David Lee, MD

All Publications

• Safety and Efficacy of Renal Denervationin Patients Taking Antihypertensive Medications. Journal of the American College of Cardiology Kandzari, D. E., Townsend, R. R., Kario, K., Mahfoud, F., Weber, M. A., Schmieder, R. E., Pocock, S., Tsioufis, K., Konstantinidis, D., Choi, J., East, C., Lauder, L., Cohen, D. L., Kobayashi, T., Schmid, A., Lee, D. P., Ma, A., Weil, J., Agdirlioglu, T., Schlaich, M. P., Shetty, S., Devireddy, C. M., Lea, J., Aoki, J., Sharp, A. S., Anderson, R., Fahy, M., DeBruin, V., Brar, S., Bohm, M., SPYRAL HTN-ON MED Investigators, Wang, Y., Jay, D., McLaurin, B., Lomboy, C., Allaqaband, S., Jan, F., Gummadi, B., Litt, M., Garcia, F., Singh, J., Brown, A., Choi, J., Paul, A., Sharp, A., Coulson, J., Nanjundappa, A., Thakker, G., Campbell, J., Honton, B., Farah, B., Patel, M., Gutierrez, A., Tyson, C., Svetkey, L., Fudim, M., Pagidipati, N., Jones, S., Vemulapalli, S., Devireddy, C., Kulshreshtha, A., Wells, B., Lea, J., Batson, B., Wilkins, R., Sharif, F., Khair, A. M., Pallippattu, A. W., Alhmoudi, A. M., Gaffney, B., Cawley, C., Gorry, C., Hamed, H., Carron, J., Birrane, J., Rosseel, L., Lunardi, M., Cronin, M., McKittrick, M., Almagal, N., Khalid, N., Shehahd, Q., Shahzad, S., Fezzi, S., Tyulkin, S., Bel, X. A., Jolly, S., Yip, G., Schwalm, J., Tsang, M., Mehta, S., Lurz, P. C., Binner, C., Obradovic, D., Fahr, F., Richter, I., Rotta Detto Loria, J., Fengler, K., Rommel, K., Cuartas, M. M., Lerche, M., Hartung, P., Munch, P., Hollriegel, R., John, S., Otsuji, S., Kusumoto, H., Tamaru, H., Ishibuchi, K., Hasegawa, K., Sugimoto, K., Kakishita, M., Ishii, R., Takiuchi, S., Yasuda, S., Nakabayashi, S., Yamamoto, W., Higashino, Y., Shimatani, Y., Taniguchi, Y., Tsioufis, K., Kasiakogias, A., Konstantinidis, D., Andrikou, E., Konstantinou, K., Dimitriadis, K., Kalos, T., Cohen, D., Rene, G., Cohen, J., Bonanni, M., Denker, M., Wickramisinghe, R., Wilensky, R., Kobayashi, T., Anjan, V., Huan, Y., Haught, W. H., Krasnow, J., Vasquez, A., Gessler, C., Roth, C., Drenning, D., Velasquez, E., Soliman, G., Murphy, J., Jain, K., Butler, M., Kanitkar, M., Laney, P., Hunter, R., Cheng, S., Wright, T., Haught, W. H., Chapman, N., Arnold, A., Nowbar, A., Janmohamed, A., Corden, B., Cook, C., Rajkumar, C., Keene, D., Thompson, D., Seligman, H., Howard, J., Davies, J., Sweeney, M., Shun-Shin, M., Foley, M., Quaife, N., Al-Lamee, R., Hadjiphilippou, S., Sen, S., Ahmad, Y., Kario, K., Shimizu, H., Waki, H., Narita, K., Shimpo, M., Hoshide, S., Komori, T., Ogoyama, Y., Ogata, Y., Oba, Y., Bisharat, M., Lishmanov, A., Bisharat, M., Jeffords, T., Ghali, M., Chia, B., Onsrud, R., Rough, R., Aoki, J., Tomii, D., Mori, F., Kikushima, H., Ninomiya, K., Yahagi, K., Tanabe, K., Nakamura, K., Komiyama, K., Nakase, M., Asami, M., Setoguchi, N., Tanaka, T., Horiuchi, Y., Watanabe, Y., Feldman, D., Bergman, G., Sherifi, I., Kim, L., Amin, N., Minutello, R., Wong, S. C., McCullough, S., D'Souza, R., Sharp, A., Kurdi, H., D'Souza, R., Statton, S., Watkinson, T., Bertolet, B., Gupta, A., Blossom, B., Bell, C., Hill, D., Sierra, F., Johnson, J., Estess, J., Adams, J., McDuffie, K., Ferguson, L., Little, N., Ballard, R. D., Williams, R., Ikeda, W., Calhoun, W., Carroll, W., Singh, A., Hirsh, B., Meraj, P., Jauhar, R., Golwala, H., Rueda, J., Graham, K., Al-Hakim, R., Rope, R., Kandzari, D., Bahrami, D., Reedus, D., David, S., Rehman, I., Zakaria, K., Choksi, N., Kazziha, S., Kumar, S., Saba, S., Steigerwalt, S., Sirajeldin, Y., Hyder, O., Aronow, H., Connors, A., Shemin, D., Bent, C., Levy, T., Kodoth, V., Schlaich, M., Kiuchi, M., Carnagarin, R., Shetty, S., Torre, S., Levitt, H., Chen, L., Fan, S., Waxman, S., Porr, W., Mangos, G., Smyth, B., Lane, C., Sader, M., Patel, K. K., Rao, A., Milford, B., Ahluwalia, G., Sennott, J., Field, J., Jena, N., Loree, S., Graham, J., Al-Hesayen, A., Bagai, A., Shite, J., Kozuki, A., Suzuki, A., Masuko, E., Soga, F., Asada, H., Shibata, H., Nagoshi, R., Fujiwara, R., Kyo, S., Miyata, T., Kijima, Y., Weil, J., Griesinger, L., Hafer, L., Starick, R., Keil, S., Agdirlioglu, T., Desch, U., Saito, S., Koyama, E., Yamanaka, F., Yokoyama, H., Tobita, K., Shishido, K., Yamaguchi, M., Murakami, M., Moriyama, N., Takahashi, S., Mizuno, S., Yokota, S., Hayashi, T., Yamada, T., Yamagishi, T., Sugiyama, Y., Mashimo, Y., Tamaki, Y., Tanaka, Y., Lee, D., Ma, A., Yeung, A., Noel, T., Umana, E., Katopodis, J., Dixon, W., Walton, T., Rischin, A., Chee, A., Leaney, A., Fernando, H., Hopper, I., Bloom, J., Fairley, J., Stehli, J., Segan, J., Sharma, M., Fitzgerald, M., Papandony, M., Whyler, N., Noaman, S., Ali, S., Jefferson, B., Reyes, D., Johnston, T., Bohm, M., Hofling, A., Berger, A., Cremers, B., Millenaar, D., Mahfoud, F., Zivanovic, I., Lucic, J., Dederer, J., Lauder, L., Fischer, P., Kulenthiran, S., Ewen, S., Bewarder, Y., Schmieder, R., Bosch, A., Schmid, A., Ott, C., Kannenkeril, D., Akarca, E., Kistner, I., Kolwelter, J., Bihlmaier, K., Striepe, K., Karg, M., Gunes-Altan, M., Anna Friedrich, S. S., Jung, S., Dienemann, T., Ziakas, A., Kouparanis, A., Pagiantza, A., Peteinidou, E., Didagelos, M., Psochias, P. A., Shishehbor, M., Meade, A., Linetsky, E., Robinson, M., Kotter, J., Ziada, K., Kotter, J., Bachinsky, W., Garton, A., Stuck, J., Papademetriou, V., Chung, A., Li, P., Nagpal, S., Remetz, M., Shah, S., Lynch, S. 2023; 82 (19): 1809-1823

  Abstract

  BACKGROUND: Renal denervation (RDN) reduces blood pressure (BP) in patients with uncontrolled hypertension in the absence of antihypertensive medications.OBJECTIVES: This trial assessed the safety and efficacy of RDN in the presence of antihypertensive medications.METHODS: SPYRAL HTN-ON MED is a prospective, randomized, sham-controlled, patient- and assessor-blinded trial enrolling patients from 56 clinical centers worldwide. Patients were prescribed 1 to 3 antihypertensive medications. Patients were randomized to radiofrequency RDN or sham control procedure. The primary efficacy endpoint was the baseline-adjusted change in mean 24-hour ambulatory systolic BP at 6months between groups using a Bayesian trial design and analysis.RESULTS: The treatment difference in the mean 24-hour ambulatory systolic BP from baseline to 6months between the RDN group (n=206;-6.5± 10.7mmHg) and sham control group (n=131;-4.5 ± 10.3mmHg) was-1.9mmHg (95%CI:-4.4 to 0.5 mm Hg; P = 0.12). There was no significant difference between groups in the primary efficacy analysis with a posterior probability of superiority of 0.51 (Bayesian treatment difference:-0.03mmHg [95%CI:-2.82 to 2.77 mm Hg]). However, there were changes and increases in medication intensity among sham control patients. RDN was associated with a reduction in office systolic BP compared with sham control at 6months (adjusted treatment difference:-4.9mmHg; P = 0.0015). Night-time BP reductions and win ratio analysis also favored RDN. There was 1 adverse safety event among 253 assessed patients.CONCLUSIONS: There was no significant difference between groups in the primary analysis. However, multiple secondary endpoint analyses favored RDN over sham control. (SPYRAL HTN-ON MED Study [Global Clinical Study of Renal Denervation With the Symplicity Spyral Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension in the Absence of Antihypertensive Medications]; NCT02439775).

  View details for DOI 10.1016/j.jacc.2023.08.045

  View details for PubMedID 37914510

• No Functional Nerve Recovery To 6 Months Post Renal Denervation With Rf Energy In A Normotensive Pig Model Sharp, A., Tunev, S., Schlaich, M. P., Lee, D. P., Finn, A., Trudel, J., Kandzari, D. E. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1161/hyp.78.suppl_1.P195

  View details for Web of Science ID 000714476600221

• Renal denervation in hypertension patients: Proceedings from an expert consensus roundtable cosponsored by SCAI and NKF. Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions Kandzari, D. E., Townsend, R. R., Bakris, G., Basile, J., Bloch, M. J., Cohen, D. L., East, C., Ferdinand, K. C., Fisher, N., Kirtane, A., Lee, D. P., Puckrein, G., Rader, F., Vassalotti, J. A., Weber, M. A., Willis, K., Secemsky, E. 2021

  View details for DOI 10.1002/ccd.29884

  View details for PubMedID 34343406

• Early outcomes from the CLASP IID trial roll-in cohort for prohibitive risk patients with degenerative mitral regurgitation. Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions Lim, D. S., Smith, R. L., Zahr, F., Dhoble, A., Laham, R., Lazkani, M., Kodali, S., Kliger, C., Hermiller, J., Vora, A., Sarembock, I. J., Gray, W., Kapadia, S., Greenbaum, A., Rassi, A., Lee, D., Chhatriwalla, A., Shah, P., Rodes-Cabau, J., Ibrahim, H., Satler, L., Herrmann, H. C., Mahoney, P., Davidson, C., Petrossian, G., Guerrero, M., Koulogiannis, K., Marcoff, L., Gillam, L., CLASP IID Pivotal Trial Investigators 2021

  Abstract

  OBJECTIVES: We report the 30-day outcomes from the roll-in cohort of the CLASP IID trial, representing the first procedures performed by each site.BACKGROUND: The currently enrolling CLASP IID/IIF pivotal trial is a multicenter, prospective, randomized trial assessing the safety and effectiveness of the PASCAL transcatheter valve repair system in patients with clinically significant MR. The trial allows for up to three roll-in patients per site.METHODS: Eligibility criteria were: DMR ≥3+, prohibitive surgical risk, and deemed suitable for transcatheter repair by the local heart team. Trial oversight included a central screening committee and echocardiographic core laboratory. The primary safety endpoint was a 30-day composite MAE: cardiovascular mortality, stroke, myocardial infarction (MI), new need for renal replacement therapy, severe bleeding, and non-elective mitral valve re-intervention, adjudicated by an independent clinical events committee. Thirty-day echocardiographic, functional, and quality of life outcomes were assessed.RESULTS: A total of 45 roll-in patients with mean age of 83years and 69% in NYHA class III/IV were treated. Successful implantation was achieved in 100%. The 30-day composite MAE rate was 8.9% including one cardiovascular death (2.2%) due to severe bleeding from a hemorrhagic stroke, one MI, and no need for re-intervention. MR≤1+ was achieved in 73% and ≤2+ in 98% of patients. 89% of patients were in NYHA class I/II (p<.001) with improvements in 6MWD (30m; p = .054) and KCCQ (17 points; p<.001).CONCLUSIONS: Early results representing sites with first experience with the PASCAL repair system showed favorable 30-day outcomes in patients with DMR≥3+ at prohibitive surgical risk.

