Effects of enhanced external counterpulsation on skeletal muscle gene expression in patients with severe heart failure

Enhanced external counterpulsation (EECP) is a non-invasive treatment in which leg cuff compressions increase diastolic aortic pressure and coronary perfusion. EECP is offered to patients with refractory angina pectoris and increases physical capacity. Benefits in heart failure patients have been noted, but EECP is still considered to be experimental and its effects must be confirmed. The mechanism of action is still unclear. The aim of this study was to evaluate the effect of EECP on skeletal muscle gene expression and physical performance in patients with severe heart failure. Patients (n=9) in NYHA III-IV despite pharmacological therapy were subjected to 35h of EECP during 7weeks. Before and after, lateral vastus muscle biopsies were obtained, and functional capacity was evaluated with a 6-min walk test. Skeletal muscle gene expression was evaluated using Affymetrix Hugene 1.0 arrays. Maximum walking distance increased by 15%, which is in parity to that achieved after aerobic exercise training in similar patients. Skeletal muscle gene expression analysis using Ingenuity Pathway Analysis showed an increased expression of two networks of genes with FGF-2 and IGF-1 as central regulators. The increase in gene expression was quantitatively small and no overlap with gene expression profiles after exercise training could be detected despite adequate statistical power. EECP treatment leads to a robust improvement in walking distance in patients with severe heart failure and does induce a skeletal muscle transcriptional response, but this response is small and with no significant overlap with the transcriptional signature seen after exercise training.