Research Spotlight

Mack, M.J. and Adams, D.H. (2020). “Regulatory Approval and Practice Guidelines Involving Cardiovascular Valve Devices: Determining the Right Evidentiary Bar.” J Am Coll Cardiol 76(8): 992-995.

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Recently, a number of criticisms and concerns have been raised regarding the design as well as findings of randomized trials in the fields of coronary revascularization and transcatheter valve therapy, including a thought-provoking critique of the low-risk trials of transcatheter aortic valve replacement (TAVR) by Kaul in this issue of the Journal. Kaul thoroughly analyzes the 2 low-risk RCTs of TAVR (3,4) compared with surgical aortic valve replacement and concludes that there is not sufficiently robust evidence to justify a Class I or even a Class IIa guideline recommendation for TAVR in low-risk patients at the current time. He cites a number of concerns that he feels make the evidence insufficient for changing guideline class, including a smaller number of patients enrolled who had fewer events than were included in the previous higher-risk TAVR trials, the wide margins of noninferiority, the trial design endpoints, the differences in findings between the 2 trials, and the short time of follow-up for the primary endpoints. He also raises concerns regarding using imputation for 90.2% of the patients for the 2-year endpoint in one of the trials. [No abstract; excerpt from Editorial.].

Hara, H., Takahashi, K., van Klaveren, D., Wang, R., Garg, S., Ono, M., Kawashima, H., Gao, C., Mack, M., Holmes, D.R., Morice, M.C., Head, S.J., Kappetein, A.P., Thuijs, D., Onuma, Y., Noack, T., Mohr, F.W., Davierwala, P.M. and Serruys, P.W. (2020). “Sex Differences in All-Cause Mortality in the Decade Following Complex Coronary Revascularization.” J Am Coll Cardiol 76(8): 889-899.

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BACKGROUND: The poorer prognosis of coronary artery disease in females compared with males is related mainly to differences in baseline characteristics. In the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) trial, the effect of treatment with percutaneous coronary intervention (PCI) versus coronary artery bypass grafting surgery (CABG) on mortality at 5 years differed significantly between females and males; however, the optimal revascularization beyond 5 years according to sex has not been evaluated. OBJECTIVES: The aim of this study was to investigate the impact of sex on mortality and sex-treatment interaction at 10 years. METHODS: The SYNTAXES (SYNTAX Extended Survival) study evaluated vital status up to 10 years in 1,800 patients with de novo 3-vessel and/or left main coronary artery disease randomized to treatment with PCI or CABG in the SYNTAX trial. All-cause death at 10 years was separately evaluated in female and male patients with complex coronary artery disease. RESULTS: Of 1,800 patients, 402 (22.3%) were female and 1,398 (77.7%) were males. Females had a higher 10-year mortality rate compared with males (32.8% vs. 24.7%; log-rank p = 0.002), but female sex was not an independent predictor of mortality (adjusted hazard ratio: 1.02; 95% confidence interval: 0.76 to 1.36). Mortality at 10 years tended to be lower after CABG than after PCI, with a similar treatment effect for female and male patients (adjusted hazard ratio for females: 0.90 [95% confidence interval: 0.54 to 1.51]; adjusted hazard ratio for males: 0.76 [95% confidence interval: 0.56 to 1.02]; p for interaction = 0.952). CONCLUSIONS: Female sex was not an independent predictor of mortality at 10 years in patients with complex coronary artery disease. The interaction between sex and treatment with PCI or CABG that was observed at 5 years was no longer present at 10 years. (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES], NCT03417050; SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX], NCT00114972).

Edwards, A.S., Kaplan, B. and Jie, T. (2020). “A Primer on Machine Learning.” Transplantation Aug 18. [Epub ahead of print.].

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In transplant medicine, large collections of data from patients, and various procedures have been stored and organized in registries and databases. With the increase in data volume, there has been a demand for tools that can handle the challenges presented by so called “big data”. In recent years, mathematical and statistical tools such as machine learning are being utilized in an increasing number of analyses. In addition, machine learning has been utilized in various other domains where a large amount of complex data needs to be interrogated (eg, genomics). While the term ‘machine learning’ has become a term commonly mentioned, the techniques, strengths, and limitations are often not fully understood by readers of transplant literature. This commentary will cover some of the history and basic concepts of Machine learning. [No abstract; excerpt from article.].

Grayburn, P.A., Sannino, A., Cohen, D.J., Kar, S., Lim, D.S., Mishell, J.M., Whisenant, B.K., Rinaldi, M.J., Kapadia, S.R., Rajagopal, V., Crowley, A., Kotinkaduwa, L.N., Lindenfeld, J., Abraham, W.T., Mack, M.J. and Stone, G.W. (2020). “Predictors of Clinical Response to Transcatheter Reduction of Secondary Mitral Regurgitation: The COAPT Trial.” J Am Coll Cardiol 76(9): 1007-1014.

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BACKGROUND: Transcatheter mitral valve repair with the MitraClip results in marked clinical improvement in some but not all patients with secondary mitral regurgitation (MR) and heart failure (HF). OBJECTIVES: This study sought to evaluate the clinical predictors of a major response to treatment in the COAPT trial. METHODS: Patients with HF and severe MR who were symptomatic on maximally tolerated guideline-directed medical therapy (GDMT) were randomly assigned to MitraClip plus GDMT or GDMT alone. Super-responders were defined as those alive without HF hospitalization and with ≥20-point improvement in the Kansas City Cardiomyopathy Questionnaire overall summary (KCCQ-OS) score at 12 months. Responders were defined as those alive without HF hospitalization and with a 5 to <20-point KCCQ-OS improvement at 12 months. Nonresponders were those who either died, were hospitalized for HF, or had <5-point improvement in KCCQ-OS at 12 months. RESULTS: Among 614 enrolled patients, 41 (6.7%) had missing KCCQ-OS data and could not be classified. At 12 months, there were 79 super-responders (27.2%), 55 responders (19.0%), and 156 nonresponders (53.8%) in the MitraClip arm compared with 29 super-responders (10.2%), 46 responders (16.3%), and 208 nonresponders (73.5%) in the GDMT-alone arm (overall p < 0.0001). Independent baseline predictors of clinical responder status were lower serum creatinine and KCCQ-OS scores and treatment assignment to MitraClip. MR grade and estimated right ventricular systolic pressure at 30 days were improved to a greater degree in super-responders and responders but not in nonresponders. CONCLUSIONS: Baseline predictors of clinical super-responders in patients with HF and severe secondary MR in the COAPT trial were lower serum creatinine, KCCQ-OS score and MitraClip treatment. Improved MR severity and reduced right ventricular systolic pressure at 30 days are associated with a long-term favorable clinical response after transcatheter mitral valve repair. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [COAPT]; NCT01626079).

Grayburn, P.A. and Sannino, A. (2020). “Patient selection for transcatheter edge-to-edge mitral valve repair for severe functional mitral regurgitation.” EuroIntervention 16(5): 367-369.

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In 2018, two randomised clinical trials of transcatheter edge-to-edge mitral valve repair (TMVr) for functional mitral regurgitation (FMR) reported very different outcomes. The MITRA-FR trial showed no statistically significant difference in the combined endpoint of death or hospitalisation for heart failure (HF) at one year. The COAPT trial showed marked improvements in total HF hospitalisations at two years, as well as mortality and multiple other pre-specified secondary endpoints. We hypothesised that the divergent outcomes of the two trials could be explained largely by enrolment of different patient populations. [No abstract; excerpt from article.].