Prognostic role of cardiopulmonary exercise testing in wild-type transthyretin amyloid cardiomyopathy patients treated with tafamidis

Abstract

Objectives: Tafamidis has demonstrated survival benefits in transthyretin amyloid cardiomyopathy (ATTR-CM), yet variability in therapeutic response underscores the need for reliable tools to predict outcomes. This study evaluates the prognostic utility of cardiopulmonary exercise testing (CPET) in this population.

Methods: This retrospective study included tafamidis treated wild-type (ATTRwt) CM patients who completed CPET. Univariable and multivariable Cox regression models were used to evaluate predictors of mortality and composite secondary endpoint (mortality and heart failure admissions).

Results: Total of 105 ATTRwt-CM patients were enrolled with median age of 80 years. During median follow-up of 2.1 years, 33 (31%) died and 67 (63.8%) had composite outcome of mortality and heart failure hospitalisations. Multivariable analysis showed VE/VCO₂ slope (HR 1.61 per SD, 95% CI: 1.13-2.30, p = 0.01), peak circulatory power [CP] (HR 0.43 per SD, 95% CI 0.21-0.89, p = 0.02), Mayo stage 3 (HR 5.34, 95% CI: 1.07-26.7, p = 0.04) were independent predictors of mortality. The VE/VCO₂ slope (HR 1.57 per SD, 95% CI 1.2, 2.05, p= <0.01), creatinine (HR 1.37 per SD, 95% CI 1.07, 1.76, p = 0.01) and Mayo stage 3 (HR 2.49, 95% CI 1.10, 5.66, p = 0.03) were independent predictors of composite outcome.

Conclusions: CPET provides prognostic insights for ATTRwt-CM patients in addition to known prognostic laboratory factors.

Keywords: Wild-type transthyretin amyloid cardiomyopathy; cardio-pulmonary exercise testing; peak VO2, VE/VCO2 slope, and exercise duration; tafamidis.