazawa, A., Ako, J., Hassan, A., Hasegawa, T., Abizaid, A., Verheye, S., McClean, D., Neumann, F. J., Grube, E., Honda, Y., Fitzgerald, P. J. 2007; 70 (7): 952-957

  Abstract

  The aim of this intravascular ultrasound (IVUS) study was to assess the efficacy of the AXXESS Plus stent system for the treatment of bifurcation coronary lesions.The AXXESS Plus is a novel bifurcation drug-eluting stent, comprised of a self-expanding flare-shaped stent platform and bioabsorbable polymer coating that releases Biolimus A9.Data were obtained from the AXXESS PLUS trial, a prospective, multicenter, nonrandomized, single-arm study to evaluate safety and efficacy. Six-month follow-up IVUS analysis was available in 49 cases. Volumetric analysis using Simpson's method within the AXXESS stent, and cross-sectional analysis at the ostium of main branch and/or side branch was performed. Impact of bifurcation angle on stent expansion at the carina was also evaluated. Results: Within the AXXESS stent, neointimal volume obstruction percentage was 2.3% +/- 2.2%, with a minimum lumen area of 7.9 +/- 2.6 mm(2). Lumen area was 5.2 +/- 1.7 mm(2) at main branch ostium, and 4.0 +/- 1.5 mm(2) at side branch ostium. In two cases, incomplete stent apposition was observed at the proximal edge of the AXXESS stent. In one case, a gap between the AXXESS stent and an additional stent was observed. Greater bifurcation angle inversely correlated with smaller stent area at side branch ostium (r = -0.54, P = 0.03) but not at main branch ostium (r = -0.2, P = 0.29).This novel self-expanding, drug-eluting bifurcation stent demonstrated effective lesion coverage along with significant neointimal suppression equivalent to current generation balloon-expandable drug-eluting stent technology.

  View details for DOI 10.1002/ccd.21269

  View details for Web of Science ID 000251442900009

  View details for PubMedID 18044777

• Determinants of lumen loss between years 1 and 2 after cardiac transplantation TRANSPLANTATION Sakurai, R., Yamasaki, M., Nakamura, M., Hirohata, A., Honda, Y., Bonneau, H. N., Luikart, H., Yock, P. G., Fitzgerald, P. J., Yeung, A. C., Valantine, H. A., Fearon, W. F. 2007; 84 (9): 1097-1102

  Abstract

  We previously reported that negative remodeling, not plaque progression, correlated with lumen loss during the first year after cardiac transplantation and that cytomegalovirus antibody seropositivity correlated with increased negative remodeling and greater lumen loss. Whether these findings persist between years 1 and 2 after transplantation is unknown.Serial 3-dimensional intravascular ultrasound analysis in the left anterior descending coronary artery was performed in 30 cardiac transplant recipients at year 1 and 2 after transplantation. Vessel, lumen, and plaque area were determined at 0.5-mm axial intervals in the first 50 mm of the left anterior descending coronary artery, and volumes were computed using Simpson's method. Univariate and multivariate regression analyses were performed to identify clinical predictors of change in coronary dimensions.Although mean vessel area did not change (13.6+/-3.4 to 13.4+/-3.3 mm/mm(3), P=0.45), mean plaque area increased (3.4+/-2.3 to 3.8+/-2.2 mm/mm(3), P=0.012), resulting in significant mean lumen area loss (10.3+/-2.5 to 9.6+/-2.3 mm/mm(3), P=0.016). However, the degree of luminal change strongly correlated with the degree of change in vessel size (R=0.81, P<0.0001), but not with change in plaque amount (R=-0.19, P=0.32). In fact, in 57% of the patients who demonstrated lumen loss, negative remodeling contributed more to lumen loss than did plaque progression. Diabetes at 2 years was the only significant independent clinical predictor of plaque progression and lumen loss.Despite significant plaque progression, negative remodeling correlated with coronary lumen loss between years 1 and 2 after cardiac transplantation.

  View details for DOI 10.1097/01.tp.0000285987.27033.65

  View details for PubMedID 17998863

• Intravascular ultrasound findings in ENDEAVOR II and ENDEAVOR III AMERICAN JOURNAL OF CARDIOLOGY Sakurai, R., Bonneau, H. N., Honda, Y., Fitzgerald, P. J. 2007; 100 (8B): 71M-76M

  Abstract

  The results of 2 randomized controlled trials of the Endeavor zotarolimus-eluting stent (ZES; Medtronic Vascular, Santa Rosa, CA) were recently reported: ENDEAVOR II, in which the Endeavor stent was compared with the Driver bare metal stent (BMS; Medtronic Vascular), and ENDEAVOR III, in which the Endeavor stent was compared with the first-generation Cypher sirolimus-eluting stent (SES; Cordis Corporation, Miami Lakes, FL). To examine in detail the vascular responses to the Endeavor stent, serial intravascular ultrasound (IVUS) analyses were performed in subsets of patients in the 2 trials at baseline and 8-month follow-up. The investigators report results for various IVUS parameters and compare those with published results for the first-generation SES and paclitaxel-eluting stent (PES). The ZES demonstrated significantly improved effectiveness and equivalent safety compared with the BMS in ENDEAVOR II. Although the ZES seems to be slightly less effective at inhibiting intimal hyperplasia than the SES and PES, early results are indicative of an acceptable safety profile. This finding may be due in part to the relatively complete and uniform neointimal coverage associated with the ZES.

  View details for DOI 10.1016/j.amjcard.2007.08.025

  View details for Web of Science ID 000250759000010

  View details for PubMedID 17950835

• Four-year clinical follow-up after implantation of the endeavor zotarolimus-eluting stent: ENDEAVOR I, the first-in-human study AMERICAN JOURNAL OF CARDIOLOGY Meredith, I. T., Ormiston, J., Whitbourn, R., Kay, I. P., Muller, D., Popma, J. J., Cutlip, D. E., Fitzgerald, P. J. 2007; 100 (8B): 56M-61M

  Abstract

  The Endeavor zotarolimus-eluting stent (ZES; Medtronic Vascular, Santa Rosa, CA) has been found to provide event-free clinical outcomes to 2 years for the treatment of symptomatic CAD by suppressing neointimal proliferation of the target lesion. The clinical outcomes of patients treated with the Endeavor ZES were evaluated at 4 years after implantation. One hundred consecutive patients with symptomatic ischemic heart disease due to de novo stenotic lesions of native coronary arteries were treated with the Endeavor ZES at 8 centers according to a standardized procedure. At 4 years, 3 patients were lost to follow-up analysis. The incidence of major adverse cardiac events (MACE; defined as death, myocardial infarction, emergent cardiac surgery, or repeat revascularization of the target lesion) was 2% at 4 months, 2% at 1 year, 3% at 2 years, 6.1% at 3 years, and 7.2% at 4 years. The difference in these rates was due to 4 deaths caused by cancer (metastatic melanoma, metastatic adenocarcinoma, small-cell cancer of the bladder, and lung carcinoma). From 2-4 years, there was an additional reported case of target lesion revascularization (TLR). A single case of stent thrombosis occurred at 10 days after the index procedure but no cases occurred thereafter. The treatment of patients with symptomatic CAD due to de novo lesions in native coronary arteries with the Endeavor ZES has sustained clinical benefits to 4 years, with very low rates of MACE and TLR.

  View details for Web of Science ID 000250759000008

  View details for PubMedID 17950833

• Zotarolimus-eluting stents in patients with native coronary artery disease: Clinical and angiographic outcomes in 1,317 patients AMERICAN JOURNAL OF CARDIOLOGY Gershlick, A., Kandzari, D. E., Leon, M. B., Wijns, W., Meredith, I. T., Fajadet, J., Popma, J. J., Fitzgerald, P. J., Kuntz, R. E. 2007; 100 (8B): 45M-55M

  Abstract

  Early studies of a cobalt-based alloy stent coated with the novel antiproliferative agent zotarolimus and a phosphorylcholine polymer have demonstrated significant reductions in angiographic restenosis and target vessel revascularization compared with bare metal stents. However, the generalizability of the angiographic outcomes and clinical benefit of zotarolimus-eluting stents (ZESs) to a more real-world patient population is undetermined. Clinical and angiographic outcomes in 1,317 patients treated with the ZES in the first 4 trials of the Endeavor ZES (Medtronic Vascular, Santa Rosa, CA) clinical trials program were pooled for systematic analysis. Protocol-specified follow-up angiography was performed at 8 or 12 months for a subset of 750 of these patients, and clinical follow-up was performed at 9 months after the index procedures in all patients. Diabetes mellitus was present in 22.5% of patients, the mean reference vessel diameter was 2.73 mm, and the mean lesion length was 14.59 mm. At 8 months (12 months for ENDEAVOR I), mean +/- SD in-stent late luminal loss was 0.61 +/- 0.49 mm. In-stent late luminal loss was greatest in larger caliber (>2.9 mm) vessels (0.65 +/- 0.49 mm) and longer (>16.3 mm) lesions (0.70 +/- 0.52 mm) but did not statistically vary according to diabetic status. At 9 months, overall rates of target lesion revascularization (TLR) and major adverse cardiac events (MACE) were 4.9% and 7.7%, respectively. The rate of TLR at 12 months was not significantly different relative to diabetes and lesion length >16.3 mm (7.2% and 7.7%, respectively), although TLR was significantly more common when reference vessel diameter was <2.5 mm (8.5%; p = 0.013). At 24 months, overall rates of TLR and MACE were 6.5% and 9.9%, respectively. The overall 24-month rate of stent thrombosis was 0.3%, with no events occurring >14 days after the procedure. Despite varied clinical and angiographic characteristics, treatment with the ZES is associated with consistently low rates of TLR and overall major adverse events, including stent thrombosis. Although these findings indicate the efficacy and safety of the ZES over the time course of the first 4 ENDEAVOR clinical trials, additional ongoing study with more open patient inclusion criteria (including long lesions, small vessels, bifurcations, etc) will be important for discerning whether comparable clinical outcomes can be extended to lesion subsets of higher complexity.

  View details for DOI 10.1016/j.amjcard.2007.08.021

  View details for Web of Science ID 000250759000007

  View details for PubMedID 17950832

• Design criteria for the ideal drug-eluting Stent AMERICAN JOURNAL OF CARDIOLOGY Ako, J., Bonneau, H. N., Honda, Y., Fitzgerald, P. J. 2007; 100 (8B): 3M-9M

  Abstract

  The deployment of drug-eluting stents (DESs) is an integral treatment option for patients with coronary artery disease. Although the development and testing of the first-generation DESs focused to a considerable degree on efficacy parameters, including restenosis, recent concerns over late clinical events have prompted a refinement of the design criteria for succeeding generations of these devices. This review assesses design criteria for the ideal DES from 3 complementary perspectives: deliverability, efficacy, and safety. Most new investigational balloon-expandable DES systems have lowered crossing profiles by thinning stent struts using a cobalt chromium alloy, while investigational self-expanding DESs often use nitinol as the platform material. Stents designed to be fully biodegradable are also being developed, with deliverability and performance to be determined in future clinical trials. Refinements in bifurcation-dedicated stents will secure branch accessibility to offer better deliverability in complex lesion morphologies. Experimentation in stent design is already realizing multiple-lesion stenting and the in situ customization of stent length. Rather than simply targeting further reductions in restenosis rates, efforts to improve efficacy are shifting toward a lesion-specific approach, including the design of stents dedicated to bifurcation lesions. Another future direction is a disease-specific approach, or an approach using DESs as local drug-delivery devices. The identification of long-term safety issues with the first-generation DESs has reignited clinical interest in the development of stents that are more biologically based, including fully biodegradable stents and stents using biomimetic and biodegradable polymers. Important performance criteria for future DES agents include more cell-type specificity, broader safety margins, and greater facility at promoting endothelialization and healing.

  View details for DOI 10.1016/j.amjcard.2007.08.016

  View details for Web of Science ID 000250759000002

  View details for PubMedID 17950830

• Characteristics of late incomplete stent apposition: A comparison between sirolimus- and zotarblimds-eluting stents 80th Annual Scientific Session of the American-Heart-Association (AHA) Waseda, K., Ako, J., Tsujino, I., Yamasaki, M., Koizumi, T., Miyazawa, A., Shimada, Y., Yock, P. G., Meredith, I., Fitzgerald, P. J., Honda, Y. LIPPINCOTT WILLIAMS & WILKINS. 2007: 468–68

  View details for Web of Science ID 000250394302160

• Neointimal hyperplasia patterns among 3 drug-eluting stents: A comparative intravascular ultrasound analysis of everolimus-, sirolimus-, and paclitaxel-eluting stents 80th Annual Scientific Session of the American-Heart-Association (AHA) Sakurai, R., Courtney, B. K., Yamasaki, M., Tsujino, I., Waseda, K., Hasegawa, T., Shimohama, T., Ako, J., Hongo, Y., Morino, Y., Miyazawa, A., Hur, S., Koizumi, T., Honda, Y., Yock, P. G., Lansky, A. J., Sudhir, K., Stone, G. W., Fitzgerald, P. J. LIPPINCOTT WILLIAMS & WILKINS. 2007: 615–15

  View details for Web of Science ID 000250394302771

• The SIRIUS-DIRECT trial: A multi-center study of direct stenting using the sirolimus-eluting stent in patients with de novo native coronary artery lesions CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Moses, J. W., Weisz, G., Mishkel, G., Caputo, R., O'Shaughnessey, C., Wong, S. C., Fischell, T. A., Mooney, M., Williams, D. O., Popma, J. J., Fitzgerald, P., Smith, S., Kuntz, R. E., Collins, M., Cohen, S. A., Leon, M. B. 2007; 70 (4): 505-512

  Abstract

  To assess the safety and efficacy of direct stenting using the sirolimus-eluting BX Velocitytrade mark stent in patients with coronary lesions.Although direct coronary stenting has become a widespread practice, there have been no systematic assessments of direct stenting with drug-eluting stents.Total of 225 patients with identical inclusion and exclusion criteria as the original SIRIUS trial were enrolled in this prospective single-arm study. They were compared in a no-inferiority design with 412 similar patients from the SIRIUS trial who had sirolimus-eluting stents deployed after predilatation and were preassigned to angiographic follow-up evaluation.Direct stenting was successful in 85.8% of the patients. Compared with the predilatation group, direct stenting was associated with shorter median procedure duration (33 min vs. 45 min, P < 0.001). Angiographic follow-up at 8 months revealed similar late loss (in-stent-0.19 +/- 0.47 mm vs. 0.17 +/- 0.44 mm, and in-lesion-0.23 +/- 0.41 mm vs. 0.24 +/- 0.47 mm) and similar frequency of binary restenosis (in-stent-4.6% vs. 3.2% and in-lesion-6.1% vs. 8.9%) between the two treatment strategies. However, stent-edge restenosis was lower with direct stenting than in the predilatation control group (2.1% vs. 6.9%, P = 0.02). At 12-months, there were no significant differences in target lesion revascularization (3.7% vs. 5.1%, P = ns) or composite major adverse cardiac events (7.0% vs. 8.3%, P = ns).In patients similar to those treated in the SIRIUS trial, direct stenting using sirolimus-eluting stents achieves excellent short- and long-term clinical and angiographic results with shorter procedure time and less frequent stent edge restenosis compared with predilation stent implantation techniques.

  View details for DOI 10.1002/ccd.21162

  View details for Web of Science ID 000250104300007

  View details for PubMedID 17896408

• Detailed intravascular ultrasound analysis of Zotarolimus-eluting phosphorylcholine-coated cobalt-chromium alloy stent in de Novo Coronary lesions (results from the ENDEAVOR II trial) AMERICAN JOURNAL OF CARDIOLOGY Sakurai, R., Hongo, Y., Yamasaki, M., Honda, Y., Bonneau, H. N., Yock, P. G., Cutlip, D., Popma, J. J., Zimetbaum, P., Fajadet, J., Kuntz, R. E., Wijns, W., Fitzgerald, P. J. 2007; 100 (5): 818-823

  Abstract

  Zotarolimus-eluting phosphorylcholine-coated cobalt-chromium alloy Driver stents (ZES) demonstrated significant reductions in target lesion revascularization rate with few apparent adverse events compared with bare metal stents (BMS; uncoated Driver stents) in a prospective, multicenter, double-blind, randomized controlled trial in de novo coronary lesions. The aim of this study was to examine detailed vascular responses to ZES compared with BMS using serial intravascular ultrasound analysis. A total of 343 patients (ZES n = 178, BMS n = 165) were enrolled in this formal, prespecified intravascular ultrasound substudy of the Randomized Controlled Trial to Evaluate the Safety and Efficacy of the Medtronic AVE Zotarolimus-Eluting Driver Coronary Stent in de Novo Native Coronary Artery Lesions (ENDEAVOR II), a prospective, multicenter, double-blind, randomized controlled trial to compare ZES and BMS in de novo native coronary artery lesions. Quantitative and qualitative intravascular ultrasound analyses were performed postprocedurally and at 8-month follow-up in stented and reference segments. ZES showed significantly less neointima, with a larger lumen than BMS at 8 months (percentage neointimal volume 17.6 +/- 10.1% vs 29.4 +/- 17.2%, p <0.0001; maximum percentage neointimal area 32.9 +/- 13.0% vs 47.6 +/- 18.6%, p <0.0001; minimum luminal area 4.9 +/- 1.6 vs 4.0 +/- 1.7 mm(2), p <0.0001) and no unfavorable edge effect. In the 18-mm single stents, ZES showed evenly inhibited neointima compared with BMS. Neither persistent stent-edge dissection nor late-acquired incomplete stent apposition was observed in either group. In conclusion, ZES showed evenly inhibited neointima with no apparent adverse vascular response in stented and reference segments at 8 months compared with BMS.

  View details for DOI 10.1016/j.amjcard.2007.04.016

  View details for Web of Science ID 000249226100013

  View details for PubMedID 17719326

• Neointimal progression and luminal narrowing in sirolimus-eluting stent treatment for bare metal in-stent restenosis: A quantitative intravascular ultrasound analysis AMERICAN HEART JOURNAL Sakurai, R., Ako, J., Hassan, A. H., Bonneau, H. N., Neumann, F., Desmet, W., Holmes, D. R., Yock, P. G., Fitzgerald, P. J., Honda, Y. 2007; 154 (2): 361-365

  Abstract

  Recurrent restenosis may occur after drug-eluting stent implantation for in-stent restenosis (ISR) of bare metal stents (BMSs), especially in areas involving drug-eluting stent gaps.To investigate the details of neointimal progression and luminal narrowing after the treatment of ISR using sirolimus-eluting stents (SESs), serial intravascular ultrasound analysis was performed in 65 patients with ISR at postintervention and at 6-month follow-up. The total stented segment was categorized into 3 compartments: new SES (N), new SES and old BMS overlap (N/O), and old BMS (O). In each of the 190 compartments, serial intravascular ultrasound parameters were analyzed at the cross section of the maximum change in neointimal area (delta neointimal area) from postintervention to follow-up or the minimum lumen area at follow-up if delta neointimal area was 0. Minimum lumen area in each compartment was also investigated serially.At postintervention, lumen area was the smallest in compartment N/O (N 5.8 +/- 1.5, N/O 5.1 +/- 1.3, O 6.0 +/- 1.4 mm2, P = .005). Not only the average of maximum delta neointimal area (N 0.2 +/- 0.4, N/O 0.2 +/- 0.4, O 0.8 +/- 1.0 mm2, P < .0001) but also the frequency of minimum lumen area decreasing from > or = 4.0 mm2 at postintervention to < 4.0 mm2 at follow-up (N 4.0%, N/O 5.1%, O 23.5%, P = .012) was the largest in compartment O.Neointimal progression and consequent luminal narrowing tend to occur where BMS is uncovered with SES in treatment of ISR, even in the absence of an obvious stenosis at postintervention.

  View details for DOI 10.1016/j.ahj.2007.04.023

  View details for Web of Science ID 000248511000025

  View details for PubMedID 17643589

• The risks and benefits of drug-eluting stents. The American heart hospital journal Shimohama, T., Honda, Y., Fitzgerald, P. J. 2007; 5 (3): 146-150

  View details for PubMedID 17673855

• Six-month clinical and angiographic results of a dedicated drug-eluting Stent for the treatment of coronary bifurcation narrowings AMERICAN JOURNAL OF CARDIOLOGY Grube, E., Buellesfeld, L., Neumann, F. J., Verheye, S., Abizaid, A., McClean, D., Mueller, R., Lansky, A., Mehran, R., Costa, R., Gerckens, U., Trauthen, B., Fitzgerald, P. J. 2007; 99 (12): 1691-1697

  Abstract

  Percutaneous intervention for coronary bifurcation lesions has been associated with increased clinical complication rates compared with nonbifurcation lesions, primarily as a result of restenosis. Therefore, there is a need for new techniques. The purpose of this study was to evaluate a new drug-eluting stent and implantation technique for the treatment of de novo coronary bifurcation lesions. The Axxess Plus trial was a prospective multicenter single-arm study that enrolled 139 patients. Each patient received a self-expanding, conically shaped nickel-titanium Axxess Plus biolimus A9-eluting stent at the level of the carina. Depending on the lesion anatomy, additional nonstudy stents were placed distally if necessary. Clinical and angiographic follow-up were scheduled at 6 months after the procedure. The overall rate of target lesion revascularization was 7.5% at 6 months. A mean of 2.4 stents were implanted per patient; 51.2% of patients received a stent to the side branch, 29.4% received balloon angioplasty only, and 20.6% of side branches were not treated. In-stent late loss in the Axxess stents was 0.09 mm. Incidences of angiographic in-stent restenosis were 7.1% in the parent vessel stents and 9.2% in the group receiving stents in the side branch (7.9% excluding bare metal stents placed distal to the Axxess stent), compared with 25% for balloon angioplasty treatment and 12% for no treatment. Late stent thrombosis was observed in 3 cases, 2 of which were associated with confirmed premature cessation of antiplatelet therapy. In conclusion, the Axxess Plus conical stent effectively treats bifurcation lesions alone or in conjunction with other drug-eluting stents.

  View details for DOI 10.1016/j.amjcard.2007.01.043

  View details for Web of Science ID 000247867100014

  View details for PubMedID 17560877

• Changes in coronary anatomy and physiology after heart transplantation AMERICAN JOURNAL OF CARDIOLOGY Hirohata, A., Nakamura, M., Waseda, K., Honda, Y., Lee, D. P., Vagelos, R. H., Hunt, S. A., Valantine, H. A., Yock, P. G., Fitzgerald, P. J., Yeung, A. C., Fearon, W. F. 2007; 99 (11): 1603-1607

  Abstract

  Cardiac allograft vasculopathy (CAV) is a progressive process involving the epicardial and microvascular coronary systems. The timing of the development of abnormalities in these 2 compartments and the correlation between changes in physiology and anatomy are undefined. The invasive evaluation of coronary artery anatomy and physiology with intravascular ultrasound, fractional flow reserve, coronary flow reserve, and the index of microcirculatory resistance (IMR) was performed in the left anterior descending coronary artery during 151 angiographic evaluations of asymptomatic heart transplant recipients from 0 to >5 years after heart transplantation (HT). There was no angiographic evidence of significant CAV, but during the first year after HT, fractional flow reserve decreased significantly (0.89 +/- 0.06 vs 0.85 +/- 0.07, p = 0.001), and percentage plaque volume derived by intravascular ultrasound increased significantly (15.6 +/- 7.7% to 22.5 +/- 12.3%, p = 0.0002), resulting in a significant inverse correlation between epicardial physiology and anatomy (r = -0.58, p <0.0001). The IMR was lower in these patients compared with those > or =2 years after HT (24.1 +/- 14.3 vs 29.4 +/- 18.8 units, p = 0.05), suggesting later spread of CAV to the microvasculature. As the IMR increased, fractional flow reserve increased (0.86 +/- 0.06 to 0.90 +/- 0.06, p = 0.0035 comparing recipients with IMRs < or =20 to those with IMRs > or =40), despite no difference in percentage plaque volume (21.0 +/- 11.2% vs 20.5 +/- 10.5%, p = NS). In conclusion, early after HT, anatomic and physiologic evidence of epicardial CAV was found. Later after HT, the physiologic effect of epicardial CAV may be less, because of increased microvascular dysfunction.

  View details for DOI 10.1016/j.amjcard.2007.01.039

  View details for PubMedID 17531589

• Comparison of nonuniform strut distribution between two drug-eluting stent platforms. journal of invasive cardiology Hasegawa, T., Ako, J., Ikeno, F., Waseda, K., Suzuki, Y., Honda, Y., Fitzgerald, P. J. 2007; 19 (6): 244-246

  Abstract

  To compare the difference of strut distribution between two clinically available drug-eluting stent platforms (Bx Velocity and Express II stents) using intravascular ultrasound (IVUS).Nonuniform strut distribution (NSD) has been shown to be associated with increased intimal hyperplasia after drug-eluting stent implantation.IVUS imaging was performed on Bx Velocity (n = 6) and Express II stents (n = 6) after inflation pressures of 10, 16, and 26 atm in a bench test model. Percent NSD was defined as the length of segments with NSD (interstrut angle > 90 degrees) divided by stent length. NSD was also assessed in postprocedure IVUS images in 53 clinical cases (32 Cypher, 21 Taxus) using 3-dimensional IVUS analysis.Frequency of NSD segment and %NSD were lower in Bx Velocity stents than in Express II stents at the inflation pressures of 16 and 26 atm (%NSD: 16 atm, 0% vs. 13.8 +/- 9.4%; p < 0.005; 26 atm, 1.1 +/- 2.6% vs. 19.9 +/- 6.9% p < 0.0001). In postprocedural images from clinical cases, the frequency of NSD segment and %NSD were lower in Cypher stents than in Taxus stents (%NSD: 0.5 +/- 1.6 vs. 6.8 +/- 7.2; p < 0.0001).NSD segment was observed less in Bx Velocity stents than in Express II stents.

  View details for PubMedID 17541122

• Serial intravascular ultrasonic study of outcomes of coronary culprit lesions with plaque rupture following bare metal stent implantation in patients with angina pectoris AMERICAN JOURNAL OF CARDIOLOGY Hur, S., Hassan, A. H., Rekhi, R., Ako, J., Shimada, Y., Nakamura, M., Yamasaki, M., Bonneau, H. N., Sudhir, K., Yock, P. G., Honda, Y., Fitzgerald, P. J. 2007; 99 (10): 1394-1398

  Abstract

  Coronary culprit lesions with plaque rupture (PR) have been treated with different coronary interventions. However, it is unknown whether the presence of PR affects the restenotic process after coronary intervention. One hundred forty-two patients undergoing coronary bare metal stent implantation were enrolled in the present retrospective analysis. Case selection was based on availability of intravascular ultrasound (IVUS) and quantitative coronary angiographic examinations at baseline (before and after intervention) and at follow-up. Serial comparative analyses included qualitative and quantitative features of the culprit lesion and reference segments. PR was defined as an intraplaque cavity in communication with the lumen in the presence of a residual, disrupted cap. Patients were categorized according to the presence/absence of PR. Pre-interventional IVUS detected PR in 54 patients (38%). Baseline patient demographics were similar between the +PR and -PR groups. Quantitative IVUS analysis showed higher rates of positive remodeling and larger vessel and plaque areas in the +PR compared with -PR lesions (p <0.001 for all). At follow-up (7.2 +/- 2.6 months), no statistically significant difference was observed between the 2 groups in quantitative coronary angiographic or IVUS measurements. In conclusion, culprit lesions with PR exhibited larger plaque mass and higher rates of positive remodeling at preintervention IVUS examination. However, when treated with bare metal stents, the absence/presence of preintervention PR was not found to affect the rate or severity of in-stent restenosis in these culprit lesions.

  View details for DOI 10.1016/j.amjcard.2006.12.067

  View details for Web of Science ID 000246715900010

  View details for PubMedID 17493467

• Percutaneous coronary revascularization using a trilayer metal phosphorylcholine-coated zotarolimus-eluting stent AMERICAN JOURNAL OF CARDIOLOGY Abizaid, A., Lansky, A. J., Fitzgerald, P. J., Tanajura, L. F., Feres, F., Staico, R., Mattos, L., Abizaid, A., Chaves, A., Centemero, M., Sousa, A. G., Sousa, J. E., Zaugg, M. J., Schwartz, L. B. 2007; 99 (10): 1403-1408

  Abstract

  The ZoMaxx Coronary Stent System elutes the antiproliferative agent zotarolimus via a biocompatible phosphorylcholine polymer loaded onto a novel, thin, stainless steel stent platform containing an 0.0007-inch inner layer of tantalum that enhances fluoroscopic radiopacity. The objective of this single-arm prospective clinical trial was to assess the safety and performance of the ZoMaxx stent for the treatment of coronary artery stenosis. Forty consecutive patients with ischemic coronary occlusive disease due to single de novo obstructive lesions of native coronary arteries were treated with 3 x 18 mm ZoMaxx stents at the Dante Pazzanese de Cardiologie in Saõ Paulo, Brazil, between April and July 2005. Independent core laboratories analyzed quantitative coronary angiography and intravascular ultrasound results immediately after stent implantation, and after 4 months. The lesion, procedure, and device-deployment success rates were all 100% (40 of 40). There were no major adverse cardiac events during the study. Follow-up quantitative coronary angiography at 4 months revealed in-stent and in-segment late lumen losses of 0.20 +/- 0.35 and 0.17 +/- 0.35 mm, respectively. Follow-up intravascular ultrasound at 4 months revealed 6.5 +/- 6.2% neointimal volume obstruction. There were no instances of late acquired stent incomplete apposition or stent thrombosis. In conclusion, the ZoMaxx Coronary Stent can be safely implanted for the treatment of de novo coronary artery stenosis. The inhibition of neointima formation as measured by follow-up angiography and IVUS after 4 months suggests therapeutic potential for the reduction of restenosis.

