My name is Tomohiro Kaneko from Juntendo University, Japan.

What are the current unmet needs in AFMR management, and what is the reasoning behind the registry-based study?

Atrial functional mitral regurgitation, AFMR, is now recognised as a distinct subtype of mitral regurgitation mainly characterised by annular dilatation due to left atrial enlargement. Its prevalence increases significantly with age, especially elderly populations.

Currently, surgical intervention is considered one of the main treatment options for AFMR. However, many AFMR patients are elderly and frail which makes them poor candidates for conventional surgery. In this cohort, transcatheter edge-to-edge repair, TEER, has emerged as a promising option for patients with high surgical risk.

Still, to date no study has clearly evaluated the prognostic impact of TEER compared with medical therapy specifically in patients in AFMR. That's why we conducted this registry-based study by combining data from large Japanese registries, aiming to explore the association between TEER and clinical outcomes in this specific patient population.

What was the study design and patient population?

We combined two large-scale Japanese registries: the OCEAN-Mitral registry and the REVEAL-AFMR registry. The OCEAN-Mitral registry is an ongoing, prospective, multicentre study including 21 Japanese centres to evaluate the safety and efficacy of TEER for mitral regurgitation. It has enrolled consecutive patients who underwent TEER with MitraClip from 2018 to 2023.

The REVEAL-AFMR study is a multicentre, retrospective, real-world, observational study including 26 Japanese centres to investigate the prevalence and treatment options for AFMR. This registry included consecutive patients who underwent transthoracic echocardiography at each institution in 19 regardless of their treatment plan. We selected patients with moderate or severe AFMR who met the overlapping criteria of both registries.

AFMR was defined as mitral regurgitation without the degenerative change in the mitral valve, with normal left ventricular size and function under dilated left atrium. In the final analysis, 441 patients in the TEER group were compared with 640 patients in the medication group.

In the original cohort, patients in the TEER group were older and had more severe heart failure symptoms and mitral regurgitation. Kaplan-Meier survival curves demonstrated a worse prognosis for the TEER group. To address this imbalance in baseline characteristics and to estimate the association between TEER and clinical outcomes, we applied propensity score-based overlap weighting.

After weighting, both groups were well balanced and the original sample size was preserved. The mean age was 81.7 years, 28% had severe heart failure symptoms and 42.6% had moderate mitral regurgitation at rest.

What were the key findings, and were there any unexpected results?

In our study, we found that the TEER group had a significantly lower risk of heart failure hospitalisation and all-cause mortality compared with the medication group. This benefit was especially clear in patients whose mitral regurgitation was reduced to mild or less after the procedure, which really highlights how important it is to achieve effective MR reduction in this group.

Regardless of widespread use of TEER for AFMR, there haven't been specific guideline recommendations or large-scale data until now. One unexpected finding was from our subgroup analysis which explored potential factors related to clinical outcomes after TEER.

Surprisingly, we found that neither the presence of moderate or severe tricuspid regurgitation, TR, nor left atrial size was significantly associated with the primary outcomes. In a previous study we had reported that TR coexisting AFMR was strongly associated with worse prognosis, so this result was a bit surprising.

One possible explanation is that when we compare the TR severity before and after TEER, we noticed a slight trend towards improvement after the procedure, which might have influenced the outcome. As for left atrial size, we know that extreme left atrial enlargement can make effective MR reduction more difficult due to ateriogenic tethering and posterior reflex shortening.

But one important finding in our study was that even in a cohort with massive left atrium, our mean left atrial volume index was 95, MR was reduced to mild or less in 78% and moderate or less in 97%.

What are the next steps?

The promising result from our study highlights the need for randomised control trials to clearly establish the effectiveness and safety of TEER in patients with AFMR. In reality, however, TEER for AFMR has already become widely adopted in clinical practise which may make conducting such trials challenging.

Looking ahead, randomised trials comparing TEER with surgical repair in lower-risk patients may be needed to ensure the success of these trials. It's also important to identify predictors of adequate MR reduction after TEER.

In addition, future research should investigate the potential benefits of combined transcatheter intervention that target both mitral and tricuspid regurgitation after TEER. These studies would not only help refine treatment strategies but could also inform updates to clinical guidelines, ultimately improving the management of AFMR, particularly in elderly patient populations.