  View details for DOI 10.1002/ccd.29749

  View details for PubMedID 34004077

• A Phase II Study of Autologous Mesenchymal Stromal Cells and c-kit Positive Cardiac Cells, Alone or in Combination, in Patients with Ischemic Heart Failure: The CCTRN CONCERT-HF Trial. European journal of heart failure Bolli, R., Mitrani, R. D., Hare, J. M., Pepine, C. J., Perin, E. C., Willerson, J. T., Traverse, J. H., Henry, T. D., Yang, P. C., Murphy, M. P., March, K. L., Schulman, I. H., Ikram, S., Lee, D. P., O'Brien, C., Lima, J. A., Ostovaneh, M. R., Ambale-Venkatesh, B., Lewis, G., Khan, A., Bacallao, K., Valasaki, K., Longsomboon, B., Gee, A. P., Richman, S., Taylor, D. A., Lai, D., Sayre, S. L., Bettencourt, J., Vojvodic, R. W., Cohen, M. L., Simpson, L., Aguilar, D., Loghin, C., Moye, L., Ebert, R. F., Davis, B. R., Simari, R. D., Cardiovascular Cell Therapy Research Network (CCTRN) 2021

  Abstract

  AIMS: CONCERT-HF is an NHLBI-sponsored, double-blind, placebo-controlled, Phase II trial designed to determine whether treatment with autologous bone marrow-derived mesenchymal stromal cells (MSCs) and c-kit positive cardiac cells (CPCs), given alone or in combination, is feasible, safe, and beneficial in patients with heart failure (HF) caused by ischemic cardiomyopathy.METHODS AND RESULTS: Patients were randomized (1:1:1:1) to transendocardial injection of MSCs combined with CPCs, MSCs alone, CPCs alone, or placebo, and followed for 12months. Seven centers enrolled 125 participants with left ventricular ejection fraction (LVEF) of 28.6±6.1% and scar size 19.4±5.8%, in NYHA class II or III. The proportion of major adverse cardiac events (MACE) was significantly decreased by CPCs alone (-22% vs. placebo, P=0.043). Quality of life (MLHFQ score) was significantly improved by MSCs alone (P=0.050) and MSCs+CPCs (P=0.023) vs. placebo. LVEF, LV volumes, scar size, 6-min walking distance, and peak VO2 did not differ significantly among groups.CONCLUSIONS: This is the first multicenter trial assessing CPCs and a combination of two cell types from different tissues in HF patients. The results show that treatment is safe and feasible. Even with maximal guideline-directed therapy, both CPCs and MSCs were associated with improved clinical outcomes (MACE and quality of life, respectively) in ischemic HF without affecting LV function or structure, suggesting possible systemic or paracrine cellular mechanisms. Combining MSCs with CPCs was associated with improvement in both these outcomes. These results suggest potential important beneficial effects of CPCs and MSCs and support further investigation in HF patients.

  View details for DOI 10.1002/ejhf.2178

  View details for PubMedID 33811444

• Allogeneic Mesenchymal Cell Therapy in Anthracycline-Induced Cardiomyopathy Heart Failure Patients: The CCTRN SENECA Trial. JACC. CardioOncology Bolli, R., Perin, E. C., Willerson, J. T., Yang, P. C., Traverse, J. H., Henry, T. D., Pepine, C. J., Mitrani, R. D., Hare, J. M., Murphy, M. P., March, K. L., Ikram, S., Lee, D. P., O'Brien, C., Durand, J., Miller, K., Lima, J. A., Ostovaneh, M. R., Ambale-Venkatesh, B., Gee, A. P., Richman, S., Taylor, D. A., Sayre, S. L., Bettencourt, J., Vojvodic, R. W., Cohen, M. L., Simpson, L. M., Lai, D., Aguilar, D., Loghin, C., Moye, L., Ebert, R. F., Davis, B. R., Simari, R. D., Cardiovascular Cell Therapy Research Network (CCTRN) 2020; 2 (4): 581–95

  Abstract

  BACKGROUND: Anthracycline-induced cardiomyopathy (AIC) may be irreversible with a poor prognosis, disproportionately affecting women and young adults. Administration of allogeneic bone marrow-derived mesenchymal stromal cells (allo-MSCs) is a promising approach to heart failure (HF) treatment.OBJECTIVES: SENECA (Stem Cell Injection in Cancer Survivors) was a phase 1 study of allo-MSCs in AIC.METHODS: Cancer survivors with chronic AIC (mean age 56.6 years; 68% women; NT-proBNP 1,426 pg/ml; 6 enrolled in an open-label, lead-in phase and 31 subjects randomized 1:1) received 1 * 108 allo-MSCs or vehicle transendocardially. Primary objectives were safety and feasibility. Secondary efficacy measures included cardiac function and structure measured by cardiac magnetic resonance imaging (CMR), functional capacity, quality of life (Minnesota Living with Heart Failure Questionnaire), and biomarkers.RESULTS: A total of 97% of subjects underwent successful study product injections; all allo-MSC-assigned subjects received the target dose of cells. Follow-up visits were well-attended (92%) with successful collection of endpoints in 94% at the 1-year visit. Although 58% of subjects had non-CMR compatible devices, CMR endpoints were successfully collected in 84% of subjects imaged at 1 year. No new tumors were reported. There were no significant differences between allo-MSC and vehicle groups with regard to clinical outcomes. Secondary measures included 6-min walk test (p = 0.056) and Minnesota Living with Heart Failure Questionnaire score (p = 0.048), which tended to favor the allo-MSC group.CONCLUSIONS: In this first-in-human study of cell therapy in patients with AIC, transendocardial administration of allo-MSCs appears safe and feasible, and CMR was successfully performed in the majority of the HF patients with devices. This study lays the groundwork for phase 2 trials aimed at assessing efficacy of cell therapy in patients with AIC.

  View details for DOI 10.1016/j.jaccao.2020.09.001

  View details for PubMedID 33403362

• Evaluation of Nerve Injury and Regrowth Following Renal Denervation in Swine Model Sharp, A., Tunev, S., Schlaich, M., Lee, D., Finn, A., Mahfoud, F., Melder, R., Trudel, J., Coates, P., Kandzari, D. ELSEVIER SCIENCE INC. 2020: B179

  View details for Web of Science ID 000597114500400

• Renal Denervation: History and Current Status. Interventional cardiology clinics Lee, D. P. 2020; 9 (4): 483–88

  Abstract

  This review examines the early roots of renal denervation from its conceptualization and the creation of a percutaneous catheter system from a start-up company. As excitement began to grow with early animal experiments and human trials, renal denervation began to focus on the treatment of hypertension, culminating in a disappointing pivotal trial. Lessons learned from this trial are pushed forward, and renal denervation begins to gain clinical momentum as a new set of successful clinical trials emerge. The future for renal denervation eventually may extend beyond hypertension.

  View details for DOI 10.1016/j.iccl.2020.07.004

  View details for PubMedID 32921372

• Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial. Lancet (London, England) Bohm, M., Kario, K., Kandzari, D. E., Mahfoud, F., Weber, M. A., Schmieder, R. E., Tsioufis, K., Pocock, S., Konstantinidis, D., Choi, J. W., East, C., Lee, D. P., Ma, A., Ewen, S., Cohen, D. L., Wilensky, R., Devireddy, C. M., Lea, J., Schmid, A., Weil, J., Agdirlioglu, T., Reedus, D., Jefferson, B. K., Reyes, D., D'Souza, R., Sharp, A. S., Sharif, F., Fahy, M., DeBruin, V., Cohen, S. A., Brar, S., Townsend, R. R., SPYRAL HTN-OFF MED Pivotal Investigators, Akarca, E., Allaqaband, S., Andrikou, E., Aoki, J., Arnold, A., Aronow, H., Asami, M., Bachinsky, W., Barton, J., Bass, K., Batson, B., Bell, C., Bertolet, B., Bewarder, Y., Bihlmaier, K., Binner, C., Bloom, J., Blossom, B., Brar, S., Brown, A., Burke, R., Burke, M. N., Butler, M., Calhoun, W., Campbell, J., Carroll, S., Chapman, N., Chasen, C., Cheng, S., Chia, B., Choksi, N., Cohen, J., Connolly, N., Contreras, J., Cusack, R., Dangas, G., David, S., Davies, J., Dederer, J., Denker, M., Desch, U., Didangelos, M., Dienemann, T., Dimitriadis, K., Dorval, J., Estess, J., Fan, S., Fengler, K., Ferguson, L., Fudim, M., Fuster, V., Garcia, F., Garcia, S., Garton, A., Gessler, C., Ghali, M., Gummadi, B., Gupta, A., Gutierrez, A., Hardesty, P., Hartung, P., Haught, W. H., Haun, Y., Hays, S., Helmreich, W., Hill, D., Hopper, I., Horiuchi, Y., Hoshide, S., Howard, J., Ikeda, W., Jan, F., Jauhar, R., Jay, D., Johnson, J., Johnston, T., Jones, S., Jung, S., Kalos, T., Kanitkar, M., Kannenkeril, D., Kasiakogias, A., Kazziha, S., Keene, D., Khitha, J., Kikushima, H., Kobayashi, T., Komiyama, K., Komori, T., Kotter, J., Kouparanis, A., Krasnow, J., Kulenthiran, S., Kumar, S., L'Allier, P., Laney, P., Lauder, L., Lavoie, M. A., Lerche, M., Linesky, E., Little, N., Lomboy, C., Lucic, J., Lurz, P., Lynch, S., Mansukhani, P., McDuffie, K., McGrath, B., McLaurin, B., Meade, A., Meraj, P., Millenaar, D., Moore, N., Mori, F., Munch, P., Murphy, J., Murray, J., Nanjundappa, A., Ninomiya, K., Oba, Y., O'Connor, T., Ogata, Y., Ogoyama, Y., Onsrud, R., Ott, C., Padaliya, B., Pagidipati, N., Patel, M., Patel, K., Petteinidou, E., Porr, W., Rao, A., Razi, R., Regan, C., Remetz, M., Rizik, D., Robison, M., Rommel, K., Rosseel, L., Rothstein, M., Rough, R., Saavedra, J., Saba, S., Schwartz, R., Selcer, S., Sen, S., Sennott, J., Shadman, R., Shah, S., Shemin, D., Shimizu, H., Shimpo, M., Shishehbor, M., Shun-Shin, M., Sierra, F., Singh, J., Singh, A., Sirajeldin, Y., Skeik, N., Soliman, G., Statton, S., Stehli, J., Steigerwalt, S., Striepe, K., Stuck, J., Suppan, M., Svetkey, L., Takker, G., Tanabe, K., Tanaka, T., Tomii, D., Torre, S., Traverse, J., Tyson, C., Vasquez, A., Velasquez, E., Vemulapalli, S., Waki, H., Walton, T., Wang, Y., Weber, T., Wells, B., Wilkins, R., Wright, T., Yahagi, K., Yeung, A., Zadegan, R., Zeller, T., Ziada, K., Ziakas, A., Zidar, D. 2020

  Abstract

  BACKGROUND: Catheter-based renal denervation has significantly reduced blood pressure in previous studies. Following a positive pilot trial, the SPYRAL HTN-OFF MED (SPYRAL Pivotal) trial was designed to assess the efficacy of renal denervation in the absence of antihypertensive medications.METHODS: In this international, prospective, single-blinded, sham-controlled trial, done at 44 study sites in Australia, Austria, Canada, Germany, Greece, Ireland, Japan, the UK, and the USA, hypertensive patients with office systolic blood pressure of 150 mm Hg to less than 180 mm Hg were randomly assigned 1:1 to either a renal denervation or sham procedure. The primary efficacy endpoint was baseline-adjusted change in 24-h systolic blood pressure and the secondary efficacy endpoint was baseline-adjusted change in office systolic blood pressure from baseline to 3 months after the procedure. We used a Bayesian design with an informative prior, so the primary analysis combines evidence from the pilot and Pivotal trials. The primary efficacy and safety analyses were done in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT02439749.FINDINGS: From June 25, 2015, to Oct 15, 2019, 331 patients were randomly assigned to either renal denervation (n=166) or a sham procedure (n=165). The primary and secondary efficacy endpoints were met, with posterior probability of superiority more than 0·999 for both. The treatment difference between the two groups for 24-h systolic blood pressure was -3·9 mm Hg (Bayesian 95% credible interval -6·2 to -1·6) and for office systolic blood pressure the difference was -6·5 mm Hg (-9·6 to -3·5). No major device-related or procedural-related safety events occurred up to 3 months.INTERPRETATION: SPYRAL Pivotal showed the superiority of catheter-based renal denervation compared with a sham procedure to safely lower blood pressure in the absence of antihypertensive medications.FUNDING: Medtronic.