  View details for DOI 10.1016/j.amjcard.2006.12.064

  View details for Web of Science ID 000246715900012

  View details for PubMedID 17493469

• Drug delivery via nano-, micro and macroporous coronary stent surfaces EXPERT OPINION ON DRUG DELIVERY Tsujino, I., Ako, J., Honda, Y., Fitzgerald, P. J. 2007; 4 (3): 287-295

  Abstract

  Drug-eluting stents (DESs) have revolutionized the treatment of occlusive coronary artery disease via marked reduction of in-stent restenosis. One critical feature for successful DESs is the sustained release of drugs, which is achieved using a polymer coating in the present generation of DESs. However, recent studies have raised a concern that polymers may trigger allergic reactions and/or prolonged inflammation in some patients. These untoward reactions may eventually lead to undesirable clinical events, including stent thrombosis and sudden cardiac death. A new drug delivery technology, using a porous stent surface, may offer desirable drug elution properties without the use of polymers, and may translate into an improved safety profile for the next-generation DESs.

  View details for DOI 10.1517/17425247.4.3.287

  View details for Web of Science ID 000252856900008

  View details for PubMedID 17489655

• Comparison of vessel response following sirolimus-eluting stent implantation as assessed by serial 3-D intravascular ultrasound study. journal of invasive cardiology Waseda, K., Ako, J., Shimada, Y., Morino, Y., Tsujino, I., Hongo, Y., Sudhir, K., Yock, P. G., Fitzgerald, P. J., Honda, Y. 2007; 19 (4): 171-173

  Abstract

  Recent sirolimus-eluting stent (SES) studies have suggested higher rates of restenosis in non-left anterior descending (LAD) artery lesions. The aim of this study was to evaluate differential vessel response (LAD versus non-LAD) to SES implantation using serial intravascular ultrasound (IVUS). A total of 94 patients who underwent SES implantation and serial (post-PCI and 8 months) 3-dimensional IVUS were enrolled from our database. Volumetric analysis was performed throughout the stent as well as the adjacent reference segment (up to 5 mm). Volume index (volume/length) was calculated for vessel (VVI), lumen (LVI), and plaque (PVI). Cross-sectional narrowing (CSN) was defined as neointimal area divided by stent area (%). With respect to the in-stent segment, VVI, PVI, and LVI at post-PCI were not significantly different between the LAD (n = 41) and non-LAD (n = 53) lesions. At follow up, however, maximum CSN was significantly greater in the non-LAD lesions (18.3 +/- 15.2% versus 12.2 +/- 10.0%; p = 0.029). At the proximal reference segment, the non-LAD lesions showed a significantly greater LVI decrease than the LAD lesions (p <0.05), primarily due to mild vessel shrinkage observed in the non-LAD lesions. There were no significant differences at the distal reference segment between the LAD and non-LAD lesions. This detailed IVUS analysis suggests that there are minimal differences in the vessel responses following SES implantation. These findings may have potential implications for mechanical and pharmacokinetic properties of next-generation drug-eluting stent technology.

  View details for PubMedID 17404402

• Impact of gender on neointimal hyperplasia following coronary artery stenting AMERICAN JOURNAL OF CARDIOLOGY Kaneda, H., Ako, J., Kataoka, T., Takahashi, T., Terashima, M., Waseda, K., Miyazawa, A., Hassan, A. H., Honda, Y., Yock, P. G., Fitzgerald, P. J. 2007; 99 (4): 491-493

  Abstract

  Whether gender affects long-term outcomes after bare metal stent implantation remains controversial. The aim of this study was to examine the impact of gender on neointimal hyperplasia in a large cohort of patients after stent implantation using 3-dimensional intravascular ultrasound. Lumen and stent areas were manually traced at 0.5-mm intervals throughout the stented segment. Using Simpson's method, lumen, stent, and neointimal (stent - lumen) volumes were calculated and standardized by stent length. Women were older, presented more often with hyperlipidemia or hypertension, and had smaller reference vessel diameter and mean stent area, compared with men. Although neointimal hyperplasia and neointimal thickness in women were similar to that in men, the percentage of neointimal hyperplasia (neointimal area divided by stent area) was higher in women due to the smaller stent area. After adjusting for stent area, the percentage of neointimal hyperplasia did not differ by gender. In conclusion, the results of this study indicate that neointimal hyperplasia after bare metal stent implantation in women is similar to that seen in men. Despite the similarity in outcome, there are several gender-specific differences in baseline characteristics.

  View details for DOI 10.1016/j.amjcard.2006.09.094

  View details for Web of Science ID 000244514500014

  View details for PubMedID 17293191

• Comparison of zotarolimus-eluting and sirolimus-eluting stents in patients with native coronary artery disease - A randomized controlled trial JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Kandzari, D. E., Leon, M. B., Popma, J. J., Fitzgerald, P. J., O'Shaughnessy, C., Ball, M. W., Turco, M., Applegate, R. J., Gurbel, P. A., Midei, M. G., Badre, S. S., Mauri, L., Thompson, K. P., LeNarz, L. A., Kuntz, R. E. 2006; 48 (12): 2440-2447

  Abstract

  This trial examined the relative clinical efficacy, angiographic outcomes, and safety of zotarolimus-eluting coronary stents (ZES) with a phosphorylcholine polymer versus sirolimus-eluting stents (SES).Whether a cobalt-based alloy stent coated with the novel antiproliferative agent, zotarolimus, and a phosphorylcholine polymer may provide similar angiographic and clinical benefit compared with SES is undetermined.A prospective, multicenter, 3:1 randomized trial was conducted to evaluate the safety and efficacy of ZES (n = 323) relative to SES (n = 113) in 436 patients undergoing elective percutaneous revascularization of de novo native coronary lesions with reference vessel diameters between 2.5 mm and 3.5 mm and lesion length > or =14 mm and < or =27 mm. The primary end point was 8-month angiographic in-segment late lumen loss.Angiographic in-segment late lumen loss was significantly higher among patients treated with ZES compared with SES (0.34 +/- 0.44 mm vs. 0.13 +/- 0.32 mm, respectively; p < 0.001). In-hospital major adverse cardiac events were significantly lower among patients treated with ZES (0.6% vs. 3.5%, p = 0.04). In-segment binary angiographic restenosis was also higher in the ZES cohort (11.7% vs. 4.3%, p = 0.04). Total (clinically and non-clinically driven) target lesion revascularization rates at 9 months were 9.8% and 3.5% for the ZES and SES groups, respectively (p = 0.04). However, neither clinically driven target lesion revascularization (6.3% zotarolimus vs. 3.5% sirolimus, p = 0.34) nor target vessel failure (12.0% zotarolimus vs. 11.5% sirolimus, p = 1.0) differed significantly.Compared with SES, treatment with a phosphorylcholine polymer-based ZES is associated with significantly higher late lumen loss and binary restenosis at 8-month angiographic follow-up. (The Endeavor III CR; http://clinicaltrials.gov/ct/show/NCT00265668?order=1?).

  View details for DOI 10.1016/j.jacc.2006.08.035

  View details for Web of Science ID 000242916100005

  View details for PubMedID 17174180

• Comparison of the efficacy of direct coronary stenting with sirolimus-eluting stents versus stenting with predilation by intravascular ultrasound imaging (from the DIRECT trial) AMERICAN JOURNAL OF CARDIOLOGY Hirohata, A., Morino, Y., Ako, J., Sakurai, R., Buchbinder, M., Caputo, R. P., Karas, S. P., Mishkel, G. J., Mooney, M. R., O'Shaughnessy, C. D., Raizner, A. E., Wilensky, R. L., Williams, D. O., Wong, S., Yock, P. G., Honda, Y., Moses, J. W., Fitzgerald, P. J. 2006; 98 (11): 1464-1467

  Abstract

  A direct coronary stenting technique using drug-eluting stents may decrease drug-eluting stent efficacy due to possible damage to the surface coating of the stent. The DIRECT is a multicenter, prospective, nonrandomized trial designed to evaluate the direct stenting strategy for the sirolimus-eluting Bx-Velocity stent compared with the historical control (SIRIUS trial, stenting with predilation). Volumetric and cross-sectional intravascular ultrasound analyses at 8-month follow-up were performed in 115 patients (DIRECT n= 64, control n = 51). Patient and lesion characteristics were comparable between groups. The DIRECT group achieved an equivalent uniform expansion index, defined as minimum stent area/maximum stent area x 100, compared with the control group (65.9 +/- 11.7 vs 63.1 +/- 12.7, p = NS). At 8-month follow-up, vessel, stent, lumen, and neointimal volume index (volume in cubic millimeters/length in millimeters) and percent neointimal volume were similar between the DIRECT and control groups (vessel volume index 13.9 +/- 4.40 vs 15.0 +/- 3.83; stent volume index 6.83 +/- 2.02 vs 6.94 +/- 2.04; lumen volume index 6.71 +/- 2.04 vs 6.81 +/- 2.07; neointimal volume index 0.14 +/- 0.24 vs 0.16 +/- 0.23; percent neointimal volume 3.73 +/- 6.97 vs 3.14 +/- 5.32, p = NS for all). In addition, in-stent neointimal hyperplasia distribution was significantly smaller near the distal stent edge (0.22 vs 0.098 mm(3)/mm, p = 0.01 for an average neointimal volume index within 3 mm from the distal stent edge). In conclusion, direct coronary stenting with the sirolimus-eluting Bx-Velocity stent is equally effective in terms of uniform stent expansion and long-term quantitative intravascular ultrasound results compared with conventional stenting using predilation. This strategy appears to be associated with less neointimal hyperplasia near the distal stent edge.

  View details for DOI 10.1016/j.amjcard.2006.06.046

  View details for Web of Science ID 000242595300010

  View details for PubMedID 17126651

• Impact of donor-transmitted atherosclerosis on early cardiac allograft vasculopathy; New findings by 3-D IVUS 79th Annual Scientific Session of the American-Heart-Association Yamasaki, M., Sakurai, R., Hirohata, A., Honda, Y., Yock, P. G., Fitzgerald, P. J., Yeung, A. C., Valantine, H. A., Fearon, W. F. LIPPINCOTT WILLIAMS & WILKINS. 2006: 533–33

  View details for Web of Science ID 000241792803414

• Influence of diabetes mellitus on vessel response following zotarolimus-eluting stent: Volumetric intravascular ultrasound analysis from the ZOMAXX IVUS trial 18th Annual Transcatheter Cardiovascular Therapeutics Symposium Waseda, K., Hasegawa, T., Ako, J., Yock, P. G., Honda, Y., Abizaid, A., Fitzgerald, P. J. EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2006: 125M–125M

  View details for Web of Science ID 000241442800302

• Predictors of recurrent in-stent restenosis after beta-radiation: An analysis from the START 40/20 trial. Journal of interventional cardiology Kaneda, H., Honda, Y., Morino, Y., Lansky, A. J., Yock, P. G., Bonan, R., Fitzgerald, P. J. 2006; 19 (5): 376-380

  Abstract

  The purpose of this study was to identify potential predictors, including clinical, procedural, angiographic, and intravascular ultrasound (IVUS) parameters, for recurrent in-stent restenosis (ISR) following beta-radiation 90Strontium/Yttrium (90Sr/Y) in a large multicenter trial.Although adjunct brachytherapy reduces recurrent ISR after primary catheter-based intervention, recurrence of stenosis after brachytherapy still occurs.We analyzed 185 IVUS cohort patients in the STent And Restenosis Therapy (START) 40/20 trial where a 40-mm, 90Sr/Y, radioactive source train was exclusively used for treatment of ISR to be treatable with a 20-mm balloon.Thirty-nine patients underwent target lesion revascularization. Preliminary univariate analysis showed that age, smoking, balloon/artery ratio, geographic miss, minimum lumen diameter, and diameter stenosis at baseline were associated with target lesion revascularization, while none of IVUS variables were (minimum lumen area, minimum stent area, or residual plaque burden). The multivariate logistic regression analysis showed that younger age, lower balloon/artery ratio, and presence of geographic miss were independent predictors of target lesion revascularization.Even with adjunct beta-radiation therapy, initial mechanical optimization, such as appropriate balloon sizing and positioning, may be critical for the prevention of recurrent ISR.

  View details for PubMedID 17020560

• Randomized, double-blind, multicenter study of the Endeavor zotarolimus-eluting phosphorylcholine encapsulated stent for treatment of native coronary artery lesions: Clinical and angiographic results of the ENDEAVOR II trial CIRCULATION Fajadet, J., Wijns, W., Laarman, G., Kuck, K., Ormiston, J., Munzel, T., Popma, J. J., Fitzgerald, P. J., Bonan, R., Kuntz, R. E. 2006; 114 (8): 798-806

  Abstract

  The use of the Endeavor stent might reduce restenosis and stent thrombosis at 9 months.Patients (n = 1197) treated for single coronary artery stenosis were enrolled in a prospective, randomized, double-blind study and randomly assigned to receive the Endeavor zotarolimus-eluting phosphorylcholine polymer-coated stent (n = 598) or the same bare metal stent but without the drug or the polymer coating (n = 599). The 2 groups were well matched in baseline characteristics. Diabetes was present in 20.1% of patients; the mean reference vessel diameter was 2.75 mm; and the mean lesion length was 14.2 mm. The primary end point of target vessel failure at 9 months was reduced from 15.1% with the bare metal stent to 7.9% with the Endeavor (P = 0.0001), and the rate of major adverse cardiac events was reduced from 14.4% with the bare metal stent to 7.3% with the Endeavor (P = 0.0001). Target lesion revascularization was 4.6% with Endeavor compared with 11.8% with the bare metal stent (P = 0.0001). The rate of stent thrombosis was 0.5% with the Endeavor, which was not significantly different from 1.2% with the bare metal stent. In 531 patients submitted to angiographic follow-up, late loss was reduced from 1.03 +/- 0.58 to 0.61 +/- 0.46 (P < 0.001) in stent and from 0.72 +/- 0.61 to 0.36 +/- 0.46 (P < 0.001) in segment. The rate of in-segment restenosis was reduced from 35.0% to 13.2% with Endeavor (P < 0.0001). There was no excessive edge stenosis, aneurysm formation, or late acquired malapposition by intravascular ultrasound imaging. Differences in clinical outcome were maintained at 12 and 24 months (P < 0.0001).Compared with bare metal stents, the Endeavor stent is safe and reduces the rates of clinical and angiographic restenosis at 9, 12, and 24 months.

  View details for DOI 10.1161/CIRCULATIONHA.105.591206

  View details for Web of Science ID 000239920000011

  View details for PubMedID 16908773

• Effect of Everolimus-eluting stents in different vessel sizes (from the pooled FUTURE I and II trials) AMERICAN JOURNAL OF CARDIOLOGY Tsuchiya, Y., Lansky, A. J., Costa, R. A., Mehran, R., Pietras, C., Shimoda, Y., Sonoda, S., Cristea, E., Negoita, M., Dangas, G. D., Moses, J. W., Leon, M. B., Fitzgerald, P. J., Mueller, R., Stoerger, H., Hauptmann, K. E., Grube, E. 2006; 98 (4): 464-469

  Abstract

  The everolimus-eluting stent (EES) has been shown to significantly decrease neointimal proliferation at 6 months compared with the bare metal stent (BMS) in patients with de novo coronary lesions. We report mid-term outcomes based on different vessel sizes in the combined FUTURE I and II trials. In the prospective, randomized, FUTURE I trial (single center) and expanded FUTURE II trial (multicenter), 106 patients (107 lesions) were randomized to EESs (n = 49 lesions) or BMSs (n = 58 lesions). Patients were categorized into 3 groups based on preprocedure reference diameter as assessed by quantitative coronary angiography (small vessel < 2.75 mm, medium vessel 2.75 to 3.25 mm, and large vessel > 3.25 mm). At 6-month follow-up, EESs decreased in-stent late lumen loss (decreased rate range of 78% to 94%), resulting in significantly larger minimum lumen area as assessed by intravascular ultrasound (increased range of 34% to 42%) compared with the BMS across all vessel sizes. There were no cases of in-stent restenosis with EESs at any vessel size but 8 cases with BMSs (5 in small vessels). No stent thrombosis, aneurysm formation, or late stent incomplete apposition was observed in any group. The EES appears to be effective for treatment of de novo coronary lesions in decreasing neointimal proliferation at 6-month follow-up compared with BMSs, regardless of vessel size.

  View details for DOI 10.1016/j.amjcard.2006.02.054

  View details for Web of Science ID 000240039500007

  View details for PubMedID 16893698

• Axial plaque redistribution after coronary stent deployment. journal of invasive cardiology Hirohata, A., Honda, Y., Fitzgerald, P. 2006; 18 (8): E225-6

  Abstract

  We report a case of axial plaque redistribution after coronary stent deployment assessed by intravascular ultrasound (IVUS) as well as coronary angiography. A 72-year-old male with a history of hypertension, hyperlipidemia and a nuclear stress test demonstrating anterior and lateral ischemia was admitted for cardiac catheterization. Coronary angiography and IVUS examination revealed eccentric stenoses in the left anterior descending artery (LAD) and the left circumflex artery (LCx), just before the bifurcation of the first obtuse marginal branch. After successful LAD stent placement, the LCx was also stented, jailing the obtuse marginal branch. Immediately after dilatation, however, the coronary angiogram showed a new significant stenosis at the distal adjacent segment. IVUS examination after administration of nitroglycerin revealed a secondary critical lesion that was not observed before the interventional procedure. A significant plaque increase at the new lesion site presumably resulted from axial plaque redistribution (extrusion from the stented segment, otherwise known as plaque shift). After additional stenting, the patient had an uneventful course.

  View details for PubMedID 16877793

• Intravascular ultrasonic analysis of atherosclerotic vessel remodeling and plaque distribution of stenotic left anterior descending coronary arterial bifurcation lesions upstream and downstream of the side branch AMERICAN JOURNAL OF CARDIOLOGY Shimada, Y., Courtney, B. K., Nakamura, M., Hongo, Y., Sonoda, S., Hassan, A. H., Yock, P. G., Honda, Y., Fitzgerald, P. J. 2006; 98 (2): 193-196

  Abstract

  Bifurcation lesions remain a challenging lesion subset, even in the era of drug-eluting stents. The aim of this study was to investigate the longitudinal remodeling pattern and cross-sectional plaque location of bifurcation lesions. Seventy-four preintervention intravascular ultrasound studies of left anterior descending bifurcation lesions were analyzed, in which the lesion was located proximal (type A, n=32) or distal (type B, n=42) to the side branch. Vessel area and plaque area at the lesion (VAlesion and PAlesion) and at the reference site (VAreference and PAreference) were measured. The remodeling ratio was defined as VAlesion/VAreference, and the vessel compensation ratio was defined as (VAlesion-VAreference)/(PAlesion-PAreference). The geometric center of the lumen at the lesion site was identified, and the lesion site was divided into circumferential equal arcs to compare the cross-sectional distribution of percentage plaque area (100x[PAlesion/VAlesion]) between the 2 groups. The remodeling ratio (1.03+/-0.15 vs 0.94+/-0.14, p=0.01) and the vessel compensation ratio (0.0+/-0.36 vs -0.37+/-0.61, p<0.01) were significantly greater in type A than in type B lesions. The circumferential distribution pattern of percentage plaque area was significantly different between the groups (analysis of variance p<0.005), with greater percentage plaque area for the vessel wall opposite from the side branch in type B lesions (46.3+/-18.0% vs 54.6+/-15.4%, type A vs type B lesions, p<0.05). In conclusion, these results suggest that a major side branch may affect longitudinal lesion remodeling as well as the circumferential location of atherosclerotic plaque.

  View details for DOI 10.1016/j.amjcard.2006.01.073

  View details for PubMedID 16828591

• Safety of beta radiation exposure to the non-target segment: an intravascular ultrasound dosimetric analysis. journal of invasive cardiology Kaneda, H., Honda, Y., Morino, Y., Fox, T., Crocker, I., Lansky, A. J., Yock, P. G., Bonan, R., Fitzgerald, P. J. 2006; 18 (7): 309-312

  Abstract

  The use of longer radioactive seed trains to avoid geographic miss may lead to greater radiation exposure to distal vasculature due to the natural tapering of coronary arteries. The aim of this study was to use IVUS-based dosimetric analysis to evaluate the effect of beta-radiation on angiographically normal, noninjured distal segments.We analyzed 17 in-stent restenosis cases (stent length: 20 +/- 8 mm) treated with a 40 mm 90Sr/Y source train. The prescribed dose was 18.4 Gy (reference less than or equal to 3.3 mm) or 23 Gy (reference > 3.3 mm) at 2 mm from the source. Noninjured, but fully radiated, distal reference sites were determined by angiography. Based upon the three-dimensional vessel contours obtained at baseline, the minimum dose delivered to 90% of plaque volume (Dv90) was determined. Vessel, plaque and lumen volumes and Dv90 were computed in every 2 mm subsegment (n = 52).On average, no significant serial change was observed in plaque area (5.0 +/- 2.5 mm3/mm post-treatment to 5.6 +/- 3.1 mm3/mm at 8-month follow up; p = 0.09), vessel area (10.2 +/- 3.7 to 10.3 +/- 4.0 mm3/mm; p = 0.84), or lumen area (5.2 +/- 2.0 to 4.7 +/- 1.8 mm3/mm; p = 0.19). Subsegment analysis, however, revealed a wide range of dose distribution, with a significant positive correlation between Dv90 and plaque increase (p = 0.008), as well as vessel change (p < 0.001), representing dose-dependent positive vessel remodeling following beta radiation. Consequently, no significant relationship was observed between Dv90 and lumen change.Detailed IVUS-based dosimetric analysis demonstrated that beta radiation promoted positive remodeling, preventing lumen loss despite a mild increase in plaque mass on angiographically normal, noninjured distal segments.

  View details for PubMedID 16816435

• Discordant changes in epicardial and microvascular coronary physiology after cardiac transplantation: Physiologic investigation for transplant arteriopathy II (PITA II) study JOURNAL OF HEART AND LUNG TRANSPLANTATION Fearon, W. F., Hirohata, A., Nakamura, M., Luikart, H., Lee, D. P., Vagelos, R. H., Hunt, S. A., Valantine, H. A., Fitzgerald, P. J., Yock, P. G., Yeung, A. C. 2006; 25 (7): 765-771

  Abstract

  Investigating changes in coronary physiology that occur after cardiac transplantation has been challenging. Simultaneous and independent assessment of the epicardial artery by measuring fractional flow reserve (FFR) and of the microvasculature by calculating the index of microvascular resistance (IMR) with a single coronary pressure wire may be useful.Twenty-five asymptomatic patients with normal coronary angiograms underwent FFR, thermodilution-derived IMR and coronary flow reserve (CFR) and intravascular ultrasound (IVUS) evaluation soon after cardiac transplantation and 1 year later.FFR significantly worsened (0.90 +/- 0.05 at baseline to 0.85 +/- 0.06 at 1 year, p = 0.004). FFR correlated strongly with percent plaque volume as measured by IVUS (r = -0.58, p < 0.0001). IMR improved significantly (29.2 +/- 15.9 at baseline to 19.3 +/- 7.6 units at 1 year, p = 0.007). CFR increased, but not significantly (2.6 +/- 1.4 at baseline to 3.2 +/- 1.2 at 1 year, p = not significant). Diabetes and donor heart ischemic time independently predicted baseline IMR. Treatment with rapamycin independently predicted FFR at 1 year.New coronary physiologic measures, FFR and IMR, show that epicardial artery physiology worsens and correlates with anatomic changes, whereas microvascular physiology improves during the first year after cardiac transplantation. CFR, the traditional method for evaluating coronary circulatory physiology, did not identify these changes.

  View details for DOI 10.1016/j.healun.2006.03.003

  View details for PubMedID 16818118

• Long-term histopathologic and IVUS evaluations of a novel coiled sheet stent in porcine carotid arteries CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY Kaneda, H., Ikeno, F., Lyons, J., Rezaee, M., Yeung, A. C., Fitzgerald, P. J. 2006; 29 (3): 413-419

  Abstract

  Carotid angioplasty with stent placement has been proposed as an alternative method for revascularization of carotid artery stenosis. A novel stent with a laser-cut, rolled sheet of Nitinol (EndoTex Interventional Systems, Inc., Cupertino, CA) has been developed to customize treatment of stenotic lesions in carotid arteries utilizing a single stent, designed to adapt to multiple diameters and to tapered or nontapered configurations. The purpose of this study is to evaluate the conformability and vascular response to a novel stent in a chronic porcine carotid model using serial three-dimensional intravascular ultrasound (IVUS) analysis as well as histological examination. Ten Yucatan pigs underwent stent implantation in both normal carotid arteries with adjunctive balloon angioplasty. Three-dimensional IVUS analysis was performed before stent implantation, after adjunctive balloon angioplasty, and at follow-up [1 month (n = 6), 3 months (n = 6), or 6 months (n = 8)]. Histological examination (injury score, percent plaque obstruction, and qualitative analysis) was also performed. All stents were successfully deployed and well apposed in different sized vessels (lumen area range: 19-30 mm(2)). Volumetric IVUS analysis showed no significant difference between the lumen areas before stent implantation and after adjunctive balloon angioplasty and no stent area change at each follow-up point compared to immediately postprocedure. Histological examination revealed minimal injury and neointimal hyperplasia at each follow-up point. In the chronic porcine carotid model, the novel stent system demonstrated good conformability, resulting in minimal vessel injury and neointimal formation.

  View details for DOI 10.1007/s00270-005-0137-6

  View details for Web of Science ID 000236751300014

  View details for PubMedID 16502176

• Novel stent system for bifurcation lesions: Examination by intravascular ultrasound CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Miyazawa, A., Webster, M. W., Fitzgerald, P. J., Ormiston, J. A. 2006; 67 (6): 900-903

  Abstract

  Bifurcation disease represents a mechanical and biological challenge for definitive interventional treatment. This case report discusses an experience with a novel stent system designed for the treatment of bifurcation lesions.

  View details for DOI 10.1002/ccd.20719

  View details for Web of Science ID 000238082300010

  View details for PubMedID 16649244

• Influence of plaque calcium on neointimal hyperplasia following bare metal and drug-eluting stent implantation CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Shimada, Y., Kataoka, T., Courtney, B. K., Morino, Y., Bonneau, H. N., Yock, P. G., Grube, E., Honda, Y., Fitzgerald, P. J. 2006; 67 (6): 866-869

  Abstract

  To examine the influence of vessel wall calcium on neointimal hyperplasia (NIH) following bare metal stent (BMS) and drug-eluting stent (DES) implantation.While procedural complications with coronary stenting in calcified lesions are well reported, little is known about subsequent NIH on plaque calcium following either BMS or DES implantation.In the Study to COmpare REstenosis Rate between QueST and QuaDDS-QP2 (SCORE) trial, 6 months follow-up volumetric intravascular ultrasound data were available for 41 lesions (BMS, 19; DES, 22). NIH thicknesses on superficial, deep, and noncalcified plaque were calculated at every 0.5 mm intervals over the stented segment. Calcified and less-calcified cross-sections were defined as those containing arcs of plaque calcium > or = 90 degrees and < 90 degrees , respectively.In BMS, mean NIH thickness on both superficial (0.24 +/- 0.23 mm) and deep calcium (0.25 +/- 0.21 mm) was significantly smaller than that of noncalcified plaque (0.31 +/- 0.22 mm) (P < 0.0005). NIH area was significantly smaller in calcified cross-sections compared to less-calcified cross-sections (2.1 +/- 1.2 mm2 vs. 3.1 +/- 1.9 mm2, P < 0.0001). While in contrast, in DES, mean NIH thickness was similar, irrespective of the presence or location of calcium (0.03 +/- 0.05 mm vs. 0.03 +/- 0.06 mm vs. 0.03 +/- 0.05 mm, superficial vs. deep vs. noncalcified plaque, P = NS). NIH area was also similar between calcified and less-calcified cross-sections (0.3 +/- 0.6 mm2 vs. 0.3 +/- 0.6 mm2, P = NS).These results suggest that while plaque calcium may influence NIH following BMS implantation, NIH suppression using DES does not appear to be affected by the presence or location of calcium.

  View details for DOI 10.1002/ccd.20708

  View details for PubMedID 16649232

• Location of focal vasospasm provoked by ergonovine maleate within coronary arteries in patients with vasospastic angina pectoris AMERICAN JOURNAL OF CARDIOLOGY Koizumi, T., Yokoyama, M., Namikawa, S., Kuriyama, N., Nameki, M., Nakayama, T., Kaneda, H., Sudhir, K., Yock, P. G., Komiyama, N., Fitzgerald, P. J. 2006; 97 (9): 1322-1325

  Abstract

  This study examined whether coronary focal vasospasm occurs in a nonuniform distribution within the coronary tree and whether a longitudinal plaque distribution pattern is present in patients with vasospastic angina using 3-dimensional intravascular ultrasound analysis. Of 121 patients with clinically suspected angina without fixed stenosis in the coronary arteries, vasospasm was provoked in 82 patients with 92 lesions (42 focal, 50 diffuse) by intravenous ergonovine maleate injection. Most focal vasospasms occurred in the proximal third of the coronary arteries (proximal 28, mid 8, distal 6, p <0.01), corresponding to the historical high-risk zones for acute coronary occlusion. More plaque burden also existed in the proximal third of the coronary arteries in patients with focal vasospasm.

