Cerebrovascular responses to muscle metaboreflex activation in patients living with heart failure with reduced ejection fraction

Impaired cerebrovascular control in patients with heart failure with reduced ejection fraction (HFrEF) has been attributed to cardiac impairment and exaggerated sympathetic-mediated cerebral vasoconstriction. The goal of this study was to examine the effect of muscle metaboreflex activation (MMA) on cerebrovascular hemodynamics in patients with HFrEF under conditions of preserved cardiac output. It was hypothesized that reductions in the index of cerebral blood flow and cerebrovascular conductance (CVCi) during MMA would be exaggerated in HFrEF and independent of reduced cardiac output. Middle cerebral blood velocity (MCA_Vmean; transcranial Doppler), blood pressure, cardiac output (Finometer), and end-tidal CO₂ were examined at rest, during isometric handgrip, and during muscle MMA (postexercise circulatory occlusion) in 18 patients with HFrEF and 21 healthy, sex-, and age-matched controls. To minimize differences in β-adrenergic control, patients with HFrEF withdrew from β-blockade medications before the study. Cardiac index and blood pressure were not significantly different between groups under any condition. The MCA_Vmean was lower at rest and during exercise in HFrEF. The CVCi (MCA_Vmean/mean arterial pressure) and MCA_Vmean decreased during MMA in the control group. In contrast, the CVCi remained unchanged and MCA_Vmean increased during MMA in the HFrEF group. Despite similar systemic hemodynamics, patients with HFrEF display lower MCA_Vmean at rest and an increase in MCA_Vmean during MMA. These novel findings implicate aspects other than reduced cardiac output or exaggerated sympathetic constriction as underlying causes of altered cerebrovascular regulation in HFrEF.<b>NEW & NOTEWORTHY</b> Compared with controls, patients with heart failure with reduced ejection fraction (HFrEF) displayed reduced indices of cerebral perfusion at rest and increases in perfusion in response to postexercise circulatory occlusion (PECO, method to isolate muscle metaboreflex activation). This occurred despite similar cardiac output and blood pressure values between groups. Thus, lower resting indices of cerebral perfusion and increased perfusion during sympathoexcitation in HFrEF may occur independently from differences in systemic hemodynamics.