A strategy of mitral transcatheter edge-to-edge repair (TEER) plus medical therapy in patients with heart failure and moderate to severe mitral regurgitation (MR), who were not eligible for surgery, was found to be more effective than optimal medical therapy alone, investigators in the RESHAPE-HF2 trial have reported at the European Society of Cardiology (ESC) 2024 Congress (30 August–2 September, London, UK).
The trial’s principal investigator, Stefan Anker (Charite University Hospital, Berlin, Germany) said the findings should provide reassurance about the benefits of TEER using the MitraClip device (Abbott) in patients with moderate to severe functional MR and heart failure and could strengthen and broaden recommendations for its future use. Critics, however, are less enthusiastic about the conclusions.
RESHAPE-HF2 comes against the backdrop of two previous trials having delivered diverging results of transcatheter therapy in this patient population.
COAPT, which included patients with less advanced left ventricular (LV) dysfunction and more severe functional MR, demonstrated significant benefits of the treatment in reducing heart failure hospitalisations and mortality. However, MITRA-FR included patients with more advanced LV dysfunction, did not enforce as rigorous a standard for medical therapy optimisation, and did not show a significant benefit from the transcatheter therapy.
This latest trial, an investigator-initiated randomised study, recruited patients with symptoms of heart failure despite optimal guideline-directed medical therapy, who had left ventricular ejection fraction (LVEF) ≥20% and ≤50%, MR grade 3+ or 4+—meaning that they had slightly more severe LV dysfunction than COAPT, but less than MITRA-FR—and had a recent hospitalisation for heart failure or elevated plasma natriuretic peptide concentrations within the last 90 days.
Patients for whom mitral valve surgery was recommended were not eligible. Patients were randomised 1:1 to TEER using the MitraClip device plus optimal medical therapy or optimal medical therapy alone.
The three primary endpoints were a composite rate of total (first and recurrent) heart failure hospitalisations and cardiovascular death within 24 months; the rate of total heart failure hospitalisations within 24 months; and the change from baseline to 12 months in the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall score, which assesses the impact of heart failure on quality of life.
In total, 505 patients were randomised from 30 centres in nine countries. The mean age was 70 years and 20% were female. The mean LVEF was 31% and HF was New York Heart Association (NYHA) class III or IV in around three-quarters of patients. The mean KCCQ overall summary score was 46, which indicates significant symptoms and limitations due to heart failure.
At 24 months, Anker reported that the rate of total hospitalisations for heart failure and cardiovascular death was significantly lower in the TEER group compared to the control group (37 per 100 patient-years vs. 58.9 per 100 patient-years; rate ratio 0.64; 95% confidence interval [CI] 0.48–0.85; p=0.002).
The rate of total hospitalisations for heart failure within 24 months was significantly reduced by 41% in the TEER group vs. the control group (26.9 per 100 patient-years vs. 57.8 per 100 patient-years; rate ratio 0.59; 95% CI 0.42–0.82; p=0.002).
In addition, the mean (standard deviation [SD]) change from baseline to 12 months in the KCCQ overall summary score was greater (improved) in the TEER group (+21.6 [26.9]) than in the control group (+8.0 [24.5]), he reported, resulting in a mean difference of +10.9 points (95% CI 6.8–15.0; p<0.001).
During the total follow-up of 38.1 (18.1) months, there was no difference between the groups for all-cause mortality (17% in the M-TEER group vs. 18.5% in the control group; hazard ratio 0.90; 95% CI 0.71–1.13). Periprocedural adverse events were reported in four patients (1.6%) in the TEER group.
Speaking to Cardiovascular News, Anker said that the results should conclusively demonstrate the impact of transcatheter therapy in patients with severe functional MR, and potentially point to a benefit in patients with less severe disease.
“I would hope that many colleagues in the power to make such recommendations will start to see that even patients with less than severe functional MR should at least be considered for this treatment approach, it may be a soft recommendation,” he said. “It is certainly not a negative [result]—I am positive about the results. They indicate to me that there is benefit to be had for these patients but we need confirmation of this to make this as valid a standpoint as we can. For severe functional MR, I think we have now, taking the results here together a good indication that this should be done.”
Questions as to whether the results of RESHAPE-HF2 close down the debate caused by the divergent results of the preceding trials still remain, however.
“I would be less enthusiastic than your conclusion,” Jean-Francois Obadia (Civils Hospices of Lyon, Lyon, France), the principal investigator in the MITRA-FR trial, said of the results of RESHAPE-HF2 in discussion that followed the presentation at ESC 2024, pointing in particular to the fact that there was no difference between the groups for all-cause mortality.
“The positive [result] relies mainly on criteria that have some weaknesses. If we stick on unquestionable criteria, like mortality—because death is death—or all hospitalisation, because an hospitalisation is a hospitalisation, [there is] no discussion, whatever the quality of the adjudication committee.
“Therefore, in RESHAPE, you have no impact on mortality [and] no impact on hospitalisation, which is not far from the result we have with MITRA-FR. So, what I mean is that RESHAPE does not conclude the discussion [of] the discrepancy observed between MITRA-FR and COAPT, and my feeling today is that we should merge the three databases and try to perform a meta-analysis of the three studies.”
Anker agreed that analysing data from the three datasets in the form of an individual patient data meta-analysis would be a positive step in answering some of these points.
“What can I say—we all agree on the need for an individual patient meta-analysis to sort out, not only the overall effect size, because that is a question that people might estimate already and form their opinion about, but getting an idea for the reasons for the variability in results between trials and look at sub-groups to see who can particularly benefit.”
Results of the trial were published simultaneously in the New England Journal of Medicine.