  View details for DOI 10.1016/j.amjcard.2005.11.073

  View details for Web of Science ID 000237483100012

  View details for PubMedID 16635604

• Sirolimus-eluting stents vs vascular brachytherapy for in-stent restenosis within bare-metal stents - The SISR randomized trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Holmes, D. R., Teirstein, P., Satler, L., Sketch, M., O'Malley, J., Popma, J. J., Kuntz, R. E., Fitzgerald, P. J., Wang, H., Caramanica, E., Cohen, S. A. 2006; 295 (11): 1264-1273

  Abstract

  Although vascular brachytherapy is the only approved therapy for restenosis following bare-metal stent implantation, drug-eluting stents are now being used. Data on the relative merits of each are limited.To determine the safety and efficacy of the sirolimus-eluting stent compared with vascular brachytherapy for the treatment of patients with restenosis within a bare-metal stent.Prospective, multicenter, randomized trial of 384 patients with in-stent restenosis who were enrolled between February 2003 and July 2004 at 26 academic and community medical centers. Data presented represent all follow-up as of June 30, 2005.Vascular brachytherapy (n = 125) or the sirolimus-eluting stent (n = 259).Target vessel failure (cardiac death, myocardial infarction, or target vessel revascularization) at 9 months postprocedure.Baseline patient characteristics were well matched. Lesion length was similar between vascular brachytherapy and sirolimus-eluting stent patients (mean [SD], 16.76 [8.55] mm vs 17.22 [7.97] mm, respectively; P = .61). Procedural success was 99.2% (124/125) in the vascular brachytherapy group and 97.3% (250/257) in the sirolimus-eluting stent group (P = .28). The rate of target vessel failure was 21.6% (27/125) with vascular brachytherapy and 12.4% (32/259) with the sirolimus-eluting stent (relative risk [RR], 1.7; 95% confidence interval [CI], 1.1-2.8; P = .02). Target lesion revascularization was required in 19.2% (24/125) of the vascular brachytherapy group and 8.5% (22/259) of the sirolimus-eluting stent group (RR, 2.3 [95% CI, 1.3-3.9]; P = .004). At follow-up angiography, the rate of binary angiographic restenosis for the analysis segment was 29.5% (31/105) for the vascular brachytherapy group and 19.8% (45/227) for the sirolimus-eluting stent group (RR, 1.5 [95% CI, 1.0-2.2]; P = .07). Compared with the vascular brachytherapy group, minimal lumen diameter was larger in the sirolimus-eluting stent group at 6-month follow-up (mean [SD], 1.52 [0.63] mm vs 1.80 [0.63] mm; P<.001), reflecting greater net lumen gain in the analysis segment (0.68 [0.60] vs 1.0 [0.61] mm; P<.001) due to stenting and no edge restenosis.Sirolimus-eluting stents result in superior clinical and angiographic outcomes compared with vascular brachytherapy for the treatment of restenosis within a bare-metal stent.ClinicalTrials.gov Identifier: NCT00231257.

  View details for Web of Science ID 000235972600024

  View details for PubMedID 16531619

• Mechanisms of lumen narrowing of saphenous vein bypass grafts 12 months after implantation: An intravascular ultrasound study AMERICAN HEART JOURNAL Kaneda, H., Terashima, M., Takahashi, T., Iversen, S., Felderhoff, T., Grube, E., Yock, P. G., Honda, Y., Fitzgerald, P. J. 2006; 151 (3): 726-729

  Abstract

  Previous long-term (>1 year) studies have suggested that saphenous vein bypass grafts (SVGs) undergo vascular remodeling similar to native coronary arteries. However, early morphologic stages of SVG remodeling have not been characterized in vivo.Thirty SVGs were studied 12 months after implantation using an intravascular ultrasound automated pullback system. Intravascular ultrasound images were analyzed between 10 and 60 mm from the tip of the guide. Lumen area (LA), intima area (IA), and vessel area (VA, defined as the area within the outer border of a hypoechoic intimal layer) were computed at 3 cross sections: the minimum LA (MLA) site and the proximal and distal reference sites. Area changes (Delta) were calculated as the MLA site minus the average of the reference sites.In this cohort, 70% of the MLA sites had a smaller VA than the average references. On average, MLA sites had significantly smaller VA (9.7 +/- 2.9 vs 10.7 +/- 3.2 mm2, P < .01) and larger IA (2.5 +/- 2.1 vs 1.2 +/- 1.3 mm2, P < .01) than at the reference sites. The relative contribution of DeltaVA (-1.0 +/- 1.4 mm2) and DeltaIA (1.3 +/- 1.3 mm2) to lumen compromise (-2.3 +/- 1.4 mm2) were 43% and 57%, respectively. On the other hand, simple linear regression analysis revealed a significant positive correlation between DeltaIA and DeltaVA (y = -1.7 + 0.52x, r = 0.50, P < .01).Within the first year, the mechanism of lumen compromise in SVG is a combination of negative remodeling and intimal hyperplasia. Positive remodeling is seen in a minority of cases. However, the direction and extent of remodeling correlated with change in intimal thickness.

  View details for DOI 10.1016/j.ahj.2005.05.011

  View details for Web of Science ID 000236353900027

  View details for PubMedID 16504641

• Longitudinal distribution of neointimal hyperplasia within ABT-578 eluting phosphorylcholine-coated stents in de novo coronary lesions i2 Summit 2006 on Innovation in Intervention Sakurai, R., Hongo, Y., Wijns, W., Fajadet, J., Kuntz, R. E., Cutlip, D., Popma, J. J., Zimetbaum, P., Yock, P. G., Fitzgerald, P. J., Honda, Y. ELSEVIER SCIENCE INC. 2006: 3B–3B

  View details for Web of Science ID 000235530500011

• Novel intra-operative fluorescence imaging system for on-site assessment of off-pump coronary artery bypass graft 55th Annual Scientific Session of the American-College-of-Cardiology Waseda, K., Hasegawa, T., SHIMADA, Y., Ako, J., Ikeno, F., Yock, P. G., Honda, Y., Fitzgerald, P. J., Takahashi, M. ELSEVIER SCIENCE INC. 2006: 178A–178A

  View details for Web of Science ID 000235530401084

• Acute and long-term outcomes of the novel side access (SLK-View (TM)) stent for bifurcation coronary lesions: A multicenter nonrandomized feasibility study CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Ikeno, F., Kim, Y. H., Luna, J., Condado, J. A., Colombo, A., Grube, E., Fitzgerald, P. J., Park, S. J., Yeung, A. C. 2006; 67 (2): 198-206

  Abstract

  To evaluate technical feasibility and procedural safety of SLK-View stent for treating bifurcation lesions.Percutaneous treatment of coronary bifurcation lesions represents a technical challenge. Several stenting techniques and dedicated devices have proven unsuccessful, with high rates of side branch occlusion at index procedure and follow-up.Eighty one patients with 84 de novo coronary artery lesions involving a major side branch underwent SLK-View (Advanced Stent Technologies, Inc., Pleasanton, CA) stent implantation with subsequent kissing balloon post dilatation. SLK-View stent is a new scaffolding device incorporating a side aperture that allows access to the side-branch of a bifurcation after deployment of the stent in main vessel. All patients underwent angiographic follow-up at 6 months. Procedural, in-hospital, and 6-month follow-up outcomes were examined.The lesions were located in left main (n = 11), left anterior descending (n = 50), left circumflex (n = 8), right coronary artery (n = 7), and 1 ramus intermedius. The most frequent lesions (44.1%) were true bifurcations. Successful stent delivery to bifurcation was accomplished in 82/84 of the cases (97.6%). Technical success was obtained in 99 and 94% of main vessel and side branches, respectively. Stenting in side-branch was performed in 21 lesions (25%). Side-branches were accessed effectively in 100% of bifurcations postprocedurally. Binary restenosis rate at 6-month follow-up was 28.3% and 37.7% for main vessel and side-branch, respectively. TLR rate at 6-month follow-up was 21% and CABG rate of 6%.In this consecutive multicenter series of patients with coronary bifurcation lesions, this novel side-branch access stent proved feasible, with a high procedural success rate, while maintaining side-branch access.

  View details for DOI 10.1002/ccd.20556

  View details for Web of Science ID 000235145100005

  View details for PubMedID 16404749

• Heterogeneity of neointimal distribution of in-stent restenosis in patients with diabetes mellitus AMERICAN JOURNAL OF CARDIOLOGY Kaneda, H., Ako, J., Kataoka, T., Takahashi, T., Terashima, M., Waseda, K., Miyazawa, A., Hassan, A., Honda, Y., Yock, P. G., Fitzgerald, P. J. 2006; 97 (3): 340-342

  Abstract

  Diabetes mellitus is an independent predictor of restenosis after percutaneous coronary intervention. The pattern of restenosis after bare metal stent implantation in diabetic patients was examined with 3-dimensional intravascular ultrasound analysis. Lumen and stent were manually traced at every 0.5-mm interval in stented segments. Using Simpson's method, stent, luminal, and neointimal (stent minus lumen) volumes were calculated and average area was calculated as volume data divided by length. To measure the cross-sectional and longitudinal severities of luminal encroachment by the neointima, percent neointimal area (neointimal area divided by stent area) and neointimal hyperplasia 50 (IH50) (defined as percent stent length with percent neointimal area >50%) were calculated. In 278 patients (68 with diabetes and 210 without diabetes), there was a significantly higher percentage of maximal percent neointimal area with significantly longer percent stent length that was severely encroached by the neointima in diabetic patients. Diabetic patients showed a more heterogenous pattern of the neointima after bare metal stenting, resulting in longer high-grade obstruction segments. This may have important implications for stent design and pharmacokinetic properties of next-generation drug-eluting technology for this complex patient subset.

  View details for DOI 10.1016/j.amjcard.2005.08.067

  View details for Web of Science ID 000235265400009

  View details for PubMedID 16442392

• Selective renal arterial infusion of fenoldopam for the prevention of contrast-induced nephropathy. Journal of interventional cardiology Ng, M. K., Tremmel, J., Fitzgerald, P. J., Fearon, W. F. 2006; 19 (1): 75-79

  Abstract

  Contrast-induced nephropathy (CIN) remains an important complication of angiographic procedures, particularly among patients with significant renal impairment. To date, vasodilator therapies such as fenoldopam have failed to prevent CIN, possibly because significant hypotension as a result of systemic infusion has limited the ability to deliver adequate drug levels to the renal vasculature. We present a case of averted CIN after multivessel coronary intervention in a diabetic patient with severe renal insufficiency, potentially due to bilateral renal arterial infusion of fenoldopam. Our subsequent experience with intrarenal fenoldopam in nine additional procedures in eight other high risk patients resulted in one case of asymptomatic transient CIN. Further studies are warranted to evaluate the efficacy of intrarenal administration of vasodilator therapies such as fenoldopam for the prevention of CIN.

  View details for PubMedID 16483344

• Latent plaque rupture in a patient undergoing stenting for acute coronary syndrome and diffuse coronary disease: A case report and review of literature CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Koizumi, T., Wilson, A. M., Clark, D. A., Fitzgerald, P. J. 2006; 67 (2): 241-245

  Abstract

  Secondary prevention of plaque rupture following percutaneous coronary intervention in patients with acute coronary syndrome is not well studied. This case report describes a 53-year-old man who experienced plaque rupture between two previously successfully implanted stents in the right coronary artery, as documented during the 3rd intervention using intravascular ultrasound.

  View details for DOI 10.1002/ccd.20596

  View details for Web of Science ID 000235145100011

  View details for PubMedID 16400671

• Transient left ventricular dysfunction under severe stress: Brain-heart relationship revisited AMERICAN JOURNAL OF MEDICINE Ako, J., Sudhir, K., Farouque, H. M., Honda, Y., Fitzgerald, P. J. 2006; 119 (1): 10-17

  Abstract

  Transient left ventricular dysfunction in patients under emotional or physical stress, also known as tako-tsubo-like left ventricular dysfunction, has been recently been recognized as a distinct clinical entity. The aims of this review are to define this phenomenon and to explore its similarities to the left ventricular dysfunction seen in patients with acute brain injury.MEDLINE database, bibliographies of each citation for relevant articles, and consultation with clinical experts were used to examine the clinical picture of tako-tsubo-like left ventricular dysfunction.We identified case series and a systematic review that report on patients with this syndrome. This phenomenon occurs predominantly in female patients, presenting with a variety of ST-T segment changes and mildly elevated cardiac enzymes that mimic an acute coronary syndrome. The left ventricular dysfunction, typically showing a hyperkinetic basal region and an akinetic apical half of the ventricle, occurs in the absence of obstructed epicardial coronary arteries. The ventricular dysfunction usually resolves within weeks with a generally favorable prognosis. This phenomenon has similarities to that seen in patients with acute brain injury with regard to clinical presentation, pathology, and its reversible nature.Transient left ventricular dysfunction occurs in the absence of obstructive epicardial coronary artery disease. In its broadest sense, this phenomenon may encompass a range of disorders including left ventricular dysfunction after central nervous system injury.

  View details for DOI 10.1016/j.amjmed.2005.08.022

  View details for Web of Science ID 000234912000005

  View details for PubMedID 16431176

• Vascular response to Sirolimus-Eluting Stents delivered with a NonAggressive implantation technique: Comparison of intravascular ultrasound results from the multicenter, Randomized E-SIRIUS, and SIRIUS trials 76th Annual Scientific Session of the American-Heart-Association Hoffmann, R., Guagliumi, G., Musumeci, G., Reimers, B., Petronio, A. S., Disco, C., Amoroso, G., Moses, J. W., Fitzgerald, P. J., Schofer, J., Leon, M. B., Breithardt, G. WILEY-LISS. 2005: 499–506

  Abstract

  The effectiveness of SES to reduce the risk of restenosis was initially demonstrated in short lesions using stent implantation with routine pre-dilatation and post-dilatation. This intravascular ultrasound (IVUS) substudy of the E-SIRIUS trial sought to evaluate local arterial responses to sirolimus-eluting stents (SES) delivered with a stent implantation technique allowing direct stenting and only selectively applying high-pressure post-dilatation.IVUS was performed immediately after intervention and at 8-month follow-up in 51 patients randomised to either bare-metal stents (BMS; Bx-Velocitytrade mark; N=20) or SES (Cyphertrade mark N=31). Direct stenting was allowed (24%) and post-dilation was performed only selectively (32%). Lumen dimensions, intimal hyperplasia and vessel remodeling were compared between SES and BMS. Subsequently, results of SES in the E-SIRIUS IVUS substudy (N=31) were compared to those of SES in the IVUS substudy of the SIRIUS trial (N=137). SES in SIRIUS IVUS substudy were delivered with 100% pre-dilatation and 77% post-dilatation. Baseline stent and reference segment measurements were similar between BMS and SES in E-SIRIUS IVUS patients. Using SES there was a 96% reduction in intimal hyperplasia volume within the stented segment (1.8+/-4.9 vs 50.6+/-39.7 mm3, P<0.001) and a significantly larger minimal lumen cross sectional area at 8-month follow-up (4.5+/-1.1 vs 2.3+/-0.9 mm2, P<0.001). No vessel remodeling was observed with the use of SES. The applied stent implantation technique resulted in a minimal stent/reference vessel area ratio of 0.75+/-0.17 in E-SIRIUS SES as compared to 0.84+/-0.23 in SIRIUS SES (P=0.046). Mean intimal hyperplasia cross-sectional area at follow-up was 0.1+/-0.2 mm2 in the SES group of E-SIRIUS and 0.5+/-0.8 mm2 in the SES group of SIRIUS (P=0.003).An implantation technique of SES which includes direct stenting and minimizes the use of high-pressure post-dilatation results in less optimal stent expansion. However, follow-up results compare very favourable to those of BMS and are characterised by even less intimal hyperplasia than after a more forceful implantation of SES.

  View details for DOI 10.1002/ccd.20542

  View details for Web of Science ID 000233800100008

  View details for PubMedID 16273564

• IMPACT trial: Angiographic and intravascular ultrasound observations of the first human experience with mycophenolic acid-eluting polymer Stent system CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Abizaid, A., Albertal, M., Ormiston, J., Londero, H., Ruygrok, P., Seixas, A. C., Feres, F., Mattos, L. A., Staico, R., Silva, R. L., Webster, M., STEWART, J., Paoletti, F., Kataoka, T., Fitzgerald, P., Sousa, A., Sousa, J. E. 2005; 66 (4): 491-495

  Abstract

  The purpose of the study was to examine the safety and efficacy of two different formulations of mycophenolic acid (MPA)-eluting Duraflex stents on coronary de novo lesions. Recent data indicate that local delivery of MPA in the porcine overstretch coronary model significantly reduces neointimal hyperplasia (NIH). Patients were divided into three consecutive groups. The first (n=50) and second (n=55) groups received moderate- and slow-release MPA-eluting Duraflex stent, respectively. The last group (n=50) received the bare metal Duraflex stent. Clinical, angiographic, and intravascular ultrasound analysis were performed at 6-month follow-up. All stents were successfully deployed and patients were discharged home without clinical events. Compared to controls, 6-month in-lesion and in-stent minimum luminal diameter as well as late lumen loss were not significantly different in the moderate- and slow-release treatment groups. At follow-up, percentage obstruction and NIH volume were also similar between the three groups. At 30 days and 6 and 12 months, there were no differences noted between the three groups with respect to major adverse cardiac events as well as the individual rates of mortality, myocardial infarction, or repeat revascularization. There were no cases of subacute or late thrombosis. In this feasibility trial, the MPA-eluting Duraflex stents in either slow- or moderate-release formulations were well tolerated, but showed no benefit for treatment of coronary lesions when compared to controls. Further testing with different drug dosing or delivery rate might improve these results.

  View details for DOI 10.1002/ccd.20454

  View details for Web of Science ID 000233800100006

  View details for PubMedID 16283680

• Impact of asymmetric stent expansion on neointimal hyperplasia following sirolimus-eluting stent implantation AMERICAN JOURNAL OF CARDIOLOGY Kaneda, H., Ako, J., Honda, Y., Terashima, M., Morino, Y., Yock, P. G., Popma, J. J., Leon, M. B., Moses, J. W., Fitzgerald, P. J. 2005; 96 (10): 1404-1407

  Abstract

  To assess whether asymmetric stent expansion affects suppression of neointimal hyperplasia after sirolimus-eluting stent implantation, 64 patients in the SIRolImUS-coated Bx Velocity stent trial who underwent single 18-mm stent implantation and 3-dimensional intravascular ultrasonography at 8-month follow-up were enrolled. To assess the longitudinal stent asymmetric expansion, 2 cross sections with a maximal/minimal stent area were chosen in each patient. To assess for tomographic stent asymmetric expansion, stent eccentricity was determined by dividing the minimum stent diameter by the maximum stent diameter. At the 2 cross sections with a maximal/minimal stent area, a sirolimus-eluting stent reduced neointimal hyperplasia significantly with no interaction between the treatment and stent areas. A sirolimus-eluting stent also significantly reduced neointimal hyperplasia in the concentric and eccentric stent groups.

  View details for DOI 10.1016/j.amjcard.2005.07.044

  View details for Web of Science ID 000233509900012

  View details for PubMedID 16275187

• Predictors of edge stenosis following sirolimus-eluting stent deployment (A quantitative intravascular ultrasound analysis from the SIRIUS trial) AMERICAN JOURNAL OF CARDIOLOGY Sakurai, R., Ako, J., Morino, Y., Sonoda, S., Kaneda, H., Terashima, M., Hassan, A. H., Leon, M. B., Moses, J. W., Popma, J. J., Bonneau, H. N., Yock, P. G., Fitzgerald, P. J., Honda, Y. 2005; 96 (9): 1251-1253

  Abstract

  To study the interaction of the sirolimus-eluting stent and vessel margins, we analyzed the intravascular ultrasound parameters in 317 edges of 167 stents having 18 edge stenoses at 8 months of follow-up from the SIRIUS trial. Of the baseline parameters, a larger reference percentage of plaque area and a larger edge stent area/reference minimum lumen area were associated with edge stenosis in the sirolimus-eluting stent cohort compared with the incidence of edge stenosis in the bare metal stent cohort. Thus, full lesion coverage and matching the stented segment properly to the adjacent segment using intravascular ultrasound guidance may improve sirolimus-eluting stent implantation efficacy further.

  View details for DOI 10.1016/j.amjcard.2005.06.066

  View details for Web of Science ID 000233343500015

  View details for PubMedID 16253592

• Humanitarian use devices/humanitarian device exemptions in cardiovascular medicine 2nd Dartmouth Drug and Device Development Symposium Kaplan, A. V., Harvey, E. D., Kuntz, R. E., Shiran, H., Robb, J. F., Fitzgerald, P. LIPPINCOTT WILLIAMS & WILKINS. 2005: 2883–86

  Abstract

  The Second Dartmouth Device Development Symposium held in October 2004 brought together leaders from the medical device community, including clinical investigators, senior representatives from the US Food and Drug Administration, large and small device manufacturers, and representatives from the financial community to examine difficult issues confronting device development. The role of the Humanitarian Use Device/Humanitarian Device Exemption (HUD/HDE) pathway in the development of new cardiovascular devices was discussed in this forum. The HUD/HDE pathway was created by Congress to facilitate the availability of medical devices for "orphan" indications, ie, those affecting <4000 individuals within the United States each year. The HUD/HDE pathway streamlines the approval process and permits less well-characterized devices to enter the market. HDE approval focuses primarily on issues of safety and scientific soundness and does not require demonstration of efficacy. In the 7 years since the first device was approved in 1997, a total of 35 HDEs have been granted (23 devices, 6 diagnostic tests). As the costs to gain regulatory approval for commonly used devices increase, companies often seek alternative ways to gain market access, including the HUD/HDE pathway. For a given device, there may be multiple legitimate and distinct indications, including indications that meet the HUD criteria. Companies must choose how and when to pursue each of these indications. The consensus of symposium participants was for the HUD/HDE pathway to be reserved for true orphan indications and not be viewed strategically as part of the clinical development plan to access a large market.

  View details for DOI 10.1161/CIRCULATIONAHA.105.553701

  View details for Web of Science ID 000232988900020

  View details for PubMedID 16267261

• Impact of intravascular ultrasound lesion characteristics on neointimal hyperplasia following sirolimus-eluting stent implantation AMERICAN JOURNAL OF CARDIOLOGY Kaneda, H., Koizumi, T., Ako, J., Terashima, M., Morino, Y., Honda, Y., Yock, P. G., Leon, M. B., Moses, J. W., Fitzgerald, P. J. 2005; 96 (9): 1237-1241

  Abstract

  The effect of lesion characteristics on neointimal hyperplasia after sirolimus-eluting stent implantation was examined in 45 patients who underwent successful preinterventional intravascular ultrasound. There were no differences in neointimal hyperplasia between the moderate/severe calcified lesion group (calcium arc >120 degrees ) and the non/mild calcified lesion group or between the positive vessel remodeling group (external elastic membrane area at the minimal lumen area site larger than that at the proximal reference site) and negative vessel remodeling group. No correlation between preinterventional plaque burden and neointimal hyperplasia was found. In patients who have coronary artery disease, sirolimus-eluting stents continue to demonstrate striking suppression of neointimal proliferation, irrespective of lesion characteristics previously associated with greater restenotic risk.

  View details for DOI 10.1016/j.amjcard.2005.06.063

  View details for Web of Science ID 000233343500012

  View details for PubMedID 16253589

• Changes in the anatomy and physiology of the coronary circulation after cardiac transplantation: Novel structural and physiologic evidence of cardiac transplant arteriopathy 78th Annual Scientific Session of the American-Heart-Association Hirohata, A., Nakamura, M., Waseda, K., Valantine, H. A., Hunt, S. A., Honda, Y., Yock, P. G., Fitzgerald, P. J., Yeung, A. C., Fearon, W. F. LIPPINCOTT WILLIAMS & WILKINS. 2005: U517–U517

  View details for Web of Science ID 000232956403127

• A randomized comparison of ABT-578 eluting phosphorylcholine-coated cobalt-chromium stents with bare metal stents in de novo coronary lesions: Final intravascular ultrasound results from the ENDEAVOR II trial 78th Annual Scientific Session of the American-Heart-Association Sakurai, R., Hongo, Y., Honda, Y., Cutlip, D., Popma, J. J., Zimetbaum, P., Yock, P. G., Fajadet, J., Pasteur, C., Kuntz, R. E., Wijns, W., Fitzgerald, P. J. LIPPINCOTT WILLIAMS & WILKINS. 2005: U748–U748

  View details for Web of Science ID 000232956404509

• Different vessel response between LAD and non-LAD after treatment with sirolimus-eluting stent: A serial 3D-intravascular ultrasound study 78th Annual Scientific Session of the American-Heart-Association Waseda, K., Ako, J., SHIMADA, Y., Morino, Y., Hongo, Y., Sudhir, K., Yock, P. G., Fitzgerald, P. J., Honda, Y. LIPPINCOTT WILLIAMS & WILKINS. 2005: U799–U799

  View details for Web of Science ID 000232956405102

• Intravascular ultrasound analysis of ABT-578 eluting phosphorylcholine-coated cobalt-chromium stents compared to bare metal stents in de novo coronary lesions: Results from the ENDEAVOR II trial 17th Annual Transcatheter Cardiovascular Therapeutics Symposium/4th Annual Transcatheter Cardiovascular Therapeutics Inflammation Summit Sakurai, R., Hongo, Y., Honda, Y., Cutlip, D., Popma, J. J., Zimetbaum, P., Yock, P. G., Fajadet, J., Kuntz, R. E., Wijns, W., Fitzgerald, P. J. EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2005: 184H–184H

  View details for Web of Science ID 000232725200470

• Late incomplete stent apposition after sirolimus-eluting stent implantation - A serial intravascular ultrasound analysis JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Ako, J., Morino, Y., Honda, Y., Hassan, A., Sonoda, S., Yock, P. G., Leon, M. B., Moses, J. W., Bonneau, H. N., Fitzgerald, P. J. 2005; 46 (6): 1002-1005

  Abstract

  We sought to identify the frequency of incomplete stent apposition (ISA) in sirolimus-eluting stents (SES) and clarify its findings and clinical sequelae.Late-acquired ISA has been reported in bare-metal stents (BMS) and brachytherapy and recently in drug-eluting stents. However, the characteristics of late ISA in SES have not been clarified.From the SIRIUS trial, a randomized, multicenter study comparing SES and BMS, serial qualitative intravascular ultrasound (IVUS; at stent implantation and eight-month follow-up) was available in 141 patients (BMS: n = 61; SES: n = 80). The IVUS images were reviewed for the presence of ISA.Incomplete stent apposition at follow-up was observed in 19 patients (BMS: n = 6 [9.8%]; SES: n = 13 [16.3%]; p = NS). Among these, 12 had ISA after intervention and at follow-up (persistent ISA). Late-acquired ISA was seen in the remaining seven cases, all from the SES group (BMS: n = 0; SES: n = 7 [8.7%]; p < 0.05). In late-acquired ISA, there was an increase in external elastic membrane area (after intervention: 16.2 +/- 2.7 m2; follow-up: 18.9 +/- 3.6 mm2; p < 0.05). The location of stent-vessel wall separation was primarily at the stent edges in persistent ISA cases, whereas late-acquired ISA in SES occurred mostly in the mid portion of the stent. There were no negative clinical events reported for any ISA cases at 12-month clinical follow-up.Late ISA was observed in 8.7% of patients after SES implantation. There were no negative clinical events associated with this IVUS finding at 12-month clinical follow-up; however, careful long-term follow-up will be necessary.

  View details for DOI 10.1016/j.jacc.2005.05.068

  View details for Web of Science ID 000231991600009

  View details for PubMedID 16168282

• Effect of lumen narrowing within coronary stents on proximal and distal vessel segments following bare metal stent implantation AMERICAN JOURNAL OF CARDIOLOGY Kaneda, H., Ako, J., Kataoka, T., Miyazawa, A., Terashima, M., Ikeno, F., Sonoda, S., SHIMADA, Y., Morino, Y., Honda, Y., Yock, P. G., Fitzgerald, P. J. 2005; 96 (3): 376-378

  Abstract

  Adjacent reference vessel response to smaller lumens at stented segments was examined with 3-dimensional intravascular ultrasound analysis. In 128 patients after bare metal stent implantation, minimal lumen area (MLA) within the stent and average lumen area at distal/proximal adjacent reference segments (5 mm) were obtained at baseline and follow-up. In the smaller in-stent MLA group (MLA <3 mm2), lumen area decreased significantly at the distal edge compared with the larger in-stent MLA group (MLA > or =3 mm2), although no significant difference was seen at the proximal edge. In-stent lumen patency may influence vascular responses at adjacent reference segments after bare metal stent implantation.