  View details for DOI 10.1016/S0140-6736(20)30554-7

  View details for PubMedID 32234534

• Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial LANCET Townsend, R. R., Mahfoud, F., Kandzari, D. E., Kario, K., Pocock, S., Weber, M. A., Ewen, S., Tsioufis, K., Tousoulis, D., Sharp, A. P., Watkinson, A. F., Schmieder, R. E., Schmid, A., Choi, J. W., East, C., Walton, A., Hopper, I., Cohen, D. L., Wilensky, R., Lee, D. P., Ma, A., Devireddy, C. M., Lea, J. P., Lurz, P. C., Fengler, K., Davies, J., Chapman, N., Cohen, S. A., DeBruin, V., Fahy, M., Jones, D. E., Rothman, M., Boehm, M., SPYRAL HTN-OFF MED Trial 2017; 390 (10108): 2160–70

  Abstract

  Previous randomised renal denervation studies did not show consistent efficacy in reducing blood pressure. The objective of our study was to evaluate the effect of renal denervation on blood pressure in the absence of antihypertensive medications.SPYRAL HTN-OFF MED was a multicentre, international, single-blind, randomised, sham-controlled, proof-of-concept trial. Patients were enrolled at 21 centres in the USA, Europe, Japan, and Australia. Eligible patients were drug-naive or discontinued their antihypertensive medications. Patients with an office systolic blood pressure (SBP) of 150 mm Hg or greater and less than 180 mm Hg, office diastolic blood pressure (DBP) of 90 mm Hg or greater, and a mean 24-h ambulatory SBP of 140 mm Hg or greater and less than 170 mm Hg at second screening underwent renal angiography and were randomly assigned to renal denervation or sham control. Patients, caregivers, and those assessing blood pressure were blinded to randomisation assignments. The primary endpoint, change in 24-h blood pressure at 3 months, was compared between groups. Drug surveillance was done to ensure patient compliance with absence of antihypertensive medication. The primary analysis was done in the intention-to-treat population. Safety events were assessed at 3 months. This study is registered with ClinicalTrials.gov, number NCT02439749.Between June 25, 2015, and Jan 30, 2017, 353 patients were screened. 80 patients were randomly assigned to renal denervation (n=38) or sham control (n=42) and followed up for 3 months. Office and 24-h ambulatory blood pressure decreased significantly from baseline to 3 months in the renal denervation group: 24-h SBP -5·5 mm Hg (95% CI -9·1 to -2·0; p=0·0031), 24-h DBP -4·8 mm Hg (-7·0 to -2·6; p<0·0001), office SBP -10·0 mm Hg (-15·1 to -4·9; p=0·0004), and office DBP -5·3 mm Hg (-7·8 to -2·7; p=0·0002). No significant changes were seen in the sham-control group: 24-h SBP -0·5 mm Hg (95% CI -3·9 to 2·9; p=0·7644), 24-h DBP -0·4 mm Hg (-2·2 to 1·4; p=0·6448), office SBP -2·3 mm Hg (-6·1 to 1·6; p=0·2381), and office DBP -0·3 mm Hg (-2·9 to 2·2; p=0·8052). The mean difference between the groups favoured renal denervation for 3-month change in both office and 24-h blood pressure from baseline: 24-h SBP -5·0 mm Hg (95% CI -9·9 to -0·2; p=0·0414), 24-h DBP -4·4 mm Hg (-7·2 to -1·6; p=0·0024), office SBP -7·7 mm Hg (-14·0 to -1·5; p=0·0155), and office DBP -4·9 mm Hg (-8·5 to -1·4; p=0·0077). Baseline-adjusted analyses showed similar findings. There were no major adverse events in either group.Results from SPYRAL HTN-OFF MED provide biological proof of principle for the blood-pressure-lowering efficacy of renal denervation.Medtronic.

  View details for DOI 10.1016/S0140-6736(17)32281-X

  View details for Web of Science ID 000415642200021

  View details for PubMedID 28859944

• Diabetes Mellitus and Prevention of Late Myocardial Infarction After Coronary Stenting in the Randomized Dual Antiplatelet Therapy Study CIRCULATION Meredith, I. T., Tanguay, J., Kereiakes, D. J., Cutlip, D. E., Yeh, R. W., Garratt, K. N., Lee, D. P., Steg, P. G., Weaver, W. D., Holmes, D. R., Brindis, R. G., Trebacz, J., Massaro, J. M., Hsieh, W., Mauri, L. 2016; 133 (18): 1772-?

  Abstract

  Patients with diabetes mellitus (DM) are at high risk for recurrent ischemic events after coronary stenting. We assessed the effects of continued thienopyridine among patients with DM participating in the Dual Antiplatelet Therapy (DAPT) Study as a prespecified analysis.After coronary stent placement and 12 months treatment with open-label thienopyridine plus aspirin, 11 648 patients free of ischemic or bleeding events and who were medication compliant were randomly assigned to continued thienopyridine or placebo, in addition to aspirin, for 18 more months. After randomization, patients with DM (n=3391), in comparison with patients without DM (n=8257), had increased composite outcome of death, myocardial infarction (MI), or stroke (6.8% versus 4.3%, P<0.001), increased death (2.5% versus 1.4%, P<0.001), and MI (4.2% versus 2.6%, P<0.001). Among patients with DM, in a comparison of continued thienopyridine versus placebo, rates of stent thrombosis were 0.5% versus 1.1%, P=0.06, and rates of MI were 3.5% versus 4.8%, P=0.058; and among patients without DM the rates were 0.4% versus 1.4%, P<0.001 (stent thrombosis, P interaction=0.21) and 1.6% versus 3.6%, P<0.001 (MI, P interaction=0.02). Bleeding risk with continued thienopyridine was similar among patients with or without DM (interaction P=0.61).In patients with DM, continued thienopyridine beyond 1 year after coronary stenting is associated with reduced risk of MI, although this benefit is attenuated in comparison with patients without DM.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00977938.

  View details for DOI 10.1161/CIRCULATIONAHA.115.016783

  View details for Web of Science ID 000375604400007

  View details for PubMedID 26994121

• Long-term outcomes of septal reduction for obstructive hypertrophic cardiomyopathy JOURNAL OF CARDIOLOGY Sedehi, D., Finocchiaro, G., Tibayan, Y., Chi, J., Pavlovic, A., Kim, Y. M., Tibayan, F. A., Reitz, B. A., Robbins, R. C., Woo, J., Ha, R., Lee, D. P., Ashley, E. A. 2015; 66 (1-2): 57-62

  Abstract

  Surgical myectomy and alcohol septal ablation (ASA) aim to decrease left ventricular outflow tract (LVOT) gradient in hypertrophic cardiomyopathy (HCM). Outcome of myectomy beyond 10 years has rarely been described. We describe 20 years of follow-up of surgical myectomy and 5 years of follow-up for ASA performed for obstructive HCM.We studied 171 patients who underwent myectomy for symptomatic LVOT obstruction between 1972 and 2006. In addition, we studied 52 patients who underwent ASA for the same indication and who declined surgery. Follow-up of New York Heart Association (NYHA) functional class, echocardiographic data, and vital status were obtained from patient records. Mortality rates were compared with expected mortality rates of age- and sex-matched populations.Surgical myectomy improved NYHA class (2.74±0.65 to 1.54±0.74, p<0.001), reduced resting gradient (67.4±43.4mmHg to 11.2±16.4mmHg, p<0.001), and inducible LVOT gradient (98.1±34.7mmHg to 33.6±34.9mmHg, p<0.001). Similarly, ASA improved functional class (2.99±0.35 to 1.5±0.74, p<0.001), resting gradient (67.1±26.9mmHg to 23.9±29.4mmHg, p<0.001) and provoked gradient (104.4±34.9mmHg to 35.5±38.6mmHg, p<0.001). Survival after myectomy at 5, 10, 15, and 20 years of follow-up was 92.9%, 81.1%, 68.9%, and 47.5%, respectively. Of note, long-term survival after myectomy was lower than for the general population [standardized mortality ratio (SMR)=1.40, p<0.005], but still compared favorably with historical data from non-operated HCM patients. Survival after ASA at 2 and 5 years was 97.8% and 94.7%, respectively. Short-term (5 year) survival after ASA (SMR=0.61, p=0.48) was comparable to that of the general population.Long-term follow-up of septal reduction strategies in obstructive HCM reveals that surgical myectomy and ASA are effective for symptom relief and LVOT gradient reduction and are associated with favorable survival. While overall prognosis for the community HCM population is similar to the general population, the need for surgical myectomy may identify a sub-group with poorer long-term prognosis. We await long-term outcomes of more extensive myectomy approaches adopted in the past 10 years at major institutions.

  View details for DOI 10.1016/j.jjcc.2014.08.010

  View details for Web of Science ID 000359684600010

• Antiplatelet Therapy Duration Following Bare Metal or Drug-Eluting Coronary Stents The Dual Antiplatelet Therapy Randomized Clinical Trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Kereiakes, D. J., Yeh, R. W., Massaro, J. M., Driscoll-Shempp, P., Cutlip, D. E., Steg, P. G., Gershlick, A. H., Darius, H., Meredith, I. T., Ormiston, J., Tanguay, J. F., Windecker, S., Garratt, K. N., Kandzari, D. E., Lee, D. P., Simon, D. I., Iancu, A. C., Trebacz, J., Mauri, L. 2015; 313 (11): 1113-1121

  Abstract

  Despite antirestenotic efficacy of coronary drug-eluting stents (DES) compared with bare metal stents (BMS), the relative risk of stent thrombosis and adverse cardiovascular events is unclear. Although dual antiplatelet therapy (DAPT) beyond 1 year provides ischemic event protection after DES, ischemic event risk is perceived to be less after BMS, and the appropriate duration of DAPT after BMS is unknown.To compare (1) rates of stent thrombosis and major adverse cardiac and cerebrovascular events (MACCE; composite of death, myocardial infarction, or stroke) after 30 vs 12 months of thienopyridine in patients treated with BMS taking aspirin and (2) treatment duration effect within the combined cohorts of randomized patients treated with DES or BMS as prespecified secondary analyses.International, multicenter, randomized, double-blinded, placebo-controlled trial comparing extended (30-months) thienopyridine vs placebo in patients taking aspirin who completed 12 months of DAPT without bleeding or ischemic events after receiving stents. The study was initiated in August 2009 with the last follow-up visit in May 2014.Continued thienopyridine or placebo at months 12 through 30 after stent placement, in 11,648 randomized patients treated with aspirin, of whom 1687 received BMS and 9961 DES.Stent thrombosis, MACCE, and moderate or severe bleeding.Among 1687 patients treated with BMS who were randomized to continued thienopyridine vs placebo, rates of stent thrombosis were 0.5% vs 1.11% (n = 4 vs 9; hazard ratio [HR], 0.49; 95% CI, 0.15-1.64; P = .24), rates of MACCE were 4.04% vs 4.69% (n = 33 vs 38; HR, 0.92; 95% CI, 0.57-1.47; P = .72), and rates of moderate/severe bleeding were 2.03% vs 0.90% (n = 16 vs 7; P = .07), respectively. Among all 11,648 randomized patients (both BMS and DES), stent thrombosis rates were 0.41% vs 1.32% (n = 23 vs 74; HR, 0.31; 95% CI, 0.19-0.50; P < .001), rates of MACCE were 4.29% vs 5.74% (n = 244 vs 323; HR, 0.73; 95% CI, 0.62-0.87; P < .001), and rates of moderate/severe bleeding were 2.45% vs 1.47% (n = 135 vs 80; P < .001).Among patients undergoing coronary stent placement with BMS and who tolerated 12 months of thienopyridine, continuing thienopyridine for an additional 18 months compared with placebo did not result in statistically significant differences in rates of stent thrombosis, MACCE, or moderate or severe bleeding. However, the BMS subset may have been underpowered to identify such differences, and further trials are suggested.clinicaltrials.gov Identifier: NCT00977938.

