Why the study?
In ATTR-CM, restrictive low-flow hemodynamics may cause conventional echocardiographic criteria derived from non-amyloid populations to underestimate tricuspid regurgitation severity. Disease-specific TR risk thresholds needed to be defined, validated, and compared against guideline and TVARC definitions.
Does a disease-specific multiparametric 4-grade conceptual framework for tricuspid regurgitation improve prediction of all-cause mortality and heart failure hospitalisation compared to conventional guideline and TVARC definitions in patients with newly diagnosed transthyretin amyloid cardiomyopathy?
Cohort (n=1,124)
Blinded core-laboratory analysis
Yes
Does a disease-specific multiparametric 4-grade conceptual framework for tricuspid regurgitation improve prediction of all-cause mortality and heart failure hospitalisation compared to conventional guideline and TVARC definitions in patients with newly diagnosed transthyretin amyloid cardiomyopathy?
In patients with ATTR-CM, quantitative tricuspid regurgitation risk thresholds are substantially lower than current guideline cut-offs, and a newly validated disease-specific 4-grade framework improves the prediction of mortality and heart failure hospitalisation.
Background and Aims In transthyretin amyloid cardiomyopathy (ATTR-CM), tricuspid regurgitation (TR) severity may be underestimated by conventional (semi-)quantitative echocardiographic criteria derived from non-amyloid populations, given restrictive low-flow hemodynamics. We sought to define and validate disease-specific TR risk thresholds and compare their prognostic performance with guideline definitions and the tricuspid valve academic research consortium (TVARC) 5-grade extension. Methods In this international multicenter cohort study (8 centres, 4 countries), 1,124 patients with newly diagnosed ATTR-CM (derivation: n=745, validation: n=379) underwent standardised echocardiography with blinded core-laboratory analysis including TR parameters [vena contracta width (VCW), effective regurgitant orifice area (EROA), and regurgitant volume (RegVol)]. All-cause mortality and time to first heart failure hospitalisation (HFH) served as endpoints. Prognostic thresholds were derived from restricted cubic spline analysis, externally validated, and integrated into a multiparametric 4-grade conceptual framework (grade defined by the worst-risk category across VCW/EROA/RegVol). Prognostic performance was compared with 2025 ESC/EACTS, 2020 AHA/ACC, 2017 ASE, and TVARC definitions using multivariable Cox regression and time-dependent discrimination analyses. Results During a median follow-up of 25.2 months (IQR 12.2–43.2), 324 (28.8%) patients died, and 251 (22.3%) experienced HFH. Spline-derived thresholds identified stepwise risk strata at VCW 3/5/8 mm, EROA 0.15/0.25/0.50 cm², and RegVol 10/20/40 mL, delineating intermediate-, high-, and extreme-risk ranges (Figure 1). Integration into the conceptual framework yielded 411 (36.6%) patients classified as low risk, 379 (33.7%) as intermediate risk, 234 (20.8%) as high risk, and 100 (8.9%) as extreme risk, with clear separation of Kaplan–Meier curves in the overall cohort and consistent stepwise separation in both derivation and validation cohorts. Compared with guideline-based and TVARC grading (each 11.6%), the framework classified a significantly higher proportion (29.7%) as ≥severe TR (all comparisons: p<0.001) and demonstrated the strongest independent association with outcomes after multivariable adjustment for disease stage and ATTR-specific therapy (mortality: HR 1.45, 95% CI 1.29–1.64; HFH: HR 1.32, 95% CI 1.14–1.52). Time-dependent analyses confirmed superior discrimination of the framework for mortality from 12–60 months in the derivation and validation cohorts (Figure 2). Conclusions Quantitative TR thresholds in ATTR-CM are substantially lower than current guideline cut-offs. A validated, risk-based conceptual framework improves prediction of both mortality and HFH, better reflecting restrictive low-flow pathophysiology and supporting disease-specific TR grading in ATTR-CM.Figure 1.Spline CurvesFigure 2.
No takes yet. Share an insight, caveat, or question.
Hauptmann et al. (2026) conducted a cohort in Transthyretin amyloid cardiomyopathy (ATTR-CM) with tricuspid regurgitation (n=1,124). Multiparametric 4-grade disease-specific tricuspid regurgitation (TR) risk framework vs. 2025 ESC/EACTS, 2020 AHA/ACC, 2017 ASE, and TVARC 5-grade TR definitions was evaluated on All-cause mortality and time to first heart failure hospitalisation (HFH) (HR 1.45, 95% CI 1.29-1.64).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: