Michael J. Mack M.D.

Bapat, V., V. Rajagopal, C. Meduri, R. S. Farivar, A. Walton, S. J. Duffy, R. Gooley, A. Almeida, M. J. Reardon, N. S. Kleiman, K. Spargias, S. Pattakos, M. K. Ng, M. Wilson, D. H. Adams, M. Leon, M. J. Mack, S. Chenoweth and P. Sorajja (2017). “Early experience with new transcatheter mitral valve replacement.” J Am Coll Cardiol: 2017 Oct [Epub ahead of print].

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BACKGROUND: Transcatheter mitral valve replacement (TMVR) is a potential therapy for patients with symptomatic, severe mitral regurgitation (MR). The feasibility of this therapy remains to be defined. OBJECTIVE: We report our early experience with TMVR using a new valve system. METHODS: The valve is a self-expanding, nitinol valve with bovine pericardial leaflets that is placed using a transapical delivery system. Patients with symptomatic MR who were deemed high or extreme risk by the local heart teams were enrolled in a global pilot study at 14 sites (U.S., Australia, and Europe). RESULTS: 50 consecutively enrolled patients (mean age, 73+/-9 years; 58.0% men; 84% secondary MR) underwent TMVR with the valve. The mean STS score was 6.4+/-5.5%; 86% of patient were NYHA class III or IV, and the mean left ventricular ejection fraction was 43+/-12%. Device implant was successful in 48 patients with a median deployment time of 14 (IQR, 12, 17) minutes. The 30-day mortality was 14%, with no disabling strokes, or repeat interventions. Median follow-up was 173 (IQR, 54, 342) days. At latest follow-up, echocardiography confirmed mild or no residual MR in all implanted patients. Improvements in symptom class (79% in NYHA I or II at follow-up; p<0.0001 vs. baseline), and Minnesota heart failure questionnaire scores (56.2+/-26.8 vs. 31.7+/-22.1; p=0.011) were observed. CONCLUSIONS: TMVR with the valve was feasible in a population at high-or extreme-risk for conventional mitral valve replacement. These results inform trial design of TMVR in lower-risk patients with severe mitral valve regurgitation.

Douglas, P. S., M. B. Leon, M. J. Mack, L. G. Svensson, J. G. Webb, R. T. Hahn, P. Pibarot, N. J. Weissman, D. C. Miller, S. Kapadia, H. C. Herrmann, S. K. Kodali, R. R. Makkar, V. H. Thourani, S. Lerakis, A. M. Lowry, J. Rajeswaran, M. T. Finn, M. C. Alu, C. R. Smith and E. H. Blackstone (2017). “Longitudinal hemodynamics of transcatheter and surgical aortic valves in the partner trial.” JAMA Cardiol: 2017 Sep [Epub ahead of print].

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Importance: Use of transcatheter aortic valve replacement (TAVR) for severe aortic stenosis is growing rapidly. However, to our knowledge, the durability of these prostheses is incompletely defined. Objective: To determine the midterm hemodynamic performance of balloon-expandable transcatheter heart valves. Design, Setting, and Participants: In this study, we analyzed core laboratory-generated data from echocardiograms of all patients enrolled in the Placement of Aortic Transcatheter Valves (PARTNER) 1 Trial with successful TAVR or surgical AVR (SAVR) obtained preimplantation and at 7 days, 1 and 6 months, and 1, 2, 3, 4, and 5 years postimplantation. Patients from continued access observational studies were included for comparison. Interventions: Successful implantation after randomization to TAVR vs SAVR (PARTNER 1A; TAVR, n = 321; SAVR, n = 313), TAVR vs medical treatment (PARTNER 1B; TAVR, n = 165), and continued access (TAVR, n = 1996). Five-year echocardiogram data were available for 424 patients after TAVR and 49 after SAVR. Main Outcomes and Measures: Death or reintervention for aortic valve structural indications, measured using aortic valve mean gradient, effective orifice area, Doppler velocity index, and evidence of hemodynamic deterioration by reintervention, adverse hemodynamics, or transvalvular regurgitation. Results: Of 2795 included patients, the mean (SD) age was 84.5 (7.1) years, and 1313 (47.0%) were female. Population hemodynamic trends derived from nonlinear mixed-effects models showed small early favorable changes in the first few months post-TAVR, with a decrease of -2.9 mm Hg in aortic valve mean gradient, an increase of 0.028 in Doppler velocity index, and an increase of 0.09 cm2 in effective orifice area. There was relative stability at a median follow-up of 3.1 (maximum, 5) years. Moderate/severe transvalvular regurgitation was noted in 89 patients (3.7%) after TAVR and increased over time. Patients with SAVR showed no significant changes. In TAVR, death/reintervention was associated with lower ejection fraction, stroke volume index, and aortic valve mean gradient up to 3 years, with no association with Doppler velocity index or valve area. Reintervention occurred in 20 patients (0.8%) after TAVR and in 1 (0.3%) after SAVR and became less frequent over time. Reintervention was caused by structural deterioration of transcatheter heart valves in only 5 patients. Severely abnormal hemodynamics on echocardiograms were also infrequent and not associated with excess death or reintervention for either TAVR or SAVR. Conclusions and Relevance: This large, core laboratory-based study of transcatheter heart valves revealed excellent durability of the transcatheter heart valves and SAVR. Abnormal findings in individual patients, suggestive of valve thrombosis or structural deterioration, were rare in this protocol-driven database and require further investigation.