  View details for DOI 10.1001/jama.2015.1671

  View details for PubMedID 25781440

• Predictors of blood pressure response in the SYMPLICITY HTN-3 trial. European heart journal Kandzari, D. E., Bhatt, D. L., Brar, S., Devireddy, C. M., Esler, M., Fahy, M., Flack, J. M., Katzen, B. T., Lea, J., Lee, D. P., Leon, M. B., Ma, A., Massaro, J., Mauri, L., Oparil, S., O'Neill, W. W., Patel, M. R., Rocha-Singh, K., Sobotka, P. A., Svetkey, L., Townsend, R. R., Bakris, G. L. 2015; 36 (4): 219-227

  Abstract

  The SYMPLICITY HTN-3 randomized, blinded, sham-controlled trial confirmed the safety of renal denervation (RDN), but did not meet its primary efficacy endpoint. Prior RDN studies have demonstrated significant and durable reductions in blood pressure. This analysis investigated factors that may help explain these disparate results.Patients with resistant hypertension were randomized 2 : 1 to RDN (n = 364) or sham (n = 171). The primary endpoint was the difference in office systolic blood pressure (SBP) change at 6 months. A multivariable analysis identified predictors of SBP change. Additional analyses examined the influence of medication changes, results in selected subgroups and procedural factors. Between randomization and the 6-month endpoint, 39% of patients underwent medication changes. Predictors of office SBP reduction at 6 months were baseline office SBP ≥180 mmHg, aldosterone antagonist use, and non-use of vasodilators; number of ablations was a predictor in the RDN group. Non-African-American patients receiving RDN had a significantly greater change in office SBP than those receiving sham; -15.2 ± 23.5 vs. -8.6 ± 24.8 mmHg, respectively (P = 0.012). Greater reductions in office and ambulatory SBP, and heart rate were observed with a higher number of ablations and energy delivery in a four-quadrant pattern.Post hoc analyses, although derived from limited patient cohorts, reveal several potential confounding factors that may partially explain the unexpected blood pressure responses in both the sham control and RDN groups. These hypothesis-generating data further inform the design of subsequent research to evaluate the potential role of RDN in the treatment of resistant hypertension.NCT01418261.

  View details for DOI 10.1093/eurheartj/ehu441

  View details for PubMedID 25400162

  View details for PubMedCentralID PMC4301597

• Prasugrel plus aspirin beyond 12 months is associated with improved outcomes after taxus liberté Paclitaxel-eluting coronary stent placement. Circulation Garratt, K. N., Weaver, W. D., Jenkins, R. G., Pow, T. K., Mauri, L., Kereiakes, D. J., Winters, K. J., Christen, T., Allocco, D. J., Lee, D. P. 2015; 131 (1): 62-73

  Abstract

  The TAXUS Liberté Post Approval Study (TL-PAS) contributed patients treated with TAXUS Liberté paclitaxel-eluting stent and prasugrel to the Dual Antiplatelet Therapy Study (DAPT) that compared 12 and 30 months thienopyridine plus aspirin therapy after drug-eluting stents.Outcomes for 2191 TL-PAS patients enrolled into DAPT were assessed. The DAPT coprimary composite end point (death, myocardial infarction [MI], or stroke) was lower with 30 compared with 12 months prasugrel treatment (3.7% versus 8.8%; hazard ratio [HR], 0.407; P<0.001). Rates of death and stroke were similar between groups, but MI was significantly reduced with prolonged prasugrel treatment (1.9% versus 7.1%; HR, 0.255; P<0.001). The DAPT coprimary end point, stent thrombosis, was also lower with longer therapy (0.2% versus 2.9%; HR, 0.063; P<0.001). MI related to stent thrombosis (0% versus 2.6%; P<0.001) and occurring spontaneously (1.9% versus 4.5%; HR, 0.407; P=0.007) were both reduced with prolonged prasugrel. MI rates increased within 90 days of prasugrel cessation after both 12 and 30 months treatment. Composite Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) moderate or severe bleeds were modestly increased (2.4% versus 1.7%; HR, 1.438; P=0.234) but severe bleeds were not more frequent (0.3% versus 0.5%; HR, 0.549; P=0.471) in the prolonged treatment group.Prasugrel and aspirin continued for 30 months reduced ischemic events for the TAXUS Liberté paclitaxel-eluting stent patient subset from DAPT through reductions in MI and stent thrombosis. Withdrawal of prasugrel was followed by an increase in MI after both 12 and 30 months therapy. The optimal duration of dual antiplatelet therapy with prasugrel after TAXUS Liberté paclitaxel-eluting stent remains unknown, but appears to be >30 months.http://www.clinicaltrials.gov. Unique identifier: NCT00997503.

  View details for DOI 10.1161/CIRCULATIONAHA.114.013570

  View details for PubMedID 25400062

• Twelve or 30 Months of Dual Antiplatelet Therapy after Drug-Eluting Stents NEW ENGLAND JOURNAL OF MEDICINE Mauri, L., Kereiakes, D. J., Yeh, R. W., Driscoll-Shempp, P., Cutlip, D. E., Steg, P. G., Normand, S. T., Braunwald, E., Wiviott, S. D., Cohen, D. J., Holmes, D. R., Krucoff, M. W., Hermiller, J., Dauerman, H. L., Simon, D. I., Kandzari, D. E., Garratt, K. N., Lee, D. P., Pow, T. K., Lee, P. V., Rinaldi, M. J., Massaro, J. M. 2014; 371 (23): 2155-2166

  Abstract

  Dual antiplatelet therapy is recommended after coronary stenting to prevent thrombotic complications, yet the benefits and risks of treatment beyond 1 year are uncertain.Patients were enrolled after they had undergone a coronary stent procedure in which a drug-eluting stent was placed. After 12 months of treatment with a thienopyridine drug (clopidogrel or prasugrel) and aspirin, patients were randomly assigned to continue receiving thienopyridine treatment or to receive placebo for another 18 months; all patients continued receiving aspirin. The coprimary efficacy end points were stent thrombosis and major adverse cardiovascular and cerebrovascular events (a composite of death, myocardial infarction, or stroke) during the period from 12 to 30 months. The primary safety end point was moderate or severe bleeding.A total of 9961 patients were randomly assigned to continue thienopyridine treatment or to receive placebo. Continued treatment with thienopyridine, as compared with placebo, reduced the rates of stent thrombosis (0.4% vs. 1.4%; hazard ratio, 0.29 [95% confidence interval {CI}, 0.17 to 0.48]; P<0.001) and major adverse cardiovascular and cerebrovascular events (4.3% vs. 5.9%; hazard ratio, 0.71 [95% CI, 0.59 to 0.85]; P<0.001). The rate of myocardial infarction was lower with thienopyridine treatment than with placebo (2.1% vs. 4.1%; hazard ratio, 0.47; P<0.001). The rate of death from any cause was 2.0% in the group that continued thienopyridine therapy and 1.5% in the placebo group (hazard ratio, 1.36 [95% CI, 1.00 to 1.85]; P=0.05). The rate of moderate or severe bleeding was increased with continued thienopyridine treatment (2.5% vs. 1.6%, P=0.001). An elevated risk of stent thrombosis and myocardial infarction was observed in both groups during the 3 months after discontinuation of thienopyridine treatment.Dual antiplatelet therapy beyond 1 year after placement of a drug-eluting stent, as compared with aspirin therapy alone, significantly reduced the risks of stent thrombosis and major adverse cardiovascular and cerebrovascular events but was associated with an increased risk of bleeding. (Funded by a consortium of eight device and drug manufacturers and others; DAPT ClinicalTrials.gov number, NCT00977938.).

  View details for DOI 10.1056/NEJMoa1409312

  View details for Web of Science ID 000345976700004

  View details for PubMedID 25399658

• 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

  Abstract

  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

• Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial LANCET Esler, M. D., Krum, H., Sobotka, P. A., Schlaich, M. P., Schmieder, R. E., Boehm, M., Mahfoud, F., Sievert, H., Wunderlich, N., Rump, L. C., Vonend, O., Uder, M., Lobo, M., Caulfield, M., Erglis, A., Azizi, M., Sapoval, M., Thambar, S., Persu, A., Renkin, J., Schunkert, H., Weil, J., Hoppe, U. C., Walton, T., Scheinert, D., Binder, T., Januszewicz, A., Witkowski, A., Ruilope, L. M., Whitbourn, R., Bruck, H., Downes, M., Luescher, T. F., Jardine, A. G., Webster, M. W., Zeller, T., Sadowski, J., Bartus, K., Straley, C. A., Barman, N. C., Lee, D. P., Witteles, R. M., Bhalla, V., Massaro, J. M. 2010; 376 (9756): 1903-1909

  Abstract

  Activation of renal sympathetic nerves is key to pathogenesis of essential hypertension. We aimed to assess effectiveness and safety of catheter-based renal denervation for reduction of blood pressure in patients with treatment-resistant hypertension.In this multicentre, prospective, randomised trial, patients who had a baseline systolic blood pressure of 160 mm Hg or more (≥150 mm Hg for patients with type 2 diabetes), despite taking three or more antihypertensive drugs, were randomly allocated in a one-to-one ratio to undergo renal denervation with previous treatment or to maintain previous treatment alone (control group) at 24 participating centres. Randomisation was done with sealed envelopes. Data analysers were not masked to treatment assignment. The primary effectiveness endpoint was change in seated office-based measurement of systolic blood pressure at 6 months. Primary analysis included all patients remaining in follow-up at 6 months. This trial is registered with ClinicalTrials.gov, number NCT00888433.106 (56%) of 190 patients screened for eligibility were randomly allocated to renal denervation (n=52) or control (n=54) groups between June 9, 2009, and Jan 15, 2010. 49 (94%) of 52 patients who underwent renal denervation and 51 (94%) of 54 controls were assessed for the primary endpoint at 6 months. Office-based blood pressure measurements in the renal denervation group reduced by 32/12 mm Hg (SD 23/11, baseline of 178/96 mm Hg, p<0·0001), whereas they did not differ from baseline in the control group (change of 1/0 mm Hg [21/10], baseline of 178/97 mm Hg, p=0·77 systolic and p=0·83 diastolic). Between-group differences in blood pressure at 6 months were 33/11 mm Hg (p<0·0001). At 6 months, 41 (84%) of 49 patients who underwent renal denervation had a reduction in systolic blood pressure of 10 mm Hg or more, compared with 18 (35%) of 51 controls (p<0·0001). We noted no serious procedure-related or device-related complications and occurrence of adverse events did not differ between groups; one patient who had renal denervation had possible progression of an underlying atherosclerotic lesion, but required no treatment.Catheter-based renal denervation can safely be used to substantially reduce blood pressure in treatment-resistant hypertensive patients.Ardian.

