{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T23:52:50Z","timestamp":1794009170383,"version":"4.8.0"},"reference-count":22,"publisher":"American Medical Association (AMA)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Cardiol"],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"\n Importance<\/jats:title>\n \n Left ventricular (LV) dilatation is an established prognosticator in aortic regurgitation (AR). Current guidelines recommend aortic valve surgery (AVS) using LV end-systolic diameter index (LVESDi) with a uniform threshold, irrespective of sex. While LV end-systolic volume index (LVESVi) may better characterize LV remodeling, it was only recently included in European guideline recommendations, with a threshold of 45 mL\/m\n 2<\/jats:sup>\n for both men and women.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To assess sex differences in LV remodeling using linear and volumetric dimensions and their association with outcomes in AR.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This was a multicenter cohort study of patients with moderate-severe AR and preserved LV ejection fraction (LVEF) between December 2003 and December 2022, with a median (IQR) follow-up of 7 (4-11) years. The study took place at 5 centers in the Netherlands, Singapore, Hong Kong, Canada, and Romania. Patients with at least moderate-severe AR and preserved LVEF (\u226550%) were included. Those with symptoms, acute AR, significant other valvular disease, or prior valve surgery were excluded. Data were analyzed from January to November 2024.<\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n LV dilatation assessed by LVESDi and LVESVi.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n All-cause mortality during medical management and following AVS.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 808 patients (mean [SD] age, 56 [19] years; 488 men and 320 women) were included, 323 of whom underwent AVS. Mean (SD) baseline LVESDi did not differ between sexes (women: 20 [5] mm\/m\n 2<\/jats:sup>\n vs men: 20 [4] mm\/m\n 2<\/jats:sup>\n ;\n P<\/jats:italic>\n \u2009=\u2009.77), whereas men had larger mean (SD) LVESVi (39 [16] mL\/m\n 2<\/jats:sup>\n vs 31 [15] mL\/m\n 2<\/jats:sup>\n ;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001). During follow-up under medical management, 74 patients died. Adjusted 6-year survival was lower in women (80% vs 89%;\n P<\/jats:italic>\n \u2009=\u2009.001). Receiver operating characteristic curve analysis identified LVESDi 20 mm\/m\n 2<\/jats:sup>\n or greater for both sexes, LVESVi 40 mL\/m\n 2<\/jats:sup>\n or greater for women, and LVESVi 45 mL\/m\n 2<\/jats:sup>\n or greater for men as thresholds associated with mortality. These cutoffs were validated using age-adjusted cubic splines and remained associated with outcomes after multivariable adjustment, with a differential effect by sex for LVESVi but not for LVESDi. After AVS, survival did not differ by sex (85% women vs 89% men;\n P<\/jats:italic>\n \u2009=\u2009.31). Only preoperative LVESVi was associated with mortality, with a significant sex interaction (HR, 1.03; 95% CI, 1.00-1.06;\n P<\/jats:italic>\n \u2009=\u2009.04).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n In this study among individuals with moderate-severe AR, similar LVESDi thresholds (20 mm\/m\n 2<\/jats:sup>\n ) for both sexes, but lower than currently recommended by guidelines, were independently associated with mortality. In turn, LVESVi thresholds were 40 mL\/m\n 2<\/jats:sup>\n for women and 45 mL\/m\n 2<\/jats:sup>\n for men, suggesting the need for sex-specific cutoffs to improve risk stratification.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamacardio.2025.5249","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T16:00:37Z","timestamp":1769011237000},"page":"239","source":"Crossref","is-referenced-by-count":4,"title":["Sex Differences in Left Ventricular Remodeling for Risk Stratification of Patients With Aortic Regurgitation"],"prefix":"10.1001","volume":"11","author":[{"given":"Pilar","family":"Lopez Santi","sequence":"first","affiliation":[{"name":"Department of Cardiology, Heart Lung Center, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Fortuni","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Lung Center, Leiden University Medical Center, Leiden, the Netherlands"},{"name":"Department of Cardiology, San Giovanni Battista Hospital, Foligno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00e9my","family":"Bernard","sequence":"additional","affiliation":[{"name":"Cardiology, Institut universitaire de cardiologie et de pneumologie de Qu\u00e9bec-Universit\u00e9 Laval, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Sarrazyn","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Lung Center, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aileen P.","family":"Chua","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Lung Center, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steele C.","family":"Butcher","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Lung Center, Leiden University Medical Center, Leiden, the Netherlands"},{"name":"Department of Medicine Royal Perth Hospital, Perth, Western Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria C.","family":"Meucci","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Lung Center, Leiden University Medical Center, Leiden, the Netherlands"},{"name":"Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingnan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana","family":"Enache","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Medicine and Pharmacy \u2018Carol Davila\u2019, Euroecolab, Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar","family":"Tay","sequence":"additional","affiliation":[{"name":"Department of Cardiology, National University Heart Centre, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Bergeron","sequence":"additional","affiliation":[{"name":"Cardiology, Institut universitaire de cardiologie et de pneumologie de Qu\u00e9bec-Universit\u00e9 Laval, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Hang","family":"Yiu","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Annick","family":"Clavel","sequence":"additional","affiliation":[{"name":"Cardiology, Institut universitaire de cardiologie et de pneumologie de Qu\u00e9bec-Universit\u00e9 Laval, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Pibarot","sequence":"additional","affiliation":[{"name":"Cardiology, Institut universitaire de cardiologie et de pneumologie de Qu\u00e9bec-Universit\u00e9 Laval, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen J.","family":"Bax","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Lung Center, Leiden University 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