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Bio

Clinical Focus


  • Cardiovascular Disease

Academic Appointments


Professional Education


  • Board Certification: American Board of Internal Medicine, Cardiovascular Disease (1983)
  • Fellowship: Stanford University School of Medicine (1983) CA
  • Board Certification: American Board of Internal Medicine, Internal Medicine (1981)
  • Residency: Stanford University Hospital -Clinical Excellence Research Center (1981) CA
  • Internship: McGill University (1980) Canada
  • Medical Education: McGill University (1978) Canada

Publications

All Publications


  • Transcatheter Aortic Valve Replacement in Low-Risk Patients: 2-Year Results from the LRT Trial. American heart journal Waksman, R., Torguson, R., Medranda, G. A., Shea, C., Zhang, C., Gordon, P., Ehsan, A., Wilson, S. R., Levitt, R., Hahn, C., Parikh, P., Bilfinger, T., Butzel, D., Buchanan, S., Hanna, N., Buchbinder, M., Asch, F., Weissman, G., Ben-Dor, I., Shults, C., Garcia-Garcia, H. M., Satler, L. F., Rogers, T. 2021

    Abstract

    BACKGROUND: Previous studies from the Low Risk TAVR (LRT) trial demonstrated that transcatheter aortic valve replacement (TAVR) is safe and feasible in low-risk patients, with excellent 30-day and 1-year outcomes. The objective of this study was to report clinical outcomes and the impact of 30-day hypoattenuated leaflet thickening (HALT) on structural valve deterioration (SVD) 2 years after TAVR.METHODS: The LRT trial was the first Food and Drug Administration-approved Investigational Device Exemption trial in the United States to evaluate the safety and feasibility of TAVR in low-risk patients with symptomatic severe tricuspid aortic stenosis (AS). Valve hemodynamics and SVD by echo were recorded 30 days, 1 year, and 2 years post-TAVR.RESULTS: The LRT trial enrolled 200 low-risk patients to receive TAVR. Their mean age was 73.6 years and 61.5% were men. At 2-year follow-up, the mortality rate was 4.2%; the cardiovascular death rate was 1.6%. The disabling stroke rate was 1.1%, permanent pacemaker implantation rate was 8.6%, and 4 patients (2.2%) presented with endocarditis (2 between year 1 and 2). Of the 14% of TAVR subjects who had evidence of HALT at 30 days, there was no impact on valve hemodynamics, endocarditis or stroke at 2 years.CONCLUSIONS: TAVR for low-risk patients with symptomatic severe tricuspid AS is safe at 2 years. The presence of HALT at 30 days did not impact the early hemodynamic improvements nor the durability of the valve structure.

    View details for DOI 10.1016/j.ahj.2021.03.006

    View details for PubMedID 33713618

  • Anatomical characteristics associated with hypoattenuated leaflet thickening in low-risk patients undergoing transcatheter aortic valve replacement. Cardiovascular revascularization medicine : including molecular interventions Khan, J. M., Rogers, T., Weissman, G., Torguson, R., Rodriguez-Weisson, F. J., Chezar-Azerrad, C., Greenspun, B., Gupta, N., Medvedofsky, D., Zhang, C., Gordon, P., Ehsan, A., Wilson, S. R., Goncalves, J., Levitt, R., Hahn, C., Parikh, P., Bilfinger, T., Butzel, D., Buchanan, S., Hanna, N., Garrett, R., Shults, C., Buchbinder, M., Garcia-Garcia, H. M., Kolm, P., Satler, L. F., Hashim, H., Ben-Dor, I., Asch, F. M., Waksman, R. 2020

    Abstract

    BACKGROUND/PURPOSE: This sub-analysis of the prospective Low Risk TAVR (LRT) trial determined anatomical characteristics associated with hypoattenuated leaflet thickening (HALT), which may contribute to early transcatheter heart valve (THV) degeneration.METHODS/MATERIALS: The LRT trial enrolled 200 low-risk patients between February 2016 and February 2018. All subjects underwent baseline and 30-day CT studies, analyzed by an independent core laboratory. Additional measurements, namely THV expansion, eccentricity, depth, and commissural alignment, were made by consensus of three independent readers. HALT was observed only in the Sapien 3 THV, so Evolut valves were excluded from this analysis.RESULTS: In the LRT trial, 177 subjects received Sapien 3 THVs, of whom 167 (94.3%) had interpretable 30-day CTs and were eligible for this analysis. Twenty-six subjects had HALT (15.6%). Baseline characteristics were similar between groups. There was no difference in THV size implanted and baseline aortic-root geometry between groups. In patients who developed HALT, THV implantation depth was shallower than in patients who did not develop HALT (2.6±1.1mm HALT versus 3.3±1.8mm no-HALT, p=0.03). There were more patients in the HALT group with commissural malalignment (40% vs. 28%; p=0.25), but this did not reach statistical significance. In a univariable regression model, no predetermined variables were shown to independently predict the development of HALT.CONCLUSIONS: This study did not find anatomical or THV implantation characteristics that predicted the development of HALT at 30days. This study cannot exclude subtle effects or interaction between factors because of the small number of events.SUMMARY: This sub-analysis of the prospective Low Risk TAVR trial found that hypoattenuated leaflet thickening (HALT) was associated with shallower transcatheter heart valve implantation. No predictors of HALT were found in a univariable regression analysis.

    View details for DOI 10.1016/j.carrev.2020.09.034

    View details for PubMedID 33129688

  • Coronary Artery Disease Assessed by Computed Tomography-Based Leaman Score in Patients With Low-Risk Transcatheter Aortic Valve Implantation. The American journal of cardiology Ozaki, Y. n., Garcia-Garcia, H. M., Rogers, T. n., Torguson, R. n., Craig, P. E., Hideo-Kajita, A. n., Gordon, P. n., Ehsan, A. n., Parikh, P. n., Bilfinger, T. n., Butzel, D. n., Buchanan, S. n., Levitt, R. n., Hahn, C. n., Buchbinder, M. n., Hanna, N. n., Garrett, R. n., Wilson, S. R., Goncalves, J. A., Ali, S. n., Asch, F. M., Weissman, G. n., Shults, C. n., Ben-Dor, I. n., Satler, L. F., Waksman, R. n. 2020

    Abstract

    We aimed to evaluate the burden of coronary artery disease (CAD) using the computed tomography (CT) Leaman score in low-risk transcatheter aortic valve implantation (TAVI) patients. The extent of CAD in low-risk patients with aortic stenosis who are candidates for TAVI has not been accurately quantified. The CT Leaman score was developed to quantify coronary CT angiography (CCTA) atherosclerotic burden and has been validated to evaluate the extent of CAD. CT Leaman score >5 has been associated with an increase in major adverse cardiac events over long-term follow-up. The study population included patients enrolled in the Low Risk TAVI trial who underwent CCTA before the procedure. For the CT Leaman score, we used 3 sets of weighting factors: (1) location of coronary plaques, (2) type of plaque, and (3) degree of stenosis. A total of 200 patients were enrolled in the Low Risk TAVI trial. Excluded were 31 patients who had no analyzable CCTA imaging. For the remaining 169 patients, the mean CT Leaman score was 6.27 ± 0.27, of whom 102 (60.4%) had CT Leaman score >5. Nearly all analyzed patients (97%) had coronary plaques. Furthermore, 33 patients (19.5%) had potentially obstructive coronary plaques (>50% stenosis by CCTA) in proximal segments. Most low-risk TAVI patients have significant CAD burden by CCTA. It should be a priority for future TAVI devices to guarantee unimpeded access to the coronary arteries for selective angiography and interventions.