  View details for DOI 10.1016/S0140-6736(10)62039-9

  View details for Web of Science ID 000285439800031

  View details for PubMedID 21093036

• LONG-TERM PATHOLOGICAL CHANGES IN ABLATED RENAL NERVES FOLLOWING CATHETER-BASED RADIOFREQUENCY RENAL DENERVATION IN A NORMOTENSIVE SWINE MODEL Schlaich, M., Tunev, S., Sharp, A., Lee, D. P., Finn, A., Trudel, J., Kandzari, D. E. LIPPINCOTT WILLIAMS & WILKINS. 2023: E282-E283

  View details for Web of Science ID 000921768301070

• Translational value of preclinical models for renal denervation: a histological comparison of human versus porcine renal nerve anatomy. EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology Sato, Y., Sharp, A. S., Mahfoud, F., Tunev, S., Forster, A., Ellis, M., Gomez, A., Dhingra, R., Ullman, J., Schlaich, M., Lee, D., Trudel, J., Hettrick, D. A., Kandzari, D. E., Virmani, R., Finn, A. V. 2022

  Abstract

  BACKGROUND: Preclinical models have provided key insights into the response of local tissues to radiofrequency (RF) renal denervation (RDN) that is unobtainable from human studies. However, the anatomic translatability of these models to the procedure in humans is incompletely understood. Aims: We aimed to compare the renal arterial anatomy in normotensive pigs treated with RF-RDN to that of human cadavers to evaluate the suitability of normotensive pigs for determining the safety of RF-RDN.METHODS: Histopathologic analyses were performed on RF-treated renal arteries in a porcine model and untreated control renal arteries. Similar analyses were performed on untreated renal arteries from human cadavers. Results: In both human and porcine renal arteries, the median number of nerves was lower in the more distal sections (the numbers in the proximal, middle, distal, 1st bifurcation, and 2nd bifurcation sections were 65, 58, 47, 22.5, and 14.7 in humans, respectively, and 39, 26, 29, 16.5, and 9.3 in the porcine models, respectively). Renal nerves were common in the regions between arteries and adjacent veins, but only 3% and 13% of the renal nerves in humans and pigs, respectively, were located behind the renal vein. The semiquantitative score of RF-induced renal arterial nerve necrosis was significantly greater at 7 days than 28 days (0.98 vs 0.75; p=0.01), and injury to surrounding organs was rarely observed.CONCLUSIONS: The distribution of nerve tissue and the relative distribution of extravascular anatomic structures along the renal artery was similar between humans and pigs, which validates the translational value of the normotensive porcine model for RDN.

  View details for DOI 10.4244/EIJ-D-22-00369

  View details for PubMedID 36214318

• Improving on the 5. JACC. Asia Lee, D. P. 2022; 2 (5): 557-558

  View details for DOI 10.1016/j.jacasi.2022.08.006

  View details for PubMedID 36624788

• Hypertension urgencies in the SPYRAL HTN-OFF MED Pivotal trial. Clinical research in cardiology : official journal of the German Cardiac Society Weber, M. A., Schmieder, R. E., Kandzari, D. E., Townsend, R. R., Mahfoud, F., Tsioufis, K., Kario, K., Pocock, S., Tatakis, F., Ewen, S., Choi, J. W., East, C., Lee, D. P., Ma, A., Cohen, D. L., Wilensky, R., Devireddy, C. M., Lea, J. P., Schmid, A., Fahy, M., Bohm, M. 2022

  Abstract

  The SPYRAL HTN-OFF MED Pivotal trial ( https://clinicaltrials.gov/ct2/show/NCT02439749 ) demonstrated significant reductions in blood pressure (BP) after renal denervation (RDN) compared to sham control in the absence of anti-hypertensive medications. Prior to the 3-month primary endpoint, medications were immediately reinstated for patients who met escape criteria defined as office systolic BP (SBP)≥180mmHg or other safety concerns. Our objective was to compare the rate of hypertensive urgencies in RDN vs. sham control patients. Patients were enrolled with office SBP≥150 and<180mmHg, office diastolic BP (DBP)≥90mmHg and mean 24h SBP≥140 and<170mmHg. Patients had been required to discontinue any anti-hypertensive medications and were randomized 1:1 to RDN or sham control. In this post-hoc analysis, cumulative incidence curves with Kaplan-Meier estimates of rate of patients meeting escape criteria were generated for RDN and sham control patients. There were 16 RDN (9.6%) and 28 sham control patients (17.0%) who met escape criteria between baseline and 3months. There was a significantly higher rate of sham control patients meeting escape criteria compared to RDN for all escape patients (p=0.032), as well as for patients with a hypertensive urgency with office SBP≥180mmHg (p=0.046). Rate of escape was similar between RDN and sham control for patients without a measured BP exceeding 180mmHg (p=0.32). In the SPYRAL HTN-OFF MED Pivotal trial, RDN patients were less likely to experience hypertensive urgencies that required immediate use of anti-hypertensive medications compared to sham control.

  View details for DOI 10.1007/s00392-022-02064-5

  View details for PubMedID 35852582

• Histological evidence supporting the durability of successful radiofrequency renal denervation in a normotensive porcine model. Journal of hypertension Sharp, A. S., Tunev, S., Schlaich, M., Lee, D. P., Finn, A. V., Trudel, J., Hettrick, D. A., Mahfoud, F., Kandzari, D. E. 2022

  Abstract

  BACKGROUND: Sustained blood pressure reductions after radiofrequency (RF) renal denervation (RDN) have been reported to 3 years in patients with uncontrolled hypertension. However, mechanistic data to support procedural durability are lacking. We aimed to quantify the long-term nerve anatomic and functional effects of RF RDN in a preclinical model.METHODS: Bilateral RF RDN was performed in 20 normotensive swine. Renal tissue samples were obtained in the RDN-treated groups at 7 (n = 6), 28 (n = 6), and 180 days (n = 8) postprocedure for quantification of cortical norepinephrine (NE) levels and renal cortical axon density. Tissue fibrosis, necrosis and downstream nerve fiber atrophy (axonal loss) were also scored for each sample. Three additional untreated groups (n = 6, n = 6 and n = 8, respectively) served as control.RESULTS: Pathologic nerve changes were characterized by necrosis in the ablated region at 7 days that partially resolved by 28 days and fully resolved at 180 days. Axonal loss was apparent within and downstream to the ablation regions and was evident at 7, 28 and 180 days in the main vessel and branch vessels. Consequently, renal cortical axon density and corresponding cortical NE levels were significantly reduced at 7 days in the RDN vs. control group and remained suppressed at 180 days.CONCLUSIONS: Reductions in renal NE, cortical axon density and downstream axonal loss caused by axonal destruction persisted through 180 days post-RDN in a normotensive swine model. These results suggest functional nerve regrowth after RF RDN is unlikely and support published clinical evidence that the procedure results in durable blood pressure reduction.

  View details for DOI 10.1097/HJH.0000000000003236

  View details for PubMedID 35866489

• Phosphoproteomic mapping reveals distinct signaling actions and activation of muscle protein synthesis by Isthmin-1 eLife Zhao, M., Banhos Danneskiold-Samsøe, N., Ulicna, L., Nguyen, Q., Voilquin, L., Lee, D. E., White, J. P., Jiang, Z., Cuthbert, N., Paramasivam, S., Bielczyk-Maczynska, E., van Rechem, C., Svensson, K. J. 2022

  View details for DOI 10.7554/eLife.80014

• Durability of Radio-Frequency Catheter-Based Renal Denervation Associated With Lack of Functional Nerve Recovery at 6 Months in Normotensive Swine Model Sharp, A., Tunev, S., Schlaich, M., Lee, D., Finn, A., Mahfoud, F., Trudel, J., Kandzari, D. ELSEVIER SCIENCE INC. 2021: B9

  View details for Web of Science ID 000715526900020

• Modest Gains After an 8-Week Exercise Program Correlate With Reductions in Non-traditional Markers of Cardiovascular Risk FRONTIERS IN CARDIOVASCULAR MEDICINE Liang, G., Huang, X., Hirsch, J., Mehmi, S., Fonda, H., Chan, K., Huang, N. F., Aalami, O., Froelicher, V. F., Lee, D. P., Myers, J., Lee, A. S., Nguyen, P. K. 2021; 8: 669110

  Abstract

  Background: Although engaging in physical exercise has been shown to reduce the incidence of cardiovascular events, the molecular mechanisms by which exercise mediates these benefits remain unclear. Based on epidemiological evidence, reductions in traditional risk factors only accounts for 50% of the protective effects of exercise, leaving the remaining mechanisms unexplained. The objective of this study was to determine whether engaging in a regular exercise program in a real world clinical setting mediates cardiovascular protection via modulation of non-traditional risk factors, such as those involved in coagulation, inflammation and metabolic regulation. Methods and Results: We performed a prospective, cohort study in 52 sedentary patients with cardiovascular disease or cardiovascular risk factors at two tertiary medical centers between January 1, 2016 and December 31, 2019. Prior to and at the completion of an 8-week exercise program, we collected information on traditional cardiovascular risk factors, exercise capacity, and physical activity and performed plasma analysis to measure levels of fibrinolytic, inflammatory and metabolic biomarkers to assess changes in non-traditional cardiovascular risk factors. The median weight change, improvement in physical fitness, and change in physical activity for the entire cohort were: -4.6 pounds (IQR: +2 pounds, -11.8 pounds), 0.37 METs (IQR: -0.076 METs, 1.06 METs), and 252.7 kcals/week (IQR: -119, 921.2 kcals/week). In addition to improvement in blood pressure and cholesterol, patients who lost at least 5 pounds, expended at least 1,000 additional kcals/week, and/or achieved ≥0.5 MET increase in fitness had a significant reduction in plasminogen activator inhibitor-1 [9.07 ng/mL (95% CI: 2.78-15.35 ng/mL); P = 0.026], platelet derived growth factor beta [376.077 pg/mL (95% CI: 44.69-707.46 pg/mL); P = 0.026); and angiopoietin-1 [(1104.11 pg/mL (95% CI: 2.92-2205.30 pg/mL); P = 0.049)]. Conclusion: Modest improvements in physical fitness, physical activity, and/or weight loss through a short-term exercise program was associated with decreased plasma levels of plasminogen activator inhibitor, platelet derived growth factor beta, and angiopoietin, which have been associated with impaired fibrinolysis and inflammation.

  View details for DOI 10.3389/fcvm.2021.669110

  View details for Web of Science ID 000668338500001

  View details for PubMedID 34222367

  View details for PubMedCentralID PMC8245677

• ANATOMY OF RENAL DENERVATION DURABILITY Sharp, A., Tunev, S., Schlaich, M., Lee, D., Finn, A., Melder, R., Trudel, J., Kandzari, D. LIPPINCOTT WILLIAMS & WILKINS. 2021: E10

  View details for Web of Science ID 000672599900028

• Insights To Lesion Formation For Percutaneous Renal Denervation: Human And Porcine Histological Analyses Kandzari, D., Tunev, S., Schlaich, M. P., Lee, D. P., Finn, A., Mahfoud, F., Melder, R., Trudel, J., Coates, P., Sharp, A. S. LIPPINCOTT WILLIAMS & WILKINS. 2020

  View details for DOI 10.1161/hyp.76.suppl_1.P203

  View details for Web of Science ID 000619826700261

• Dose-Response Relationship Between Intracoronary Acetylcholine and Minimal Lumen Diameter in Coronary Endothelial Function Testing of Women and Men With Angina and No Obstructive Coronary Artery Disease. Circulation. Cardiovascular interventions Pargaonkar, V. S., Lee, J. H., Chow, E. K., Nishi, T., Ball, R. L., Kobayashi, Y., Kimura, T., Lee, D. P., Stefanick, M. L., Fearon, W. F., Yeung, A. C., Tremmel, J. A. 2020; 13 (4): e008587

  Abstract

  BACKGROUND: Intracoronary acetylcholine (Ach) provocation testing is the gold standard for assessing coronary endothelial function. However, dosing regimens of Ach are quite varied in the literature, and there are limited data evaluating the optimal dose. We evaluated the dose-response relationship between Ach and minimal lumen diameter (MLD) by sex and studied whether incremental intracoronary Ach doses given during endothelial function testing improve its diagnostic utility.METHODS: We evaluated 65 men and 212 women with angina and no obstructive coronary artery disease who underwent endothelial function testing using the highest tolerable dose of intracoronary Ach, up to 200 mug. Epicardial endothelial dysfunction was defined as a decrease in MLD >20% after intracoronary Ach by quantitative coronary angiography. We used a linear mixed effects model to evaluate the dose-response relationship. Deming regression analysis was done to compare the %MLD constriction after incremental doses of intracoronary Ach.RESULTS: The mean age was 53.5 years. Endothelial dysfunction was present in 186 (68.1%). Among men with endothelial dysfunction, there was a significant decrease in MLD/10 g of Ach at doses above 50 mug and 100 g, while this decrease in MLD was not observed in women (P<0.001). The %MLD constriction at 20 mug versus 50 mug and 50 mug versus 100 mug were not equivalent while the %MLD constriction at 100 mug versus 200 mug were equivalent.CONCLUSIONS: Women and men appear to have different responses to Ach during endothelial function testing. In addition to having a greater response to intracoronary Ach at all doses, men also demonstrate an Ach-MLD dose-response relationship with doses up to 200 mug, while women have minimal change in MLD with doses above 50 g. An incremental dosing regimen during endothelial function testing appears to improve the diagnostic utility of the test and should be adjusted based on the sex of the patient.

