Clinical Focus

  • Cardiology (Heart)
  • Coronary Artery Disease
  • Chronic Total Occlusions
  • Complex Coronary Angioplasty
  • Mitral Valvuloplasty
  • Percutaneous Aortic Valve Replacement
  • Interventional Cardiology

Academic Appointments

Administrative Appointments

  • Senior Medical Director, International Medical Service, Stanford Medicine (2016 - Present)
  • Medical Director, Cardiovascular Health, Stanford Medicine (2011 - Present)
  • Chief(Clinical), Division of Cardiovascular Medicine, Stanford University School of Medicine (2000 - Present)

Honors & Awards

  • Li Ka Shing Professor, Stanford University (2008)

Professional Education

  • Fellowship:Brigham and Women's Hospital Harvard Medical School (1990) MA
  • Residency:Massachusetts General Hospital (1987) MA
  • Board Certification: Cardiovascular Disease, American Board of Internal Medicine (1989)
  • Board Certification: Internal Medicine, American Board of Internal Medicine (1987)
  • Board Certification: Interventional Cardiology, American Board of Internal Medicine (2000)
  • Internship:Massachusetts General Hospital (1985) MA
  • Medical Education:Harvard Medical School (1984) MA

Current Research and Scholarly Interests

Coronary artery disease is the leading cause of death in men and women in the United States. Our group is interested in studying both the early and late phases of atherosclerosis so that we can better develop prevention and treatment strategies. Our current studies include:

1) non-invasive methods of assessing vascular endothelial function so that we can better stratefy high risk coronary artery disease patients.

2) structural and functional studies of atherosclerosis in transplant coronary artery disease patients in order to define the the relationship between the two.

3) intravascular ultrasound studies to define the time-course in the devlopment of transplant coronary disease.

4) development of novel techniques to devliver drug imbedded particles into the atherosclerotic wall.

5) study the restenosis process in a vivo pig model.

2019-20 Courses

All Publications

  • New CENTERA Transcatheter AorticValve: Best of the Balloon-Expandable and Self-Expanding ValveWorlds? JACC. Cardiovascular interventions Yeung, A. C. 2019; 12 (7): 681–83

    View details for PubMedID 30947943

  • In Vivo Translation of the CIRPI System---Revealing Molecular Pathology of Rabbit Aortic Atherosclerotic Plaques. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Zaman, R., Yousufi, S., Chibana, H., Ikeno, F., Long, S. R., Gambhir, S. S., Chin, F. T., McConnell, M. V., Xing, L., Yeung, A. 2019


    Introduction: Thin-cap fibro atheroma (TCFA), unstable lesions in coronary artery disease (CAD), that prones to rupture resulting in substantial morbidity and mortality worldwide. However, their small size and complex morphological/biological features make early detection and risk assessment difficult. To overcome this limitation, we tested our newly developed catheter-based Circumferential-Intravascular-Radioluminescence-Photoacoustic-Imaging (CIRPI) system in vivo rabbit abdominal aorta to detect and characterize TCFA. Methods: The CIRPI system includes a novel optical probe combining circumferential radioluminescence imaging (CRI) and photoacoustic tomography (PAT). The CIRPI system was tested in rabbit abdominal aorta in vivo (WHHL, n = 5) and controls (NZW, n = 2). Rabbits were fasted for 6 hours before 5.55*107 Bq 18F-FDG was injected one hour prior to the imaging procedure. The experiment was done under anesthetic. A bare metal stent was implanted in the dorsal abdominal aorta as landmark, followed by the 7F imaging catheters that were advanced up to the proximal stent edge (PSE). Our CIRPI and clinical OCT were performed using pullback and non-occlusive flushing techniques. Results were verified with histochemical analysis. Results: Our CIRPI system successfully detected the locations and characterized both stable and vulnerable aortic plaques in vivo among all WHHL rabbits. Calcification was detected from the stable plaque (540/560 nm), whereas TCFA exhibited phospholipids/cholesterol (1040 nm, 1210 nm). These findings were verified with clinical OCT showing an area of low attenuation filled with lipids within TCFA. PAT image illustrated broken elastic fiber/collagen that could be verified with the histochemical analysis. All WHHL rabbits exhibited sparse to severe macrophages. However, 4 WHHL rabbits showed both moderate to severe level of calcifications and cholesterol clefts. However, all rabbits exhibited broken elastic fibers and collagen deposition. Control rabbits showed normal wall thickness with no presence of plaque tissue compositions. These findings were verified with the OCT and histochemical analysis. Conclusion: Our novel multi-modality hybrid system has been successfully translated to in vivo evaluation of atherosclerotic plaque structure and biology in a pre-clinical rabbit models. This proposed a paradigm shift that unites molecular and pathologic imaging technologies. Therefore, it may enhance the clinical evaluation of TCFA, as well as expand our understanding of CAD.

    View details for PubMedID 30737298

  • Association of Endothelin-1 with Accelerated Cardiac Allograft Vasculopathy and Late Mortality Following Heart Transplantation. Journal of cardiac failure Parikh, R. V., Khush, K., Pargaonkar, V. S., Luikart, H., Grimm, D., Yu, M., Akada, K., Honda, Y., Yeung, A. C., Valantine, H., Fearon, W. F. 2018


    BACKGROUND: Endothelin-1 (ET-1) has been implicated in the development of post-heart transplantation (HT) cardiac allograft vasculopathy (CAV), but has not been well-studied in humans.METHODS AND RESULTS: In 90 HT patients, plasma ET-1 was measured within 8 weeks of HT (baseline) via a competitive enzyme-linked immunosorbent assay. 3D volumetric intravascular ultrasound of the left anterior descending artery was performed at baseline and at 1 year. Accelerated CAV (lumen volume loss) was defined using the 75th percentile as a cutoff. Patients were followed beyond the first year post-HT for late death or re-transplantation. A receiver operative characteristic curve demonstrated that a baseline ET-1 concentration of 1.75 pg/mL provided the best accuracy for diagnosis of accelerated CAV at 1 year [area under the curve=0.69 (0.57-0.82), p=0.007]. In multivariate logistic regression, a higher baseline ET-1 concentration was independently associated with accelerated CAV [odds ratio (OR)=2.13, 95% confidence interval (CI): 1.15-3.94; p=0.01]; this relationship persisted when ET-1 was dichotomized at 1.75 pg/mL (OR=4.88, 95% CI: 1.69-14.10; p=0.003). Eighteen deaths occurred during a median follow-up period of 3.99 (2.51-9.95) years. Treated as a continuous variable, baseline ET-1 was not associated with late mortality in multivariate Cox regression [hazard ratio (HR)=1.22, 95% CI: 0.72-2.05; p=0.44]. However, ET-1 >1.75 pg/mL conferred a significantly lower cumulative event-free survival on Kaplan-Meier analysis (p=0.047), and was independently associated with late mortality (HR=2.94, 95% CI: 1.12-7.72; p=0.02).CONCLUSIONS: Elevated ET-1 early after HT is an independent predictor of accelerated CAV and late mortality, suggesting that ET-1 has durable prognostic value in the HT arena.

    View details for PubMedID 30543947

  • Cytokines profile of reverse cardiac remodeling following transcatheter aortic valve replacement. International journal of cardiology Kim, J. B., Kobayashi, Y., Kuznetsova, T., Moneghetti, K. J., Brenner, D. A., O'Malley, R., Dao, C., Wu, J. C., Fischbein, M., Craig Miller, D., Yeung, A. C., Liang, D., Haddad, F., Fearon, W. F. 2018; 270: 83–88


    OBJECTIVE: Previous studies have suggested that cytokines and growth factors may predict ventricular recovery following aortic valve replacement (AVR). The primary objective of this study was to identify cytokines that predict ventricular recovery following transcatheter AVR (TAVR).METHODS: We prospectively enrolled 121 consecutive patients who underwent TAVR. Standard echocardiographic assessment at baseline, 1-month and 1-year after TAVR included left ventricular (LV) mass index (LVMI) and global longitudinal strain (GLS). Blood samples were obtained at the time of the procedure to measure cytokines using a 63-plex Luminex platform. Partial least squares-discriminant analysis was performed to identify cytokines associated with ventricular remodeling and function at baseline as well as 1 year after TAVR.RESULTS: The mean age was 84 ± 9 years, with a majority of male subjects (59%), a mean LVMI of 120.4 ± 45.1 g/m2 and LVGLS of -13.0 ± 3.2%. On average, LV mass decreased by 8.1% and GLS improved by 20.3% at 1 year following TAVR. Among cytokines assayed, elevated hepatocyte growth factor (HGF) emerged as a common factor significantly associated with worse baseline LVMI and GLS as well as reduced ventricular recovery (p < 0.005). Other factors associated with ventricular recovery included a select group of vascular growth factors, inflammatory mediators and tumor necrosis factors, including VEGF-D, ICAM-1, TNFbeta, and IL1beta.CONCLUSION: We identified a network of cytokines, including HGF, that are significantly correlated with baseline LVMI and GLS, and ventricular recovery following TAVR.

    View details for PubMedID 30219541

  • Outcomes of Transcatheter Aortic Valve Replacement compared to Surgical Aortic Valve Replacement in patients with prior Chest Radiation Chacko, Y., Zhang, X., Jaluba, K., Lee, A., Miller, D., Yeung, A. C., Kim, B., Fearon, W. ELSEVIER SCIENCE INC. 2018: B244–B245
  • PREDICTING MORTALITY WITH AORTOMITRAL CALCIFICATIONS IN 317 TAVR PATIENTS Willemink, M., Maret, E., Moneghetti, K., Kim, J., Haddad, F., Kobayashi, Y., Higashigaito, K., Yeung, A., Lee, A., Miller, D., Fischbein, M., Fearon, W., Fleischmann, D. ELSEVIER SCIENCE INC. 2018: 1591
  • THE PROGNOSTIC VALUE OF COMPUTED TOMOGRAPHY FRAILTY MEASURES FOR PROLONGED HOSPITAL STAY AFTER TAVR IN 429 PATIENTS Maret, E., Willemink, M., Moneghetti, K., Kim, J., Haddad, F., Kobayashi, Y., Miller, C., Yeung, A., Fishbein, M., Fearon, W., Fleischmann, D. ELSEVIER SCIENCE INC. 2018: 1414
  • Accuracy of non-invasive stress testing in women and men with angina in the absence of obstructive coronary artery disease. International journal of cardiology Pargaonkar, V. S., Kobayashi, Y., Kimura, T., Schnittger, I., Chow, E. K., Froelicher, V. F., Rogers, I. S., Lee, D. P., Fearon, W. F., Yeung, A. C., Stefanick, M. L., Tremmel, J. A. 2018


    While >20% of patients presenting to the cardiac catheterization laboratory with angina have no obstructive coronary artery disease (CAD), a majority (77%) have an occult coronary abnormality (endothelial dysfunction, microvascular dysfunction (MVD), and/or a myocardial bridge (MB)). There are little data regarding the ability of noninvasive stress testing to identify these occult abnormalities in patients with angina in the absence of obstructive CAD.We retrospectively evaluated 155 patients (76.7% women) with angina and no obstructive CAD who underwent stress echocardiography and/or electrocardiography before angiography. We evaluated Duke treadmill score, heart rate recovery (HRR), metabolic equivalents, and blood pressure response. During angiography, patients underwent invasive testing for endothelial dysfunction (decrease in epicardial coronary artery diameter >20% after intracoronary acetylcholine), MVD (index of microcirculatory resistance ≥25), and intravascular ultrasound for the presence of an MB.Stress echocardiography and electrocardiography were positive in 58 (43.6%) and 57 (36.7%) patients, respectively. Endothelial dysfunction was present in 96 (64%), MVD in 32 (20.6%), and an MB in 83 (53.9%). On multivariable logistic regression, stress echo was not associated with any abnormality, while stress ECG was associated with endothelial dysfunction. An abnormal HRR was associated with endothelial dysfunction and MVD, but not an MB.Conventional stress testing is insufficient for identifying occult coronary abnormalities that are frequently present in patients with angina in the absence of obstructive CAD. A normal stress test does not rule out a non-obstructive coronary etiology of angina, nor does it negate the need for comprehensive invasive testing.

    View details for DOI 10.1016/j.ijcard.2018.10.073

    View details for PubMedID 30527992

  • Long-term prognostic value of invasive and non-invasive measures early after heart transplantation. International journal of cardiology Kobayashi, Y., Kobayashi, Y., Yang, H. M., Bouajila, S., Luikart, H., Nishi, T., Choi, D. H., Schnittger, I., Valantine, H. A., Khush, K. K., Yeung, A. C., Haddad, F., Fearon, W. F. 2018; 260: 31–35


    Invasively assessed coronary microvascular resistance early after heart transplantation predicts worse long-term outcome; however, little is known about the relationship between microvascular resistance, left ventricular function and outcomes in this setting.A total of 100 cardiac transplant recipients had fractional flow reserve (FFR) and the index of microcirculatory resistance (IMR) measured in the left anterior descending artery and echocardiographic assessment of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) at 1 year after heart transplantation. The primary endpoint was the composite of death and retransplantation occurring beyond the first post-operative year.The mean FFR, IMR, LVEF, and GLS values at 1 year were 0.87 ± 0.06, 21.3 ± 17.3, 60.4 ± 5.4%, and 14.2 ± 2.4%, respectively. FFR and IMR had no significant correlation with LVEF and GLS. During a mean follow-up of 6.7 ± 4.2 years, the primary endpoint occurred in 24 patients (24.0%). By ROC curve analysis, IMR = 19.3 and GLS = 13.3% were the best cutoff values for predicting death or retransplantation. Cumulative event-free survival was significantly lower in patients with higher IMR (log-rank p = 0.02) and lower GLS (log-rank p < 0.001). Cumulative event-free survival can be further stratified by the combination of IMR and GLS (long-rank p < 0.001). By multivariable Cox proportional hazards model, higher IMR and lower GLS were independently associated with long-term death or retransplantation (elevated IMR, hazard ratio = 2.50, p = 0.04 and reduced GLS, hazard ratio = 3.79, p = 0.003, respectively).Invasively assessed IMR does not correlate with GLS at 1 year after heart transplantation. IMR and GLS determined at 1 year may be used as independent predictors of late death or retransplantation.

    View details for PubMedID 29622448

  • Dose-Dependent Cardioprotection of Moderate (32°C) Versus Mild (35°C) Therapeutic Hypothermia in Porcine Acute Myocardial Infarction. JACC. Cardiovascular interventions Dash, R., Mitsutake, Y., Pyun, W. B., Dawoud, F., Lyons, J., Tachibana, A., Yahagi, K., Matsuura, Y., Kolodgie, F. D., Virmani, R., McConnell, M. V., Illindala, U., Ikeno, F., Yeung, A. 2018; 11 (2): 195–205


    The study investigated whether a dose response exists between myocardial salvage and the depth of therapeutic hypothermia.Cardiac protection from mild hypothermia during acute myocardial infarction (AMI) has yielded equivocal clinical trial results. Rapid, deeper hypothermia may improve myocardial salvage.Swine (n = 24) undergoing AMI were assigned to 3 reperfusion groups: normothermia (38°C) and mild (35°C) and moderate (32°C) hypothermia. One-hour anterior myocardial ischemia was followed by rapid endovascular cooling to target reperfusion temperature. Cooling began 30 min before reperfusion. Target temperature was reached before reperfusion and was maintained for 60 min. Infarct size (IS) was assessed on day 6 using cardiac magnetic resonance, triphenyl tetrazolium chloride, and histopathology.Triphenyl tetrazolium chloride area at risk (AAR) was equivalent in all groups (p = 0.2), but 32°C exhibited 77% and 91% reductions in IS size per AAR compared with 35°C and 38°C, respectively (AAR: 38°C, 45 ± 12%; 35°C, 17 ± 10%; 32°C, 4 ± 4%; p < 0.001) and comparable reductions per LV mass (LV mass: 38°C, 14 ± 5%; 35°C, 5 ± 3%; 32°C 1 ± 1%; p < 0.001). Importantly, 32°C showed a lower IS AAR (p = 0.013) and increased immunohistochemical granulation tissue versus 35°C, indicating higher tissue salvage. Delayed-enhancement cardiac magnetic resonance IS LV also showed marked reduction at 32°C (38°C: 10 ± 4%, p < 0.001; 35°C: 8 ± 3%; 32°C: 3 ± 2%, p < 0.001). Cardiac output on day 6 was only preserved at 32°C (reduction in cardiac output: 38°C, -29 ± 19%, p = 0.041; 35°C: -17 ± 33%; 32°C: -1 ± 28%, p = 0.041). Using linear regression, the predicted IS reduction was 6.7% (AAR) and 2.1% (LV) per every 1°C reperfusion temperature decrease.Moderate (32°C) therapeutic hypothermia demonstrated superior and near-complete cardioprotection compared with 35°C and control, warranting further investigation into clinical applications.

    View details for PubMedID 29348013

  • The effect of negative remodeling on fractional flow reserve after cardiac transplantation INTERNATIONAL JOURNAL OF CARDIOLOGY Fearon, W. F., Felix, R., Hirohata, A., Sakurai, R., Jose, P. O., Yamasaki, M., Nakamura, M., Fitzgerald, P. J., Valantine, H. A., Yock, P. G., Yeung, A. C. 2017; 241: 283–87


    Negative remodeling is a common occurrence early after cardiac transplantation. Its impact on the development of myocardial ischemia is not well documented. The aim of this study is to investigate the impact of negative remodeling on fractional flow reserve after cardiac transplantation.Thirty-four cardiac transplant recipients underwent intravascular ultrasound (IVUS) and fractional flow reserve (FFR) assessment soon after transplantation and one year later. Patients were divided into those with and without negative remodeling based on IVUS, and the impact on FFR was assessed. In the 19 patients with negative remodeling, there was no significant change in plaque volume (119.3±82.0 to 131.3±91.2mm3, p=0.21), but vessel volume (775.6±212.0 to 621.9±144.1mm3, p<0.0001) and lumen volume (656.3±169.1 to 490.7±132.0mm3, p<0.0001) decreased significantly and FFR likewise decreased significantly (0.88±0.06 to 0.84±0.07, p=0.04). In the 15 patients without negative remodeling, vessel volume did not change (711.7±217.6 to 745.7±198.5, p=0.28), but there was a significant increase in plaque volume (126.8±88.3 to 194.4±92.7, p<0.001) and a resultant significant decrease in FFR (0.89±0.05 to 0.85±0.05, p=0.01).Negative remodeling itself, without any change in plaque volume can cause a significant decrease in fractional flow reserve after cardiac transplantation and appears to be another possible mechanism for myocardial ischemia.

    View details for PubMedID 28413112

  • Dynamic changes in aortic impedance after transcatheter aortic valve replacement and its impact on exploratory outcome. international journal of cardiovascular imaging Kobayashi, Y., Kim, J. B., Moneghetti, K. J., Kobayashi, Y., Zhang, R., Brenner, D. A., O'Malley, R., Schnittger, I., Fischbein, M., Miller, D. C., Yeung, A. C., Liang, D., Haddad, F., Fearon, W. F. 2017


    Valvulo-arterial impedance (Zva) has been shown to predict worse outcome in medically managed aortic stenosis (AS) patients. We aimed to investigate the association between Zva and left ventricular (LV) adaptation and to explore the predictive value of Zva for cardiac functional recovery and outcome after transcatheter aortic valve replacement (TAVR). We prospectively enrolled 128 patients with AS who underwent TAVR. Zva was calculated as: (systolic blood pressure + mean transaortic gradient)/stroke volume index). Echocardiographic assessment occurred at baseline, 1-month and 1-year after TAVR. The primary endpoints were to investigate associations between Zva and global longitudinal strain (GLS) at baseline as well as GLS change after TAVR. The secondary was to compare all-cause mortality after TAVR between patients with pre-defined Zva (=5 mmHg m(2)/ml), stroke volume index (=35 ml/m(2)), and GLS (=-15%) cutoffs. The mean GLS was reduced (-13.0 ± 3.2%). The mean Zva was 5.2 ± 1.6 mmHg*m(2)/ml with 55% of values ≥5.0 mmHg*m(2)/ml, considered to be abnormally high. Higher Zva correlated with worse GLS (r = -0.33, p < 0.001). After TAVR, Zva decreased significantly (5.1 ± 1.6 vs. 4.5 ± 1.6 mmHg*m(2)/ml, p = 0.001). A reduction of Zva at 1-month was associated with GLS improvement at 1-month (r = -0.31, p = 0.001) and at 1-year (r = -0.36 and p = 0.001). By Kaplan-Meier analysis, patients with higher Zva at baseline had higher mortality (Log-rank p = 0.046), while stroke volume index and GLS did not differentiate outcome (Log-rank p = 0.09 and 0.25, respectively). As a conclusion, Zva is correlated with GLS in AS as well as GLS improvement after TAVR. Furthermore, a high baseline Zva may have an additional impact to traditional parameters on predicting worse mortality after TAVR.

    View details for DOI 10.1007/s10554-017-1155-6

    View details for PubMedID 28516313

  • THE INFLAMMASOME PATHWAY IS ASSOCIATED WITH ADVERSE VENTRICULAR REMODELING FOLLOWING TRANSCATHETER AORTIC VALVE REPLACEMENT Kim, J., Kobayashi, Y., Kouznetsova, T., Moneghetti, K., Brenner, D., O'Malley, R., Dao, C., Schnittger, I., Liang, D., Wu, J., Fischbein, M., Lee, A., Miller, D., Yeung, A., Fearon, W., Haddad, F. ELSEVIER SCIENCE INC. 2017: 1040
  • Acute Right Ventricular Failure After Successful Opening of Chronic Total Occlusion in Right Coronary Artery Caused by a Large Intramural Hematoma. Circulation. Cardiovascular interventions Kawana, M., Lee, A. M., Liang, D. H., Yeung, A. C. 2017; 10 (2)
  • GDF-15 (Growth Differentiation Factor 15) Is Associated With Lack of Ventricular Recovery and Mortality After Transcatheter Aortic Valve Replacement. Circulation. Cardiovascular interventions Kim, J. B., Kobayashi, Y., Moneghetti, K. J., Brenner, D. A., O'Malley, R., Schnittger, I., Wu, J. C., Murtagh, G., Beshiri, A., Fischbein, M., Miller, D. C., Liang, D., Yeung, A. C., Haddad, F., Fearon, W. F. 2017; 10 (12)


    Recent data suggest that circulating biomarkers may predict outcome in patients undergoing transcatheter aortic valve replacement (TAVR). We examined the association between inflammatory, myocardial, and renal biomarkers and their role in ventricular recovery and outcome after TAVR.A total of 112 subjects undergoing TAVR were included in the prospective registry. Plasma levels of B-type natriuretic peptide, hs-TnI (high-sensitivity troponin I), CRP (C-reactive protein), GDF-15 (growth differentiation factor 15), GAL-3 (galectin-3), and Cys-C (cystatin-C) were assessed before TAVR and in 100 sex-matched healthy controls. Among echocardiographic parameters, we measured global longitudinal strain, indexed left ventricular mass, and indexed left atrial volume. The TAVR group included 59% male, with an average age of 84 years, and 1-year mortality of 18%. Among biomarkers, we found GDF-15 and CRP to be strongly associated with all-cause mortality (P<0.001). Inclusion of GDF-15 and CRP to the Society of Thoracic Surgeons score significantly improved C index (0.65-0.79; P<0.05) and provided a category-free net reclassification improvement of 106% at 2 years (P=0.01). Among survivors, functional recovery in global longitudinal strain (>15% improvement) and indexed left ventricular mass (>20% decrease) at 1 year occurred in 48% and 22%, respectively. On multivariate logistic regression, lower baseline GDF-15 was associated with improved global longitudinal strain at 1 year (hazard ratio=0.29; P<0.001). Furthermore, improvement in global longitudinal strain at 1 month correlated with lower overall mortality (hazard ratio=0.45; P=0.03).Elevated GDF-15 correlates with lack of reverse remodeling and increased mortality after TAVR and improves risk prediction of mortality when added to the Society of Thoracic Surgeons score.

