Effect of enhanced external counterpulsation on circulating CD34+ progenitor cell subsets

Enhanced external counterpulsation (EECP) is associated with improvement in endothelial function, angina and quality of life in patients with symptomatic coronary artery disease, although the mechanisms underlying the observed clinical benefits are not completely clear. The purpose of this study was to examine the effects of EECP on circulating haematopoietic progenitor cells (HPCs) and endothelial progenitor cells (EPCs) in patients with refractory angina. We compared HPC and EPC counts between patients scheduled for EECP and patients with normal angiographic coronary arteries, with and without coronary endothelial dysfunction. We hypothesized that an increase in circulating bone marrow derived progenitor cells in response to EECP may be part of the mechanism of action of EECP.

Thirteen consecutive patients scheduled to receive EECP treatment were prospectively enrolled. Clinical characteristics were recorded and venous blood (5 ml) was drawn on day 1, day 17, day 35 (final session) and one month post completion of EECP therapy. Buffy coat was extracted and HPCs and EPCs were counted by flow cytometry.

Median Canadian Cardiovascular Society (CCS) angina class decreased and Duke Activity Status Index (DASI) functional score increased significantly (both, p < 0.05) in response to EECP, an effect that was maintained at one month after termination of treatment. Flow cytometric analysis revealed an accompanying significant increase in CD34+, CD133+ and CD34+, CD133+ CPC counts over the course of treatment (p < 0.05). DASI scores correlated significantly with CD34+ (R = 0.38 p = 0.02), CD133+ (R = 0.5, p = 0.006) and CD34+, CD133+ (R = 0.47, p = 0.01) CPC counts.

This study shows that HPCs, but not EPCs are significantly increased in response to EECP treatment and correlate with reproducible measures of clinical improvement. These findings are the first to link the functional improvement observed with EECP treatment with increased circulating progenitor cells.