  View details for DOI 10.1161/CIRCINTERVENTIONS.119.008587

  View details for PubMedID 32279562

• Optimizing Safety and Efficacy of Lesion Formation for Percutaneous Renal Denervation: Human and Porcine Histological Analysis Sharp, A., Tunev, S., Schlaich, M., Lee, D., Finn, A., Melder, R., Coates, P., Trudel, J. ELSEVIER SCIENCE INC. 2019: B596

  View details for Web of Science ID 000487306300597

• Novel Multiphase Assessment for Predicting Left Ventricular Outflow Tract Obstruction Before Transcatheter Mitral Valve Replacement. JACC. Cardiovascular interventions Meduri, C. U., Reardon, M. J., Scott Lim, D. n., Howard, E. n., Dunnington, G. n., Lee, D. P., Liang, D. n., Gooley, R. n., O'Hair, D. n., Ng, M. K., Walton, A. n., Spargias, K. n., Blackman, D. n., Coisne, A. n., Hildick-Smith, D. n., De Gouy, M. n., Chenoweth, S. n., Kar, S. n., McCarthy, P. M., Piazza, N. n., Qasam, A. n., Martin, R. P., Leon, M. B., Mack, M. J., Adams, D. H., Bapat, V. n. 2019

  Abstract

  This study proposes a physiologic assessment of left ventricular outflow tract obstruction (LVOTO) that accommodates changes in systolic flow and accounts for the dynamic neo-left ventricular outflow tract (LVOT).Patients considered for transcatheter mitral valve replacement trials often screen-fail because of the perceived risk of LVOTO. In the Intrepid Global Pilot Study, assumed risk of LVOTO was based on computed tomography estimates of the neo-LVOT area computed at end-systole. However, this may overestimate actual risk.Retrospective analyses were performed for screen-failed patients for potential LVOTO (n = 33) and treated patients (n = 29) with available dynamic computed tomography. A multiphase assessment of the neo-LVOT area was performed and represented as: 1) multiphase average; and 2) early systolic value. Prospective evaluation was performed in 9 patients approved for enrollment with multiphase and early systole methods that would have previously screen-failed with the end-systolic approach.Of 166 patients screened for possible inclusion; 32 were screen-failed for nonanatomical reasons. Screen failure for assumed LVOTO risk occurred in 37 of 134 (27.6%) patients. Retrospective analysis indicated a potential enrollment increase of 11 of 33 (33.3%) and 18 of 33 (54.5%) patients using multiphase and early systolic assessment methods. In the prospective cohort, there were no clinical observations of LVOTO 30 days post-procedure, despite assumed risk based on end-systolic estimates.Multiphase, and specifically early systolic, assessment of the neo-LVOT may better determine risk of LVOTO with transcatheter mitral valve replacement compared with end-systolic estimates. This novel approach has the potential to significantly increase patient eligibility, with over one-half of patients previously screen-failed now eligible for treatment.

  View details for DOI 10.1016/j.jcin.2019.06.015

  View details for PubMedID 31629753

• Atrial Septal Defect as Unexpected Cause of Pulmonary Artery Hypertension TEXAS HEART INSTITUTE JOURNAL Parikh, R., Boyd, J., Lee, D. P., Witteles, R. 2018; 45 (1): 42–44

  Abstract

  Methamphetamine abuse is an increasingly prevalent cause of pulmonary artery hypertension in the United States. Conversely, an atrial septal defect rarely presents late as pulmonary artery hypertension. We present the case of a 44-year-old methamphetamine abuser who had a 3-month history of worsening fatigue and near-syncope. She had elevated cardiac enzyme levels and right-sided heart strain. Angiographic findings suggested methamphetamine-induced pulmonary artery hypertension; however, we later heard S2 irregularities that raised suspicion of an atrial septal defect. Ultimately, the diagnosis was pulmonary artery hypertension and a large secundum atrial septal defect with left-to-right flow. One year after defect closure, the patient was asymptomatic. In addition to discussing this unexpected case of a secundum atrial septal defect masquerading as methamphetamine-induced pulmonary artery hypertension, we briefly review the natural history of atrial septal defects and emphasize the importance of thorough examination in avoiding diagnostic anchoring bias.

  View details for DOI 10.14503/THIJ-17-6208

  View details for Web of Science ID 000426402700011

  View details for PubMedID 29556152

  View details for PubMedCentralID PMC5832086

• 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. n., Kimura, T. n., Schnittger, I. n., 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

  Abstract

  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

• Impact of Septal Reduction on Left Atrial Size and Diastole in Hypertrophic Cardiomyopathy ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES Finocchiaro, G., Haddad, F., Kobayashi, Y., Lee, D., Pavlovic, A., Schnittger, I., Sinagra, G., Magavern, E., Myers, J., Froelicher, V., Knowles, J. W., Ashley, E. 2016; 33 (5): 686-694

  Abstract

  Both myectomy and alcohol septal ablation (ASA) can substantially reduce left ventricular (LV) outflow obstruction, relieve symptoms, and improve outcomes in hypertrophic cardiomyopathy (HCM). It is unclear whether septal reduction decreases left atrial (LA) size and improves diastolic function. The aim of this study was to analyze the consequences of septal reduction on LA size and diastolic function in a cohort of patients with HCM.Forty patients (mean age: 50 ± 14, male sex 64%) with HCM who underwent septal reduction (myectomy or alcohol septal ablation) were studied. Retrospective analyses of echocardiograms preprocedure, postprocedure, and at 1 year of follow-up were performed.Thirty-one patients had septal myectomy and 9 ASA. The degree of reduction in rest peak LV outflow tract gradient was significant (57 ± 32 vs. 23 ± 20 mmHg at 1 year, P < 0.001). Maximal interventricular septal thickness decreased from 22 ± 6 mm preprocedure to 19 ± 4 mm postprocedure (P < 0.001); moderate-to-severe mitral regurgitation (MR) was initially present in 34% of the sample and only 2% after the procedure. Average LA volume index (LAVI) decreased from 63 ± 20 to 55 ± 20 mL/m(2) at the 1-year follow-up (P < 0.001). We did not observe a significant improvement in diastolic function at Doppler (E/A 1.2 ± 0.4 vs. 1.1 ± 0.5, P = 0.07; E' 7.6 ± 3.6 vs. 6.9 ± 3.0, P = 0.4) pre- and postprocedure, respectively). At 1 year, only 5% of the patients were severely symptomatic (NYHA III). On multivariate analysis, a significant change in the LVOT gradient during stress (Δ gradient ≥30 mmHg) was the only variable independently associated with LAVI reverse remodeling >10 mL/m(2) [OR = 6.4 (CI 95% 1.12-36.44), P = 0.04].Septal reduction is effective in the relief of LV obstruction and symptoms in patients with HCM. The hemodynamic changes result in a significant LA reverse remodeling, but not in an improvement of diastolic function in these patients.

  View details for DOI 10.1111/echo.13158

  View details for PubMedID 26926154

• 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

• Stent Thrombosis in Drug-Eluting or Bare-Metal Stents in Patients Receiving Dual Antiplatelet Therapy JACC-CARDIOVASCULAR INTERVENTIONS Kereiakes, D. J., Yeh, R. W., Massaro, J. M., Driscoll-Shempp, P., Cutlip, D. E., Steg, P. G., Gershlick, A. H., Darius, H., Meredith, I. T., Ormiston, J., Tanguay, J., Windecker, S., Garratt, K. N., Kandzari, D. E., Lee, D. P., Simon, D. I., Iancu, A. C., Trebacz, J., Mauri, L. 2015; 8 (12): 1552-1562

  Abstract

  This study sought to compare rates of stent thrombosis and major adverse cardiac and cerebrovascular events (MACCE) (composite of death, myocardial infarction, or stroke) after coronary stenting with drug-eluting stents (DES) versus bare-metal stents (BMS) in patients who participated in the DAPT (Dual Antiplatelet Therapy) study, an international multicenter randomized trial comparing 30 versus 12 months of dual antiplatelet therapy in subjects undergoing coronary stenting with either DES or BMS.Despite antirestenotic efficacy of coronary DES compared with BMS, the relative risk of stent thrombosis and adverse cardiovascular events is unclear. Many clinicians perceive BMS to be associated with fewer adverse ischemic events and to require shorter-duration dual antiplatelet therapy than DES.Prospective propensity-matched analysis of subjects enrolled into a randomized trial of dual antiplatelet therapy duration was performed. DES- and BMS-treated subjects were propensity-score matched in a many-to-one fashion. The study design was observational for all subjects 0 to 12 months following stenting. A subset of eligible subjects without major ischemic or bleeding events were randomized at 12 months to continued thienopyridine versus placebo; all subjects were followed through 33 months.Among 10,026 propensity-matched subjects, DES-treated subjects (n = 8,308) had a lower rate of stent thrombosis through 33 months compared with BMS-treated subjects (n = 1,718, 1.7% vs. 2.6%; weighted risk difference -1.1%, p = 0.01) and a noninferior rate of MACCE (11.4% vs. 13.2%, respectively, weighted risk difference -1.8%, p = 0.053, noninferiority p < 0.001).DES-treated subjects have long-term rates of stent thrombosis that are lower than BMS-treated subjects. (The Dual Antiplatelet Therapy Study [DAPT study]; NCT00977938).

  View details for DOI 10.1016/j.jcin.2015.05.026

  View details for Web of Science ID 000363268600010

  View details for PubMedID 26493248

• Response to Letters Regarding Article, "Prasugrel Plus Aspirin Beyond 12 Months Is Associated With Improved Outcomes After TAXUS Liberte Paclitaxel-Eluting Coronary Stent Placement" CIRCULATION Garratt, K. N., Weaver, W., Jenkins, R. G., Pow, T. K., Mauri, L., Kereiakes, D. J., Winters, K. J., Christen, T., Allocco, D. J., Lee, D. P. 2015; 132 (13): E166–E167

  View details for PubMedID 26416639

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

  Abstract

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

  View details for DOI 10.1016/j.jcin.2015.03.045

  View details for Web of Science ID 000361757600013

• 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): 1433-41

  Abstract

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

  View details for DOI 10.1016/j.jcin.2015.03.045

  View details for PubMedID 26404195

• Contrast-Enhanced C-arm Computed Tomography Imaging of Myocardial Infarction in the Interventional Suite INVESTIGATIVE RADIOLOGY Girard, E. E., Al-Ahmad, A., Rosenberg, J., Luong, R., Moore, T., Lauritsch, G., Chan, F., Lee, D. P., Fahrig, R. 2015; 50 (6): 384-391

  Abstract

  Cardiac C-arm computed tomography (CT) uses a standard C-arm fluoroscopy system rotating around the patient to provide CT-like images during interventional procedures without moving the patient to a conventional CT scanner. We hypothesized that C-arm CT can be used to visualize and quantify the size of perfusion defects and late enhancement resulting from a myocardial infarction (MI) using contrast-enhanced techniques similar to previous CT and magnetic resonance imaging studies.A balloon occlusion followed by reperfusion in a coronary artery was used to study acute and subacute MI in 12 swine. Electrocardiographically gated C-arm CT images were acquired the day of infarct creation (n = 6) or 4 weeks after infarct creation (n = 6). The images were acquired immediately after contrast injection, then at 1 minute, and every 5 minutes up to 30 minutes with no additional contrast. The volume of the infarct as measured on C-arm CT was compared against pathology.The volume of acute MI, visualized as a combined region of hyperenhancement with a hypoenhanced core, correlated well with pathologic staining (concordance correlation, 0.89; P < 0.0001; mean [SD] difference, 0.67 [2.98] cm). The volume of subacute MI, visualized as a region of hyperenhancement, correlated well with pathologic staining at imaging times 5 to 15 minutes after contrast injection (concordance correlation, 0.82; P < 0.001; mean difference, -0.64 [1.94] cm).C-arm CT visualization of acute and subacute MI is possible in a porcine model, but improvement in the imaging technique is important before clinical use. Visualization of MI in the catheterization laboratory may be possible and could provide 3-dimensional images for guidance during interventional procedures.