  View details for DOI 10.1016/j.amjcard.2005.03.079

  View details for Web of Science ID 000231057000011

  View details for PubMedID 16054461

• Plasma low-density lipoprotein reduction and structural effects on coronary atherosclerotic plaques by atorvastatin as clinically assessed with intravascular ultrasound radio-frequency signal analysis: A randomized prospective study AMERICAN HEART JOURNAL Yokoyama, M., Komiyama, N., Courtney, B. K., Nakayama, T., Namikawa, S., Kuriyama, N., Kuizumi, T., Nameki, M., Fitzgerald, P. J., Komuro, I. 2005; 150 (2)

  Abstract

  Plaque stabilization by statins is important for reduction of cardiovascular events but has not been demonstrated enough in vivo. We examined whether statins clinically alter the structure of coronary atherosclerotic plaques using intravascular ultrasound (IVUS) radio-frequency (RF) signal analysis.Fifty consecutive patients undergoing percutaneous coronary intervention were enrolled. Intravascular ultrasound radio-frequency signals were acquired from non-percutaneous coronary intervention-targeted echolucent plaques. The patients were randomly assigned into 2 groups: group S (n = 25) taking atorvastatin 10 mg/d and group C (n = 25) as control. After 6-month follow-up, IVUS-RF signals were sampled at the same plaque sites. Several regions of interest were placed on each plaque. Intravascular ultrasound radio-frequency parameters were blindly calculated in all regions of interests (group S, n = 148; group C, n = 191). Targeted plaque volumes were also measured. Those data were compared between baseline and follow-up.In group S after 6 months, plasma low-density lipoprotein level was significantly decreased (133 +/- 13 to 87 +/- 29 mg/dL, P < .0001), integrated backscatter of IVUS-RF signals was substantially increased (-53.8 +/- 4.5 to -51.2 +/- 4.9 dB, P < .0001), and plaque volume was significantly reduced, whereas no change was demonstrated in group C.These results suggest that statins alter properties as well as volumes of coronary plaques within 6 months, which may be related to plasma low-density lipoprotein reduction. Intravascular ultrasound radio-frequency signal analysis may be useful to evaluate the effects of drugs on stabilization of coronary atherosclerotic plaques.

  View details for DOI 10.1016/j.ahj.2005.03.059

  View details for Web of Science ID 000232273100017

  View details for PubMedID 16086932

• Impact of different definitions on the interpretation of coronary remodeling determined by intravascular ultrasound CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Hibi, K., Ward, M. R., Honda, Y., Suzuki, T., Jeremias, A., Okura, H., Hassan, A. H., Maehara, A., Yeung, A. C., Pasterkamp, G., Fitzgerald, P. J., Yock, P. G. 2005; 65 (2): 233-239

  Abstract

  The objective of this study was to compare the categorizations and determinants related to remodeling by the three definitions commonly used. Several morphological and intravascular ultrasound (IVUS) studies have demonstrated the fundamental importance of arterial remodeling in atherosclerosis. However, lack of consensus on how to define remodeling has led to conflicting analyses of factors that influence this process. Analysis of pre-interventional IVUS images of 514 lesions in native coronary arteries was performed. Arterial remodeling was defined as outward by definition 1, when [cross-sectional area (CSA) of the external elastic membrane (EEM) at the lesion site (EEM(lesion))]/[EEM CSA either at the proximal (EEM(prox ref)) or distal (EEM(distal ref)) reference site with the least amount of plaque] was > 1.05, intermediate when this ratio was between 0.95 and 1.05, and inward when < 0.95. Remodeling was defined as outward by definition 2 when EEM(lesion) > both EEM(prox ref) and EEM(distal ref), inward when EEM(lesion) < both EEM(prox ref) and EEM(distal ref), and intermediate when EEM(lesion) was intermediate between EEM(prox ref) and EEM(distal ref). By definition 3, vessel remodeling was defined as outward when EEM(lesion) > (EEM(prox ref) + EEM(distal ref))/2 and intermediate/inward when EEM(lesion) < or = (EEM(prox ref) + EEM(distal ref))/2. The frequency of outward remodeling was significantly higher by definitions 1 and 3 than by definition 2, whereas a higher frequency of inward remodeling was observed in definition 1, resulting in significantly different remodeling distributions between the three definitions (P < 0.0001). By multivariate logistic analysis, the only clinical determinants related to outward remodeling was younger age, and only by definition 3. IVUS determinants varied significantly between the three definitions. The only consistent determinants among the three definitions were smaller lumen CSA at the reference site and larger plaque + media CSA at the lesion site. This study demonstrates the significant impact of different remodeling definitions on the incidence and determinants of remodeling patterns. The marked variability in categorization of remodeling underscores the importance of developing a standard methodology.

  View details for DOI 10.1002/ccd.20366

  View details for Web of Science ID 000229557600015

  View details for PubMedID 15812811

• Impact of final Stent dimensions on long-term results following sirolimus-eluting stent implantation - Serial intravascular ultrasound analysis from the SIRIUS trial JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Sonoda, S., Morino, Y., Ako, J., Terashima, M., Hassan, A. H., Bonneau, H. N., Leon, M. B., Moses, J. W., Yock, P. G., Honda, Y., Kuntz, R. E., Fitzgerald, P. J. 2004; 43 (11): 1959-1963

  Abstract

  We assessed the predictive value of minimum stent area (MSA) for long-term patency of sirolimus-eluting stents (SES) implantation compared to bare metal stents (BMS).Although MSA is a consistent predictor of in-stent restenosis, its predictive value in BMS is still limited because of biologic variability in the restenosis process.From the SIRolImUS (SIRIUS) trial, 122 cases (SES: 72; BMS: 50) with complete serial intravascular ultrasound (IVUS) (baseline and 8-month follow-up) were analyzed. Postprocedure MSA and follow-up minimum lumen area (MLA) were obtained. Based on previous physiologic studies, adequate stent patency at follow-up was defined as MLA >4 mm(2).In both groups, a significant positive correlation was observed between baseline MSA and follow-up MLA (SES: p < 0.0001, BMS: p < 0.0001). However, SES showed higher correlation than BMS (0.8 vs. 0.65) with a higher regression coefficient (0.92 vs. 0.59). The sensitivity and specificity curves identified different optimal thresholds of MSA to predict adequate follow-up MLA: 5 mm(2) for SES and 6.5 mm(2) for BMS. The positive predictive values with these cutoff points were 90% and 56%, respectively.In this SIRIUS IVUS substudy, SES reduced both biologic variability and restenosis, resulting in increased predictability of long-term stent patency with postprocedure MSA. In addition, SES had a considerably lower optimal MSA threshold compared to BMS.

  View details for DOI 10.1016/j./jacc.2004.01.044

  View details for Web of Science ID 000221715800006

  View details for PubMedID 15172398

• Validation of a thermographic guidewire for endoluminal mapping of atherosclerotic disease: An in vitro study CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Courtney, B. K., Nakamura, M., Tsugita, R., Lilly, R., Basisht, R., Grube, E., Honda, Y., Yock, P. G., Fitzgerald, P. J. 2004; 62 (2): 221-229

  Abstract

  Temperature heterogeneity along the inner surface of an artery may be a surrogate marker of impending plaque rupture and has been associated with an increased likelihood of future coronary events. Initial studies using catheter-based thermographic devices have demonstrated that the changes in temperature are subtle, while the effects of coronary flow on measured temperature have not yet been examined. A novel guidewire-based system (ThermoCoil, Imetrx) designed to measure surface temperature in coronary arteries was used to study the effects of heat source intensity and flow on measured temperature. An in vitro model of a focal, eccentric, heat-generating lesion demonstrated that a guidewire-based system can detect changes in surface temperature with a precision of less than 0.08 degrees C. In this model, temperature measurements increased linearly with source temperature and decreased with increases in flow by an exponent of -0.33 (P < 0.001 for both). Flow rates and heat source properties can significantly influence the measurement and interpretation of thermographic data. The incorporation of 2D thermographic images may contribute further to the characterization of metabolically active plaques likely to cause acute coronary syndromes.

  View details for DOI 10.1002/ccd.10750

  View details for PubMedID 15170716

• Microvascular resistance is not influenced by epicardial coronary artery stenosis severity - Experimental validation CIRCULATION Fearon, W. F., Aarnoudse, W., Pijls, N. H., De Bruyne, B., Balsam, L. B., Cooke, D. T., Robbins, R. C., Fitzgerald, P. J., Yeung, A. C., Yock, P. G. 2004; 109 (19): 2269-2272

  Abstract

  The effect of epicardial artery stenosis on myocardial microvascular resistance remains controversial. Recruitable collateral flow, which may affect resistance, was not incorporated into previous measurements.In an open-chest pig model, distal coronary pressure was measured with a pressure wire, and the apparent minimal microvascular resistance was calculated during peak hyperemia as pressure divided by flow, measured either with a flow probe around the coronary artery (R(micro app)) or with a novel thermodilution technique (apparent index of microcirculatory resistance [IMR(app)]). These apparent resistances were compared with the actual R(micro) and IMR after the coronary wedge pressure and collateral flow were incorporated into the calculation. Measurements were made at baseline (no stenosis) and after creation of moderate and severe epicardial artery stenoses. In 6 pigs, 189 measurements of R(micro) and IMR were made under the various epicardial artery conditions. Without consideration of collateral flow, R(micro app) (0.43+/-0.12 to 0.46+/-0.10 to 0.51+/-0.11 mm Hg/mL per minute) and IMR(app) (14+/-4 to 17+/-7 to 20+/-10 U) increased progressively and significantly with increasing epicardial artery stenosis (P<0.001 for both). With the incorporation of collateral flow, neither R(micro) nor IMR increased as a result of increasing epicardial artery stenosis.After collateral flow is taken into account, the minimum achievable microvascular resistance is not affected by increasing epicardial artery stenosis.

  View details for DOI 10.1161/01.CIR.0000128669.99355.CB

  View details for PubMedID 15136503

• Pseudo-candy wrapper: bifocal radial artery graft spasm following stent implantation. journal of invasive cardiology Kaneda, H., Nakamura, M., Fitzgerald, P. J. 2004; 16 (4): 201-203

  Abstract

  We encountered a case of intractable radial artery graft spasm after stent implantation which was partially responsive to nominal nitroglycerin therapy. We report this case with intravascular ultrasound imaging at the radial artery spasm site.

  View details for PubMedID 15152147

• Optimal geometry is still important with sirolimus-eluting stents: Incomplete stent expansion as a risk for target lesion revascularization 53rd Annual Scientific Session of the American-College-of-Cardiology Ako, J., Morino, Y., Terashima, M., Honda, Y., Sonoda, S., Leon, M. B., Moses, J. W., Yock, P. G., Fitzgerald, P. ELSEVIER SCIENCE INC. 2004: 84A–84A

  View details for Web of Science ID 000189388500354

• Evaluation of high-pressure retrograde coronary venous delivery of FGF-2 protein CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Fearon, W. F., Ikeno, F., Bailey, L. R., Hiatt, B. L., Herity, N. A., Carter, A. J., Fitzgerald, P. J., Rezaee, M., Yeung, A. C., Yock, P. G. 2004; 61 (3): 422-428

  Abstract

  Delivery of angiogenic factors to ischemic myocardium remains a practical challenge. We evaluated the efficiency and efficacy of delivery of fibroblast growth factor-2 (FGF-2) protein via high-pressure retrograde injection into the anterior interventricular vein (AIV) in a porcine model of chronic myocardial ischemia. Labeled FGF-2 protein was delivered to the myocardium of three pigs via the AIV and the left anterior descending (LAD) coronary artery in three others. At 1 hr, the amount of protein in the left ventricle and the LAD region was quantified. Copper stents were implanted in the LAD of 25 pigs, resulting in chronic myocardial ischemia. At 4 weeks, microsphere-derived myocardial blood flow was assessed at rest and during pacing. In eight pigs (AIV FGF), FGF-2 protein (6 microg/kg) was delivered via high-pressure retrograde injection into the AIV. Six pigs (intracoronary FGF) received the same amount of FGF-2 by intracoronary delivery. Five pigs (AIV saline) received a placebo injection into the AIV and six pigs (control) served as controls. Four weeks later, myocardial blood flow was reassessed. At 1 hr, significantly more FGF remained in the left ventricle (1.3 vs. 0.82 microg; P < 0.04) and in the LAD region (1.2 vs. 0.64 microg; P = 0.03) after AIV compared to intracoronary delivery. Four weeks after treatment, resting LAD blood flow (normalized to right ventricular flow) improved slightly in the AIV FGF and intracoronary FGF arms (1.32-1.37 for both; P = 0.11), while it decreased significantly in the AIV saline (1.32-1.23; P = 0.02) and the control arms (1.32-1.19; P = 0.0004). Pacing LAD blood flow decreased significantly in the control arm (1.30-1.23; P < 0.05), but did not change significantly in the other three arms. High-pressure retrograde injection into the AIV may represent an efficient and effective means for delivering angiogenic factors to ischemic myocardium.

  View details for DOI 10.1002/ccd.10790

  View details for PubMedID 14988909

• Late incomplete stent apposition and focal vessel expansion after bare metal stenting AMERICAN JOURNAL OF CARDIOLOGY Nakamura, M., Kataoka, T., Honda, Y., Bonneau, H. N., Hibi, K., Kitamura, K., Tamai, H., Aizawa, T., Yock, P. G., Fitzgerald, P. J. 2003; 92 (10): 1217-1219

  Abstract

  Late incomplete stent apposition was observed in 2.4% of the 412 stented segments studied by serial intravascular ultrasound analyses. Most of these phenomena and all late vessel expansions with incomplete stent apposition developed in vessels in which lesions were treated by atherectomy before stenting, suggesting a potential association between mechanical injury from debulking and these phenomena.

  View details for Web of Science ID 000186638600019

  View details for PubMedID 14609603

• Comparison of coronary thermodilution and Doppler velocity for assessing coronary flow reserve CIRCULATION Fearon, W. F., Farouque, H. M., Balsam, L. B., Cooke, D. T., Robbins, R. C., Fitzgerald, P. J., Yeung, A. C., Yock, P. G. 2003; 108 (18): 2198-2200

  Abstract

  Thermodilution coronary flow reserve (CFRthermo) is a new technique for invasively measuring coronary flow reserve (CFR) with a coronary pressure wire and is based on the ability of the pressure transducer to also measure temperature changes. Whether CFRthermo correlates well enough with absolute flow-derived CFR (CFRflow) to replace Doppler wire-derived CFR (CFRDoppler) remains unclear.In an open-chest pig model, CFRthermo was measured in the left anterior descending (LAD) artery and compared with CFRDoppler and CFRflow, measured with an external flow probe placed around the LAD. In 9 pigs, CFR was measured simultaneously by all 3 means in the normal LAD and after creation of an epicardial LAD stenosis. To determine the added effect of microvascular disease, measurements of flow reserve were also performed after disruption of the coronary microcirculation with embolized microspheres. Intracoronary papaverine (20 mg) was used to induce hyperemia. In a total of 61 paired measurements, CFRthermo correlated strongly with the reference standard CFRflow (r=0.85, P<0.001). CFRDoppler correlated less well with CFRflow (r=0.72, P<0.001). Bland-Altman analysis showed a closer agreement between CFRthermo and CFRflow.CFRthermo correlates better with CFRflow than does CFRDoppler.

  View details for DOI 10.1161/01.CIR.0000099521.31396.9D

  View details for PubMedID 14568891

• Simultaneous assessment of fractional and coronary flow reserves in cardiac transplant recipients - Physiologic investigation for transplant arteriopathy (PITA study) CIRCULATION Fearon, W. F., Nakamura, M., Lee, D. P., Rezaee, M., Vagelos, R. H., Hunt, S. A., Fitzgerald, P. J., Yock, P. G., Yeung, A. C. 2003; 108 (13): 1605-1610

  Abstract

  The utility of measuring fractional flow reserve (FFR) to assess cardiac transplant arteriopathy has not been evaluated. Measuring coronary flow reserve (CFR) as well as FFR could add information about the microcirculation, but until recently, this has required two coronary wires. We evaluated a new method for simultaneously measuring FFR and CFR with a single wire to investigate transplant arteriopathy.In 53 cases of asymptomatic cardiac transplant recipients without angiographically significant coronary disease, FFR and thermodilution-derived CFR (CFRthermo) were measured simultaneously with the same coronary pressure wire in the left anterior descending artery and compared with volumetric intravascular ultrasound (IVUS) imaging. The average FFR was 0.88+/-0.07; in 75% of cases, the FFR was less than the normal threshold of 0.94; and in 15% of cases, the FFR was < or =0.80, the upper boundary of the gray zone of the ischemic threshold. There was a significant inverse correlation between FFR and IVUS-derived measures of plaque burden, including percent plaque volume (r=0.55, P<0.0001). The average CFRthermo was 2.5+/-1.2; in 47% of cases, CFRthermo was < or =2.0. In 14%, the FFR was normal (> or =0.94) and the CFR was abnormal (<2.0), suggesting predominant microcirculatory dysfunction.FFR correlates with IVUS findings and is abnormal in a significant proportion of asymptomatic cardiac transplant patients with normal angiograms. Simultaneous measurement of CFR with the same pressure wire, with the use of a novel coronary thermodilution technique, is feasible and adds information to the physiological evaluation of these patients.

  View details for DOI 10.1161/01.CIR.0000091116.84926.6F

  View details for PubMedID 12963639

• Late incomplete apposition with excessive remodeling of the stented coronary artery following intravascular brachytherapy AMERICAN JOURNAL OF CARDIOLOGY Okura, H., Lee, D. P., Lo, S., Yeung, A. C., Honda, Y., Waksman, R., Kaluza, G. L., Ali, N. M., Bonneau, H. N., Yock, P. G., Raizner, A. E., Mintz, G. S., Fitzgerald, P. J. 2003; 92 (5): 587-590

  Abstract

  Intravascular brachytherapy may cause "exaggerated" vessel remodeling with late incomplete apposition in segments that have little disease, which are exposed to higher radiation doses. The long-term clinical impact of this finding is unclear.

  View details for DOI 10.1016/S0002-9149(03)00728-8

  View details for PubMedID 12943881

• Novel index for invasively assessing the coronary microcirculation CIRCULATION Fearon, W. F., Balsam, L. B., Farouque, H. M., Robbins, R. C., Fitzgerald, P. J., Yock, P. G., Yeung, A. C. 2003; 107 (25): 3129-3132

  Abstract

  A relatively simple, invasive method for quantitatively assessing the status of the coronary microcirculation independent of the epicardial artery is lacking.By using a coronary pressure wire and modified software, it is possible to calculate the mean transit time of room-temperature saline injected down a coronary artery. The inverse of the hyperemic mean transit time has been shown to correlate with absolute flow. We hypothesize that distal coronary pressure divided by the inverse of the hyperemic mean transit time provides an index of microcirculatory resistance (IMR) that will correlate with true microcirculatory resistance (TMR), defined as the distal left anterior descending (LAD) pressure divided by hyperemic flow, measured with an external ultrasonic flow probe. A total of 61 measurements were made in 9 Yorkshire swine at baseline and after disruption of the coronary microcirculation, both with and without an epicardial LAD stenosis. The mean IMR (16.9+/-6.5 U to 25.9+/-14.4 U, P=0.002) and TMR (0.51+/-0.14 to 0.79+/-0.32 mm Hg x mL(-1) x min(-1), P=0.0001), as well as the % change in IMR (147+/-66%) and TMR (159+/-105%, P=NS versus IMR % change), increased significantly and to a similar degree after disruption of the microcirculation. These changes were independent of the status of the epicardial artery. There was a significant correlation between mean IMR and TMR values, as well as between the % change in IMR and % change in TMR.Measuring IMR may provide a simple, quantitative, invasive assessment of the coronary microcirculation.

  View details for DOI 10.1161/01.CIR.0000080700.98607.D1

  View details for PubMedID 12821539

• Treatment by mycophenolate mofetil of advanced graft vascular disease in non-human primate recipients of orthotopic aortic allografts AMERICAN JOURNAL OF TRANSPLANTATION Klupp, J., Dambrin, C., Hibi, K., Luna, J., Suzuki, T., Hausen, B., Birsan, T., van Gelder, T., Fitzgerald, P. J., Berry, G., Morris, R. E. 2003; 3 (7): 817-829

  Abstract

  Failure to control chronic graft dysfunction [e.g. graft vascular disease (GVD)] is the primary cause of immunologic graft failure. This is the first study of mycophenolate mofetil (MMF) for the treatment of GVD in non-human primate recipients of aortic allografts. Abdominal aortic allografts were exchanged between mixed leukocyte reaction (MLR) -mismatched, blood-group-compatible cynomolgus monkeys. Six control recipients were untreated. Individualized treatment with frequent dose adjustments of MMF insured that treatment was close to the maximum tolerated dose (mean 99.2 mg/kg/day). Immune-mediated injury proceeded unhindered until day 45, after which MMF treatment began. Changes in intimal volume (IV) were quantified by intravascular ultrasound (IVUS) and compared to histology on day 105. Serial IVUS measurements of IV (mm(3)) in controls showed progressive GVD. In four out of six animals, MMF was well tolerated, thus enabling optimum treatment; in all these animals, IV was significantly less than in the control animals (p = 0.02). In the two remaining animals, high doses were not tolerated; at day 105, there was no significant difference in IV between them and the controls. We found a significant correlation between the mean MMF tolerated dose and the inhibition of progression of IV (r = -0.88, p = 0.015). When high MMF doses were tolerated, MMF slowed progression of GVD.

  View details for Web of Science ID 000184032600007

  View details for PubMedID 12814473

• Sirolimus (rapamycin) monotherapy prevents graft vascular disease in nonhuman primate recipients of orthotopic aortic allografts CIRCULATION Dambrin, C., Klupp, J., Birsan, T., Luna, J., Suzuki, T., Lam, T., Stahr, P., Hausen, B., Christians, U., Fitzgerald, P., Berry, G., Morris, R. 2003; 107 (18): 2369-2374

  Abstract

  Delayed treatment with sirolimus (SRL) halts progression of graft vascular disease (GVD) in nonhuman primate (NHP) aortic allograft recipients. In this study, we investigated whether SRL monotherapy prevents the development of GVD.Pairs of 3-cm infrarenal aortic segments were exchanged between mixed lymphocyte reaction-mismatched, blood group-compatible NHPs (n=12). Six NHPs were untreated controls, and 6 were treated orally with SRL starting on the day of transplantation. Follow-up was 105 days. SRL doses were adjusted individually by assessing SRL blood concentrations, immune function, and clinical status. The severity of GVD was determined every 3 weeks by intravascular ultrasound, which quantified intimal area (IA) and intimal volume (IV) for the middle 1-cm graft segments. The mean+/-SEM SRL plasma levels were 14.5+/-9 ng/mL. In grafts from treated NHPs, IA and IV values on days 63, 84, and 105 were significantly lower than for controls (P<0.05 to P<0.001). On day 105, in the grafts from SRL-treated NHPs compared with grafts from controls, values (mean+/-SEM) were IA, 2.9+/-0.9 versus 5.5+/-0.7 mm2, P<0.001 and IV, 29.6+/-4.6 versus 55.2+/-2.8 mm3, P<0.001; IA and IV values for grafts from SRL-treated NHPs did not increase significantly between days 21 and 105.We show that SRL monotherapy prevented GVD in NHP aortic allograft recipients, suggesting the value of SRL for controlling GVD in clinical transplantation.

  View details for DOI 10.1161/01.CIR.0000065576.80196.A4

  View details for Web of Science ID 000182807000028

  View details for PubMedID 12719285

• Effect of a change in gender on coronary arterial size - A longitudinal intravascular ultrasound study in transplanted hearts 49th Annual Scientific Session of the American-College-of-Cardiology Herity, N. A., Lo, S., Lee, D. P., Ward, M. R., Filardo, S. D., Yock, P. G., Fitzgerald, P. J., Hunt, S. A., Yeung, A. C. ELSEVIER SCIENCE INC. 2003: 1539–46

  Abstract

  We sought to document whether a physiologic change in gender has any effect on coronary arterial size.The coronary arteries are smaller in women, even after correction for body surface area (BSA). These differences may contribute to adverse clinical outcomes after coronary artery bypass graft surgery and myocardial infarction in women. In male and female transsexuals, pharmacologic doses of estrogens and androgens significantly influence vascular diameter. Thus, gender differences in the coronary vasculature may be a reflection of the hormonal environment.In 86 patients who had undergone orthotopic heart transplantation, serial intravascular ultrasound studies of the proximal left anterior descending coronary artery (LAD) were analyzed. Changes in vessel area (VA) over the first or second post-transplant year were recorded, and comparisons were made between donor hearts that were transplanted in a patient of the same gender and those that were transplanted in a patient of the opposite gender.Vessel area of the proximal LAD increased over time in all patient groups. In hearts transplanted within the same gender and in male donor hearts transplanted to female recipients, the change was small and not significant. However, in hearts transplanted from female donors to male recipients, there was a substantial and highly significant increase in LAD VA (median 16.13 to 17.88 mm(2); p = 0.01). This increase was not explained by confounding due to changes in BSA or left ventricular wall thickness.This pattern of arterial remodeling early after heart transplantation supports a link between host gender and coronary arterial size.

  View details for DOI 10.1016/S0735-1097(03)00246-8

  View details for PubMedID 12742295

• Taxol-based eluting stents from theory to human validation: clinical and intravascular ultrasound observations. journal of invasive cardiology Sonoda, S., Honda, Y., Kataoka, T., Bonneau, H. N., Sudhir, K., Yock, P. G., Mintz, G. S., Fitzgerald, P. J. 2003; 15 (3): 109-114

  Abstract

  Treatment with antiproliferative drugs via coated stents appears to be a promising approach to both mechanically remodel target lesions and biologically reduce neointimal hyperplasia. Drug-eluting stents can maximize local drug effects and minimize the potential for systemic toxic effects. The purpose of this review is to describe the effects of a lipophilic microtubular inhibitor, paclitaxel, a strong antiproliferative agent under clinical investigation, and to define the vascular response to taxol-based eluting stents by intravascular ultrasound.

  View details for PubMedID 12612382

• Relationship between neointimal regrowth and mechanism of acute lumen gain during the treatment of in-stent restenosis with or without supplementary intravascular radiation CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Morino, Y., Limpijankit, T., Honda, Y., Somrantin, M., Waksman, R., Bonneau, H. N., Yock, P. G., Mintz, G. S., Fitzgerald, P. J. 2003; 58 (2): 162-167

  Abstract

  We investigated whether neointimal regrowth is related to the mechanism of acute lumen gain during the treatment of in-stent restenosis (ISR) lesions both with and without adjunct intravascular brachytherapy. From the WRIST (Washington Radiation for In-Stent Restenosis Trial) cohort, 54 ISR patients ((192)Ir, 29; placebo, 25) were treated with nonrepeat stenting percutaneous interventions (excimer laser, rotational atherectomy, and/or balloon angioplasty) prior to (192)Ir or placebo therapy. Using Simpson's method, serial volumetric intravascular ultrasound (IVUS) analyses (pre- and posttreatment and 6-month follow-up) were analyzed to obtain stent, lumen, and intimal hyperplasia (IH) volumes that were then adjusted for stent length to create stent, lumen, and IH volume indexes. In the placebo group, the acute reduction of neointima (1.6 +/- 1.4 mm(3)/mm) was counteracted by intimal regrowth (2.1 +/- 1.7 mm(3)/mm). The amount of intimal regrowth correlated directly with the intimal reduction due to the intervention (r = 0.76; P < 0.001), but not with the amount of additional stent expansion. In the (192)Ir-treated group, intimal regrowth was significantly less than in the placebo group (-0.3 +/- 0.1 vs. 2.1 +/- 1.7 mm(3)/mm; P < 0.001) despite a similar initial intimal reduction (1.3 +/- 0.9 vs. 1.6 +/- 1.4 mm(3)/mm; P = NS). No correlation was found between intimal reduction at the time of the procedure and intimal regrowth in the (192)Ir group. In this study, neointimal regrowth following treatment of ISR lesions correlates directly with the extent of acute intimal volume reduction, but not with the extent of additional stent expansion. This relation is not seen in ISR segments treated with radiation, where intimal regrowth is substantially inhibited.

  View details for DOI 10.1002/ccd.10405

  View details for Web of Science ID 000182814600005

  View details for PubMedID 12552537

• Impact of deep vessel wall injury on acute response and remodeling of coronary artery segments after cutting balloon angioplasty AMERICAN JOURNAL OF CARDIOLOGY Nakamura, M., Yock, P. G., Kataoka, T., Bonneau, H. N., Suzuki, T., Yamaguchi, T., Honda, Y., Fitzgerald, P. J. 2003; 91 (1): 6-11

  Abstract

  Deep vessel wall injury is believed to affect vessel dimension following coronary intervention. The cutting balloon is designed to treat coronary artery stenoses with dilatation and surgical incisions, thereby reducing excess vessel injury. This study examines the effect of deep vessel wall injury on acute and late coronary arterial response after cutting balloon angioplasty. Serial volumetric intravascular ultrasound (IVUS) analyses were performed in 63 lesions treated with cutting balloon angioplasty alone. Before intervention, the longitudinal range of the lesion segment that included the smallest lumen area (LA) was determined as LA <4 mm(2) and/or LA stenosis >60%. The exact corresponding site at postintervention and follow-up was aligned using peri- and intravascular landmarks. Average vessel area (VA), plaque area (PA), and LA were measured. Lesion segments were categorized as with or without deep vessel wall injury, which was defined as the presence of plaque/vessel wall fracture extending to the sonolucent (medial) layer. Before intervention, the lesion vessel size of deep injury group was smaller than that of the nondeep injury group (p <0.05 for average VA and PA), whereas average lesion LA, lesion length, and reference vessel size did not differ. Immediately after cutting balloon angioplasty, the deep injury group showed a significant increase in VA (p <0.0001) and a lesser decrease in PA (p <0.01) compared with the nondeep injury group. During follow-up, the increase of VA tended to be greater in the deep injury group than in the nondeep injury group (p = 0.06), whereas the change of PA did not differ. Consequently, LA decrease was less in the deep injury group than in the nondeep injury group (p <0.05). From these results, it is suggested that deep vessel wall injury tends to occur in lesions with relatively small size and such lesions show favorable vessel response after cutting balloon angioplasty.

