Association of sarcopenia and oxygen uptake efficiency slope in male patients with heart failure: The skeletal muscle hypothesis in practice
Authors: Fonseca GWP , Bispo HN , Rondon E , Dos Santos MR , De Souza FR , Da Costa MJA , Carson BP , Pereira RMR , Negrao CE , Alves MJNN 
Published: May 2022

Abstract

Funding Acknowledgements
Type of funding sources: Foundation. Main funding source(s): Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Background
Sarcopenia, a generalized loss of muscle mass and function, is a common comorbidity in patients with heart failure (HF). The skeletal muscle, through afferent nerve pathways, modulates the respiratory response during physical efforts. However, whether ventilatory behavior is affected by the presence of sarcopenia is still unknown.

Purpose
To evaluate the impact of sarcopenia in ventilatory parameters of patients with HF.

Methods
We enrolled 169 male patients with stable chronic HF with left ventricular ejection fraction &lt;40% (LVEF). Muscle strength was measured by handgrip dynamometer. Body composition was measured with dual-energy X-ray absorptiometry (DXA). Appendicular skeletal muscle (ASM) was comprised by lean muscle mass of both arms and legs. Sarcopenia was defined by handgrip strength and ASM/height2 lower than 27 kg and 7.0 kg/m2, respectively. Ventilation (VE), oxygen consumption (VO2), and carbon dioxide output (VCO2) were evaluated using breath-by-breath measurements during a cardiopulmonary exercise test performed on a cycle ergometer. Oxygen uptake efficiency slope (OUES) was calculated from data taken at exercise peak.

Results
Sarcopenia was identified in 29 patients (17.2%). Patients with sarcopenia had lower body mass index (BMI; 21.2±2.4 vs. 26.5±3.8 kg/m2, p&lt;0.0001) with higher C-reactive protein [CRP; 12.4 (2.8-22.4) vs. 2.4 (1.0-6.3) mg/L, p&lt;0.001] and brain natriuretic peptide [BNP; 949 (446-1722) vs. 374 (127-885) pg/mL, p&lt;0.001] compared to patients without sarcopenia, respectively. At the first ventilatory threshold, VE/VO2 (36.9±5.9 vs. 32.7±6.5, p=0.003) and VE/VCO2 (39.8±7.2 vs. 35.3±6.9, p=0.004) were higher in sarcopenic patients compared to those without sarcopenia. At the exercise peak, comparing to patients without sarcopenia, sarcopenic patients had lower OUES (1,186±295 vs. 1,634±564, p&lt;0.001), absolute VO2 (0.93±0.25 vs. 1.43±0.47 L/min, p&lt;0.0001), relative VO2 (16.2±5.0 vs. 19.5±6.5 ml/kg/min, p=0.011), and VE (47.3±10.1 vs. 63.0±18.2 L/min, p&lt;0.001), while VE/VCO2 (42.9±8.9 vs. 38.7±8.4, p=0.025) was increased and VE/VO2 (49.6±11.5 vs. 45.1±10.8, p=0.066) showed a tendency to be higher. OUES was positively correlated with total lean body mass (r=0.38; p&lt;0.0001), ASM/height2 (r=0.36; p&lt;0.0001), and handgrip strength (r=0.31; p&lt;0.001). In a multivariate logistic regression model using OUES as the dependent variable, ASM/height2 (OR, 1.466; 95% CI, 1.003–2.141; p=0.048), haemoglobin (OR, 0.346; 95% CI, 0.135–0.886; p=0.027), and creatinine (OR, 0.391; 95% CI, 0.166–0.918; p=0.031) were independently associated with OUES adjusted by age, BMI, LVEF, BNP, CRP, and beta-blocker use.

Conclusion
Our results suggest that sarcopenia, possibly by reducing thoracic skeletal muscle mass or inefficiently modulating ventilation through afferent pathways, is related to impaired ventilatory response during exercise in patients with HF.