Tafamidis and Functional Capacity: Analysis of Cardiopulmonary Exercise Testing Parameters in Patients With Transthyretin Amyloid Cardiomyopathy

Background Tafamidis improves survival and slows functional decline in transthyretin cardiac amyloidosis (ATTR–CM), but early changes in cardiopulmonary performance are poorly characterized. Objective We evaluated whether the same cardiopulmonary exercise testing (CPET) variables previously shown to improve at longer–term follow–up, together with 4–m gait speed, already improve after 6 months of tafamidis without further therapeutic changes, thereby isolating the drug effect. Methods In this prospective single–centre study, patients with a new diagnosis of ATTR–CM and indication for tafamidis underwent CPET on cycle ergometer and a 4–m gait–speed test at baseline (T0) and after 6 months of therapy (T6). Peak oxygen consumption (VO₂ peak), ventilatory efficiency (VE/VCO₂ slope), VO₂/work slope, heart rate/VO₂ slope, oxygen pulse, respiratory exchange ratio (RER), maximal workload and gait speed were measured. Background medical therapy was kept unchanged whenever possible. Paired tests and linear mixed–effects models were applied to compare T0 and T6. Results Fifteen patients completed both assessments (five additional patients are still in follow–up). At 6 months, VO₂ peak increased from 16.9±3.7 to 18.4±4.1 mL/kg/min (p=0.03) (File 2), oxygen pulse from 11.0±2.8 to 12.0±3.1 mL/beat (p=0.03) and maximal workload from 79.9±25.7 to 90.9±30.4 W (p=0.02). VE/VCO₂ slope decreased from 35.9±6.7 to 33.8±6.4 (p=0.02), with a modest improvement in VO₂/work slope. The increase in VO₂peak correlated with the reduction in VE/VCO₂ slope (File 3). Gait speed rose from 0.83±0.22 to 1.03±0.25 m/s (p=0.01) (File 1); in 60% of patients the gain exceeded the threshold for clinically meaningful improvement (≥0.10 m/s). Conclusions In patients with ATTR–CM, tafamidis was associated with early, clinically relevant improvement in cardiopulmonary performance and physical function, detectable 6 months after treatment initiation despite stable background therapy. CPET combined with gait speed appears to be a sensitive strategy to capture therapeutic benefit and may complement imaging and biomarker–based follow–up in ATTR–CM. Larger multicentre studies are warranted to confirm these findings and to define the prognostic value of early CPET changes under tafamidis therapy.