Sex-Related Differences in Baseline Characteristics and Clinical Outcomes of Patients Undergoing Transcatheter Edge-to-Edge Repair for Primary Mitral Regurgitation: Insights from the PRIME-MR Registry

B. Köll (Hamburg)¹, E. Pezzola (Brescia)², L. Serafini (Brescia)², S. Ludwig (Hamburg)¹, J. Weimann (Hamburg)¹, D. Patel (Los Angeles)³, L. Stolz (München)⁴, T. Tanaka (Bonn)⁵, T. Trenkwalder (München)⁶, F. Rudolph (Bad Oeynhausen)⁷, D. Samim (Bern)⁸, P. von Stein (Köln)⁹, C. Giannini (Pisa)¹⁰, J. Dreyfus (Saint-Denis)¹¹, A. Scotti (New York)¹², J.-M. Paradis (Quebec)¹³, N. Karam (Paris)¹⁴, Y. Bohbot (Amiens)¹⁵, A. Bernard (Tours)¹⁶, B. Melica (Porto)¹⁷, A. Quagliana (Copenhagen)¹⁸, Y. Lavie-Badie (Toulouse)¹⁹, M. Keßler (Ulm)²⁰, O. Chehab (London)²¹, S. Redwood (London)²², E. Lubos (Hamburg)²³, O. De Backer (Copenhagen)²⁴, M. Metra (Brescia)²⁵, A. Latib (Ney York)²⁶, M. De Carlo (Pisa)²⁷, C. Iliadis (Köln)⁹, F. Praz (Bern)²⁸, M. Gercek (Bad Oeynhausen)⁷, T. Modine (Bordeaux)²⁹, E. Donal (Rennes)³⁰, J. Hausleiter (München)⁴, A. Coisne (Lille)³¹, M. Adamo (Brescia)²⁵, D. Kalbacher (Hamburg)^32
1Universitäres Herz- und Gefäßzentrum Hamburg Klinik für Kardiologie Hamburg, Deutschland; ²Cardiac Catheterization Laboratory and Cardiology, ASST Spedali Civili and University of Brescia, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, Brescia, Italy Brescia, Italien; ³Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA Los Angeles, USA; ⁴LMU Klinikum der Universität München Medizinische Klinik und Poliklinik I München, Deutschland; ⁵Universitätsklinikum Bonn Medizinische Klinik und Poliklinik II Bonn, Deutschland; ⁶Deutsches Herzzentrum München Klinik für Herz- und Kreislauferkrankungen München, Deutschland; ⁷Herz- und Diabeteszentrum NRW Allgemeine und Interventionelle Kardiologie/Angiologie Bad Oeynhausen, Deutschland; ⁸Inselspital - Universitätsspital Bern Bern, Schweiz; ⁹Herzzentrum der Universität zu Köln Klinik III für Innere Medizin Köln, Deutschland; ¹⁰University of Pisa Pisa, Italien; ¹¹Centre Cardiologique du Nord Department of Cardiology Saint-Denis, Frankreich; ¹²Montefiore Medical Center, Albert Einstein College of Medicine Montefiore-Einstein Center for Heart and Vascular Care New York, USA; ¹³Laval University Quebec Heart & Lung Institute Quebec, Kanada; ¹⁴European Hospital, Georges Pompidou, Paris, France; and the eUniversity of Paris, PARCC, INSERM, Paris, France Advanced Heart Failure Unit Paris, Frankreich; ¹⁵Amiens University Hospital Department of Cardiology Amiens, Frankreich; ¹⁶CHRU de Tours Cardiology Department Tours, Frankreich; ¹⁷Centro Hospitalar Vila Nova de Gaia/Espinho Porto, Portugal; ¹⁸Rigshospitalet, Copenhagen University Hospital Copenhagen Copenhagen, Dänemark; ¹⁹Rangueil University Hospital Department of Cardiology Toulouse, Deutschland; ²⁰Universitätsklinikum Ulm Klinik für Innere Medizin II Ulm, Deutschland; ²¹St. Thomas' Hospital Department of Cardiology London, Großbritannien; ²²St. Thomas' Hospital Department of Cardiology London, Deutschland; ²³Katholisches Marienkrankenhaus gGmbH Kardiologie und Angiologie Hamburg, Deutschland; ²⁴University hospital Copenhagen Copenhagen, Dänemark; ²⁵University of Brescia Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health Brescia, Italien; ²⁶Montefiore Medical Center, Albert Einstein College of Medicine Montefiore-Einstein Center for Heart and Vascular Care Ney York, USA; ²⁷Azienda Ospedaliero-Universitaria Pisana Cardiothoracic and Vascular Department Pisa, Italien; ²⁸Inselspital - Universitätsspital Bern Universitätsklinik für Kardiologie Bern, Schweiz; ²⁹Centre Hospitalier Universitaire Bordeaux Service Médico-Chirurgical: Valvulopathies-Chirurgie Cardiaque-Cardiologie Interventionelle Structurelle Bordeaux, Frankreich; ³⁰University of Rennes CHU Rennes, Inserm, LTSI - UMR 1099 Rennes, Frankreich; ³¹Heart Valve Clinic, CHU Lille Department of Clinical Physiology and Echocardiography Lille, Frankreich; ³²Universitäres Herz- und Gefäßzentrum Hamburg Allgemeine und Interventionelle Kardiologie Hamburg, Deutschland