  View details for Web of Science ID 000354380900003

  View details for PubMedID 25635589

• 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

  Abstract

  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

• CONTRAST-ENHANCED ROTATIONAL ANGIOGRAPHIC C-ARM CT IMAGING OF MYOCARDIAL INFARCTION IN THE INTERVENTIONAL SUITE: OPTIMIZED IMAGING PROTOCOL FOR ACUTE AND CHRONIC INFARCTS 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC)/Conference on ACC-i2 with TCT Girard, E., Moore, T., Lauritsch, G., Rosenberg, J., Al-Ahmad, A., Chan, F., Lee, D., Fahrig, R. ELSEVIER SCIENCE INC. 2012: E169–E169

  View details for Web of Science ID 000302326700170

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

  Abstract

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

  View details for DOI 10.1016/j.jacc.2011.09.079

  View details for Web of Science ID 000301443000003

  View details for PubMedID 22421299

• Cardiac Paraganglioma: Diagnostic and Surgical Challenges JOURNAL OF CARDIAC SURGERY Huo, J. L., Choi, J. C., DeLuna, A., Lee, D., Fleischmann, D., Berry, G. J., Deuse, T., Haddad, F. 2012; 27 (2): 178-182

  Abstract

  Primary cardiac paragangliomas are rare extra-adrenal tumors. Though they account for less than 1% of all primary cardiac tumors, they are considerable sources of morbidity and mortality. In this case review, we discuss the challenges associated with the diagnosis and management of cardiac paragangliomas.

  View details for DOI 10.1111/j.1540-8191.2011.01378.x

  View details for Web of Science ID 000302172800009

  View details for PubMedID 22273468

• Rationale and design of the TAXUS Liberte Post-Approval Study: Examination of patients receiving the TAXUS Liberte stent with concomitant prasugrel therapy in routine interventional cardiology practice AMERICAN HEART JOURNAL Garratt, K. N., Lee, D. P., Rose, E. M., Windle, K. J., Liao, H., Nwachuku, C. E., Winters, K. J., Bowman, T. S., Dawkins, K. D. 2012; 163 (2): 142-U226

  Abstract

  Observational studies of new coronary stents are necessary to assess performance in a variety of complex patient and lesion types. Furthermore, the optimal dose and duration of thienopyridine treatment is unclear, particularly in patients with complex clinical conditions. The TAXUS Libertē Post-Approval Study is designed to provide 5-year data on the TAXUS Liberté paclitaxel-eluting stent with concomitant prasugrel therapy in routine clinical practice and to contribute data to the DAPT study.The TAXUS Libertē Post-Approval Study is a prospective, multicenter, observational study. Enrollment of approximately 4,200 patients receiving ≥1 TAXUS Liberté stents is planned. All patients without a contraindication will be prescribed prasugrel plus aspirin for 1 year. The 12-month primary end point of cardiac death or myocardial infarction in on-label stent patients will be compared with historical TAXUS Express stent data from the TAXUS ATLAS and TAXUS ARRIVE studies. Secondary clinical end points include stent thrombosis, all-cause death, stroke, revascularization, and bleeding in all patients. In addition, this study will be the first to evaluate prasugrel use in a routine practice setting (including 5 and 10 mg daily doses) and will contribute data to the DAPT Study, comparing 12 versus 30 months of dual antiplatelet therapy after drug-eluting stent placement.The TAXUS Libertē Post-Approval Study will be the first to provide long-term real-world data on use of the TAXUS Liberté Stent with prasugrel treatment. The study is currently enrolling, and primary end point data are expected in mid 2013.

  View details for DOI 10.1016/j.ahj.2011.11.002

  View details for Web of Science ID 000300226600003

  View details for PubMedID 22305829

• Coil Embolization of a Left Circumflex Feeder Branch in a Patient With a Mediastinal Paraganglioma JACC-CARDIOVASCULAR INTERVENTIONS Ho, M. Y., Fleischmann, D., Forrester, M. D., Lee, D. P. 2011; 4 (12): 1345-1346

  View details for DOI 10.1016/j.jcin.2011.06.021

  View details for PubMedID 22192376

• 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

  Abstract

  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

• In-Hospital Experience of "Real World" Patients Enrolled in the TAXUS Liberte Post-Approval Study: The TAXUS Liberte Stent with Concomitant Prasugrel Therapy 23rd Annual Scientific Symposium of Transcatheter Cardiovascular Therapeutics (TCT) Lee, D. P., Garratt, K. N., Paulus, R., Carr, J., Giri, K., Kabour, A., Winters, K. J., Bowman, T. S., Dawkins, K. D. ELSEVIER SCIENCE INC. 2011: B58–B58

  View details for Web of Science ID 000296891900224

• 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

  Abstract

  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

• Managing Pre-Hospital ECGs: The Devil Is in the Details JOURNAL OF INVASIVE CARDIOLOGY Ko, J., Lee, D. P. 2010; 22 (11): 526-526

  View details for Web of Science ID 000284808400006

  View details for PubMedID 21041848

• Outcomes of Septal Myectomy and Alcohol Septal Ablation for Obstructive Hypertrophic Cardiomyopathy: The Stanford Experience 82nd National Conference and Exhibitions and Scientific Sessions of the American-Heart-Association Tibayan, Y., Sedehi, D., Chi, J., Pavlovic, A., Salisbury, H., Wheeler, M., Ho, M. Y., Sgroi, M., Kim, Y., Tibayan, F. A., Reitz, B. A., Robbins, R. C., Lee, D. P., Ashley, E. A. LIPPINCOTT WILLIAMS & WILKINS. 2009: S864–S864

  View details for Web of Science ID 000271831502680

• On and Off: The Dilemma of Managing STEMI After Hours JOURNAL OF INVASIVE CARDIOLOGY Patel, S., Lee, D. P. 2009; 21 (10): 523-524

  View details for Web of Science ID 000284807100008

  View details for PubMedID 19805839

• Safety and Efficacy of Drug Eluting Stents for Treatment of Cardiac Allograft Vasculopathy: A Prospective Clinical and Angiographic Study 21st Annual Transcatheter Cardiovascular Therapeutics Conference Ng, M. K., Tremmel, J., Ikeno, F., Lee, D. P., Yeung, A. C., Fearon, W. F. EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2009: 138D–138D

  View details for Web of Science ID 000269981600385

• Does the Presence of a Corporate Representative Affect Choice of Coronary Stent? 21st Annual Transcatheter Cardiovascular Therapeutics Conference Van, H., Yamen, E., Blanchard, J., Yeung, A. C., Lee, D. P. EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2009: 204D–204D

  View details for Web of Science ID 000269981600563

• Biopsy of Cardiac Masses Using a Stabilized Intracardiac Echocardiography-guided System JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY Sze, D. Y., Lee, D. P., Hofmann, L. V., Petersen, B. 2008; 19 (11): 1662-1667

  Abstract

  Biopsy of a cardiac mass remains a difficult and risky procedure. Successful sampling of target tissue is hampered by continuous cardiac motion and blood flow. Because the surrounding tissues are vascular, complications can include hemorrhage, tamponade, arrhythmia, embolization, and death. Conventional imaging modalities are of limited utility in this dynamic environment. The present report describes the use of the instrumentation system originally designed for creation of direct portocaval shunts with intracardiac echocardiography imaging to perform core biopsies of cardiac and juxtacardiac masses in six patients. There were no hemorrhagic complications, and pathologic diagnoses were obtained in five of six cases.

  View details for DOI 10.1016/j.jvir.2008.08.001

  View details for Web of Science ID 000260694700020

  View details for PubMedID 18818096

• 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)

  Abstract

  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

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

  Abstract

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

  View details for DOI 10.1016/j.jacc.2007.08.062

  View details for PubMedID 18237685

• A Cagey Proposition JOURNAL OF INVASIVE CARDIOLOGY Ho, Y., Lee, D. P. 2008; 20 (1): 28-28

  View details for Web of Science ID 000207734600007

  View details for PubMedID 18174615

• Femoral artery puncture above the proximal third of the femoral head better predicts retroperitoneal hemorrhage in percutaneous coronary intervention than arteriotomies above the most inferior border or origin of the inferior epigastric artery 19th Annual Transcatheter Cardiovascular Therapeutics Symposium Ho, Y., O'Loughlin, A. J., Chat, T. C., Lee, D. P., Tremmel, J. A. EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2007: 228L–228L

  View details for Web of Science ID 000250393900582

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

  Abstract

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

  View details for DOI 10.1016/j.amjcard.2007.01.039

  View details for PubMedID 17531589

• Spontaneous coronary artery dissection in a woman with depression without coronary atherosclerotic risk factors. journal of invasive cardiology Ho, Y., Koizumi, T., Lee, D. P. 2007; 19 (6): E166-8

  View details for PubMedID 17541140

• Recurrent spontaneous coronary artery dissection with transient left ventricular systolic dysfunction. International journal of cardiology Ardehali, R., Brinton, T. J., Wilson, A. M., Gradman, M., Vagelos, R. H., Lee, D. P. 2007; 116 (2): e48-50

  Abstract

  Spontaneous coronary artery dissection (SCAD) is a potentially life-threatening entity with a variety of clinical presentations. We report a patient who presented with chest pain and angiographic evidence of coronary dissection. Due to the rapid resolution of symptoms and benign-appearing nature of the dissection, no intervention was pursued and the patient was maintained on medical therapy. She represented 2 days later with substernal chest pain, dynamic EKG changes, positive cardiac biomarkers and a transient depression of her left ventricular function.

  View details for PubMedID 16930750

• Index of microcirculatory resistance: A novel measure for predicting myocardial damage in patients with acute myocardial infarction 79th Annual Scientific Session of the American-Heart-Association Shah, M., Tremmel, J., Brinton, T., Wilson, A., Schnittger, I., Lee, D. P., Yeung, A. C., Fearon, W. F. LIPPINCOTT WILLIAMS & WILKINS. 2006: 586–87

  View details for Web of Science ID 000241792803637

• Final results from the US multi-center trial of the AngioSculpt scoring balloon catheter for the treatment of complex coronary artery lesions 18th Annual Transcatheter Cardiovascular Therapeutics Symposium Mooney, M. R., Teirstein, P. S., Moses, J. W., Turco, M., Reisman, M., Waksman, R., Saucedo, J. F., Mauri, L., Lee, D., Gershony, G., Mehran, R., Carlier, S. G., Lansky, A. J., Leon, M. B. EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2006: 121M–121M

  View details for Web of Science ID 000241442800292

• Percutaneous translurninal coronary angioplasty in a two-month old with coronary stenosis presenting as congenital cardiomyopathy: Acute results and intermediate follow-up CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Cheng, C. W., Lee, D. P., Rosenthal, D. N., Feinstein, J. A. 2006; 68 (4): 632-636

  Abstract

  Congenital or nonsurgically acquired obstructive coronary artery disease in infancy is exceedingly rare, and previous reports of catheter-based therapies in very young patients have been solely in patients having undergone arterial switch or other cardiovascular surgical procedures. We describe a previously unreported cause for ventricular dysfunction and heart failure in an infant, isolated congenital circumflex coronary artery stenosis, and successful treatment with percutaneous transluminal coronary angioplasty. Technical considerations, immediate results, and 3-year follow-up are provided.

