Transcatheter Mitral Valve Repair: Guideline Changes, Evidence Gaps and Future Directions

April 22th Plenary Session of TCTAP 2021 Virtual

Transcatheter aortic valve replacement (TAVR) has gained unprecedented success in the past decade by establishing more and more evidence as the standard treatment for severe aortic stenosis.

Cardiologists have been increasingly focusing on the neighboring mitral valve, which has anintrinsically more complex structure due to its three-dimensional saddle shape and the presence of subvalvular apparatus.

The normal function of the mitral valves requires the dynamic balance among the mitral annulus, mitral valve leaflets, the chordea tendinease, the papillary muscles and the left ventricular wall.

Mitral regurgitation (MR) is the most common mitral valve disease. It could be classified into primary MR, where the pathology lies at the valve leaflets or the supporting valvular apparatus; or secondary MR, where the pathology lies at the left ventricle or left atrium causing geometric disturbance to the mitral annulus or papillary muscle.

Gregg W. Stone (Icahn School of Medicine, New York, USA), during his keynote lecture at TCTAP 2021 Virtual, noted that although surgical repair is “clearly the standard of care for MR” based on observational studies, although the same could not be said for patients who received open heart surgery for secondary MR.

“The standard of care for secondary MR leading to heart failure is really guideline-directed heart failure medications,” Stone said. “This is where transcatheter mitral valve repair may play a role.”

MitraClip System, which is a transcatheter edge-to-edge mitral valve repair device, was demonstrated in the early multicenter randomized EVEREST II trial to be safer but not as effective when compared to open heart surgery in treating severe MR with mixed etiologies.

In subgroup analysis, MitraClip was clearly inferior to open heart surgery in treating primary MR but there was no difference between the two groups when treating secondary MR.

In view of the study and associated registries data, the U.S. Food and Drug Administration (FDA) approved MitraClip in 2013 for the treatment of symptomatic severe primary MR who were at prohibitive risk for open heart surgery. This approval led to the incorporation of MitraClip by American guidelines as a Class IIb recommendation.

More evidence on the treatment of primary MR using MitraClip is to be published from the on-going REPAIR MR trial, which is a randomized study comparing MitraClip with mitral surgery in patients with severe primary MR who are at moderate surgical risk.

For treatment of secondary MR, the landmark COAPT trial was a game-changer, Stone said. COAPT was a parallel-controlled, open-label, multi-center trial involving 614 patients with heart failure and moderate to severe secondary MR fulfilling some stringent echocardiographic parameters.

The trial compared MitraClip plus guideline-directed medical therapy (GDMT) vs GDMT alone. The primary outcome was met after 24 months, showing around a 50 percent reduction in all hospitalizations for heart failure (HR 0.53; 95% CI 0.40-0.70; p<0.001) in the MitraClip arm.

The number-needed-to-treat (NNT) to prevent one heart failure admission was only 3.1 at 24 months. The mortality was also reduced (HR 0.62; 95% CI 0.46-0.82; p<0.001).

“The number-needed-to-treat is six patients to save one life” Stone said, “This is an incredibly highly effective therapy that can impact patients’ lives and is one of the safest procedures done in the cath lab.”

Freedom from device-related complications at 12-months was 96.6 percent.
Stone pointed out that the degree of MR reduction achieved served as the main benefit of MitraClip in the study. At 30 days, up to 93 percent of patients receiving MitraClip had a mitral regurgitation grade from 3+ (nine patients) or above to 2+ or below (33 patients), while up to 73 percent of patients had1+ or lower (214 patients).

The MITRA-FR trial was designed similarly to the MitraClip trial for secondary MR treatment, but produced an entirely different result. At 24 months, MITRA-FR showed MitraClip plus medical therapy was not different from medical therapy alone for symptomatic severe secondary MR in terms of death or heart failure hospitalization (HR 1.01, 95% CI 0.77-1.34; p=0.92).

“The biggest difference between these two trials is probably the difference in the severity of mitral regurgitation relative to the size of the ventricles that were enrolled in these two studies,” Stone said.

The type of patients recruited in the COAPT trials were those had disproportionately severe MR in relation to the degree of left ventricular dilatation, whereas those in the MITRA-FR study were those having less severe MR.

“In COAPT, we were very careful with the inclusion and exclusion criteria to first, exclude the largest left ventricles (left ventricular end systolic dimension >70mm) and second, require severe MR from a multi-parametric approach,” Stone said.

The FDA approved MitraClip in 2019 for the treatment of selected patients with severe secondary MR who remain symptomatic despite GDMT. American guidelines also recommended MitraClip (Class IIa) for the treatment of severe secondary MR when the patient remains symptomatic despite GDMT.

In summary, Stone explained that the MitraClip is an established treatment for primary MR patients at high surgical risk. For secondary MR, MitraClip should be available for severe MR patients who remain symptomatic despite GDMT and also fit the inclusion and exclusion criteria of the COAPT trial.

“Many new devices in addition to MitraClip are being developed based on innovations like edge-to-edge repair approach, direct/indirect annuloplasty approach, or even transcatheter mitral replacement approach,” Stone said. “We’ve taken the first major steps in transcatheter treatment of mitral regurgitation both for primary and secondary mitral regurgitation, and the future looks very bright.”

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Editor: Anthony Yiu Tung Wong, MD (Queen Mary Hospital, Hong Kong)

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