Clinical trial design principles and endpoint definitions for transcatheter mitral valve repair and replacement: part 2: endpoint definitions

Abstract

Mitral regurgitation (MR) is one of the most prevalent valve disorders and has numerous aetiologies, including primary (organic) MR, due to underlying degenerative/structural mitral valve (MV) pathology, and secondary (functional) MR, which is principally caused by global or regional left ventricular remodelling and/or severe left atrial dilation. Diagnosis and optimal management of MR requires integration of valve disease and heart failure specialists, MV cardiac surgeons, interventional cardiologists with expertise in structural heart disease, and imaging experts. The introduction of trans- catheter MV therapies has highlighted the need for a consensus approach to pragmatic clinical trial design and uniform endpoint definitions to evaluate outcomes in patients with MR. The Mitral Valve Academic Research Consortium is a collaboration between leading academic research organizations and physician-scientists specializing in MV disease from the United States and Europe. Three in-person meetings were held in Virginia and New York during which 44 heart failure, valve, and imaging experts, MV surgeons and interventional cardiologists, clinical trial specialists and statisticians, and representatives from the U.S. Food and Drug Administration considered all aspects of MV pathophysiology, prognosis, and therapies, culminating in a 2-part document describing consensus recommendations for clinical trial design (Part 1) and endpoint definitions (Part 2) to guide evaluation of transcatheter and surgical therapies for MR. The adoption of these recommendations will afford robustness and consistency in the comparative effectiveness evaluation of new devices and approaches to treat MR. These principles may be useful for regulatory assessment of new transcatheter MV devices, as well as for monitoring local and regional outcomes to guide quality improvement initiatives.

Mitraclip therapy in patients with functional mitral regurgitation and missing leaflet coaptation: is it still an exclusion criterion?

“…We applied the MVARC criteria, which were recently published aiming to standardize clinical outcome evaluation after percutaneous mitral valve intervention . Therefore, the comparison with previous data could be partially limited.…”

“…The safety and efficacy endpoints were defined according to the recent Mitral Valve Academic Research Consortium (MVARC) classification …”

MicroRNA‐30c suppresses the pro‐fibrogenic effects of cardiac fibroblasts induced by TGF‐β1 and prevents atrial fibrosis by targeting TGFβRII

“…Notably, miR‐30c up‐regulation was inversely correlated with the decreased expression levels of Col I and Col3α1 in cells treated with TGF‑β1. ECM metabolic imbalance is involved in various cardiovascular diseases such as myocardial infarction, heart failure and AF 68, 69, 70. Moreover, miR‐30c overexpression decreased the ECM‐regulated gene expression levels of Col I and Col3α1 in CFs, whereas MiR‐30c inhibition promoted these processes.…”

Current MitraClip experience, safety and feasibility in the Netherlands

“…The primary endpoints were procedural safety expressed in ‘technical success’ and procedural efficacy expressed in ‘device success’, both were modified from the Mitral Valve Research Consortium (MVARC) criteria [10].

Technical success is defined as successful deployment of the device with absence of procedural mortality and freedom from emergency surgery.

Device success is defined as proper placement of the device without procedural mortality and with reduction in post-procedural MR by ≥1 grade from baseline and to an absolute level of ≤moderate MR.

Significant MR reduction: reduction in post-procedural MR by ≥1 grade from baseline.

Device time is defined as the time from guide catheter insertion to guide catheter removal.

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