Right Ventricular to Pulmonary Artery Uncoupling Is Associated With Impaired Exercise Capacity in Patients With Transthyretin Cardiac Amyloidosis

Background: Exercise capacity is related to mortality and morbidity in heart failure (HF) patients. Determinants of exercise capacity in transthyretin cardiac amyloidosis (ATTR-CA) have not been established. Methods and Results: This single-center study retrospectively evaluated ATTR-CA patients and patients with non-amyloidosis HF with preserved/mildly reduced ejection fraction (HFpEF/HFmrEF) (n=32 and n=51, respectively). In the ATTR-CA group, the median age was 75.5 years (interquartile range [IQR] 71.3-78.8 years), 90.6% were male, and the median left ventricular (LV) ejection fraction was 53.5% (IQR 41.4-65.6%). Cardiopulmonary exercise tests revealed a median peak oxygen consumption and anaerobic threshold of 15.9 (IQR 11.6-17.4) and 10.6 (IQR 8.5-12.0] mL/min/kg, respectively, and ventilatory efficiency (minute ventilation/ carbon dioxide production [VE/VCO2] slope) of 35.5 (IQR 32.0-42.5). Among exercise variables, VE/VCO2 slope has the greatest prognostic value. Univariate analysis revealed a significant correlation between VE/VCO2 slope and age, LV global longitudinal strain, tricuspid annular plain systolic excursion/pulmonary arterial systolic pressure (TAPSE/PASP) ratio, and mixed venous oxygen saturation. In multivariate analyses, the TAPSE/PASP ratio was an independent predictor of VE/VCO2 slope (95% confidence interval -44.5, -10.8; P=0.0067). In non-amyloidosis HFpEF/HFmrEF patients, the TAPSE/PASP ratio was not independently correlated with VE/VCO2 slope. Conclusions: Right ventricular-pulmonary artery coupling estimated by the TAPSE/PASP ratio determines exercise capacity in ATTR-CA patients. This highlights the importance of early therapeutic intervention against underappreciated right ventricular dysfunction associated with ATTR-CA.