    View details for PubMedID 29222133

  • Impact of Asymmetric Dimethylarginine on Coronary Physiology Early After Heart Transplantation. The American journal of cardiology Parikh, R. V., Khush, K. K., Luikart, H., Pargaonkar, V. S., Kobayashi, Y., Lee, J. H., Sinha, S., Cohen, G., Valantine, H. A., Yeung, A. C., Fearon, W. F. 2017


    Cardiac allograft vasculopathy is a major cause of long-term graft failure following heart transplantation. Asymmetric dimethylarginine (ADMA), a marker of endothelial dysfunction, has been mechanistically implicated in the development of cardiac allograft vasculopathy, but its impact on coronary physiology early after transplantation is unknown. Invasive indices of coronary physiology, namely, fractional flow reserve (FFR), the index of microcirculatory resistance, and coronary flow reserve, were measured with a coronary pressure wire in the left anterior descending artery within 8 weeks (baseline) and 1 year after transplant. Plasma levels of ADMA were concurrently assayed using high-performance liquid chromatography. In 46 heart transplant recipients, there was a statistically significant correlation between elevated ADMA levels and lower FFR values at baseline (r = -0.33; p = 0.024); this modest association persisted 1 year after transplant (r = -0.39; p = 0.0085). Patients with a baseline FFR <0.90 (a prognostically validated cutoff) had significantly higher baseline ADMA levels (0.63 ± 0.16 vs 0.54 ± 0.12 µM; p = 0.034). Baseline ADMA (odds ratio 1.80 per 0.1 µM; 95% confidence interval 1.07 to 3.03; p = 0.027) independently predicted a baseline FFR <0.90 after multivariable adjustment. Even after dichotomizing ADMA (≥0.60 µM, provides greatest diagnostic accuracy by receiver operating characteristic curve), this association remained significant (odds ratio 7.52, 95% confidence interval 1.74 to 32.49; p = 0.006). No significant relationship between ADMA and index of microcirculatory resistance or coronary flow reserve was detected. In conclusion, baseline ADMA was a strong independent predictor of FFR <0.90, suggesting that elevated ADMA levels are associated with abnormal epicardial function soon after heart transplantation.

    View details for PubMedID 28754566

  • Coronary Endothelial Dysfunction and the Index of Microcirculatory Resistance as a Marker of Subsequent Development of Cardiac Allograft Vasculopathy. Circulation Lee, J. H., Okada, K., Khush, K., Kobayashi, Y., Sinha, S., Luikart, H., Valantine, H., Yeung, A. C., Honda, Y., Fearon, W. F. 2017; 135 (11): 1093–95

    View details for PubMedID 28289008

  • 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., Okada, K., Kimura, T., Yock, P. G., Lansky, A. J., Popma, J. J., Yeung, A. C., Fitzgerald, P. J., Honda, Y. 2017; 10 (10)


    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

  • Feasibility of Obtaining Measures of Lifestyle From a Smartphone App: The MyHeart Counts Cardiovascular Health Study. JAMA cardiology McConnell, M. V., Shcherbina, A., Pavlovic, A., Homburger, J. R., Goldfeder, R. L., Waggot, D., Cho, M. K., Rosenberger, M. E., Haskell, W. L., Myers, J., Champagne, M. A., Mignot, E., Landray, M., Tarassenko, L., Harrington, R. A., Yeung, A. C., Ashley, E. A. 2017; 2 (1): 67-76


    Studies have established the importance of physical activity and fitness, yet limited data exist on the associations between objective, real-world physical activity patterns, fitness, sleep, and cardiovascular health.To assess the feasibility of obtaining measures of physical activity, fitness, and sleep from smartphones and to gain insights into activity patterns associated with life satisfaction and self-reported disease.The MyHeart Counts smartphone app was made available in March 2015, and prospective participants downloaded the free app between March and October 2015. In this smartphone-based study of cardiovascular health, participants recorded physical activity, filled out health questionnaires, and completed a 6-minute walk test. The app was available to download within the United States.The feasibility of consent and data collection entirely on a smartphone, the use of machine learning to cluster participants, and the associations between activity patterns, life satisfaction, and self-reported disease.From the launch to the time of the data freeze for this study (March to October 2015), the number of individuals (self-selected) who consented to participate was 48 968, representing all 50 states and the District of Columbia. Their median age was 36 years (interquartile range, 27-50 years), and 82.2% (30 338 male, 6556 female, 10 other, and 3115 unknown) were male. In total, 40 017 (81.7% of those who consented) uploaded data. Among those who consented, 20 345 individuals (41.5%) completed 4 of the 7 days of motion data collection, and 4552 individuals (9.3%) completed all 7 days. Among those who consented, 40 017 (81.7%) filled out some portion of the questionnaires, and 4990 (10.2%) completed the 6-minute walk test, made available only at the end of 7 days. The Heart Age Questionnaire, also available after 7 days, required entering lipid values and age 40 to 79 years (among 17 245 individuals, 43.1% of participants). Consequently, 1334 (2.7%) of those who consented completed all fields needed to compute heart age and a 10-year risk score. Physical activity was detected for a mean (SD) of 14.5% (8.0%) of individuals' total recorded time. Physical activity patterns were identified by cluster analysis. A pattern of lower overall activity but more frequent transitions between active and inactive states was associated with equivalent self-reported cardiovascular disease as a pattern of higher overall activity with fewer transitions. Individuals' perception of their activity and risk bore little relation to sensor-estimated activity or calculated cardiovascular risk.A smartphone-based study of cardiovascular health is feasible, and improvements in participant diversity and engagement will maximize yield from consented participants. Large-scale, real-world assessment of physical activity, fitness, and sleep using mobile devices may be a useful addition to future population health studies.

    View details for DOI 10.1001/jamacardio.2016.4395

    View details for PubMedID 27973671

  • Angiotensin-Converting Enzyme Inhibition Early After Heart Transplantation. Journal of the American College of Cardiology Fearon, W. F., Okada, K., Kobashigawa, J. A., Kobayashi, Y., Luikart, H., Sana, S., Daun, T., Chmura, S. A., Sinha, S., Cohen, G., Honda, Y., Pham, M., Lewis, D. B., Bernstein, D., Yeung, A. C., Valantine, H. A., Khush, K. 2017; 69 (23): 2832–41


    Cardiac allograft vasculopathy (CAV) remains a leading cause of mortality after heart transplantation (HT). Angiotensin-converting enzyme inhibitors (ACEIs) may retard the development of CAV but have not been well studied after HT.This study tested the safety and efficacy of the ACEI ramipril on the development of CAV early after HT.In this prospective, multicenter, randomized, double-blind, placebo-controlled trial, 96 HT recipients were randomized to undergo ramipril or placebo therapy. They underwent coronary angiography, endothelial function testing; measurements of fractional flow reserve (FFR) and coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR); and intravascular ultrasonography (IVUS) of the left anterior descending coronary artery, within 8 weeks of HT. At 1 year, the invasive assessment was repeated. Circulating endothelial progenitor cells (EPCs) were quantified at baseline and 1 year.Plaque volumes at 1 year were similar between the ramipril and placebo groups (162.1 ± 70.5 mm(3) vs. 177.3 ± 94.3 mm(3), respectively; p = 0.73). Patients receiving ramipril had improvement in microvascular function as shown by a significant decrease in IMR (21.4 ± 14.7 to 14.4 ± 6.3; p = 0.001) and increase in CFR (3.8 ± 1.7 to 4.8 ± 1.5; p = 0.017), from baseline to 1 year. This did not occur with IMR (17.4 ± 8.4 to 21.5 ± 20.0; p = 0.72) or CFR (4.1 ± 1.8 to 4.1 ± 2.2; p = 0.60) in the placebo-treated patients. EPCs decreased significantly at 1 year in the placebo group but not in the ramipril group.Ramipril does not slow development of epicardial plaque volume but does stabilize levels of endothelial progenitor cells and improve microvascular function, which have been associated with improved long-term survival after HT. (Angiotensin Converting Enzyme [ACE] Inhibition and Cardiac Allograft Vasculopathy; NCT01078363).

    View details for PubMedID 28595700

  • Baseline growth differentiation factor 15 (GDF15) is an independent predictor of reverse left atrial remodeling and mortality at 1-year following Transcatheter Aortic Valve Replacement Kim, J., Kobayashi, Y., Brenner, D., Moneghetti, K., O'Malley, R., Dao, C., Vu, T., Schnittger, I., Liang, D., Wu, J., Fischbein, M., Lee, A., Miller, D., Yeung, A., Haddad, F., Fearon, W. ELSEVIER SCIENCE INC. 2016: B298
  • Early Left Ventricular Dysfunction is Associated with Cardiac Allograft Vasculopathy and Late Mortality After Heart Transplantation Okada, K., Honda, Y., Luikart, H., Yock, P. G., Fitzgerald, P. J., Yeung, A. C., Valantine, H., Khush, K., Fearon, W. ELSEVIER SCIENCE INC. 2016: B331
  • Myocardial Bridge and Acute Plaque Rupture. Journal of investigative medicine high impact case reports Perl, L., Daniels, D., Schwartz, J., Tanaka, S., Yeung, A., Tremmel, J. A., Schnittger, I. 2016; 4 (4): 2324709616680227-?


    A myocardial bridge (MB) is a common anatomic variant, most frequently located in the left anterior descending coronary artery, where a portion of the coronary artery is covered by myocardium. Importantly, MBs are known to result in a proximal atherosclerotic lesion. It has recently been postulated that these lesions predispose patients to acute coronary events, even in cases of otherwise low-risk patients. One such mechanism may involve acute plaque rupture. In this article, we report 2 cases of patients with MBs who presented with acute coronary syndromes despite having low cardiovascular risk. Their presentation was life-risking and both were treated urgently and studied with coronary angiographies and intravascular ultrasound. This latter modality confirmed a rupture of an atherosclerotic plaque proximal to the MB as a likely cause of the acute events. These cases, of unexplained acute coronary syndrome in low-risk patients, raise the question of alternative processes leading to the event and the role MB play as an underlying cause of ruptured plaques. In some cases, an active investigation for this entity may be warranted, due to the prognostic implications of the different therapeutic modalities, should an MB be discovered.

    View details for DOI 10.1177/2324709616680227

    View details for PubMedID 28251167

  • 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


    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

  • Incidence and predictors of unplanned non-target lesion revascularisation up to three years after drug-eluting stent implantation: insights from a pooled analysis of the RESOLUTE Global Clinical Trial Program EUROINTERVENTION Abdel-Wahab, M., Neumann, F., Serruys, P., Silber, S., Leon, M., Mauri, L., Yeung, A., Belardi, J. A., Widimsky, P., Meredith, I., Saito, S., Richardt, G. 2016; 12 (4): 465-472


    To compare the incidence and predictors of target lesion revascularisation (TLR) and non-TLR after percutaneous coronary intervention with drug-eluting stents (DES).We pooled patient-level data on 6,137 patients (Resolute zotarolimus-eluting stent: 5,016, XIENCE everolimus-eluting stent: 1,121) in the RESOLUTE Global Program. At three years, clinically driven TLR, unplanned non-TLR, and no revascularisation occurred in 186, 618, and 5,333 patients, respectively. On multivariate analysis, predictors of both TLR and non-TLR were pre-procedure diameter stenosis (%) (odds ratio [OR] 1.01, 95% confidence interval [CI] [1.01-1.02], and OR 0.99 [0.99-1.00]), diabetes (OR 1.46 [1.07-1.99], and OR 1.37 [1.15-1.64]), and prior PCI (OR 1.42 [1.01-2.00], and OR 1.41 [1.18-1.68]). Baseline characteristics associated with TLR only were prior coronary artery bypass graft surgery (OR 2.85 [1.91-4.27]), in-stent restenosis (OR 2.35 [1.43-3.83]), age (OR 0.98 per year [0.97-1.00]), hypertension (OR 1.64 [1.10-2.44]), and pre-procedure reference vessel diameter (OR 0.74 per mm [0.55-0.99]). Baseline characteristics associated with non-TLR only were lesion location (left anterior descending vs. all others) (OR 0.70 [0.59-0.83]), and hyperlipidaemia (OR 1.42 [1.15-1.75]).The cumulative incidence of non-TLR at three years in patients treated with current-generation DES was almost three times higher than TLR.

    View details for DOI 10.4244/EIJY15M07_07

    View details for Web of Science ID 000381777500009

    View details for PubMedID 26477642

  • 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


    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

  • Salvage Extracorporeal Membrane Oxygenation Prior to "Bridge" Transcatheter Aortic Valve Replacement. Journal of cardiac surgery Chiu, P., Fearon, W. F., Raleigh, L. A., Burdon, G., Rao, V., Boyd, J. H., Yeung, A. C., Miller, D. C., Fischbein, M. P. 2016; 31 (6): 403-405


    We describe a patient who presented in profound cardiogenic shock due to bioprosthetic aortic valve stenosis requiring salvage Extracorporeal Membrane Oxygenation followed by a "bridge" valve-in-valve transcatheter aortic valve replacement. doi: 10.1111/jocs.12750 (J Card Surg 2016;31:403-405).

    View details for DOI 10.1111/jocs.12750

    View details for PubMedID 27109017

  • Invasive Assessment of Coronary Physiology Predicts Late Mortality After Heart Transplantation CIRCULATION Yang, H., Khush, K., Luikart, H., Okada, K., Lim, H., Kobayashi, Y., Honda, Y., Yeung, A. C., Valantine, H., Fearon, W. F. 2016; 133 (20): 1945-1950


    -The aim of this study is to determine the prognostic value of invasively assessing coronary physiology early after heart transplantation.-Seventy-four cardiac transplant recipients had fractional flow reserve (FFR), coronary flow reserve (CFR), the index of microcirculatory resistance (IMR) and intravascular ultrasound (IVUS) performed down the left anterior descending coronary artery soon after (baseline) and 1 year after heart transplantation. The primary endpoint was the cumulative survival free of death or retransplantation at a mean follow-up of 4.5±3.5 years. The cumulative event-free survival was significantly lower in patients with an FFR<0.90 at baseline (42 vs 79%, p=0.01) or an IMR≥20 measured one year after heart transplantation (39 vs. 69%, p=0.03). Patients in whom IMR decreased or did not change from baseline to 1 year had higher event-free survival compared to those patients with an increase in IMR (66 vs. 36%, p=0.03). FFR<0.90 at baseline (hazards ratio [HR] 0.13, 95% confidence interval [CI] 0.02-0.81, p=0.03), IMR ≥20 at 1 year (HR 3.93, 95% CI 1.08-14.27, p=0.04) and rejection during the first year (HR 6.00, 95% CI 1.56-23.09, p=0.009) were independent predictors of death/retransplantation, while IVUS parameters were not.-Invasive measures of coronary physiology (FFR and IMR) determined early after heart transplantation are significant predictors of late death or retransplantation.

    View details for DOI 10.1161/CIRCULATIONAHA.115.018741

    View details for PubMedID 27143679

  • Transcatheter Aortic Valve Replacement in the Asian Population What Did We Learn and Not Learn? JACC-CARDIOVASCULAR INTERVENTIONS Yeung, A. C. 2016; 9 (9): 934–36

    View details for PubMedID 27151608

  • Transcatheter or Surgical Aortic-Valve Replacement in Intermediate-Risk Patients NEW ENGLAND JOURNAL OF MEDICINE Leon, M. B., Smith, C. R., Mack, M. J., Makkar, R. R., Svensson, L. G., Kodali, S. K., Thourani, V. H., Tuzcu, E. M., Miller, D. C., Herrmann, H. C., Doshi, D., Cohen, D. J., Pichard, A. D., Kapadia, S., Dewey, T., Babaliaros, V., Szeto, W. Y., Williams, M. R., Kereiakes, D., Zajarias, A., Greason, K. L., Whisenant, B. K., Hodson, R. W., Moses, J. W., Trento, A., Brown, D. L., Fearon, W. F., Pibarot, P., Hahn, R. T., Jaber, W. A., Anderson, W. N., Alu, M. C., Webb, J. G. 2016; 374 (17): 1609-1620


    Previous trials have shown that among high-risk patients with aortic stenosis, survival rates are similar with transcatheter aortic-valve replacement (TAVR) and surgical aortic-valve replacement. We evaluated the two procedures in a randomized trial involving intermediate-risk patients.We randomly assigned 2032 intermediate-risk patients with severe aortic stenosis, at 57 centers, to undergo either TAVR or surgical replacement. The primary end point was death from any cause or disabling stroke at 2 years. The primary hypothesis was that TAVR would not be inferior to surgical replacement. Before randomization, patients were entered into one of two cohorts on the basis of clinical and imaging findings; 76.3% of the patients were included in the transfemoral-access cohort and 23.7% in the transthoracic-access cohort.The rate of death from any cause or disabling stroke was similar in the TAVR group and the surgery group (P=0.001 for noninferiority). At 2 years, the Kaplan-Meier event rates were 19.3% in the TAVR group and 21.1% in the surgery group (hazard ratio in the TAVR group, 0.89; 95% confidence interval [CI], 0.73 to 1.09; P=0.25). In the transfemoral-access cohort, TAVR resulted in a lower rate of death or disabling stroke than surgery (hazard ratio, 0.79; 95% CI, 0.62 to 1.00; P=0.05), whereas in the transthoracic-access cohort, outcomes were similar in the two groups. TAVR resulted in larger aortic-valve areas than did surgery and also resulted in lower rates of acute kidney injury, severe bleeding, and new-onset atrial fibrillation; surgery resulted in fewer major vascular complications and less paravalvular aortic regurgitation.In intermediate-risk patients, TAVR was similar to surgical aortic-valve replacement with respect to the primary end point of death or disabling stroke. (Funded by Edwards Lifesciences; PARTNER 2 number, NCT01314313.).

    View details for DOI 10.1056/NEJMoa1514616

    View details for PubMedID 27040324

  • CLINICAL PRESENTATION, MANAGEMENT AND PROGNOSIS OF PATIENTS WITH SPONTANEOUS CORONARY ARTERY DISSECTION Pargaonkar, V., Khandelwal, A., Krishnan, G., Sears, K., Hoover, V., Fearon, W., Lee, D., Yeung, A., Tsai, S., Nejedly, M., Naderi, S., Tremmel, J. ELSEVIER SCIENCE INC. 2016: 53
  • 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


    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

  • 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


    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 PubMedID 26577615

  • Response to Letters Regarding Article, "Invasive Evaluation of Patients With Angina in the Absence of Obstructive Coronary Artery Disease" CIRCULATION Tremmel, J. A., Fearon, W. F., Lee, B., Lim, H., Yong, A. S., Yamada, R., Tanaka, S., Lee, D. P., Yeung, A. C. 2015; 132 (20): E244

    View details for PubMedID 26572677

  • Clinical Relevance of Myocardial Injury After Transcatheter Aortic Valve Replacement JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Fearon, W. F., Yeung, A. C. 2015; 66 (19): 2089–91

    View details for PubMedID 26541918

  • Poorer Left Ventricular Global Longitudinal Strain and Less Tricuspid Regurgitation Predicts Improvement in Left Ventricular Function Following Transcatheter Aortic Valve Replacement Kim, J. B., Brenner, D., Kobayashi, Y., O'Malley, R., Kobayashi, Y., Dao, C., Thu Vu, Yeung, A., Miller, D., Fischbein, M., Wu, J. C., Haddad, F., Fearon, W. F. ELSEVIER SCIENCE INC. 2015: B263–B264
  • Endovascular hypothermia treatment dose-modulates cardioprotection in favor of 32 degrees C target temperature before reperfusion in porcine myocardial infarction Mitsutake, Y., Dash, R., Ikeno, F., Pyun, W., Lyons, J., Dawoud, F., Illindala, U., Yeung, A. ELSEVIER SCIENCE INC. 2015: B94
  • Rationale and design of the Fractional Flow Reserve versus Angiography for Multivessel Evaluation (FAME) 3 Trial: A comparison of fractional flow reserve-guided percutaneous coronary intervention and coronary artery bypass graft surgery in patients with multivessel coronary artery disease. American heart journal Zimmermann, F. M., De Bruyne, B., Pijls, N. H., Desai, M., Oldroyd, K. G., Park, S., Reardon, M. J., Wendler, O., Woo, J., Yeung, A. C., Fearon, W. F. 2015; 170 (4): 619-626 e2


    Guidelines recommend coronary artery bypass graft (CABG) surgery over percutaneous coronary intervention (PCI) for the treatment of 3-vessel coronary artery disease (3-VD). The inferior results of PCI demonstrated by previous large randomized trials comparing PCI and CABG might be explained by the use of suboptimal stent technology and by the lack of fractional flow reserve (FFR) guidance of PCI.The objective of this investigator-initiated, multicenter, randomized clinical trial is to investigate whether FFR-guided PCI with new-generation stents is noninferior to CABG in patients with 3-VD, not including the left main coronary artery. Eligible patients must have ≥50% coronary stenoses in all 3 major epicardial vessels or major side branches. Patients with a nondominant right coronary artery may be included only if the left anterior descending artery and left circumflex have ≥50% stenoses. Consecutive patients who meet all of the inclusion criteria and none of the exclusion criteria will be randomized in a 1:1 fashion to either CABG or FFR-guided PCI. Coronary artery bypass graft will be performed based on the angiogram as per clinical routine. Patients assigned to FFR-guided PCI will have FFR measured in each diseased vessel and only undergo stenting if the FFR is ≤0.80. The primary end point of the study is a composite of major adverse cardiac and cerebrovascular events, including death, myocardial infarction, repeat coronary revascularization, and stroke at 1 year. Key secondary end point will be a composite of death, myocardial infarction, and stroke at 3-year follow-up. Other secondary end points include the individual adverse events, cost-effectiveness, and quality of life at 2-year, 3-year, with up to 5-year follow-up.The FAME 3 study will compare in a multicenter, randomized fashion FFR-guided PCI with contemporary drug-eluting stents to CABG in patients with 3-VD.

    View details for DOI 10.1016/j.ahj.2015.06.024

    View details for PubMedID 26386784

  • 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


    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

  • Manganese-Enhanced Magnetic Resonance Imaging Enables In Vivo Confirmation of Peri-Infarct Restoration Following Stem Cell Therapy in a Porcine Ischemia-Reperfusion Model. Journal of the American Heart Association Dash, R., Kim, P. J., Matsuura, Y., Ikeno, F., Metzler, S., Huang, N. F., Lyons, J. K., Nguyen, P. K., Ge, X., Foo, C. W., McConnell, M. V., Wu, J. C., Yeung, A. C., Harnish, P., Yang, P. C. 2015; 4 (7)


    The exact mechanism of stem cell therapy in augmenting the function of ischemic cardiomyopathy is unclear. In this study, we hypothesized that increased viability of the peri-infarct region (PIR) produces restorative benefits after stem cell engraftment. A novel multimodality imaging approach simultaneously assessed myocardial viability (manganese-enhanced magnetic resonance imaging [MEMRI]), myocardial scar (delayed gadolinium enhancement MRI), and transplanted stem cell engraftment (positron emission tomography reporter gene) in the injured porcine hearts.Twelve adult swine underwent ischemia-reperfusion injury. Digital subtraction of MEMRI-negative myocardium (intrainfarct region) from delayed gadolinium enhancement MRI-positive myocardium (PIR and intrainfarct region) clearly delineated the PIR in which the MEMRI-positive signal reflected PIR viability. Human amniotic mesenchymal stem cells (hAMSCs) represent a unique population of immunomodulatory mesodermal stem cells that restored the murine PIR. Immediately following hAMSC delivery, MEMRI demonstrated an increased PIR viability signal compared with control. Direct PIR viability remained higher in hAMSC-treated hearts for >6 weeks. Increased PIR viability correlated with improved regional contractility, left ventricular ejection fraction, infarct size, and hAMSC engraftment, as confirmed by immunocytochemistry. Increased MEMRI and positron emission tomography reporter gene signal in the intrainfarct region and the PIR correlated with sustained functional augmentation (global and regional) within the hAMSC group (mean change, left ventricular ejection fraction: hAMSC 85±60%, control 8±10%; P<0.05) and reduced chamber dilatation (left ventricular end-diastole volume increase: hAMSC 24±8%, control 110±30%; P<0.05).The positron emission tomography reporter gene signal of hAMSC engraftment correlates with the improved MEMRI signal in the PIR. The increased MEMRI signal represents PIR viability and the restorative potential of the injured heart. This in vivo multimodality imaging platform represents a novel, real-time method of tracking PIR viability and stem cell engraftment while providing a mechanistic explanation of the therapeutic efficacy of cardiovascular stem cells.

