Association of beta blocker therapy and functional parameters in patients with transthyretin amyloid cardiomyopathy

Introduction The role of beta-blockers (BB) therapy in transthyretin amyloid cardiomyopathy (ATTR-CM) remains controversial, and its effects on functional capacity in this patient collective have not been systematically evaluated. This study is the first to assess BB therapy in ATTR-CM using cardiopulmonary exercise testing (CPET) to characterize its association with exercise performance and hemodynamic response. Methods We analysed data from 157 patients with confirmed diagnosis of ATTR-CM who underwent baseline CPET assessment before initiation of disease-specific therapy. Patients were divided into groups according to BB therapy at the time of assessment. Cox regression and Kaplan-Meier analysis were performed to assess the prognostic relevance of CPET-derived parameters. Furthermore, functional, laboratory and imaging parameters were compared exploratively between groups. Results Of the total cohort (mean age 77.9 ±6.8 years, 89% male), 52 % received BB therapy. Functional capacity was significantly lower in the BB group, as reflected in reduced peak oxygen uptake (13.7±3.9 vs. 16.2±4.6 ml/min/kg, p=0.0005) and higher VE/VCO2 slope (40.6±8.0 vs. 37.8±9.4, p=0.052). Moreover, patients without BB therapy showed better performance in six-minute walk test ( 437.8±115.9 vs. 357.2 ±113.5 m, p<0.0001). BB cohort also demonstrated a blunted chronotropic response in maximal heart rate (118.6±22.2 vs. 133.1±35.8 bpm, p=0.0045), while peak oxygen pulse remained comparable between groups (10.8±3.9 vs. 10.9±3.9 ml/beat, p=0.92). In survival analysis, lower peak oxygen pulse was associated with adverse outcomes (log-rank p=0.002). Cox regression confirmed the prognostic relevance of key CPET-parameters. Conclusions BB-therapy in ATTR-CM is commonly used but associated with reduced exercise performance and chronotropic response, while stroke volume adaptation appears preserved. Peak oxygen pulse emerged as a prognostic marker, linking impaired outcomes to reduced stroke volume reserve. Our findings suggest that BB use should be individualized particularly when guided by comprehensive assessment using CPET.