{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T09:46:51Z","timestamp":1791884811612,"version":"4.3.4"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"abstract":"\n BACKGROUND:<\/jats:title>\n In transthyretin amyloid cardiomyopathy, mitral regurgitation (MR) severity may be underestimated by conventional (semi-)quantitative echocardiographic criteria due to restrictive low-flow hemodynamics. We sought to define and validate disease-specific MR risk thresholds and compare their prognostic performance with guideline definitions.<\/jats:p>\n <\/jats:sec>\n \n METHODS:<\/jats:title>\n In a multicenter cohort study (8 centers, 4 countries), 1101 patients with newly diagnosed transthyretin amyloid cardiomyopathy (derivation, n=722; validation, n=379) underwent standardized echocardiography with blinded core laboratory analysis, including MR measures (vena contracta width, effective regurgitant orifice area, regurgitant volume, and regurgitant fraction). All-cause mortality and time to first heart failure hospitalization (HFH) served as end points. Prognostic thresholds were derived from spline analysis, validated externally, and compared with American Heart Association\/American College of Cardiology, European Society of Cardiology\/European Association for Cardiothoracic Surgery, and American Society of Echocardiography definitions.<\/jats:p>\n <\/jats:sec>\n \n RESULTS:<\/jats:title>\n \n During a median follow-up of 24.9 months (interquartile range, 12.0\u201342.0), 314 patients (28.5%) died and 244 (22.2%) experienced HFH. All MR metrics independently predicted mortality and HFH (all\n P<\/jats:italic>\n <0.05). Spline-derived thresholds identified intermediate risk at vena contracta width \u22653.0 mm, effective regurgitant orifice area \u22650.10 cm\n 2<\/jats:sup>\n , regurgitant volume \u226515 mL, and regurgitant fraction \u226520% and high risk at effective regurgitant orifice area >0.25 cm\n 2<\/jats:sup>\n , regurgitant volume >38 mL, and regurgitant fraction >35%. Compared with guideline grading (\u224812%\u201313%), the composite MR grading scheme classified a significantly higher proportion (21%) as severe MR and provided superior discrimination for clinical outcomes at 12 and 24 months in both the derivation and validation cohort. After multivariable adjustment, only the composite MR grading scheme remained strongly predictive for both mortality (hazard ratio, 1.20 [1.07\u20131.36]) and HFH (hazard ratio, 1.21 [1.05\u20131.38]).\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS:<\/jats:title>\n Quantitative MR thresholds in transthyretin amyloid cardiomyopathy are substantially lower than current guideline cutoffs. A validated, risk-based composite MR grading scheme improves prediction of both mortality and HFH, better reflecting the restrictive low-flow pathophysiology of transthyretin amyloid cardiomyopathy and supporting disease-specific MR grading.<\/jats:p>\n <\/jats:sec>\n \n REGISTRATION:<\/jats:title>\n \n URL:\n https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n ; Unique identifier: NCT06836011.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/circulationaha.125.079085","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T09:02:10Z","timestamp":1791882130000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Definition and Prognosis of Mitral Regurgitation in Transthyretin Amyloid Cardiomyopathy: A Multicenter International Cohort Study"],"prefix":"10.1161","clinical-trial-number":[{"clinical-trial-number":"nct06836011","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2674-3796","authenticated-orcid":true,"given":"Laurenz","family":"Hauptmann","sequence":"first","affiliation":[{"name":"Clinical Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Austria (L.H., C.K., S.K., M. Autherith, C.J., C.D., F.D., A.K., C.H., P.E.B., C.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3866-3710","authenticated-orcid":true,"given":"Christina","family":"Kronberger","sequence":"additional","affiliation":[{"name":"Clinical Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Austria (L.H., C.K., S.K., M. Autherith, C.J., C.D., F.D., A.K., C.H., P.E.B., C.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5954-5695","authenticated-orcid":true,"given":"St\u00e9phanie K.","family":"Schwarting","sequence":"additional","affiliation":[{"name":"Department of Medicine I, LMU University Hospital, Ludwig Maximilian University of Munich, Germany (S.K.S., J.H.)."},{"name":"Department of Cardiology, Angiology and Respiratory Medicine, University Hospital Heidelberg, Germany (S.K.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7584-2857","authenticated-orcid":true,"given":"Daniela","family":"Tomasoni","sequence":"additional","affiliation":[{"name":"Cardiology, ASST Spedali Civili di Brescia and Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Italy (D.T., M. Adamo)."},{"name":"Department of Clinical Science and Education, S\u00f6dersjukhuset, Karolinska Institutet, Stockholm, Sweden (D.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6161-9295","authenticated-orcid":true,"given":"Lara S.","family":"Schlender","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital Frankfurt, Germany (L.S.S., M.P.)."},{"name":"German Center for Cardiovascular Research, Partner Site Rhein-Main, Frankfurt, Germany (L.S.S., M.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0918-8217","authenticated-orcid":true,"given":"Sophia","family":"Koschatko","sequence":"additional","affiliation":[{"name":"Clinical Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Austria (L.H., C.K., S.K., M. Autherith, C.J., C.D., F.D., A.K., C.H., P.E.B., C.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Autherith","sequence":"additional","affiliation":[{"name":"Clinical Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Austria (L.H., C.K., S.K., M. Autherith, C.J., C.D., F.D., A.K., C.H., P.E.B., C.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0780-0526","authenticated-orcid":true,"given":"Charlotte","family":"Jantsch","sequence":"additional","affiliation":[{"name":"Clinical Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Austria (L.H., C.K., S.K., M. Autherith, C.J., C.D., F.D., A.K., C.H., P.E.B., C.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1966-0637","authenticated-orcid":true,"given":"Caglayan","family":"Demirel","sequence":"additional","affiliation":[{"name":"Clinical Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Austria (L.H., C.K., S.K., M. Autherith, C.J., C.D., F.D., A.K., C.H., P.E.B., C.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7519-5274","authenticated-orcid":true,"given":"Franz","family":"Duca","sequence":"additional","affiliation":[{"name":"Clinical Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Austria (L.H., C.K., S.K., M. 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