P3670Effect of cyclosporine on lymphocyte kinetics and left ventricular remodelling in patients with acute myocardial infarction

Abstract

Background: Following a favourable Pilot study by Piot et al. using a single‐bolus of cyclosporine, it has been unclear why two large studies (CYCLE and CIRCUS) failed to prevent reperfusion injury in myocardial infarction (MI). OBJECTIVES The single centre, double‐blinded CAPRI Pilot study investigated the effect of a single bolus cyclosporine before reperfusion on infarct size and LV‐remodelling by cardiac MRI in patients with acute STEMI undergoing primary PCI for ST‐segment elevation MI. In addition, lymphocyte kinetics during the reperfusion phase were quantified by flow cytometry. Methods: We randomly assigned 52 acute STEMI patients with an onset of pain of less than 6h and blocked culprit artery to a single bolus of cyclosporine (n=26) or placebo (n=26) prior to reperfusion by stent PCI. The primary endpoint was infarct size at 12 weeks. Results: Infarct size at 12 weeks was identical in both groups (9.1%±0.7 vs 9.1%±0.7, p=0.99). However, remodelling appeared more favourable in the cyclosporine group with reduced end‐systolic (‐12.2 vs +1.4 ml) as well as enddiastolic volumes (‐2.0 vs +9.1 ml) after 3 months compared to 2‐7 days post infarction. Accordingly, ejection fraction also improved in the cyclosporine group (+6.3% vs +2.0%). CD4 T‐lymphocytes dropped by 30% post reperfusion to similar levels at 90 min (867 vs 852 cells/ul). Reactive proliferation of CD4 T‐cells between 90 min and 24 hours post reperfusion was reduced in the cyclosporine group when compared to placebo (+344 vs +520 cells/ul). Conclusions: In our CAPRI Pilot trial a single cyclosporine bolus did not affect acute reperfusion injury. Despite identical scar size in both groups, remodelling was more favourable in the cyclosporine group and coincided with less CD4 T‐cell proliferation at 24h. Proinflammatory CD4 T‐lymphocytes might provide a genuine target after STEMI in order to improve left ventricular remodelling.