CONGRESS ABSTRACT

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 (VO₂peak), 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, VO₂peak 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.