Inotropic myocardial reserve deficiency is the predominant feature of exercise haemodynamics in cardiac amyloidosis

Aims This study aimed to characterize invasive haemodynamics during exercise in subjects with cardiac amyloidosis ( CA ). Methods and results The study population numbered 44 subjects. Group A ( CA ‐positive, n  = 24) comprised wild‐type transthyretin patients ( n  = 10), familial transthyretin amyloidosis mutation carriers ( ATTRm ) with cardiac involvement ( n  = 5), and light‐chain amyloidosis patients with cardiac involvement ( n  = 9). Group B ( CA ‐negative, n  = 20) comprised four healthy ATTRm subjects without cardiac involvement documented by 11 C‐PIB positron emission tomography and 16 healthy controls. All subjects underwent a symptom‐limited, semi‐supine exercise test with expired gas analysis and simultaneous right heart catheterization. CA patients had lower peak oxygen consumption [15 ± 6  mL /min/kg bodyweight (bwt) vs. 33 ± 7  mL /min/kg bwt; P  < 0.0001] than controls. Myocardial reserve during exercise was significantly reduced in CA patients as reflected in a small increase in stroke volume index ( SVI ) and cardiac index ( CI ) compared with controls [ ΔSVI : 4  mL /m 2 (range: −1 to 8) vs. 14  mL /m 2 (range: 5–25); P  < 0.0001; ΔCI : 2 ± 2 L/min vs. 7 ± 2 L/min; P  < 0.0001]. During exercise, CA patients had significantly higher left and right ventricular filling pressures than controls. Furthermore, CA patients had severely impaired pulmonary arterial compliance ( PAC ) compared with controls [2.9  mL / mmHg (range: 2.1–4.5) vs. 7.5  mL / mmHg (range: 5.7–10.4); P  < 0.0001]. Conclusions Cardiac amyloid deposits are associated with severely reduced inotropic myocardial reserve and increased left and right ventricular filling pressures during exercise. Furthermore, CA subjects have severely reduced PAC , which may contribute to right heart failure and reduced exercise capacity.