    View details for DOI 10.1016/j.amjcard.2020.01.022

    View details for PubMedID 32087995

  • Feasibility of Coronary Access and Aortic Valve Reintervention in Low-Risk TAVR Patients. JACC. Cardiovascular interventions Rogers, T. n., Greenspun, B. C., Weissman, G. n., Torguson, R. n., Craig, P. n., Shults, C. n., Gordon, P. n., Ehsan, A. n., Wilson, S. R., Goncalves, J. n., Levitt, R. n., Hahn, C. n., Parikh, P. n., Bilfinger, T. n., Butzel, D. n., Buchanan, S. n., Hanna, N. n., Garrett, R. n., Buchbinder, M. n., Asch, F. n., Garcia-Garcia, H. M., Okubagzi, P. n., Ben-Dor, I. n., Satler, L. F., Waksman, R. n. 2020; 13 (6): 726?35

    Abstract

    The aim of this study was to evaluate the feasibility of coronary access and aortic valve reintervention in low-risk patients undergoing transcatheter aortic valve replacement (TAVR) with a balloon-expandable transcatheter heart valve (THV).Younger, low-risk TAVR patients are more likely than older, higher risk patients to require coronary angiography, percutaneous coronary intervention, or aortic valve reintervention, but their THVs may impede coronary access and cause coronary obstruction during TAVR-in-TAVR.The LRT (Low Risk TAVR) trial (NCT02628899) enrolled 200 subjects with symptomatic severe aortic stenosis to undergo TAVR using commercially available THVs. Subjects who received balloon-expandable THVs and who had 30-day cardiac computed tomographic scans were included in this study. In a subgroup, the feasibility of intentional THV crimping on the delivery catheter to pre-determine commissural alignment was tested.In the LRT trial, 168 subjects received balloon-expandable THVs and had 30-day cardiac computed tomographic scans, of which 137 were of adequate image quality for analysis. The most challenging anatomy for coronary access (THV frame above and commissural suture post in front of a coronary ostium) was observed in 9% to 13% of subjects. Intentional THV crimping did not appear to meaningfully affect commissural alignment. The THV frame extended above the sinotubular junction in 21% of subjects, and in 13%, the distance between the THV and the sinotubular junction was <2 mm, signifying that TAVR-in-TAVR may not be feasible without causing coronary obstruction.TAVR may present challenges to future coronary access and aortic valve reintervention in a substantial number of low-risk patients.

    View details for DOI 10.1016/j.jcin.2020.01.202

    View details for PubMedID 32192693

  • Ticagrelor in Patients with Stable Coronary Disease and Diabetes. The New England journal of medicine Steg, P. G., Bhatt, D. L., Simon, T., Fox, K., Mehta, S. R., Harrington, R. A., Held, C., Andersson, M., Himmelmann, A., Ridderstrale, W., Leonsson-Zachrisson, M., Liu, Y., Opolski, G., Zateyshchikov, D., Ge, J., Nicolau, J. C., Corbalan, R., Cornel, J. H., Widimsky, P., Leiter, L. A., THEMIS Steering Committee and Investigators 2019

    Abstract

    BACKGROUND: Patients with stable coronary artery disease and diabetes mellitus who have not had a myocardial infarction or stroke are at high risk for cardiovascular events. Whether adding ticagrelor to aspirin improves outcomes in this population is unclear.METHODS: In this randomized, double-blind trial, we assigned patients who were 50 years of age or older and who had stable coronary artery disease and type 2 diabetes mellitus to receive either ticagrelor plus aspirin or placebo plus aspirin. Patients with previous myocardial infarction or stroke were excluded. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety outcome was major bleeding as defined by the Thrombolysis in Myocardial Infarction (TIMI) criteria.RESULTS: A total of 19,220 patients underwent randomization. The median follow-up was 39.9 months. Permanent treatment discontinuation was more frequent with ticagrelor than placebo (34.5% vs. 25.4%). The incidence of ischemic cardiovascular events (the primary efficacy outcome) was lower in the ticagrelor group than in the placebo group (7.7% vs. 8.5%; hazard ratio, 0.90; 95% confidence interval [CI], 0.81 to 0.99; P=0.04), whereas the incidence of TIMI major bleeding was higher (2.2% vs. 1.0%; hazard ratio, 2.32; 95% CI, 1.82 to 2.94; P<0.001), as was the incidence of intracranial hemorrhage (0.7% vs. 0.5%; hazard ratio, 1.71; 95% CI, 1.18 to 2.48; P=0.005). There was no significant difference in the incidence of fatal bleeding (0.2% vs. 0.1%; hazard ratio, 1.90; 95% CI, 0.87 to 4.15; P=0.11). The incidence of an exploratory composite outcome of irreversible harm (death from any cause, myocardial infarction, stroke, fatal bleeding, or intracranial hemorrhage) was similar in the ticagrelor group and the placebo group (10.1% vs. 10.8%; hazard ratio, 0.93; 95% CI, 0.86 to 1.02).CONCLUSIONS: In patients with stable coronary artery disease and diabetes without a history of myocardial infarction or stroke, those who received ticagrelor plus aspirin had a lower incidence of ischemic cardiovascular events but a higher incidence of major bleeding than those who received placebo plus aspirin. (Funded by AstraZeneca; THEMIS ClinicalTrials.gov number, NCT01991795.).

