Cardiovascular responses to rhythmic handgrip exercise in heart failure with preserved ejection fraction

Abstract

While the contribution of non-cardiac complications to the pathophysiology of heart failure with preserved ejection fraction (HFpEF) have been increasingly recognized, disease-related changes in peripheral vascular control remain poorly understood. We utilized small muscle mass handgrip exercise to concomitantly evaluate exercising muscle blood flow and conduit vessel endothelium-dependent vasodilation in individuals with HFpEF (n = 25) compared to hypertensive controls (HTN) (n = 25). Heart rate (HR), stroke volume (SV), cardiac output (CO), mean arterial pressure (MAP), brachial artery blood velocity, and brachial artery diameter were assessed during progressive intermittent handgrip (HG) exercise (15-30-45% MVC). Forearm blood flow (FBF) and vascular conductance (FVC) were determined to quantify the peripheral hemodynamic response to HG exercise, and changes in brachial artery diameter were evaluated to assess endothelium-dependent vasodilation. HR, SV, and CO were not different between groups across exercise intensities. However, although FBF was not different between groups at the lowest exercise intensity, FBF was significantly lower (20-40%), in individuals with HFpEF at the two higher exercise intensities (30% MVC: 229±8 vs. 274±23 ml/min; 45% MVC: 283±17 vs. 399±34 ml/min, HFpEF vs. HTN). FVC was not different between groups at 15 and 30% MVC, but was ≈20% lower in HFpEF at the highest exercise intensity. Brachial artery diameter increased across exercise intensities in both HFpEF and HTN, with no difference between groups. These findings demonstrate an attenuation in muscle blood flow during exercise in HFpEF in the absence of disease-related changes in central hemodynamics or endothelial function.

Matching of O2 Utilization and O2 Delivery in Contracting Skeletal Muscle in Health, Aging, and Heart Failure

“…Only very few studies have investigated hemodynamic and metabolic variables in HFpEF patients during isolated forearm and knee-extensor exercise. In one study, skeletal muscle vascular conductance and blood flow were found to be reduced at higher submaximal intensities in patients in the absence of macrovascular dysfunction and dysregulated central hemodynamics ( Ratchford et al, 2020 ). In another study, a-vO 2 difference was reduced across all brachial blood flows in patients, however, peak O 2 uptake was preserved in HFpEF through a statistically non-significant enhancement (∼14%) of blood flow ( Zamani et al, 2020 ).…”

Tetrahydrobiopterin Administration Augments Exercise-Induced Hyperemia and Endothelial Function in Patients With Systemic Sclerosis

“…Therefore, brachial artery vasodilation during progressive handgrip exercise can be used as a measurement of endothelium-dependent dilation. Our group has utilized this ‘sustained stimulus flow-mediated dilation' in a variety of populations to detect endothelial dysfunction in both health and disease ( 8 , 13 , 33 , 34 ), and importantly, have identified the NO-dependent nature of brachial artery vasodilation using this experimental model ( 19 ).…”

Isolated knee extensor exercise training improves skeletal muscle vasodilation, blood flow, and functional capacity in patients with HFpEF

“…Relatively, few studies have quantified the vasodilatory response to exercise in HFpEF patients. Previously, a series of investigations identified severe reductions in the leg and forearm vascular conductance during exercise in HFpEF that are not attributable to disease‐related decrements in cardiac or conduit arterial dysfunction (Lee, Barrett‐O'Keefe, Nelson, et al, 2016 ; Ratchford et al, 1985 ; Ratchford et al, 2019 ). These findings are in line with findings of microvascular dysfunction and skeletal muscle structural and oxidative deficiencies in HFpEF (Kitzman et al, 2014 ; Zamani et al, 2021 ).…”