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MITRA-FR: MitraClip does not change prognosis in HFrEF, mitral regurgitation
MUNICH — In patients with HF with reduced ejection fraction and secondary mitral valve regurgitation, percutaneous mitral valve repair plus medical therapy offered no advantage over medical therapy alone, according to the MITRA-FR trial.
Jean-Francois Obadia, MD, PhD, from Hopital Cardiovasculaire Louis Pradel, Lyon, France, said during a presentation at the European Society of Cardiology Congress that secondary mitral valve regurgitation often portends poor prognosis in patients with HFrEF, so the MITRA-FR trial was launched to see whether percutaneous mitral valve repair with the MitraClip device (Abbott Vascular) would lead to improved outcomes.
“We don’t know if the regurgitation is a consequence or cause of disease or just a marker, but what we know for sure is that it is directly correlated to the prognosis,” Obadia said at a press conference. “The more severe the regurgitation, the poorer the prognosis. As a consequence, it has been proposed to treat this regurgitation by surgery … or by a new technique with a clip. But we did not know if the correction of the regurgitation modifies the prognosis.”
He noted that evidence for treatment with medical therapy is weak and has just a Class IIb recommendation in the guidelines.
Obadia and colleagues randomly assigned 304 patients with severe secondary mitral regurgitation, defined as effective regurgitant orifice area > 20 mm2 or regurgitant volume > 30 ml per beat, and HF with EF between 15% and 40% to receive percutaneous mitral valve repair plus medical therapy (mean age, 70 years; 79% men) or medical therapy alone (mean age, 71 years; 70% men).
The primary outcome was all-cause mortality or unplanned HF hospitalization at 12 months. The results were simultaneously published in The New England Journal of Medicine.
According to the researchers, the primary outcome occurred in 54.6% of the intervention group and 51.3% of the control group (OR = 1.16; 95% CI, 0.73-1.84).
All-cause mortality did not differ between the groups (intervention, 24.3%; control, 22.4%; HR = 1.11; 95% CI, 0.69-1.77), nor did unplanned HF hospitalization (intervention, 48.7%; control, 47.4%; HR = 1.13; 95% CI, 0.81-1.56), Obadia said.
The percutaneous mitral valve repair procedure was safe with few complications and there were no conversions to open surgery, he said. In the intervention group, 96% of patients had decreased mitral regurgitation after the procedure, he noted.
“This is the first randomized trial in this area, and we answered two questions,” Obadia said during the press conference. “Is the procedure safe and efficient? The answer is yes. The device did its job to decrease regurgitation. Does it improve the clinical outcomes? For this part of the question, the answer is no. The main cause of the disease is the underlying cardiomyopathy, and the regurgitation is probably just a signal or marker of the disease, but not the real cause of the prognosis of the patient. It is also important to consider that this conclusion should be applied to a population of patients corresponding to our inclusion criteria. Therefore, we cannot exclude a positive answer in a subgroup of patients with better ventricular function treated at an earlier stage of the disease.”
In a discussant presentation, Stephan Windecker, MD, physician-in-chief and director of invasive cardiology at the department of cardiology, Swiss Cardiovascular Center Bern, Switzerland, said that use of the MitraClip in this population as palliative care may be considered in patients who are severely symptomatic and with contractile reserve. – by Erik Swain
Reference:
Obadia J-F, et al. Hot Line Session 3. Presented at: European Society of Cardiology Congress; Aug. 25-29, 2018; Munich.
Obadia J-F, et al. N Engl J Med. 2018;doi:10.1056/NEJMoa1805374.
Disclosure: The study was funded mainly by the French Ministry of Health and in part by Abbott Vascular. Obadia reports he received grants from Abbott and Neochord and personal fees from Delacroix-Chevalier, Edwards Lifesciences, Landanger, Medtronic, Novartis and Servier. Please see the study for a list of the other authors’ relevant financial disclosures.
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The take-home message is that in the first good prospective randomized trial of catheter treatment of functional mitral regurgitation, percutaneous mitral valve repair was of no benefit for hard endpoints. The investigators indicated that they did not have enough follow-up to fully analyze the data.
Nothing has really worked for treatment of functional mitral regurgitation. The ventricle is the culprit, not the valve. If you fix the valve, the ventricle remains unchanged.
I have questions about patient selection. I’m not sure they picked patients with the most severe mitral regurgitation. A lot of people think it should be defined as effective regurgitant orifice area > 40 mm2 and a regurgitant fraction closer to 50%. With a more severe degree of valvular regurgitation, one could speculate there might be some benefit. However, a subanalysis based on severity of regurgitation did not show any interaction.
The treatment of functional mitral regurgitation has been a huge question. There are many more patients with functional mitral regurgitation than with degenerative mitral regurgitation. Had MITRA-FR been positive, especially if COAPT, a similar trial being presented at TCT 2018, was also positive, then that would have opened doors to doing MitraClip procedures in a huge number of patients. It would have exponentially increased the number of people receiving the procedure.
It is also important to remember there was not a sham control. The people in the control group knew they were in the control group, so that is a limitation.
This is yet another negative trial of treatment of functional mitral regurgitation, which surgery, ventricular compression devices and other strategies have failed to treat. In randomized controlled trials, nothing has prolonged survival in these patients. I suspect that even if COAPT is positive, MITRA-FR will blunt the effect of it, and we might need a tiebreaker.
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We have not yet demonstrated that fixing functional mitral regurgitation matters in patients with symptomatic HF and low ejection fraction. As a ventricular assist device/transplant cardiologist, seeing patients after mitral valve surgery for functional mitral regurgitation is not uncommon. These patients often have progressive HF. I’m sure this study will result in us reconsidering referring these patients for mitral regurgitation procedures.
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The most important takeaway was that the researchers found no significant difference between intervening to reduce regurgitation vs. aggressive medical therapy. Medical therapy was quite good, at least at baseline. It is not clear what the medical therapy was after baseline. We can assume most patients stayed on their drug regimens, but we do not know for sure. If the people who received the intervention thought they were cured and stopped taking their medical therapy, that could explain the results, but I think that is unlikely. The bottom line is that there are no improved outcomes from treating the mitral regurgitation in this population. This is a disease of ventricular dysfunction, which makes the valve leak. It appears that if you do not improve the ventricular function, there will be no impact on survival.
Among the patients who had follow-up echocardiograms, those who had the intervention had a greater reduction in ventricular size, as might be expected. But there are a lot of missing data on those patients, so that finding could be confounded.
There was residual regurgitation in a large number of patients. That could also perhaps explain why there was no benefit.
These findings are consistent with surgical data. This is the first prospective trial to repair the mitral valve by any means in this population. The uncertainly now is that a similar U.S. trial, COAPT, will be reported at TCT 2018. That will help determine whether this is the final nail in the coffin or whether we get different results. The study design is a bit different in that only patients who continued to be symptomatic despite medical therapy were allowed to be enrolled, and the drugs were up-titrated. We will see if that makes a difference, but so far, the data are very suggestive that intervention on the valve itself when there is primary ventricular disease does not lead to a better outcome.
Before the advent of the MitraClip, it was common to do surgical mitral valve repair in patients with severe symptomatic functional mitral regurgitation, and it was never recommended to prolong life, but instead to reduce pressures in the lungs and making the patient feel better. But we do not have quality-of-life data to support that. If percutaneous mitral valve repair is to be used as palliation in this population, it must be shown to be an effective way of reducing pressures. Anecdotally, the procedure has worked quite well in terms of improving symptoms in some patients, but not in others, and trying to predict which patients will improve and which will not has been somewhat difficult.