To clip, or not to clip heart failure patients, that is the question

Abstract

Functional mitral regurgitation (FMR) occurs in up to 60% of heart failure (HF) patients with reduced left ventricular (LV) ejection fraction. Its frequency and severity depend on the clinical stage of advancement of HF as well as the immediate haemodynamic and therapeutic patient status at presentation. 1,2 FMR results from various LV remodelling mechanisms that prevent coaptation of structurally normal valve leaflets. 3 FMR multiplies the risk of HF decompensation and death by roughly two depending on the HF patient population. 1,4,5 Because of its volatile nature in time and the variety of underlying mechanisms causing mitral regurgitation (MR), the management of HF patients with FMR is complex. This is in clear contrast with organic MR, where MR is the primary cause of symptoms and the benefits of surgical repair/replacement are clearly demonstrated. Percutaneous mitral valve repair (PMVR) has recently emerged as an efficient technique to correct or significantly reduce FMR. 6 Whether this repair translates in significant clinical benefit on HF rehospitalizations and death remained to be demonstrated in randomized clinical trials. Now, two randomized controlled trials have been performed with contradictory results. 7The MITRA-FR study was the first randomized controlled trial assessing efficacy of PMVR against medical therapy in chronic HF patients. It showed no significant difference between the device and control groups for the composite of death and HF hospitalization or for all-cause death at 1 year (P = 0.53 and P = 0.66, respectively). 8 The industry-sponsored COAPT trial was the second and conversely shed an incredible reduction in the repeat-event of all consecutive HF hospitalizations at 2 years (P < 0.001). 9 Some might say MITRA-FR is a false-negative, but they could be biased. In the light of all previous trials performed in this setting, 10,11 others might suggest COAPT is a false-positive, but they could also be biased.Therefore, in this peculiar situation of two trials with different results, without any overlap in confidence intervals for the primary endpoint, it is of upmost importance to go beyond the emotions triggered by the COAPT survival curves and keep our wits together! That is, if you have any.

Who and when to clip: that is the question

“…In their editorial ‘To clip, or not to clip heart failure patients, that is the question’, Mewton and Cucherat imply that by virtue of the disparate outcomes observed between COAPT and MITRA‐FR, the benefits of mitral valve repair using the MitraClip device for heart failure patients with secondary mitral regurgitation (SMR) remain uncertain. We respectfully disagree and appreciate the opportunity to respond to several of the concerns raised by the authors as they relate to the COAPT trial.…”

Treatment of Secondary Mitral Regurgitation in Heart Failure: A Shifting Paradigm in the Wake of the COAPT Trial

“…Although concerns have been raised by Mitra.FR investigators about baseline differences in use of renin-angiotensin-aldosterone inhibitors among COAPT-enrolled patients, which were marginally significant by chance, a multivariable analysis published in the original COAPT manuscript demonstrated that the point estimates for benefit were similar after accounting for this consideration. 12,16 Similarly, while…”

“…14 While the discordant results from COAPT and Mitra.FR have yet to be fully reconciled, several key points are worth noting. 15,16 First, patient enrollment in COAPT was contingent on confirmation by a central eligibility committee that patients with reduced left ventricular function were taking maximally tolerated doses of GDMT. This requirement was not the case in Mitra.FR.…”

“…Mitra.FR investigators have expressed concerns about potential differences in baseline heart rate and blood pressure among COAPTenrolled patients, these parameters have been recently reported, demonstrating no significant differences between GDMT and GDMT+MitraClip. 15,16 One final difference is that COAPT enrolled only NYHA class IV ambulatory patients, whereas Mitra.FR did not require NYHA class IV patients to be ambulatory. 12,14 Whatever the explanation for the discordant results from the two trials, the statistically robust COAPT results (p=0.000006 for the primary effectiveness endpoint) have ignited interest in percutaneous therapies for SMR and highlighted the importance of a multidisciplinary approach that begins with the heart failure cardiologist and relies heavily on expertise from interventionalists, surgeons and cardiac imaging experts.…”