  View details for Web of Science ID 000180201000002

  View details for PubMedID 12505563

• Efficacy and feasibility of helixcision for debulking neointimal hyperplasia for in-stent restenosis CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Nakamura, M., Fitzgerald, P. J., Ikeno, F., Honda, Y., Sousa, J. E., Abizaid, A., de Brito, F. S., Tofte, A., Grube, E., Patterson, G. R., Yock, P. G., Yeung, A. C., Carter, A. J. 2002; 57 (4): 460-466

  Abstract

  The Helixcision system is a novel 6 Fr-compatible catheter designed to debulk tissue for in-stent restenosis lesions. The purpose of this study was to determine the efficacy and feasibility of this new system for removing neointimal hyperplasia. A total of 32 in-stent restenosis lesions in 32 patients were treated with helixcision followed by balloon angioplasty. Debulking efficacy was assessed with serial baseline intravascular ultrasound (IVUS) in a subset of 18 lesions. To investigate longitudinal efficacy, 3D analysis was also performed in 12 lesions with automated pullback to calculate average cross-sectional areas across the stent. Prior to procedure, the angiographic reference diameter was 2.60 +/- 0.46 mm. Immediately after procedure, minimum lumen diameter improved from 0.84 +/- 0.33 to 2.19 +/- 0.41 mm (P < 0.0001). IVUS showed a significant reduction of intimal area (IA) after helixcision (from 4.95 +/- 2.04 to 2.88 +/- 1.48 mm(2); P < 0.001). Adjunctive balloon angioplasty further improved lumen area (LA) mainly by stent expansion rather than IA reduction at the site of minimum lumen area. The degrees of IA reduction and LA improvement were closely similar in volumetric analysis. Thirty-day and 6-month clinical follow-up were available in 97% (n = 31) and 72% (n = 23) of the enrolled patients, respectively. At 30-day follow-up, no major adverse cardiac event was reported except for periprocedural CK elevation in two patients (6%). Target legion revascularization within 6 months was performed in six patients (26%). Preliminary results of helixcision indicate that this system is safe and feasible for the treatment of in-stent restenosis. The concordant results between 2D and 3D IVUS analyses suggest that this unique technology can achieve uniform longitudinal debulking throughout the stent. The long-term outcomes appeared to be favorable, considering the relatively diffuse lesion morphology.

  View details for DOI 10.1002/ccd.10352

  View details for Web of Science ID 000182814400006

  View details for PubMedID 12455079

• Mechanisms of acute lumen gain following cutting balloon angioplasty in calcified and noncalcified lesions: An intravascular ultrasound study CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Okura, M., Hayase, M., Shimodozono, S., Kobayashi, T., Sano, K., Matsushita, T., Kondo, T., Kijima, M., Nishikawa, H., Kurogane, H., Aizawa, T., Hosokawa, H., Suzuki, T., Yamaguchi, T., Bonneau, H. N., Yock, P. G., Fitzgerald, P. J. 2002; 57 (4): 429-436

  Abstract

  Several studies have shown that mechanisms for lumen enlargement following conventional balloon angioplasty (BA) consist of plaque reduction and vessel expansion. To assess the mechanisms of lumen enlargement after Cutting Balloon (CB) angioplasty, intravascular ultrasound images were analyzed in 180 lesions (89 CB and 91 BA). External elastic membrane (EEM) cross-sectional area (CSA), lumen CSA, and plaque plus media (P+M) CSA were measured before and after angioplasty. In the CB group, lower balloon pressure was utilized (P < 0.0001). DeltaP+M CSA was significantly larger (P = 0.02) and deltalumen CSA showed a trend toward being larger (P = 0.07) compared to BA group. For noncalcified lesions, CB resulted in a larger deltaP+M CSA (P < 0.05) and a smaller deltaEEM CSA (P = 0.10) than BA. For calcified lesions, deltalumen CSA was significantly larger in the CB group (P < 0.05) without significant differences in deltaEEM CSA and deltaP+M CSA. Dissections complicated with calcified lesions were associated with larger deltalumen CSA for the CB group. In conclusion, for noncalcified lesions, CB achieves similar luminal dimensions with larger plaque reduction and less vessel expansion compared to BA. On the other hand, for calcified lesions, the CB achieves larger lumen gain, especially in lesions with evidence of dissections.

  View details for DOI 10.1002/ccd.10344

  View details for Web of Science ID 000182814400002

  View details for PubMedID 12455075

• Quantitative and spatial relation of baseline atherosclerotic plaque burden and subsequent in-stent neointimal proliferation as determined by intravascular ultrasound AMERICAN JOURNAL OF CARDIOLOGY Hibi, K., Suzuki, T., Honda, Y., Hayase, M., Bonneau, H. N., Yock, P. G., Yeung, A. C., Fitzgerald, P. J. 2002; 90 (10): 1164-?

  View details for Web of Science ID 000179262600027

  View details for PubMedID 12423727

• Delivered dose and vascular response after beta-radiation for in-stent restenosis - Retrospective dosimetry and volumetric intravascular ultrasound analysis CIRCULATION Morino, Y., Kaneda, H., Fox, T., Takagi, A., Hassan, A. H., Bonan, R., Crocker, I., Lansky, A. J., Laskey, W. K., Suntharalingam, M., Bonneau, H. N., Yock, P. G., Honda, Y., Fitzgerald, P. J. 2002; 106 (18): 2334-2339

  Abstract

  Observations from previous intracoronary radiation therapy trials noted a considerable discrepancy between the prescribed radiation dose and the dose actually delivered. The aims of this study were to investigate the effect of actual delivered dose on vascular changes and to test the appropriateness of the current dose prescription.Serial volumetric intravascular ultrasound (IVUS) analysis was performed in 30 in-stent restenosis cases treated with a 40-mm (90)Sr/Y source train. The fixed dose was prescribed at 2 mm from the centerline of the source train (18.4 Gy at 2 mm for reference diameter < or =3.35 mm and 23 Gy for diameter > or =3.36 mm). Only stent segments with full radiation coverage and device injury were enrolled and divided into 2-mm-long subsegments (n=202). D(S90)EEM (the minimum dose absorbed by 90% of the external elastic membrane surface) was calculated as the delivered dose corresponding to each segment, assuming that the radiation catheter occupied the same position in the vessel as the IVUS catheter. Mean D(S90)EEM of 23.5+/-5.82 Gy (range 12.3 to 41.7 Gy) was delivered to these subsegments. Overall, intimal hyperplasia volume remained constant from postintervention to follow-up (2.23+/-1.10 to 2.32+/-1.09 mm3/m; P=NS). Regression analysis revealed there was no correlation between delivered dose intensity and changes in intimal hyperplasia volume. No particular dose-dependent complications were appreciated in this delivered dose range.The current dose-prescription protocol of (90)Sr/Y radiation to native in-stent restenosis lesions may provide substantial inhibition of neointimal reproliferation regardless of the actual delivered dose intensity.

  View details for DOI 10.1161/01.CIR.0000036367.17043.03

  View details for Web of Science ID 000179046600017

  View details for PubMedID 12403663

• 7-hexanoyltaxol-eluting stent for prevention of neointimal growth - An intravascular ultrasound analysis from the study to COmpare REstenosis rate between QueST and QuaDS-QP2 (SCORE) CIRCULATION Kataoka, T., Grube, E., Honda, Y., Morino, Y., Hur, S. H., Bonneau, H. N., Colombo, A., Di Mario, C., Guagliumi, G., Hauptmann, K. E., Pitney, M. R., Lansky, A. J., Stertzer, S. H., Yock, P. G., Fitzgerald, P. J. 2002; 106 (14): 1788-1793

  Abstract

  Inhibition of neointimal tissue growth has been demonstrated in preliminary human feasibility studies with a stent-based polymer sleeve delivering 7-hexanoyltaxol. The Study to COmpare REstenosis rate between QueST and QuaDS-QP2 (SCORE) trial is a human, randomized, multicenter trial comparing 7-hexanoyltaxol (QP2)-eluting stents (qDES) with bare metal stents (BMS) in the treatment of de novo coronary lesions. The purpose of this substudy was to evaluate the acute expansion property and long-term neointimal responses of qDES compared with BMS as assessed by intravascular ultrasound (IVUS).A total of 122 (qDES 66, BMS 56) patients were enrolled into the IVUS substudy. All IVUS images (immediately after the procedure and at 6-month follow-up) were analyzed at an independent core laboratory in a blind manner. At baseline, qDES achieved stent expansion similar to BMS. At follow-up, qDES showed reduced neointimal growth by 70% at the tightest cross section and by 68% over the stented segment (P<0.0001 for both), resulting in a significantly larger lumen in qDES than in BMS. Unlike intracoronary brachytherapy, there was no evidence of negative edge effects, unhealed dissections, or late stent-vessel wall malapposition over the stented and adjacent references segments in either group.Detailed IVUS analysis revealed that qDES had comparable acute mechanical and superior long-term biological effects to BMS. Although the long-term benefits and limitations of this technology require further investigation, the reduction in neointimal thickenings demonstrated that local delivery of 7-hexanoyltaxol through polymer sleeves augments conventional mechanical treatment of atherosclerotic disease.

  View details for Web of Science ID 000178385700012

  View details for PubMedID 12356631

• New catheter-based technology for the treatment of restenosis. Journal of interventional cardiology Kataoka, T., Honda, Y., Bonneau, H. N., Yock, P. G., Fitzgerald, P. J. 2002; 15 (5): 371-379

  Abstract

  Catheter-based vascular interventions have been in development worldwide for several decades, leading to remarkable progress in device technology. Mechanical interventional devices, such as angioplasty balloons, atherectomy devices, and stents, were invented and have contributed greatly to the treatment of atherosclerotic vascular stenosis. However, mechanical approaches do not effectively prevent subsequent intimal growth. Recently, several biological approaches, including radiation therapy and drug-eluting stents, have shown striking inhibition of intimal growth. These significant results are likely to change the treatment strategy in the field of interventional cardiology. Furthermore, additional catheter-based technologies for vascular interventions are presently being evaluated. These latest technologies designed to prevent intimal proliferation include intravascular sonotherapy, cryotherapy, photoangioplasty, and soft X ray. To date, intravascular sonotherapy has proven its efficacy in animal studies and safety in human studies. Cryotherapy, the application of cold thermal energy during angioplasty, enhances the acute effects of conventional dilation while decreasing the likelihood of restenosis. Photoangioplasty has a unique property based on its selective mechanism of action to treat atheromatous plaque. Soft X ray systems provide convenient device handling and well-controlled radiation dose. Some of these technologies may play an important role in vascular interventions in the near future.

  View details for PubMedID 12440180

• Impact of deep vessel wall injury and vessel stretching on subsequent arterial remodeling after balloon angioplasty: A serial intravascular ultrasound study AMERICAN HEART JOURNAL Okura, H., Shimodozono, S., Hayase, M., Bonneau, H. N., Yock, P. G., Fitzgerald, P. J. 2002; 144 (2): 323-328

  Abstract

  Arterial remodeling has been shown to be responsible for lumen narrowing after nonstent interventions.To examine the impact of deep vessel wall injury (DI) after balloon angioplasty on the subsequent vessel remodeling process, we performed serial intravascular ultrasound (IVUS) analysis in 47 native coronary artery lesions that underwent balloon angioplasty. An IVUS study was performed before and after balloon angioplasty and repeated at follow-up. Vessel and lumen area were measured at the narrowest site before intervention. Plaque area was calculated as vessel area minus lumen area. DI was defined as the presence of plaque/vessel wall fracture deep in the medial layer (sonolucent zone by IVUS) after angioplasty.After angioplasty, DI was present in 18 (38%, DI group) and absent in 29 (62%, non-DI group) of lesions. During follow-up, changes in vessel area in the DI group were significantly larger than in the non-DI group (P =.007). There were no significant differences in changes in plaque area. A trend toward greater late lumen loss was observed in the non-DI group (P =.05). In the DI group, changes in lumen area correlated better with changes in vessel area (r = 0.81, P <.0001) than with changes in plaque area (r = 0.32, P =.20). However, in the non-DI group, changes in lumen area correlated with changes in plaque area (r = -0.55, P =.002), but not with changes in vessel area (r = 0.30, P =.11).Deep vessel wall injury after balloon angioplasty is associated with the magnitude of the subsequent vessel remodeling process. The differences in the remodeling process may have implications regarding adjunctive therapies to prevent restenosis after balloon angioplasty.

  View details for DOI 10.1067/mhj.2002.122282

  View details for Web of Science ID 000177501400022

  View details for PubMedID 12177652

• Impact of vessel curvature on the accuracy of three-dimensional intravascular ultrasound: Validation by phantoms and coronary segments JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Stahr, P., Voigtlander, T., Rupprecht, H. J., Aschenbrucker, P., Mamtimin, H., Brennecke, R., Otto, M., Fitzgerald, P. J., Meyer, J. 2002; 15 (8): 823-830

  Abstract

  Three-dimensional intravascular ultrasound (IVUS) is used for volumetric assessment of arteriosclerotic plaque burden and restenotic tissue at follow-up after coronary interventions. However, the accuracy of these measurements, especially in tortuous vessels, is unclear.A commercially available electrocardiogram (ECG)-gated 3-dimensional-IVUS system was tested in volume-validated straight and curved hydrocolloid phantoms and in volume-validated coronary specimens. Catheter withdrawal (30 MHz, 3.2F) was triggered using standardized ECG source with 0.2-mm step intervals per cardiac cycle simulation.On the basis of automated phantom volume measurements, IVUS overestimated true phantom volume (relative error = [measured V - true V]/true V x 100) by a median of 0.9%, 0.25%, and 1.96% for straight, mildly curved, and severely curved segments, respectively. The true volume of the coronary specimens was overestimated by a median of 5.79%.A median percentage deviation of 3-dimensional-IVUS-measured volumes from the true volumes of less than 10% in phantoms and coronary artery segments can be achieved.

  View details for DOI 10.1067/mje.2002.120700

  View details for Web of Science ID 000177431800010

  View details for PubMedID 12174352

• Discrimination of early/intermediate and advanced/complicated coronary plaque types by radiofrequency intravascular ultrasound analysis AMERICAN JOURNAL OF CARDIOLOGY Stahr, P. M., Hofflinghaus, T., Voigtlander, T., Courtney, B. K., Victor, A., Otto, M., Yock, P. G., Brennecke, R., Fitzgerald, P. J. 2002; 90 (1): 19-23

  Abstract

  Radiofrequency intravascular ultrasound (IVUS-RF) analysis, as an extension of conventional IVUS imaging, may provide more accurate plaque discrimination. Thirty-two autopsy atherosclerotic coronary arteries were investigated. Corresponding sectors in different plaques were matched by histologic and RF analysis. Histologic analysis utilized the American Heart Association plaque classification. The backscattered ultrasound RF signal was analyzed by fast-Fourier transform, providing the underlying frequency components of its power spectrum. The normalized backscattered signal power (in decibels [dB]) for frequencies between 15.3 and 40.3 MHz was then measured for plaque discrimination. Advanced/complicated plaque types showed a higher signal power at all frequencies than early/intermediate lesion types (p <0.001 to p = 0.005). Discrimination of advanced/complicated lesion types was best at 15.3 MHz, with a cut-off point of 2.5 dB (sensitivity 93%, specificity 79%), and second best at 17.6 MHz (sensitivity 87%, specificity 71%, cut-off point 1.9 dB). With conventional IVUS, plaque discrimination was weaker; the best sensitivity for diagnosing early/intermediate lesion types was reached for "soft plaque" (sensitivity 63%, specificity 73%). Compared with conventional IVUS, IVUS-RF can discriminate between advanced/complicated and early/intermediate coronary atherosclerotic lesions with relatively high sensitivity and specificity in vitro.

  View details for PubMedID 12088773

• Late vascular response to repeat stenting for in-stent restenosis with and without radiation - An intravascular ultrasound volumetric analysis CIRCULATION Morino, Y., Limpijankit, T., Honda, Y., Lansky, A. J., Waksman, R., Bonneau, H. N., Yock, P. G., Mintz, G. S., Fitzgerald, P. J. 2002; 105 (21): 2465-2468

  Abstract

  Re-stenting of in-stent restenosis (ISR) improves acute angiographic results. Methods and Results- Volumetric intravascular ultrasound analysis was performed in 70 ISR lesions that received either placebo (n=36) or (192)Ir radiation (n=34). ISR lesions treated by re-stenting were divided into 3 groups: old stent not re-stented (A), old/new stent overlap (B), and new stent only (C). ISR lesions treated without re-stenting were categorized as D. In placebo patients, postintervention lumen volume index (LVI) was significantly greater in re-stented segments B and C than in non-re-stented segment A (P<0.05).At follow-up, however, LVI was similar in all 4 segments secondary to the increased intimal hyperplasia (IH) reaccumulation within the re-stented segments. In patients treated with (192)Ir radiation, LVI was maintained from baseline to follow-up only in non-re-stented segments A and D. Conversely, there was a significant decrease in LVI in re-stented segments B and C (P<0.05). Qualitatively, 79% of patients in the irradiated group had stent struts with undetectable neointimal versus only 27% in the placebo group (P<0.001). Coefficient of variation of IH reaccumulation was greater in re-stented segments of (192)Ir patients (B=57.3% and C=58.9%) than in re-stented segments in placebo patients (B=27.3% and C 26.8%) and non-re-stented segments in irradiated patients.Additional lumen gain from re-stenting ISR lesions is counteracted by exaggerated neointimal proliferation in placebo patients. Maximum effectiveness and safety of radiation can be achieved for ISR lesions when treated without re-stenting. Thus, regardless of supplementary intravascular brachytherapy, repeat stenting strategies provided little long-term advantage.

  View details for DOI 10.1161/01.CIR.0000018949.39445.40

  View details for Web of Science ID 000175927500011

  View details for PubMedID 12034650

• Effect of local delivery of L-arginine on in-stent restenosis in humans AMERICAN JOURNAL OF CARDIOLOGY Suzuki, T., Hayase, M., Hibi, K., Hosokawa, H., Yokoya, K., Fitzgerald, P. J., Yock, P. G., Cooke, J. P., Suzuki, T., Yeung, A. C. 2002; 89 (4): 363-367

  Abstract

  To determine whether intramural administration of L-arginine reduces intimal thickening after optimal Palmaz-Schatz stent deployment in humans, 50 patients with native coronary artery disease who received a single Palmaz-Schatz stent were enrolled in this pilot study. Patients were randomized into 2 treatment groups: an L-arginine group (n = 25) and a saline group (n = 25). After stent deployment, L-arginine (600 mg/6 ml) or saline (6 ml) was locally delivered via the Dispatch catheter (Scimed) over 15 minutes. Serial angiography and intravascular ultrasound examinations (motorized pull-back at 0.5 mm/s) were performed before and after the procedure, and at 6-month follow-up. Measurements of stent area, lumen area, and neointimal area were computed within the stents at 1-mm intervals, by technicians who were blinded to the treatment assignment. Using Simpson's rule, stent, plaque, and lumen volumes, neointimal volume within the stent, and percent neointimal volume were measured before and after the procedure, and at 6-month follow-up. The 6-month volume data in quantitative coronary ultrasound showed that neointimal volume in the L-arginine group was significantly less than in the saline group (25 vs 39 mm(3); p = 0.049). Similarly, percent neointimal volume was significantly less in the L-arginine group at 6-month follow-up (17 +/- 13% vs 27 +/- 21%; p = 0.048). Thus, these results showed that local delivery of L-arginine reduces in-stent neointimal hyperplasia in humans, indicating that this approach may be a novel strategy to prevent in-stent restenosis.

  View details for Web of Science ID 000173816400001

  View details for PubMedID 11835911

• Predictors and outcomes of stent thrombosis - An intravascular ultrasound registry EUROPEAN HEART JOURNAL Uren, N. G., Schwarzacher, S. P., Metz, J. A., Lee, D. R., Honda, Y., Yeung, A. C., Fitzgerald, P. J., Yock, P. G. 2002; 23 (2): 124-132

  Abstract

  To investigate whether intravascular ultrasound provides additional information regarding the prediction of stent thrombosis, a retrospective multicentre registry was designed to enrol patients with stent thrombosis following stent deployment under ultrasound guidance.A total of 53 patients were enrolled (mean age 61+/-9 years) with stable angina (43%), unstable angina (36%), and post-infarct angina (21%) who underwent intracoronary stenting. The majority had balloon angioplasty alone prior to stenting (94%) with 6% also undergoing rotational atherectomy. The indication for stenting was elective (53%), suboptimal result (32%) and bailout (15%). There were 1.6+/-0.8 stents/artery with 87% undergoing high-pressure dilatation (> or =14 atmospheres). The minimum stent area was 7.7+/-2.8 mm(2)with a mean stent expansion of 81.5+/-21.9%. Overall, 94% of cases demonstrated one abnormal ultrasound finding (stent under-expansion, malapposition, inflow/outflow disease, dissection, or thrombus). Angiography demonstrated an abnormality in only 32% of cases (chi-square=30.0, P<0.001). Stent thrombosis occurred at 132+/-125 h after deployment. Myocardial infarction occurred in 67% and there was an overall mortality of 15%.On comparison with angiography, the vast majority of stents associated with subsequent thrombosis have at least one abnormal feature by intravascular ultrasound at the time of stent deployment.

  View details for DOI 10.1053/euhj.2001.2707

  View details for Web of Science ID 000173390100009

  View details for PubMedID 11785994

• Effects of transducer position on backscattered intensity in coronary arteries ULTRASOUND IN MEDICINE AND BIOLOGY Courtney, B. K., Robertson, A. L., Maehara, A., Luna, J., Kitamura, K., Morino, Y., Achalu, R., Kirti, S., Yock, P. G., Fitzgerald, P. J. 2002; 28 (1): 81-91

  Abstract

  Acute myocardial infarction is a frequent cause of sudden death, and is typically initiated by the rupture of coronary artery plaques. The likelihood and severity of rupture are influenced by the plaque structures and components. Radiofrequency (RF) intravascular ultrasound (US) (IVUS-RF) measurements extend current IVUS imaging techniques and may eventually enable the in vivo identification of these features. However, IVUS-RF measurements are affected by the transducer's instantaneous position in the vessel. Specifically, backscattered intensity (BI) decreases as either the distance between the tissue and the transducer increases, or as the beam's angle of incidence on the tissue increases. IVUS-RF data were acquired from seven disease-free coronary arteries in vitro. The 0-dB level for BI was defined as the peak intensity of the reflection from a stainless-steel flat reflector at each distance. The baseline BI measured in adventitial tissue was -32.5 dB (at 0 degrees, 0 mm) with angle and distance dependencies of -0.172 dB/ degrees and -3.37 dB/mm. In contrast, the BI from combined intima and media was -38.2 dB with dependencies of -0.111 dB/ degrees and -4.46 dB/mm (p < 0.05 for all three parameters). Acknowledging and compensating for these effects may allow IVUS-RF to develop into a rapidly deployable tool for the clinical detection of vulnerable plaques and to monitor coronary artery disease progression and regression.

  View details for PubMedID 11879955

• Intravascular ultrasound and quantitative coronary angiography CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Takahashi, T., Honda, Y., Russo, R. J., Fitzgerald, P. J. 2002; 55 (1): 118-128

  View details for Web of Science ID 000172956000024

  View details for PubMedID 11793508

• Impact of pre-interventional arterial remodeling on subsequent vessel behavior after balloon angioplasty: A serial intravascular ultrasound study JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Okura, H., Hayase, M., Shimodozono, S., Bonneau, H. N., Yock, P. G., Fitzgerald, P. J. 2001; 38 (7): 2001-2005

  Abstract

  The purpose of this study was to assess the impact of pre-intervention arterial remodeling on subsequent vessel behavior following balloon angioplasty.Positive arterial remodeling before intervention has been shown to have a negative impact on the clinical outcome after nonstented coronary interventional procedures. However, the mechanism of interventions in coronary vessel geometry over time is less well characterized.Serial (pre-, post- and follow-up) intravascular ultrasound analysis was performed in 46 native coronary lesions. Positive remodeling (PR) was defined as vessel area (VA) at the target lesion greater than that of average reference segments. Intermediate or negative remodeling (IR/NR) was defined as VA at the target lesion less than or equal to that of average reference segment. Remodeling index was defined as VA at the target lesion site divided by that of average references.Pre-interventional PR and IR/NR were present in 21 (46%) and 25 (54%) of 46 patients, respectively. At follow-up, the change in plaque area was similar between the two groups (1.3 +/- 2.1 vs. 1.2 +/- 2.1 mm(2), p = 0.840). Lesions with PR showed a significantly smaller change in VA than those with IR/NR (-0.2 +/- 2.5 vs. 1.4 +/- 2.3 mm(2), p = 0.03). As a result, late lumen loss was significantly larger in lesions whose pre-intervention configuration exhibited PR (-1.5 +/- 1.8 vs. 0.2 +/- 1.6 mm(2), p = 0.002).Lesions with PR appear to have less capacity to compensate for further plaque growth after balloon angioplasty and thus show a proportional increase in late lumen loss. This may in part explain the less favorable clinical outcomes of positively remodeled lesions.

  View details for Web of Science ID 000172458000035

  View details for PubMedID 11738307

• Efficacy of postdeployment balloon dilatation for current generation stents as assessed by intravascular ultrasound AMERICAN JOURNAL OF CARDIOLOGY Hur, S. H., Kitamura, K., Morino, Y., Honda, Y., Jones, M., Korr, K. S., Reen, B., Cooper, C. J., Niess, G. S., Christie, L., Corey, W., Messenger, J., Yock, P. G., Cummins, F., Fitzgerald, P. J. 2001; 88 (10): 1114-1119

  Abstract

  Adjunctive balloon dilatation strategy has been shown to improve optimal stent deployment. As improvements in current stent designs evolve, less adjunctive balloon dilatation may be needed. However, few data currently exist to support this practice. We evaluated 88 native coronary lesions treated with single stent implantation (Nir, Tristar or S670). Serial intravascular ultrasound was performed after successful stent deployment and again after adjunctive balloon dilatation. To investigate further the precise expansion characteristics of the stents, serial volumetric intravascular ultrasound analyses were performed in 40 patients with automated pullback. After adjunctive balloon dilatation, minimal stent area increased significantly, from 6.4 +/- 2.1 to 7.4 +/- 2.2 mm(2) (p <0.001). Volumetric analysis showed a corresponding increase in stent volume index (6.6 +/- 1.8 to 7.5 +/- 2.0 mm(3)/mm, p <0.001). In the analysis of cross sections at 0.5-mm axial intervals, the percentage of cross sections, where stent area was > or =80% of the average reference lumen area, increased from 51% to 78% (p <0.001). Similarly, the percentage of cross sections, where stent area was > or =90% of the average reference lumen area, increased from 29% to 56% (p <0.001) with postdilatation. Postdeployment high- pressure balloon dilatation improved minimal stent area and volumetric expansion throughout the stented segment.

  View details for Web of Science ID 000172412300006

  View details for PubMedID 11703954

• The renaissance of directional coronary atherectomy: a second look from the inside. journal of invasive cardiology Honda, Y., Fitzgerald, P. J. 2001; 13 (11): 748-751

  View details for PubMedID 11689719

• Fractional flow reserve compared with intravascular ultrasound guidance for optimizing stent deployment CIRCULATION Fearon, W. F., Luna, J., Samady, H., Powers, E. R., Feldman, T., Dib, N., Tuzcu, E. M., Cleman, M. W., Chou, T. M., Cohen, D. J., Ragosta, M., Takagi, A., Jeremias, A., Fitzgerald, P. J., Yeung, A. C., Kern, M. J., Yock, P. G. 2001; 104 (16): 1917-1922

  Abstract

  Determination of fractional flow reserve (FFR) has been proposed as a means to assess stent deployment. In this prospective, multicenter trial, we evaluate the use of FFR to optimize stenting by comparing it with standard intravascular ultrasound (IVUS) criteria.Eighty-four stable patients with isolated coronary lesions underwent coronary stent deployment starting at 10 atm and increased serially by 2 atm until the FFR was >/=0.94 or 16 atm was achieved. IVUS was then performed. FFR was measured with a coronary pressure wire with intracoronary adenosine to induce hyperemia. The diagnostic characteristics of an FFR <0.94 to predict suboptimal stent expansion by IVUS, defined in both absolute and relative terms, were calculated. Over a range of IVUS criteria, the highest sensitivity, specificity, and predictive accuracy of FFR were 80%, 30%, and 42%, respectively. Receiver operator characteristic analysis defined an optimal FFR cut point at >/=0.96; at this threshold, the sensitivity, specificity, and predictive accuracy of FFR were 75%, 58%, and 62%, respectively (P=0.03 for comparison of predictive accuracy, P=0.01 for concordance between FFR and IVUS). The negative predictive value was 88%. Significantly better diagnostic performance was achieved in a subgroup that received higher doses (>30 microgram) of intracoronary adenosine during pressure measurements, suggesting that FFR might be overestimated in the other group.A fractional flow reserve <0.96, measured after stent deployment, predicts a suboptimal result based on validated intravascular ultrasound criteria; however, an FFR >/=0.96 does not reliably predict an optimal stent result. Higher doses of intracoronary adenosine than previously used to measure FFR improve these results.

