Characterization of real world contemporary attr-cm patients treated with standard of care: focus on biomarkers and exercise capacity

Background/Purpose Real-world data on the longitudinal trajectories of biomarkers and exercise capacity in transthyretin amyloid cardiomyopathy (ATTR-CM) under contemporary disease-modifying therapy remain scarce. In particular, the prognostic value of cardiopulmonary exercise testing (CPET) in this setting has not been fully established. We aimed to characterise the clinical and functional profile of a real-world ATTR-CM cohort over 12 months of tafamidis therapy, and to identify prognostic determinants of all-cause mortality and heart failure hospitalisation. Methods We prospectively enrolled 163 consecutive patients diagnosed with ATTR-CM at a single tertiary centre (Vito Fazzi Hospital, Lecce, Italy). Diagnosis required characteristic echocardiographic or cardiac magnetic resonance findings combined with Perugini grade 2–3 myocardial uptake on bone scintigraphy, after exclusion of light-chain amyloidosis. All patients underwent genetic testing. Clinical evaluation, laboratory assessment (NT-proBNP, high-sensitivity troponin I, eGFR) and NAC staging were performed at baseline, 6 and 12 months. A subgroup of 44 patients underwent CPET at baseline, of whom 26 completed serial testing at 6 and 12 months. Univariable Cox regression analysis was used to identify predictors of all-cause mortality and the composite endpoint of all-cause mortality or heart failure hospitalisation. Results Median age was 77 years; 73.6% were male. Wild-type ATTR accounted for 62% of cases. Most patients were symptomatic (53.4% NYHA class II, 23.3% class III). Median NT-proBNP was 959 ng/L and median eGFR was 64.6 mL/min/1.73 m². Over 12 months, biomarkers and CPET parameters remained globally stable (peak VO2: 15.4 → 16.4 → 15.4 mL/kg/min; VE/VCO2 slope: 36.8 → 36.7 → 37.2), suggesting disease stabilisation under tafamidis. On Cox regression, significant predictors of all-cause mortality included age (HR 1.06, 95% CI 1.01–1.11, p=0.019), NYHA class (HR 4.61, 95% CI 2.10–10.13, p<0.001), Perugini score (HR 2.23, 95% CI 1.21–4.11, p=0.011), eGFR (HR 0.96, 95% CI 0.93–0.98, p=0.002) and loop diuretic dose (HR 1.01, 95% CI 1.006–1.013, p<0.001). For the composite endpoint, atrial fibrillation (HR 2.24, p=0.013), oxygen pulse (HR 0.68, p=0.040) and high-sensitivity troponin I (HR 1.008, p=0.011) also reached significance. Conclusions In this real-world ATTR-CM cohort, tafamidis therapy was associated with stability of biomarkers and cardiopulmonary exercise parameters over 12 months, supporting its disease-modifying effect. Age, functional class, renal function, Perugini score and diuretic requirement emerged as key prognostic determinants. Notably, CPET-derived parameters — particularly peak VO2 and oxygen pulse — provided incremental prognostic information for the composite endpoint beyond conventional biomarkers, supporting the integration of functional testing into longitudinal risk stratification of patients with ATTR-CM.