P2686Endothelial reaction mediates enhanced external counterpulsation effects in post-MI cardiac rehabilitation

Abstract

Abstract Introduction The mechanisms mediating benefits of enhanced external counterpulsation (EECP) are disputable since the origin of the method. One of the possible explanations presumes increased diastolic flow leads to changes of endothelial function and plays a crucial role in alleviating the symptoms of angina and heart failure; the exact mechanisms of action are still under investigation, though the endothelial hypothesis possesses strong evidence. Purpose To reveal the impact of repeated EECP on endothelial function of patients undergoing cardiac rehabilitation program after myocardial infarction (MI) and to identify possible clinical implications of these changes. Methods The randomized sham-controlled study included 46 patients with coronary artery disease who suffered from ST-elevation MI (STEMI) 4–8 weeks prior to enrollment in 2017–2018. All patients had undergone primary PCI due to STEMI in 2–24 hours after the event. Echo parameters, exercise tolerance and the levels of ADMA and nitric oxide (NO) metabolites (total content, nitrite and nitrate) in plasma were determined at the enrollment stage and at three month follow-up. Patients were randomized and given 35 h of active counterpulsation (main group, n=24) or inactive counterpulsation (control group, n=22) over a six-week period after enrollment. Results The analysis showed no significant difference between groups at baseline: mean ejection fraction was 46% in the main group and 45% in the control group, no difference in exercise tolerance. The mean characteristics of endothelial function at baseline were similar in both main and control groups: total NO metabolites (17.3±2.14 μmol/L vs. 19.6±3.31, p=0. 42), nitrite level (0.76±0.17 μmol/L vs. 0.75±0.21, p=0. 36), ADMA level (0.78±0.15 μmol/L vs. 0.81±0.20, p=0. 22). At three month follow up 41,7% of patients of the main group showed improvement of one class of NYHA classification compared to 22,7% in the control group (U=122.3, p=0.012), agreed with improved exercise tolerance: average +2.8 MET in main group in opposite to only +0.8 MET in the controls (U=104, p=0.007). Control group demonstrated no significant dynamics of NO metabolites concentration comparing to baseline values, while in the main group there was a significant decrease of ADMA – 0.57±0.11 μmol/L (Z=r=−2.46, p=0.013) and increase of nitrite level – 1,12±0. 18 μmol/L (Z=r=−2.57, p=0.011), with no changes in total NO metabolites content. The further analysis demonstrated strong correlation between exercise capacity gain and ADMA decrease (R=r=−0.52, p=0.008) or nitrite elevation (R=0.48, p=0.012), with ADMA/nitrite ratio being the strongest predictor of clinical improvement (R=0.68, p=0.002). Conclusion Active EECP improves exercise capacity and heart failre symptoms in patients undergoing post-MI rehabilitation, with those effects being associated with endothelial function enhancement.