Pibarot, P., R. T. Hahn, N. J. Weissman, M. Arsenault, J. Beaudoin, M. Bernier, A. Dahou, O. K. Khalique, F. M. Asch, O. Toubal, J. Leipsic, P. Blanke, F. Zhang, R. Parvataneni, M. Alu, H. Herrmann, R. Makkar, M. Mack, R. Smalling, M. Leon, V. H. Thourani and S. Kodali (2017). “Association of paravalvular regurgitation with 1-year outcomes after transcatheter aortic valve replacement with the sapien 3 valve.” JAMA Cardiol: 2017 Sep [Epub ahead of print].

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Importance: Moderate/severe and even mild paravalvular regurgitation (PVR) are associated with increased mortality following transcatheter aortic valve replacement (TAVR) with first and second generations of transcatheter valves. Objective: To examine the incidence, evolution, and effect on 1-year outcomes of PVR following TAVR with a third-generation balloon-expandable transcatheter heart valve. Design, Setting, and Participants: Prespecified analysis of PVR in the Placement of Aortic Transcatheter Valves (PARTNER) II SAPIEN 3 trial, conducted between October 1, 2013, and September 3, 2014. Multicenter, nonrandomized registry of 1661 patients at intermediate or high surgical risk undergoing TAVR with the SAPIEN 3. Patients with severe, symptomatic aortic stenosis and high/intermediate surgical risk were enrolled in the registry at 51 sites in the United States and Canada. Interventions: Transcatheter aortic valve replacement with the SAPIEN 3 valve. Main Outcomes and Measures: Paravalvular regurgitation was assessed in a core laboratory at 30 days and 1 year according to a 5-class scheme: 0, none or trace; 1, mild; 2, mild to moderate; 3, moderate; 4, moderate to severe; and 5, severe. We assessed the effect of PVR on 1-year mortality and heart failure rehospitalization. Results: Among the 1661 included in the registry, 1592 received a SAPIEN 3 valve and had assessment of PVR. Of these patients, 55.7% had none-trace PVR, 32.6% had mild, 8.2% had mild to moderate, and 3.5% had at least moderate PVR at 30 days. At 1 year, 9.3% of patients had died and 14.2% had been rehospitalized. Only patients with at least moderate PVR had higher 1-year mortality (hazard ratio [HR], 2.40; 95% CI, 1.30-4.43; P = .005) and composite of mortality/rehospitalization (HR, 2.35; 95% CI, 1.52-3.62; P < .001). In a paired comparison including 1213 patients, 73% of the patients with at least moderate PVR at 30 days showed a reduction in PVR severity of at least 1 PVR class at 1 year. Conclusions and Relevance: In this series of patients undergoing TAVR with the SAPIEN 3 valve, at least moderate PVR was rare but associated with increased risk of death and heart failure rehospitalization at 1 year. Even the upper range of the mild class in the 3-class grading scheme (ie, mild to moderate in the 5-class scheme) had no significant effect on short-term mortality or rehospitalization. Most patients with at least moderate PVR at 30 days showed a decrease of PVR severity grade at 1 year.

Sannino, A., R. C. Stoler, R. F. Hebeler, Jr., M. Szerlip, M. J. Mack and P. A. Grayburn (2017). “Clinical relevance of baseline tcp in transcatheter aortic valve replacement.” J Invasive Cardiol 29(10): 353-358.

