Michael J. Mack M.D.

Meduri, C. U., M. J. Reardon, D. Scott Lim, E. Howard, G. Dunnington, D. P. Lee, D. Liang, R. Gooley, D. O’Hair, M. K. Ng, A. Walton, K. Spargias, D. Blackman, A. Coisne, D. Hildick-Smith, M. De Gouy, S. Chenoweth, S. Kar, P. M. McCarthy, N. Piazza, A. Qasam, R. P. Martin, M. B. Leon, M. J. Mack, D. H. Adams and V. Bapat (2019). “Novel Multiphase Assessment for Predicting Left Ventricular Outflow Tract Obstruction Before Transcatheter Mitral Valve Replacement.” JACC Cardiovasc Interv Oct 11. [Epub ahead of print].

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OBJECTIVES: 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). BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Vemulapalli, S., J. D. Carroll and M. J. Mack (2019). “Volume and Outcomes for Transcatheter Aortic-Valve Replacement. Reply.” New England Journal of Medicine 381(14): 1394-1395.

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We agree with Noble and Frei that 30-day mortality should not be the sole indicator of site quality. We are currently deriving and validating metrics that emphasize a composite of 30-day morbidity and mortality as well as “alive and well” status at 1 year on the basis of survival and improved quality of life. Yet, the measurement of 30-day mortality remains vital for patient safety. Our analyses of volume suggest that it is a surrogate for quality and that adequate volume is necessary to accurately estimate expected risk-adjusted outcomes. Goldberg et al. raise the complex issue of geographic access to TAVR, for which there are few data. In the United States, we have a “spoke and hub” medical system with centralization of some services because of cost, infrastructure, and quality considerations. As a result, TAVR is not unique in being restricted to certain centers. Despite this, the United States has more hospitals, and more hospitals per capita, performing TAVR than any other country. Although geography is relatively easily measured, access to care is a complex construct of geographic location, socioeconomic status, ethnic group, race, insurance status, patients’ preferences, and physician-related factors, among others. More research is needed to clarify the extent to which each of these factors contributes to access to care issues for TAVR. Our analysis did not fully address access to TAVR, and the analysis that Goldberg and Gray suggested may lead to interesting results. We agree with Sharma that the results of our study were relevant to the CMS National Coverage Determination. However, we differ with Sharma’s interpretation of our results and their relationship to the findings of Russo et al. Russo and colleagues examined only one commercially approved device, defined the beginning of the learning curve on the basis of the first use of the latest generation of the SAPIEN system rather than on the basis of all previous experience, and probably underestimated the site volume by not including CoreValve use. We constructed hierarchical models that accounted for operator case number and then modeled the marginal effect of annual volume on mortality beyond the contribution of operator case number. Since the “learning curve” is essentially defined by mortality as a function of case number, modeling the association between volume and mortality after taking into account case number effectively isolates the annual volume–mortality relationship from the learning curve. With this technique, we found that there was a volume–mortality relationship beyond the learning curve and that it was independent of procedure year and patient risk. (Authors’ reply to correspondence about their article, Vemulapalli S, Carroll JD, Mack MJ, et al. Procedural volume and outcomes for transcatheter aortic-valve replacement. N Engl J Med 2019;380:2541-2550.)

Baron, S. J., K. Wang, S. V. Arnold, E. A. Magnuson, B. Whisenant, A. Brieke, M. Rinaldi, A. W. Asgar, J. Lindenfeld, W. T. Abraham, M. J. Mack, G. W. Stone and D. J. Cohen (2019). “Cost-Effectiveness of Transcatheter Mitral Valve Repair versus Medical Therapy in Patients with Heart Failure and Secondary Mitral Regurgitation: Results from the COAPT Trial.” Circulation Sep 29. [Epub ahead of print].

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Background: The COAPT trial demonstrated that edge-to-edge transcatheter mitral valve repair (TMVr) using the MitraClip resulted in reduced mortality and heart-failure hospitalizations and improved quality of life when compared with maximally-tolerated guideline-directed medical therapy (GDMT) in heart-failure patients with 3-4+ secondary mitral regurgitation (SMR). Whether TMVr is cost-effective compared with GDMT in this population is unknown. Methods: We used data from the COAPT trial to perform a formal, patient-level economic analysis of TMVr + GDMT vs. GDMT alone for patients with heart failure and 3-4+ SMR from the perspective of the US health care system. Costs for the index TMVr hospitalization were assessed using a combination of resource-based accounting and hospital billing data (when available). Follow-up medical care costs were estimated based on medical resource use collected during the COAPT trial. Health utilities were estimated for all patients at baseline, 1, 6, 12 and 24 months using the SF-6D. Results: Initial costs for the TMVr procedure and index hospitalization were $35,755 and $48,198, respectively. Although follow-up costs were significantly lower with TMVr compared with GDMT ($26,654 vs. $38,345; p=0.018), cumulative 2-year costs remained higher with TMVr due to the up-front cost of the index procedure ($73,416 vs. $38,345; p<0.001). When intrial survival, health utilities, and costs were modeled over a lifetime horizon, TMVr was projected to increase life-expectancy by 1.13 years and quality-adjusted life-years (QALYs) by 0.82 years at a cost of $45,648, yielding a lifetime incremental cost-effectiveness ratio of $40,361/life-year gained and $55,600/QALY gained. Conclusions: For symptomatic heart-failure patients with 3-4+ SMR, TMVr increases lifeexpectancy and quality-adjusted life-expectancy compared with GDMT at an incremental cost per QALY gained that represents acceptable economic value based on current U.S. thresholds. Clinical Trial Registration: NCT01626079.

