Heart Failure with Preserved Ejection Fraction Diminishes Peripheral Hemodynamics and Accelerates Exercise-induced Neuromuscular Fatigue

This study investigated the impact of HFpEF on neuromuscular fatigue and peripheral hemodynamics during small muscle mass exercise not limited by cardiac output. Eight HFpEF patients (NYHA II-III, ejection-fraction: 61 ± 2%) and eight healthy controls performed dynamic knee extension exercise (80% peak workload) to task failure and maximal intermittent quadriceps contractions (8 × 15 s). Controls repeated knee extension at the same absolute intensity as HFpEF. Leg blood flow (Q) was quantified using Doppler ultrasound. Pre/postexercise changes in quadriceps twitch torque (ΔQ; peripheral fatigue), voluntary activation (ΔVA; central fatigue), and corticospinal excitability were quantified. At the same relative intensity, HFpEF (24 ± 5 W) and controls (42 ± 6 W) had a similar time-to-task failure (∼10 min), ΔQ (∼50%), and ΔVA (∼6%). This resulted in a greater exercise-induced change in neuromuscular function per unit work in HFpEF, which was significantly correlated with a slower Q response time. Knee extension exercise at the same absolute intensity resulted in an ∼40% lower Q and greater ΔQ and ΔVA in HFpEF than in controls. Corticospinal excitability remained unaltered during exercise in both groups. Finally, despite a similar ΔVA, ΔQ was larger in HFpEF versus controls during isometric exercise. In conclusion, HFpEF patients are characterized by a similar development of central and peripheral fatigue as healthy controls when tested at the same relative intensity during exercise not limited by cardiac output. However, HFpEF patients have a greater susceptibility to neuromuscular fatigue during exercise at a given absolute intensity, and this impairs functional capacity. The patients' compromised Q response to exercise likely accounts, at least partly, for the patients' attenuated fatigue resistance. The susceptibility to neuromuscular fatigue during exercise is substantially exaggerated in individuals with heart failure with a preserved ejection fraction. The faster rate of fatigue development is associated with the compromised peripheral hemodynamic response characterizing these patients during exercise. Given the role of neuromuscular fatigue as a factor limiting exercise, this impairment likely accounts for a significant portion of the exercise intolerance typical for this population.