Heart failure with preserved ejection fraction diminishes peripheral hemodynamics and accelerates exercise-induced neuromuscular fatigue

Abstract

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 (QL) was quantified using Doppler ultrasound. Pre/postexercise changes in quadriceps twitch torque (ΔQtw; 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), ΔQtw (∼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 QL response time. Knee extension exercise at the same absolute intensity resulted in an ∼40% lower QL and greater ΔQtw and ΔVA in HFpEF than in controls. Corticospinal excitability remained unaltered during exercise in both groups. Finally, despite a similar ΔVA, ΔQtw 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 QL response to exercise likely accounts, at least partly, for the patients' attenuated fatigue resistance.NEW & NOTEWORTHY 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.

Keywords: exercise intolerance; fatigue; heart failure; hemodynamics.

Figures

Figure 1.

Schematic illustration of the 2 exercise protocols. Protocol A included the assessment of neuromuscular and corticospinal function before and after exercise. In protocol B, fatigue was quantified during exercise using femoral nerve stimulations (F). EMG, electromyography; MVC, maximal voluntary quadriceps contraction; T, transcranial magnetic stimulation; Tlim, time-to-task failure: 20% EMG contraction, 20% of the EMG attained during the preexercise MVC.

Figure 2.

Femoral blood flow (A and D), mean arterial pressure (B and E), and leg vascular conductance (C and F) in control participants (n = 8) and patients with heart failure with preserved ejection fraction (HFpEF; n = 8) during dynamic knee extension exercise at the same relative intensity (A–C) and the same absolute (D–F) work rate. Main effects were determined via 2-way mixed-model ANOVAs (group × time). Data are presented as means ± SD.

Figure 3.

A and B: representative (A) and group mean (B) data for the femoral blood flow mean response time in healthy controls (n = 8) and patients with heart failure with preserved ejection fraction (HFpEF; n = 8). C: correlation between peripheral fatigability [i.e., change in quadriceps twitch torque (Qtw) from baseline per unit of work] and the mean response time of femoral blood flow for these participants. A Mann-Whitney U test was utilized to determine differences between groups (B), and a Pearson product-moment correlation was used to assess the correlation between the mean response time and fatigability (C). Data are presented as means ± SD. *Significantly different from HFpEF, P < 0.05.

Figure 4.

Pre- to postexercise changes in neuromuscular function in control (open bars; n = 8) and patients with heart failure with preserved ejection fraction (HFpEF; filled bars; n = 8) performed at a given relative exercise intensity (left) or absolute work rate (right). Group differences were determined by independent group t tests. Data are presented as means ± SD. #Not significantly changed from preexercise, P > 0.2; *significantly different from HFpEF, P < 0.05.

Figure 5.

Second-by-second plots of heart rate (A), stroke volume (B), cardiac output (C), mean arterial pressure (D), and systemic vascular conductance (E) for controls (open bars; n = 8) and patients with heart failure with preserved ejection fraction (HFpEF; filled bars; n = 8). Shaded regions represent the maximal 15-s isometric contraction. Main effects were determined via 2-way mixed-model ANOVAs (group × time); independent group t tests were used to determined group differences for the area under the curve for each variable (A–E; presented in bar graph at the right). Data are presented as means ± SD, except that the SD was omitted in the across-time figures for clarity. *Significant difference between groups, P < 0.05.

Figure 6.

Development of central and peripheral fatigue during the intermittent isometric exercise protocol (A, C, and E) and the ensuing pre- to postexercise change (B, D, and F) in neuromuscular function for controls (n = 8) and patients with heart failure with preserved ejection fraction (HFpEF; n = 8). Main effects were determined via 2-way mixed-model ANOVAs (group × time) for A, C, and E; independent group t tests were used to assess group differences in the pre- to postexercise change in neuromuscular function (B, D, and F). Data are presented as means ± SD. *Significant difference between groups, P < 0.05.