Impaired Chronotropic and Vasodilator Reserves Limit Exercise Capacity in Patients With Heart Failure and a Preserved Ejection Fraction

TLDR

Nearly half of heart‑failure patients have preserved ejection fraction, and exercise intolerance in HFpEF is usually attributed to diastolic dysfunction, though impaired systolic or arterial vasodilator reserve may also contribute. The study compared 17 HFpEF patients and 19 matched controls using maximal upright cycle ergometry combined with radionuclide ventriculography to assess rest and exercise cardiovascular function. HFpEF patients showed markedly reduced exercise capacity, with about 40 % lower heart‑rate and cardiac‑output responses and impaired vasodilation at low workloads, delayed heart‑rate recovery, and exercise performance linked to changes in cardiac output, heart rate, and vascular resistance rather than diastolic function, underscoring chronotropic, vasodilator, and cardiac‑output reserve deficits as potential therapeutic targets.

Abstract

Nearly half of patients with heart failure have a preserved ejection fraction (HFpEF). Symptoms of exercise intolerance and dyspnea are most often attributed to diastolic dysfunction; however, impaired systolic and/or arterial vasodilator reserve under stress could also play an important role.Patients with HFpEF (n=17) and control subjects without heart failure (n=19) generally matched for age, gender, hypertension, diabetes mellitus, obesity, and the presence of left ventricular hypertrophy underwent maximal-effort upright cycle ergometry with radionuclide ventriculography to determine rest and exercise cardiovascular function. Resting cardiovascular function was similar between the 2 groups. Both had limited exercise capacity, but this was more profoundly reduced in HFpEF patients (exercise duration 180+/-71 versus 455+/-184 seconds; peak oxygen consumption 9.0+/-3.4 versus 14.4+/-3.4 mL x kg(-1) x min(-1); both P<0.001). At matched low-level workload, HFpEF subjects displayed approximately 40% less of an increase in heart rate and cardiac output and less systemic vasodilation (all P<0.05) despite a similar rise in end-diastolic volume, stroke volume, and contractility. Heart rate recovery after exercise was also significantly delayed in HFpEF patients. Exercise capacity correlated with the change in cardiac output, heart rate, and vascular resistance but not end-diastolic volume or stroke volume. Lung blood volume and plasma norepinephrine levels rose similarly with exercise in both groups.HFpEF patients have reduced chronotropic, vasodilator, and cardiac output reserve during exercise compared with matched subjects with hypertensive cardiac hypertrophy. These limitations cannot be ascribed to diastolic abnormalities per se and may provide novel therapeutic targets for interventions to improve exercise capacity in this disorder.