Journal Article Ahead of print
PubMed: 42866868 DOI: 10.1161/CIRCULATIONAHA.125.079085
Definition and Prognosis of Mitral Regurgitation in Transthyretin Amyloid Cardiomyopathy: A Multicenter International Cohort Study.
Circulation
Authors: Laurenz Hauptmann, Christina Kronberger, Stéphanie K Schwarting, Daniela Tomasoni, Lara S Schlender, Sophia Koschatko, Maximilian Autherith, Charlotte Jantsch, Caglayan Demirel, Franz Duca, Andreas Kammerlander, Luca Bordignon, Gabriele Guidi Colombi, Nora Schwegel, Matteo Serenelli, Aldostefano Porcari, Steven A Muller, Nicolas Verheyen, Marish I F J Oerlemans, Maria Papathanasiou, Christian Hengstenberg, Marco Merlo, Jörg Hausleiter, Marianna Adamo, Philipp E Bartko, Christian Nitsche
Affiliations
- 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.).
- Department of Medicine I, LMU University Hospital, Ludwig Maximilian University of Munich, Germany (S.K.S. J.H.).
- Department of Cardiology, Angiology and Respiratory Medicine, University Hospital Heidelberg, Germany (S.K.S.).
- 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).
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden (D.T.).
- Department of Cardiology, University Hospital Frankfurt, Germany (L.S.S. M.P.).
- German Center for Cardiovascular Research, Partner Site Rhein-Main, Frankfurt, Germany (L.S.S. M.P.).
- Center for Diagnosis and Treatment of Cardiomyopathies, Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI), University of Trieste, Italy (L.B. A.P. M.M.).
- European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), Amsterdam, the Netherlands (L.B. A.P. S.A.M. M.I.F.J.O. M.M.).
- Cardiology Unit, Azienda Ospedaliero Universitaria di Ferrara, Italy (G.G.C. M.S.).
- Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Austria (N.S. N.V.).
- Department of Cardiology, University Medical Center, Utrecht, the Netherlands (S.A.M. M.I.F.J.O.).
Abstract
BACKGROUND
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.
METHODS
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.
RESULTS
During a median follow-up of 24.9 months (interquartile range, 12.0-42.0), 314 patients (28.5%) died and 244 (22.2%) experienced HFH. All MR metrics independently predicted mortality and HFH (all P<0.05). Spline-derived thresholds identified intermediate risk at vena contracta width ≥3.0 mm, effective regurgitant orifice area ≥0.10 cm 2, regurgitant volume ≥15 mL, and regurgitant fraction ≥20% and high risk at effective regurgitant orifice area >0.25 cm 2, regurgitant volume >38 mL, and regurgitant fraction >35%. Compared with guideline grading (≈12%-13%), 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 [1.07-1.36]) and HFH (hazard ratio, 1.21 [1.05-1.38]).
CONCLUSIONS
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.
REGISTRATION
URL: https://www.clinicaltrials.gov; Unique identifier: NCT06836011.
MeSH
Heart Valve Diseases, Mortality, Cardiovascular System, Cohort Studies, Prealbumin, Amyloid, Blood Circulation, Mitral Valve Insufficiency, Prognosis, Cardiomyopathies, Transthyretin Amyloid Cardiomyopathy