Michael J. Mack M.D.

Ailawadi, G., D. S. Lim, M. J. Mack, A. Trento, S. Kar, P. A. Grayburn, D. D. Glower, A. Wang, E. Foster, A. Qasim, N. J. Weissman, J. Ellis, L. Crosson, F. Fan, I. L. Kron, P. J. Pearson and T. Feldman (2019). “One-Year Outcomes After MitraClip for Functional Mitral Regurgitation.” Circulation 139(1): 37-47.

Full text of this article.

BACKGROUND: Secondary mitral regurgitation (SMR) occurs in the absence of organic mitral valve disease and may develop as the left ventricle dilates or remodels or as a result of leaflet tethering with impaired coaptation, most commonly from apical and lateral distraction of the subvalvular apparatus, with late annular dilatation. The optimal therapy for SMR is unclear. This study sought to evaluate the 1-year adjudicated outcomes of all patients with SMR undergoing the MitraClip procedure in the EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) Investigational Device Exemption program, which is comprised of the randomized clinical trial, the prospective High-Risk Registry, and the REALISM Continued Access Registry (Multicenter Study of the MitraClip System). METHODS: Patients with 3+/4+ SMR enrolled in EVEREST II were stratified by non-high surgical risk (non-HR) and high surgical risk (HR) status (defined as Society of Thoracic Surgeons risk of mortality >/=12% or predefined risk factors). Clinical, echocardiographic, and functional outcomes at 1 year were evaluated. RESULTS: A total of 616 patients (482 HR, 134 non-HR; mean age, 73.3+/-10.5 years; Society of Thoracic Surgeons risk, 10.2+/-6.9%) with SMR underwent the MitraClip procedure. At baseline, 80.5% of patients were in New York Heart Association class III/IV. Major adverse events at 30 days included death (3.6%), stroke (2.3%), and renal failure (1.5%). At discharge, 88.8% had MR

Arnold, S. V., Z. Li, S. Vemulapalli, S. J. Baron, M. J. Mack, A. S. Kosinski, M. R. Reynolds, J. B. Hermiller, J. S. Rumsfeld and D. J. Cohen (2018). “Association of Transcatheter Mitral Valve Repair With Quality of Life Outcomes at 30 Days and 1 Year: Analysis of the Transcatheter Valve Therapy Registry.” JAMA Cardiol Nov 21. [Epub ahead of print].

Full text of this article.

Importance: Improvements in symptoms, functional capacity, and quality of life are among the key goals of edge-to-edge transcatheter mitral valve repair (TMVR) for mitral regurgitation. Objective: To examine health status outcomes among patients undergoing TMVR in clinical practice and the factors associated with improvement. Design, Setting, and Participants: This cohort study used the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry, which contains data on patients with severe mitral regurgitation treated with TMVR from 2013 through 2017 in 217 US hospitals. Main Outcomes and Measures: Change in disease-specific health status (Kansas City Cardiomyopathy Questionnaire-Overall Summary score [KCCQ-OS]; range 0-100 points, with higher scores indicating better health status) at 30 days and 1 year after TMVR. We also examined factors associated with health status at 30 days after TMVR, by means of multivariable linear regression using a generalized estimating equations approach to account for clustering of patients within sites. Results: The KCCQ data were available in 81.2% at baseline, 69.3% of survivors at 30 days, and 47.4% of survivors at 1 year. Among 4226 patients who underwent TMVR, survived 30 days, and completed the KCCQ at baseline and follow-up, the KCCQ-OS increased from 41.9 before TMVR to 66.7 at 30 days (mean change 24.8 [95% CI, 24.0-25.6] points; P < .001), representing a large clinical improvement. The KCCQ scores remained stable from 30 days to 1 year after TMVR, with no further significant increase or decline. On multivariable analysis, atrial fibrillation (-2.2 [95% CI, -3.7 to -0.6] points; P = .01), permanent pacemaker (-2.1 [95% CI, -3.7 to -0.4] points; P = .01), severe lung disease (-3.9 [95% CI, -6.2 to -1.5] points; P = .001), home oxygen (-2.7 [95% CI, -4.9 to -0.4] points; P = .02), and lower KCCQ scores at baseline (3.9 points for each 10-point increase [95% CI, 3.6-4.2]; P < .001) were independently associated with lower 30-day KCCQ-OS scores. In-hospital renal failure was uncommon but was also associated with significant reductions in 30-day KCCQ-OS scores (-7.3 [95% CI -13.3 to -1.2] points). In estimates calculated with inverse probability weighting, after 1 year after TMVR, 54.2% (95% CI 52.2%-56.1%) of patients were alive and well; 23.0% had died, 21.9% had persistently poor health status (KCCQ-OS <60 points), 5.5% had a health status decline from baseline, and 4.6% had both poor health status and health status decline. Conclusions and Relevance: In a national cohort of US patients undergoing edge-to-edge TMVR in clinical practice, health status was impaired prior to the procedure, improved within 30 days, and remained stable through 1 year among surviving patients with available data. While long-term mortality remains high, most surviving patients demonstrate improvements in symptoms, functional status, and quality of life, with only modest differences by patient-level factors.

