MitraClip improves outcomes in patients with less severe mitral regurgitation, heart failure
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Key takeaways:
- Transcatheter mitral valve repair improved outcomes and symptoms in patients with moderate to severe mitral regurgitation and HF.
- Prior studies enrolled patients with more severe disease.
Transcatheter mitral valve repair in addition to medical therapy led to a lower rate of CV events and hospitalizations and better health status compared with medical therapy alone for patients with HF and moderate to severe mitral regurgitation.
Results of the randomized RESHAPE-HF2 trial, which assessed outcomes after transcatheter mitral valve repair with MitraClip (Abbott Vascular) for the treatment of concomitant functional mitral regurgitation and HF, were presented at the European Society of Cardiology Congress and simultaneously published in The New England Journal of Medicine.
“This trial tried to investigate whether patients with functional mitral regurgitation, who typically have a poor prognosis and lots of symptoms and hospitalizations, would benefit from treatment with a procedure that improves mitral regurgitation,” Stefan D. Anker, MD, PhD, heart failure cardiologist at Charité Berlin, Germany, said during a press conference.
RESHAPE-HF2 is different from its predecessor trials, COAPT and MITRA-FR, as this trial enrolled patients with moderate to severe mitral regurgitation, while the other two included only patients with severe mitral regurgitation.
As Healio previously reported, in COAPT, transcatheter mitral valve repair reduced risk for HF hospitalization and mortality compared with medical therapy alone in patients with HF and severe secondary mitral regurgitation.
Conversely, in MITRA-FR, transcatheter mitral valve repair was not associated with improvement in death and unplanned hospitalization for HF in patients with HF and severe secondary mitral regurgitation.
For RESHAPE-HF2, Anker and colleagues randomly assigned 505 patients to undergo transcatheter mitral valve repair with MitraClip in addition to guideline-directed medical therapy or medical therapy alone. Those enrolled had NYHA class II to IV HF, left ventricular ejection fraction of 20% to 50%, grade 3+ to 4+ mitral regurgitation and one HF hospitalization in the previous year or elevated natriuretic peptides.
The trial had three primary endpoints: the rate of CV death or first or recurrent HF hospitalization during 24 months; first or recurrent HF hospitalization during 24 months; and change in HF symptoms, as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ) score, from baseline to 12 months.
At 24 month follow-up in the MitraClip arm, the researchers reported a 36% lower rate of CV death or first or recurrent hospitalizations for HF (37 vs. 58.9 events per 100 patient-years; RR = 0.64; 95% CI, 0.48-0.85; P = .002) and a 41% lower rate of first or recurrent HF hospitalizations only (26.9 vs. 46.6 events per 100 patient-years; RR = 0.59; 95% CI, 0.42-0.82; P = .002).
At 12-month follow-up, KCCQ score improved by 21 points in the MitraClip arm and 8 points in the medical therapy only arm (P < .001).
Transcatheter mitral valve repair was also associated with greater improvement to mitral regurgitation grade 2 or less at 12 months (OR = 21.3; 95% CI, 10.7-45.8; P < .001), greater improvement to NYHA class I or II at 12 months (OR = 2.35; 95% CI, 1.48-3.77; P < .001) and a greater change in 6-minute walk distance from baseline to 12 months (least-squares means difference, 20.5 m; 95% CI, 0.3-40.7; P = .05).
Rates of death from any cause during complete follow-up and recurrent hospitalization for any cause during 24 months were not significantly different between the groups.
“We may consider now that a treatment like MitraClip for the improvement of functional mitral regurgitation can be considered in patients with less than severe functional mitral regurgitation,” Anker said during the press conference. “This needs validation in future studies, but really indicates that there is a likelihood for a bigger application of these interventions.”
Reference:
Perspective
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What we have seen is that in a second clinical trial, MitraClip immensely improved hard endpoints, particularly HF hospitalization, in patients with moderate to severe mitral regurgitation. We had two previous clinical trials of MitraClip in patients with severe mitral regurgitation: COAPT and MITRA-FR. MITRA-FR was negative. COAPT was positive, and possibly one of the most positive trials I have ever seen. After COAPT, we started implanting the device, but with one negative and one positive trial, we needed a third to break the tie. I do not think RESHAPE-HF2 necessarily breaks the tie because the populations are not the same, but it definitely confirms the efficacy of MitraClip in patients with moderate to severe mitral regurgitation.
A key issue is that the populations of the three trials are not the same. In COAPT, patients had very severe mitral regurgitation (average affected regurgitant orifice, 0.4 mm2). MITRA-FR included patients with slightly less severe mitral regurgitation (average affected regurgitant orifice, 0.31 mm2). RESHAPE-HF2 patients had more moderate mitral regurgitation (average affected regurgitant orifice, 0.25 mm2). Also, the regurgitant volume was 35 mL per beat, while usually the echo criteria for severe mitral regurgitation is more than 60 mL per beat. Clearly, they are not patients with severe mitral regurgitation, but the fact remains that the trial is positive, with a 36% reduction in the main endpoint of HF hospitalization or CV death. If we take CV death out of the equation and just focus on HF hospitalization, we see a 41% reduction if HF hospitalization at 24 months.
Apart from that, if we focus on other, non-heart endpoints, everything is positive. RESHAPE-HF2 had an improvement in KCCQ of 11 points, and this is an incredible improvement in quality of life.
You can argue that it was because the patients were not blinded; hence, they knew whether they were randomized to medical therapy or MitraClip, but the fact remains that improvement in quality of life is huge.
The improvement in the 6-minute walk test is remarkable — more than 20 m.
All of the results are parallel, showing huge improvements with MitraClip in patients with HF and moderate to severe mitral regurgitation.
The number needed to treat to prevent one HF hospitalization is only five patients, a similar number to COAPT at three patients. That is huge.
Overall, RESHAPE-HF2 is a very positive trial that the CV community was overwhelmingly waiting for.
Perspective
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Sean Pinney, MD, FACC, FAST, FHFSA
Knowing there is such a high event rate associated with severe secondary mitral regurgitation, it makes sense to ask whether performing mitral valve transcatheter edge-to-edge repair (TEER) in patients with slightly less severe mitral regurgitation may produce a clinical benefit similar to that seen in COAPT.
The RESHAPE-HF2 investigators showed that mitral TEER successfully reduced the rate of CV death or first or recurrent hospitalization for HF over a 24-month period. This is a very encouraging result. Reducing hospitalizations for HF is a major accomplishment and being able to stay home greatly improves patient quality of life.
As exciting as these results may be, some points bear further clarification. First, in spite of having “only” moderate to severe mitral regurgitation, these patients with HF were quite advanced, as evidenced by their high baseline natriuretic peptide levels, poor NYHA functional class and 23% 2-year mortality rate. Yet the rate of transplantation and use of durable left ventricular assist devices was low and CV mortality was not improved by mitral TEER.
Second, it will be important to learn more about how baseline and subsequent use of guideline-directed medical therapy may have impacted overall HF readmission rates.
Third, since the goal of mitral valve therapy is to completely eliminate mitral regurgitation, it is concerning that 10% of patients remained with more than grade 2+ mitral regurgitation. It will be important to know how many had 1+ residual mitral regurgitation as well.
Nonetheless, this is a major trial that informs about the dangers of mitral regurgitation and the need for effective therapies to completely eliminate it to further improve HF outcomes.
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Anker S, et al. Hot line 3. Presented at: European Society of Cardiology Congress; Aug. 30-Sept. 2, 2024; London (hybrid meeting).
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