    View details for DOI 10.1056/NEJMoa1908077

    View details for PubMedID 31475798

  • Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI): a phase 3, placebo-controlled, randomised trial. Lancet (London, England) Bhatt, D. L., Steg, P. G., Mehta, S. R., Leiter, L. A., Simon, T., Fox, K., Held, C., Andersson, M., Himmelmann, A., Ridderstrale, W., Chen, J., Song, Y., Diaz, R., Goto, S., James, S. K., Ray, K. K., Parkhomenko, A. N., Kosiborod, M. N., McGuire, D. K., Harrington, R. A., THEMIS Steering Committee and Investigators, Santos, V., Jain, A., Lendel, I., Russo, M., Haught, W. H., Bouza, M., Gogia, H., Banerjee, S., Kichura, G., Kantaros, L., Padron, F., Passi, R., Stone, J., Pursley, M., D'Urso, M., Gardner, T., Bennett, J., Nour, K., Saini, S., Zhang, W., Kumbhani, D., Thomas, D., Angiolillo, D., Bertolet, B., Roman-Miranda, A., Black, R., Manshadi, R., Vaca, C., Blanco, A., Napoli, M., Brabham, D., Akyea-Djamson, A., Desai, P., Prasada, S., Khaira, A., Forgosh, L., Lieber, I., Umpierrez, G., Singal, D., Londono, J., Fraser, N., Ruiz, J., Vega, D., Rodriguez, L., Brown, C., Syed, F., Aggarwala, G., Eaves, W., Foster, M., Gupta, D., Avino, D., Asfour, W., Tonnessen, G., Zhao, X., Singh, N., Brockmyre, A., Lepor, N., Shammas, N., Blick, D., Hearne, S., Prodafikas, J., Carell, E., Izzo, M., Karim, A., Zakhary, B., Atieh, M., Leichter, S., Meadows, C., Hotchkiss, D., Abu-Fadel, M., Wiseman, A., Bander, J., Shah, M., Banerjee, S., Ganim, R., Sopko, K., Khan, M., Lloret, R., Weirick, T., Mehta, R., Thadani, U., Bhargava, A., Kosiborod, M., Moya, J., Staniloae, C., Guerra, Y. D., Chhabra, A., Kosmicki, D., Shaheen, W., Mohammed, A., Bitters, J., Pattanayak, J., Javier, J., Srivastava, S., Phillips, R., Al-Amin, J., Lillestol, M., Simpson, P., Hazan, L., Amin, A., Shah, G., Korpas, D., Platt, B., Dickert, J., Puente, O., Hiotis, L., Doyle, T., Rajan, R., Meholick, A., Gring, C., Hage-Korban, E., Feldman, R., Colfer, H., Butman, S., Foster, M., Hart, T., Huling, R., Eshaghian, S., Quintana, O., Cheung, D., Handel, F., Rodriguez, M., Suh, D., Gordon, P., Pressman, G., Bauer, M., French, W., Barettella, M., Chatrathi, S., Suresh, D., Goldberg, R., Huth, M., Younis, L., Rahman, A., Mascolo, R., Welch, M., Suneja, R., Smith, S., Shurmur, S., Agaiby, J., Jingo, A., Johnston, J., Beth, M., Vlastaris, A., Kemp, S., Taheri, H., Pereira, E., Deyoung, M., Hawa, Z., Smith, R., Galski, T., Garas, S., Reddy, M., Sharma, S., Hargrove, J., Treasure, C., Emerson, R., Haddad, T., Rohr, K., Levinson, L., Gaona, R., Uretsky, B., Maheshwari, H., Lee, D., Kinnaman, S., Singal, R., Geohas, J., Gigliotti, O., Raisinghani, A., Khurana, C., Hella, B., Kelberman, M., Voyce, S., Singh, S., Lo, E., Singh, P., Goodfellow, R., Fischer, S., Lorraine, R., Turner, T., Shanes, J., Busch, R., Broker, R., Zaniewski, M., Pounds, K., Debs-Perez, G., Ong, S., Frandsen, B., Fullington, D., Jaffrani, N., Khan, A., Lee, M., Pouzar, J., Revtyak, G., Gonzalez, J., Nakhle, S., Murillo, A., Young, D., Makam, S., Syed, M., Woolf, K., Grena, P., Alfata, S., Mahal, S., Hoffman, D., Kizhakekuttu, T., Deering, J., Bhavsar, J., Mikesell, S., Wilson, W., Wilson, V., El, S., Spinale, F., Kannarkat, V., Rao, S., Hanson, L., Bertsch, J., Gonzalez-Ortiz, E., Severino, N., Willis, J., Schock, J., Bakhtari, L., Gazmuri, R., Ansari, S., Hall, J., Mehta, A., Shealy, N., Zarich, S., Singh, D., Vora, K., Andrawis, N., Molter, D., Maron, D., Cardona, J., D'Agostino, R., Arshad, T., Samaan, R., Jones, D., Presser, D., Heath, J., Green, S., Bittar, G., Henry, S., Korn, D., Schmedtje, J., Nadar, V., Graham, B., Labroo, A., Clavijo, L., Roseman, H., Ledesma, G., Rosen, R., Dor, I., Kirby, W., Sutton, J., Eder, F., Iteld, B., Gomez-Cortes, J., Buchbinder, M., Kasper, J., Terrelonge, A., Torres, G., Jagielo, T., Alvarez, J., Handelsman, Y., Guillen, M., Richwine, R., Lewy-Alterbaum, L., Corder, C., Arvind, M., Bolshoun, D., Mikhail, M., Minton, S., Alvarado, O., Abbott, J., Cauthen, B., Welter, R., Mintz, R., Cox, J., Quick, A., Weiss, M., Dy, J., Zebrack, J., Gandelman, G., Hegde, V., Silver, M., DeGregorio, M., Lawson, W., Paa, C., Bortnick, A., Krolick, M., Sotolongo, R., Cheirif, J., Kumar, P., Nadar, V., Jetty, P., Patel, A., Kruk, M., Kobielusz-Gembala, I., Rewerska, B., Madrzejewski, A., Milewski, K., Cygler, J., Petryka-Mazurkiewicz, J., Jastrzebski, W., Korecki, J., Fil, W., Prokopczuk, J., Bochenek, A., Wujkowski, M., Witek, R., Konczakowski, P., Miekus, P., Szczasny, M., Musial, W., Cymerman, K., Lampart, J., Mikosinski, J., Szynal, S., Fares, I., Opolski, G., Mazur, S., Wozakowska-Kaplon, B., Bijata-Bronisz, R., Wierucki, L., Losa, B., Drelich, G., Konieczny, M., Starczewski, P., Pawlowicz, L., Jesionowski, P., Jurowiecki, J., Gniot, J., Czyzycki, M., Stania, K., Kucharczyk-Bauman, I., Busz-Papiez, B., Karczmarczyk, A., Sudnik, W., Koszek, A., Kolodziej, P., Skwarna, B., Jaramillo, N., Jankowski, M., Czochra, W., Kinasz, L., Miklaszewicz, B., Stasinska, T., Pluta, W., Basiak, M., Rusicka, T., Niedbal-Yahfouf, I., Popenda, G., Korzeniak, R., Mirek, A., Mariankowski, R., Wojnowski, L., Korol, M., Baszak, J., Podolec, P., Piesiewicz, W., Zurakowski, A., Luengas, C., Skura, M., Pilecki, P., Majchrzak, P., Krzyzagorska, E., Drozd, M., Kaczmarek, B., Sliwinska, T., Zelazowska, K., Sztembis, R., Landa, K., Matyszczak-Toniak, L., Strojek, K., Piepiorka, M., Malinowski, R., Gorska, M., Stolarczyk-Sowa, E., Romanowski, L., Zinka, E., Reszka, Z., Skierkowska, J., Uzunow, A., Laskowska-Derlaga, E., Puntus, E., Kosmacheva, E. D., Koziolova, N., Pavlov, P., Supryadkina, T., Didenko, Y., Kopylov, P., Kazakov, A., Aksentiev, S., Vishneva, E., Repin, A., Smolenskaya, O., Mantserova, O., Khrustalev, O., Privalova, E., Konstantinov, V., Boldueva, S., Ezhov, A., Chernyavsky, A., Kamalov, G., Galyavich, A., Zubeeva, G., Nechaeva, G., Shustov, S., Dzhaiani, N., Treshkur, T., Osokina, N., Panov, A., Shutemova, E., Makukhin, V., Kropotina, T., Tsyba, L., Karpov, Y., Sizova, J. M., Ballyuzek, M., Tarasov, N., Demchenko, E., Barbarash, O., Moiseev, V., Markov, V., Kuznetsov, V., Viktorova, I., Sergienko, I., Ermoshkina, L., Khasanov, N., Khlevchuk, T., Baglikov, A., Shalaev, S., Zonova, E., Reznik, E., Haisheva, L., Morugova, T., Lomakin, N., Vishnevsky, A., Shvarts, Y., Magnitskaya, O., Mikhailusova, M., Pavlysh, E., Libov, I., Zateyschikova, A., Kostenko, V., Edin, A., Khovaeva, Y., Zakharov, K., Stryuk, R., Khirmanov, V., Kanorskiy, S., Yakushin, S., Barabashkina, A., Li, H., Zhao, Q., Zhang, J., Ma, J., He, Y., Luo, M., Zhang, A., Zhang, N., Chai, Y., Ma, G., Wang, H., Liu, Z., He, L., Song, Z., Dong, X., Tao, L., Li, Z., Su, X., Kong, X., Niu, H., Ge, J., Luo, Z., Huang, W., Peng, D., Yuan, Z., Milanova, M., Tenev, D., Gogov, A., Karageorgiev, D., Kolchev, T., Rusev, N., Georgieva, N., Kondov, R., Rusinov, V., Petrov, I., Stanchev, G., Konteva, M., Dincheva, A., Yaneva, Z., Vatova, R., Ilieva, K., Runev, N., Kolomanov, B., Petrov, I., Iliev, N., Tisheva, S., Chompalova, B., Tokmakova, M., Raev, D., Byanov, K., Markov, D., Mihov, L., Mihov, A., Milcheva, N., Minchev, M., Mollov, M., Borisov, B., Tihchev, T., Karakolev, V., Dimov, B., Georgiev, S., Smilov, L., Koo, B. K., Ahn, T., Hong, S. J., Yoon, J., Oh, S. K., Jeong, M. H., Kim, D., Chang, K., Kim, W., Hahn, J., Cha, K. S., Lee, J., Choi, S., Nam, C., Chae, I., Park, Y. H., Tahk, S., Shin, W., Chae, J., Kim, B. J., Bae, J., Park, W. J., Rha, S. W., Choi, Y. J., Hwang, J., Park, H. S., Baracioli, L., Guimaraes, F., Vasconcellos, E., Saraiva, J., Pereira, A., Santos, Q., Rossi, P., Maia, L., Madeira, M., Pereira, M., Botelho, R., Reis, G., Eliaschewitz, F., Borges, J., Nascimento, C., Fortes, J. A., de Souza, W., Pimentel, P., Hissa, M., Franchetti, M., Precoma, D., Ortiz, C., Hernandes, M., Saporito, W., Dos Santos, F. R., Kormann, A., Neuenschwander, F., Dutra, O., Rassi, N., Tanajura, L., Souza, J., Junior, D. S., Leaes, P., Forte, A., Bonansea, T. C., Marin, J., Machado, B., Cerqueira, M. J., Silva, F., Michalaros, Y., Manenti, E., Cercato, C., Figueiredo, E., Liu, M., Wang, Y., Lee, T., Fang, C., Wu, Y., Ueng, K., Sheu, H., Lai, W. T., Hsieh, I., Chen, Z., Lee, M., Chiang, C., Shyu, K., Hsia, C., Mar, G., Chan, S., Wu, C., Tseng, W., Chang, K., Yeh, H., Wang, J., Hou, C., Sorokina, I., Dolzhenko, M., Horoshko, O., Karpenko, O., Rudenko, L., Vakaliuk, I., Kulyk, A., Levchenko, O., Prokhorov, O., Reshotko, D., Sorokivskyy, M., Velichko, N., Maslovskyi, V., Teliatnikova, Z., Dotsenko, S., Krakhmalova, O., Kraiz, I., Zharinova, V., Bula, L., Kaydashev, I., Molodtsov, V., Rasputina, L., Pidlisna, V., Lysunets, O., Kravchenko, A., Glushko, L., Khomazyuk, T., Svyshchenko, Y., Parkhomenko, O., Mankovsky, B., Abrahamovych, O., Yagensky, A., Stanislavchuk, M., Vasilyeva, L., Sokolova, L., Sychov, O., Tseluyko, V., Kyrychenko, I., Rishko, M., Furkalo, S., Gallo, R., Bertrand, O., Mehta, S., Constance, C., Sussex, B., Zadra, R., Kouz, S., Chehayeb, R., Pandey, A., Dion, D., Bailey, G., Hill, L., Ramanathan, K., Dorsch, M., Nanji, A., Babapulle, M., Montigny, M., Gosselin, G., Dehghani, P., Rupka, D., Le May, M., Pichette, F., St-Maurice, F., Teefy, P., Mansour, S., Kassam, S., Cheung, S., Siega, A. D., O'Keefe, D., Sabbah, E., Bell, A., Chouinard, G., Wong, B., Miller, M., Gaudet, D., Lachance, P., Bata, I., Petrella, R., Gossard, D., Dumas, R., Ing, D., Boyrazian, H., Bessoudo, R., Huynh, T. T., Hart, R., Belle-Isle, J., Shukla, D., Kelly, A., Mazza, G., Cha, J., Henein, S., Frechette, A., Vizel, S., Liutkus, J. F., O'Mahony, M., Halperin, F., Kooy, J., Graham, J., Bailey, A., Wojcik, R., Wilderman, I., Turi, T., Motyovszki, A., Merkely, B., Kiss, R. G., Kiraly, C., Andrassy, P., Sarszegi, Z., Fulop, T., Zilahi, Z., Edes, I., Papp, A., Muller, G., Czigany, A., Zolyomi, S., Koranyi, L., Takacs, J., Juhasz, F., Benczur, B., Kancz, S., Foldi, A., Nagy, A. C., Bakai, J., Greschik, I., Puski, L., Nagy, L., Kirschner, R., Kuchar, R., Hajek, P., Busak, L., Michalik, D., Matyasek, I., Marusincova, I., Kucera, D., Jerabek, O., Honkova, M., Dedek, V., Rihacek, I., Kos, P., Slaby, J., Machkova, M., Zidkova, E., Elbl, L., Grunfeldova, H., Carda, J., Mrozek, V., Maly, J., Milkovic, R., Malecha, J., Skalicka, H., Oral, I., Krcova, E., Lisa, L., Belohlavek, J., Miklik, R., Cermak, O., Bednarova, J., Peroutka, Z., Spinar, J., Wilke, A., Appel, K., Taggeselle, J., Forster, A., Toursarkissian, N., Schmidt, E., Bott, J., Al-Zoebi, A., Hennig, D., Fischer, S., Schon, N., Sauter, J., Simonis, G., Nischik, R., Rieker, W., Schenkenberger, I., Behnke, T., Klausmann, G., Jeserich, M., Trenk, D., Weigmann, I., Reuter, H., Rummel, R., von Munchhausen, C., von Engelhardt, C., Horibe, E., Shibasaki, T., Sato, T., Kakuta, T., Michishita, I., Tan, M., Ishiki, R., Aoyama, T., Higashiue, S., Niijima, Y., Idogaki, A., Hasegawa, T., Kiyosue, A., Tomobuchi, Y., Kawamitsu, K., Kawasaki, S., Hata, Y., Fukui, K., Seki, K., Takenaka, T., Abe, M., Utsu, N., Oono, A., Mitsuo, K., Sueyoshi, A., Hirohata, A., Tsujimoto, M., Ueda, O., Takase, S., Suzuki, M., Sakuragi, S., Yamamoto, F., Fujimoto, N., Kakinoki, S., Sugiura, T., Sugino, H., Nakamura, T., Goto, S., Kadokami, T., Uehara, H., Ono, M., Yokoya, K., Koike, A., Komatsu, S., Sonoda, M., Ueno, H., Doi, T., Takagi, Y., Fujimoto, K., Eki, Y., Okubo, M., Sasaki, K., van Eck, M., Ronner, E., The, S., van de Wal, R., Nierop, P., de Nooijer, C., The, S., The, S., Werner, H., Westendorp, I., van der Zwaan, C., Crijns, H., Cornel, J. H., Strikwerda, S., Bos, R., de Melker, E., Kuijper, A., Louwerenburg, H., Plomp, J., Dantzig, J., Prins, F., van Kesteren, H., Willems, F., Amoroso, G., Carnero, G., Duronto, E., Besada, D., Chacon, C., Zangroniz, P., Solis, S., Liberman, A., Sernia, V., Alvarisqueta, A., Maffei, L., Vilamajo, O. G., Garcia, C., Sicer, M., Muntaner, J., Bordonava, A., Albisu, J., Zanini, A., Rista, L., Hominal, M., Estrada, J. N., Prado, A., Gosparini, D. M., Schiavi, B., Castillo, A. G., Ruiz, J. G., Martinez, G. R., Lopez, V. G., Rosas, E. L., Lopez, G. R., Cantu, E. G., de