    View details for DOI 10.1161/JAHA.115.002044

    View details for PubMedID 26215972

  • Impact of Body Mass Index on Long-Term Clinical Outcomes After Second-Generation Drug Eluting Stent Implantation: Insights From the International Global RESOLUTE Program CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Diletti, R., Garcia-Garcia, H. M., Bourantas, C., Van Mieghem, N. M., van Geuns, R. J., Muramatsu, T., Zhang, Y., Mauri, L., Belardi, J., Silber, S., Widimsky, P., Leon, M., Windecker, S., Meredith, I., Neumann, F., Yeung, A. C., Saito, S., Liu, M., van Leeuwen, F., Serruys, P. W. 2015; 85 (6): 952-958


    An increased body mass index (BMI) is associated with a high risk of cardiovascular disease and reduction in life expectancy. However, several studies reported improved clinical outcomes in obese patients treated for cardiovascular diseases. The aim of the present study is to investigate the impact of BMI on long-term clinical outcomes after implantation of zotarolimus eluting stents.Individual patient data were pooled from the RESOLUTE Clinical Program comprising five trials worldwide. The study population was sorted according to BMI tertiles and clinical outcomes were evaluated at 2-year follow-up.Data from a total of 5,127 patients receiving the R-ZES were included in the present study. BMI tertiles were as follow: I tertile (≤ 25.95 kg/m(2) -Low or normal weight) 1,727 patients; II tertile (>25.95 ≤ 29.74 kg/m(2) -overweight) 1,695 patients, and III tertile (>29.74 kg/m(2) -obese) 1,705 patients. At 2-years follow-up no difference was found for patients with high BMI (III tertile) compared with patients with normal or low BMI (I tertile) in terms of target lesion failure (I-III tertile, HR [95% CI] = 0.89 [0.69, 1.14], P = 0.341; major adverse cardiac events (I-III tertile, HR [95% CI] = 0.90 [0.72, 1.14], P = 0.389; cardiac death (I-III tertile, HR [95% CI] = 1.20 [0.73, 1.99], P = 0.476); myocardial infarction (I-III tertile, HR [95% CI] = 0.86 [0.55, 1.35], P = 0.509; clinically-driven target lesion revascularization (I-III tertile, HR [95% CI] = 0.75 [0.53, 1.08], P = 0.123; definite or probable stent thrombosis (I-III tertile, HR [95% CI] = 0.98 [0.49, 1.99], P = 0.964.In the present study, the patients' body mass index was found to have no impact on long-term clinical outcomes after coronary artery interventions.

    View details for DOI 10.1002/ccd.25828

    View details for Web of Science ID 000353360800005

    View details for PubMedID 25689692

  • Trial of Everolimus-Eluting Stents or Bypass Surgery for Coronary Disease NEW ENGLAND JOURNAL OF MEDICINE Park, S., Ahn, J., Kim, Y., Park, D., Yun, S., Lee, J., Kang, S., Lee, S., Lee, C. W., Park, S., Choo, S. J., Chung, C. H., Lee, J. W., Cohen, D. J., Yeung, A. C., Hur, S. H., Seung, K. B., Ahn, T. H., Kwon, H. M., Lim, D., Rha, S., Jeong, M., Lee, B., Tresukosol, D., Fu, G. S., Ong, T. K. 2015; 372 (13): 1204-1212


    Most trials comparing percutaneous coronary intervention (PCI) with coronary-artery bypass grafting (CABG) have not made use of second-generation drug-eluting stents.We conducted a randomized noninferiority trial at 27 centers in East Asia. We planned to randomly assign 1776 patients with multivessel coronary artery disease to PCI with everolimus-eluting stents or to CABG. The primary end point was a composite of death, myocardial infarction, or target-vessel revascularization at 2 years after randomization. Event rates during longer-term follow-up were also compared between groups.After the enrollment of 880 patients (438 patients randomly assigned to the PCI group and 442 randomly assigned to the CABG group), the study was terminated early owing to slow enrollment. At 2 years, the primary end point had occurred in 11.0% of the patients in the PCI group and in 7.9% of those in the CABG group (absolute risk difference, 3.1 percentage points; 95% confidence interval [CI], -0.8 to 6.9; P=0.32 for noninferiority). At longer-term follow-up (median, 4.6 years), the primary end point had occurred in 15.3% of the patients in the PCI group and in 10.6% of those in the CABG group (hazard ratio, 1.47; 95% CI, 1.01 to 2.13; P=0.04). No significant differences were seen between the two groups in the occurrence of a composite safety end point of death, myocardial infarction, or stroke. However, the rates of any repeat revascularization and spontaneous myocardial infarction were significantly higher after PCI than after CABG.Among patients with multivessel coronary artery disease, the rate of major adverse cardiovascular events was higher among those who had undergone PCI with the use of everolimus-eluting stents than among those who had undergone CABG. (Funded by CardioVascular Research Foundation and others; BEST number, NCT00997828.).

    View details for DOI 10.1056/NEJMoa1415447

    View details for PubMedID 25774645

  • Invasive Evaluation of Patients With Angina in the Absence of Obstructive Coronary Artery Disease CIRCULATION Lee, B., Lim, H., Fearon, W. F., Yong, A. S., Yamada, R., Tanaka, S., Lee, D. P., Yeung, A. C., Tremmel, J. A. 2015; 131 (12): 1054-1060


    More than 20% of patients presenting to the cardiac catheterization laboratory with angina have no angiographic evidence of coronary artery disease. Despite a "normal" angiogram, these patients often have persistent symptoms, recurrent hospitalizations, a poor functional status, and adverse cardiovascular outcomes, without a clear diagnosis.In 139 patients with angina in the absence of obstructive coronary artery disease (no diameter stenosis >50%), endothelial function was assessed; the index of microcirculatory resistance, coronary flow reserve, and fractional flow reserve were measured; and intravascular ultrasound was performed. There were no complications. The average age was 54.0±11.4 years, and 107 (77%) were women. All patients had at least some evidence of atherosclerosis based on an intravascular ultrasound examination of the left anterior descending artery. Endothelial dysfunction (a decrease in luminal diameter of >20% after intracoronary acetylcholine) was present in 61 patients (44%). Microvascular impairment (an index of microcirculatory resistance ≥25) was present in 29 patients (21%). Seven patients (5%) had a fractional flow reserve ≤0.80. A myocardial bridge was present in 70 patients (58%). Overall, only 32 patients (23%) had no coronary explanation for their angina, with normal endothelial function, normal coronary physiological assessment, and no myocardial bridging.The majority of patients with angina in the absence of obstructive coronary artery disease have occult coronary abnormalities. A comprehensive invasive assessment of these patients at the time of coronary angiography can be performed safely and provides important diagnostic information that may affect treatment and outcomes.

    View details for DOI 10.1161/CIRCULATIONAHA.114.012636

    View details for PubMedID 25712205

  • IMPACT OF MYOCARDIAL BRIDGING ON CORONARY ARTERY PLAQUE FORMATION AND LONG-TERM MORTALITY AFTER HEART TRANSPLANTATION Tanaka, S., Okada, K., Kitahara, H., Kobayashi, Y., Luikart, H., Yock, P., Yeung, A., Schnittger, I., Fitzgerald, P., Khush, K., Fearon, W., Honda, Y. ELSEVIER SCIENCE INC. 2015: A1741
  • Efficacy and Safety of Novel Multi-Lumen Catheter for Chronic Total Occlusions: From Preclinical Study to First-in-Man Experience CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Mitsutake, Y., Ebner, A., Yeung, A. C., Taber, M. D., Davidson, C. J., Ikeno, F. 2015; 85 (3): E70-E75


    To report our initial animal and human experience with a new multi-lumen catheter called MultiCross™ (Roxwood Medical, Inc.) in a porcine coronary model and patients with a chronic total occlusion (CTO).Preclinical safety study was done in the coronary vasculature of a porcine model. In a clinical setting, patients with a CTO of a coronary artery (n = 5) were enrolled. After an initial unsuccessful attempt using a conventional guidewire, operators could use the MultiCross system. The primary efficacy endpoint was successful recanalization (technical success) and the primary safety endpoint was serious adverse events through 30 days post-procedure.The MultiCross catheter was used for all patients after failure of the initial attempt with a guidewire. Successful recanalization was achieved in all CTOs attempted (100%). No patients reported any adverse events at 30 days post-procedure.In this first-in-man experience, the MultiCross catheter has the potential to enhance crossing of CTOs.

    View details for DOI 10.1002/ccd.25711

    View details for Web of Science ID 000349962400002

    View details for PubMedID 25331940

  • Manganese-Enhanced Magnetic Resonance Imaging Enables In Vivo Confirmation of Peri-Infarct Restoration Following Stem Cell Therapy in a Porcine Ischemia-Reperfusion Model. Journal of the American Heart Association Dash, R., Kim, P. J., Matsuura, Y., Ikeno, F., Metzler, S., Huang, N. F., Lyons, J. K., Nguyen, P. K., Ge, X., Wong Po Foo, C., McConnell, M. V., Wu, J. C., Yeung, A. C., Harnish, P., Yang, P. C. 2015; 4 (7)

    View details for DOI 10.1161/JAHA.115.002044

    View details for PubMedID 26215972

  • APPOSITION V: STENTYS coronary stent system clinical trial in subjects with ST-segment elevation myocardial infarction-Rationale and design AMERICAN HEART JOURNAL Grundeken, M. J., Lu, H., Mehran, R., Cutlip, D. E., Leon, M. B., Yeung, A., Koch, K. T., Montalescot, G., van Geuns, R., Spaargaren, R., Buchbinder, M. 2014; 168 (5): 652-660


    Primary percutaneous coronary intervention (PCI) has considerably improved clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) when compared with thrombolytic therapy. Prognosis after primary PCI might be further improved by decreasing stent-related complications such as stent thrombosis. The STENTYS self-apposing stent has been shown to be superior compared with balloon-expandable stents with regard to stent apposition. The current prospective randomized trial was designed to evaluate whether the superior stent apposition of the STENTYS stent results in clinical outcomes that are at least noninferior to a conventional balloon-expandable stent.The APPOSITION V is a prospective, multicenter, international, single-blinded, randomized controlled trial in STEMI patients. Randomization will be performed in a 2:1 ratio between the self-apposing nitinol bare-metal STENTYS stent and the balloon-expandable bare-metal MULTI-LINK. The primary end point is defined as target vessel failure, which is a composite of cardiac death, target vessel-related recurrent myocardial infarction, or clinically driven target vessel revascularization, at 1-year follow-up. Baseline intravascular ultrasound and optical coherence tomography (OCT) substudies will be performed in 212 and 60 subjects, respectively, and a repeat angiography at 12 to 13 months will be performed in 105 subjects, including intravascular ultrasound and OCT (in the 60 OCT patients). This study is registered on with number NCT01732341.APPOSITION V will be the first randomized trial powered on clinical end points that directly compares the STENTYS self-apposing stent with a conventional balloon-expandable stent in patients presenting with STEMI undergoing primary PCI.

    View details for DOI 10.1016/j.ahj.2014.07.011

    View details for Web of Science ID 000344434300006

  • Outcomes After Transfemoral Transcatheter Aortic Valve Replacement A Comparison of the Randomized PARTNER (Placement of AoRTic TraNscathetER Valves) Trial With the NRCA (Nonrandomized Continued Access) Registry JACC-CARDIOVASCULAR INTERVENTIONS Fearon, W. F., Kodali, S., Doshi, D., Fischbein, M. P., Yeung, A. C., Tuzcu, E. M., Rihal, C. S., Babaliaros, V., Zajarias, A., Herrmann, H. C., Brown, D. L., Mack, M., Teirstein, P. S., Whisenant, B. K., Makkar, R., Kapadia, S., Leon, M. B. 2014; 7 (11): 1245-1251


    This study sought to determine whether outcomes for transfemoral (TF) transcatheter aortic valve replacement (TAVR) differ between the randomized controlled trial (RCT) and the subsequent NRCA (Nonrandomized Continued Access) registry of the PARTNER (Placement of AoRTic TraNscathetER Valves) trial.The PARTNER RCT demonstrated that TAVR with the Edwards Sapien valve (Edwards Lifesciences, Irvine, California) is noninferior to surgery in high-risk patients and superior to standard therapy for inoperable patients.The inclusion and exclusion criteria, data collection, monitoring, and core laboratories were the same for the RCT and NRCA registry. Baseline characteristics, procedural results, and 1-year outcomes were compared between patients undergoing TF-TAVR as part of the RCT and as part of the NRCA registry.In the RCT, 415 patients underwent TF-TAVR, whereas in the NRCA, 1,023 patients did. At 30 days, death, cardiac death, stroke, and transient ischemic attacks were not different in the NRCA registry than in the RCT. Major vascular complications (8.0% vs. 15.7%, p < 0.0001) and major bleeding (6.8% vs. 15.3%, p < 0.0001) were significantly lower in the NRCA registry. At 1 year, death rates were significantly lower in the NRCA cohort (19.0% vs. 25.3%, p = 0.009) and cardiac death tended to be lower (8.4% vs. 11.1%, p = 0.12). Stroke or transient ischemic attack (6.2% vs. 8.7%, p = 0.10) and stroke alone (5.0% vs. 7.1%, p = 0.13) also tended to be lower.The large NRCA registry demonstrates further improvement in procedural and longer-term outcomes after TF-TAVR when compared with the favorable results from the PARTNER RCT. (THE PARTNER TRIAL: Placement of AoRTic TraNscathetER Valve Trial; NCT00530894).

    View details for DOI 10.1016/j.jcin.2014.05.033

    View details for Web of Science ID 000345288400013

  • Continuous flow left ventricular assist device placement complicated by aortic valve thrombus and myocardial infarction INTERNATIONAL JOURNAL OF CARDIOLOGY Kim, J. B., Rhee, J., Brenner, D. A., Ha, R., Banerjee, D., Yeung, A. C., Tremmel, J. A. 2014; 176 (3): E102-E103
  • Appropriate Intravascular Ultrasound Measurement Intervals for Assessment of Cardiac Allograft Vasculopathy after Heart Transplantation Okada, K., Kitahara, H., Otagiri, K., Tanaka, S., Kobayashi, Y., Yock, P., Yeung, A., Fitzgerald, P. J., Valantine, H. A., Khush, K. K., Fearon, W. F., Honda, Y. ELSEVIER SCIENCE INC. 2014: B105
  • Impact of Coronary Artery Size on Physiologic Microcirculatory Indices: A Volumetric Intravascular Ultrasound Study with Coronary Flow Assessment Kobayashi, Y., Honda, Y., Fearon, W. F., Tanaka, S., Fitzgerald, P., Yeung, A., Tremmel, J. A. ELSEVIER SCIENCE INC. 2014: B91
  • Attenuated-Signal Plaque and Cardiac Allograft Vasculopathy: A Serial Volumetric IVUS Study of Heart Transplant Recipients Okada, K., Kitahara, H., Otagiri, K., Tanaka, S., Kobayashi, Y., Yock, P., Yeung, A., Fitzgerald, P., Valantine, H. A., Khush, K. K., Fearon, W. F., Honda, Y. ELSEVIER SCIENCE INC. 2014: B102
  • Performance of the Resolute Zotarolimus-Eluting Stent in Small Vessels CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Caputo, R., Leon, M., Serruys, P., Neumann, F., Yeung, A., Windecker, S., Belardi, J. A., Silber, S., Meredith, I., Widimsky, P., Saito, S., Mauri, L. 2014; 84 (1): 17-23


    Drug eluting stents for the treatment of small vessel coronary artery disease have traditionally yielded inferior clinical outcomes compared to the use of DES in large vessels. The benefit of the second-generation Resolute zotarolimus-eluting stent (R-ZES) in small vessels was examined.Two-year clinical outcomes from five combined R-ZES studies were compared between patients with small (reference vessel diameter [RVD] ≤2.5 mm; n = 1,956) and large (RVD >2.5 mm; n = 3174) vessels.Despite a higher incidence of comorbidities in the small vessel group, there was no significant difference in target lesion failure (TLF) (10.1% vs. 8.7%; P = 0.54) at 2 years. When the subgroup of patients with diabetes was examined (n = 1,553) there was no significant difference in 2-year TLF in small compared to large vessels (11.2% vs. 11.1%; P = 0.17). Similarly, within the small vessel cohort, no significant difference was seen regarding TLF at 2 years between people with and without diabetes (11.2% vs 9.6%; P = 0.28).When used for the treatment of small vessels, the R-ZES appears to provide acceptable clinical results at 2 years when compared to its performance in large vessels.

    View details for DOI 10.1002/ccd.25485

    View details for Web of Science ID 000337970100007

    View details for PubMedID 24659581

  • CORONARY PHYSIOLOGICAL INDICES IN PATIENTS WITH MYOCARDIAL BRIDGING Tanaka, S., Honda, Y., Yamada, R., Kobayashi, Y., Schnittger, I., Yock, P., Yeung, A., Fitzgerald, P., Fearon, W., Tremmel, J. ELSEVIER SCIENCE INC. 2014: A1691
  • Clinical interpretation and implications of whole-genome sequencing. JAMA : the journal of the American Medical Association Dewey, F. E., Grove, M. E., Pan, C., Goldstein, B. A., Bernstein, J. A., Chaib, H., Merker, J. D., Goldfeder, R. L., Enns, G. M., David, S. P., Pakdaman, N., Ormond, K. E., Caleshu, C., Kingham, K., Klein, T. E., Whirl-Carrillo, M., Sakamoto, K., Wheeler, M. T., Butte, A. J., Ford, J. M., Boxer, L., Ioannidis, J. P., Yeung, A. C., Altman, R. B., Assimes, T. L., Snyder, M., Ashley, E. A., Quertermous, T. 2014; 311 (10): 1035-1045


    Whole-genome sequencing (WGS) is increasingly applied in clinical medicine and is expected to uncover clinically significant findings regardless of sequencing indication.To examine coverage and concordance of clinically relevant genetic variation provided by WGS technologies; to quantitate inherited disease risk and pharmacogenomic findings in WGS data and resources required for their discovery and interpretation; and to evaluate clinical action prompted by WGS findings.An exploratory study of 12 adult participants recruited at Stanford University Medical Center who underwent WGS between November 2011 and March 2012. A multidisciplinary team reviewed all potentially reportable genetic findings. Five physicians proposed initial clinical follow-up based on the genetic findings.Genome coverage and sequencing platform concordance in different categories of genetic disease risk, person-hours spent curating candidate disease-risk variants, interpretation agreement between trained curators and disease genetics databases, burden of inherited disease risk and pharmacogenomic findings, and burden and interrater agreement of proposed clinical follow-up.Depending on sequencing platform, 10% to 19% of inherited disease genes were not covered to accepted standards for single nucleotide variant discovery. Genotype concordance was high for previously described single nucleotide genetic variants (99%-100%) but low for small insertion/deletion variants (53%-59%). Curation of 90 to 127 genetic variants in each participant required a median of 54 minutes (range, 5-223 minutes) per genetic variant, resulted in moderate classification agreement between professionals (Gross κ, 0.52; 95% CI, 0.40-0.64), and reclassified 69% of genetic variants cataloged as disease causing in mutation databases to variants of uncertain or lesser significance. Two to 6 personal disease-risk findings were discovered in each participant, including 1 frameshift deletion in the BRCA1 gene implicated in hereditary breast and ovarian cancer. Physician review of sequencing findings prompted consideration of a median of 1 to 3 initial diagnostic tests and referrals per participant, with fair interrater agreement about the suitability of WGS findings for clinical follow-up (Fleiss κ, 0.24; P < 001).In this exploratory study of 12 volunteer adults, the use of WGS was associated with incomplete coverage of inherited disease genes, low reproducibility of detection of genetic variation with the highest potential clinical effects, and uncertainty about clinically reportable findings. In certain cases, WGS will identify clinically actionable genetic variants warranting early medical intervention. These issues should be considered when determining the role of WGS in clinical medicine.

    View details for DOI 10.1001/jama.2014.1717

    View details for PubMedID 24618965

    View details for PubMedCentralID PMC4119063

  • 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


    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

  • Most accurate definition of a high femoral artery puncture: Aiming to better predict retroperitoneal hematoma in percutaneous coronary intervention CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Tremmel, J. A., Tibayan, Y. D., O'Loughlin, A. J., Chan, T., Fearon, W. F., Yeung, A. C., Lee, D. P. 2012; 80 (1): 37-42


    Retroperitoneal hematoma (RPH) increases morbidity and mortality in percutaneous coronary intervention (PCI). High femoral arteriotomy is an independent predictor of RPH, but the optimal angiographic criterion for defining a high puncture is unknown.We retrospectively identified 557 consecutive PCI cases with femoral angiograms. Arteriotomy sites were categorized as high based on three angiographic criteria: at or above the proximal third of the femoral head (criterion A), at or above the most inferior border of the inferior epigastric artery (criterion B), and at or above the origin of the inferior epigastric artery (criterion C). Cases of RPH were then identified.Of the 557 PCI patients, 26 had a high femoral arteriotomy by criterion A, 17 by criterion B, and 6 by criterion C. Among these patients with a high arteriotomy, RPH occurred in four with criterion A, in three with criterion B, and in one with criterion C. Of the three criteria, criterion A most strongly correlated with RPH (odds ratio [OR] 96, 95% confidence interval [CI] 10.3-898.4; p < 0.0001) compared with criterion B (OR 58, 95% CI 8.9 to 372.6; p < 0.0001) or C (OR 27, 95% CI 2.6 to 290.1; p = 0.053). All criteria had high specificity (A, 96%; B, 97%; C, 99%), but the sensitivity was higher with criterion A (80%) than criterion B (60%) or C (20%), and statistically, the use of criterion A led to the most accurate risk-stratification for RPH (A, κ = 0.79; B, κ = 0.59; C, κ = 0.19).Among the three common definitions of high arteriotomy, femoral artery puncture at or above the proximal third of the femoral head is the landmark that most accurately risk stratifies PCI patients for development of RPH.

    View details for DOI 10.1002/ccd.23175

    View details for PubMedID 22511409

  • Comparison of the Frequency of Coronary Artery Disease in Alcohol-Related Versus Non-Alcohol-Related Endstage Liver Disease AMERICAN JOURNAL OF CARDIOLOGY Patel, S., Kiefer, T. L., Ahmed, A., Ali, Z. A., Tremmel, J. A., Lee, D. P., Yeung, A. C., Fearon, W. F. 2011; 108 (11): 1552-1555


    There are conflicting data as to the prevalence of coronary artery disease (CAD) in patients with end-stage liver disease (ESLD) being assessed for liver transplantation (LT). The aims of this study were to compare the prevalence of CAD in patients with alcohol-related versus non-alcohol-related ESLD and to assess the diagnostic utility of dobutamine stress echocardiography (DSE) in predicting angiographically important CAD. Consecutive patients with ESLD being assessed for LT (n = 420, mean age 56 ± 8 years) were identified and divided into groups of those with alcohol-related ESLD (n = 125) and non-alcohol-related ESLD (n = 295). Demographic characteristics, CAD risk factors, results of DSE, and coronary angiographic characteristics were recorded. There were no significant differences in age or CAD risk factors between groups. The incidence of severe CAD (>70% diameter stenosis) was 2% in the alcohol-related ESLD group and 13% in the non-alcohol-related ESLD group (p <0.005). In the 2 groups, the presence of ≥1 CAD risk factor was associated with significant CAD (p <0.05 for all). Absence of cardiac risk factors was highly predictive in ruling out angiographically significant disease (negative predictive value 100% for alcohol-related ESLD and 97% for non-alcohol-related ESLD). DSE was performed in 205 patients. In the 2 groups, DSE had poor predictive value for diagnosing significant CAD but was useful in ruling out patients without significant disease (negative predictive value 89% for alcohol-related ESLD and 80% for non-alcohol-related ESLD). In conclusion, there was a significantly lower prevalence of severe CAD in patients with alcohol-related ESLD. These findings suggest that invasive coronary angiography may not be necessary in this subgroup, particularly in the absence of CAD risk factors and negative results on DSE.

