Impact of HFpEF on the Development of Neuromuscular Fatigue during Exercise
Authors: Weavil Joshua C , Thurston Taylor S , Hureau Thomas J , Gifford Jayson R , Bledsoe Amber D , Nativi Jose N , Richardson Russell S , Amann Markus 
Published: November 2023

BACKGROUNDPatients with heart failure and a preserved (≥50%) ejection fraction (HFpEF) suffer from severe exercise intolerance. Although the exact mechanisms accounting for this impairment are not fully understood, an exaggerated development of neuromuscular fatigue during physical activity may play a critical role.PURPOSETo examine the influence of HFpEF on the development of neuromuscular fatigue during exercise characterized by a small muscle mass and, subsequently, minimal central hemodynamic (i.e. cardiac output) constraints.METHODSSeven HFpEF (64 ± 1 yr) and 7 age‐matched controls (CON) performed dynamic single‐leg knee extensor exercise (KE) to exhaustion at a given relative intensity (80% Wpeak; DYN), and intermittent maximal isometric knee extensions (8×15 s, 20 s rest, ISO). CON repeated DYN at the same absolute work rate and same duration as HFpEF. Quadriceps fatigue was quantified as pre‐ to post‐exercise decrease in maximum voluntary contraction torque (MVC). Peripheral and central fatigue were quantified via pre‐ to post‐exercise changes in quadriceps twitch torque (Qtw; electrical femoral nerve stimulation) and voluntary quadriceps activation (VA). Maximal rate of torque development (MRTD) and peak relaxation rate (PRR) were derived from the Qtw kinetics.RESULTSDYNWpeak was higher in CON compared to HFpEF (53 ± 2 W vs 31 ± 3 W; P < 0.01). When the exercise was matched in terms of absolute work rate (24 ± 2 W) and duration (10 ± 1 min), patients with HFpEF demonstrated a greater exercise‐induced reduction in MVC (‐30 ± 4% vs ‐6 ± 4%) and QTW (−54 ± 6% vs −11 ± 4%) compared to CON (all P < 0.05); VA was not affected in either group. At the same relative intensity (80% Wpeak, corresponding to 24 ± 2 W and 43 ± 2 W in HFpEF and CON, respectively), task failure occurred at a comparable time (~10 min, P = 0.53) and both groups demonstrated a similar exercise‐induced reduction in MVC (~27%) and QTW (~50%) (P > 0.4). However, compared to CON, HFpEF exhibited a significantly greater exercise‐induced reduction in MRTD (−67 ± 5% vs −47 ± 6%) and PRR (−61 ± 5% vs −37 ± 4%). VA fell significantly in CON (−6 ± 2%), but remained unaltered in HFpEF (P = 0.23).ISOQuadriceps MVC was similar between groups at baseline (~160 Nm; P = 0.68). Although the exercise did not affect VA in either group (P > 0.12), HFpEF demonstrated a greater exercise‐induced reduction in MVC (−26 ± 4% vs −13 ± 4%), QTW (−49 ± 4% vs −23 ± 7%), MRTD (−53 ± 6% vs –20 ± 9%), and PRR (−51 ± 7% vs –26 ± 7%) (all P < 0.05) compared to CON.CONCLUSIONDuring physical activity characterized by minimal central hemodynamic constraint, HFpEF patients exhibit a compromised functional capacity compared to CON and an exacerbated development of neuromuscular fatigue during exercise at a given absolute workload. Furthermore, although the development of fatigue is similar between HFpEF and CON during dynamic small muscle mass exercise performed at the same relative intensity, it is critical to emphasize that the absolute workload at a given relative intensity is substantially lower in the patients. This finding further highlights the greater susceptibility to fatigue in this population. Consequently, targeting abnormalities within the skeletal muscle may be a priority in improving exercise tolerance in HFpEF.Support or Funding InformationThis study was supported by National Heart, Lung, and Blood InstituteGrants HL‐103786, HL‐116579, and HL‐091830, Veterans Affairs Merit GrantE6910R, and Veterans Affairs SPiRE Grant E1572P.