Los Rios Ibarra, M., Padilla, F. P., Carrasco, J. P., Carrillo, L. V., Garcia, J. D., Askar, A. N., Salinas, C. A., Gamba, M. A., Sanchez, C. G., Cantu, A. G., Sanchez, R. V., Madrigal, J. C., Urbano, R. H., Romo, A. I., Gonzalez Juanatey, J. R., Racugno, P., Fillat, A. C., de la Torre Hernandez, J. M., Pelaez, J. A., Cortada, J. B., Pavia, P. G., Navarro, M. J., Asenjo, R. M., Diaz, F. F., Peligero, E. B., Manterola, F. A., Ortiz, A. F., Mediavilla Garcia, J. D., Ortuno, F. M., Vera, T. R., Gonzalez, A. S., Vinas, J. A., Fernandez Portales, F. J., Mayordomo, P. S., Ojeda, F. B., Dominguez, A. R., Gonzalez, R. S., Guerrero, D. B., Ruiz Nodar, J. M., Marimon, X. G., Margaez, J. G., Aguilera, R. M., Diaz Fernandez, J. F., Zamorano Gomez, J. L., Gonzalez, V. B., Del Blanco, B. G., Perez, I. P., Moreno, M. R., Ereno, A. R., Garcia Lledo, J. A., Prieto, J., Villablanca, A., Raffo, C., Pincetti, C., Conejeros, C., Roman, O., Rodriguez, M., Varleta, P., Goldberg, C., Sandoval, J., Arriagada, G., Corbalan, R., Leon, L., Potthoff, S., Cobos, J., Figueroa, C., Makotoko, E., Fourie, N., Burgess, L., Nortje, H., Theron, R., Pillai, P., Ranjith, N., Trokis, J., Pillay, S., Reddy, J., Nunkoo, T., Kapp, C., Urbach, D., Distiller, L., Horak, A., van Zyl, L., Coetzee, K., Punt, Z., Bayat, J., Dawood, S., Mitha, I., Padayachee, T., Hoosen, F., Dalby, A., Prabhavathi, Gowdaiah, P., Mehta, V., Chag, M., Gadkari, M., Ramamurthee, K., Das, A., Sawhney, J. S., Banerjee, S., Sathe, P., Adhyapak, S., Nguyen, T., Pham, V., Do, H., Nguyen, A., Nguyen, H., Truong, B., Jamil-Copley, S., Lang, C., Pell, A., Zaman, A., Storey, R., Swanson, N., Smith, S., Sharman, D., Braganza, D., Hammond, P., Moriarty, A., Bain, S., Pye, M., Sharp, A., Blagden, M., Randeva, H., Myhill, T., Viswanathan, G., Keeling, P., Clifford, P., Saxena, M., Lyons, K., McMurray, J., Jaafar, F., Murphy, C., Cartwright, S., Abouglila, K., Antalik, L., Krajci, P., Urban, M., Fazekas, F., Pella, D., Koleny, D., Vykoukalova, T., Macek, V., Vinanska, D., Jamriskova, L., Such, S., Fulop, P., Farsky, S., Bugan, V., Strbova, J., Micko, K., Palka, J. J., Sivak, V., Kristensen, D., Refsgaard, J., Holmvang, L., Dixen, U., Nielsen, H., Egstrup, K., Jensen, L. O., Sykulski, R., Rasmussen, O., Andries, A., Luckow, A., Nielsen, G., Sorensen, T., Wongvipaporn, C., Chamnarnphol, N., Srimahachota, S., Sansanayudh, N., Kuanprasert, S., Tresukosol, D., Sookananchai, B., Kanadasi, M., Ozcan, T., Kucuk, M., Ongen, Z., Okuyan, E., Arat, A., Acikel, S., Yalcin, A., Guray, U., Ceyhan, C., Ozer, N., Arslan, S., Angeras, O., Johnston, N., Weiderman, A., Bandh, S., Hansen, O., Larnefeldt, H., Kusiak, D., Lindholm, C., Hedman, A., Erlinge, D., Curiac, D., Lundman, P., Zucconi-Mazzini, R., Aladellie, L., Jensen, J., Verwerft, J., Vrolix, M., Faes, D., Striekwold, H., Sinnaeve, P., Timmermans, P., Guedes, A., Delforge, M., Nimmegeers, J., Stammen, F., Buysschaert, I., Hoffer, E., Hollanders, G., Vervoort, G., Coussement, P., de Maeseneire, S., Janssens, L., Gravdal, S. A., Risberg, K., Gullestad, L., Hofseth, O. D., Nilsen, D., Lappegard, K. T., van den Heuvel, C., Gibbs, C., Khusrawi, A., Arora, S., Tomala, T., Kjarnli, T., Berg-Johansen, J., Hagemeier, R., Skjelvan, G., Colquhoun, D., Amerena, J., Morbey, C., Hammett, C., Dart, A., Lehman, R., Hamilton, A., Worthley, M., Purnell, P., Whelan, A., MacIsaac, R., Arya, K., Linjawi, S., Proietto, J., Prasad, L., Rodriguez, A., Godoy, A., Rodriguez, V., Berrospi, P., Chavez, C., Negron, S., Heredia, J., Medina, F., Manrique, H., Cabrera, W., Cordova, F., Quinteros, T., Haro, J. M., Regalado, S., Guitton, J., Arbanil, H., Pansieri, M., Decoulx, E., Goube, P., de Labriolle, A., Labeque, J. N., Range, G., Cottin, Y., Montalescot, G., Cayla, G., Danchin, N., Angoulvant, D., Ferrario, E., Elbaz, M., Dubreuil, O., Steg, P. G., Fontaine, C., Sorbets, E., Omer, H., Al-Saif, S., Al-Faleh, H., Al-Shehri, A., El-Amin, O., Alshehri, H., Bazari, R., Hei, P., Ying, M., Chan, M., Wong, M., Ma, R., Siu, S. C., Tsang, C. C., Ferrario, M., Assanelli, E., Senni, M., Piatti, P., Calabro, P., Urbinati, S., Michisanti, M., Varbella, F., de Cosmo, S., Trevisan, R., Bellotti, S., Di Pasquale, G., Bongo, A. S., Uguccioni, M., Mannucci, E., Mauro, C., Ragonese, M., Fresco, C., Turturo, M., Marcucci, R., Lievano Triana, M. J., Arana, C., Accini, J., Botero, R., Muzyk-Osikowicz, M., Dada, F. T., Vallejo, G. S., Manzur, F., Isaza, D., Molina, D., Mesa, J. G., Quintero, A., Nyman, K., Makela, J., Strand, J., Nieminen, S., Taurio, J., Kuusela, M., Valle, T., Pietila, M., Kekki, S., Strandberg, T., Klutstein, M., Greenberg, G., Rozenman, Y., Chorin, E., Roguin, A., Lewis, B., Bashkin, A., Tan, E., Prado, J. P., Ferrolino, A., Babilonia, N., Barbas, B., Matiga, G., Coching, R. M., Drexel, H., Brath, H., Schnack, C., Hanusch, U., FlieSSer-Gorzer, E., Paulweber, B., Ebenbichler, C., Prager, R., Huber, K., Wolzt, M., Auer, J., Berger, R., Schernthaner, G., Stanciulescu, G., Creteanu, M., Spiridon, M., Dobreanu, V., Vinereanu, D., Iosipescu, L. C., Istratoaie, O., Coman, I., Militaru, C., Cinteza, M., Bhatt, D. L., Fox, K., Harrington, R. A., Leiter, L. A., Mehta, S. R., Simon, T., Andersson, M., Himmelmann, A., Steg, P. G., Diaz, R., Amerena, J., Huber, K., Sinnaeve, P. R., Nicolau, J. C., Kerr Saraiva, J. F., Petrov, I., Leiter, L. A., Mehta, S. R., Corbalan, R., Ge, J., Zhao, Q., Botero, R., Widimsky, P., Kristensen, S. D., Hartikainen, J., Danchin, N., Darius, H., Tse, H. F., Kiss, R. G., Pais, P., Lev, E., de Luca, L., Goto, S., Ramos Lopez, G. A., Cornel, J. H., Kontny, F., Medina, F., Babilonia, N. A., Opolski, G., Vinereanu, D., Zateyshchikov, D. A., Ruda, M., Elamin, O., Kovar, F., Dalby, A. J., Jeong, M. H., Bueno, H., James, S. K., Chiang, C., Tresukosol, D., Ongen, Z., Ray, K. K., Parkhomenko, A., McGuire, D. K., Kosiborod, M. N., Nguyen, T. Q., Andersson, M., Chen, J., Himmelmann, A., Leonsson-Zachrisson, M., Ridderstrale, W. 2019