    View details for DOI 10.1016/j.amjcard.2011.07.013

    View details for PubMedID 21890080

  • Preclinical Derivation and Imaging of Autologously Transplanted Canine Induced Pluripotent Stem Cells JOURNAL OF BIOLOGICAL CHEMISTRY Lee, A. S., Xu, D., Plews, J. R., Nguyen, P. K., Nag, D., Lyons, J. K., Han, L., Hu, S., Lan, F., Liu, J., Huang, M., Narsinh, K. H., Long, C. T., de Almeida, P. E., Levi, B., Kooreman, N., Bangs, C., Pacharinsak, C., Ikeno, F., Yeung, A. C., Gambhir, S. S., Robbins, R. C., Longaker, M. T., Wu, J. C. 2011; 286 (37): 32697-32704


    Derivation of patient-specific induced pluripotent stem cells (iPSCs) opens a new avenue for future applications of regenerative medicine. However, before iPSCs can be used in a clinical setting, it is critical to validate their in vivo fate following autologous transplantation. Thus far, preclinical studies have been limited to small animals and have yet to be conducted in large animals that are physiologically more similar to humans. In this study, we report the first autologous transplantation of iPSCs in a large animal model through the generation of canine iPSCs (ciPSCs) from the canine adipose stromal cells and canine fibroblasts of adult mongrel dogs. We confirmed pluripotency of ciPSCs using the following techniques: (i) immunostaining and quantitative PCR for the presence of pluripotent and germ layer-specific markers in differentiated ciPSCs; (ii) microarray analysis that demonstrates similar gene expression profiles between ciPSCs and canine embryonic stem cells; (iii) teratoma formation assays; and (iv) karyotyping for genomic stability. Fate of ciPSCs autologously transplanted to the canine heart was tracked in vivo using clinical positron emission tomography, computed tomography, and magnetic resonance imaging. To demonstrate clinical potential of ciPSCs to treat models of injury, we generated endothelial cells (ciPSC-ECs) and used these cells to treat immunodeficient murine models of myocardial infarction and hindlimb ischemia.

    View details for DOI 10.1074/jbc.M111.235739

    View details for Web of Science ID 000294726800078

    View details for PubMedID 21719696

    View details for PubMedCentralID PMC3173214

  • Dual Manganese-Enhanced and Delayed Gadolinium-Enhanced MRI Detects Myocardial Border Zone Injury in a Pig Ischemia-Reperfusion Model CIRCULATION-CARDIOVASCULAR IMAGING Dash, R., Chung, J., Ikeno, F., Hahn-Windgassen, A., Matsuura, Y., Bennett, M. V., Lyons, J. K., Teramoto, T., Robbins, R. C., McConnell, M. V., Yeung, A. C., Brinton, T. J., Harnish, P. P., Yang, P. C. 2011; 4 (5): 574-582


    Gadolinium (Gd)-based delayed-enhancement MRI (DEMRI) identifies nonviable myocardium but is nonspecific and may overestimate nonviable territory. Manganese (Mn(2+))-enhanced MRI (MEMRI) denotes specific Mn(2+) uptake into viable cardiomyocytes. We performed a dual-contrast myocardial assessment in a porcine ischemia-reperfusion (IR) model to test the hypothesis that combined DEMRI and MEMRI identifies viable infarct border zone (BZ) myocardium in vivo.Sixty-minute left anterior descending coronary artery IR injury was induced in 13 adult swine. Twenty-one days post-IR, 3-T cardiac MRI was performed. MEMRI was obtained after injection of 0.7 mL/kg Mn(2+) contrast agent. DEMRI was then acquired after injection of 0.2 mmol/kg Gd. Left ventricular (LV) mass, infarct, and function were analyzed. Subtraction of MEMRI defect from DEMRI signal identified injured BZ myocardium. Explanted hearts were analyzed by 2,3,5-triphenyltetrazolium chloride stain and tissue electron microscopy to compare infarct, BZ, and remote myocardium. Average LV ejection fraction was reduced (30±7%). MEMRI and DEMRI infarct volumes correlated with 2,3,5-triphenyltetrazolium chloride stain analysis (MEMRI, r=0.78; DEMRI, r=0.75; P<0.004). MEMRI infarct volume percentage was significantly lower than that of DEMRI (14±4% versus 23±4%; P<0.05). BZ MEMRI signal-to-noise ratio (SNR) was intermediate to remote and core infarct SNR (7.5±2.8 versus 13.2±3.4 and 2.9±1.6; P<0.0001), and DEMRI BZ SNR tended to be intermediate to remote and core infarct SNR (8.4±5.4 versus 3.3±0.6 and 14.3±6.6; P>0.05). Tissue electron microscopy analysis exhibited preserved cell structure in BZ cardiomyocytes despite transmural DEMRI enhancement.The dual-contrast MEMRI-DEMRI detects BZ viability within DEMRI infarct zones. This approach may identify injured, at-risk myocardium in ischemic cardiomyopathy.

    View details for DOI 10.1161/CIRCIMAGING.110.960591

    View details for PubMedID 21719779

  • Comparison of Drug-Eluting Versus Bare Metal Stents in Cardiac Allograft Vasculopathy AMERICAN JOURNAL OF CARDIOLOGY Tremmel, J. A., Ng, M. K., Ikeno, F., Hunt, S. A., Lee, D. P., Yeung, A. C., Fearon, W. F. 2011; 108 (5): 665-668


    Although not a definitive treatment, percutaneous coronary intervention offers a palliative benefit to patients with cardiac allograft vasculopathy. Given the superior outcomes with drug-eluting stents (DESs) over bare metal stents (BMSs) in native coronary artery disease, similar improvements might be expected in transplant patients; however, the results have been mixed. Consecutive cardiac transplantation recipients at a single center receiving a stent for de novo cardiac allograft vasculopathy from 1997 to 2009 were retrospectively analyzed according to receipt of a DES versus a BMS. The angiographic and clinical outcomes were subsequently evaluated at 1 year. The baseline clinical and procedural characteristics were similar among those receiving DESs (n = 18) and BMSs (n = 16). Quantitative coronary angiography revealed no difference in the reference diameter, lesion length, or pre-/postprocedural minimal luminal diameter. At the 12-month angiographic follow-up visit, the mean lumen loss was significantly lower in the DES group than in the BMS group (0.19 ± 0.73 mm vs 0.76 ± 0.97 mm, p = 0.02). The DES group also had a lower rate of in-stent restenosis (12.5% vs 33%, p = 0.18), as well as a significantly lower rate of target lesion revascularization (0% vs 19%, p = 0.03). At 1 year, DESs were associated with a lower composite rate of cardiac death and nonfatal myocardial infarction (12% vs 38%, p = 0.04). In conclusion, DESs are safe and effective in the suppression of neointimal hyperplasia after percutaneous coronary intervention for cardiac allograft vasculopathy, resulting in significantly lower rates of late lumen loss and target lesion revascularization, as well as a reduced combined rate of cardiac death and nonfatal myocardial infarction.

    View details for DOI 10.1016/j.amjcard.2011.04.014

    View details for PubMedID 21684511

  • 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


    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

  • 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


    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

  • Images in intervention. Intramural hematoma appearing as a new lesion after coronary stenting. JACC. Cardiovascular interventions Tremmel, J. A., Koizumi, T., O'Loughlin, A., Yeung, A. C. 2011; 4 (1): 129-130

    View details for DOI 10.1016/j.jcin.2010.07.019

    View details for PubMedID 21251640

  • 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


    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

  • Intriguing Pen-Strut Low-Intensity Area Detected by Optical Coherence Tomography After Coronary Stent Deployment CIRCULATION JOURNAL Teramoto, T., Ikeno, F., Otake, H., Lyons, J. K., van Beusekom, H. M., Fearon, W. F., Yeung, A. C. 2010; 74 (6): 1257-1259


    Although peri-strut low-intensity area (PLIA) is frequently observed on post-stenting optical coherence tomography (OCT) images, the histology associated with PLIA is undocumented.The 36 porcine coronary lesions treated with bare-metal (BMS: n=16) or drug-eluting (DES: n=20) stents were assessed by OCT and histology at 28 days. DES showed a significantly higher incidence of PLIA than BMS. Also, +PLIA stents had greater neointima than PLIA stents. Histological analysis revealed the existence of fibrinoid and proteoglycans at the site of PLIA.PLIA might be represented by the presence of fibrinoid and proteoglycans, and associated with neointimal proliferation after stenting.

    View details for DOI 10.1253/circj.CJ-10-0189

    View details for PubMedID 20453394

  • Use of a Low-Profile, Compliant Balloon for Percutaneous Aortic Valvuloplasty CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Yamen, E., Daniels, D. V., Van, H., Yeung, A. C., Fearon, W. F. 2010; 75 (5): 794-798


    To determine the safety and immediate efficacy after balloon aortic valvuloplasty (BAV) with a new, low-profile balloon.BAV has a continuing role in the management of high-risk patients with severe aortic stenosis (AS). BAV with traditional noncompliant balloons requires a large femoral arteriotomy and is associated with high rates of access site complications.We retrospectively reviewed medical records of 20 consecutive patients undergoing BAV for severe AS. Retrograde transfemoral BAV was performed with a low-profile, compliant valvuloplasty balloon. Before and after BAV, transaortic gradients were measured invasively and by echocardiography, and aortic valve area (AVA) calculated. Access site complications, functional class and survival were recorded.Patients were 79 +/- 12 years old and had an estimated mortality from open aortic valve replacement of (12.5 +/- 9.6)%. By catheterization, mean aortic gradient fell from 44 +/- 15 to 29 +/- 10 mm Hg (P < 0.001) and AVA increased from 0.63 +/- 0.22 to 0.89 +/- 0.33 cm(2) (P < 0.001). New York Heart Association functional class improved from 3.5 +/- 0.7 to 2.7 +/- 0.8. Procedural mortality was 0%. There were no vascular complications or significant worsening of aortic regurgitation.Transfemoral BAV using a low-profile compliant balloon is feasible with acceptable immediate results and safety.

    View details for DOI 10.1002/ccd.22355

    View details for PubMedID 20146311

  • Impact of C-Reactive Protein on In-Stent Restenosis A Meta-Analysis TEXAS HEART INSTITUTE JOURNAL Li, J., Ren, Y., Chen, K., Yeung, A. C., Xu, B., Ruan, X., Yang, Y., Chen, J., Gao, R. 2010; 37 (1): 49-57


    We sought to evaluate the impact of C-reactive protein (CRP) levels on in-stent restenosis after percutaneous coronary intervention.The plasma level of CRP is considered a risk predictor for cardiovascular diseases. However, the relationship between CRP and in-stent restenosis has been a matter of controversy. Meta-analysis reduces variability and better evaluates the correlation.We performed a systemic search for literature published in March 2008 and earlier, using MEDLINE(R), the Cochrane clinical trials database, and EMBASE(R). We also scanned relevant reference lists and hand-searched all review articles or abstracts from conference reports on this topic. Of the 245 studies that we initially searched, we chose 9 prospective observational studies (1,062 patients).Overall, CRP concentration was higher in patients who experienced in-stent restenosis. The weighted mean difference in CRP levels between the patients with in-stent restenosis and those without was 1.67, and the Z-score for overall effect was 2.12 (P=0.03). Our subgroup analysis that compared patients with stable and unstable angina showed a weighted mean difference in the CRP levels of 2.22 between the patients with and without in-stent restenosis, and the Z-score for overall effect was 2.23 (P=0.03) in 5 studies of unstable-angina patients. There was no significance in 4 studies of stable-angina patients.In spite of significant heterogeneity across the studies, our meta-analysis suggests that preprocedurally elevated levels of CRP are associated with greater in-stent restenosis after stenting and that this impact appears more prominent in unstable-angina patients.

    View details for Web of Science ID 000274555100010

    View details for PubMedID 20200627

    View details for PubMedCentralID PMC2829784

  • Development of Animal Model for Calcified Chronic Total Occlusion CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Suzuki, Y., Oyane, A., Ikeno, F., Lyons, J. K., Yeung, A. C. 2009; 74 (3): 468-475


    Chronic total coronary occlusion (CTO) remains a major problem for percutaneous revascularization, with relatively low primary success rates and a high incidence of restenosis and reocclusion compared with those of subtotal stenoses. No reproducible animal model simulating human CTOs has previously been developed. We hypothesized that an apatite-coated bioabsorbable polymer sponge could be implanted to produce calcified CTO lesions in animal coronary arteries/peripheral arteries. A total of 10 swine and six rabbits were used for this study. The apatite-coated bioabsorbable polymer sponges were implanted into a preselected segment of coronary and peripheral arteries. Four weeks after implantation, both angiography and histopathology were performed to document the presence or absence of CTO lesions. We could reproducibly develop CTO lesions in animal coronary/peripheral arteries that mimic human CTO lesions. These lesions were found to have microvascular channels and microcalcification similar to those of human older CTO lesions and demonstrate the development of adventitial arterioles, a consistent finding in human CTO. This CTO model might provide a platform for evaluating future CTO technologies as well as contributing to a better understanding of CTOs in both educational and practical terms.

    View details for DOI 10.1002/ccd.22024

    View details for Web of Science ID 000269389200019

    View details for PubMedID 19360862

  • Imaging Gene Expression in Human Mesenchymal Stem Cells: From Small to Large Animals RADIOLOGY Willmann, J. K., Paulmurugan, R., Rodriguez-Porcel, M., Stein, W., Brinton, T. J., Connolly, A. J., Nielsen, C. H., Lutz, A. M., Lyons, J., Ikeno, F., Suzuki, Y., Rosenberg, J., Chen, I. Y., Wu, J. C., Yeung, A. C., Yock, P., Robbins, R. C., Gambhir, S. S. 2009; 252 (1): 117-127


    To evaluate the feasibility of reporter gene imaging in implanted human mesenchymal stem cells (MSCs) in porcine myocardium by using clinical positron emission tomography (PET)-computed tomography (CT) scanning.Animal protocols were approved by the Institutional Administrative Panel on Laboratory Animal Care. Transduction of human MSCs by using different doses of adenovirus that contained a cytomegalovirus (CMV) promoter driving the mutant herpes simplex virus type 1 thymidine kinase reporter gene (Ad-CMV-HSV1-sr39tk) was characterized in a cell culture. A total of 2.25 x 10(6) transduced (n = 5) and control nontransduced (n = 5) human MSCs were injected into the myocardium of 10 rats, and reporter gene expression in human MSCs was visualized with micro-PET by using the radiotracer 9-(4-[fluorine 18]-fluoro-3-hydroxymethylbutyl)-guanine (FHBG). Different numbers of transduced human MSCs suspended in either phosphate-buffered saline (PBS) (n = 4) or matrigel (n = 5) were injected into the myocardium of nine swine, and gene expression was visualized with a clinical PET-CT. For analysis of cell culture experiments, linear regression analyses combined with a t test were performed. To test differences in radiotracer uptake between injected and remote myocardium in both rats and swine, one-sided paired Wilcoxon tests were performed. In swine experiments, a linear regression of radiotracer uptake ratio on the number of injected transduced human MSCs was performed.In cell culture, there was a viral dose-dependent increase of gene expression and FHBG accumulation in human MSCs. Human MSC viability was 96.7% (multiplicity of infection, 250). Cardiac FHBG uptake in rats was significantly elevated (P < .0001) after human MSC injection (0.0054% injected dose [ID]/g +/- 0.0007 [standard deviation]) compared with that in the remote myocardium (0.0003% ID/g +/- 0.0001). In swine, myocardial radiotracer uptake was not elevated after injection of up to 100 x 10(6) human MSCs (PBS group). In the matrigel group, signal-to-background ratio increased to 1.87 after injection of 100 x 10(6) human MSCs and positively correlated (R(2) = 0.97, P < .001) with the number of administered human MSCs.Reporter gene imaging in human MSCs can be translated to large animals. The study highlights the importance of co-administering a "scaffold" for increasing intramyocardial retention of human MSCs.

    View details for DOI 10.1148/radiol.2513081616

    View details for Web of Science ID 000268362900015

    View details for PubMedID 19366903

    View details for PubMedCentralID PMC2702468

  • The Pre-Clinical Animal Model in the Translational Research of Interventional Cardiology JACC-CARDIOVASCULAR INTERVENTIONS Suzuki, Y., Yeung, A. C., Ikeno, F. 2009; 2 (5): 373-383


    Scientific discoveries for improvement of human health must be translated into practical applications. Such discoveries typically begin at "the bench" with basic research, then progress to the clinical level. In particular, in the field of interventional cardiology, percutaneous cardiovascular intervention has rapidly evolved from an experimental procedure to a therapeutic clinical setting. Pre-clinical studies using animal models play a very important role in the evaluation of efficacy and safety of new medical devices before their use in human clinical studies. This review provides an overview of the emerging role, results of pre-clinical studies and development, and evaluation of animal models for percutaneous cardiovascular intervention technologies for patients with symptomatic cardiovascular disease.

    View details for DOI 10.1016/j.jcin.2009.03.004

    View details for Web of Science ID 000278971000001

    View details for PubMedID 19463458

  • The importance of pre-clinical animal testing in interventional cardiology. Arquivos brasileiros de cardiologia Suzuki, Y., Yeung, A. C., Ikeno, F. 2008; 91 (5): 348-360


    The treatment of cardiovascular disease has changed dramatically over the past 2 decades, allowing patients to live longer and better quality lives. The introduction of new therapies has contributed much to this success. Nowhere has this been more evident than in interventional cardiology, where percutaneous cardiovascular intervention has evolved in the past 2 decades from a quirky experimental procedure to a therapeutic cornerstone for patients with symptomatic cardiovascular disease. The development of these technologies from the earliest stages requires preclinical experiments using animal models. Once introduced into the clinical arena, an understanding of therapeutic mechanisms of these devices can be ascertained through comparisons of animal model research findings with clinical pathological specimens. This review provides an overview of the emerging role, results of preclinical studies and development, and evaluation of animal models for percutaneous cardiovascular intervention technologies for patients with symptomatic cardiovascular disease.

    View details for PubMedID 19142381

  • Multimodality Evaluation of the Viability of Stem Cells Delivered Into Different Zones of Myocardial Infarction CIRCULATION-CARDIOVASCULAR IMAGING Hung, T., Suzuki, Y., Urashima, T., Caffarelli, A., Hoyt, G., Sheikh, A. Y., Yeung, A. C., Weissman, I., Robbins, R. C., Bulte, J. W., Yang, P. C. 2008; 1 (1): 6-13


    We tested the hypothesis that multimodality imaging of mouse embryonic stem cells (mESCs) provides accurate assessment of cellular location, viability, and restorative potential after transplantation into different zones of myocardial infarction.Mice underwent left anterior descending artery ligation followed by transplantation of dual-labeled mESCs with superparamagnetic iron oxide and luciferase via direct injection into 3 different zones of myocardial infarction: intra-infarction, peri-infarction, and normal (remote). One day after transplantation, magnetic resonance imaging enabled assessment of the precise anatomic locations of mESCs. Bioluminescence imaging allowed longitudinal analysis of cell viability through detection of luciferase activity. Subsequent evaluation of myocardial regeneration and functional restoration was performed by echocardiography and pressure-volume loop analysis. Using 16-segment analysis, we demonstrated precise localization of dual-labeled mESCs. A strong correlation between histology and magnetic resonance imaging was established (r=0.962, P=0.002). Bioluminescent imaging data demonstrated that cell viability in the remote group was significantly higher than in other groups. Echocardiography and pressure-volume loop analysis revealed improved functional restoration in animals treated with mESCs, although myocardial regeneration was not observed.Multimodality evaluation of mESC engraftment in the heterogeneous tissue of myocardial infarction is possible. Magnetic resonance imaging demonstrated accurate anatomic localization of dual-labeled mESCs. Bioluminescent imaging enabled assessment of variable viability of mESCs transplanted into the infarcted myocardium. Echocardiography and pressure-volume loop analysis validated the restorative potential of mESCs. Although mESCs transplanted into the remote zone demonstrated the highest viability, precise delivery of mESCs into the peri-infarction region might be equally critical in restoring the injured myocardium.

    View details for DOI 10.1161/CIRCIMAGING.108.767343

    View details for PubMedID 19808509

  • Effect of rapamycin therapy on coronary artery physiology early after cardiac transplantation AMERICAN HEART JOURNAL Sinha, S. S., Pham, M. X., Vagelos, R. H., Perlroth, M. G., Hunt, S. A., Lee, D. P., Valantine, H. A., Yeung, A. C., Fearon, W. F. 2008; 155 (5)


    Rapamycin has been shown to reduce anatomical evidence of cardiac allograft vasculopathy, but its effect on coronary artery physiology is unknown.Twenty-seven patients without angiographic evidence of coronary artery disease underwent measurement of fractional flow reserve (FFR), coronary flow reserve (CFR), and the index of microcirculatory resistance (IMR) within 8 weeks and then 1 year after transplantation using a pressure sensor/thermistor-tipped guidewire. Measurements were compared between consecutive patients who were on rapamycin for at least 3 months during the first year after transplantation (rapamycin group, n = 9) and a comparable group on mycophenolate mofetil (MMF) instead (MMF group, n = 18).At baseline, there was no significant difference in FFR, CFR, or IMR between the 2 groups. At 1 year, FFR declined significantly in the MMF group (0.87 +/- 0.06 to 0.82 +/- 0.06, P = .009) but did not change in the rapamycin group (0.91 +/- 0.05 to 0.89 +/- 0.04, P = .33). Coronary flow reserve and IMR did not change significantly in the MMF group (3.1 +/- 1.7 to 3.2 +/- 1.0, P = .76; and 27.5 +/- 18.1 to 19.1 +/- 7.6, P = .10, respectively) but improved significantly in the rapamycin group (2.3 +/- 0.8 to 3.8 +/- 1.4, P < .03; and 27.0 +/- 11.5 to 17.6 +/- 7.5, P < .03, respectively). Multivariate regression analysis revealed that rapamycin therapy was an independent predictor of CFR and FFR at 1 year after transplantation.Early after cardiac transplantation, rapamycin therapy is associated with improved coronary artery physiology involving both the epicardial vessel and the microvasculature.

    View details for DOI 10.1016/j.ahj.2008.02.004

    View details for PubMedID 18440337

  • 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


    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

  • The Porcine Restenosis Model Using Thermal Balloon Injury: Comparison with the Model by Coronary Stenting JOURNAL OF INVASIVE CARDIOLOGY Suzuki, Y., Lyons, J. K., Yeung, A. C., Ikeno, F. 2008; 20 (3): 142-146


    Percutaneous coronary intervention (PCI) continues to revolutionize the treatment of coronary atherosclerosis and technologic advances require a preclinical coronary stenosis model. The purpose of this study was to systematically evaluate a porcine restenosis model of thermal balloon injury compared to stent overstretching.To evaluate this injury model, 22 swine were utilized. For the induction of coronary stenoses, the thermal balloon-to-artery ratio was equal to the range of 1.2-1.3 and was placed at a desired location in the coronary arteries, inflated with 2 atm, and heated to 80 degrees C for 80 seconds. Quantitative coronary angiography was analyzed at baseline, immediately postprocedure, and 4 weeks at harvest. Quantitative coronary ultrasound analysis and histopathologic evaluation were also performed at 4 weeks postprocedure.A total of 54 coronary arteries (thermal balloon injury [Thermo]; n = 43, coronary stenting [Stent]; n = 11) from a total of 18 animals were analyzed for this study. At 4 weeks postprocedure, significantly greater coronary stenoses were observed in the Thermo Group versus the Stent Group (minimum lumen diameter: 1.00 % 0.63 mm vs. 1.58 % 0.44 mm; p = 0.009, % diameter stenosis [DS]: 66.2 +/- 21.6% vs. 48.1 +/- 11.4%; p = 0.02). There were significant linear correlations between the balloon-to-artery ratio, post %DS and %DS at 4 weeks (balloon-to-artery ratio; r = 0.538; p = 0.0012, post %DS; r = -0.744; p < 0.0001, respectively).This methodology may provide reproducible and consistent coronary stenoses. This model can be useful fnot only for the evaluation of medical devices, but also for technical training in PCI and development of coronary imaging technologies.

