Disease-Specific Mitral Regurgitation Grading Improves Prognosis Assessment in Transthyretin Amyloid Cardiomyopathy

Conventional echocardiographic criteria may underestimate mitral regurgitation (MR) severity in transthyretin amyloid cardiomyopathy because of restrictive, low-flow hemodynamics. A study in Circulation evaluated 1,101 newly diagnosed patients across eight centers in four countries, using derivation (n=722) and external validation (n=379) cohorts. Standardized echocardiography underwent blinded core laboratory analysis; endpoints were all-cause mortality and first heart failure hospitalization (HFH).

Over a median 24.9 months, 314 patients (28.5%) died and 244 (22.2%) experienced HFH. Intermediate-risk thresholds were vena contracta width ≥3.0 mm, effective regurgitant orifice area ≥0.10 cm², regurgitant volume ≥15 mL, and regurgitant fraction ≥20%. High-risk thresholds were orifice area >0.25 cm², regurgitant volume >38 mL, and regurgitant fraction >35%.

The composite grading scheme classified 21% as having severe MR, compared with approximately 12%–13% using guideline definitions, and improved outcome discrimination at 12 and 24 months in both cohorts. After multivariable adjustment, only the composite scheme remained strongly predictive of both mortality (hazard ratio, 1.20; 95% CI, 1.07–1.36) and HFH (1.21; 1.05–1.38).

These findings support disease-specific MR risk assessment in transthyretin amyloid cardiomyopathy. However, this observational study establishes prognostic associations, not whether intervention at these lower thresholds improves outcomes. Full-text methods and limitations were not available for assessment.