Asch, F. M., P. A. Grayburn, R. J. Siegel, S. Kar, D. S. Lim, J. G. Zaroff, J. M. Mishell, B. Whisenant, M. J. Mack, J. Lindenfeld, W. T. Abraham, G. W. Stone and N. J. Weissman (2019). “Transcatheter Mitral Valve Replacement in Patients with Heart Failure and Secondary Mitral Regurgitation: From COAPT Trial.” Journal of the American College of Cardiology Sep 19. [Epub ahead of print].

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BACKGROUND: In the COAPT trial among patients with heart failure (HF) and moderate-to-severe (3+) or severe (4+) secondary mitral regurgitation (SMR), patients treated with the transcatheter mitral valve replacement (TMVR) had reduced rates of HF hospitalization and mortality compared with guideline-directed medical therapy (GDMT) alone. OBJECTIVES: To describe the echocardiographic patient qualification process for COAPT, baseline echocardiographic characteristics, changes over time, and the interaction between treatment group and echocardiographic parameters on clinical outcomes. METHODS: A novel echocardiographic algorithm was implemented for grading MR severity during the screening process. Standardized echocardiograms were obtained at baseline and during regular follow-up intervals through 2 years, and analyzed by a core laboratory. RESULTS: A total of 614 patients were randomized to TMVR plus maximally- tolerated GDMT or GDMT alone. Mean baseline left ventricular ejection fraction (LVEF) was 31.3+/-9.3%, LV end-diastolic volume was 192.7+/-71 ml, and effective regurgitant orifice area was 0.41+/-0.15 cm(2). The beneficial effect of TMVR compared with GDMT alone was consistent in all echocardiographic subgroups, independent of the severity of LV dysfunction, LV dilatation, pulmonary hypertension, severity of tricuspid regurgitation or individual MR characteristics. The LVEF decreased and the LV volumes progressively increased in both groups during follow-up, although less after TMVR (P<0.05). CONCLUSIONS: HF patients in the COAPT trial with 3+ or 4+ SMR, selected using strict echocardiographic criteria, benefitted from TMVR with reduced 2-year rates of death and HF hospitalization. Strict application of these echocardiographic criteria should enable the COAPT results to be translated to clinical practice.

Baron, S. J., E. A. Magnuson, M. Lu, K. Wang, K. Chinnakondepalli, M. Mack, V. H. Thourani, S. Kodali, R. Makkar, H. C. Herrmann, S. Kapadia, V. Babaliaros, M. R. Williams, D. Kereiakes, A. Zajarias, M. C. Alu, J. G. Webb, C. R. Smith, M. B. Leon and D. J. Cohen (2019). “Health Status after Transcatheter vs. Surgical Aortic Valve Replacement in Low-Risk Patients with Aortic Stenosis.” Journal of the American College of Cardiology Sep 18. [Epub ahead of print].

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BACKGROUND: In patients with severe aortic stenosis (AS) at low surgical risk, treatment with transcatheter aortic valve replacement (TAVR) results in lower rates of death, stroke, and re-hospitalization at 1 year compared with surgical aortic valve replacement; however, the effect of treatment strategy on health status is unknown. OBJECTIVES: This study sought to compare health status outcomes of TAVR vs. surgery in low-risk patients with severe AS. METHODS: Between 3/2016 and 10/2017, 1000 low-risk AS patients were randomized to transfemoral TAVR using a balloon-expandable valve or surgery in the PARTNER 3 Trial. Health status was assessed at baseline, 1, 6 and 12 months using the Kansas City Cardiomyopathy Questionnaire (KCCQ), SF-36 and EQ-5D. The primary endpoint was change in KCCQ-Overall Summary (KCCQ-OS) score over time. Longitudinal growth curve modeling was used to compare changes in health status between treatment groups over time. RESULTS: At 1 month, TAVR was associated with better health status than surgery (mean difference in KCCQ-OS 16.0 points; p<0.001). At 6 and 12 months, health status remained better with TAVR, although the effect was reduced (mean difference in KCCQ-OS 2.6 and 1.8 points respectively; p<0.04 for both). The proportion of patients with an excellent outcome (alive with KCCQ-OS >/= 75 and no significant decline from baseline) was greater with TAVR than surgery at 6 months (90.3% vs. 85.3%; p=0.03) and 12 months (87.3% vs. 82.8%; p=0.07). CONCLUSIONS: Among low-risk patients with severe AS, TAVR was associated with meaningful early and late health status benefits compared with surgery.