    Abstract

    BACKGROUND: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor.METHODS: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population).FINDINGS: Between Feb 17, 2014, and May 24, 2016, 11?154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8-3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74-0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, pinteraction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78-1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75-1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48-2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36-3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74-1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75-0·95, p=0·005, in contrast to patients without PCI where it did not, pinteraction=0·012. Benefit was present irrespective of time from most recent PCI.INTERPRETATION: In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk.FUNDING: AstraZeneca.

    View details for DOI 10.1016/S0140-6736(19)31887-2

    View details for PubMedID 31484629

  • Outcomes of Veterans Undergoing TAVR Within Veterans Affairs Medical Centers: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program. JACC. Cardiovascular interventions Hall, P. S., O'Donnell, C. I., Mathew, V., Garcia, S., Bavry, A. A., Banerjee, S., Jneid, H., Denktas, A. E., Giacomini, J. C., Grossman, P. M., Aggarwal, K., Zimmet, J. M., Tseng, E. E., Gozdecki, L., Burke, L., Bertog, S. C., Buchbinder, M., Plomondon, M. E., Waldo, S. W., Shunk, K. A. 2019

    Abstract

    OBJECTIVES: This study sought to describe clinical and procedural characteristics of veterans undergoing transcatheter aortic valve replacement (TAVR) within U.S. Department of Veterans Affairs (VA) centers and to examine their association with short- and long-term mortality, length of stay (LOS), and rehospitalization within 30days.BACKGROUND: Veterans with severe aortic stenosis frequently undergo TAVR at VA medical centers.METHODS: Consecutive veterans undergoing TAVR between 2012 and 2017 were included. Patient and procedural characteristics were obtained from the VA Clinical Assessment, Reporting, and Tracking system. The primary outcomes were 30-day and 1-year survival, LOS >6days, and rehospitalization within 30days. Logistic regression and Cox proportional hazards analyses were performed to evaluate the associations between pre-procedural characteristics and LOS and rehospitalization.RESULTS: Nine hundred fifty-nine veterans underwent TAVR at 8 VA centers during the study period, 860 (90%) by transfemoral access, 50 (5%) transapical, 36 (3.8%) transaxillary, and 3 (0.3%) transaortic. Men predominated (939 of 959 [98%]), with an average age of 78.1 years. There were 28 deaths within 30days (2.9%) and 134 at 1 year (14.0%). Median LOS was 5days, and 141 veterans were rehospitalized within 30days (14.7%). Nonfemoral access (odds ratio: 1.74; 95% confidence interval [CI]: 1.10 to 2.74), heart failure (odds ratio: 2.51; 95%CI: 1.83 to 3.44), and atrial fibrillation (odds ratio: 1.40; 95%CI: 1.01 to 1.95) were associated with increased LOS. Atrial fibrillation was associated with 30-day rehospitalization (hazard ratio: 1.79; 95%CI: 1.22 to 2.63).CONCLUSIONS: Veterans undergoing TAVR at VA centers are predominantly elderly men with significant comorbidities. Clinical outcomes of mortality and rehospitalization at 30days and 1-year mortality compare favorably with benchmark outcome data outside the VA.

    View details for DOI 10.1016/j.jcin.2019.04.040

    View details for PubMedID 31473239

  • TAVR in Low-Risk Patients 1-Year Results From the LRT Trial JACC-CARDIOVASCULAR INTERVENTIONS Waksman, R., Corso, P. J., Torguson, R., Gordon, P., Ehsan, A., Wilson, S. R., Goncalves, J., Levitt, R., Hahn, C., Parikh, P., Bilfinger, T., Butzel, D., Buchanan, S., Hanna, N., Garrett, R., Buchbinder, M., Asch, F., Weissman, G., Ben-Dor, I., Shults, C., Bastian, R., Craig, P. E., Ali, S., Garcia-Garcia, H. M., Kolm, P., Zou, Q., Satler, L. F., Rogers, T. 2019; 12 (10): 901?7
  • Transcatheter Aortic Valve Replacement in Low-Risk Patients: One-Year Results from the LRT Trial. JACC. Cardiovascular interventions Waksman, R., Corso, P. J., Torguson, R., Gordon, P., Ehsan, A., Wilson, S. R., Goncalves, J., Levitt, R., Hahn, C., Parikh, P., Bilfinger, T., Butzel, D., Buchanan, S., Hanna, N., Garrett, R., Buchbinder, M., Asch, F., Weissman, G., Ben-Dor, I., Shults, C., Bastian, R., Craig, P. E., Ali, S., Garcia-Garcia, H. M., Kolm, P., Zou, Q., Satler, L. F., Rogers, T. 2019

    Abstract

    OBJECTIVES: To evaluate clinical outcomes and transcatheter heart valve hemodynamics at 1 year after transcatheter aortic valve replacement (TAVR) in low-risk patients.BACKGROUND: Early results from the Low Risk TAVR (LRT) trial demonstrated that TAVR is safe in patients with symptomatic severe aortic stenosis (AS) who are low risk for surgical valve replacement.METHODS: The LRT trial was an investigator-initiated, prospective, multicenter study and was the first Food and Drug Administration-approved Investigational Device Exemption trial to evaluate feasibility of TAVR in low-risk patients. The primary endpoint was all-cause mortality at 30 days. Secondary endpoints included clinical outcomes and valve hemodynamics at 1 year.RESULTS: The LRT trial enrolled 200 low-risk patients with symptomatic severe AS to undergo TAVR at 11 centers. Mean age was 73.6 years and 61.5% were male. At 30 days, there was zero mortality, zero disabling stroke, and low permanent pacemaker implantation rate (5.0%), At 1-year follow-up, mortality was 3.0%, stroke rate was 2.1%, and permanent pacemaker implantation rate was 7.3%. Two subjects (1.0%) underwent surgical reintervention for endocarditis. Of the 14% of TAVR subjects who had evidence of hypoattenuated leaflet thickening at 30 days, there was no impact on valve hemodynamics at 1 year, but the stroke rate was numerically higher (3.8% vs. 1.9%, p=0.53).CONCLUSIONS: TAVR in low-risk patients with symptomatic severe AS appears to be safe at 1 year. Hypoattenuated leaflet thickening, observed in a minority of TAVR patients at 30 days, did not impact valve hemodynamics in the longer term.

    View details for PubMedID 30860059

  • Hemodynamics and Subclinical Leaflet Thrombosis in Low-Risk Patients Undergoing Transcatheter Aortic Valve Replacement. Circulation. Cardiovascular imaging Khan, J. M., Rogers, T. n., Waksman, R. n., Torguson, R. n., Weissman, G. n., Medvedofsky, D. n., Craig, P. E., Zhang, C. n., Gordon, P. n., Ehsan, A. n., Wilson, S. R., Goncalves, J. n., Levitt, R. n., Hahn, C. n., Parikh, P. n., Bilfinger, T. n., Butzel, D. n., Buchanan, S. n., Hanna, N. n., Garrett, R. n., Shults, C. n., Garcia-Garcia, H. M., Kolm, P. n., Satler, L. F., Buchbinder, M. n., Ben-Dor, I. n., Asch, F. M. 2019; 12 (12): e009608

    Abstract

    This analysis evaluated echocardiographic predictors of hypoattenuated leaflet thickening (HALT) in low-risk patients undergoing transcatheter aortic valve replacement and assessed 1-year clinical and hemodynamic consequences. HALT by computed tomography may be associated with early valve degeneration and increased neurological events.Echocardiograms were performed at baseline, discharge, 30 days, and 1 year post-procedure. Four-dimensional contrast-enhanced computed tomography assessed HALT at 30 days. Independent core laboratories analyzed images. Doppler hemodynamic parameters were tested in a univariable regression model to identify HALT predictors. One-year clinical and hemodynamic outcomes were compared between HALT (+) and (-) patients.Analysis included 170 patients with Sapien 3 valves and diagnostic 30-day computed tomographies, of whom 27 (16%) had HALT. Baseline characteristics were similar between groups. After transcatheter aortic valve replacement, aortic flow was nonsignificantly reduced in patients who developed HALT. Regression analysis did not show significant association between baseline or discharge valve hemodynamics and development of HALT at 30 days. Patients with HALT had smaller aortic valve areas (1.4±0.4 versus 1.7±0.5 cm2; P=0.018) and Doppler velocity index (0.4±0.1 versus 0.5±0.1; P=0.003) than those without HALT at 30 days but not at 1 year. There was no difference in aortic mean gradient at 30 days. There was no difference between the groups in New York Heart Association class, 6-minute walk distance, and mortality at 1 year.There were no early hemodynamic predictors of HALT. At 30 days, patients with HALT had worse valve hemodynamics than those without HALT, but hemodynamic and clinical outcomes at 1 year were similar.URL: http://www.clinicaltrials.gov. Unique identifier: NCT02628899.

