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 (Q_C ; 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.

FIGURE 1

Experimental protocol. Patients with HFpEF (n = 9) completed graded cardiopulmonary exercise testing on a cycle ergometer to determine peak V̇O₂, cardiac output (Q̇c) and a‐v O₂ difference, and Q_c/V̇O₂ slope during maximal exercise. Patients also completed assessments of hemodynamics and a leg blood flow during isolated knee extension exercise to quantify vascular function during exercise independent of central cardiac limitations. Patients were then trained for 8 weeks using the IKE method to maximize peripheral adaptations to exercise. At the end of 8 weeks, graded exercise testing and IKE testing were repeated to determine the effect of IKE training on peripheral vascular function and whole‐body functional capacity. HFpEF, heart failure with preserved ejection fraction; IKE, isolated knee extension; UL, unloaded exercise.

FIGURE 2

IKE training improves skeletal muscle vascular function in HFpEF. Change in (a) mean arterial pressure, (b) leg blood flow (femoral artery), and (c) vascular conductance during graded isolated knee extension exercise (IKE) in healthy, sedentary senior controls (N = 9), and HFpEF patients (n = 8) before and after 8 weeks of IKE training. HFpEF, heart failure with preserved ejection fraction; IKE, isolated knee extension. *HFpEF pre vs. Control; †HFpEF post vs. HFpEF pre.

FIGURE 3

(a) IKE training improves functional capacity in HFpEF. V̇O₂, (b) Cardiac Output, and (c) a‐vO₂ difference during peak cycle exercise in healthy, sedentary, senior controls (n = 9), and HFpEF patients before and after 8 weeks of IKE training. (d) Q̇c/V̇O₂ slope during graded cycle exercise testing in controls and HFpEF patients after 8 weeks of IKE training. HFpEF, heart failure with preserved ejection fraction; IKE, isolated knee extension. *HFpEF pre vs. Control; †HFpEF post vs. HFpEF pre.