  View details for PubMedID 11602494

• An optimal diagnostic threshold for minimal stent area to predict target lesion revascularization following stent implantation in native coronary lesions AMERICAN JOURNAL OF CARDIOLOGY Morino, Y., Honda, Y., Okura, H., Oshima, A., Hayase, M., Bonneau, H. N., Kuntz, R. E., Yock, P. G., Fitzgerald, P. J. 2001; 88 (3): 301-?

  View details for Web of Science ID 000170090500020

  View details for PubMedID 11472713

• Novel drug-delivery stent - Intravascular ultrasound observations from the first human experience with the QP2-eluting polymer stent system CIRCULATION Honda, Y., Grube, E., de la Fuente, L. M., Yock, P. G., Stertzer, S. H., Fitzgerald, P. J. 2001; 104 (4): 380-383

  Abstract

  The aim of this study was to use serial intravascular ultrasound (IVUS) to evaluate the long-term effect of stent-based 7-hexanoyltaxol (QP2, a taxane analogue) delivery on neointimal tissue growth within the stent and on vessel dimensions at the adjacent reference segments.Serial IVUS analyses (immediately after intervention and at follow-up at 8.3 months) were performed in 15 native coronary lesions treated with the QuaDS-QP2 stent. IVUS measurements were performed at 8 cross-sections in each target segment (4 cross-sections within the stent and 2 cross-sections in each reference segment). At baseline, no significant plaque protrusion or thrombus was detected in the target segment. Mild incomplete stent apposition and edge dissection were observed in one and two cases, respectively. Percent expansion of the stent (minimum stent area/average reference lumen area) was 96.0+/-21.7%. At follow-up, mean neointimal area within the stent was 1.2+/-1.3 mm(2), and mean cross-sectional narrowing (neointimal area/stent area) was 13.6+/-14.9%. At the vessel segments immediately adjacent to the stent, a significant increase in plaque area (1.9+/-2.6 mm(2), P=0.001) was observed, but vessel area remained unchanged. However, no patients showed clinically significant in-stent or edge restenosis (diameter stenosis >/=50%) during the follow-up period.The first human experience with the new drug-delivery stent showed a minimal amount of neointimal proliferation in the stented segment. Late lumen loss at the reference sites adjacent to the stent was acceptable and predominantly due to plaque proliferation.

  View details for Web of Science ID 000170116200003

  View details for PubMedID 11468196

• Vascular brachytherapy: what have we learned from intravascular ultrasound? journal of invasive cardiology Morino, Y., Bonneau, H. N., Fitzgerald, P. J. 2001; 13 (5): 409-416

  Abstract

  With the advent of intravascular brachytherapy (IVBT), a striking reduction in the rate of restenosis has been observed. The use of intravascular ultrasound (IVUS) during IVBT trials has shown many aspects and relevant pathophysiologic mechanisms following this practical therapy. Specifically, IVUS quantitative assessments have demonstrated a drastic inhibition of both neointimal formation and negative remodeling to be the predominant vascular response to IVBT. Moreover, IVBT has shown promise for challenging high-risk restenosis cases, such as patients with diabetes mellitus and smaller caliber target vessels. However, unexpected radiation-induced complications have also been discovered, as more patients have been treated for a broad class of lesion subsets. Edge effect, induced by catheter-based radiation, was seen to be due to geographic miss of the radiation source, advocating a new concept known as "radiation edge". Furthermore, late thrombosis, which is known to be strongly associated with new stent implantation following IVBT, may be avoided with novel antiplatelet agents. Two additional complications, whose clinical significance remains unclear, are unhealed dissection and late stent malapposition featured by IVUS qualitative assessment. Unhealed dissection was observed in half of radiated dissections and late stent malapposition has been seen for all radiation sources in a small percentage of cases at 6-12 months follow-up. Radiation sources, dosimetry, and delivery methods continue to improve and should ultimately translate to more effective treatment for the patient with atherosclerotic coronary disease.

  View details for PubMedID 11385159

• Impact of peri-stent remodeling on restenosis - A volumetric intravascular ultrasound study CIRCULATION Nakamura, M., Yock, P. G., Bonneau, H. N., Kitamura, K., Aizawa, T., Tamai, H., Fitzgerald, P. J., Honda, Y. 2001; 103 (17): 2130-2132

  Abstract

  Vessel remodeling is an important mechanism of late lumen loss after nonstent coronary interventions. However, its impact on in-stent restenosis has not been systematically investigated.Serial volumetric intravascular ultrasound analyses (poststent and follow-up) were performed in 55 lesions treated with a balloon-expandable stent (ACS MultiLink) using standard stent deployment techniques. The vessel volume (VV), lumen volume (LV), and volume bordered by the stent (SV) were measured using Simpson's method. The volume of plaque and neointima outside the stent (peri-stent volume, PSV) and volume of neointima within the stent (intrastent volume) were also measured. The change of each parameter during the follow-up period (follow-up minus poststent) was calculated and then divided by SV to normalize these values (designated as percent change [%]). As expected, %PSV directly correlated with %VV (P<0.0001, r=0.935), with no significant SV. A highly significant inverse correlation was seen between %PSV and the percent change of intrastent volume (P<0.0001, r=0.517). Consequently, %LV significantly correlated with peri-stent remodeling, as measured by %VV (P<0.0001, r=0.602).Positive remodeling of the vessel exterior to a coronary stent occurs to a variable degree after stent implantation. There is a distinct trade-off between positive remodeling and in-stent hyperplasia: in segments in which the degree of peri-stent remodeling is less, intrastent neointimal proliferation is greater and accompanied by more significant late lumen loss.

  View details for Web of Science ID 000168583700002

  View details for PubMedID 11331251

• Intravascular sonotherapy decreases neointimal hyperplasia after stent implantation in swine CIRCULATION Fitzgerald, P. J., Takagi, A., Moore, P., Hayase, M., Kolodgie, F. D., Corl, D., Nassi, M., Virmani, R., Yock, P. 2001; 103 (14): 1828-1831

  Abstract

  Intimal hyperplasia and subsequent in-stent restenosis remain a major limitation after stent implantation. In vitro cell culture studies show that low-frequency, noncavitational ultrasound energy may impact smooth muscle cell proliferation. Accordingly, we assessed the efficacy of intravascular sonotherapy treatment on intimal hyperplasia in a swine stent model.After balloon injury, biliary stents (Johnson & Johnson) were implanted in the femoral arteries of 14 swine. A total of 48 stented sites were randomized to sonotherapy or sham treatment using a custom-built, 8-French catheter intravascular sonotherapy system (URX, PharmaSonics Inc). After stent deployment, ultrasound energy (700 KHz) was applied to the treatment group for up to 5 minutes. Smooth muscle cell proliferation was assessed using bromodeoxyuridine histology preparation (BrdU) at 7 days in 28 stented sites. At 28 days, the neointimal thickness and the ratio of neointimal/stent area (percent stenosis) was calculated by histomorphometric quantification in 20 stented sites. At 7 days, percent of BrdU staining was significantly reduced in the sonotherapy group compared with the sham group (24.1+/-7.0% versus 31.2+/-3.0%, P<0.05). At 28 days, percent stenosis was significantly less in the sonotherapy group than in the sham group (36+/-24% versus 44+/-27%, P<0.05), and the mean neointimal thickness in the sonotherapy group was less than in the sham group (417+/-461 micrometer versus 643+/-869 micrometer, P=0.06).In this swine peripheral model, intravascular sonotherapy seemed to decelerate cellular proliferation and decrease in-stent hyperplasia. Therefore, intravascular sonotherapy may be an effective form of nonionizing energy to reduce in-stent restenosis.

  View details for Web of Science ID 000168122300010

  View details for PubMedID 11294798

• Long-term vessel response to a self-expanding coronary stent: A serial volumetric intravascular ultrasound analysis from the ASSURE trial JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Kobayashi, Y., Honda, Y., Christie, L. G., Teirstein, P. S., Bailey, S. R., Brown, C. L., Matthews, R. V., De Franco, A. C., Schwartz, R. S., Goldberg, S., Popma, J. J., Yock, P. G., Fitzgerald, P. J. 2001; 37 (5): 1329-1334

  Abstract

  We sought to investigate the in vivo mechanical properties of a new self-expanding coronary stent (RADIUS) and, particularly, the subsequent vessel response over time.Preclinical studies have suggested that self-expanding stents may produce less vessel wall injury at initial deployment, leading to larger follow-up lumens than with balloon-expandable stents. However, the influence of the chronic stimulus from self-expanding stents on the vessel wall remains unknown.Sixty-two patients were randomly assigned to either the RADIUS self-expanding stent group (n = 32) or the Palmaz-Schatz balloon-expandable stent group (n = 30). Intravascular ultrasound was performed after stent deployment and at six-month follow-up.At follow-up, the RADIUS stents had increased 23.6% in overall volume, while the Palmaz-Schatz stents had remained unchanged. Due to the greater mean neointimal area (3.0 +/- 1.7 mm2 vs. 1.9 +/- 1.2 mm2, p = 0.02) in the RADIUS group, no significant difference in net late lumen loss was observed between the two groups. On the other hand, analysis at the peristent margins demonstrated that mean late loss was significantly smaller in the RADIUS group than it was in the Palmaz-Schatz group (0.1 +/- 2.1 mm2 vs. 1.9 +/- 2.4 mm2, p = 0.02).Serial volumetric IVUS revealed that the RADIUS stents continued to enlarge during the follow-up period. In this stent implantation protocol, this expansion was accompanied by a greater amount of neointima than the Palmaz-Schatz stents, resulting in similar late lumen loss in both configurations. In the peristent margins, however, late lumen loss was minimized with the RADIUS stents.

  View details for Web of Science ID 000167901700027

  View details for PubMedID 11300443

• Preintervention arterial remodeling affects clinical outcome following stenting: An intravascular ultrasound study JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Okura, H., Morino, Y., Oshima, A., Hayase, M., Ward, M. R., Popma, J. J., Kuntz, R. E., Bonneau, H. N., Yock, P. G., Fitzgerald, P. J. 2001; 37 (4): 1031-1035

  Abstract

  The study was done to elucidate the relationship between baseline arterial remodeling and clinical outcome following stenting.The impact of preintervention arterial remodeling on subsequent vessel response and clinical outcome has been reported following nonstent coronary interventions. However, in stented segments, the impact of preintervention remodeling on clinical outcome has not been clarified.Preintervention remodeling was assessed in 108 native coronary lesions by using intravascular ultrasound (IVUS). Positive remodeling (PR) was defined as vessel area (VA) at the target lesion greater than that of average reference segments. Intermediate or negative remodeling (IR/NR) was defined as VA at the target lesion less than or equal to that of average reference segment. Remodeling index expressed as a continuous variable was defined as VA at the target lesion site divided by that of average reference segments.Positive remodeling was present in 59 (55%) and IR/NR in 49 (45%) lesions. Although final minimal stent areas were similar (7.76 +/- 1.80 vs. 8.09 +/- 1.90 mm2, p = 0.36), target vessel revascularization (TVR) rate at nine-month follow-up was significantly higher in the PR group (22.0% vs. 4.1%, p = 0.01). By multivariate logistic regression analysis, higher remodeling index was the only independent predictor of TVR (p = 0.02).Lesions with PR before intervention appear to have a worse clinical outcome following IVUS-guided stenting. Intravascular ultrasound imaging before stenting may be helpful to stratify lesions at high risk for accelerated intimal proliferation.

  View details for Web of Science ID 000167515700010

  View details for PubMedID 11263604

• The influence of plaque orientation (pericardial or myocardial) on coronary arterial remodeling ATHEROSCLEROSIS Ward, M. R., Jeremias, A., Hibi, K., Herity, N. A., Lo, S. T., Filardo, S. D., Lee, D. P., Fitzgerald, P. J., Yeung, A. C. 2001; 154 (1): 179-183

  Abstract

  Many systemic, regional and lesion factors have been identified which may influence arterial remodeling, but little is known about the importance of extravascular resistance to vessel enlargement. As myocardial systolic splinting may significantly affect vessel expansion the effect of plaque orientation on arterial remodeling in eccentric coronary atherosclerotic lesions was examined.Using intravascular ultrasound imaging to obtain cross-sectional vessel area (VA), plaque area (PA) and lumen area (LA), remodeling in eccentric left anterior descending coronary artery lesions was compared which predominantly involved the pericardial or free arc (P, n=25) and the myocardial side (M, n=40) of the vessel wall. Normalized vessel area (NVA, VA(lesion)/VA(reference)) was compared as a continuous and categorical variable (positive>1.05, intermediate 0.95-1.05, negative<0.95) as well as remodeling index (RI, VA(lesion)-VA(reference)/PA(lesion)-PA(reference)).The two groups were well matched for clinical and lesion characteristics known to affect remodeling. Reference segments areas were similar in the two groups; while lesion LA was also similar, in the pericardial group there was significantly greater lesion PA (P 12.78+/-0.72, M 10.26+/-0.50 mm(2), P<0.05) and VA (P 15.71+/-0.90, M 12.82+/-0.57 mm(2), P<0.05) demonstrating enhanced compensatory remodeling. Outward remodeling was significantly greater in P than in M by both NVA (P 1.03+/-0.03, M 0.86+/-0.03, P<0.01) and RI (P 0.02+/-0.07, M -1.10+/-0.32, P<0.01). Positive, intermediate and negative remodeling occurred in nine, nine and seven lesions in P and in four, ten and 26 lesions in M (P<0.01).Remodeling compensates more for plaque growth in eccentric coronary lesions which are surrounded by the pericardium than those surrounded by the myocardium. Extravascular resistance appears to influence arterial remodeling.

  View details for Web of Science ID 000166116000022

  View details for PubMedID 11137098

• Impact of plaque burden on subsequent intimal proliferation and remodeling of the stented coronary arteries following intracoronary beta-radiation therapy. Cardiovascular radiation medicine Okura, Lee, Yeung, OESTERLE, Waksman, Kaluza, Ali, Yock, Raizner, Fitzgerald 2001; 2 (1): 57-?

  View details for PubMedID 11068273

• Longitudinal plaque redistribution during stent expansion AMERICAN JOURNAL OF CARDIOLOGY Maehara, A., Takagi, A., Okura, H., Hassan, A. H., Bonneau, H. N., Honda, Y., Yock, P. G., Fitzgerald, P. J. 2000; 86 (10): 1069-1072

  Abstract

  The purpose of this study was to clarify the 3-dimensional behavior of plaque during coronary stent expansion. Serial intravascular ultrasound (IVUS) studies, preintervention, and poststenting were evaluated in 32 patients treated with a single-balloon expandable tubular stent. External elastic membrane (EEM), lumen, stent, and plaque + media cross-sectional area were measured at 1-mm intervals through the entire stent as well as proximal and distal reference segments 5 mm from the stent edge. Volumetric calculations were based on Simpson's rule. Overall, the plaque + media volume through the entire lesion did not change during stent expansion (218 +/- 51 vs 217 +/- 47 mm3, p = 0.69). However, EEM and lumen volume increased significantly (EEM volume, 391 +/- 84 vs 448 +/- 87 mm3 [p < 0.0001]; lumen volume, 173 +/- 52 vs 231 +/- 54 mm3 [p < 0.0001]). The change in lumen volume correlated strongly with the change in EEM volume (r = 0.85, p < 0.0001), but poorly with the change in plaque + media volume (r = 0.37, p = 0.03). Plaque + media volume decreased in the midstent zone (59 +/- 14 vs 53 +/- 11 mm3, p = 0.0005), and increased in the distal stent zone (40 +/- 11 vs 44 +/- 9 mm3, p = 0.003), but did not change in either the proximal stent zone or reference segments. The mechanism of stent expansion is a combination of vessel stretch and plaque redistribution, translating disease accumulation from the midstent zone to the distal stent zone.

  View details for Web of Science ID 000165185500003

  View details for PubMedID 11074201

• Photoangioplasty for human peripheral atherosclerosis - Results of a phase I trial of photodynamic therapy with motexafin lutetium (Antrin) 72nd Annual Scientific Session of the American-Heart-Association Rockson, S. G., Kramer, P., Razavi, M., Szuba, A., Filardo, S., Fitzgerald, P., Cooke, J. P., Yousuf, S., DeVault, A. R., Renschler, M. F., Adelman, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2000: 2322–24

  Abstract

  In photoangioplasty, light activation of a photosensitive drug offers the potential for treatment of long segments of vascular disease. This is a brief description of a study designed to evaluate the safety and tolerability of a new photosensitizer, Antrin (motexafin lutetium), in the endovascular treatment of atherosclerosis.An open-label, single-dose, escalating drug- and light-dose study was performed in patients with atherosclerotic peripheral arterial insufficiency. Clinical evaluation, serial quantitative angiography, and intravascular ultrasonography were performed. Therapy was well tolerated, and only minor side effects were observed. Treatment produced no deleterious vascular effects. Although this study was not designed to examine clinical efficacy, several secondary end points suggested a favorable therapeutic effect.This phase I study demonstrates that photoangioplasty with motexafin lutetium is well tolerated and safe. Preliminary efficacy data suggest a future role for the treatment of flow-limiting atherosclerosis.

  View details for Web of Science ID 000165169200001

  View details for PubMedID 11067782

• Selective regional myocardial infiltration by the percutaneous coronary venous route: A novel technique for local drug delivery CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Herity, N. A., Lo, S. T., Oei, F., Lee, D. P., Ward, M. R., Filardo, S. D., Hassan, A., Suzuki, T., Rezaee, M., Carter, A. J., Yock, P. G., Yeung, A. C., Fitzgerald, P. J. 2000; 51 (3): 358-363

  Abstract

  Recent advances in the treatment of heart disease, in particular cardiovascular gene therapy and therapeutic angiogenesis, highlight the need for efficient and practical local delivery methods for the heart. We assessed the feasibility of percutaneous selective coronary venous cannulation and injection as a novel approach to local myocardial drug delivery. In anesthetized swine, the coronary sinus was cannulated percutaneously and a balloon-tipped catheter advanced to the anterior interventricular vein (AIV) or middle cardiac vein (MCV). During balloon occlusion, venous injection of radiographic contrast caused regional infiltration of targeted myocardial regions. Complete AIV occlusion had no impact on LAD flow parameters. Videodensitometric analysis following venous injection showed that radiographic contrast persisted for at least 30 min. Selective regional myocardial infiltration is feasible by this approach, targeting selected myocardial beds, including the apex, anterior wall, septum, and inferoposterior wall. This novel technique has potential application for local myocardial drug or growth factor delivery. Cathet. Cardiovasc. Intervent. 51:358-363, 2000.

  View details for PubMedID 11066126

• Feasibility of a novel blood noise reduction algorithm to enhance reproducibility of ultra-high-frequency intravascular ultrasound images CIRCULATION Hibi, K., Takagi, A., Zhang, X. M., Teo, T. J., Bonneau, H. N., Yock, P. G., Fitzgerald, P. J. 2000; 102 (14): 1657-1663

  Abstract

  Ultra-high-frequency (40- to 50-MHz) intravascular ultrasound (IVUS) improves image quality compared with conventional 20- to 30-MHz IVUS. However, as the frequency of IVUS increases, high-intensity backscatter from blood components may cause visual difficulties in discrimination between the lumen and arterial wall structure. The purpose of this study was to evaluate the effect of a novel blood noise reduction algorithm (BNR) on quantitative coronary ultrasound measurements.IVUS studies using a 40-MHz transducer were performed in 35 patients with coronary artery disease. A total of 620 gray-scale images (310 pairs) were processed with and without the BNR, and lumen cross-sectional area (CSA) was determined by 2 independent observers. With the BNR, the intraobserver and interobserver correlation coefficients for lumen CSA were significantly improved (0.85 to 0.99 and 0.80 to 0.98, respectively). In the 270 images (135 pairs) in which vessel wall measurements were possible, the BNR significantly improved the intraobserver and interobserver correlation coefficients for plaque plus media CSA (0.83 to 0.99 and 0.76 to 0.97, respectively), whereas no influence was observed for external elastic membrane CSA (1.00 to 1.00 and 0.99 to 0.99, respectively).This study demonstrates the feasibility of this novel algorithm to reduce blood noise, thereby enabling accurate lumen border delineation and providing reproducible measurements of both the lumen and plaque plus media CSAs. Incorporating a digital BNR may serve as an important adjunct to ultra-high-frequency IVUS imaging for improving accurate quantitative evaluation of vessel dimensions.

  View details for Web of Science ID 000089593000012

  View details for PubMedID 11015344

• Adequacy of intracoronary versus intravenous adenosine-induced maximal coronary hyperemia for fractional flow reserve measurements AMERICAN HEART JOURNAL Jeremias, A., Whitbourn, R. J., Filardo, S. D., Fitzgerald, P. J., Cohen, D. J., Tuzcu, M., Anderson, W. D., Abizaid, A. A., Mintz, G. S., Yeung, A. C., Kern, M. J., Yock, P. G. 2000; 140 (4): 651-657

  Abstract

  Fractional flow reserve (FFR) is a measure of coronary stenosis severity that is based on pressure measurements obtained at maximal hyperemia. The most widely used pharmacologic stimulus for maximal coronary hyperemia is adenosine, administered either as a continuous intravenous (IV) infusion or intracoronary (IC) bolus. IV adenosine has more side effects and is more costly than IC adenosine but has a more stable and prolonged hyperemic effect.We compared the efficacy of IC and IV adenosine administration for the measurement of FFR in a multicenter trial. Fifty-two patients with 60 lesions underwent determination of FFR with both IV and IC adenosine. IV adenosine was administered as a continuous infusion at a rate of 140 microgram/kg per minute until a steady state hyperemia was achieved. IC adenosine boluses were administered at a dose of 15 to 20 microgram in the right and 18 to 24 microgram in the left coronary artery. FFR was calculated as the ratio of the distal coronary pressure (from pressure guide wire) to the aortic pressure (guide catheter) at maximal hyperemia.A total of 26 left anterior descending, 23 right, 9 left circumflex, and 3 left main coronary arteries were evaluated. Mean percent stenosis for both groups was 55.8% +/- 23.6% (range 0% to 95%), and mean FFR was 0.78 +/- 0.15 (range 0.41 to 0.98). There was a strong and linear correlation between FFR measurements with IV and IC adenosine (R = 0.978, y = 0. 032 + 0.964x, P <.001). The agreement between the 2 sets of measurements was also high, with a mean difference in FFR of -0.004 +/- 0.03. However, a small random scatter in both directions of FFR measurements was noted with 5 lesions (8.3%) where FFR with IC adenosine was higher by 0.05 or more compared with IV infusions, suggesting a suboptimal hyperemic response in these patients. Changes in heart rate and blood pressure were significantly higher with IV adenosine. Two patients with IV, but none with IC adenosine, had severe side effects (bronchospasm and severe nausea).These results suggest that IC adenosine is equivalent to IV infusion for the determination of FFR in the majority of patients. However, in a small percentage of cases, coronary hyperemia was suboptimal with IC adenosine.

  View details for Web of Science ID 000089692600016

  View details for PubMedID 11011341

• Tissue characterization of atherosclerotic plaques by intravascular ultrasound radiofrequency signal analysis: An in vitro study of human coronary arteries AMERICAN HEART JOURNAL Komiyama, N., Berry, G. J., Kolz, M. L., Oshima, A., Metz, J. A., Preuss, P., Brisken, A. F., Moore, M. P., Yock, P. G., Fitzgerald, P. J. 2000; 140 (4): 565-574

  Abstract

  Conventional gray-scale images of intravascular ultrasound (IVUS) cannot accurately differentiate histologic subtypes of sonolucent coronary plaques with or without a lipid core.We analyzed radiofrequency signals obtained in vitro from 24 regions of interest (ROI) of noncalcified (sonolucent) plaques in 10 atherosclerotic coronary artery specimens pressure-fixed by formalin. Radiofrequency signals were sampled with a 30-MHz IVUS catheter and digitized at 500 MHz in 8-bit resolution. The ROIs were histologically categorized into 12 plaques with a lipid core and 12 plaques without it. Integrated backscatter and statistical parameters of the radiofrequency envelope (mean/SD ratio [MSR], skewness, and kurtosis) within the ROI were calculated offline, and their ability to detect a lipid core was compared with visual analysis of the IVUS video images. In the group with lipid cores, percent area of a lipid core in each ROI was measured in a digitized histologic image by a computerized planimeter.Sensitivity and specificity of MSR, skewness, and kurtosis for lipid core detection were substantially greater than visual video image analysis (83.3% and 91.7%, 100% and 91.7%, 100% and 91.7% vs 53.3% and 71.7%). Furthermore, the parameters of integrated backscatter, MSR, skewness, and kurtosis were significantly correlated to percent of core area (r = -0.64, -0.73, 0.78, and 0.63, respectively; P<.05).Compared with IVUS video images, the parameters of radiofrequency signal analysis may be used to aid in more accurate detection and quantitative evaluation of a lipid core, which is one of the major factors of a vulnerable coronary plaque.

  View details for Web of Science ID 000089692600005

  View details for PubMedID 11011329

• Spatial orientation of atherosclerotic plaque in non-branching coronary artery segments ATHEROSCLEROSIS Jeremias, A., Huegel, H., Lee, D. P., Hassan, A., Wolf, A., Yeung, A. C., Yock, P. G., Fitzgerald, P. J. 2000; 152 (1): 209-215

  Abstract

  It has been postulated that atherosclerotic plaque deposition is spatially related to regions of low shear in non-branching vessel segments. Intravascular ultrasound (IVUS) allows precise spatial orientation of coronary artery plaque formation in humans. The objective of this study was to test the hypothesis that coronary plaques have a higher prevalence on the myocardial side in regions that encounter low surface shear stress. IVUS allows the determination of the inner versus the outer curve of the vessel based on vascular and perivascular landmarks. We studied 30 consecutive patients pre-intervention using IVUS and measured vessel area, lumen area and plaque area (vessel-lumen area) during a motorized pullback at 1 mm intervals. Vessel segments near a side branch (within two times the diameter of the vessel) were excluded from analysis because of flow disturbances. All plaques were classified as concentric or eccentric and all eccentric plaques were further divided with respect to their spatial orientation in the vessel into quadrants: myocardial (inner curve, lower shear stress), epicardial (outer curve, higher shear stress) and lateral (two quadrants intermediate). A total of 613 cross-sections were analyzed in 14 left anterior descending, six left circumflex, and ten right coronary arteries. Plaque distribution was found to be concentric in 321 (52.4%) and eccentric in 292 (47.6%) cross sections. Of all eccentric plaques, 184 cross sections were oriented toward the myocardial side (62.6%) compared to only 54 toward the epicardial side (17.3%) and 54 in the 2 lateral quadrants (19.5%, P<0.001). No difference in plaque area (6.75+/-2.70 vs. 6.76+/-2.60 mm(2)), vessel area (15.28+/-4.73 vs. 15.35+/-4.40 mm(2)), or plaque thickness (1.26+/-0.37 vs. 1.25+/-0.43 mm) was noted between myocardial or epicardial plaques. These results suggest that atherosclerotic plaques develop more frequently on the myocardial side of the vessel wall, which may relate to lower shear stress. However, plaque size is similar on the epicardial and myocardial side.

  View details for PubMedID 10996357

• Coronary artery compliance and adaptive vessel remodelling in patients with stable and unstable coronary artery disease HEART Jeremias, A., Spies, C., Herity, N. A., Pomerantsev, E., Yock, P. G., Fitzgerald, P. J., Yeung, A. C. 2000; 84 (3): 314-319

  Abstract

  To test the hypothesis that patients with unstable coronary syndromes show accentuated compensatory vessel enlargement compared with patients with stable angina, and that this may in part be related to increased coronary artery distensibility.In 23 patients with unstable coronary syndromes (10 with non-Q wave myocardial infarction and 13 with unstable angina), the culprit lesion was investigated by intravascular ultrasound before intervention. The vessel cross sectional area (VA), lumen area (LA), and plaque area (VA minus LA) were measured at end diastole and end systole at the lesion site and at the proximal and distal reference segments. Similar measurements were made in 23 patients with stable angina admitted during the same period and matched for age, sex, and target vessel. Calculations were made of remodelling index (VA at lesion site / VA at reference site), distensibility index ([(delta A/A)/delta P] x 10(3), where delta A is the luminal area change in systole and diastole and delta P the difference in systolic and diastolic blood pressure measured at the tip of the guiding catheter during a cardiac cycle), and stiffness index beta ([ln(P(sys)/P(dias))]/(delta D/D), where P(sys) is systolic pressure, P(dias) is diastolic pressure, and delta D is the difference between systolic and diastolic lumen diameters). Positive remodelling was defined as when the VA at the lesion was > 1.05 times larger than at the proximal reference site, and negative remodelling when the VA at the lesion was < 0.95 of the reference site.Mean (SD) LA at the lesion site was similar in both groups (4.03 (1.8) v 4.01 (1. 93) mm(2)), while plaque area was larger in the unstable group (13. 29 (4.04) v 8.34 (3.6) mm(2), p < 0.001). Remodelling index was greater in the unstable group (1.14 (0.18) v 0.83 (0.15), p < 0.001). Positive remodelling was observed in 15 patients in the unstable group (65%) but in only two (9%) in the stable group (p < 0.001). Negative remodelling occurred only in two patients with unstable symptoms (9%) but in 17 (74%) with stable symptoms. At the proximal reference segment, the difference in LA between systole and diastole was 0.99 (0.66) mm(2) in the unstable group and 0.39 (0.3) mm(2) in the stable group (p < 0.001), and the calculated coronary artery distensibility was 3.09 (2.69) and 0.94 (0.83) per mm Hg in unstable and stable patients, respectively (p < 0.001). The stiffness index beta was lower in patients with unstable angina (1.95 (0.94) v 3.1 (0.96), p < 0.001).Compensatory vessel enlargement occurs to a greater degree in patients with unstable than with stable coronary syndromes, and is associated with increased coronary artery distensibility.

