Transcatheter Edge-to-Edge Repair Shows Benefit in Moderate MR

NEW YORK, NY—The vast majority of symptomatic patients with moderate mitral regurgitation (MR) treated with transcatheter edge-to-edge repair (TEER) have a sustained reduction in MR grade at 1 year, as well as significant reductions in left ventricular volumes, according to an analysis presented last week at New York Valves 2024.

Treating moderate MR also led to improvements in NYHA functional class and quality of life, say investigators. 

Anita Asgar, MD (Montreal Heart Institute, Canada), who presented the results during a late-breaking clinical trials session at what was previously known as the TVT meeting, said these data suggest that intervening earlier in the disease provides clinical benefit, a concept that should be tested in a randomized, controlled trial.

“If the risk is low and the procedure is successful, what's the downside of treating people earlier?” she told TCTMD. “If we could treat patients in heart failure sooner, if we could prevent their ventricle from this horrible remodeling where it gets so big that they're beyond treatment, or beyond [a chance of] meaningful benefit, we've won a little bit.”

In COAPT, TEER with MitraClip (Abbott) was shown to be an effective treatment for patients with heart failure (HF) and moderate-to-severe or severe MR, with the device significantly reducing the risk of HF hospitalizations and mortality at 2 years compared with medical therapy alone.

One aspect of the trial that can’t be ignored, said Asgar, is that even though TEER reduced the risks relative to guideline-directed medical therapy (GDMT), mortality remained high in those with severe MR. In the similar MITRA-FR trial, there was no benefit with TEER in a heart failure population with symptomatic severe MR, a finding that some experts speculate might be because the French investigators included patients too sick to benefit.

“One of the criticisms of MITRA-FR was that the ventricles were too big, that we intervened too late,” said Asgar. “So why not intervene upstream? What’s impressive about these data is that if you treat moderate MR, the ventricle remodels. You make it smaller so they may not progress to severe and there’s potentially more opportunity to make an impact in these patients.”

“The whole discussion about when to treat functional MR has very much focused on at the end of the spectrum of the disease,” Philipp Lurz, MD, PhD (University of Leipzig, Germany), who discussed the trial following the late-breaking presentation, told TCTMD. “I think it's the time to refocus the discussion a little bit more on the other end of the spectrum, the early [in the disease] spectrum. But if you really want to have definite proof, there's always a need for randomized trials.”

LV Remodeling With TEER

To analyze whether TEER provided any clinical benefit in a less sick population, Asgar turned to 2,205 patients enrolled in the EXPAND and EXPAND G4 postmarketing studies with the third- and fourth-generation MitraClip device (NTR/XTR and G4). Of these, 968 patients had secondary MR, including 335 and 525 with moderate MR (2+) and severe MR (≥ 3+), respectively. To be included in EXPAND and EXPAND G4, all patients met the entry criteria of their specific regions, but all were meant to have severe MR. However, adjudication by the EXPAND core laboratory found that 36% had moderate MR. 

Baseline characteristics were similar in patients with moderate and severe MR, but there were more prior HF hospitalizations in the severe MR group and higher markers of MR severity (effective regurgitant orifice area, for example).  

What’s impressive about these data is that if you treat moderate MR, the ventricle remodels. Anita Asgar

All-cause mortality was similar in those with moderate and severe MR treated with TEER (15.2% vs 16.0%, respectively), as were HF hospitalizations (21.9% vs 23.7%, respectively), at 1 year. To put those results in perspective, the 1-year mortality rates in COAPT were 19.6% in the MitraClip arm versus roughly 23% in the medical therapy arm, said Asgar. Both those with moderate and severe MR had a similarly significant reduction in the cumulative HF hospitalization rate from baseline to 1 year, with no difference seen between groups.

Overall, 97% of those with moderate MR at baseline had MR grade reduced to mild or better (MR ≤ 1+), a significant improvement from baseline. In the severe group, 92.4% had mild MR a year after TEER. The patients with moderate and severe MR both had significant improvements in LV end-diastolic and end-systolic volumes after TEER, including those who started with LVEF ≤ 35% at baseline. In these patients with very low EF, reduction in LV volumes was greater in those with moderate MR than in those with severe.  

Even Moderate MR Matters for Symptoms

In his discussion, Lurz noted that clinical guidelines do not recommend TEER for patients with moderate TEER, leaving him wondering why so many patients were treated with MitraClip on the advice of the local heart team. 

“The question is whether none of us adhere to guidelines anymore or whether it's also a matter of how we grade MR,” he said. To TCTMD, Lurz noted that unlike aortic stenosis, grading MR is challenging because it’s a dynamic condition, which leaves open the question as to whether those treated in EXPAND had moderate MR or “maybe something in between.” 

Nonetheless, these data show MR plays an important role in the patient’s overall symptomatic burden, said Lurz, noting that even those with moderate MR had improvements in quality of life similar to the gains seen in patients with severe MR. Some have speculated that a moderate degree of MR doesn’t matter much when it comes to symptoms given a patient’s advanced age and comorbidities, he said.

As for why there was no difference in survival between those with moderate and severe MR treated with TEER, Lurz said the finding, at first blush, may appear confusing.

“That's a bit surprising, maybe even counterintuitive, but when you have a procedure which is as successful as clipping, almost all patients don’t have MR anymore,” he said. “You take away the prognostic reference of MR in both cohorts, and this may be why you end up with the same survival.”

“You can’t separate the valve from the ventricle,” added Asgar. “Even though we've reduced the MR, there is certainly still that ventricular disease, which has a natural history associated with it. [Patients] also have comorbidities, so that's going to reflect their mortality. It doesn't mean that it's futile to treat it. It can't be futile if the ventricle is remodeled. We can't change their diabetes or previous MI. We can't change any of those things, but we can lower their heart failure hospitalizations. We can make them feel better.”

During the panel discussion, surgeons Michael Reardon, MD (Houston Methodist DeBakey Heart & Vascular Center, TX), and Vinayak Bapat, MD (Allina Health Minneapolis Heart Institute, MD), said the time is ripe for a randomized trial, with Reardon pointing out that all patients would be optimized on GDMT that includes the new SGLT2 inhibitors.

“I see these people degenerating in my clinic,” said Reardon. “And it’s true, we can treat them better [with medical therapy], but if you reduce their MR to a significant amount, you'll treat them even better than better. I think a trial would be ideal.”