    View details for Web of Science ID 000207738600011

    View details for PubMedID 18316831

  • 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


    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

  • In vivo porcine model of reperfused myocardial infarction: In situ double staining to measure precise infarct area/area at risk CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Suzuki, Y., Lyons, J. K., Yeung, A. C., Ikeno, F. 2008; 71 (1): 100-107


    The aim of this study is to evaluate a catheter-based porcine model for reperfused myocardial infarction and investigate the appropriate location and duration of the occlusion.A balloon catheter was placed in the left descending coronary artery (LAD) in 78 swine, and used to occlude the LAD. To evaluate this model, left ventricular ejection fraction (LVEF), infarct size, incidence of ventricular fibrillation (VF), and mortality was compared among three groups: 60-min proximal LAD occlusion (60P), 60-min mid LAD occlusion (60M), and 30-min proximal LAD occlusion (30P).In 72 of the 78 pigs, the procedures were successfully completed. Both mortality and incidence of VF were highest in the 60P group (66.7% and 91.7%, respectively). Myocardial infarction was successfully induced in all 72 animals and in situ double-staining with Evans blue dye and 2,3,5-triphenyltetrazolium chloride was performed to delineate area at risk for ischemia and infarcted myocardium. There was no difference in infarct size, expressed as a percentage of the area at risk, between the 60P and 60M groups (49.5% +/- 3.9% vs. 45.4% +/- 13.3%, respectively). Serial changes in LVEF of the 60M group demonstrated that until 14 days after reperfusion, LVEF improved naturally over time (36.4% +/- 6.6% at 24 hr, and 47.3% +/- 10.1% at 14 days).This model and methodology could provide a reproducible and consistent infarct size. The current study demonstrated that 60-min mid LAD occlusion can be the most feasible to serve as a porcine reperfused myocardial infarction model.

    View details for DOI 10.1002/ccd.21329

    View details for Web of Science ID 000252139500016

    View details for PubMedID 17985383

  • 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


    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/

    View details for PubMedID 17998863

  • In vitro comparison of the biological effects of three transfection methods for magnetically labeling mouse embryonic stem cells with ferumoxides MAGNETIC RESONANCE IN MEDICINE Suzuki, Y., Zhang, S., Kundu, P., Yeung, A. C., Robbins, R. C., Yang, P. C. 2007; 57 (6): 1173-1179


    In vivo MRI of stem cells (SCs) is an emerging application to evaluate the role of cell therapy in restoring the injured myocardium. The high spatial and temporal resolution combined with iron-oxide-based intracellular labeling techniques will provide a sensitive, noninvasive, dual imaging modality for both cells and myocardium. In order to facilitate this novel imaging approach, much effort has been directed towards developing efficient transfection methods. While techniques utilizing poly-L-lysine (PLL), protamine sulfate (PS), and electroporation (ELP) have been proposed, the fundamental biological effects of these methods on mouse embryonic SCs (mESC) have not been investigated systematically. In this study a longitudinal in vitro evaluation of cellular viability, apoptosis, proliferation, and cardiac differentiation of magnetically labeled mESC was conducted. No significant difference was seen in these biological parameters among the three transfection methods. However, cardiac differentiation was most attenuated by ELP, and iron uptake was most effective by PS.

    View details for DOI 10.1002/mrm.21219

    View details for PubMedID 17534917

  • 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


    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

  • Arteriotomy closure device application following percutaneous coronary intervention may prevent bleeding complications in patients with acute myocardial infarction INTERNATIONAL JOURNAL OF CARDIOLOGY Ikeno, F., Sadoughi, M. A., Lyons, J. K., Shabari, F. R., Pourdehmobed, K., Hashemi, V., Emami, S., Kaneda, H., Yeung, A. C., Rezaee, M. 2007; 117 (1): 131-132


    The current study was performed to determine whether application of arteriotomy closure devices (ACDs) affect bleeding complications as compared to manual compression in patients with ST-elevated acute myocardial infarction (STEMI) who undergo primary or rescue percutaneous intervention (PCI). 314 consecutive cases of STEMI treated with PCI were retrospectively evaluated. Overall, 82.8% of patients received ACDs with total bleeding rate of 4.2% vs. 11.1% in patients who had manual compression, p=0.042. This difference in bleeding rates did not correlate with any clinical characteristic or utilization of GPIIb/IIIa inhibitors. Accordingly, ACDs can improve the acute results of PCI in STEMI patients.

    View details for DOI 10.1016/j.ijcard.2006.03.082

    View details for Web of Science ID 000245839200019

    View details for PubMedID 16935367

  • Interplay between systemic inflammation and markers of insulin resistance in cardiovascular prognosis after heart transplantation JOURNAL OF HEART AND LUNG TRANSPLANTATION Biadi, O., Potena, L., Fearon, W. F., Luikart, H. I., Yeung, A., Ferrara, R., Hunt, S. A., Mocarski, E. S., Valantine, H. A. 2007; 26 (4): 324-330


    Metabolic and immuno-inflammatory risk factors contribute to cardiac allograft vasculopathy (CAV) pathogenesis. Although systemic inflammation, as detected by C-reactive protein (CRP), predicts CAV development, the relationship between CRP and markers of metabolic abnormalities remains unexplored.CRP and the entire metabolic panel were evaluated in 98 consecutive heart transplant recipients at the time of annual coronary angiography, 5.8 years after transplant (range, 1-12 years). A ratio of triglycerides (TG) to high-density lipoproteins (HDL) of 3.0 or more was considered a marker of insulin resistance. CAV prevalence was defined by angiography, and subsequent prognosis was evaluated as incidence of major cardiac adverse events.CRP was higher in the 34 patients with angiographic CAV than in those without CAV (1.10 +/- 0.20 vs 0.50 +/- 0.05 mg/dl, p < 0.001). Patients with insulin resistance had higher CRP concentrations (p = 0.023) and higher CAV prevalence (p = 0.005). High CRP and a TG/HDL of 3.0 or more were independently associated with an increased likelihood of CAV (odds ratio, > or = 3.9; p = 0.02) and predicted an increased risk of major cardiac adverse events. The combination of high CRP and a TG/HDL of 3.0 or more identified a subgroup of patients having a 4-fold increased risk for CAV and a 3-fold increased risk for major cardiac adverse events compared with patients with low CRP and normal values for metabolic indicators.Both CRP and insulin resistance, as estimated by TG/HDL, appear to be strong, synergic risk factors for CAV and for major cardiac adverse events. These findings support the hypothesis that in heart transplant recipients, systemic inflammation may be an important mediator of graft vascular injury associated with metabolic syndrome.

    View details for DOI 10.1016/j.healun.2007.01.020

    View details for PubMedID 17403472

  • Mechanism of luminal gain with plaque excision in atherosclerotic coronary and peripheral arteries: assessment by histology and intravascular ultrasound. Journal of interventional cardiology Ikeno, F., Braden, G. A., Kaneda, H., Hongo, Y., Hinohara, T., Yeung, A. C., Simpson, J. B., Kandzari, D. E. 2007; 20 (2): 107-113


    Using intravascular ultrasound (IVUS) and histology, the purpose of this study was to evaluate the occurrence of arterial wall overstretch and Dotter effect following revascularization with a plaque excision (PE) catheter compared with balloon angioplasty.Previous studies have demonstrated the safety and feasibility of plaque excision for the treatment of de novo coronary and peripheral atherosclerotic disease. However, whether mechanical vessel dilatation related to catheter insertion contributes to gains in the final luminal diameter is uncertain.Treatment with PE was assessed in both a porcine model (6 lesions treated with balloon angioplasty or PE) using histology and in humans with IVUS. In the latter part of the study, IVUS study was performed before and immediately following PE in 21 patients with either coronary artery disease (N = 13) or femoral artery disease (N = 8). Ultrasound measures in the femoral artery group were then compared with a control group of atherosclerotic lesions treated with conventional angioplasty that was matched according to lesion location and vessel diameter.Among individuals with coronary and peripheral arterial lesions treated with PE, the relative increases in luminal area secondary to reductions in plaque volume were 89% and 83%, respectively, with minimal increase in vessel diameter. In contrast, balloon angioplasty was associated with significantly greater vessel expansion and less plaque volume reduction. Vessel dissection also tended to occur less frequently and to a lesser extent with PE.Improvement in luminal dimensions using PE is principally due to a reduction in plaque volume rather than mechanical vessel expansion. The potential to increase luminal area while minimizing arterial dissection and barotrauma merits further clinical study with this method of revascularization.

    View details for PubMedID 17391218

  • Novel stent system for accurate placement in aorto-ostial renal artery disease: preclinical study in porcine renal artery model. Cardiovascular revascularization medicine : including molecular interventions Suzuki, Y., Ikeno, F., Lyons, J. K., Koizumi, T., Yeung, A. C. 2007; 8 (2): 99-102


    Treatment of aorto-ostial renal artery stenosis has been associated with a lower procedural success and higher complication and restenosis rate, as compared to nonostial lesions. The design and delivery of currently available stent systems in ostial lesions can result in inaccurate stent positioning and placement leading to stent protrusion into the parent vessel lumen or geographic miss. A novel stent system (SquareOne Inc., Campbell, CA, USA) has been designed specifically for aorto-ostial lesions in the renal artery. This stent system aims to provide both tactile and visual confirmation of the ostium at the aorta, allow for improved accuracy during stent positioning and placement, provide complete scaffolding of the lesion at the aortic junction to the native vessel, and enable future vessel reaccess.Stents (n=12) were implanted in both renal arteries of six swine. For histology, two animals were euthanized immediately after stent implantation, and each two animals were then followed up at 2 and 4 weeks, respectively. Intravascular ultrasound (IVUS) studies were performed immediately after stent implantation and at follow-up.Proper stent positioning and implantation was obtained in all animals. Angiographic and IVUS assessments indicated no dissection or thrombus formation. Histology demonstrated good apposition and endothelialization of the stent strut surface.The unique flared shape of this novel ostial stent system allows for improved accuracy during stent positioning and placement, as well as complete apposition and coverage/scaffolding of the similarly-shaped luminal ostium. Future studies will determine if this novel stent system fulfills the unmet clinical need in aorto-ostial stenoses.

    View details for PubMedID 17574168

  • Changes in coronary arterial dimensions early after cardiac transplantation TRANSPLANTATION Fearon, W. F., Potena, L., Hirohata, A., Sakurai, R., Yamasaki, M., Luikart, H., Lee, J., Vana, M. L., Cooke, J. P., Mocarski, E. S., Yeung, A. C., Valantine, H. A. 2007; 83 (6): 700-705


    Significant changes in coronary artery structure, including intimal thickening and vessel remodeling, occur early after cardiac transplantation. The degree to which these changes compromise coronary lumen dimensions, and the clinical factors that affect these changes, remain controversial.Thirty-eight adult cardiac transplant recipients underwent coronary angiography and volumetric intravascular ultrasound (IVUS) evaluation of the left anterior descending artery within 8 weeks of transplantation and at 1 year. Clinical parameters including donor and recipient characteristics, rejection episodes, and serology were prospectively recorded. Two-dimensional IVUS measurements and vessel, lumen and plaque volume were calculated at both time points and compared. Multivariate regression analysis was performed to reveal clinical predictors of change in coronary dimensions.During the first year after transplantation, significant decreases in vessel size (negative remodeling) and lumen size were observed with significant increases in plaque burden based on IVUS analyses. Loss of lumen volume correlated significantly with the degree of negative remodeling (R=0.82, P<0.0001), but not with changes in plaque burden (R=0.08, P=0.64). Patients with the greatest increase in plaque volume had significantly less negative remodeling (R=0.53, P=0.0006). Transplant recipient cytomegalovirus (CMV) antibody seropositivity and lack of aggressive prophylaxis against CMV infection/reactivation were significant independent predictors of greater negative remodeling (P<0.01 and P=0.03, respectively) and greater lumen loss (P=0.02 and P=0.03, respectively).Negative remodeling is primarily responsible for coronary artery lumen loss during the first year after cardiac transplantation. CMV seropositivity and lack of aggressive CMV prophylaxis correlate with increased negative remodeling, resulting in greater lumen loss.

    View details for DOI 10.1097/

    View details for PubMedID 17414701

  • Ischemic heart disease in women: An appropriate time to discriminate REVIEWS IN CARDIOVASCULAR MEDICINE Tremmel, J. A., Yeung, A. C. 2007; 8 (2): 61-68


    Although cardiovascular mortality for men has been declining, the number of women dying from cardiovascular disease has slightly increased. Differences between women and men have been identified throughout the entire spectrum of ischemic heart disease, from risk factors to presentation and from diagnosis to treatment and outcomes. In the setting of an acute coronary syndrome or acute myocardial infarction, women are significantly more likely than men to report multiple non-chest pain symptoms, including dyspnea, nausea/vomiting, abdominal pain, back pain, neck pain, and jaw pain. Investigations into the pathophysiology of ischemic heart disease in women have broken away from the traditional thinking that coronary artery disease simply equals epicardial stenosis. In women, the new paradigm of coronary artery disease also focuses on diffuse atherosclerosis, endothelial dysfunction, and microvascular disease. Further research focusing on sex differences in cardiovascular disease is needed, but enough is currently known to offer a sex-based approach, which may ultimately lead to improved outcomes.

    View details for Web of Science ID 000247793600003

    View details for PubMedID 17603424

  • Cardiovascular MRI for stem cell therapy. Current cardiology reports Suzuki, Y., Yeung, A. C., Yang, P. C. 2007; 9 (1): 45-50


    Stem cell therapy may provide an alternative therapeutic option for severe congestive heart failure (CHF). Despite the promise generated by this novel approach, precise in vivo monitoring of the transplanted cells and of subsequent myocardial restoration remains a challenge. The development of a sensitive, noninvasive imaging technology to track stem cells while assessing cardiac function is critical to monitor therapeutic efficacy. In vivo cardiovascular MRI of stem cells is an emerging application to identify, localize, and monitor stem cells while simultaneously evaluating the restoration of the injured myocardium following stem cell therapy. Furthermore, advances in scanner technology, pulse sequence design, and associated hardware have resulted in real-time guidance of catheter-based intervention to deliver cells accurately to the regions of myocardial injury. These capabilities have positioned MRI as the primary comprehensive imaging modality to monitor cell therapy.

    View details for PubMedID 17362684

  • Novel stent and delivery systems for the treatment of bifurcation lesions: porcine coronary artery model. Cardiovascular revascularization medicine : including molecular interventions Ikeno, F., Buchbinder, M., Yeung, A. C. 2007; 8 (1): 38-42


    In percutaneous treatment of bifurcation coronary lesions, side-branch restenosis remains a significant limitation in current therapeutic approaches. Coronary stents with a side aperture and a sleeve may be clinically advantageous to maintain access to side branch, stabilize the side-branch orifice, and deliver the appropriate drug to the side-branch ostium.A novel stent system (PETAL stent; Advanced Stent Technologies, Pleasanton, CA), incorporating a side aperture with deployable struts, was compared within porcine coronary model to the prior stent version having only the side aperture (SLK-View stent). In six pigs, each stent was implanted either in the left anterior descending coronary artery or the left circumflex coronary artery with adjunctive kissing balloon dilatation. At 28-day follow-up, coronary angiography was performed.A total of six SLK-View stents and six PETAL stents were implanted in coronary arteries without any complication, and adjunctive kissing balloon dilatations were successful in all lesions. Quantitative coronary angiography (QCA) data at 28 days showed that PETAL stents exhibited superior QCA in mean diameter compared with SLK-View stents for side branch, inferring efficacy of PETAL ostial struts.AST-PETAL stent has the potential to be a new solution for treatment of bifurcation lesions. Antirestenosis drug elution should be considered with this successful platform.

    View details for PubMedID 17293267

  • The conversion in application of percutaneous coronary intervention following the introduction of drug eluting stents INTERNATIONAL JOURNAL OF CARDIOLOGY Ikeno, F., Shabari, F. R., Sadoughi, A., Lyons, J. K., Pourdehmobed, K., Hasherni, V., Ernarni, S., Kanada, H., Yeung, A. C., Rezaee, M. 2006; 113 (2): 279-280


    In order to determine the changes in the pattern of techniques applied during elective coronary intervention, data from 688 patients prior to Sirolimus. Drug-Eluting Stents (DES) approval was compared to 438 patients who underwent coronary intervention after DES approval. There was increased intervention to higher risk lesions, including smaller vessels and re-stenotic lesions after DES approval. Total number of stents per patient significantly decreased, despite longer stent length per patient or per lesion after DES approval. No significant difference was found in multivessel interventions.

    View details for DOI 10.1016/j.ijcard.2005.09.038

    View details for Web of Science ID 000242312500031

    View details for PubMedID 16318883

  • Successful removal of a paradoxical coronary embolus using an aspiration catheter NATURE CLINICAL PRACTICE CARDIOVASCULAR MEDICINE Wilson, A. M., Ardehali, R., Brinton, T. J., Yeung, A. C., Vagelos, R. 2006; 3 (11): 633-636


    A 28-year-old man presented at hospital with persistent pain in his chest and left arm, a paced rhythm on electrocardiography and elevated levels of cardiac enzymes. He was known to have patent foramen ovale and a dual-chamber pacemaker, which had been implanted following electrophysiological ablation to treat supraventricular tachycardia 3 years previously. The patient did not have a history of cardiovascular risk factors, recent travel, immobilization or clinical features of infection, and he was not taking any medication.Electrocardiography, cardiac enzyme studies, coronary angiography and transthoracic echocardiography.Acute myocardial infarction, paradoxical coronary embolus and patent foramen ovale.Coronary aspiration embolectomy and systemic anticoagulation.

    View details for DOI 10.1038/ncpcardio0681

    View details for Web of Science ID 000241556000012

    View details for PubMedID 17063168

  • Cutting balloon inflation for drug-eluting stent underexpansion due to unrecognized coronary arterial calcification. Cardiovascular revascularization medicine : including molecular interventions Wilson, A., Ardehali, R., Brinton, T. J., Yeung, A. C., Lee, D. P. 2006; 7 (3): 185-188


    Unrecognized calcification is a cause of stent underexpansion which significantly increases the subsequent risks of restenosis and/or stent thrombosis. We describe the use of cutting balloon inflation within the implanted stent which overcame calcific restraint unresponsive to high pressure inflations with non-compliant balloons.

    View details for PubMedID 16945827

  • 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


    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


    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

  • Invasive assessment of the coronary microcirculation - Superior reproducibility and less hemodynamic dependence of index of microcirculatory resistance compared with coronary flow reserve CIRCULATION Ng, M. K., Yeung, A. C., Fearon, W. F. 2006; 113 (17): 2054-2061


    A simple, reproducible invasive method for assessing the coronary microcirculation is lacking. A novel index of microcirculatory resistance (IMR) has been shown in animals to correlate with true microvascular resistance and, unlike coronary flow reserve (CFR), to be independent of the epicardial artery. We sought to compare the reproducibility and hemodynamic dependence of IMR with CFR in humans.Using a pressure-temperature sensor-tipped coronary wire, thermodilution-derived CFR and IMR were measured, along with fractional flow reserve (FFR), in 15 coronary arteries (15 patients) under the following hemodynamic conditions: (1) twice at baseline; (2) during right ventricular pacing at 110 bpm; (3) during intravenous infusion of nitroprusside; and (4) during intravenous dobutamine infusion. Mean CFR did not change during baseline measurements or during nitroprusside infusion but decreased during pacing (from 3.1+/-1.1 at baseline to 2.3+/-1.2 during pacing, P<0.05) and during dobutamine infusion (from 3.0+/-1.0 to 1.7+/-0.6 with dobutamine, P<0.0001). By comparison, mean values for IMR and FFR remained similar throughout all hemodynamic conditions. The mean coefficient of variation between 2 baseline measurements was significantly lower for IMR (6.9+/-6.5%) and FFR (1.6+/-1.6%) than for CFR (18.6+/-9.6%; P<0.01). Mean correlation between baseline measurements and each hemodynamic intervention was superior for IMR (r=0.90+/-0.05) and FFR (r=0.86+/-0.12) compared with CFR (r=0.70+/-0.05; P<0.05).Compared with CFR, IMR provides a more reproducible assessment of the microcirculation, which is independent of hemodynamic perturbations. Simultaneous measurement of FFR and IMR may provide a comprehensive and specific assessment of coronary physiology at both epicardial and microvascular levels, respectively.

    View details for DOI 10.1161/CIRCULATIONAHA.105.603522

    View details for PubMedID 16636168

  • Atherosclerosis. The role of C-reactive protein. Reviews in cardiovascular medicine Yeung, A. C. 2006; 7 (2): 106-107

    View details for PubMedID 16915129

  • Drug-eluting stent strut distribution: a comparison between Cypher and Taxus by optical coherence tomography. journal of invasive cardiology Suzuki, Y., Ikeno, F., Yeung, A. C. 2006; 18 (3): 111-114


    The purpose of this study is to compare the stent strut distribution between Cypher and Taxus stents by using optical coherence tomography (OCT) in a phantom model.Previous studies demonstrated that the distribution of stent struts might affect amount of neointima proliferation after drug-eluting stent (DES) implantation.We developed experimental models made of silicon tubing angled at 0 degrees, 30 degrees, and 60 degrees. Testing was performed on two types of stents, Cypher and Taxus, which represent current FDA-approved DES. After deployment, OCT was performed and measurements were obtained as follows at two cross sections; maximum and minimum numbers of visualized stent strut sites: (1) number of visualized stent struts; (2) angle between stent struts (interstrut angle); (3) mean interstrut angle; (4) the delta mean angle was defined as the margin between each value of the interstrut angle and mean interstrut angle.In the Cypher stent, both the interstrut angle and the delta mean angle were significantly better than all other stents evaluated (all comparisons between stents; p < 0.05, respectively).The present study found that the stent strut distribution of two stents, Cypher and Taxus, which represent current FDA-approved drug-eluting systems, were significantly different and suggested that the Cypher stent maintained a more regular strut distribution despite expansion in various anatomical situations, and therefore would provide the most regular and predictable drug delivery.

    View details for PubMedID 16598109

  • 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


    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

  • Left main coronary artery disease: is CABG still the gold standard? Reviews in cardiovascular medicine Ng, M. K., Yeung, A. C. 2005; 6 (4): 187-193


    Severe stenosis of the left main coronary artery (LMCA) is a coronary artery-disease manifestation of critical prognostic importance. As a consequence of the survival advantage conferred by coronary artery bypass grafting (CABG) over medical therapy, lesions in the LMCA have been considered a standard indication for CABG for nearly 3 decades. Initial attempts to treat LMCA disease percutaneously by balloon angioplasty resulted in poor clinical outcomes, leading many to regard significant LMCA disease as a contraindication for percutaneous coronary intervention (PCI). However, the development and refinement of coronary stenting over the last 15 years, followed by the recent introduction of drug-eluting stents, has fueled renewed interest in percutaneous treatment of LMCA disease. Outcomes of recent studies using sirolimus- and/or paclitaxel-eluting stents for treatment of LMCA disease have yielded rates of in-hospital and 1-year mortality that compare favorably with those of surgery. This article will review the natural history of LMCA disease, the outcomes of CABG for LMCA disease, and the history and recent developments regarding PCI for LMCA disease.

