Restrictive cardiac phenotype as primary cause of impaired aerobic capacity in Afro-Caribbean patients with val122ile variant transthyretin amyloid cardiomyopathy.

Background: Impaired aerobic capacity in cardiac amyloidosis patients may be related to limited inotropic myocardial reserve and heart rate (HR) response limiting cardiac output rise. This study sought to investigate whether chronotropic incompetence (CI) and blunted HR recovery would be prevalent in patients with mutant transthyretin (ATTRv) cardiomyopathy.Methods and results: Eighteen ATTRv (Val122Ile) patients (72 ± 8-year) and 15 age-matched controls (73 ± 3-year) were prospectively enrolled. Patients' medical records, pulmonary function and cardiopulmonary exercise testing, including non-invasive cardiac hemodynamics and chronotropic response were studied. Compared with age-matched controls, maximal workload (91 ± 8 vs. 65 ± 20 watts) and peak VO2 (19.5 ± 3.0 vs. 14.4 ± 4.1 mL.kg-1.min-1) were lower in ATTRv patients. Despite reaching similar age-predicted maximal HR, ATTRv patients displayed smaller changes in stroke volume (SV) index relative to change in VO2 (49 ± 26 vs. 67 ± 18%). Adequate chronotropic-metabolic index was prevalent in ATTRv patients. HR recovery, as percent decrease in peak HR at 1 and 3-min, was blunded ATTv patients.Conclusions: In Val122Ile ATTRv patients, chronotropic response was appropriate relative to exercise intensity with only few patients displaying CI. HR response to exercise was further characterised by blunted HR recovery in ATTRv patients suggesting lower parasympathetic activity and greater sympathetic stimulation compared with controls.