Definition and Prognosis of Mitral Regurgitation in Transthyretin Amyloid Cardiomyopathy: A Multicenter International Cohort Study

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: , 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.

Authors

Institutions

Publication Details

Journal
Circulation
Published
2026-10-13
DOI
https://doi.org/10.1161/circulationaha.125.079085
Primary Topic
Amyloidosis: Diagnosis, Treatment, Outcomes
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Definition and Prognosis of Mitral Regurgitation in Transthyretin Amyloid Cardiomyopathy: A Multicenter International Cohort Study

Christian Hengstenberg, Matteo Serenelli, Philipp Emanuel Bartko, Lara S. Schlender et al.
Circulation
Amyloidosis: Diagnosis, Treatment, Outcomes
article

Definition and Prognosis of Mitral Regurgitation in Transthyretin Amyloid Cardiomyopathy: A Multicenter International Cohort Study

Christian Hengstenberg, Matteo Serenelli, Philipp Emanuel Bartko, Lara S. Schlender, Christian Nitsche, Μαρία Παπαθανασίου, Sophia Koschatko, Caglayan Demirel, Jörg Hausleiter, Stéphanie Kristina Schwarting, Laurenz Hauptmann, Nicolas Verheyen, Steven A. Muller, Franz Duca, Daniela Tomasoni, Marco Merlo, Charlotte Jantsch, Marianna Adamo, Aldostefano Porcari, Christina Kronberger, Marish I.F.J. Oerlemans, Nora Schwegel, Andreas Anselm Kammerlander, Gabriele Guidi Colombi, Luca Bordignon, Maximilian Autherith
article en

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: , 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.

Circulation
Goethe University Frankfurt (DE), Utrecht University (NL), Medical University of Graz (AT), Heidelberg University (DE), University Hospital Heidelberg (DE), Stockholm South General Hospital (SE), Surgical Specialties (Canada) (CA), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), German Center for Infection Research (DE), Arcispedale Sant'Anna (IT), German Centre for Cardiovascular Research (DE), University Hospital Frankfurt (DE), ERN GUARD-Heart (NL), Azienda Sanitaria Universitaria Integrata di Trieste (IT), University of Brescia (IT), Ludwig-Maximilians-Universität München (DE)
Openalex Percentile: Top 24%
Amyloidosis: Diagnosis, Treatment, Outcomes
DOISourceOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.