Skeletal muscle transcriptomes associate with physiological and clinical profiles in patients undergoing cardiac pacemaker implantation.
N Almulhim, C W Cheng, F Bartoli, N Makava, O I Brown, S Straw, S Kamalathasan, M Paton, R Cubbon, K Witte, M T Kearney, D J Beech, J GierulaAbstract
Background
Exercise intolerance is an adverse quality of life factor in heart failure arising from relationships between cardiovascular and skeletal muscle functions that are incompletely understood. Transcriptomic variability uncovers underlying gene expression patterns that could inform understanding of altered muscle function. In this exploratory study, skeletal muscle transcriptomes were examined in individuals undergoing implantation of a cardiac implantable electronic device (CIED).
Aim
To explore relationships between gene expression and demographics, clinical and biochemical markers and exercise physiological variables in people with and without heart failure with reduced ejection fraction (HFrEF).
Methods
Chest skeletal muscle samples were obtained with ethical approval for 30 participants. Cardiopulmonary exercise testing was performed after CIED implantation. RNA was isolated and RNA-sequencing performed. Transcriptomes were filtered to focus on robust gene expression that was classified as observations. Normalized observations were subjected to Principal Component (PC) analysis. Leading PCs were compared to participant demographics, laboratory biomarkers including Hb and electrolytes, left ventricular ejection fraction, physiological variables measured during exercise testing, and exposure to medications.
Results
PC1 was the largest source of transcriptome variations associated with participant age (r = 0.45, p = 0.012) and negatively associated with ACEi medication (r= -0.42, p = 0.02). Physiological measures obtained from exercise testing (peak VO2, AT, change in BB and HR) aligned most with PC5, while PC4 showed negative associations to these measures and positive association with female biological sex (r= 0.58, p <0.001).
Conclusion
Skeletal muscle transcriptome profiles associate with age and biological sex while contrasting profiles shape physiological and functional exercise capacity. Further studies will explore validation strategies and the biological pathways of the leading gene expression candidates.