    View details for DOI 10.1161/CIRCIMAGING.119.009608

    View details for PubMedID 31826675

  • Effect of Mechanically Expanded vs Self-Expanding Transcatheter Aortic Valve Replacement on Mortality and Major Adverse Clinical Events in High-Risk Patients With Aortic Stenosis The REPRISE III Randomized Clinical Trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Feldman, T. E., Reardon, M. J., Rajagopal, V., Makkar, R. R., Bajwa, T. K., Kleiman, N. S., Linke, A., Kereiakes, D. J., Waksman, R., Thourani, V. H., Stoler, R. C., Mishkel, G. J., Rizik, D. G., Iyer, V. S., Gleason, T. G., Tchetche, D., Rovin, J. D., Buchbinder, M., Meredith, I. T., Gotberg, M., Bjursten, H., Meduri, C., Salinger, M. H., Allocco, D. J., Dawkins, K. D. 2018; 319 (1): 27?37

    Abstract

    Transcatheter aortic valve replacement (TAVR) is established for selected patients with severe aortic stenosis. However, limitations such as suboptimal deployment, conduction disturbances, and paravalvular leak occur.To evaluate if a mechanically expanded valve (MEV) is noninferior to an approved self-expanding valve (SEV) in high-risk patients with aortic stenosis undergoing TAVR.The REPRISE III trial was conducted in 912 patients with high or extreme risk and severe, symptomatic aortic stenosis at 55 centers in North America, Europe, and Australia between September 22, 2014, and December 24, 2015, with final follow-up on March 8, 2017.Participants were randomized in a 2:1 ratio to receive either an MEV (n = 607) or an SEV (n = 305).The primary safety end point was the 30-day composite of all-cause mortality, stroke, life-threatening or major bleeding, stage 2/3 acute kidney injury, and major vascular complications tested for noninferiority (margin, 10.5%). The primary effectiveness end point was the 1-year composite of all-cause mortality, disabling stroke, and moderate or greater paravalvular leak tested for noninferiority (margin, 9.5%). If noninferiority criteria were met, the secondary end point of 1-year moderate or greater paravalvular leak was tested for superiority in the full analysis data set.Among 912 randomized patients (mean age, 82.8 [SD, 7.3] years; 463 [51%] women; predicted risk of mortality, 6.8%), 874 (96%) were evaluable at 1 year. The primary safety composite end point at 30 days occurred in 20.3% of MEV patients and 17.2% of SEV patients (difference, 3.1%; Farrington-Manning 97.5% CI, -? to 8.3%; P?=?.003 for noninferiority). At 1 year, the primary effectiveness composite end point occurred in 15.4% with the MEV and 25.5% with the SEV (difference, -10.1%; Farrington-Manning 97.5% CI, -? to -4.4%; P<.001 for noninferiority). The 1-year rates of moderate or severe paravalvular leak were 0.9% for the MEV and 6.8% for the SEV (difference, -6.1%; 95% CI, -9.6% to -2.6%; P?

    View details for PubMedID 29297076

    View details for PubMedCentralID PMC5833545

  • The Assessment of the Watchman Device in Patients Unsuitable for Oral Anticoagulation (ASAP-TOO) trial. American heart journal Holmes, D. R., Reddy, V. Y., Buchbinder, M. n., Stein, K. n., Elletson, M. n., Bergmann, M. W., Schmidt, B. n., Saw, J. n. 2017; 189: 68?74

    Abstract

    Oral anticoagulants (OACs) reduce stroke risks with nonvalvular atrial fibrillation (AF); however, they are underused because of absolute or relative contraindications due to real or perceived risk of bleeding. Although left atrial appendage closure is increasingly performed in OAC-ineligible patients, this has not been studied in a randomized controlled trial.The ASAP-TOO study is designed to establish the safety and effectiveness of the Watchman left atrial appendage closure device in patients with nonvalvular AF who are deemed ineligible for OAC. The primary effectiveness end point is the time to first occurrence of ischemic stroke or systemic embolism. The primary safety end point includes all-cause death, ischemic stroke, systemic embolism, or device- or procedural-related event requiring open cardiac surgery or major endovascular intervention.This is a multinational, multicenter prospective randomized trial. Patients meeting the inclusion criteria with CHA2DS2-VASc score?2 and who are deemed by 2 study physicians to be unsuitable for OAC will be randomized in a 2:1 allocation ratio to Watchman versus control. Control patients will be prescribed single antiplatelet therapy or no therapy at the discretion of the study physician. Up to 888 randomized subjects will be enrolled from up to 100 global investigational sites. Both device group and control patients will have follow-up visits at 3, 6, and 12months and then every 6months through 60months.This trial will assess the safety and efficacy of Watchman in this challenging population of high-stroke risk AF patients.

    View details for PubMedID 28625383

  • Cryotherapy increases features of plaque stability in atherosclerotic rabbits EUROINTERVENTION Verheye, S., Roth, L., De Meyer, I., Van Hove, C. E., Nahon, D., Santoianni, D., Yianni, J., Martinet, W., Buchbinder, M., De Meyer, G. R. 2016; 12 (6): 748-756

    Abstract

    In the last 10 years, cryotherapy has been investigated as a new technology to treat vascular disease. The efficiency of cryotherapy in stabilising atherosclerotic plaques has never been described. The purpose of the present study was to evaluate the effect of catheter-based cryotherapy on atherosclerotic plaque composition in a rabbit model of atherosclerosis.Twenty-four New Zealand white rabbits were fed a 0.3% cholesterol-supplemented diet for 24 weeks. At two predefined sites of the atherosclerotic thoracic aorta, catheter-based cryotherapy, applying either single-dose, double-dose cryotherapy or control inflation, was performed after randomisation. Rabbits were continued on a cholesterol-supplemented diet for one day (acute) or four weeks (chronic). One day after cryotherapy, apoptotic cell death of smooth muscle cells (SMCs) and endothelial cells (ECs) was observed, whereas macrophages were unaffected. Four weeks later, the amount of SMCs was restored, the EC layer was regenerated, and a subendothelial macrophage-free layer was formed, indicative of a more stable plaque. In addition, both the thickness and the type I collagen content of the fibrous cap were increased.The present study demonstrated that cryotherapy is feasible and appears to stabilise atherosclerotic plaques in a rabbit model.

    View details for Web of Science ID 000383640700011

    View details for PubMedID 26448576

  • Transcatheter CoreValve valve-in-valve implantation in a stentless porcine aortic valve for severe aortic regurgitation. Clinical case reports Yong, C. M., Buchbinder, M., Giacomini, J. C. 2014; 2 (6): 281-285

    Abstract

    We describe the first valve-in-valve Corevalve transcatheter aortic valve replacement in the St. Jude Toronto stentless porcine aortic valve in the United States, which enabled this 59-year-old patient with a history of bacterial endocarditis and aortic regurgitation to avoid heart transplant with complete resolution of his severe left ventricular dysfunction.

    View details for DOI 10.1002/ccr3.113

    View details for PubMedID 25548631

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

    Abstract

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

    View details for DOI 10.1016/j.ahj.2014.07.011

    View details for Web of Science ID 000344434300006

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

    Abstract

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

    View details for DOI 10.1016/j.ahj.2014.07.011

    View details for PubMedID 25440792

  • Targeted vascular drug delivery. A new day for an old way. Panminerva medica Buchbinder, M., Solar, R. 2013; 55 (4): 353-361

    Abstract

    Local drug delivery for the treatment of vascular disease has been studied for many years. In coronary artery disease, drug eluting stents are routinely deployed. However, with concerns regarding late thrombosis, and clinical applications where stenting is not desirable, such as peripheral vascular disease, a new direction to "leave nothing behind" has emerged. In Europe, paclitaxel-coated balloons have shown promise in reducing restenosis in both peripheral and coronary applications. However, a number of technical, economic and regulatory limitations of the current devices have been identified. Local or targeted fluid delivery of drugs may offer a relatively simple solution.