    View details for PubMedID 16379014

  • 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


    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

  • Experience of percutaneous coronary intervention in the management of pediatric cardiac allograft vasculopathy JOURNAL OF HEART AND LUNG TRANSPLANTATION Tham, E. B., Yeung, A. C., Cheng, C. W., Bernstein, D., Chin, C., Feinstein, J. A. 2005; 24 (6): 769-773


    In a retrospective study, we examined the procedural success rate and the short-, intermediate-, and long-term outcomes of coronary interventional procedures in children with cardiac allograft vasculopathy. Seven patients underwent 13 interventional procedures: balloon angioplasty alone (n = 3), angioplasty with stenting (n = 9), or angioplasty with brachytherapy (n = 1), with procedural success in all. Two major complications (cardiac arrest) and a single death occurred in the immediate postprocedural period. Five (83%) of the remaining 6 patients developed moderate to severe restenosis, diffuse disease, or progressive vasculopathy; 3 have been retransplanted, 1 died from progressive cardiac allograft vasculopathy, and 1 is awaiting retransplantation, 40 months after the procedure.

    View details for DOI 10.1016/j.healun.2004.04.009

    View details for PubMedID 15949739

  • Risk factors for the development of retroperitoneal hematoma after percutaneous coronary intervention in the era of glycoprotein IIb/IIIa inhibitors and vascular closure devices JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Farouque, H. M., Tremmel, J. A., Shabari, F. R., Aggarwal, M., Fearon, W. F., Ng, M. K., Rezaee, M., Yeung, A. C., Lee, D. P. 2005; 45 (3): 363-368


    We sought to determine the incidence, clinical features, and risk factors for retroperitoneal hematoma (RPH) after percutaneous coronary intervention (PCI).Little is known about the clinical features, outcomes, and determinants of this serious complication in the contemporary era of PCI.A retrospective analysis yielded 26 cases of RPH out of 3,508 consecutive patients undergoing PCI between January 2000 and January 2004. Cases were compared with a randomly selected sample of 50 control subjects without RPH.The incidence of RPH was 0.74%. Features of RPH included abdominal pain (42%), groin pain (46%), back pain (23%), diaphoresis (58%), bradycardia (31%), and hypotension (92%). The mean systolic blood pressure nadir was 75 mm Hg. The hematocrit dropped by 11.5 +/- 5.1 points from baseline in RPH patients, as compared with 2.3 +/- 3.3 points in controls (p < 0.0001). The mean hospital stay was longer in RPH patients (2.9 +/- 3.8 days vs. 1.7 +/- 1.5 days, p = 0.06). The following variables were found to be independent predictors of RPH: female gender (odds ratio [OR] 5.4, p = 0.005), low body surface area (BSA <1.73 m(2); OR 7.1, p = 0.008), and higher femoral artery puncture (OR 5.3, p = 0.013). There was no association between RPH and arterial sheath size, use of glycoprotein IIb/IIIa inhibitors, or deployment of a vascular closure device.Female gender, low BSA, and higher femoral artery puncture are significant risk factors for RPH. Awareness of the determinants and clinical features of RPH may aid in prevention, early recognition, and prompt treatment.

    View details for DOI 10.1016/j.jacc.2004.10.042

    View details for PubMedID 15680713

  • "Tako-tsubo-like left ventricular dysfunction": a clinical entity mimicking acute myocardial infarction with a favorable prognosis. American journal of geriatric cardiology Farouque, H. M., Kaltenbach, T., Ako, J., Tremmel, J. A., Fearon, W. F., Yeung, A. C., Vagelos, R. H. 2004; 13 (6): 323-326


    An emotionally-distressed, elderly Caucasian woman presented with chest pain and hypertension. Electrocardiogram showed inferior ST-segment elevation, and an urgent cardiac catheterization was performed. Coronary angiography revealed normal appearing coronary arteries; however, left ventriculography showed extensive left ventricular apical akinesis. The patient had a mild rise in cardiac enzyme levels indicative of myocardial injury. She was discharged after an uncomplicated in-hospital course. One month later, the left ventricular wall motion abnormality had improved. In this report, the authors discuss this compilation of findings known as tako-tsubo-like left ventricular dysfunction.

    View details for PubMedID 15538070

  • Initial experience with the novel 6 Fr-compatible system for debulking De Novo coronary arterial lesions CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Ikeno, F., Abizaid, A., Suzuki, T., Rezaee, M., Patterson, G. R., Yeung, A. C., Virmani, R., Sousa, J. E., Carter, A. J. 2004; 62 (3): 308-317


    The purpose of this study was to determine the efficacy of a novel system for debulking of de novo native coronary arterial lesions. The Helixciser De Novo system is a novel 6 Fr-compatible catheter with a cutter encased in a slotted-orifice housing to excise atheromatous plaque. The cutter rotates at 15,000 rpm, debulking the plaque as it tracks through the lesion over a straight wire or a self-expanding nitinol helical-shaped wire. The tissue is aspirated via an Archimedes screw pump to vacuum collection chamber. The device was evaluated in a porcine toxic coronary stent model of chronic occlusion and in five patients with focal de novo native coronary arterial lesions. Procedural variables along with outcomes were reviewed. Quantitative angiography (QCA) and volumetric intravascular ultrasound (IVUS) analysis were performed. In a porcine model of chronic occlusion, QCA demonstrated pretreatment minimal lumen diameter (MLD) increased from 0.77 +/- 0.59 to 1.88 +/- 0.25 mm postdebulking. IVUS analysis demonstrated pretreatment lumen volume (LV) increased from 15.8 +/- 22.2 to 46.4 +/- 28.9 mm(3) postdebulking. In human clinical feasibility cases, QCA demonstrated pretreatment MLD increased from 0.96 +/- 0.40 to 2.04 +/- 0.19 mm postdebulking. IVUS analysis demonstrated pretreatment LV increased from 38.40 +/- 12.78 to 52.05 +/- 15.68 mm(3) postdebulking. Preliminary results document the feasibility of Helixcision De Novo for treatment of focal de novo native coronary arterial lesions. Quantitative angiographic and IVUS analysis indicate that this system can effectively debulk plaque from selected noncalcified atherosclerotic lesions and thus may represent an alternative treatment strategy for coronary artery disease.

    View details for DOI 10.1002/ccd.20085

    View details for Web of Science ID 000222407900008

    View details for PubMedID 15224296

  • 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


    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

  • 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


    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

  • Identification and treatment of vulnerable plaque. Reviews in cardiovascular medicine Nakamura, M., Lee, D. P., Yeung, A. C. 2004; 5: S22-33


    It is now well recognized that the rupture of vulnerable plaque, which consists of an atheromatous plaque core covered by a thin fibrous cap with ongoing inflammation, is a major cause of thrombus formation leading to the development of acute coronary syndrome. Several diagnostic techniques, including vascular imaging and serologic markers, are clinically available or currently under investigation for the detection of vulnerable plaque. A combination of several diagnostic modalities might allow effective screening of individuals at high risk for future cardiovascular events. Plaque stabilization with pharmacologic interventions--statins, beta-blockers, and angiotensin-converting enzyme inhibitors--might effectively prevent the development of acute coronary syndromes caused by plaque disruption.

    View details for PubMedID 15184831

  • Expanded use of distal embolic protection devices in primary angioplasty. Reviews in cardiovascular medicine Yeung, A. C. 2004; 5 (1): 65-66

    View details for PubMedID 15085793

  • 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


    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


    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

  • Phase I drug and light dose-escalation trial of motexafin lutetium and far red light activation (phototherapy) in subjects with coronary artery disease undergoing percutaneous coronary intervention and stent deployment - Procedural and long-term results CIRCULATION Kereiakes, D. J., Szyniszewski, A. M., Wahr, D., Herrmann, H. C., Simon, D. I., Rogers, C., Kramer, P., Shear, W., Yeung, A. C., Shunk, K. A., Chou, T. M., Popma, J., Fitzgerald, P., Carroll, T. E., Forer, D., Adelman, D. C. 2003; 108 (11): 1310-1315


    Motexafin lutetium (MLu; Antrin) is a photosensitizer that is taken up by atherosclerotic plaque and concentrated within macrophages and vascular smooth muscle cells. After photoactivation with far red light, MLu facilitates production of cytotoxic oxygen radicals that mediate apoptosis. We assessed the safety and tolerability of phototherapy (PT) with MLu in patients undergoing percutaneous coronary intervention with stent deployment.An open-label, phase I, drug and light dose-escalation clinical trial of MLu PT enrolled 80 patients undergoing de novo coronary stent deployment. MLu was administered to 79 patients by intravenous infusion 18 to 24 hours before procedure, and photoactivation was performed after balloon predilatation and before stent deployment. Clinical evaluation, serial quantitative angiography, and intravascular ultrasound were performed periprocedurally and at 6 months follow-up. MLu PT was well tolerated without serious dose-limiting toxicities, and side effects (paresthesia and rash) were minor. No adverse angiographic outcomes were attributed to phototherapy.This study demonstrates that coronary MLu PT seems safe, and the maximum well-tolerated MLu dose and range of tolerated light doses were identified. These data can be used in phase II efficacy trials of MLu PT for the treatment of coronary atherosclerosis or vulnerable plaque.

    View details for DOI 10.1161/01.CIR.0000087602.91755.19

    View details for Web of Science ID 000185328800008

    View details for PubMedID 12939212

  • Segmental occlusion of the anterior intraventricular vein significantly improves regional delivery after high-pressure retroperfusion 15th Annual Transcatheter Cardiovascular Therapeutics Symposium Gnanashanmugam, S., Wei, K., Price, E. T., Ikeno, F., Lyons, J. K., Yeung, A. C., Yock, P. G., Rezaee, M. EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2003: 105L–105L
  • 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


    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


    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

  • Flow-responsive remodeling after angioplasty is enhanced by high cholesterol diet. Prevention with pyrrolidine dithiocarbamate ATHEROSCLEROSIS Ward, M. R., Tsao, P. S., Herity, N. A., Cooke, J. P., Yeung, A. C. 2003; 168 (2): 333-341


    We examined the effects of high cholesterol diet and pyrrolidine dithiocarbamate (PDTC) on flow-dependent remodeling after angioplasty. After right common carotid balloon-injury, the right external carotid (low flow) or left common carotid artery were ligated (high flow) in rabbits fed normal diet, 1% cholesterol diet without or with the antioxidant PDTC for 7 days pre- and 7-28 days post-injury. Angiographic lumen diameter was significantly greater at 28 days in high flow than low flow normal diet animals, attributable on perfusion-fixed vessel morphometry to altered remodeling (area within the external elastic lamina: high flow 1.85+/-0.24 vs. low flow 1.31+/-0.04 mm(2), P<0.05) rather than differences in neointima formation or vessel tone. In animals on 1% cholesterol diet high flow remodeling was significantly enhanced (area within the external elastic lamina 3.13+/-0.17 mm(2), P<0.05 vs. high flow normal diet) but low flow inward remodeling was similar (area within the external elastic lamina 1.29+/-0.07 mm(2)). Mean Doppler flow velocities (initial/post-ligation/28 day follow-up, cm/s) had almost normalized in normal diet animals (high flow 30/49/35, low flow 32/9/26) but showed overcompensation in 1% cholesterol diet animals (high flow 32/49/22, low flow 30/11/25). PDTC therapy markedly attenuated remodeling (area within the external elastic lamina: high flow 2.20+/-0.18, and low flow 2.00+/-0.11 both P<0.05 vs. 1% cholesterol diet alone) and flow velocities only partially normalized (high flow 26/42/34, low flow 27/7/16). We conclude that hypercholesterolemia enhances and PDTC attenuates flow-dependent remodeling after angioplasty.

    View details for DOI 10.1016/S0021-9150(03)00103-5

    View details for Web of Science ID 000183784900016

    View details for PubMedID 12801617

  • 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


    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

  • Cost-effectiveness of measuring fractional flow reserve to guide coronary interventions AMERICAN HEART JOURNAL Fearon, W. F., Yeung, A. C., Lee, D. P., Yock, P. G., Heidenreich, P. A. 2003; 145 (5): 882-887


    Most patients come to the catheterization laboratory without prior functional tests, which makes the cost-effective treatment of patients with intermediate coronary lesions a practical challenge.We developed a decision model to compare the long-term costs and benefits of 3 strategies for treating patients with an intermediate coronary lesion and no prior functional study: 1) deferring the decision for percutaneous coronary intervention (PCI) to obtain a nuclear stress imaging study (NUC strategy); 2) measuring fractional flow reserve (FFR) at the time of angiography to help guide the decision for PCI (FFR strategy); and 3) stenting all intermediate lesions (STENT strategy). On the basis of the literature, we estimated that 40% of intermediate lesions would produce ischemia, 70% of patients treated with PCI and 30% of patients treated medically would be free of angina after 4 years, and the quality-of-life adjustment for living with angina was 0.9 (1.0 = perfect health). We estimated the cost of FFR to be 761 dollars, the cost of nuclear stress imaging to be 1093 dollars, and the cost of medical treatment for angina to be 1775 dollars per year. The extra cost of splitting the angiogram and PCI as dictated by the NUC strategy was 3886 dollars by use of hospital cost-accounting data. Sensitivity and threshold analyses were performed to determine which variables affected our results.The FFR strategy saved 1795 dollars per patient compared with the NUC strategy and 3830 dollars compared with the STENT strategy. Quality-adjusted life expectancy was similar among the 3 strategies (NUC-FFR = 0.8 quality-adjusted days, FFR-STENT = 6 quality-adjusted life days). Compared with the FFR strategy, the NUC strategy was expensive (>800,000 dollars per quality-adjusted life year gained). Both screening strategies were superior to (less cost, better outcomes) the STENT strategy. Sensitivity analysis indicated that the NUC strategy would only become attractive (<50,000 dollars/quality-adjusted life years compared with FFR) if the specificity of nuclear stress imaging was >25% better than FFR. Our results were not altered significantly by changing the other assumptions.In patients with an intermediate coronary lesion and no prior functional study, measuring FFR to guide the decision to perform PCI may lead to significant cost savings compared with performing nuclear stress imaging or with simply stenting lesions in all patients.

    View details for DOI 10.1016/S0002-8703(03)00072-3

    View details for PubMedID 12766748

  • Stent-based immunosuppressive therapies for the prevention of restenosis. Cardiovascular radiation medicine Aggarwal, M., Tsao, P. S., Yeung, A., Carter, A. J. 2003; 4 (2): 98-107

    View details for PubMedID 14581091

  • Adjunctive platelet glycoprotein IIb/IIIa receptor inhibition with tirofiban before primary Angioplasty improves angiographic outcomes - Results of the TIrofiban given in the emergency room before primary angioplasty (TIGER-PA) pilot trial CIRCULATION Lee, D. P., Herity, N. A., Hiatt, B. L., Fearon, W. F., Rezaee, M., Carter, A. J., Huston, M., Schreiber, D., DiBattiste, P. M., Yeung, A. C. 2003; 107 (11): 1497-1501


    Previous work has suggested that platelet glycoprotein IIb/IIIa receptor blockade may confer benefit in the treatment of acute myocardial infarction. The TIGER-PA pilot trial was a single-center randomized study to evaluate the safety, feasibility, and utility of early tirofiban administration before planned primary angioplasty in patients presenting with acute myocardial infarction.A total of 100 patients presenting with acute myocardial infarction were randomized to either early administration of tirofiban in the emergency room or later administration in the catheterization laboratory. The primary outcome measures were initial TIMI grade flow, corrected TIMI frame counts, and TIMI grade myocardial perfusion ("blush"). Thirty-day major adverse cardiac events were also assessed. Angiographic outcomes demonstrate a significant improvement in initial TIMI grade flow, corrected TIMI frame counts, and TIMI grade myocardial perfusion when patients are given tirofiban in the emergency room before primary angioplasty. The rate of 30-day major adverse cardiac events suggests that early administration may be beneficial.This pilot study suggests that early administration of tirofiban improves angiographic outcomes and is safe and feasible in patients undergoing primary angioplasty for acute myocardial infarction.

    View details for DOI 10.1161/01.CIR.0000056120.00513.7A

    View details for PubMedID 12654606

  • Evaluating intermediate coronary lesions in the cardiac catheterization laboratory. Reviews in cardiovascular medicine Fearon, W. F., Yeung, A. C. 2003; 4 (1): 1-7


    Angiography is notoriously poor at distinguishing ischemia-producing from non-ischemia-producing intermediate coronary lesions. Here, three invasive modalities for evaluating the physiologic significance of moderate coronary stenoses are reviewed: Doppler wire-derived measurement of coronary flow reserve (CFR), coronary pressure wire-derived fractional flow reserve (FFR), and intravascular ultrasound (IVUS) imaging. Studies investigating the correlation between each of these modalities and various noninvasive tests (eg, nuclear perfusion imaging or stress echocardiography) are discussed. Each of these invasive modalities has its limitations: CFR is limited by its dependence on heart rate and blood pressure, calling into question its reproducibility; both FFR and CFR are limited by their reliance upon achieving maximal hyperemia; and IVUS is limited by the fact that it provides anatomic information only. Ultimately, FFR appears to be the ideal method for interrogating intermediate coronary lesions.

    View details for PubMedID 12684598

  • 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


    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

  • 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

  • Statin therapy - Beyond cholesterol lowering and antiinflammatory effects CIRCULATION Yeung, A. C., Tsao, P. 2002; 105 (25): 2937-2938
  • A successful strategy to improve door-to-balloon times in acute myocardial infarction: a single center experience. Critical pathways in cardiology Hiatt, B. L., Lee, D. P., Yeung, A. C. 2002; 1 (2): 103-106

    View details for PubMedID 18340293

  • Critical role of B cells in the development of T cell tolerance to aeroallergens INTERNATIONAL IMMUNOLOGY Tsitoura, D. C., Yeung, V. P., DeKruyff, R. H., Umetsu, D. T. 2002; 14 (6): 659-667


    Respiratory exposure to allergen induces the development of allergen-specific CD4(+) T cell tolerance that effectively protects against the development of allergic-sensitization and T(h)2-biased immunity. The establishment of T cell unresponsiveness to aeroallergens is an active process preceded by a transient phase of T cell activation that requires T cell co-stimulation and is critically influenced by the antigen-presenting cell type. In this study we examined the role of B cells in the development of respiratory tolerance following intranasal (i.n.) exposure to a prototypic protein antigen. We found that respiratory exposure of BCR-transgenic (Tg) mice to minute quantities of cognate antigen effectively induced T cell unresponsiveness, indicating that antigen presentation by antigen-specific B cells greatly enhanced the development of respiratory tolerance. In contrast, respiratory T cell unresponsiveness could not be induced in B cell-deficient JHD mice exposed to i.n. antigen, although T cell tolerance developed in JHD mice reconstituted with B cells, suggesting that B cells are required for the induction of respiratory T cell tolerance. Respiratory exposure of BCR-Tg mice to cognate antigen induced activation of antigen-specific T cells and partial activation of antigen-specific B cells, as demonstrated by enhanced expression by B cells of class II MHC and B7 molecules but lack of antibody secretion. Our data indicate that B cells critically influence the immune response to inhaled allergens and are required for the development of allergen-specific T cell unresponsiveness induced by respiratory allergen.

    View details for Web of Science ID 000175912100013

    View details for PubMedID 12039917

  • Acute and long-term safety of pressurized myocardial transvenous delivery: Confirmation by biochemical, echocardiographic, and histologic parameters Herity, N. A., Hiatt, B. L., Fearon, W. F., Suzuki, T., McEneaney, D. J., Berry, G., Yeung, A. C., Carter, A. J., Fitzgerald, P. J., Yock, P. G. ELSEVIER SCIENCE INC. 2002: 10A
  • A novel inhibitor of protein kinase-C as a therapeutic for ischemic reperfusion injury in acute coronary syndromes Lee, F., Inagaki, K., Chen, L., Bailey, L., Ikeno, F., Lyons, J., Bouley, D., Yock, P., Carter, A., Yeung, A., Mochly-Rosen, D. ELSEVIER SCIENCE INC. 2002: 445A–445A
  • Drug-eluting stents for the prevention of restenosis: In quest for the holy grail CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Hiatt, B. L., Ikeno, F., Yeung, A. C., Carter, A. J. 2002; 55 (3): 409-417

    View details for DOI 10.1002/ccd.10161

    View details for Web of Science ID 000174110000027

    View details for PubMedID 11870953

  • 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


    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

  • Folate treatment to prevent nitrate tolerance. Reviews in cardiovascular medicine Yeung, A. C. 2002; 3 (1): 62-63

    View details for PubMedID 12439353

  • 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


    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

  • Prevention of distal embolization during coronary angioplasty in saphenous vein grafts and native vessels using porous filter protection CIRCULATION Grube, E., Gerckens, U., Yeung, A. C., Rowold, S., Kirchhof, N., Sedgewick, J., Yadav, J. S., Stertzer, S. 2001; 104 (20): 2436-2441


    Although distal embolization and the "no-reflow" phenomenon are well described in saphenous vein graft (SVG) interventions, the frequency, magnitude, and characterization of embolized debris have not been evaluated in routine coronary interventions. A unique embolus protection device described herein provides a means of containing and retrieving plaque material dislodged during percutaneous coronary interventions. This report details the first clinical experience of the effectiveness and safety of an emboli protection system in 11 SVG lesions and 15 native coronary artery lesions.The AngioGuard Emboli Capture Guidewire (Cordis) consists of a PTCA wire with an expandable filter at the distal tip. The porous membrane permits normal distal blood flow, while trapping potential emboli by filtration. After crossing the lesion, the filter is expanded, and routine angioplasty is performed over the same wire. Emboli retrieval is achieved by collapsing the filter and retracting the emboli capture wire (ECW). In 26 patients, standard angioplasty was performed over the ECW; 20 of these 26 patients received a stent. Collected debris was sent for histopathological analysis. Plaque debris was retrieved after native coronary and SVG interventions in all cases. The ECW was positioned and retrieved without complications. No major adverse events occurred. Myocardial infarctions and no-reflow were not observed.The embolization of plaque fragments frequently occurs during coronary and SVG intervention. Distal embolization leading to microvascular obstruction and no-reflow could be successfully minimized by using the ECW.

    View details for Web of Science ID 000172260600020

    View details for PubMedID 11705821

  • 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


    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

  • The drug-eluting stent: is it the Holy Grail? Reviews in cardiovascular medicine Hiatt, B. L., Carter, A. J., Yeung, A. C. 2001; 2 (4): 190-196


    Although the restenosis rate of coronary stenting is generally 10% to 20%, it can go as high as 60% in patients with diabetes or complex lesions. Currently, the only effective treatment for restenosis is brachytherapy. Drug-eluting stents may be the way to prevent restenosis that cardiologists have been seeking: the drug-coated stents are simple to use and help prevent negative remodeling and the intimal hyperplasia caused by stenting. In studies comparing sirolimus-coated and bare-metal stents, the sirolimus-coated stents resulted in less smooth muscle cell colonization, minimal intimal hyperplasia, and no edge effect; moreover, no adverse clinical events were reported. Currently ongoing, multicenter clinical trials of drug-eluting stents may soon come up with the answers that cardiologists have been hoping for.

    View details for PubMedID 12439368

  • Stent-based delivery of sirolimus reduces neointimal formation in a porcine coronary model CIRCULATION Suzuki, T., Kopia, G., Hayashi, S., Bailey, L. R., Llanos, G., Wilensky, R., Klugherz, B. D., Papandreou, G., Narayan, P., Leon, M. B., Yeung, A. C., Tio, F., Tsao, P. S., Falotico, R., Carter, A. J. 2001; 104 (10): 1188-1193


    The purpose of this study was to determine the efficacy of stent-based delivery of sirolimus (SRL) alone or in combination with dexamethasone (DEX) to reduce in-stent neointimal hyperplasia. SRL is a potent immunosuppressive agent that inhibits SMC proliferation by blocking cell cycle progression.Stents were coated with a nonerodable polymer containing 185 microgram SRL, 350 microgram DEX, or 185 microgram SRL and 350 microgram DEX. Polymer biocompatibility studies in the porcine and canine models showed acceptable tissue response at 60 days. Forty-seven stents (metal, n=13; SRL, n=13; DEX, n=13; SRL and DEX, n=8) were implanted in the coronary arteries of 16 pigs. The tissue level of SRL was 97+/-13 ng/artery, with a stent content of 71+/-10 microgram at 3 days. At 7 days, proliferating cell nuclear antigen and retinoblastoma protein expression were reduced 60% and 50%, respectively, by the SRL stents. After 28 days, the mean neointimal area was 2.47+/-1.04 mm(2) for the SRL alone and 2.42+/-1.04 mm(2) for the combination of SRL and DEX compared with the metal (5.06+/-1.88 mm(2), P<0.0001) or DEX-coated stents (4.31+/-3.21 mm(2), P<0.001), resulting in a 50% reduction of percent in-stent stenosis.Stent-based delivery of SRL via a nonerodable polymer matrix is feasible and effectively reduces in-stent neointimal hyperplasia by inhibiting cellular proliferation.