Background
Sex differences in mitral regurgitation (MR) have been well characterized in surgical cohorts and in patients with secondary MR treated with mitral valve transcatheter edge-to-edge repair (M-TEER). However, data on sex-specific outcomes following M-TEER for primary MR (PMR) remain scarce. This study aimed to evaluate sex-related differences in baseline characteristics, echocardiographic parameters, procedural results, and long-term outcomes in a large, international registry of patients undergoing M-TEER for PMR.

Methods
The PRIME-MR registry (Outcomes of Patients Treated With Mitral Transcatheter Edge-to-Edge Repair for Primary Mitral Regurgitation) is a retrospective, multicenter registry including consecutive patients with PMR who underwent M-TEER between 2008 and 2022 across 27 European and North American centers. The primary endpoint was a 2-year composite of all-cause mortality or heart-failure hospitalization (HFH). Secondary endpoints included all-cause and cardiovascular (CV) mortality, and HFH. Survival analyses were performed using Kaplan–Meier estimates and multivariable Cox regression adjusted for clinical covariates.

Results
Among 2,078 patients, 961 (46.3%) were female. Women were older and had lower rates of comorbidities but presented with more advanced symptoms, shorter 6-minute walk distance, and more frequent prior HFH. Surgical treatment was more often withheld in women owing to advanced age or frailty. Echocardiographically, women exhibited smaller cardiac and mitral dimensions. Fewer devices were implanted in women, still resulting in higher post-procedural transmitral gradients (4.0 vs. 3.6 mmHg; p < 0.001) and a higher rate of residual MR ≥ moderate (38.5% vs. 32.1%; p = 0.0037). Major vascular complications occurred more frequently in females. At 2-year follow-up, the primary composite endpoint did not differ significantly between sexes (HR 0.85, 95% CI 0.71–1.01; p = 0.069). However, women demonstrated lower all-cause mortality (HR 0.67, 95% CI 0.53–0.86; p = 0.0013) and lower CV mortality (HR 0.52, 95% CI 0.33–0.82; p = 0.0052), independent of comorbidities. These findings are illustrated in the Kaplan–Meier curves for (A) the combined primary endpoint and (B) all-cause mortality (Figure 1).

Conclusions
Among patients with PMR undergoing M-TEER, women were older and presented at a more advanced disease stage yet achieved comparable composite outcomes and significantly better survival than men. Despite less optimal procedural results, female sex was independently associated with improved long-term survival. M-TEER represents an effective and gender-equitable treatment strategy for high-risk PMR patients, potentially mitigating the historical survival disadvantage observed in women after surgical repair.