Mack, M. J. and L. G. Svensson (2018). “Transcatheter Aortic Valve Replacement Without On-Site Cardiac Surgery: A Disappointing Step Backward!” JACC Cardiovasc Interv 11(21): 2168-2171.

Full text of this article.

Objectives: This study sought to evaluate whether a multimarker approach might identify patients with higher mortality and hospitalization rates after aortic valve replacement (AVR) for aortic stenosis (AS). Background: The society valve guidelines include accepted triggers for AVR in patients with severe asymptomatic AS, but circulating biomarkers do not have a clear role. Method: From a prospective registry of patients undergoing cardiac surgery between 2000 and 2012, 665 treated with surgical AVR (441 isolated) were evaluated. Seven biomarkers were measured on blood samples obtained before AVR. Biomarker levels were adjusted to account for the influence of age, sex, body mass index, and renal function; the median was used to determine an elevated value. Endpoints included all-cause mortality and all-cause and cardiovascular hospitalizations. Mean follow-up was 10.7 years and 299 (45%) died. Results: Patients with 0 to 1, 2 to 3, 4 to 6, and 7 biomarkers elevated had 5-year mortality of 10%, 12%, 24%, and 33%, respectively, and 10-year mortality of 24%, 35%, 58%, and 71%, respectively (log-rank p < 0.001). The association between an increasing number of elevated biomarkers and increased all-cause mortality was observed among those with minimal symptoms (New York Heart Association functional class I or II) and those with a low N-terminal pro–B-type natriuretic peptide (p < 0.01 for both). Compared with those with 0 to 1 biomarkers elevated, patients with 4 to 6 or 7 biomarkers elevated had an increased hazard of mortality after adjustment for clinical risk scores (p < 0.01) and a 2- to 3-fold higher rate of all-cause and cardiovascular rehospitalization after AVR. Similar findings were obtained when evaluating cardiovascular mortality. Among patients with no or minimal symptoms, 42% had ≥4 biomarkers elevated. Conclusions: Among patients with severe AS treated with surgical AVR, an increasing number of elevated biomarkers of cardiovascular stress was associated with higher all-cause and cardiovascular mortality and a higher rate of repeat hospitalization. A multimarker approach may be useful in the surveillance of asymptomatic patients with severe AS to optimize surgical timing.

Kapadia, S. R., C. P. Huded, S. K. Kodali, L. G. Svensson, E. M. Tuzcu, S. J. Baron, D. J. Cohen, D. C. Miller, V. H. Thourani, H. C. Herrmann, M. J. Mack, M. Szerlip, R. R. Makkar, J. G. Webb, C. R. Smith, J. Rajeswaran, E. H. Blackstone and M. B. Leon (2018). “Stroke After Surgical Versus Transfemoral Transcatheter Aortic Valve Replacement in the PARTNER Trial.” J Am Coll Cardiol 72(20): 2415-2426.

Full text of this article.

BACKGROUND: Transfemoral-transcatheter aortic valve replacement (TF-TAVR) is increasingly used to treat aortic stenosis, but risk of post-procedure stroke is uncertain. OBJECTIVES: The purpose of this study was to assess stroke risk and its association with quality of life after surgical aortic valve replacement (SAVR) versus TF-TAVR. METHODS: The authors performed a propensity-matched study of 1,204 pairs of patients with severe aortic stenosis treated with SAVR versus TF-TAVR in the PARTNER (Placement of AoRTic TraNscathetER Valves) trials from April 2007 to October 2014. Outcomes were: 1) 30-day neurological events; 2) time-varying risk of neurological events early (

Holmes, D. R., Jr., R. Hance, T. S. Syrek Jensen, D. A. Schwartz, A. Kaplan, A. Farb, B. Zuckerman, M. Leon, J. Waklowiak, M. J. Mack and J. Shuren (2018). “The 21st Century Cures Act and Early Feasibility Studies for Cardiovascular Devices: What Have We Learned, Where Do We Need to Go?” JACC Cardiovasc Interv 11(21): 2220-2225.

Full text of this article.

Performance of early feasibility studies in the United States can advance the goal of evaluating the safety and effectiveness of new devices aimed at unmet clinical needs and facilitating earlier access for U.S. patients to new technology. Early feasibility studies are an important component of the 21st Century Cures Act, enacted by Congress in 2016. Although regulatory processes have improved since the introduction of the Early Feasibility Studies Program, impediments at the hospital and clinical site level remain. In this paper, the authors review these issues and outline the structure and function of a clinical site consortium designed to address the problems and improve the U.S. clinical trial ecosystem.