The mitral valve controls blood flow between the heart’s left atrium and ventricle. When structural changes affect the atrium or valve, it may not close fully—causing blood to leak backwards, a condition known as atrial functional mitral regurgitation (AFMR). Common in frail or elderly patients, AFMR often leads to heart failure, and standard surgery is typically too risky due to other health issues.
Transcatheter edge-to-edge repair (TEER), a minimally invasive surgery, has emerged as a low-risk treatment option for various types of mitral regurgitation. TEER has demonstrated its efficacy by lowering the mortality rate in patients with ventricular functional mitral regurgitation (VFMR). While both VFMR and AFMR affect the mitral valve, their causes differ—can TEER offer the same survival benefit in AFMR?
In a large-scale collaborative study, researchers from multiple Japanese institutions—led by Assistant Professor Tomohiro Kaneko and Associate Professor Nobuyuki Kagiyama, both from the Department of Cardiovascular Biology and Medicine at the Juntendo University Graduate School of Medicine, Tokyo—evaluated the association between TEER and clinical outcomes in patients with AFMR by comparing those who underwent TEER with those who received standard medical therapy alone. The study was published in the European Heart Journal and made available online on July 09, 2025. The study was co-authored by Dr. Masanori Yamamoto (Toyohashi Heart Center) and Professor Kentaro Hayashida (Keio University School of Medicine), among other experts contributing to the registry-based research.
The study included a total of 1,081 patients with AFMR, with a mean age of 80.1 ± 8.2 years, of whom 60.5% were women. Among them, 441 patients, selected from the OCEAN-Mitral registry, underwent TEER, while the remaining 640 patients, chosen from the REVEAL-AFMR registry, were the medically managed controls. The research team used a statistical technique called propensity score-based overlap weighting to balance the characteristics of both groups, enabling an accurate estimation of treatment outcomes. The association between TEER and clinical outcomes was evaluated based on mortality and heart failure-related hospitalizations in patients with AFMR.
Patients who underwent TEER had a 35% lower risk of the primary endpoint—a composite of all-cause mortality and hospitalization due to heart failure (hazard ratio: 0.65 [0.43–0.99]). The risk of all-cause mortality alone, which was the secondary endpoint, was also 42% lower (hazard ratio: 0.58 [0.35–0.99]). Survival benefit remained evident over time. Even after three years, the estimated incidence of death or hospitalization was 44.3% in the medication group, compared to only 21.0% in the TEER group.
“Elderly patients with AFMR often fall into a therapeutic gray zone—too high-risk for surgery, yet poorly served by medical therapy alone,” says first author Dr. Kaneko. “TEER may help address this gap by providing a feasible, evidence-supported option that is associated with better outcomes in this vulnerable population.”
Outcomes were also determined by the degree of residual mitral regurgitation after TEER (residual AFMR). Among patients in whom residual AFMR was mild or less, the risk of death or hospitalization was more than 50% lower compared to the medication group. However, in cases of moderate or greater residual AFMR, outcomes were no better or worse than those who received medical therapy alone. This suggests that the degree of success after surgery is a key determinant of the benefit of TEER.
TEER success was notably high in the study’s Japanese cohort, with over 78% achieving mild or less residual AFMR at the time of discharge. Only 2.9% experienced some complications. Moreover, factors such as age, sex, and left atrial volume did not significantly affect the association between TEER and favorable outcomes. However, in cases of extreme left atrial enlargement (>100 mL/m²), this association appeared to be attenuated or possibly absent.
“This was an observational study, not a randomized trial, so unmeasured confounding cannot be ruled out,” notes Dr. Kaneko. “Nevertheless, we employed multiple statistical methods to validate our findings, and the consistency across analyses strengthens our confidence in the conclusions.”
With Japan’s growing elderly population, mitral regurgitation could become more prevalent. This study offers compelling evidence that TEER, when performed successfully, may represent a promising and low-risk treatment option for patients with AFMR who have limited alternatives.
“In an aging world where frailty limits surgical choices, TEER provides a much-needed bridge between risk and reward,” Dr. Kagiyama concluded. “Our findings support its use as a real and promising solution for this demographic.”
The authors extend their sincere appreciation to the investigators and institutions who participated in the OCEAN-Mitral and REVEAL-AFMR registries. This research would not have been possible without their dedicated efforts in data collection, patient care, and long-term follow-up.