    View details for Web of Science ID 000170922100022

    View details for PubMedID 11535578

  • Mild hyperhomocysteinemia is not associated with cardiac allograft coronary disease CLINICAL TRANSPLANTATION Giannetti, N., Herity, N. A., Alimollah, A., Gao, S. Z., Schroeder, J. S., Yeung, A. C., Hunt, S. A., Valantine, H. A. 2001; 15 (4): 247-252


    Hyperhomocysteinemia is an independent risk factor for coronary disease and elevated plasma homocysteine levels have been documented in heart transplant recipients. The aim of this study was to test the hypothesis that homocysteine levels are associated with presence or absence of transplant coronary artery disease.Forty-three non-smoking adults were recruited, all of whom had received a heart transplant between 2 and 7 yr previously. All 43 had blood drawn for fasting homocysteine level on the day of presentation. All patients had undergone diagnostic coronary angiography within the past 6 months.For all patients, the average fasting plasma homocysteine level was 17.0+/-SD 6.6 micromol/L with a range from 6.0 to 36.9 micromol/L. Twenty-six patients (60%) had fasting plasma homocysteine levels above 15.0 micromol/L. On the basis of arteriography, patients were categorized as those with angiographically normal (n=22) or abnormal (n=21) coronary arteries. There was no difference in the mean plasma homocysteine level comparing patients with angiographically normal (17.2+/-SD 7.0 micromol/L) to those with abnormal (16.8+/-SD 6.2 micromol/L) coronary arteries. Plasma homocysteine levels increased with increasing plasma creatinine levels (r=0.63, p<0.0001) and with decreasing vitamin B6 levels (r=-0.56, p<0.0001).Mild hyperhomocysteinemia is a consistent finding among heart transplant recipients. This finding was not associated with transplant coronary artery disease in our patients. The combination of renal dysfunction and vitamin B6 deficiency may explain the unusual prevalence of hyperhomocysteinemia in heart transplant recipients.

    View details for Web of Science ID 000170338600005

    View details for PubMedID 11683818

  • The topography of intimal thickening and associated remodeling pattern of early transplant coronary disease: Influence of pre-existent donor atherosclerosis JOURNAL OF HEART AND LUNG TRANSPLANTATION Wong, C. K., Yeung, A. C. 2001; 20 (8): 858-864


    With native coronary disease, intimal plaque initially accumulates at focal areas in the artery, often accompanied by compensatory vessel enlargement. With transplant coronary disease, the topography of intimal thickening and associated remodeling pattern are less studied.We studied 72 prospectively recruited transplant patients with serial intravascular ultrasound using 4.3F catheters at baseline and at 1-year follow up. We considered 175 ultrasound-recorded segments (mean, 2.4 +/- 1.1 segments per patient) exactly matched on the serial studies by both angiographic criteria and ultrasound criteria, using arterial and venous branch points, pericardium, and sinuses as anatomic landmarks.Eighty-eight segments had no donor disease, and 87 had donor disease (80 eccentric and 7 concentric intimal thickening). Progressive intimal thickening occurred in 48 segments without (55%) and 43 segments with donor disease (48%, p = NS). Thickening from segments without donor disease was mainly eccentric (81%). Thickening from segments with donor eccentric plaque was also mainly eccentric (67%, p = NS compared with segments without donor disease), with further thickening superimposed on the original plaque. Concentric intimal thickening was uncommon. Of the 58 patients who had >1 segment matched, intimal changes were discordant in 34 (59%), with progression in some and lack of progression in other segments. Total vessel area change correlated with intimal area change (r = 0.37 with a slope of 0.79, p < 0.001), including segments with (r = 0.39; slope, 0.69) and segments without (r = 0.37; slope, 1.16) donor disease.The intimal thickening of early transplant coronary disease is mainly eccentric and often discordant within each individual patient. Donor eccentric plaque often serves as a nidus for further intimal growth. The topography of intimal thickening in transplant coronary disease resembles that of native coronary disease, but the presence of a pre-existent donor plaque may impede compensatory remodeling as further intimal thickening occurs after transplantation.

    View details for Web of Science ID 000170466500008

    View details for PubMedID 11502408

  • Evaluation of the percutaneous intramyocardial injection for local myocardial treatment CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Rezaee, M., Yeung, A. C., Altman, P., Lubbe, D., Takeshi, S., Schwartz, R. S., Stertzer, S., Altman, J. D. 2001; 53 (2): 271-276


    Therapeutic angiogenesis requires the induction of new blood vessel formation for the treatment of peripheral vascular and coronary artery disease. Efficacious application of this new therapy requires optimizing multiple factors, including the therapeutic agent, dosing, frequency of administration, and delivery modality. In this study, a helical needle drug infusion catheter was applied for optimal application of percutaneous intramyocardial delivery (PIMD). (125)Iodine-labeled albumin was injected by PIMD into the left ventricle myocardium in eight swine. After 1 hr, PIMD resulted in a high concentration of radiolabel at the treatment site; 16.4% +/- 2.1% of delivered and 81.4% +/- 2.6% of the total cardiac activity was concentrated at the site of delivery. The depth of needle penetration correlated with the myocardial retention of delivered protein. The myocardial retention of radiolabel in animals with shallow injections was 10.1% +/- 0.8%, compared to 18.9% +/- 3.3% retention after deep injections. The specific activity at the treatment site (radioactive counts per gram of tissue) was 115 +/- 36, 226 +/- 55, and 47 +/- 10 times higher compared to liver, lung, and kidney, respectively. Continuous coronary sinus and aortic blood sampling indicates that within 15 min following intramyocardial injection, a significant amount of nonretained protein is found within the coronary sinus. This study defines some of the parameters that can affect optimal application of PIMD and demonstrates that PIMD is a safe and efficient method for local drug delivery.

    View details for Web of Science ID 000169010600024

    View details for PubMedID 11387620

  • Role of vascular remodeling in the pathogenesis of early transplant coronary artery disease: A multicenter prospective intravascular ultrasound study JOURNAL OF HEART AND LUNG TRANSPLANTATION Wong, C. K., Ganz, P., Miller, L., Kobashigawa, J., Schwarzkopf, A., von Kaeper, H. V., Wilensky, R., Ventura, H., Yeung, A. C. 2001; 20 (4): 385-392


    Luminal narrowing in transplant coronary artery disease is thought to be primarily caused by intimal proliferation, and the role of vascular remodeling is less certain.We studied cardiac allografts from 83 prospectively recruited patients immediately and 1 year after transplant using intravascular ultrasound in a multicenter study. We measured coronary artery dimensions in 310 angiographically matched segments (175 were also fully matched by ultrasound criteria). At 1 year, lumen area changed by -1.8 +/- 3.7 mm(2) (p < 0.0001, 14% of baseline lumen area). Thirty-three percent of this luminal loss was due to intimal thickening and 67% to vessel shrinkage. Shrinkage also occurred (-0.9 +/- 3.2 mm(2), 7% of baseline total area) in segments free of detectable intimal disease at baseline and at 1 year. Using the mean baseline total vessel area (13.9 mm(2)) as the cutoff, we divided the cohort into the large and the small coronary-segment groups. The large-segment group (n = 176) shrank more (-2.6 +/- 4.4 vs. -0.03 +/- 2.8 mm(2), p < 0.0001), but intimal growth was similar in both groups (0.8 +/- 2.2 vs. 0.4 +/- 1.3 mm(2), p = not significant). Analysis of the 175 fully ultrasound matched sub-cohort showed similar results. Changes in intimal area, total vessel area, and lumen area were similar in segments with (n = 132) and segments without (n = 178) pre-existing donor disease. Despite overall shrinkage, change in total vessel area positively correlated with change in intimal area (r = 0.29, p < 0.0001).In large coronary segments, coronary artery shrinkage plays an important role in the loss of luminal diameter early after cardiac transplantation, whereas new intimal growth occurs in both large and small segments. Pre-existent donor disease does not aggravate these processes. Compensatory remodeling with increasing intimal growth retards the rate of lumen loss. As is intimal thickening, shrinkage and compensatory remodeling are important pathogenic mechanisms in transplant coronary artery disease.

    View details for Web of Science ID 000168040900001

    View details for PubMedID 11295575

  • The role of nitric oxide in atherogenesis. Reviews in cardiovascular medicine Yeung, A. C. 2001; 2 (2): 108-?

    View details for PubMedID 12439389

  • Effect of audit on door-to-inflation times in primary angioplasty/stenting for acute myocardial infarction AMERICAN JOURNAL OF CARDIOLOGY Ward, M. R., Lo, S. T., Herity, N. A., Lee, D. P., Yeung, A. C. 2001; 87 (3): 336-?


    We found that after audit and physician-guided changes in our protocol, the door-to-inflation times for primary angioplasty/stenting were markedly reduced. Because our preaudit mean time was similar to the national average, this may have wide applicability.

    View details for Web of Science ID 000166629100017

    View details for PubMedID 11165972

  • Higher doses of intracoronary adenosine are necessary for FFR-based stent optimization Fearon, W. F., Samady, H., Powers, E. R., Feldman, T., Dib, N., Tuzcu, E. M., Cleman, M. W., Chou, T. M., Cohen, D. J., Takagi, A., Luna, J., Jeremias, A., Yeung, A. C., Kern, M. J., Yock, P. G. ELSEVIER SCIENCE INC. 2001: 12A
  • Basic fibroblast growth factor may attenuate susceptibility to ventricular tachyarrhythmias in chronically ischemic porcine myocardium Day, J. D., Rezaee, M., Chun, S. H., Yeung, A. C., Yock, P. G., Fitzgerald, P. J., Carter, A., Robertson, A. L., Sung, R. J. ELSEVIER SCIENCE INC. 2001: 135A–135A
  • Utility of mechanical rheolysis as an adjunct to rescue angioplasty and platelet inhibition in acute myocardial infarction and cardiogenic shock: A case report CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Lee, D. P., Lo, S., Herity, N. A., Ward, M., Yeung, A. C. 2001; 52 (2): 220-225


    We describe the value of mechanical rheolysis as an adjunct to rescue angioplasty and platelet glycoprotein IIb/IIIa receptor inhibition in a patient with acute myocardial infarction and cardiogenic shock in whom the severity of the intracoronary thrombus burden precluded restoration of antegrade coronary flow by conventional balloon angioplasty and stenting.

    View details for PubMedID 11170334

  • Photoangioplasty with local motexafin lutetium delivery reduces macrophages in a rabbit post-balloon injury model CARDIOVASCULAR RESEARCH Hayase, M., Woodbum, K. W., Perlroth, J., MILLER, R. A., Baumgardner, W., Yock, P. G., Yeung, A. 2001; 49 (2): 449-455


    Motexafin lutetium (Lu-Tex, Antrin Injection) is a photosensitizer that selectively accumulates in atheromatous plaque where it can be activated by far-red light. The localization and retention of intra-arterially administered Lu-Tex and its efficacy following activation by endovascularly delivered light (photoangioplasty) was evaluated.Bilateral iliac artery lesions were induced in 17 rabbits by balloon denudation, followed by a high cholesterol diet. Lu-Tex distribution within the atheroma was examined (n=8) following local injection. Fluorescence spectral imaging and chemical extraction techniques were used to measure Lu-Tex levels within the atheroma and adjacent normal tissue. Photoactivation was performed 15 min following Lu-Tex administration (180 J/cm fiber at 200 mW/cm fiber). Two weeks post photoangioplasty, vessels were harvested and hematoxylin and eosin (H&E) and RAM11 (macrophages) staining was performed.Local delivery of Lu-Tex achieved immediate high concentrations within plaque (mean 40x control iliac atheroma). Mean percent plaque area in the treated segments was significantly lower than in the non-treated contralateral lesions (73 vs. 82%, P<0.01). No medial damage was observed. Quantitative analysis using RAM11 positive cells revealed significant reduction of macrophages in treated lesions in both the intima (5 vs. 22%, P<0.01) and in media (8 vs. 23%, P<0.01) compared to untreated contralateral segments.Local delivery provides high levels of Lu-Tex selectively within atheroma. Photoactivation results in a significant decrease in macrophage and a small decrease in atheroma burden without damage to the normal vessel wall.

    View details for Web of Science ID 000166820000022

    View details for PubMedID 11164855

  • A 25-year-old with severe coronary artery disease LANCET Ward, M. R., Herity, N. A., Lee, D. P., Yeung, A. C. 2001; 357 (9250): 116-116

    View details for Web of Science ID 000166476200015

    View details for PubMedID 11197400

  • 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


    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

  • 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


    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

  • Use of fractional myocardial flow reserve to assess the functional significance of intermediate coronary stenoses AMERICAN JOURNAL OF CARDIOLOGY Fearon, W. F., Takagi, A., Jeremias, A., Yeung, A. C., Joye, J. D., Cohen, D. J., Chou, T. M., Kern, M. J., Yock, P. G. 2000; 86 (9): 1013-1014


    The goal of the present study was to compare the use of pressure-derived myocardial fractional flow reserve for detecting ischemia with nuclear stress imaging in patients undergoing stent placement for intermediate coronary lesions. We demonstrated that myocardial fractional flow reserve detects ischemia in intermediate coronary lesions accurately when compared with nuclear stress imaging.

    View details for Web of Science ID 000165096000023

    View details for PubMedID 11053717

  • 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


    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

  • Arterial remodeling - Mechanisms and clinical implications CIRCULATION Ward, M. R., Pasterkamp, G., Yeung, A. C., Borst, C. 2000; 102 (10): 1186-1191

    View details for Web of Science ID 000089157400020

    View details for PubMedID 10973850

  • 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


    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


    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

  • 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


    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

  • Understanding plaque rupture. Reviews in cardiovascular medicine Yeung, A. C. 2000; 1 (1): 19-20

    View details for PubMedID 12506935

  • 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


    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-?


    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


    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

  • Percutaneous in-situ coronary venous arterialization (PICVA) improves survival in response to acute ischemia in the porcine model Oesterle, S. N., Yeung, A. C., Lo, S., Virmani, R., Van Bibber, R., Flaherty, J. C., Lamson, T. C., Kim, S. W., Garibotto, J. T., Tumas, M. W., Makower, J. ELSEVIER SCIENCE INC. 2000: 61A–61A
  • Vascular complications in patients who receive a glycoprotein IIb/IIIa inhibitor and vascular closure with the perclose device Hiatt, B. L., Lee, D. P., Carter, A. J., Yeung, A. C. ELSEVIER SCIENCE INC. 2000: 33A–33A
  • Left anterior descending coronary blood flow is unaffected by complete occlusion of the anterior interventricular vein Herity, N. A., Lo, S. T., Oei, F., Lee, D. P., Ward, M. R., Filardo, S. D., Hassan, A., Suzuki, T., Yeung, A. C., Fitzgerald, P. J., Yock, P. G. ELSEVIER SCIENCE INC. 2000: 6A
  • Helixcision atherectomy for in-stent stenosis: Initial in vivo experience Davidson, C. J., Gershony, G., Lo, S., Carter, A. J., Yeung, A. C., Yock, P. G., Passafaro, J. ELSEVIER SCIENCE INC. 2000: 41A
  • The influence of de novo atherosclerotic remodeling on luminal narrowing follows a normal distribution. An intravascular ultrasound study Pasterkamp, G., Jeremias, A., Vink, A., Yeung, A., Fitzgerald, P., Hibi, K., de Jaegere, P., Borst, C. ELSEVIER SCIENCE INC. 2000: 47A
  • Influence of a change in gender on coronary arterial size. A longitudinal intravascular ultrasound study in transplant recipients Herity, N. A., Lo, S. T., Ward, M. R., Lee, D. P., Filardo, S. D., Hunt, S. A., Yock, P. G., Fitzgerald, P. J., Yeung, A. C. ELSEVIER SCIENCE INC. 2000: 59A
  • 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


    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

  • Clinical applications of brachytherapy for the prevention of restenosis VASCULAR MEDICINE Lee, D. P., Lo, S., Forster, K., Yeung, A. C., Oesterle, S. N. 1999; 4 (4): 257-268


    Restenosis remains the bane of percutaneous coronary intervention. Local delivery of radiation, brachytherapy, is a promising therapy for the prevention of restenosis. Animal studies have suggested that brachytherapy may be an effective treatment for preventing restenosis. The type of radiation as well as the doses and delivery systems are currently under study; several clinical trials are underway. This paper reviews the biological basis, including animal studies, of intracoronary brachytherapy as well as the current data from clinical trials.

    View details for Web of Science ID 000084256600009

    View details for PubMedID 10613631

  • Local L-arginine delivery after balloon angioplasty reduces monocyte binding and induces apoptosis CIRCULATION Niebauer, J., Schwarzacher, S. P., Hayase, M., Wang, B. Y., Kernoff, R. S., Cooke, J. P., Yeung, A. C. 1999; 100 (17): 1830-1835


    Local administration of L-arginine after balloon angioplasty has been shown to enhance NO generation and inhibit lesion formation. In this study, we assessed the mechanisms by which local delivery of L-arginine inhibits lesion formation.New Zealand White rabbits (n=56) were fed a 1% cholesterol diet. After 1 week, both iliac arteries were balloon-denuded, and a local drug delivery catheter was introduced into both iliac arteries to deliver either L-arginine (800 mg/5 mL with and without 100 microCi L-[2,3-(3)H]-arginine) or saline. Monocyte-endothelial interaction was assessed by functional binding assay; NO activity was measured by chemiluminescence. Intramural administration of radioactively labeled L-arginine led to significantly higher counts in comparison to the contralateral segment for up to 1 week after delivery (676+/-223 versus 453+/-93 cpm/mg; P<0.02); this was associated with significantly higher NO levels in the L-arginine-treated segments (394.4+/-141.6 versus 86.3+/-34.3 nmol/mg; P<0.01). Even after 2 to 3 weeks, monocyte binding was significantly decreased by treatment with L-arginine as compared with saline infusion (P<0.01). After 4 weeks, there was a 9-fold greater number of apoptotic cells in the vessel wall of L-arginine as compared with the saline-treated segments (P<0.05).Intramural delivery of L-arginine immediately after angioplasty causes a sustained increase in tissue L-arginine levels associated with enhancement of local NO synthesis. The local increase in NO synthesis is associated with an attenuation of monocyte binding and increased apoptosis of resident macrophages. This treatment strategy could be valuable for the prevention and management of restenosis.

    View details for Web of Science ID 000083348100022

    View details for PubMedID 10534472

  • 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

  • Review: Clinical aspects of vascular remodeling JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Herity, N. A., Ward, M. R., Lo, S., Yeung, A. C. 1999; 10 (7): 1016-1024


    Vascular remodeling represents a spectrum of structural changes whereby the vascular wall responds to changes in its hemodynamic environment. Such changes may be classified as vessel enlargement (outward remodeling), diminution (inward remodeling), alternatively as adaptive (compensatory, appropriate to the hemodynamic stimulus), or maladaptive (dysfunctional, inappropriate). The direction and scale of remodeling are coordinated by endothelial production of growth factors, proteases, and cellular adhesion molecules in response to sensed changes in blood flow. In early atherosclerosis, outward remodeling preserves lumen size. Although protective in the long-term, the matrix degradation involved in this process may predispose atherosclerotic plaques to rupture, hence increasing the risks of acute coronary syndromes. Inward remodeling also occurs in advanced atherosclerotic lesions, whereby the vessel shrinks rather than enlarging, exacerbating rather than ameliorating stenosis. In transplant coronary artery disease, early inward remodeling may be a more important component of vessel stenosis than intimal thickening, while inappropriate inward remodeling appears to be as least as important as excessive intimal growth in the development of restenosis after angioplasty. Increased awareness of vascular remodeling, and in particular its malaptive forms, may provide new therapeutic insights for the future.

    View details for Web of Science ID 000081152500014

    View details for PubMedID 10413382

  • 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

  • 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


    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


    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

  • Simultaneous evaluation of epicardial and microvascular function in human Beings: A technical tour de force JOURNAL OF HEART AND LUNG TRANSPLANTATION Yeung, A. C. 1998; 17 (5): 495-496

    View details for Web of Science ID 000073855800007

    View details for PubMedID 9628568

  • Primary angioplasty for acute myocardial infarction. Vascular medicine Juergens, C. P., Whitbourn, R. J., Yeung, A. C., Oesterle, S. N. 1997; 2 (4): 327-334


    The use of thrombolytic therapy has been widely accepted for the treatment of acute myocardial infarction. Despite improving mortality, thrombolytic therapy may be contraindicated in many patients presenting with myocardial infarction and is associated with a small, yet significant risk of hemorrhagic sequelae. This article outlines the rationale behind reperfusion therapy, the use of pharmacological thrombolysis and the role of adjunctive angioplasty. The potential advantages of a therapeutic strategy of primary angioplasty, instead of thrombolysis, are discussed. These include anatomical definition, risk stratification, reduced recurrent ischemia, enhanced coronary perfusion and improved coronary patency. The randomized trials in which primary angioplasty and thrombolytic therapy were compared are reviewed. We conclude that angioplasty results in a reduction of short-term mortality and nonfatal reinfarction and therefore advocate the routine use of coronary angioplasty as a primary reperfusion strategy for acute myocardial infarction. The potential limitations of primary angioplasty in the community hospital setting are discussed. Finally, we examine the roles of adjunctive mechanical (e.g. stents) and pharmacological (e.g. Abciximab) means of further enhancing outcomes after primary angioplasty.

    View details for PubMedID 9575607

  • Surveillance cardiac catheterisation in heart transplant recipients HEART Kim, C. B., Yeung, A. C. 1997; 78 (2): 103-104

    View details for Web of Science ID A1997XT73900002

    View details for PubMedID 9326977

    View details for PubMedCentralID PMC484883

  • Routine platelet transfusion in patients undergoing emergency coronary bypass surgery after receiving Abciximab AMERICAN JOURNAL OF CARDIOLOGY Juergens, C. P., Yeung, A. C., Oesterle, S. N. 1997; 80 (1): 74-?


    Abciximab has been shown to reduce the ischemic complications of high-risk angioplasty procedures. The appropriate management of patients who have received abciximab and require emergency coronary artery bypass surgery after failed coronary angioplasty is as yet undetermined. We present the outcomes of a small series of such patients who were given platelet transfusions before or during cardiopulmonary bypass.

    View details for Web of Science ID A1997XG42400015

    View details for PubMedID 9205024

  • 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


    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

  • Local intramural delivery of L-arginine enhances nitric oxide generation and inhibits lesion formation after balloon angioplasty CIRCULATION Schwarzacher, S. P., Lim, T. T., Wang, B. Y., Kernoff, R. S., Niebauer, J., Cooke, J. P., Yeung, A. C. 1997; 95 (7): 1863-1869


    Long-term oral administration of L-arginine has been shown to enhance production of nitric oxide (NO) and to reduce lesion formation. The goal of this study was to determine whether local intramural administration of L-arginine could enhance NO generation and reduce intimal thickening.New Zealand White rabbits (n = 27) received a 1% cholesterol diet. For the short-term study, after 1 week of diet, both iliac arteries were balloon injured. Four weeks later, vasoreactivity was assessed angiographically during infusion of acetylcholine (Ach) before and after delivery of L-arginine or saline into the right or left iliac artery (800 mg/5 mL; 0.2 mL/min, 15 minutes) by use of a local drug-delivery balloon. Vessels were then harvested for measurements of NO. For the long-term study, after balloon injury, drugs were delivered as above into the iliac arteries. Two and 4 weeks after L-arginine delivery, vasoreactivity was determined. Subsequently, the iliac arteries were harvested for histomorphometric analysis and measurements of NO. In the short-term study, local delivery of L-arginine restored endothelium-dependent vasodilatation (Ach 10(-5) mol/L; L-arginine +35 +/- 10%; saline -14 +/- 5%; P < .001) and enhanced local production of nitrogen oxides (L-arginine 152 +/- 28; saline 78 +/- 12 nmol/L per milligram of tissue per hour; P < .04). In the long-term study, local administration of L-arginine enhanced vascular NO production as long as 1 week after the injury (L-arginine 394.4 +/- 141.6; saline 86.3 +/- 34.3 nmol/L per milligram of tissue per hour; P < .01) and reduced intimal thickening 4 weeks later (intima/ media ratio: L-arginine 0.56 +/- 0.1; saline 1.40 +/- 0.2; P < .001), largely due to suppression of macrophage accumulation.A single intramural administration of L-arginine enhances vascular NO generation and inhibits lesion formation. Local augmentation of NO production at the site of balloon angioplasty may be a novel strategy to prevent restenosis.

