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Study Summary

Percutaneous mitral valve repair may improve symptoms and quality of life in patients with severe secondary mitral-valve regurgitation (MR) and chronic heart failure with reduced left ventricular ejection fraction; there is uncertainty about whether mitral valve reduction affects hard clinical outcomes. In the MITRA-FR study, 304 patients with symptomatic heart failure (at least New York Heart Association class II symptoms and at least 1 recent hospitalization for heart failure) despite optimal medical therapy, reduced left ventricular ejection fraction (15-40%), and severe secondary mitral regurgitation were randomized to percutaneous mitral valve repair and medical therapy or medical therapy alone. Between groups, there was no significant difference at 12 months in the primary composite endpoint of death or heart failure hospitalization (54.6% versus 51.3% respectively; OR 1.16; CI 95% 0.73-1.84, P=0.53) (see accompanying Hurst’s Central Illustration).

Commentary

Study Strengths: The strength of this trial arises from its design as a multicenter, randomized, controlled study with adequate enrollment (155 versus 152 patients) to satisfy the pre-specified power goals. The patients enrolled were highly morbid, with event rates > 50% at 12 months in each arm. Device implantation was considered successful in 95.8% of patients in the intervention group, and 76.4% of them had no or mild MR at time of hospital discharge.

Study Limitations: The major limitation of the study is that the procedure was not performed or the device implantation failed in 9.2% of the patients in the intervention group. Notably, however, a subsequent per-protocol analysis, which excluded these patients, did not reveal a significant difference in outcomes between the two groups. In addition, whereas the enrollment criteria allowed patients with less-severe MR per prior guidelines (regurgitant orifice area >20 mm2 and regurgitant volume >30 ml per beat), mean orifice area actually was 31±10 mm2 and regurgitant volume was 45±13 in the intervention group. Finally, a large amount of echocardiographic and functional status/quality of life follow-up data at 12 months were unable to be collected, but at least 48 of the patients had significant residual MR at 1 year, which might reflect suboptimal reduction. Such incomplete reduction of MR may account for the lack of clinical benefit seen among patients who underwent percutaneous mitral valve repair. This suggests that reversion of ventricular remodeling may require complete correction of MR and that patients with a left ventricular end diastolic diameter >65 mm may experience worse outcomes despite optimal intervention. It should also be noted that two-thirds of patients in both groups had ischemic MR and, although speculative on our part (there is no valve analysis in the manuscript), these patients had a lateralized culprit MR jet at P3, which makes complete and durable correction more challenging.

Next Steps/Clinical Perspective: Though there was no clinical benefit of percutaneous mitral valve repair on the primary outcome in this study, the value of such therapy should not be discounted in a significantly morbid population, as its role may not be to necessarily affect prognosis, but to improve symptoms and quality of life. Notably, the COAPT trial recently showed positive clinical outcomes among patients with heart failure and moderate-to-severe or severe secondary MR who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy. Reasons for the differences between the findings of the two studies need further elucidation.

Trial Reference

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Obadia  J-F, Messika-Zeitoun  D, Leurent  G, et al. Percutaneous repair or medical treatment for secondary mitral regurgitation. N. Engl. J. Med. doi: 10.1056/NEJMoa1805374

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