Key result
HFrEF-associated skeletal muscle gene changes correlate with worse LV remodeling and lower LVEF.
Why the study?
Although studies have highlighted skeletal muscle transcriptomic changes in chronic heart failure, it remained unclear whether these transcriptomes reflect coherent structural and physiological alterations and align with clinical phenotypes and indicators of cardiovascular reserve.
Observational (n=30)
Skeletal muscle transcriptomic alterations in HFrEF correlate with echocardiographic and clinical indicators of disease severity, suggesting peripheral molecular changes reflect systemic physiological stress.
Answers are grounded in this paper and cite their sources.
Correlations between muscle DEGs and LV measures should not alter practice; hypothesis-generating for transcriptomic biomarkers in HFrEF severity assessment.
Background Skeletal muscle (SKM) remodelling is recognised as a contributor to exercise intolerance in chronic heart failure (CHF). Although studies have highlighted SKM transcriptomic changes in CHF, it remains unclear whether CHF associated transcriptomes reflect coherent structural and physiological alterations, and whether transcriptomic patterns are consistent with clinical phenotypes Purpose To explore the relationship between differentially expressed SKM transcriptomes identified in CHF and the clinical indicators of cardiovascular reserve. Methods Pectoralis SKM biopsies obtained from individuals undergoing cardiac implantable electronic device implantation. RNA sequencing was performed and differential expression analysis using DESeq2 encountered the main confounders and identified nine differently expressed gens (DEGs) that associated with HFrEF at FDR <0.05. Spearman correlation analysis was performed to examine the association between DEGs and key demographics, comorbidities, blood biomarkers, echocardiographic parameters and cardiopulmonary exercise testing indices. Results Biopsies were obtained from 30 individuals HFrEF n= 16 (53%) non-HF n=14 (47%). Several HFrEF associated DEGs exhibited divergent associations, including positive correlation with left ventricular internal diastolic diameter (r= 0.40 to 0.44, p <0.05), and negative correlation with left ventricular ejection fraction (r= -0.38 to -0.56, p < 0.05). Identified DEGs shows positive association with NYHA class. Limited negative association were observed between individual DEGs and exercise capacity measures. Stronger transcriptomic correlations were observed between DEGs (r= 0.39 to 0.91, p < 0.05). Conclusion Identified SKM transcriptomics alterations in HFrEFclosely reflect the clinical indicators of disease severity and cardiovascular reserve. We suggest that peripheral molecular alterations reflect the systemic physiological stress in HFrEF, these findings warrant further validation in larger, independent cohorts.
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Almulhim et al. (2026) conducted an observational in Chronic heart failure (HFrEF) (n=30). HFrEF-associated differentially expressed skeletal muscle genes vs. Non-HF individuals was evaluated on Association between HFrEF-associated differentially expressed skeletal muscle genes and clinical indicators of cardiovascular reserve (LVIDD, LVEF, NYHA class, exercise capacity) (r = -0.38 to -0.56 (with LVEF); r = 0.40 to 0.44 (with LVIDD), p=<0.05). HFrEF-associated skeletal muscle differentially expressed genes correlated positively with LVIDD and negatively with LVEF.
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