Exercise limitations in amyloid cardiomyopathy assessed by cardiopulmonary exercise testing-A multicentre study

Aims Amyloid cardiomyopathy is caused by the deposition of light chain (AL) or transthyretin amyloid (ATTR) fibrils, that leads to a restrictive cardiomyopathy, often resulting in heart failure (HF) with preserved or reduced ejection fraction. This study aimed to determine whether cardiac output reduction or ventilation inefficiency plays a predominant role in limiting exercise in patients with amyloid cardiomyopathy. Methods We conducted a multicentre prospective study in patients with AL or ATTR cardiomyopathy who underwent cardiopulmonary exercise testing across four centres. Patients were compared with a propensity-score matched HF cohort based on age, gender, left ventricular ejection fraction (LVEF), and peak oxygen consumption (VO2). Results Data from 267 amyloid patients aged 77 (72, 81) years, 86% male, with a median N-terminal pro B-type natriuretic peptide (NT-proBNP) of 2187 (1140, 4383) ng/L, exercise parameters of peak VO2 of 14.1 (11.6;16.9) mL/min/kg, a minute ventilation to carbon dioxide production (VE/VCO2) slope of 37.4 (32.5, 42.6) and a LVEF of 50% (44%, 59%) were analysed. We identified 251 amyloid cardiomyopathy-HF matches. Amyloid patients had a signifnicantly higher VE/VCO2 slope [37.4, inter quartile range (IQR): 32.7, 43.1 vs. 32.1, IQR: 28.7, 37.0, P < 0.0001], NT-proBNP (2249, IQR: 1187, 4420 vs. 718, IQR: 405, 2161 ng/L, P < 0.001), peak heart rate (121 +/- 28 vs. 115 +/- 27 beats/min, P = 0.007) and peak ventilation (51, IQR: 42, 62 vs. 43, IQR: 33, 53 L/min, P < 0.0001) with earlier anaerobic threshold (VO2 at AT: 8.9, IQR: 6.8, 10.8 vs. 10.8, IQR: 8.9, 12.7 mL/min/kg, P < 0.0001) compared with HF. Between amyloid patients, AL patients (n = 27) were younger (63, IQR: 58, 70 vs. 78, IQR: 72, 81 years, P < 0.0001), had lower VE/VCO2 slope (35.0, IQR: 30.0, 38.7 vs. 38.0, IQR: 32.8, 43.1, P = 0.019), higher end-tidal carbon dioxide partial pressure both at AT (35.1 +/- 4.8 vs. 31.4 +/- 4.7 mmHg, P < 0.001) and peak exercise (32, IQR: 28, 35 vs. 30, IQR: 26, 33 mmHg, P = 0.039) as compared with ATTR (n = 233). Conclusions A higher VE/VCO2 slope and an earlier AT, determining functional capacity impairment, was assessed in patients with amyloid cardiomyopathy compared with the matched HF cohort. Additionally, patients with ATTR might display more severe exercise limitations as compared with AL.