    View details for PubMedID 24434344

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

    Abstract

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

    View details for DOI 10.1016/j.jacc.2008.01.020

    View details for Web of Science ID 000255353200003

    View details for PubMedID 18420096

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

    Abstract

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

    View details for PubMedID 17293267

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

    Abstract

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

    View details for DOI 10.1016/j.amjcard.2006.06.046

    View details for Web of Science ID 000242595300010

    View details for PubMedID 17126651

  • INFLUENCE OF MITRAL-VALVE MORPHOLOGY ON MITRAL BALLOON COMMISSUROTOMY - IMMEDIATE AND 6-MONTH RESULTS FROM THE NHLBI BALLOON VALVULOPLASTY REGISTRY AMERICAN HEART JOURNAL Reid, C. L., Otto, C. M., Davis, K. B., Labovitz, A., Kisslo, K. B., McKay, C. R., Diver, D. J., Berman, A., Safian, R. D., Grossman, W., Come, P. C., Douglas, P., McKay, R. G., Slater, A., Williams, D. O., DREW, T. M., Carnevale, R., Cimini, D., HARDINK, D., Cannon, P., Homma, S., Berke, A., Keller, A., ESCALA, E., TRESGALLO, M., Bashore, T. M., Davidson, C. J., Harrison, J. K., Kisslo, J., Kisslo, K., Brinker, J. A., Weiss, J. L., Raqueno, J., DOWGER, B., Lambrew, C. T., Cutler, J., SZE, K., TOOKER, N., Holmes, D. R., Nishimura, R., Reeder, G., MATHESON, S. J., SCHREIFELS, S., Meyer, L., Block, P. C., Palacios, I. F., Weyman, A., Block, E. H., Petitclerc, R., BROUILLETE, M., Slater, J. N., Feit, F., Kronzon, I., Attubato, M. J., GINDEA, A., BILYK, F., Kern, M. J., Labovitz, A., Stonner, T., Mechem, C., Alderman, E. L., Schnittger, I., Schwarzkopf, A., ROD, J. L., Comess, K., Ferguson, J., Massumi, A., Treistman, B., Hernandez, G., Wilansky, S., Harlan, M., Dean, L. S., Baxley, W., Nanda, N., Kirklin, J. W., Saenz, C., Helmcke, F. R., MELUCH, F. T., Buchbinder, M., Peterson, K., Dittrich, H., Daily, E., Hill, J., Miranda, A., Pepine, C., Geiser, E., SCOTTFRANCO, E., DeMaria, A. N., Wisenbaugh, T., Berk, M., Obrien, M., Weiner, B. H., Pape, L., Borbone, M. L., Nabel, E. G., Armstrong, W. F., GALEANA, A., Buda, A., GALEANA, A., Rahimtoola, S. H., Kawanishi, D. T., Reid, C., Chandraratna, P. A., Morrison, E., Powers, E. R., Smucker, M., Gibson, R., Tedesco, C., Stewart, D. K., ONEIL, W., Hauser, A., DUDLETS, P., PAVILEDES, G., Margulis, A., Vanderberg, B., Waller, B. F., Kennedy, J. W., Gillespie, M. J., Mickel, M., Solomon, R. E. 1992; 124 (3): 657-665
  • THROMBOEMBOLIC COMPLICATIONS OF PERCUTANEOUS TRANS-LUMINAL CORONARY ANGIOPLASTY FOR MYOCARDIAL-INFARCTION CATHETERIZATION AND CARDIOVASCULAR DIAGNOSIS Cameron, J., Buchbinder, M., Wexler, L., Oesterle, S. N. 1987; 13 (2): 100-106

    Abstract

    To determine the incidence of thromboembolic complications of percutaneous transluminal coronary angioplasty (PTCA) in the setting of recent and acute myocardial infarction, the clinical sequelae and coronary angiographic findings were examined in a series of 13 patients who underwent PTCA either as acute intervention during the infarction or as treatment for recurrent myocardial ischemia that occurred soon after the initial completed infarction. In all cases, the angiographic appearance in the infarct-related artery was that of thrombus in the setting of total or subtotal occlusion. Balloon dilatation without antecedent thrombolytic therapy, was performed in 14 arteries and was successful in establishing reperfusion with reduction of the degree of intraluminal narrowing to less than 50% in all cases. Residual thrombus at the site of inflation was noted in two cases (15%), and embolization was noted in four cases (29%), for an incidence of complication of 44%. In five of six instances in which either residual thrombus or embolization were noted, the initial infarction had occurred greater than 24 h before. In only one of seven cases in which PTCA was used as acute intervention during infarction of less than 4 h duration was the presence of residual thrombus noted after PTCA. Therefore, these findings suggest that thromboembolic complications after PTCA in the setting of recent or acute myocardial infarction are uncommon when the syndrome is less than 4 h duration; however, complications are relatively frequent when infarction has occurred greater than 24 h before. PTCA as a primary intervention in this latter setting should be approached cautiously.

    View details for Web of Science ID A1987G788900004

    View details for PubMedID 2953429

  • THE ANGIOGRAPHY PROGRAM AT STANFORD NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT Hughes, E. B., Rubenstein, E., Zeman, H. D., Brown, G. S., Buchbinder, M., HARRISON, D. C., Hofstadter, R., Kernoff, R. S., Otis, J. N., Thompson, A. C. 1986; 246 (1-3): 719-725
  • PROSPECTS FOR NON-INVASIVE ANGIOGRAPHY WITH TUNABLE X-RAYS NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION B-BEAM INTERACTIONS WITH MATERIALS AND ATOMS Hughes, E. B., Rubenstein, E., Zeman, H. D., Brown, G. S., Buchbinder, M., HARRISON, D. C., Hofstadter, R., Kernoff, R. S., Otis, J. N., Sommer, H. A., Thompson, A. C., Walton, J. T. 1985; 10-1 (MAY): 323-328
  • REDUCTION OF ISCHEMIC DEPOLARIZATION BY THE CALCIUM-CHANNEL BLOCKER DILTIAZEM - CORRELATION WITH IMPROVEMENT OF VENTRICULAR CONDUCTION AND EARLY ARRHYTHMIAS IN THE DOG CIRCULATION RESEARCH Clusin, W. T., Buchbinder, M., Ellis, A. K., Kernoff, R. S., Giacomini, J. C., HARRISON, D. C. 1984; 54 (1): 10-20

    Abstract

    Calcium channel blockers suppress early ischemic arrhythmias, possibly by diminishing intracellular calcium overload and its effect on the ventricular action potential. To explore this, we compared the effects of diltiazem on ischemic "injury" potentials and ventricular fibrillation during serial coronary artery occlusions in dogs. Injury potentials and ventricular fibrillation were elicited every 15-25 minutes by simultaneous occlusion of the left anterior descending and circumflex arteries during rapid atrial pacing. DC epicardial electrograms were recorded differentially between the ischemic region and a small nonischemic region supplied by a proximal branch of the left anterior descending artery. Injury potentials developed with a uniform time course during five control occlusions, but were reduced by diltiazem infusion (0.5 mg/kg over 25 minutes) in each of eight dogs. The mean diastolic injury potential (T-Q depression) at 150 seconds of ischemia was 9.1 +/- 2.7 mV before diltiazem and 6.1 +/- 1.6 mV afterward (P less than 0.001). Diltiazem increased the mean time between coronary occlusion and ventricular fibrillation from 186 to 366 seconds (P less than 10(-5), but did not change the magnitude of the diastolic injury potential at onset of ventricular fibrillation. Diltiazem also delayed ischemia-induced conduction impairment to the same extent that it delayed injury potential development. In five dogs, the effect of diltiazem on regional blood flow near the epicardial electrodes was measured by infusion of radionuclide-labeled microspheres. Coronary occlusion reduced flow to the ischemic zone from 0.86 to 0.05 ml/min per g (P = 0.001). Diltiazem increased preocclusion flow by 11% (P = 0.03), but did not significantly alter flow during occlusion. Hemodynamic measurements show that diltiazem did not diminish cardiac work. Diltiazem therefore produced a flow-independent reduction of cellular depolarization during ischemia, which may be due to relief of calcium overload, and which may explain the antifibrillatory effect.

    View details for Web of Science ID A1984SB78500002

    View details for PubMedID 6692497

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