Reference
Authors
Tomohiro Kaneko1, Nobuyuki Kagiyama1*, Shinya Okazaki1, Masashi Amano2, Yukio Sato3, Yohei Ohno4, Masaru Obokata5, Kimi Sato6, Kojiro Morita7, Shunsuke Kubo8, Yuki Izumi9, Masahiko Asami10, Yusuke Enta11, Shinichi Shirai12, Masaki Izumo3, Shingo Mizuno13, Yusuke Watanabe14, Makoto Amaki2, Kazuhisa Kodama15, Hisao Otsuki16, Toru Naganuma17, Hiroki Bota18, Masahiro Yamawaki19, Hiroshi Ueno20, Gaku Nakazawa21, Daisuke Hachinohe22, Toshiaki Otsuka23, Mike Saji9, 24, Masanori Yamamoto25, 26, 27, Kentaro Hayashida28, and on behalf of the OCEAN-Mitral and the REVEAL-AFMR Investigators
Title of original paper
Transcatheter edge-to-edge repair vs medical therapy in atrial functional mitral regurgitation: A propensity score-based comparison from the OCEAN-Mitral and REVEAL-AFMR registries
Journal
European Heart Journal
DOI
10.1093/eurheartj/ehaf511
Affiliations
1. Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
2. Department of Heart Failure and Transplantation, National Cerebral and Cardiovascular Center, Suita, Japan
3. Department of Cardiology, St. Marianna University School of Medicine, Kanagawa, Japan
4. Department of Cardiology, Tokai University School of Medicine, Isehara, Japan
5. Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan
6. Department of Cardiology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
7. Department of Nursing Administration and Advanced Clinical Nursing, Division of Health Sciences and Nursing, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
8. Department of Cardiology, Kurashiki Central Hospital, Kurashiki, Japan
9. Department of Cardiology, Sakakibara Heart Institute, Tokyo, Japan
10. Division of Cardiology, Mitsui Memorial Hospital, Tokyo, Japan
11. Department of Cardiology, Sendai Kosei Hospital, Sendai, Japan
12. Department of Cardiology, Kokura Memorial Hospital, Kitakyushu, Japan
13. Department of Cardiology, Shonan Kamakura General Hospital, Kamakura, Japan
14. Department of Cardiology, Teikyo University School of Medicine, Tokyo, Japan
15. Division of Cardiology, Saiseikai Kumamoto Hospital Cardiovascular Center, Kumamoto, Japan
16. Department of Cardiology, Tokyo Woman's Medical University, Tokyo, Japan
17. Department of Cardiology, New Tokyo Hospital, Chiba, Japan
18. Department of Cardiology, Sapporo Higashi Tokushukai Hospital, Sapporo, Japan
19. Department of Cardiology, Saiseikai Yokohama City Eastern Hospital, Yokohama, Japan
20. Second Department of Internal Medicine, Toyama University Hospital, Toyama, Japan
21. Division of Cardiology, Department of Medicine, Kindai University Faculty of Medicine, Osaka, Japan
22. Division of Cardiology, Sapporo Cardio Vascular Clinic, Sapporo, Japan
23. Department of Hygiene and Public Health, Nippon Medical School, Tokyo, Japan
24. Division of Cardiovascular Medicine, Department of Internal Medicine, Toho University Faculty of Medicine, Tokyo, Japan
25. Department of Cardiology, Toyohashi Heart Center, Toyohashi, Japan
26. Department of Cardiology, Nagoya Heart Center, Nagoya, Japan
27. Department of Cardiology, Gifu Heart Center, Gifu, Japan
28. Department of Cardiology, Keio University School of Medicine, Tokyo, Japan
About Assistant Professor Tomohiro Kaneko
Dr. Tomohiro Kaneko is an Assistant Professor in the Department of Cardiovascular Biology and Medicine at Juntendo University Graduate School of Medicine, Japan, specializing in cardiovascular research, structural heart disease, echocardiography, and interventional cardiology. He earned his MD and PhD from Juntendo University and has been instrumental in advancing multicenter registry studies in atrial functional mitral regurgitation (AFMR). Dr. Kaneko has participated in large collaborative efforts—including the REVEAL-AFMR and OCEAN-Mitral registries—that have shaped real-world evidence on AFMR progression and outcomes. His work includes evaluating the prognostic impact of transcatheter edge-to-edge repair versus medical therapy in patients with AFMR.
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