Exercise chronotropic inefficiency in patients with heart failure across distinct left ventricular ejection fraction phenotypes

To characterize the pattern of chronotropic incompetence (CI) response to exercise in patients with heart failure (HF) across distinct phenotypes of the left ventricular ejection fraction and to explore the extent to which heart rate (HR) response should be prioritized as a therapeutic target within personalized HF management strategies.

Patients with HF with preserved ejection fraction (HFpEF), HF with reduced ejection fraction (HFrEF), and healthy controls underwent incremental exercise testing with simultaneous gas exchange and echocardiography assessments. Stroke volume (SV), HR, cardiac output (CO), and arteriovenous oxygen difference [C(a-v)O2] were assessed from rest to peak exercise. Graphical analyses explored relationships amongst determinants of oxygen uptake (V̇O2).

Both HF phenotypes exhibited CI and a blunted increase in CO during exercise compared with controls. Peak HR was similarly reduced by 20% in HFpEF and 23% in HFrEF. HFpEF, however, exhibited a steeper HR-VO2 relationship. HFrEF demonstrated a greater compensatory increase in peripheral O2 extraction, with peak C(a-v)O2 73% higher than controls and 21% higher than HFpEF. In contrast, HFpEF showed limited ability to augment C(a-v)O2 and presented the lowest relative peak V̇O2 (-39% vs. controls and -16% vs. HFrEF), despite similar peak V̇O2%pred between HF phenotypes.

CI can contribute to exercise intolerance in both HF phenotypes, with distinct compensatory mechanisms. An integrated cardiopulmonary exercise testing-echocardiography approach may support identifying phenotype-specific physiological profiles that might address therapeutic strategies targeting CI, SV reserve, and peripheral O2 utilization to improve functional capacity in HF. Addressing the kinetics of HR slope and ΔHR metrics seems relevant to implement knowledge on the fundamental CI contribution in HF phenotypes.