One-minute heart rate recovery and clinical outcomes in transthyretin cardiac amyloidosis: incremental model fit beyond conventional CPET indices

To assess the association of 1-min heart rate recovery (HRR1) with clinical outcomes and its incremental contribution to model fit beyond peak VO₂ and ventilatory efficiency (VE/VCO₂ slope) in transthyretin cardiac amyloidosis (ATTR-CM).

Consecutive adults with confirmed ATTR-CM undergoing symptom-limited cardiopulmonary exercise testing (CPET) were included in this single-centre observational study. During standardized active recovery at 24 W, HRR1 was defined as peak heart rate minus heart rate exactly 60 s after exercise. Cox proportional-hazards models evaluated all-cause mortality and the composite of mortality or first heart-failure hospitalization. Principal models adjusted for age, sex, peak VO₂ and VE/VCO₂ slope; NT-proBNP and National Amyloidosis Centre (NAC) stage were examined separately. Of 161 baseline patients, 11 with unverifiable heart-rate measurements were excluded, and exact HRR1 was available in 110. Mortality analysis included 105 patients with 33 deaths; composite-outcome analysis included 107 patients with 51 events. Median HRR1 was 15.5 bpm. In conventional CPET-adjusted models, each 10-bpm greater HRR1 was associated with lower hazards of mortality [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.44–0.95; P = 0.028] and the composite outcome (HR 0.74, 95% CI 0.57–0.97; P = 0.029). Adding HRR1 improved model fit (likelihood-ratio P = 0.017 and P = 0.021, respectively); apparent C-indices increased from 0.770 to 0.795 for mortality and from 0.695 to 0.699 for the composite outcome. Associations were non-significant after separate adjustment for NT-proBNP or NAC stage.

HRR1 remained associated with outcomes after CPET adjustment and improved model fit. Discrimination gains were modest; value beyond biomarker staging was unproven.