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AIMS: To investigate the influence of baseline thrombocytopenia (TCP) on short-term and long-term outcomes after transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: A total of 732 consecutive patients with severe, symptomatic aortic stenosis undergoing TAVR from January 2012 to December 2015 were included. Primary outcomes of interest were the relationship of baseline TCP with 30-day and 1-year all-cause mortality. Secondary outcomes of interest were procedural complications and in-hospital mortality in the same subgroups. The prevalence of TCP (defined as platelet count <150 x 109/L) at baseline was 21.9%, of whom 4.0% had moderate/severe TCP (defined as platelet count <100 x 109/L). Compared to no or mild TCP, moderate/severe TCP at baseline was associated with a significantly higher 30-day mortality (23.3% vs 2.3% and 3.1%, respectively; P<.001) and 1-year mortality (40.0% vs 8.3% and 13.4%, respectively; P<.001). In Cox regression analysis, moderate/severe baseline TCP was an independent predictor of 30-day and 1-year mortality (hazard ratio [HR], 13.18; 95% confidence interval [CI], 4.49-38.64; P<.001 and HR, 5.90; 95% CI, 2.68-13.02; P<.001, respectively). CONCLUSIONS: In conclusion, baseline TCP is a strong predictor of mortality in TAVR patients, possibly identifying a specific subgroup of frail patients; therefore, it should be taken into account when addressing TAVR risk.

Mack, M. J., M. A. Acker, A. C. Gelijns, J. R. Overbey, M. K. Parides, J. N. Browndyke, M. A. Groh, A. J. Moskowitz, N. O. Jeffries, G. Ailawadi, V. H. Thourani, E. G. Moquete, A. Iribarne, P. Voisine, L. P. Perrault, M. E. Bowdish, M. Bilello, C. Davatzikos, R. F. Mangusan, R. A. Winkle, P. K. Smith, R. E. Michler, M. A. Miller, K. L. O’Sullivan, W. C. Taddei-Peters, E. A. Rose, R. D. Weisel, K. L. Furie, E. Bagiella, C. S. Moy, P. T. O’Gara and S. R. Messe (2017). “Effect of cerebral embolic protection devices on cns infarction in surgical aortic valve replacement: A randomized clinical trial.” Jama 318(6): 536-547.

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Importance: Stroke is a major complication of surgical aortic valve replacement (SAVR). Objective: To determine the efficacy and adverse effects of cerebral embolic protection devices in reducing ischemic central nervous system (CNS) injury during SAVR. Design, Setting, and Participants: A randomized clinical trial of patients with calcific aortic stenosis undergoing SAVR at 18 North American centers between March 2015 and July 2016. The end of follow-up was December 2016. Interventions: Use of 1 of 2 cerebral embolic protection devices (n = 118 for suction-based extraction and n = 133 for intra-aortic filtration device) vs a standard aortic cannula (control; n = 132) at the time of SAVR. Main Outcomes and Measures: The primary end point was freedom from clinical or radiographic CNS infarction at 7 days (+/- 3 days) after the procedure. Secondary end points included a composite of mortality, clinical ischemic stroke, and acute kidney injury within 30 days after surgery; delirium; mortality; serious adverse events; and neurocognition. Results: Among 383 randomized patients (mean age, 73.9 years; 38.4% women; 368 [96.1%] completed the trial), the rate of freedom from CNS infarction at 7 days was 32.0% with suction-based extraction vs 33.3% with control (between-group difference, -1.3%; 95% CI, -13.8% to 11.2%) and 25.6% with intra-aortic filtration vs 32.4% with control (between-group difference, -6.9%; 95% CI, -17.9% to 4.2%). The 30-day composite end point was not significantly different between suction-based extraction and control (21.4% vs 24.2%, respectively; between-group difference, -2.8% [95% CI, -13.5% to 7.9%]) nor between intra-aortic filtration and control (33.3% vs 23.7%; between-group difference, 9.7% [95% CI, -1.2% to 20.5%]). There were no significant differences in mortality (3.4% for suction-based extraction vs 1.7% for control; and 2.3% for intra-aortic filtration vs 1.5% for control) or clinical stroke (5.1% for suction-based extraction vs 5.8% for control; and 8.3% for intra-aortic filtration vs 6.1% for control). Delirium at postoperative day 7 was 6.3% for suction-based extraction vs 15.3% for control (between-group difference, -9.1%; 95% CI, -17.1% to -1.0%) and 8.1% for intra-aortic filtration vs 15.6% for control (between-group difference, -7.4%; 95% CI, -15.5% to 0.6%). Mortality and overall serious adverse events at 90 days were not significantly different across groups. Patients in the intra-aortic filtration group vs patients in the control group experienced significantly more acute kidney injury events (14 vs 4, respectively; P = .02) and cardiac arrhythmias (57 vs 30; P = .004). Conclusions and Relevance: Among patients undergoing SAVR, cerebral embolic protection devices compared with a standard aortic cannula did not significantly reduce the risk of CNS infarction at 7 days. Potential benefits for reduction in delirium, cognition, and symptomatic stroke merit larger trials with longer follow-up.