Improved Ventilatory Efficiency with Locomotor Muscle Afferent Inhibition is Strongly Associated with Leg Composition in Heart Failure

Background: Skeletal muscle atrophy contributes to increased afferent feedback (group III and IV) and may influence ventilatory control (high V_E/VCO₂ slope) in heart failure (HF). Objective This study examined the influence of muscle mass on the change in V_E/VCO₂ with afferent neural block during exercise in HF. Methods: 17 participants [9 HF (60 ± 6 yrs) and 8 controls (CTL) (63 ± 7 yrs, mean ± SD)] completed 3 sessions. Session 1: dual energy x-ray absorptiometry and graded cycle exercise to volitional fatigue. Sessions 2 and 3: 5 min of constant-work cycle exercise (65% of peak power) randomized to lumbar intrathecal injection of fentanyl (afferent blockade) or placebo. Ventilation (V_E) and gas exchange (oxygen consumption, VO₂; carbon dioxide production, VCO₂) were measured. Results: Peak work and VO₂ were lower in HF (p < 0.05). Leg fat was greater in HF (34.4 ± 3.0 and 26.3 ± 1.8%) and leg muscle mass was lower in HF (63.0 ± 2.8 and 70.4 ± 1.8%, respectively, p < 0.05). V_E/VCO₂ slope was reduced in HF during afferent blockade compared with CTL (- 18.8 ± 2.7 and - 1.4 ± 2.0%, respectively, p = 0.02) and was positively associated with leg muscle mass (r² = 0.58, p < 0.01) and negatively associated with leg fat mass (r² = 0.73, p < 0.01) in HF only. Conclusions: HF patients with the highest fat mass and the least leg muscle mass had the greatest improvement in V_E/VCO₂ with afferent blockade with leg fat mass being the only predictor for the improvement in V_E/VCO₂ slope. Both leg muscle mass and fat mass are important contributors to ventilatory abnormalities and strongly associated to improvements in V_E/VCO₂ slope with locomotor afferent inhibition in HF.