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

Abstract

Patients with HFpEF experience severe exercise intolerance due in part to peripheral vascular and skeletal muscle impairments. Interventions targeting peripheral adaptations to exercise training may reverse vascular dysfunction, increase peripheral oxidative capacity, and improve functional capacity in HFpEF. Determine if 8 weeks of isolated knee extension exercise (KE) training will reverse vascular dysfunction, peripheral oxygen utilization, and exercise capacity in patients with HFpEF. Nine HFpEF patients (66 ± 5 years, 6 females) performed graded IKE exercise (5, 10, and 15 W) and maximal exercise testing (cycle ergometer) before and after IKE training (3x/week, 30 min/leg). Femoral blood flow (ultrasound) and leg vascular conductance (LVC; index of vasodilation) were measured during graded IKE exercise. Peak pulmonary oxygen uptake (V̇O2; Douglas bags) and cardiac output (QC; acetylene rebreathe) were measured during graded maximal cycle exercise. IKE training improved LVC (pre: 810 ± 417, post: 1234 ± 347 ml/min/100 mmHg; p = 0.01) during 15 W IKE exercise and increased functional capacity by 13% (peak V̇O2 during cycle ergometry; pre:12.4 ± 5.2, post: 14.0 ± 6.0 ml/min/kg; p = 0.01). The improvement in peak V̇O2 was independent of changes in Q̇c (pre:12.7 ± 3.5, post: 13.2 ± 3.9 L/min; p = 0.26) and due primarily to increased a‐vO2 difference (pre: 10.3 ± 1.6, post: 11.0 ± 1.7; p = 0.02). IKE training improved vasodilation and functional capacity in patients with HFpEF. Exercise interventions aimed at increasing peripheral oxidative capacity may be effective therapeutic options for HFpEF patients.

α‐Adrenergic regulation of skeletal muscle blood flow during exercise in patients with heart failure with preserved ejection fraction

“…The data from the present study agree with previous reports of a diminished hyperaemic response during exercise in patients with HFpEF (Hearon et al., 2022; Lee, Barrett‐O'Keefe, Nelson et al., 2016; Ratchford et al., 2020; Weavil et al., 2021) and implicate disease‐related changes in sympathetic (α‐adrenergic) vasoconstriction as a key contributing factor. It may be speculated that the current observation of increased α‐adrenergic restraint of blood flow to exercising skeletal muscle in patients with HFpEF could be the result of elevated MSNA.…”

“…However, functional sympatholysis can be improved with exercise training in normotensive and hypertensive subjects (Mortensen et al., 2014), as well as patients with HFrEF (Munch et al., 2018), indicating the potential for functional sympatholysis as a modifiable target for improvement via exercise training. Importantly, there is now initial evidence for improvements in exercising muscle blood flow after 8 weeks of KE exercise training in patients with HFpEF (Hearon et al., 2022), demonstrating residual vascular plasticity in this patient group. However, whether this training‐induced increase in exercise hyperemia could be related to an accompanying improvement in functional sympatholysis remains to be determined.…”

“…Exercise training studies in patients with HFpEF have demonstrated the capacity to increase VO 2 peak , although the improvement often occurs in the absence of central changes, such as peak stroke volume, HR or cardiac output (Haykowsky et al, 2012;Hearon et al, 2022). These findings indicate that the training-induced improvement in VO 2 peak is most likely attributable to amelioration of deficiencies that exist in the periphery.…”

Exercise intolerance in heart failure with preserved ejection fraction: Causes, consequences and the journey towards a cure

“…Investigations utilizing smaller muscle mass exercise that isolate peripheral mechanisms of oxygen transport and utilization independent of central cardiopulmonary limitations have identified striking impairments in the regulation of skeletal muscle blood flow in patients with HFpEF. Indeed, studies utilizing isolated knee‐extensor exercise (up to 15 W, ∼75–90% of peak work rate) indicate that patients with HFpEF have 15–25% lower leg blood flow compared to age‐matched control participants due primarily to a lower vasodilatory response to exercise (Hearon, Samels et al., 2022 ; Lee, Barrett‐O'Keefe, Nelson et al., 2016 ). Similarly, investigations employing handgrip exercise (30–45% of maximal voluntary contraction, MVC) documented a 20–40% lower forearm blood flow in patients with HFpEF compared to age‐matched hypertensives that was apparent primarily at higher exercise intensities (Ratchford et al., 2020 ).…”

“…Therefore, despite the limited ability of exercise training to improve these traditional markers of vascular function (Gevaert et al., 2023 ; Tucker et al., 2018 ), habitual exercise has been shown to improve vascular responses during acute bouts of exercise. A small investigation in patients with HFpEF who completed 8 weeks of isolated knee extensor exercise training showed improvements in leg vascular conductance (vasodilatation) during exercise compared to pre‐training values that was associated with an improvement in peak a–vO 2 difference and functional capacity (Hearon, Samels et al., 2022 ). Therefore, some level of vascular plasticity may exist in patients with HFpEF.…”