  View details for DOI 10.1002/ccd.20750

  View details for PubMedID 16969876

• 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

  Abstract

  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

  Abstract

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

  View details for DOI 10.1016/j.healun.2006.03.003

  View details for PubMedID 16818118

• Rapamycin therapy improves coronary physiology after cardiac transplantation 55th Annual Scientific Session of the American-College-of-Cardiology Sinha, S. S., Lee, D. P., Pham, M. X., Vagelos, R. H., Hunt, S. A., Valentine, H. A., Yeung, A. C., Fearon, W. F. ELSEVIER SCIENCE INC. 2006: 51A–51A

  View details for Web of Science ID 000235530400222

• Index of microcirculatory resistance: A novel measure for predicting myocardial damage in patients with acute myocardial infarction 55th Annual Scientific Session of the American-College-of-Cardiology Shah, M. G., Tremmel, J., Brinton, T., Wilson, A., Schnittger, I., Lee, D. P., Yeung, A. C., Fearon, W. F. ELSEVIER SCIENCE INC. 2006: 182A–182A

  View details for Web of Science ID 000235530401102

• 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

  Abstract

  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

• Women remain at higher risk for retroperitoneal hematoma after percutaneous coronary intervention in the era of glycoprotein IIb/IIIa inhibitors and vascular closure devices 53rd Annual Scientific Session of the American-College-of-Cardiology Farouque, H. M., Tremmel, J. A., Aggarwal, M., Shabari, F. R., Fearon, W. F., Rezaee, M., Yeung, A. C., Lee, D. P. ELSEVIER SCIENCE INC. 2004: 63A–63A

  View details for Web of Science ID 000189388500266

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

  Abstract

  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

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

  Abstract

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

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

  View details for PubMedID 12963639

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

  Abstract

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

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

  View details for PubMedID 12943881

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

  Abstract

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

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

  View details for PubMedID 12742295

• 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

  Abstract

  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

• 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

  Abstract

  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

• Physiologic interrogation of transplant arterioparthy: Final results 52nd Annual Scientific Session of the American-College-of-Cardiology 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. ELSEVIER SCIENCE INC. 2003: 29A–29A

  View details for Web of Science ID 000181669500129

• Physiologic interrogation of transplant arteriopathy American-Heart-Association Abstracts From Scientific Sessions Fearon, W. F., Nakamura, M., Lee, D. P., Rezaee, M., Vagelos, R. H., Hunt, S. A., Yock, P. G., Yeung, A. C. LIPPINCOTT WILLIAMS & WILKINS. 2002: 591–91

  View details for Web of Science ID 000179142702958

• 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

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

  Abstract

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

  View details for DOI 10.1053/euhj.2001.2707

  View details for Web of Science ID 000173390100009

  View details for PubMedID 11785994

• Targeting the adventitia with intracoronary beta-radiation: Comparison of two dose prescriptions and the role of centering in coronary arteries INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Kaluza, G. L., Jenkins, T. P., Mourtada, F. A., Ali, N. M., Lee, D. P., Okura, H., Fitzgerald, P. J., Raizner, A. E. 2002; 52 (1): 184-191

  Abstract

  To compare by intravascular ultrasound (IVUS) the efficacy of delivering the prescribed dose to the adventitia between two commonly used dose prescriptions for intracoronary radiotherapy.In 59 human postangioplasty coronary vessels, one IVUS cross-section (1 mm thick) with the highest plaque burden was used for creating dose-volume histograms with different hypothetical positions of the source.On average, prescription to 1 mm beyond lumen surface resulted in delivery of the prescribed dose (20 Gy +/- 20%) to a higher fraction of adventitial volume than with the prescription to 2 mm from the source, with source placed in vessel center, lumen center, or in the IVUS catheter position. Source placement in the lumen center resulted in a low dose heterogeneity to the adventitia and the least dose heterogeneity to the intima.Prescription to 1 mm beyond lumen surface appeared more effective in delivering the prescribed dose to the adventitia than the American Association of Physicists in Medicine (AAPM) recommended prescription to 2 mm from the source center. Moreover, centering the source in the lumen provides the better balance of effective adventitial targeting and intimal dose homogeneity. Modification of the current AAPM recommendation for dose prescription for intracoronary radiotherapy should be considered.

  View details for Web of Science ID 000173105100023

  View details for PubMedID 11777637

• Clinical utility of the exercise ECG in patients with diabetes and chest pain CHEST Lee, D. P., Fearon, W. F., Froelicher, V. F. 2001; 119 (5): 1576-1581

  Abstract

  The purpose of this study was to determine the characteristics of exercise treadmill testing in diabetic patients presenting with chest pain.The diagnosis of coronary artery disease (CAD) in diabetic patients is confounded by different manifestations of coronary disease than are seen in the general population. Because of the association of diabetes with accelerated CAD, it is critical to assess the diagnostic utility of the standard exercise test in diabetic patients with chest pain.This study was a retrospective analysis of standard exercise test results in 1,282 male patients without prior myocardial infarction who had undergone coronary angiography and were being evaluated for possible CAD at two Veterans' Administration institutions.In patients with diabetes, 38% had an abnormal exercise test result, and the prevalence of angiographic CAD was 69%; the sensitivity of the exercise test was 47% (95% confidence interval [CI], 41 to 58), and specificity was 81% (95% CI, 68 to 89). In patients without diabetes, 38% had an abnormal exercise test result, and the prevalence of angiographic CAD was 58%; the sensitivity of the exercise test was 52% (95% CI, 48 to 56), and specificity was 80% (95% CI, 76 to 83). The receiver operating characteristic curves were also similar in both diabetic and nondiabetic patients (0.67 and 0.68, respectively).These data demonstrate that the standard exercise test has similar diagnostic characteristics in diabetic as in nondiabetic patients.

  View details for PubMedID 11348969

• 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

  Abstract

  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

• Safety and efficacy of high pressure retrograde cardiac venous injection. Implications for regional myocardial delivery Herity, N. A., Fearon, W., Hiatt, B. L., Rezaee, M., Suzuki, T., Lee, D. P., Yeung, A. C., Carter, A. J., Fitzgerald, P. J., Yock, P. G. ELSEVIER SCIENCE INC. 2001: 6A–6A

  View details for Web of Science ID 000166914400029

• 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-?

  Abstract

  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

• 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

• 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

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

  Abstract

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

  View details for Web of Science ID 000166116000022

  View details for PubMedID 11137098

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

  Abstract

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

  View details for PubMedID 11066126

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

  Abstract

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

  View details for PubMedID 10996357

• Experimental evaluation of a short transitional edge protection balloon for intracoronary stent deployment CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Carter, A. J., Lee, D. P., Suzuki, T., Bailey, L., Lansky, A., Jones, R., Virmani, R. 2000; 51 (1): 112-119

  Abstract

  The purpose of this study was to determine if balloon injury to the adjacent arterial wall during intracoronary stent deployment influences late in-stent neointimal formation. Stent design and deployment techniques are considered important factors in determining acute and long-term success with intracoronary stenting. Experimental and clinical studies support that the extent of neointimal formation and the probability for restenosis are influenced by the magnitude of arterial trauma induced with stenting. Nineteen 18-mm-long balloon-expandable stainless steel stents (MULTI-LINK Duet) were implanted at a 1:1 stent-to-artery ratio in the coronary arteries of swine with a conventional noncompliant balloon (n = 10) or a novel noncompliant balloon with short tapered shoulders to prevent edge dissection (n = 9). Quantitative coronary angiography and histology were used to evaluate balloon and artery interactions and the chronic vascular responses to the stents. Nineteen stents were implanted in the coronary arteries of seven swines at an inflation pressure of 14 atm using a standard noncompliant (n = 10) or a unique short transitional edge protection (n = 9) balloon. Histologic analysis at 28 days demonstrated balloon-associated barotrauma in 13 of 20 (65%) of adjacent nonstented arterial segments with the conventional balloon and only 3 of 18 (17%) of the adjacent nonstented arterial segments with the short transition edge protection balloon (P = 0.022). In-stent neointimal area and % stenosis correlated with the severity of peristent arterial injury (r = 0.43, P = 0.01). In-stent vessel injury scores were similar for stents with peristent injury (1.0+/-0.3) versus stents without peristent injury (1.0+/-0.03, P = 0.73). In-stent neointimal area and % stenosis were greater for stents with peristent injury (2.36+/-0.74 mm(2), 32%+/-9%) as compared to stents without peristent injury (1.39+/-0.70 mm(2), 20%+/-10%, P = 0.01). Arterial wall injury adjacent to a stent after high-pressure deployment contributes to late in-stent neointimal hyperplasia in this model. These experimental data suggest that further study is warranted to refine stent implantation techniques and that modifications of balloon shape or material may be useful to optimize stent deployment and reduce arterial trauma.

  View details for Web of Science ID 000089106300026

  View details for PubMedID 10973033

• Patterns of aspirin use before hospitalization for acute myocardial infarction AMERICAN JOURNAL OF CARDIOLOGY Lorenz, D. P., Lee, D. P., Alderman, E. 2000; 86 (2): 214-216

  View details for Web of Science ID 000088125300016

  View details for PubMedID 10913485

• The effect of resting ST segment depression on the diagnostic characteristics of the exercise treadmill test JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Fearon, W. F., Lee, D. P., Froelicher, V. F. 2000; 35 (5): 1206-1211

  Abstract

  The aim of this study is to demonstrate the effect of resting ST segment depression on the diagnostic characteristics of the exercise treadmill test.Previous studies evaluating the effect of resting ST segment depression on the diagnostic characteristics of exercise treadmill test have been conducted on relatively small patient groups and based only on visual electrocardiogram (ECG) analysis.A retrospective analysis of data collected prospectively was performed on consecutive patients referred for evaluation of chest pain. One thousand two hundred eighty-two patients without a prior myocardial infarction underwent standard exercise treadmill tests followed by coronary angiography, with coronary artery disease defined as a 50% narrowing in at least one major epicardial coronary artery. Sensitivity, specificity, predictive accuracy and area under the curve of the receiver operating characteristic (ROC) plots were calculated for patients with and without resting ST segment depression as determined by visual or computerized analysis of the baseline ECG.Sensitivity of the exercise treadmill test increased in 206 patients with resting ST segment depression determined by visual ECG analysis compared with patients without resting ST segment depression (77 +/- 7% vs. 45 +/- 4%) and specificity decreased (48 +/- 12% vs. 84 +/- 3%). With computerized analysis, sensitivity of the treadmill test increased in 349 patients with resting ST segment depression compared with patients without resting ST segment depression (71 +/- 6% vs. 42 +/- 4%) and specificity decreased (52 +/- 9% vs. 87 +/- 3%) (p < 0.0001 for all comparisons). There was no significant difference in the area under the curve of the ROC plots (0.66-0.69) or the predictive accuracy (62-68%) between the four subgroups.The diagnostic accuracy and high sensitivity of the exercise treadmill test in a large cohort of patients with resting ST segment depression and no prior myocardial infarction support the initial use of the test for diagnosis of coronary artery disease. The classification of resting ST segment depression by method of analysis (visual vs. computerized) did not affect the results.

  View details for PubMedID 10758962

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

  Abstract

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

  View details for Web of Science ID 000085838000018

  View details for PubMedID 12000055

• Intracardiac venous system as a novel conduit for local drug delivery Rezaee, M., Lo, S. T., Bailey, L., Suzuki, T., Lee, D. P., Yock, P. G., Fitzgerald, P. J., Yeung, A. C., Stertzer, S., Carter, A. ELSEVIER SCIENCE INC. 2000: 6A–6A

  View details for Web of Science ID 000085209700023

• 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

  View details for Web of Science ID 000085209700126

• Can the fractional flow reserve be reliably measured by contrast induced hyperemia? Filardo, S. D., Jeremias, A., Lee, D. P., Lo, S. T., Herity, N. A., Ward, M. R., Yeung, A. C., Yock, P. G. LIPPINCOTT WILLIAMS & WILKINS. 1999: 454–54

  View details for Web of Science ID 000083417102390

• 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

  Abstract

  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

• Ruptured plaques have greater degree of remodeling than stable lesions: An IVUS study Schwarzacher, S., Huegel, H., Filardo, S. D., Lee, D. P., Yeung, A. C. LIPPINCOTT WILLIAMS & WILKINS. 1998: 145–45

  View details for Web of Science ID 000076594400792

• Intracoronary radiation with a P-32 source wire HERZ Lee, D. P., Lo, S., Forster, K. M., Tate, D. J., Raizner, A., Oesterle, S. N. 1998; 23 (6): 362-365

  Abstract

  The Proliferation REduction with Vascular ENergy Trial (PREVENT) is a prospective randomized study of the safety and efficacy of intracoronary brachytherapy to reduce restenosis. A beta-emitter, 32P, is embedded on a wire tip and delivered to the target site through a centering catheter immediately following a coronary intervention. The radiation doses are 16, 20, and 24 Gy measured at 1 mm within the vessel wall. Follow-up includes an angiogram and IVUS at 6 months. Phase I of this trial has been completed with results expected in early 1999.

  View details for Web of Science ID 000076260300005

  View details for PubMedID 9816522