Functional capacity and skeletal muscle morphology are linked to N-terminal proBNP but not left ventricular ejection fraction in patients with heart failure

Chronic heart failure (CHF) involves skeletal muscle abnormalities, including atrophy, inflammation, mitochondrial dysfunction, and fibrosis, which impair contractile function. This study examines whether muscle deterioration correlates with CHF disease severity by assessing the relationship between circulating N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations, left ventricular ejection fraction (LVEF), and muscle characteristics in patients with CHF. In 36 patients with CHF (LVEF ≤ 45%, New York Heart Association class I-III), we measured circulating NT-proBNP concentrations, LVEF, muscle strength and functional measures, and myocellular features, including fiber type-specific cross-sectional area (CSA), muscle stem cell (MuSC) and myonuclei content, and capillary density. Also, muscle mitochondrial function was evaluated. The concentration of NT-proBNP inversely correlated with muscle strength (<i>R</i>² = 0.25, <i>P</i> < 0.01), mean fiber CSA (<i>R</i>² = 0.15, <i>P</i> = 0.04), and MuSC content (<i>R</i>² = 0.37, <i>P</i> < 0.01). Moreover, a nonsignificant inverse correlation was observed for capillary density (<i>R</i>² = 0.12, <i>P</i> = 0.06). The strength of associations between NT-proBNP, fiber CSA, and capillary density was primarily driven by fiber type-specific correlations. Associations with MuSC content were equally strong across fiber types. No correlation was observed for measures of mitochondrial function. For LVEF, a nonsignificant correlation was observed only for overall MuSC content (<i>R</i>² = 0.11, <i>P</i> = 0.07). Skeletal muscle deterioration in patients with CHF correlates with NT-proBNP, but not LVEF, suggesting that NT-proBNP concentration constitutes a stronger indicator of the link between CHF severity and skeletal muscle decline than LVEF as function parameter. Our findings highlight circulating NT-proBNP concentrations as a potential biomarker for the identification of patients at risk of experiencing skeletal muscle deterioration.<b>NEW & NOTEWORTHY</b> In this study, the authors reveal that elevated NT-proBNP levels are inversely associated with muscle function and cellular features in patients with chronic heart failure (CHF), including muscle fiber cross-sectional area, muscle stem cell content, and capillarization. NT-proBNP appears to be a more reliable marker than left ventricular ejection fraction (LVEF) for identifying skeletal muscle abnormalities and predicting muscle loss in CHF, offering potential for early intervention and personalized care.