    View details for Web of Science ID A1997WR51900020

    View details for PubMedID 9107174

  • Relation of donor age and preexisting coronary artery disease on angiography and intracoronary ultrasound to later development of accelerated allograft coronary artery disease JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Gao, S. Z., Hunt, S. A., Alderman, E. L., Liang, D., Yeung, A. C., Schroeder, J. S. 1997; 29 (3): 623-629


    This study assessed the influence of donor age and preexisting donor coronary disease on the later development of allograft coronary artery disease, ischemic events and overall survival.The increasing demand for heart donors has led to a tendency to liberalize age criteria for donor acceptability.A total of 233 consecutive heart transplant recipients who had baseline, early postoperative and follow-up coronary angiograms, as well as a subset of 47 patients with baseline intracoronary ultrasound imaging recordings, were analyzed (mean 3.8 years of follow-up). Patients were subclassified according to the presence of donor coronary artery disease on the baseline angiogram and stratified at age 40 years.patients without evidence of preexisting coronary artery disease on a baseline angiogram (n = 219) were significantly less likely to develop new disease than the 14 patients with preexisting coronary artery disease (p = 0.002). Although older donors exhibited earlier coronary artery disease than younger donors at 3 years of follow-up, there was no difference by 5 years (p = 0.25). There was no difference in survival or probability of developing ischemic events between the groups. Baseline ultrasound imaging revealed substantial disease in 7 of 9 older donated hearts, and in only 7 of 38 younger donated hearts (p = 0.002). Preexisting coronary artery disease, nonuse of calcium channel blocking agents, older donor age, posttransplantation cytomegalovirus infection, elevated very low density lipoprotein levels and previous ischemic heart disease in the recipient were significant predictors of allograft coronary artery disease.Heart donors with angiographic evidence of preexisting coronary artery disease and older donors are more likely to develop new allograft coronary artery disease by 3 years. However, there is no difference in survival or freedom from ischemic events between younger and older donors at a mean follow-up of 3.8 years.

    View details for Web of Science ID A1997WL49000023

    View details for PubMedID 9060902

  • Role of compensatory enlargement and shrinkage in transplant coronary artery disease - Serial intravascular ultrasound study CIRCULATION Lim, T. T., Liang, D. H., Botas, J., Schroeder, J. S., Oesterle, S. N., Yeung, A. C. 1997; 95 (4): 855-859


    Compensatory enlargement of the vessel wall has been described in the early stages of native atherosclerosis. Whether compensatory enlargement plays a role in transplant coronary artery disease is not known. The objective of this study was to determine, by use of serial intravascular ultrasound (IVUS), whether compensatory dilation occurs in transplant coronary artery disease over time.Seventy-five heart transplant recipients with 151 matched coronary segments were selected for the presence of intimal disease progression as detected by serial IVUS examinations 1 to 3 years apart. Intimal disease progression was defined as a > 10% increase in intimal area (IA). IVUS catheter location in follow-up studies was verified angiographically in relation to branch vessels. Luminal area (LA) and total vessel area (TA) were measured at each site. Intimal area (IA = TA-LA) was calculated. Changes in IA (delta IA) and TA (delta TA) between baseline and follow-up IVUS were compared: delta IA, 2.9 +/- 0.2 mm2: delta TA, 2.7 +/- 0.4 mm2. A remodeling index (RI) was defined as RI = delta TA/delta IA. Three subgroups could be distinguished: over compensation (RI > I), partial compensation (RI 0 to 1), and no compensation or shrinkage (RI < or = 0). Seventy-four segments (49%) showed overcompensation, 44 (29%) showed partial compensation, and 33 (22%) showed no compensation or shrinkage.In this study, serial IVUS shows that early after cardiac transplantation, a large proportion of the coronary segments with progression of intimal thickening have compensatory dilation of the vessel wall. However, a substantial number of coronary segments (22%) show no compensatory dilation or shrinkage. The progressive luminal narrowing in transplant patients may be due in part to vessel shrinkage or the lack of compensatory dilation over time.

    View details for Web of Science ID A1997WJ28200021

    View details for PubMedID 9054742

  • Fractional vs coronary flow reserve: Comparison of guidewire-based measurements of coronary stenosis Uren, N. G., Schwarzacher, S. P., Whitbourn, R., Hayase, M., Kernoff, R. S., Yeung, A., Fitzgerald, P. J., Yock, P. G. ELSEVIER SCIENCE INC. 1997: 42150–50
  • QCA comparison of J&JIS, cook flexstent, AVE micro stent and ACS multilink stents Pomerantsev, E. V., Juergens, C. P., Whitbourn, R. J., Yeung, A. C., Oesterle, S. N., Stertzer, S. H. ELSEVIER SCIENCE INC. 1997: 8015–15
  • Are heart-lung transplant recipients protected from developing transplant coronary artery disease? A case-matched intracoronary ultrasound study CIRCULATION Lim, T. T., Botas, J., Ross, H., Liang, D. H., Theodore, J., Hunt, S. A., Oesterle, S. N., Yeung, A. C. 1996; 94 (7): 1573-1577


    Accelerated coronary artery disease is a major cause of mortality in heart transplant recipients; however, it does not appear to play a major role in the clinical outcome of heart-lung transplant recipients. The purpose of this study was to determine whether the incidence and severity of transplant coronary artery disease as detected by intracoronary ultrasound in heart-lung transplant recipients are less than those encountered in heart transplant recipients.We studied the left anterior descending coronary artery with the use of intracoronary ultrasound imaging in 22 heart-lung transplant recipients at the time of their routine annual coronary angiogram. Twenty-two heart transplant recipients were case matched for number of years after transplant at ultrasound study, recipient age, donor age, and diagnosis of nonischemic cardiomyopathy. Mean intimal area, intimal index, Stanford class, and incidence of at least moderate disease (Stanford class > or = 3) were measured and calculated in each group and then compared between the two groups. Mean intimal area (1.6 +/- 2.5 versus 3.8 +/- 2.8 mm2), mean intimal index (0.07 +/- 0.10 versus 0.22 +/- 0.14), mean Stanford class (1.7 +/- 1.0 versus 2.7 +/- 1.2), and incidence of Stanford class > or = 3 (14% versus 45%) were significantly lower in the heart-lung transplant recipient group.The incidence and severity of transplant coronary artery disease are much less in patients receiving heart-lung transplants than in those receiving heart transplants alone.

    View details for PubMedID 8840846

  • Prediction of angiographic disease by intracoronary ultrasonographic findings in heart transplant recipients JOURNAL OF HEART AND LUNG TRANSPLANTATION Liang, D. H., Gao, S. Z., Botas, J., Pinto, F. J., Schroeder, J. S., Alderman, E. L., Yeung, A. C. 1996; 15 (10): 980-987


    Intracoronary ultrasonography has proven to be a more sensitive test than angiography for the detection of intimal thickening in transplant recipients. However, the prognostic significance of the intimal thickening detected by intracoronary ultrasonography has not been proven.During a 1-year period, 70 transplant recipients without angiographically apparent coronary artery disease underwent intracoronary ultrasonography examination. For each intracoronary ultrasonography study an intimal index, defined as the ratio of the plaque area to the area within the media, was measured for the most diseased segment imaged. The subsequent annual follow-up angiograms of these 70 patients were reviewed for the development of visually apparent coronary artery disease. The time since transplantation for the 70 patients without angiographically apparent coronary artery disease ranged from 1 to 15 years, with a mean of 4.2 years an median of 3.9 years. Mean duration of angiographic follow-up was 2.0 years (range 1 to 3 years).Angiographically apparent coronary artery disease developed on follow-up angiograms in 13 of the 70 patients, with a mean time to development of 1.5 years. Four of 46 patients (9%) with an intimal index < 0.3 subsequently had angiographically apparent coronary artery disease, whereas of 25 patients (36%) with an intimal index > or = 0.3 subsequently had angiographically apparent coronary artery disease. Odds ratio for future angiographically apparent coronary artery disease between patients with an intimal index > or = and intimal index < 0.3 was 5.9 (p < 0.01 by Fisher's Exact test). In a subgroup of 22 patients more than 5 years after transplantation at the time of intracoronary ultrasonography, 12 had an intimal index < 0.3 and 10 had an intimal index > or = 0.3. In this subgroup none of the 12 patients with an intimal index < 0.3 had angiographically apparent coronary artery disease and only 1 of the 10 with an intimal index > or = 0.3 had angiographically apparent coronary artery disease (difference not significant).The presence of moderate to severe intimal thickening by intracoronary ultrasonography is predictive of the future development of angiographically apparent coronary artery disease among patients more than 1 year and less than 5 years after transplantation. This same degree of intimal thickening may not carry the same prognostic significance among patients greater than 5 years after transplantation without the development of angiographically apparent coronary artery disease.

    View details for Web of Science ID A1996VT54800003

    View details for PubMedID 8913914

  • 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


    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

  • Outcome of narrowing related side branches after high-speed rotational atherectomy AMERICAN JOURNAL OF CARDIOLOGY Walton, A. S., Pomerantsev, E. V., Oesterle, S. N., Yeung, A. C., Singer, A. H., Shaw, R. E., Stertzer, S. H. 1996; 77 (5): 370-373


    High-speed rotational atherectomy (HSRA) is advocated for calcified and diffusely narrowed coronary arteries. There are often side branches involving these kinds of lesions. The presence of significant lesion-related side branches has been considered a relative contraindication to rotational atherectomy. This study was performed to determine the rate, predictors, and outcome of side branch occlusion after HSRA. The angiograms of 418 patients were examined with 320 side branches in 240 target vessels of > or = 1 mm in diameter being identified. Vessels were scored as either perfused (Thrombolysis In Myocardial Infarction 2 or 3 flow) or occluded (Thrombolysis In Myocardial Infarction 0 or 1 flow before and after the procedure. A detailed quantitative angiographic analysis was performed on a total of 108 side branches including all cases of branch occlusion. Clinical outcomes were determined in all cases with side branch loss. There were 24 occlusions in 21 patients after the procedure, giving a rate of branch loss of 7.5%. Follow-up angiography of > or = 24 hours was available for 13 of the occluded branches and 12 were found to be patent. In the 21 patients with branch occlusion, 6 sustained a myocardial infarct (of which 5 were non-Q-wave), 2 underwent coronary artery bypass grafting, and 2 died. There are frequently lesion-associated side branches in the types of vessels to undergo HSRA. These branches remained patent 92.5% of the time, with occlusion occurring infrequently and usually being transient. When occlusion did occur, there was a 29% incidence of myocardial infarction.

    View details for Web of Science ID A1996TV89600008

    View details for PubMedID 8602565

  • 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


    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

  • Incidence and progression of transplant coronary artery disease over 1 year: Results of a multicenter trial with use of intravascular ultrasound 2nd International Symposium on Allograft Coronary Disease - A Basic Science and Clinical Review Yeung, A. C., Davis, S. F., Hauptman, P. J., Kobashigawa, J. A., Miller, L. W., Valantine, H. A., Ventura, H. O., Wiedermann, J., Wilensky, R. ELSEVIER SCIENCE INC. 1995: S215–S220

    View details for Web of Science ID A1995TN11900019

    View details for PubMedID 8719489

  • The impact of cyclosporine dose and level on the development and progression of allograft coronary disease 2nd International Symposium on Allograft Coronary Disease - A Basic Science and Clinical Review Miller, L., Kobashigawa, J., Valantine, H., Ventura, H., Hauptman, P., ODONNELL, J., Wiedermann, J., Yeung, A. ELSEVIER SCIENCE INC. 1995: S227–S234

    View details for Web of Science ID A1995TN11900021

    View details for PubMedID 8719491

  • Does acute rejection correlate with the development of transplant coronary artery disease? A multicenter study using intravascular ultrasound 2nd International Symposium on Allograft Coronary Disease - A Basic Science and Clinical Review Kobashigawa, J. A., Miller, L., Yeung, A., Hauptman, P., Ventura, H., Wilensky, R., Valantine, H., Wiedermann, J. ELSEVIER SCIENCE INC. 1995: S221–S226

    View details for Web of Science ID A1995TN11900020

    View details for PubMedID 8719490

  • The role of nonimmune risk factors in the development and progression of graft arteriosclerosis: Preliminary insights from a multicenter intravascular ultrasound study JOURNAL OF HEART AND LUNG TRANSPLANTATION Hauptman, P. J., Davis, S. F., Miller, L., Yeung, A. C. 1995; 14 (6): S238-S242

    View details for Web of Science ID A1995TN11900023

    View details for PubMedID 8719493



    Transplant vasculopathy (TxCAD) limits longterm survival of allograft recipients. The possibility that preexistent donor coronary disease (PEDD) might accelerate this process is of concern. The serial progression of sites with and without PEDD as assessed by intravascular ultrasonic imaging is explored in this study.Thirty patients with baseline intravascular imaging within 3 weeks of cardiac transplantation who had at least one annual follow-up study were included in this study. Vessel luminal area (LA), total area (TA), intimal index (II = TA - LA/TA), mean intimal thickness (MIT), and Stanford classification were expressed for each image site and for each patient at each study. Progression of sites and of patients with and without PEDD on the baseline study was compared. Patients with PEDD (n = 9) still had significantly more intimal disease than those without PEDD (n = 21) at the first follow-up study (MIT = 0.35 +/- 0.13 versus 0.13 +/- 0.11 mm; II = 0.29 +/- 0.11 versus 0.11 +/- 0.1; class = 3.7 +/- 0.5 versus 2.2 +/- 0.94; P < .001 for all comparisons). However, the increase in intimal thickness during the 1- year interval was not significantly different between the two groups. In 4 patients in whom both types of sites were present, no difference in progression was found. Data were similar for patients and sites studied over > 1 year.PEDD does not accelerate the progression of TxCAD within the first few years after cardiac transplantation. The pathophysiology of TxCAD is most likely immune mediated and does not seem to be accelerated by native coronary artery disease.

    View details for Web of Science ID A1995RR27600012

    View details for PubMedID 7648656


    View details for Web of Science ID A1995QK03700013

    View details for PubMedID 7788693



    Intracoronary ultrasound (ICUS) is increasingly used in clinical practice to study the natural history of coronary artery disease and to assess the effects of intracoronary, catheter-based interventions. However, the risk associated with the procedure is not well documented.ICUS studies performed in 28 centers were retrospectively included; these centers agreed to contribute to the study among a total of 60 centers initially invited. Among the 2207 ICUS studies, 505 (23%) were performed in heart transplant recipients and 1702 (77%) in nontransplant patients. Indication for ICUS was diagnostic imaging in 915 (41%), drug testing in 244 (11%), and guidance for intracoronary interventions in 1048 patients (47%). There were no complications in 2034 patients (92.2%). In 87 patients (3.9%), complications occurred but were judged to be "not related" to ICUS by the operator. In 63 patients (2.9%), spasm occurred during ICUS imaging. In 9 patients (0.4%), complications other than spasm were judged to have a "certain relation" to ICUS, including acute procedural events in 6 (3 acute occlusion, 1 embolism, 1 dissection, and 1 thrombus) and major events in 3 patients (2 occlusion and 1 dissection; all resulting in myocardial infarction). In 14 patients (0.6%), complications with "uncertain relation" to ICUS were recorded, including acute procedural events in 9 (5 acute occlusion, 3 dissection, and 1 arrhythmia) and major events in 5 patients (2 myocardial infarction and 3 emergency coronary artery bypass surgery). The incidence of acute procedural or major complications judged to be associated with ICUS (uncertain relation or certain relation to ICUS) was compared in different patient groups. The complication rate was higher in patients with unstable angina or acute myocardial infarction (2.1% events) as compared with patients with stable angina pectoris and asymptomatic patients (0.8% and 0.4%, respectively; chi 2 = 10.9, P < .01). These complications were also more frequent in patients undergoing interventions (1.9%) as compared with transplant and nontransplant patients undergoing diagnostic ICUS imaging (0% and 0.6%, respectively; chi 2 = 13.5, P < .001). Adverse events were few, and no association was detected between these events and the size or type of ICUS catheter used.ICUS is associated with (but not necessarily the direct cause of) a minor acute clinical risk. Vessel spasm is the most frequent event occurring during ICUS. Other complications predominantly occur in patients with acute coronary syndromes and during guidance for intervention.

    View details for PubMedID 7828285



    Detection of transplant coronary disease remains difficult. Both intravascular ultrasound (IVUS) imaging and functional coronary vasomotion studies have been used to evaluate this process. However, the time course of intimal thickening as assessed by IVUS and the relation between structure and function have not been explored.In 40 patients 1 to 8 years after transplantation, 108 coronary artery segments were analyzed by IVUS. Intimal index [% intimal area (lumen+intimal area)] and maximal thickness were used to quantify intimal thickening. Abnormal IVUS was present in 53 of 108 segments (49%) (mean intimal index of diseased segments, 23 +/- 2%; maximal thickness, 530 +/- 47 microns). For those patients with intimal thickening in all segments of the analyzed artery, more time had elapsed since transplantation (4.3 +/- 0.6 years) than for those whose arteries contained some normal (2.6 +/- 0.3 years) or all normal segments (2.2 +/- 0.6 years, P < .05). Both the proportion of segments with intimal thickening and the degree of thickening increased as a function of time after transplantation (P < .5). By multivariate analysis, the independent predictors of intimal thickening were increasing time after transplantation and pretransplantation hypercholesterolemia (P = .02). Within the cohort of 40 patients, endothelium-dependent vasomotor function was evaluated in 26 matched segments from 11 patients studied 1 year after transplantation and in 15 matched segments from 8 patients studied > or = 5 years after transplantation by serial infusions of acetylcholine (10(-8) to 10(-6) mol/L). Of the 26 segments assessed for structure/function correlation at 1 year after transplantation, 22 had no intimal thickening by IVUS. However, endothelial dysfunction was present in 13 of these normal segments (mean diameter constriction, 18.8 +/- 2.3%). Of the 15 segments studied > or = 5 years after transplantation, 11 had intimal thickening. Nine of these 11 segments had preserved endothelial function (mean diameter dilation, 8.6 +/- 2.9%). There was no relation between the degree of intimal thickening and the magnitude of the endothelium-dependent response to acetylcholine.This study has shown that intimal thickening after transplantation begins as a heterogeneous process and increases in extent and magnitude over time. Also, endothelial dysfunction occurs early before the intimal thickening; yet in those patients surviving > or = 5 years, endothelial function may recover even in the presence of moderate intimal pathology. The variable relation between intimal pathology and endothelial function is probably a result of the episodic nature of immune injury.

    View details for Web of Science ID A1993LV72800032

    View details for PubMedID 8353871

  • Close relationship of endothelial dysfunction in coronary and brachial artery. Circulation Yeung AC, Uehata A, Gerhard MD, Meredith IT, Lieberman EL, Selwyn AP, Creager M, Polak J, Ganz P, Anderson TJ. 1993: I-618.

    View details for Web of Science ID A1992HZ31100016

    View details for PubMedID 1623004

  • Arterial dysfunction is segmental in coronary atherosclerosis and is not related to structural stenosis Circulation Yeung AC, Anderson T, Meredith I, Uehata A, Ryan TJ, Ganz P, Selwyn AP. 1992: I-853


    Obstructive coronary disease has many clinical expressions and some are used as useful indicators of risk. Apart from symptoms, transient ischaemia occurs during daily life, is mostly silent and represents one measure of risk. Ambulatory monitoring of the electrocardiogram shows that ischaemia occurs with increased frequency during the morning hours while waking and rising. This coincides with other damaging vascular events, increased sympathetic activity and changes in coronary blood supply and myocardial oxygen demand that may favour a lower threshold to ischaemia. Calcium blockers, beta-blockers and aspirin can favourably affect this process and long-acting drugs appear to be a more rational approach given the variability of ischaemia over time.

    View details for Web of Science ID A1992HV67100004

    View details for PubMedID 1600537



    Mental stress can cause angina in patients with coronary artery disease, but its effects on coronary vasomotion and blood flow are poorly understood. Because atherosclerosis affects the reactivity of coronary arteries to various stimuli, such as exercise, we postulated that atherosclerosis might also influence the vasomotor response of coronary arteries to mental stress.We studied 26 patients who performed mental arithmetic under stressful conditions during cardiac catheterization. (An additional four patients who did not perform the mental arithmetic served as controls.) Coronary segments were classified on the basis of angiographic findings as smooth, irregular, or stenosed. In 15 of the patients without focal stenoses in the left anterior descending artery, acetylcholine (10(-8) to 10(-6) mol per liter) was infused into the artery to test endothelium-dependent vasodilation. Changes in coronary blood flow were measured with an intracoronary Doppler catheter in these 15 patients.The response of the coronary arteries to mental stress varied from 38 percent constriction to 29 percent dilation, whereas the change in coronary blood flow varied from a decrease of 48 percent to an increase of 42 percent. The direction and magnitude of the change in the coronary diameter were not predicted by the changes in the heart rate, blood pressure, or plasma norepinephrine level. Segments with stenoses (n = 7) were constricted by a mean (+/- SE) of 24 +/- 4 percent, and irregular segments (n = 20) by 9 +/- 3 percent, whereas smooth segments (n = 25) did not change significantly (dilation, 3 +/- 3 percent; P less than 0.0002). Coronary blood flow increased by 10 +/- 10 percent in smooth vessels, whereas the flow in irregular vessels decreased by 27 +/- 5 percent. The degree of constriction or dilation during mental stress correlated with the response to the infusions of acetylcholine (P less than 0.0003, r = 0.58).Atherosclerosis disturbs the normal vasomotor response (no change or dilation) of large coronary arteries to mental stress; in patients with atherosclerosis paradoxical constriction occurs during mental stress, particularly at points of stenosis. This vasomotor response correlates with the extent of atherosclerosis in the artery and with the endothelium-dependent response to an infusion of acetylcholine. These data suggest that in atherosclerosis unopposed constriction caused by a local failure of endothelium-dependent dilation causes the coronary arteries to respond abnormally to mental stress.

    View details for Web of Science ID A1991GR38000005

    View details for PubMedID 1944439



    Patients with coronary atherosclerosis present with angina, myocardial infarction and sudden death, most often caused by atherosclerotic stenosis complicated by spasm and/or occlusive thrombosis. All of these events have been shown to exhibit similar diurnal rhythms, with a peak incidence in the morning after waking and rising. Other cardiovascular parameters also show a similar diurnal rhythm associated with increased sympathetic outflow and circulating catecholamines, producing increases in heart rate, blood pressure, myocardial contractility and oxygen demand soon after waking and rising. Experimental and clinical research has recently pointed to several possible mechanisms that might be responsible for these events. In patients with atherosclerosis, dysfunction of the endothelium in the epicardial coronary arteries results in a failure to limit the constrictor response to catecholamines. Catecholamines can also alter the procoagulant nature of vascular surfaces. We speculate that the interaction between increased sympathetic activity and the procoagulant and vasoconstrictor states of atherosclerotic coronary stenoses may lead to a lower threshold to ischaemia in the waking hours, with a corresponding increase in angina, myocardial infarction and sudden death. These factors may be important considerations for the selection of suitable therapies and for future research.

    View details for Web of Science ID A1991GY18900012

    View details for PubMedID 1803340