  View details for Web of Science ID 000089145800020

  View details for PubMedID 10956298

• Inhibition of restenosis with beta-emitting radiotherapy - Report of the Proliferation Reduction with Vascular Energy Trial (PREVENT) CIRCULATION Raizner, A. E., Oesterle, S. N., Waksman, R., Serruys, P. W., Colombo, A., Lim, Y. L., Yeung, A. C., van der Giessen, W. J., Vandertie, L., Chiu, J. K., White, L. R., Fitzgerald, P. J., Kaluza, G. L., Ali, N. M. 2000; 102 (9): 951-958

  Abstract

  Intracoronary gamma- and beta-radiation have reduced restenosis in animal models. In the clinical setting, the effectiveness of beta-emitters has not been studied in a broad spectrum of patients, particularly those receiving stents.A prospective, randomized, sham-controlled study of intracoronary radiotherapy with the beta-emitting (32)P source wire, using a centering catheter and automated source delivery unit, was conducted. A total of 105 patients with de novo (70%) or restenotic (30%) lesions who were treated by stenting (61%) or balloon angioplasty (39%) received 0 (control), 16, 20, or 24 Gy to a depth of 1 mm in the artery wall. Angiography at 6 months showed a target site late loss index of 11+/-36% in radiotherapy patients versus 55+/-30% in controls (P:<0.0001). A low late loss index was seen in stented and balloon-treated patients and was similar across the 16, 20, and 24 Gy radiotherapy groups. Restenosis (>/=50%) rates were significantly lower in radiotherapy patients at the target site (8% versus 39%; P:=0.012) and at target site plus adjacent segments (22% versus 50%; P:=0.018). Target lesion revascularization was needed in 5 radiotherapy patients (6%) and 6 controls (24%; P:<0.05). Stenosis adjacent to the target site and late thrombotic events reduced the overall clinical benefit of radiotherapy.beta-radiotherapy with a centered (32)P source is safe and highly effective in inhibiting restenosis at the target site after stent or balloon angioplasty. However, minimizing edge narrowing and late thrombotic events must be accomplished to maximize the clinical benefit of this modality.

  View details for Web of Science ID 000088977000013

  View details for PubMedID 10961957

• Final results of the Can Routine Ultrasound Influence Stent Expansion (CRUISE) study CIRCULATION Fitzgerald, P. J., Oshima, A., Hayase, M., Metz, J. A., Bailey, S. R., Baim, D. S., Cleman, M. W., DEUTSCH, E., Diver, D. J., Leon, M. B., Moses, J. W., Oesterle, S. N., Overlie, P. A., Pepine, C. J., Safian, R. D., Shani, J., Simonton, C. A., Smalling, R. W., Teirstein, P. S., Zidar, J. P., Yeung, A. C., Kuntz, R. E., Yock, P. G. 2000; 102 (5): 523-530

  Abstract

  Intravascular ultrasound (IVUS) can assess stent geometry more accurately than angiography. Several studies have demonstrated that the degree of stent expansion as measured by IVUS directly correlated to clinical outcome. However, it is unclear if routine ultrasound guidance of stent implantation improves clinical outcome as compared with angiographic guidance alone.The CRUISE (Can Routine Ultrasound Influence Stent Expansion) study, a multicenter study IVUS substudy of the Stent Anti-thrombotic Regimen Study, was designed to assess the impact of IVUS on stent deployment in the high-pressure era. Nine centers were prospectively assigned to stent deployment with the use of ultrasound guidance and 7 centers to angiographic guidance alone with documentary (blinded) IVUS at the conclusion of the procedure. A total of 525 patients were enrolled with completed quantitative coronary angiography, quantitative coronary ultrasound, and clinical events adjudicated at 9 months for 499 patients. The IVUS-guided group had a larger minimal lumen diameter (2.9+/-0.4 versus 2.7+/-0. 5 mm, P<0.001) by quantitative coronary angiography and a larger minimal stent area (7.78+/-1.72 versus 7.06+/-2.13 mm(2), P<0.001) by quantitative coronary ultrasound. Target vessel revascularization, defined as clinically driven repeat interventional or surgical therapy of the index vessel at 9 month-follow-up, occurred significantly less frequently in the IVUS-guided group (8.5% versus 15.3%, P<0.05; relative reduction of 44%).These data suggest that ultrasound guidance of stent implantation may result in more effective stent expansion compared with angiographic guidance alone.

  View details for Web of Science ID 000088486200010

  View details for PubMedID 10920064

• Automated contour detection for high-frequency intravascular ultrasound imaging: A technique with blood noise reduction for edge enhancement ULTRASOUND IN MEDICINE AND BIOLOGY Takagi, A., Hibi, K., Zhang, X. M., Teo, T. J., Bonneau, H. N., Yock, P. G., Fitzgerald, P. J. 2000; 26 (6): 1033-1041

  Abstract

  Automated edge detection may standardize measurements among observers, providing for rapid assessment of intravascular ultrasound (IVUS) images. However, with high frequency images, enhanced blood signals make it difficult to define and trace the lumen borders. Accordingly, we evaluated a fully automated contour analysis facilitated with a blood noise reduction algorithm (BNR) for 40-MHz IVUS images in human coronary arteries of 27 patients. This algorithm is based on the principle that blood echo speckles have higher temporal and spatial variations than the arterial wall. A total of 193 paired lumen areas and 78 external elastic membrane (EEM) areas were measured and compared. Automated measurements showed good agreement with manual tracings for lumen and EEM area, with high correlation coefficients (0.945 and 0.950, respectively) and small variability (0.4 +/- 14.4% and 0.6 +/- 9.7%, respectively). This preliminary finding suggests that automated contour detection facilitated with BNR appeared to be a feasible and reliable technique for area measurements in 40-MHz IVUS imaging.

  View details for Web of Science ID 000089463900009

  View details for PubMedID 10996703

• Review of closed dressings after laser resurfacing DERMATOLOGIC SURGERY Newman, J. P., Fitzgerald, P., Koch, R. J. 2000; 26 (6): 562-571

  Abstract

  Laser skin resurfacing has become an accepted technique for the treatment of facial rhytides and associated solar skin damage. Achieving a successful result is directly related to proper postoperative wound care during the reepithelialization process. There are open and closed approaches to the treatment of the post-laser resurfacing patient with distinct advantages and disadvantages.To review the most commonly used closed dressings after facial laser skin resurfacing and compare their advantages and disadvantages. To compare clinical findings with a group of patients treated exclusively with an open technique.Review of composite foams, polymer film, polymer mesh, and hydrogel products and prospective observations of clinical outcomes of patients treated with each dressing category after facial laser skin resurfacing. We perform a retrospective chart review of a group of patients treated exclusively with an open technique comparing crust formation, comfort, and pruritus with the prospective group of patients treated with closed dressings.The closed dressings available today each have unique structural configurations and adhesive properties intended to maintain an occlusive wound environment. Patient acceptance of these dressings was favorable, with improved comfort compared to the open dressing group. Complications of bacterial infections and contact dermatitis were not observed when closed dressings were used with a protocol for dressing changes performed at 48 hours. Rates of reepithelialization did not vary according to dressing category. Crust formation and postoperative pruritus occurred less frequently when closed occlusive dressings were worn by patients.When used properly, these dressings improve patient comfort, simplify their postoperative wound care, and do not increase the risk of infection or contact dermatitis. Overall satisfaction was highest with perforated mesh and polymer dressings for full-face wounds.

  View details for Web of Science ID 000087401300014

  View details for PubMedID 10848938

• Determinants of coronary remodeling in transplant coronary disease - A simultaneous intravascular ultrasound and Doppler flow study CIRCULATION Schwarzacher, S. P., Uren, N. G., Ward, M. R., Schwarzkopf, A., Giannetti, N., Hunt, S., Fitzgerald, P. J., Oesterle, S. N., Yeung, A. C. 2000; 101 (12): 1384-1389

  Abstract

  Coronary remodeling plays a significant role in lumen loss in transplant allograft vasculopathy (TxCAD), but the determinants of remodeling are unknown. We assessed the relationship between remodeling and plaque topography, coronary compliance, and blood flow in TxCAD.One artery in each of 27 transplant patients was investigated with simultaneous intravascular ultrasound and coronary flow measurements (basal and hyperemic by Doppler flow wire). At 4 to 8 different cross sections (mean 5.1+/-1. 2), plaque topography (concentric or eccentric) was determined, and total vessel area, lumen area, and intimal/medial area (IMA) were measured. Mean remodeling ratio (vessel area/IMA) in eccentric lesions (E, n=28) was significantly larger than that in concentric lesions (C, n=70) (E 5.87+/-0.93 versus C 3.58+/-0.62; P<0.001), despite similar IMA (E 3.89+/-0.68 versus C 3.90+/-0.41; P=NS) and distribution of imaged segments. Remodeling ratio was consistently larger in eccentric lesions in all 3 vessel segments when analyzed separately, and mean remodeling ratio for each artery was larger in vessels with predominantly eccentric lesions. Coronary compliance ([Delta lumen area/diastolic lumen area]/Delta mean arterial pressure x 10(3)) was also significantly greater in eccentric lesions versus concentric lesions (proximal 1.00+/-0.39 versus 0.22+/-0.04; mid 0.71+/-0.17 versus 0.21+/-0.10; distal 0.43+/-0.13 versus 0. 01+/-0.08; all P<0.01). Coronary flow reserve was also significantly higher in coronary arteries with primarily eccentric lesions (E 2. 49+/-0.64 versus C 1.87+/-0.28; P<0.01).Vessel remodeling in transplant vasculopathy is significantly greater in eccentric lesions than in concentric lesions, possibly due to greater coronary compliance and resistive vessel function.

  View details for Web of Science ID 000086143700014

  View details for PubMedID 10736281

• Acute myocardial infarction and vascular remodeling AMERICAN JOURNAL OF CARDIOLOGY Filardo, S. D., Schwarzacher, S. P., Lo, S. T., Herity, N. A., Lee, D. P., Huegel, H., Mullen, W. L., Fitzgerald, P. J., Ward, M. R., Yeung, A. C. 2000; 85 (6): 760-?

  Abstract

  We used intravascular ultrasound to show that outward remodeling predominates in lesions responsible for acute myocardial infarction, whereas negative remodeling is far more prevalent in lesions responsible for chronic stable angina. The total cholesterol:high-density lipoprotein ratio was also strongly correlated with outward remodeling.

  View details for Web of Science ID 000085838000018

  View details for PubMedID 12000055

• Accentuated remodeling on the upstream side of atherosclerotic lesions AMERICAN JOURNAL OF CARDIOLOGY Ward, M. R., Jeremias, A., Huegel, H., Fitzgerald, P. J., Yeung, A. C. 2000; 85 (5): 523-526

  Abstract

  Although it has been postulated that atherosclerotic stenotic lesions cannot remodel in response to altered flow, evidence to support or refute this hypothesis has been elusive. In vitro models have shown that accelerated endothelial shear stress occurs on the upstream side of stenoses, while turbulent lower shear stress is seen on the downstream side. We therefore compared vascular remodeling at paired sites 2 mm upstream and 2 mm downstream of the site of minimal lumen area in 25 atherosclerotic lesions in 23 patients using intravascular ultrasound. Remodeling was compared by 2 methods: normalized vessel area (vessel area(lesion)/vessel(reference) and remodeling index (change in vessel area/change in plaque area from reference). Normalized vessel area was significantly greater upstream than downstream (1.21+/-0.06 vs. 1.12+/-0.09; p<0.05), despite similar plaque burden (8.84+/-0.81 vs. 8.42+/-0.85 mm2) resulting in larger lumen area (8.15+/-1.02 vs. 6.10+/-0.88 mm2; p<0.05). Remodeling index was also significantly higher upstream than downstream (0.67+/-0.20 vs. 0.12+/-0.24, respectively, p<0.05). Accentuation of remodeling on the upstream side was significantly correlated (r = 0.54, p = 0.01) with the mean degree of shear acceleration expected by stenosis severity. Impaired remodeling on the downstream side may partly explain stenosis propagation down a vessel.

  View details for Web of Science ID 000085650900001

  View details for PubMedID 11078260

• Comparison of coronary stent expansion by intravascular ultrasonic imaging in younger versus older patients with diabetes mellitus AMERICAN JOURNAL OF CARDIOLOGY Gilutz, H., Russo, R. J., Tsameret, I., Fitzgerald, P. J., Yock, P. G. 2000; 85 (5): 559-562

  Abstract

  The poor long-term outcome in young diabetic patients receiving stents is not well understood. The purpose of this study was to characterize the pastprocedural results of stent placement in diabetic patients using intravascular ultrasound to identify factors that might be associated with poor clinical outcome. The acute dimensions from intravascular ultrasound studies after stent deployment at 5 sites were measured from 39 coronary segments from patients with diabetes mellitus (DM) and 161 segments from nondiabetic patients (non-DM). Within these 2 groups, segments were subgrouped into young (y) and old (o) in reference to the mean study age of 64 years, forming 4 groups: yDM (n = 20), y non-DM (n = 65), oDM (n = 19), and o non-DM (n = 96). Results are reported as mean +/- 1 SD. Diabetic patients had smaller mean lumen area within the treated segment than o non-DM (8.37+/-2.59 vs. 9.11+/-3.35 mm2, p<0.01). These differences were more pronounced at the distal reference vessel lumen of yDM than y non-DM (7.6+/-2.3 vs. 10.3+/-4.5 mm2, p<0.003), and were associated with greater percent plaque area in the distal reference vessel (43.4+/-13% vs. 34.1+/-11.2%, p<0.003). In young diabetic patients undergoing elective stent placement, underexpansion of the stented segment is common, which may contribute to the relatively poor long-term outcome in these patients. We suggest that when stenting is the procedure of choice in this subgroup of high-risk patients, special attention should be given to optimizing lumen dimensions.

  View details for Web of Science ID 000085650900008

  View details for PubMedID 11078267

• Effects of intravenous and intracoronary adenosine 5 '-triphosphate as compared with adenosine on coronary flow and pressure dynamics CIRCULATION Jeremias, A., Filardo, S. D., Whitbourn, R. J., Kernoff, R. S., Yeung, A. C., Fitzgerald, P. J., Yock, P. G. 2000; 101 (3): 318-323

  Abstract

  Measurements of Doppler derived coronary flow reserve (CFR) and pressure derived fractional flow reserve (FFR) for coronary stenosis assessment depend on the induction of maximal hyperemia. Adenosine is the most widely used pharmacological agent but is expensive and poorly tolerated by some patients.The objective of this study was to test the equivalency of adenosine 5'-triphosphate (ATP) to adenosine in their ability to cause maximal hyperemia as compared with the hyperemic response of complete coronary occlusion in 6 canines. Intracoronary administration of either ATP or adenosine resulted in a significant increase in CFR (2.79+/-0.64 and 2.22+/-0.7 for 10 microgram versus 4. 65+/-1.22 and 4.25+/-0.78 for 100 microgram for ATP and adenosine, respectively, P for trend <0.001) but not reaching the level of coronary occlusion (6.35+/-2.26). Additionally, FFR and CFR were measured in 35 different stenoses using ATP, adenosine, and coronary occlusion. There was an excellent linear correlation between ATP and adenosine for both CFR (R=0.934, P<0.001) and FFR (R=0.985, P<0.001). However, hyperemia with either ATP or adenosine was less than postocclusion hyperemia, resulting in significantly different reserve measurements (CFR: 1.93+/-0.66 and 2.08+/-0.81 versus 2.35+/-0.97, P<0.001; FFR: 0.62+/-0.24 and 0.63+/-0.23 versus 0.58+/-0.2, P<0.001).1) Step up in dosage of ATP and adenosine beyond currently recommended clinical doses resulted in a significant increase in coronary hyperemia; 2) ATP was equivalent to adenosine for both CFR and FFR; and 3) complete coronary occlusion yielded a better hyperemic response than either drug, indicating that maximal hyperemia was not achieved by either pharmacological stimulus.

  View details for Web of Science ID 000084957100031

  View details for PubMedID 10645929

• Feasibility of in vivo intravascular ultrasound tissue characterization in the detection of early vascular transplant rejection CIRCULATION Jeremias, A., Kolz, M. L., Ikonen, T. S., Gummert, J. F., Oshima, A., Hayase, M., Honda, Y., Komiyama, N., Berry, G. J., Morris, R. E., Yock, P. G., Fitzgerald, P. J. 1999; 100 (21): 2127-2130

  Abstract

  Unprocessed ultrasound radiofrequency (RF) signal analysis has been shown to distinguish different tissue structures more reliably than gray-scale interpretation of conventional ultrasound images.The objective of this study was to test the feasibility of in vivo intravascular ultrasound (IVUS) RF signal analysis in an animal model of allograft rejection. Six cynomolgus monkeys underwent transplantation of 3-cm aortic allograft segments distal to the renal arteries from immunologically mismatched donors. IVUS imaging with a 30-MHz system was performed 84 to 105 days after the operation. RF signals were acquired from cross sections of the recipient and the allograft aortas in real time with a digitizer at 500 MHz with 8-bit resolution. Sixty-five cross sections and 68 regions of interest (31 in host aorta and 37 in allograft) were analyzed in the adventitial layer with a total number of 8568 vectors processed. For each region of interest, a weighted-average attenuation was calculated on the basis of the attenuation and length for each individual vector. Histological examination was performed at every cross section imaged by IVUS. When the gray-scale images of conventional IVUS scored by an independent observer were compared, no distinction between adventitia of the native aorta and allograft was possible. Analysis of the average RF backscatter power also showed no significant difference (70.32+/-3.55 versus 70.72+/-3.38 dB). However, the average attenuation of allografts was significantly lower than that of the host aortas (2.64+/-1.38 versus 4.02+/-1.16 dB/mm, P<0.001). Histology demonstrated a marked adventitial inflammatory response in all allografts, with no inflammation observed in the host aortas.In vivo IVUS tissue characterization can be performed during routine imaging. In this model of transplant vasculopathy, RF attenuation measurements were more sensitive than visual or quantitative gray-scale analysis.

  View details for Web of Science ID 000083945000005

  View details for PubMedID 10571969

• Intravascular ultrasound volumetric assessment of intimal hyperplasia in stents treated with intracoronary radiation AMERICAN JOURNAL OF CARDIOLOGY Limpijankit, T., Waksman, P., Yock, P. G., Fitzgerald, P. J. 1999; 84 (7): 850-?

  Abstract

  Iridium-192 (gamma)-radiation is effective in preventing recurrent in-stent restenosis by reducing neointimal hyperplasia as illustrated by intravascular ultrasound study and plaque area-length plot. This analytic technique will further our understanding of vessel behavior to radiant energy source both inside and outside the stented coronary artery segments.

  View details for Web of Science ID 000082833300017

  View details for PubMedID 10513786

• Ultrasound logic: The value of intracoronary imaging for the interventionist CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Oesterle, S. N., Limpijankit, T., Yeung, A. C., Stertzer, S., Pomerantsev, E., Yock, P. G., Fitzgerald, P. J. 1999; 47 (4): 475-490

  View details for Web of Science ID 000081733400019

  View details for PubMedID 10470481

• New Approaches and Conduits: In Situ Venous Arterialization and Coronary Artery Bypass. Current interventional cardiology reports Fitzgerald, Hayase, Yeung, Virmani, Robbins, Burkhoff, Makower, Yock, OESTERLE 1999; 1 (2): 127-137

  View details for PubMedID 11096617

• Delayed radionecrosis of the larynx AMERICAN JOURNAL OF OTOLARYNGOLOGY Fitzgerald, P. J., Koch, R. J. 1999; 20 (4): 245-249

  Abstract

  Radiation has been used to treat carcinoma of the larynx for more than 70 years. Radionecrosis is a well-known complication of this modality when treating head and neck neoplasms. It has been described in the temporal bone, midface, mandible, and larynx. Laryngeal radionecrosis is manifested clinically by dysphagia, odynophagia, respiratory obstruction, hoarseness, and recurrent aspiration. The vast majority of patients who develop laryngeal radionecrosis present with these symptoms within 1 year of treatment; however, delayed presentations have been reported up to 25 years after radiotherapy. We present, in a retrospective case analysis, an unusual case of laryngeal radionecrosis in a patient who presented more than 50 years after treatment with radiotherapy for carcinoma of the larynx. The cases of delayed laryngeal necrosis in the literature are presented. This represents the longest interval between treatment and presentation in the literature. The details of the presentation, clinical course, and diagnostic imaging are discussed. The pathogenesis, clinical features, and treatment options for this rare complication are reviewed. Early stage (Chandler I and II) laryngeal radionecrosis may be treated conservatively and often observed. Late stage (Chandler III and IV) cases are medical emergencies, occasionally resulting in significant morbidity or mortality. Aggressive diagnostic and treatment measures must be implemented in these cases to improve outcome. This case represents the longest interval between initial treatment and presentation of osteoradionecrosis in the literature. A structured diagnostic and therapeutic approach is essential in managing this difficult problem.

  View details for Web of Science ID 000081541000009

  View details for PubMedID 10442778

• The progression of thrombus in an ex-vivo shunt model evaluated by intravascular ultrasound radiofrequency analysis ULTRASOUND IN MEDICINE AND BIOLOGY Komiyama, N., Chronos, N. A., Uren, N. G., Moore, M. P., Kelly, A. B., Harker, L. A., Hanson, S. R., Metz, J. A., Yock, P. G., Fitzgerald, P. J. 1999; 25 (4): 561-566

  Abstract

  We tested the ability of ultrasound radiofrequency (RF) signal analysis to characterize thrombus accumulation in a Dacron graft incorporated into the exteriorized arteriovenous shunt in 3 baboons with constant blood flow for 60 min. Thrombus formation was quantified by sequential measurements of 111Indium-labeled platelet deposition. RF signals were acquired every 15 min at 2 sites in the graft, using a 2.9 Fr intravascular ultrasound catheter-based transducer (30 MHz) and digitized at 250 MHz in 8-bit resolution. Regions of interest were placed within a 0.5-mm perimeter adjacent to the graft wall. Integrated backscatter increased significantly (p < 0.001) with increasing platelet deposition. However, mean-to-standard deviation ratio of the RF envelope showed no significant change and the distribution pattern of the RF probability function remained constant and consistent with a Rayleigh scattering process. These results provide a basis for using RF analysis to monitor the time-course of thrombus formation.

  View details for Web of Science ID 000080191900009

  View details for PubMedID 10386731

• Impact of residual plaque burden on clinical outcomes of coronary interventions CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Honda, Y., Yock, P. G., Fitzgerald, P. J. 1999; 46 (3): 265-276

  Abstract

  In this study, we summarize the role of residual plaque burden, as determined by intravascular ultrasound, on the development of restenosis following percutaneus coronary interventions. Several clinical trials have shown that the amount of residual plaque is a consistent and independent predictor of subsequent restenosis. The impact of residual plaque burden on late lumen loss is particularly augmented by negative vessel remodeling that is commonly seen after balloon angioplasty and atherectomy. However, early evidence suggests that the importance of plaque burden also applies in the context of stenting. The cotreatment of debulking may further improve the long-term outcome of stenting by maximizing an acute lumen gain with less vessel stretching, preventing stent edge problems and possibly reducing the cell source involved in the intimal hyperplastic process. Evaluation of residual plaque burden with on-line intravascular ultrasound could lead to definitive therapies via risk stratification of the treated segments.

  View details for Web of Science ID 000079175800003

  View details for PubMedID 10348121

• Spontaneous postpartum coronary dissection CIRCULATION Lee, F. H., Yeung, A. C., Fowler, M. B., Fitzgerald, P. J. 1999; 99 (5): 721-721

  View details for Web of Science ID 000078473000020

  View details for PubMedID 9950672

• Development of models of graft vascular disease in nonhuman primates: Evaluation of GVD by intravascular ultrasound in a new cynomolgus model with arterial allograft exchange XVIIth World Congress of the Transplantation-Society Ikonen, T. S., Gummert, J. F., Honda, Y., Hayase, M., Perlroth, J., Hausen, B., Barlow, C., Fitzgerald, P., Yock, P. G., Morris, R. E. ELSEVIER SCIENCE INC. 1999: 687–87

  View details for Web of Science ID 000078960600305

  View details for PubMedID 10083296

• Acute coronary closure after stenting: a lesson from intravascular ultrasound. International journal of cardiovascular interventions Kobayashi, Y. n., Amaro, M. n., Fitzgerald, P. J. 1999; 2 (1): 51–54

  Abstract

  Intravascular ultrasound (IVUS) is an imaging modality more sensitive for defining suboptimal stent deployment issues compared with conventional angiographic imaging. We report on a patient with unstable angina who underwent stent deployment using IVUS guidance. Despite an acceptable angiographic result, intrastent thrombus, incomplete expansion and an edge/marginal dissection were seen by IVUS examination. Both the incomplete expansion and the intrastent thrombus were successfully treated. The dissection, however, was not treated in the catheterization laboratory. This mechanical injury pattern at the stent edge led to vessel occlusion 4 h post-procedure.

  View details for PubMedID 12623387

• A new large-animal model for research of graft vascular disease 3rd International Conference on New Trends in Clinical and Experimental Immunosuppression Gummert, J. F., Ikonen, T., Briffa, N., Honda, Y., Hayase, M., Perlroth, J., Kobayashi, Y., Hausen, B., Barlow, C., Billingham, M. E., Fitzgerald, P., Yock, P. G., Robbins, R. C., Morris, R. E. ELSEVIER SCIENCE INC. 1998: 4023–23

  View details for Web of Science ID 000077593000033

  View details for PubMedID 9865284

• Coronary stents: In vitro aspects of an angiographic and ultrasound quantification with in vivo correlation. Circulation Pomerantsev, E. V., Kobayashi, Y., Fitzgerald, P. J., Grube, E., Sanders, W. J., Alderman, E. L., Oesterle, S. N., Yock, P. G., Stertzer, S. H. 1998; 98 (15): 1495-1503

  Abstract

  The validity of quantitative coronary angiography (QCA) after stent placement has been questioned because the optical density of a metallic stent, added to the density of a contrast-filled lumen, could affect border definition. METHODS andWe deployed 3.0- and 4.0-mm Palmaz-Schatz, Wiktor, Multilink, NIR, and InStent stents in precision-cast phantoms. Central lumens of 2.0 mm were created. There was no difference between the "true" diameters of any stented lumen by both QCA and quantitative ultrasonic (QCU) measurement poststenting. QCA systematic error (SE) varied from 0.01 for the Wiktor stents to 0.14 mm for the Palmaz-Schatz stents; the random error (RE) was 0.03 to 0.14 mm. QCU SE varied from 0.05 to 0.11 mm, and RE ranged from 0.01 to 0.07 mm. At the next stage, 4.0-mm Wiktor and Palmaz-Schatz stents were deployed into the phantom lumens; 1.5-, 2.0-, 2.5- and 3.0-mm lumens were created inside the stents. QCA and QCU measurements of 1.5- to 2.5-mm residual lumens were overestimated by 0.1 to 0.3 mm. In the 3. 0-mm residual lumen within the Wiktor stent, QCA underestimated the luminal size by -0.1 mm. There was no QCA inaccuracy for a 3.0-mm lumen within the Palmaz-Schatz stent. In patients, in 25 stented segments in both the Palmaz-Schatz and Wiktor groups, there was no difference between QCA and QCU diameters.QCU is sufficiently precise for the assessment of the coronary lumen after stenting. QCA can be used as an accurate method of poststent assessment, except when a very mild recurrence within a highly opaque stent is measured. In that instance, QCA may underestimate the luminal diameter.

  View details for PubMedID 9769302

• In vitro aspects of an angiographic and ultrasound quantification with in vivo correlation CIRCULATION Pomerantsev, E. V., Kobayashi, Y., Fitzgerald, P. J., Grube, E., Sanders, W. J., Alderman, E. L., Oesterle, S. N., Yock, P. G., Stertzer, S. H. 1998; 98 (15): 1495-1503

  Abstract

  The validity of quantitative coronary angiography (QCA) after stent placement has been questioned because the optical density of a metallic stent, added to the density of a contrast-filled lumen, could affect border definition. METHODS andWe deployed 3.0- and 4.0-mm Palmaz-Schatz, Wiktor, Multilink, NIR, and InStent stents in precision-cast phantoms. Central lumens of 2.0 mm were created. There was no difference between the "true" diameters of any stented lumen by both QCA and quantitative ultrasonic (QCU) measurement poststenting. QCA systematic error (SE) varied from 0.01 for the Wiktor stents to 0.14 mm for the Palmaz-Schatz stents; the random error (RE) was 0.03 to 0.14 mm. QCU SE varied from 0.05 to 0.11 mm, and RE ranged from 0.01 to 0.07 mm. At the next stage, 4.0-mm Wiktor and Palmaz-Schatz stents were deployed into the phantom lumens; 1.5-, 2.0-, 2.5- and 3.0-mm lumens were created inside the stents. QCA and QCU measurements of 1.5- to 2.5-mm residual lumens were overestimated by 0.1 to 0.3 mm. In the 3. 0-mm residual lumen within the Wiktor stent, QCA underestimated the luminal size by -0.1 mm. There was no QCA inaccuracy for a 3.0-mm lumen within the Palmaz-Schatz stent. In patients, in 25 stented segments in both the Palmaz-Schatz and Wiktor groups, there was no difference between QCA and QCU diameters.QCU is sufficiently precise for the assessment of the coronary lumen after stenting. QCA can be used as an accurate method of poststent assessment, except when a very mild recurrence within a highly opaque stent is measured. In that instance, QCA may underestimate the luminal diameter.

  View details for Web of Science ID 000076342700005

• The stent decade: 1987 to 1997 AMERICAN HEART JOURNAL Oesterle, S. N., Whitbourn, R., Fitzgerald, P. J., Yeung, A. C., Stertzer, S. H., Dake, M. D., Yock, P. G., Virmani, R. 1998; 136 (4): 578-599

  Abstract

  In January 1997, experts from the United States, Europe, and Japan gathered at Stanford University to review their collective experience with intracoronary and noncoronary stenting and to identify and prioritize issues requiring further clinical investigation. This report summarizes the discussions that took place during this stent summit. Knowledge of stent-tissue interaction from animal and human pathologic specimens was reviewed in the context of evolving stent designs. The relative merits of coil and slotted tubular stent designs were discussed. Stent deployment routines, including self-expansion, balloon expansion, and high-pressure delivery were debated. The potential for covered stents and coated stents was explored. Problems surrounding the routine deployment of stents were identified: small vessel disease, long lesions, bifurcation stenoses, vein graft disease, ostial disease, left main stenoses, and intrastent restenosis. The value of intravascular ultrasound, as an adjunct to stenting, was explored and debated. An algorithm for "provisional stenting" based on ultrasound criteria was developed. Noncoronary stenting of the aorta, iliacs, and carotids were discussed. Clinical applications that may lead to randomized clinical trials were identified.

  View details for Web of Science ID 000076316800005

  View details for PubMedID 9778060

• Enhancement of spatial orientation of intravascular ultrasound images with side holes in guiding catheters AMERICAN HEART JOURNAL Schwarzacher, S. P., Fitzgerald, P. J., Metz, J. A., Yeung, A. C., Oesterle, S. N., Belef, M., Kernoff, R. S., Yock, P. G. 1998; 135 (6): 1063-1066

  Abstract

  Intravascular ultrasound (IVUS) images are typically viewed and recorded in an arbitrary rotational orientation. This study was performed to validate a new method for improved orientation of sonographic vascular cross-sections.We have tested a simple technique for rotational indexing of IVUS in cases in which guiding catheters with side holes are used. Although guiding catheters are opaque to ultrasonography, the side holes transmit the beam and therefore can be easily identified. The orientation of the side holes, which is characteristic for each make of guiding catheter, can be used to determine the anatomically appropriate rotational orientation of the IVUS image. In this study images of four commercially available side-hole guiding catheters were viewed in vitro to confirm the visibility of the side holes and to characterize their orientation for purposes of rotational orientation of images. Feasibility tests of rotational orientation based on side holes were then performed in canine coronary arteries (n = 3) and in six human coronary arteries. Three serial imaging runs in each clinical case yielded a mean variability in rotational orientation of 7.5 +/- 1.5 degrees.Validation testing of the side-hole technique demonstrates the potential for consistent and anatomically appropriate orientation of intravascular ultrasound images.

  View details for Web of Science ID 000074109300018

  View details for PubMedID 9630112

• Intravascular ultrasound: State of the art and future directions 9th Annual Transcatheter Cardiovascular Therapeutics Symposium Yock, P. G., Fitzgerald, P. J. EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 1998: 27E–32E

  Abstract

  A variety of new devices in the field of intravascular ultrasound imaging are being designed and tested. Mechanical intravascular ultrasound (IVUS) devices with rotating transducers have been developed that allow transducer pullback with integrated longitudinal 2-dimensional displays. Recent advances in the area of imaging include (1) solid-state systems that combine ultrasound with balloon and stent placement; (2) combined imaging atherectomy devices; (3) imaging cores or guidewires; (4) forward-looking devices; (5) 3-dimensional reconstruction techniques; (6) high-frequency imaging; and (7) improved methods for characterizing tissue. Other promising approaches include magnetic resonance imaging, thermography, and optical coherence tomography. An important goal for long-term technologic improvement is visualization of lipid accumulations and fibrous caps during their early stages of development.

  View details for Web of Science ID 000073005600007

  View details for PubMedID 9551592

• New developments in intravascular ultrasound. Vascular medicine Oshima, A., ITCHHAPORIA, D., Fitzgerald, P. 1998; 3 (4): 281-290

  Abstract

  Intravascular ultrasound (IVUS) is a dynamic imaging modality that provides real-time in vivo visualization of atherosclerosis and other vascular pathology. The tomographic image presentation of IVUS permits detailed assessment of plaque morphology and its corresponding responses to interventional therapy. IVUS studies have confirmed vascular remodeling in vivo, have proposed a high-pressure stent implantation strategy and have shown two key mechanisms of restenosis after angioplasty: plaque proliferation and vessel shrinkage (negative remodeling). IVUS also provides accurate quantitative information regarding lumen size, vessel size and plaque burden. These observations, essential to achieving improved outcomes, have drastically changed the understanding of atherosclerotic artery disease and interventional procedures. IVUS has matured into an essential complement to daily peripheral and coronary interventional practice and is routinely incorporated as part of the interventional arsenal in the catheterization laboratory. A variety of new imaging techniques are currently being designed and tested. These include combined therapeutic devices, further miniaturization, 3-D applications and tissue characterization. These techniques may evolve to provide increased favorable clinical outcomes and more accurate information of vessel geometry and plaque composition.

  View details for PubMedID 10102669

• Orientation of intracoronary ultrasonography: Looking beyond the artery JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Fitzgerald, P. J., Yock, C., Yock, P. G. 1998; 11 (1): 13-19

  Abstract

  Over the past 5 years intravascular ultrasound imaging has achieved many technical advancements both in catheter design and image quality. In addition to improved image quality that provides clear display of the endovascular structure, efficient signal penetration permits the viewing of structures beyond the artery by highlighting the perivascular structures. These perivascular landmarks, which are unique within a particular coronary segment, help provide both axial and spatial orientation during multiple imaging runs throughout a coronary artery. Orientation on the basis of veins and pericardium assists the operator to appreciate the full three-dimensional view of a particular coronary segment. This article describes several of the common perivascular structures that may be viewed from different arteries routinely imaged during coronary procedures.

  View details for Web of Science ID 000071772900004

  View details for PubMedID 9487465

• Coronary AVE micro stents: Serial quantitative angiography and histology in a canine model CATHETERIZATION AND CARDIOVASCULAR DIAGNOSIS Pomerantsev, E. V., Kim, C., Kernoff, R. S., Oesterle, S. N., Yeung, A., Fitzgerald, P. J., Virmani, R., Yock, P. G., Stertzer, S. H. 1997; 41 (2): 213-224

  Abstract

  The AVE Micro Stent (AVE Inc., Santa Rosa, CA) is composed of helically welded 3 mm long, zigzag crowns with stent lengths from 6 to 39 mm and diameters from 2.5 to 4.5 mm. Quantitative coronary angiography and histologic analyses of acute and chronic implantation were obtained in 52 stented coronary segments of 18 dogs. Three hearts with 8 stented coronary segments were harvested after 24 hr, 3 hearts with 9 stented segments were harvested after 2 weeks, 6 hearts with 15 stented segments were harvested at 8 weeks, and 6 hearts with 20 stented segments were harvested at 24 weeks post-deployment. There were no procedural complications, deaths, or acute vessel closures. The average lumen diameter of the stented segment was largest at 2 weeks (3.3 +/- 0.3 mm). The smallest average diameters were observed at 8 weeks after the stent deployment (2.7 +/- 0.4, P < 0.05) with an increase again at 24 weeks (2.9 +/- 0.6). The pre-explant percent of stenosis was <30% in all animals. Histologically, a peak of inflammation was visible at 2 weeks; however, the extent of luminal narrowing reached its peak at 8 weeks and the lumen dimension increased somewhat at 24 weeks. The degree of intimal thickening remained relatively constant throughout the different time points (<200 microm). Overall, these data suggest that constrictive remodeling within the stented segment occurs at 8 weeks in this animal model. The later increase of the stented segment dimensions as well as higher net gain at 24 weeks compared to 8 weeks after deployment suggests that this constriction is a transitory phenomenon.

  View details for Web of Science ID A1997XC51700023

  View details for PubMedID 9184299

• Clinical use of intravascular ultrasound. Seminars in interventional cardiology : SIIC Schwarzacher, S. P., Fitzgerald, P. J., Yock, P. G. 1997; 2 (1): 1-9

  Abstract

  Intravascular ultrasound has dramatically changed our view of atherosclerotic disease and has helped to define mechanisms of therapeutic interventions, providing a new rationale for selection of appropriate devices. Currently, this technology is used for sizing and orientation of commonly performed interventions such as balloon angioplasty and directional atherectomy. The information from intravascular ultrasound has also led to a dramatic change in the deployment algorithm of stents. Further improvements in catheter design and the findings from clinical trials utilizing intravascular ultrasound will help define a practical role for this new technology.

  View details for PubMedID 9546978

• Intravascular ultrasound: basic interpretation. Cardiology clinics Metz, J. A., Yock, P. G., Fitzgerald, P. J. 1997; 15 (1): 1-15

  Abstract

  IVUS provides a new gold standard for visualization and measurement of coronary artery disease. Morphologic and morphometric observations by IVUS are in general considerably more detailed and accurate than those obtained by angiography. IVUS has led to new insights into the pathophysiology of coronary plaque accumulation with respect to adaptive vessel responses (remodeling) and their exhaustion (de-remodeling, shrinkage). Further technologic refinements need to focus on issues such as improvement in resolution and miniaturization of IVUS catheters to enhance the applicability of this imaging technique.

  View details for PubMedID 9085748

• Vessel tearing at the edge of intracoronary stents detected with intravascular ultrasound imaging CATHETERIZATION AND CARDIOVASCULAR DIAGNOSIS Schwarzacher, S. P., Metz, J. A., Yock, P. G., Fitzgerald, P. J. 1997; 40 (2): 152-155

  Abstract

  Stent deployment strategies have changed significantly in the past 2 yr, with "high-pressure" balloon inflations postdilatation being performed in the large majority of cases. There is currently little information about the effects of high pressure on the geometry of stent expansion and on the adjacent areas of the vessel wall. Intravascular ultrasound (IVUS) imaging is well-suited to investigate these issues, since it provides information not only about stent expansion and apposition but also about adjacent vessel-wall morphology at transition points such as the articulation site of the stent and the the stent borders. We report on the results of a cohort of 30 consecutive stent cases which were systematically examined by IVUS following high-pressure inflation. All deployments were deemed successful by angiographic inspection. However, in 6 cases, intimal disruptions or "edge tears" were noted at the stent borders by IVUS. In 5 cases, edge tears were seen to occur at the distal border, whereas in one case edge tears were seen at both the proximal and distal edges of the stent. No angiographic and sonographic parameters were different except percent plaque area at the stent margins, which was significantly higher (53 +/- 11%) in the lesions with edge tears, compared to 40 +/- 10% plaque area in the group without evidence of pocket flaps (P = 0.007). This experience suggests that intimal disruptions or "edge tears" are a relatively common occurrence following high-pressure stent deployment, and may be related to the extent of marginal dissections.

  View details for Web of Science ID A1997WF28200006

  View details for PubMedID 9047054

• Impact of curve distortion errors on intravascular ultrasound measurements and three-dimensional reconstructions AMERICAN JOURNAL OF CARDIOLOGY Schwarzacher, S. P., Honda, Y., Metz, J. A., Asvar, C. A., Fitzgerald, P. J., Yock, P. G. 1997; 79 (3): 384-?

  Abstract

  Intravascular ultrasound distortion errors and longitudinal reconstructions are primarily determined by the angle of curvature. The error in commonly encountered angles is relatively small.

  View details for Web of Science ID A1997WG53700029

  View details for PubMedID 9036768

• Validation of Automated Border Detection in Intravascular Ultrasound Images. Echocardiography (Mount Kisco, N.Y.) Hausmann, D., Friedrich, G., Soni, B., Daniel, W. G., Fitzgerald, P. J., Yock, P. G. 1996; 13 (6): 599-608

  Abstract

  Intravascular ultrasound (IVUS) imaging provides cross-sectional views of the vessel lumen; however, lumen measurements still rely on operator-dependent border delineation and time-consuming lumen tracings. We tested a new system for automated lumen border detection in IVUS images based on acoustic quantification of blood and vessel wall. In 10 rabbits, 29 segments of the aorta were imaged in vivo using a 2.9-Fr IVUS catheter. IVUS images were obtained during motorized pullbacks of aortic segments of 18 mm length. Automated measurements of lumen dimensions were compared to automated measurements of a second pullback through the same segment, lumen measurements derived from visual border tracings in IVUS images, and to quantitative angiography. The automated system showed good reproducibility: Correlations for repeated measurements of lumen area, maximal and minimal lumen diameters were r = 0.97, r = 0.91, and r = 0.93, respectively. Automated measurements also correlated well to visual image analysis (lumen area, r = 0.97; maximal lumen diameter, r = 0.89; minimal lumen diameter, r = 0.89) and to angiographic measurements (lumen area, r = 0.93; lumen diameter, r = 0.95). In 12% of the images, the automated system overestimated lumen dimensions because of weak wall signals in the presence of echolucent structures next to the wall. Signal artifacts from the IVUS catheter itself or strong blood backscatter resulted in lumen underestimation in 6% of the images. Over- and underestimation of lumen by the border detection system were often associated with eccentric catheter position. Thus, lumen measurements in vivo IVUS images can be performed using an automated border detection system based on acoustic quantification of blood and vessel wall. The system allows reproducible and accurate measurements of lumen area and diameters. (ECHOCARDIOGRAPHY, Volume 13, November 1996)

  View details for PubMedID 11442974

• Validation of automated border detection in intravascular ultrasound images ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES Hausmann, D., Friedrich, G., Soni, B., Daniel, W. G., Fitzgerald, P. J., Yock, P. G. 1996; 13 (6): 599-607

  Abstract

  Intravascular ultrasound (IVUS) imaging provides cross-sectional views of the vessel lumen; however, lumen measurements still rely on operator-dependent border delineation and time-consuming lumen tracings. We tested a new system for automated lumen border detection in IVUS images based on acoustic quantification of blood and vessel wall. In 10 rabbits, 29 segments of the aorta were imaged in vivo using a 2.9-Fr IVUS catheter. IVUS images were obtained during motorized pullbacks of aortic segments of 18 mm length. Automated measurements of lumen dimensions were compared to automated measurements of a second pullback through the same segment, lumen measurements derived from visual border tracings in IVUS images, and to quantitative angiography. The automated system showed good reproducibility: Correlations for repeated measurements of lumen area, maximal and minimal lumen diameters were r = 0.97, r = 0.91, and r = 0.93, respectively. Automated measurements also correlated well to visual image analysis (lumen area, r = 0.97; maximal lumen diameter, r = 0.89; minimal lumen diameter, r = 0.89) and to angiographic measurements (lumen area, r = 0.93; lumen diameter, r = 0.95). In 12% of the images, the automated system overestimated lumen dimensions because of weak wall signals in the presence of echolucent structures next to the wall. Signal artifacts from the IVUS catheter itself or strong blood backscatter resulted in lumen underestimation in 6% of the images. Over- and underestimation of lumen by the border detection system were often associated with eccentric catheter position. Thus, lumen measurements in vivo IVUS images can be performed using an automated border detection system based on acoustic quantification of blood and vessel wall. The system allows reproducible and accurate measurements of lumen area and diameters. (ECHOCARDIOGRAPHY, Volume 13, November 1996)

  View details for Web of Science ID A1996VU13200002

• Angiographically silent atherosclerosis detected by intravascular ultrasound in patients with familial hypercholesterolemia and familial combined hyperlipidemia: Correlation with high density lipoproteins JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Hausmann, D., Johnson, J. A., Sudhir, K., Mullen, W. L., Friedrich, G., Fitzgerald, P. J., Chou, T. M., Ports, T. A., Kane, J. P., Malloy, M. J., Yock, P. G. 1996; 27 (7): 1562-1570

  Abstract

  This study sought to evaluate the extent of atherosclerosis in coronary and iliac arteries in patients with heterozygous familial hypercholesterolemia or familial combined hyperlipidemia, using intravascular ultrasound imaging.Intravascular ultrasound imaging provides cross-sectional tomographic views of the vessel wall and allows quantitative assessment of atherosclerosis.Forty-eight nonsmoking, asymptomatic patients with heterozygous familial hypercholesterolemia or familial combined hyperlipidemia underwent intravascular ultrasound imaging of the left anterior descending coronary, left main coronary and common iliac arteries. Angiography showed only minimal or no narrowing in these vessels. Intravascular ultrasound images obtained during catheter pullback underwent morphometric analysis. Plaque burden was expressed as the mean and maximal intimal index (ratio of plaque area and area within the internal elastic lamina) and as the percent of vessel surface covered by plaque.Intravascular ultrasound detected plaque more frequently than angiography in the left anterior descending (80% vs. 29%, respectively), left main (44% vs. 16%) and iliac arteries (33% vs. 27%). Plaque burden was higher in the left anterior descending (mean intimal index [+/- SD] 0.25 +/- 0.16) than in the left main (0.11 +/- 0.16, p < 0.001) and iliac arteries (0.02 +/- 0.04, p < 0.001). Angiography detected lumen narrowing only in coronary arteries with a maximal intimal index > or = 0.42 (left anterior descending artery) and > or = 0.43 (left main artery). The area within the internal elastic lamina increased with plaque area in the left anterior descending (r = 0.82, p < 0.001) and left main arteries (r = 0.53, p < 0.001). By stepwise multiple regression analysis, the strongest predictor for plaque burden in the left anterior descending artery was the level of high density lipoprotein (HDL) cholesterol and total/HDL cholesterol ratio for the left main artery.In patients with heterozygous familial hypercholesterolemia and familial combined hyperlipidemia, extensive coronary plaque is present despite minimal or no angiographic changes. Compensatory vessel enlargement and diffuse involvement with eccentric plaque may account for the lack of angiographic changes. Levels of HDL cholesterol and total/HDL cholesterol ratio are far more powerful predictors of coronary plaque burden than are low density lipoprotein cholesterol levels in these patients with early, asymptomatic disease.

  View details for Web of Science ID A1996UM59800002

  View details for PubMedID 8636537

• High-speed rotational atherectomy: Six-month serial quantitative coronary angiographic follow-up AMERICAN HEART JOURNAL Stertzer, S. H., Pomerantsev, E. V., Fitzgerald, P. J., Yock, P. G., Yeung, A. C., Shaw, R. E., Walton, A. S., Singer, A. H., Sanders, W. J., Oesterle, S. N. 1996; 131 (4): 639-648

  Abstract

  One hundred twenty-three patients treated with high-speed rotational atherectomy (HSRA) were restudied 6.9 +/- 1.2 months later. At the follow-up, the number of focal concentric lesions increased from 32.2 percent to 63.0 percent, p<0.01, with decrease of type C lesions from 54.8 percent to 30.8 percent, p<0.05. Comparison of the degree of the net gain (NG) showed more severe baseline lesions in the high-gain group (NG >20 percent) compared with the moderate-gain group (20 percent > NG > 0 percent) and to the loss group (minimal luminal diameter [MLD] 0.8 +/- 0.4 mm vs 1.0 +/ 0.4 mm, p<0.05; and 1.2 +/- 0.5 mm; p<0.01, respectively). Highest initial gain (36.5 percent +/- 26.2 percent vs 24.5 percent +/- 18.1 percent; p<0.015; and 19.0 percent +/- 23.2 percent; p<0.001) as well as lowest late loss (1.8 percent +/- 21.7 percent vs 14.0 percent +/-18.4 percent; p<0.01 and 28.1 percent +/- 25.0 percent; p<0.01) were found in the high NG group. A higher interaction between burr and atheroma resulted in the lowest restenosis rate of 6 percent.

  View details for Web of Science ID A1996UE42100002

  View details for PubMedID 8721633

• Ultrasound-guided atherectomy: The vision for the future? CORONARY ARTERY DISEASE Yock, P. G., Yock, C. A., Fitzgerald, P. J. 1996; 7 (4): 299-303

  View details for Web of Science ID A1996VA98800006

  View details for PubMedID 8853582

• Effects of technique modification on immediate results of high speed rotational atherectomy in 710 procedures on 656 patients CATHETERIZATION AND CARDIOVASCULAR DIAGNOSIS Stertzer, S. H., Pomerantsev, E. V., Fitzgerald, P. J., Shaw, R. E., Walton, A. S., Singer, A. H., Yeung, A., Yock, P. G., Oesterle, S. N. 1995; 36 (4): 304-310

  Abstract

  Seven hundred ten high speed rotational atherectomy (HSRA) procedures were performed in a single consecutive series of 656 patients. Stand alone HSRA was performed in 253 patients (35%). HSRA with adjunctive low pressure (< or = 2 ATM) balloon angioplasty (LP BA) was performed in 221 patients (31%), and HSRA with adjunctive high pressure (> or = 4 ATM) balloon angioplasty (HP BA) was performed in 236 patients (34%). Prognostically unfavorable Type B2 and C lesions dominated the study group (74.7%). Procedural success rate was 96%. Emergency coronary artery bypass surgery was performed in 1.4% of cases, Q wave myocardial infarction occurred in 3.4% and death, related to procedure, was consequent in 0.5% of cases. Incidence of flow limiting dissections was 3.1%, distal spasm was 5.3%, and "no reflow" phenomenon was 1.8%. The recent technique modifications included continuous advancer/guiding catheter infusion of the nitroglycerin-verapamil mixture, limitation of duration of lesion engagement by the burr, stepwise increase in the burr size, decrease of rotational speed, and strict control of rpm drop during lesion ablation. Evolution of the interventional technique involved trends towards decrease of the use of HP BA in conjunction with steady increase in the percentage of SA and LP BA procedures over time. These technique changes resulted in complete absence of "no reflow" in 1994, as well as a generalized decrease in overall coronary vascular reactivity from all burr passes.

  View details for Web of Science ID A1995TM65600002

  View details for PubMedID 8719378

• INTRACORONARY ULTRASOUND IMAGING - INTRAOBSERVER AND INTEROBSERVER VARIABILITY OF MORPHOMETRIC MEASUREMENTS AMERICAN HEART JOURNAL Hausmann, D., LUNDKVIST, A. J., Friedrich, G. J., Mullen, W. L., Fitzgerald, P. J., Yock, P. G. 1994; 128 (4): 674-680

  Abstract

  Measurements of lumen and plaque dimensions by intracoronary ultrasound imaging are useful in assessing effects of intracoronary interventions and in quantifying plaque burden in transplant patients or during regression trials. However, these measurements are affected by inter- and intraobserver variability. In 87 patients, 120 intracoronary ultrasound images were obtained with a 4.3F, 30 MHz catheter. Morphometric measurements were performed two times by three independent observers using computerized planimetry. Intraobserver and interobserver agreement for qualitative parameters (presence of atherosclerotic plaque, calcified plaque, and residual nondiseased wall) was high (> 87%). For quantitative parameters measured directly in the images (lumen area, minimal and maximal lumen diameters, area within the internal elastic lamina, arc of calcium plaque) interobserver and intraobserver correlation between measurements was high (correlation coefficient r > 0.90) and differences between measurements were low (mean differences < 10%; SD < 20%). Measurement of the arc of nondiseased wall showed less interobserver correlation (r = 0.76 to 0.91), but percentages of difference between the measurements were low. Parameters derived from directly measured variables (plaque area, area stenosis, thickness, and eccentricity) showed slightly higher variability (correlations between measurements r = 0.78 to 0.91). SD for percentages of difference ranged between 20% and 30% (plaque area, area stenosis, and thickness) and systematic deviation between measurements (mean differences > 10%) occurred for plaque area. Thus most qualitative and quantitative measurements of lumen and plaque dimensions performed in intracoronary ultrasound images have low in intraobserver and interobserver variability; derived parameters may have slightly higher variability. Variability of morphometric measurements has to be considered, especially when serial ultrasound measurements are compared.

  View details for Web of Science ID A1994PJ92900005

  View details for PubMedID 7942437

• ANALYSIS OF PULSED WAVE DOPPLER ULTRASOUND SPECTRA OBTAINED FROM A MODEL INTRACORONARY CATHETER IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING DeNardo, S. J., Talbot, L., HARGRAVE, V. K., Fitzgerald, P. J., Selfridge, A. R., Yock, P. G. 1994; 41 (7): 635-648

  Abstract

  Abnormal arterial blood flow patterns have been implicated in the evolution of various vascular disease processes. Intravascular ultrasound techniques using the pulsed wave Doppler catheter offer the opportunity to characterize these abnormal flow patterns. We have developed a mathematical model that predicts the first two moments of the Doppler spectrum obtained using a Doppler catheter based on the distribution of ultrasonic beam power and velocity profile of fluid flow with an arbitrary distribution of flow disturbances. A scaled-up, in vitro experimental arterial system was used to confirm the validity of the model. Comparison of the predicted first two moments of the Doppler spectrum to the experimental values in this system demonstrated that the distribution of beam power significantly affects the magnitude of the first two moments. Additionally, both velocity gradient and velocity fluctuation broadening effects play prominent roles in determining the magnitude of the second moment. These phenomena must therefore be considered when evaluating in vivo Doppler spectra used for the characterization of abnormal flow patterns.

  View details for Web of Science ID A1994NY45600004

  View details for PubMedID 7927384

• DETECTION OF CORONARY ATHEROSCLEROSIS IN YOUNG-ADULT HEARTS USING INTRAVASCULAR ULTRASOUND CIRCULATION STGOAR, F. G., Pinto, F. J., Alderman, E. L., Fitzgerald, P. J., Stinson, E. B., Billingham, M. E., Popp, R. L. 1992; 86 (3): 756-763

  Abstract

  Coronary atherosclerosis has been demonstrated in young adults by postmortem pathology. Angiographic evaluation of coronary disease in young adults is limited by ethical issues and the insensitivity of angiography for detecting early pathology. Catheter-based intracoronary ultrasound has proven useful both in detecting and quantitating coronary disease, but the ultrasound appearance of young, angiographically normal, coronary arteries has not been well defined.Twenty-five subjects were examined with intracoronary ultrasound within 1 month of cardiac transplantation. Mean age of the donor hearts was 28 years (range, 14-43 years). Measurements of an index of intimal thickening were obtained at four left anterior descending coronary artery sites in each patient. All study patients had angiographically normal coronary arteries. Ultrasound in 14 subjects demonstrated a three-layered appearance of the coronary vessel wall with a mean intimal index of 0.16 +/- 0.07. The other 10 subjects, including all donors under the age of 25 years, had coronary vessel wall layers too thin to be imaged separately at the 30-MHz sound frequency. Five subjects had ultrasound evidence of focal intimal thickening greater than 500 microns. The donors of these hearts each had risk factors for coronary artery disease. Two subjects died within 5 weeks of their ultrasound study. Histological measurements of the vessel wall layers were similar to the corresponding ultrasound values.This study provides a reference for the intravascular ultrasound appearance of young adult coronary arteries and confirms pathology findings that young subjects with angiographically normal vessels have a range of coronary intimal thickening, which includes occasional evidence of focal, early atheromatous lesions.

  View details for Web of Science ID A1992JM27000006

  View details for PubMedID 1516187

• INTRAVASCULAR ULTRASOUND IMAGING OF ANGIOGRAPHICALLY NORMAL CORONARY-ARTERIES - AN INVIVO COMPARISON WITH QUANTITATIVE ANGIOGRAPHY JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY STGOAR, F. G., Pinto, F. J., Alderman, E. L., Fitzgerald, P. J., Stadius, M. L., Popp, R. L. 1991; 18 (4): 952-958

  Abstract

  Intravascular ultrasound, a new technique for real-time two-dimensional visualization of arteries and veins, delineates vessel wall morphology and measures luminal dimensions. This imaging method has been validated with in vitro systems and in peripheral vessels, but there are few in vivo coronary artery studies. Twenty cardiac transplant recipients with no angiographic coronary artery disease were scanned with a 30-MHz intravascular ultrasound catheter from the left main coronary ostium to the mid-left anterior descending coronary artery. Simultaneous angiographic measurements were performed at 76 sites. Ultrasound end-diastolic diameters in two perpendicular axes were 3.8 +/- 0.9 and 3.9 +/- 0.6 mm, respectively, and mean diameter derived from an area determined by planimetry was 3.9 +/- 0.9 mm. Angiographic coronary artery diameters measured with a computer-assisted edge detection system perpendicular to the long axis of the vessel and to the long axis of the catheter were 3.4 +/- 0.8 and 3.6 +/- 0.8 mm, respectively. Luminal diameters measured with the two imaging systems correlated closely, with an r value of 0.86 when ultrasound was compared with the angiographic diameter measured perpendicular to the vessel and 0.88 when compared with the angiographic diameter measured perpendicular to the imaging catheter. Eighty-three percent of the ultrasound-measured diameters were above the line of identity when compared with the simultaneous angiographic measurement. The more the imaging catheter deviated from the long axis of the vessel, the greater was the discrepancy between the ultrasound and angiographic measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for Web of Science ID A1991GH89700010

  View details for PubMedID 1894869