1. Cyclosporine A reduces infarct size and has no detrimental effect of LV remodeling in STEMI patients Michel Ovize Cardiology Hospital and Inserm U886 Lyon University, France

2. Previous work by Piot et al. (NEJM 2008) Objective: determine whether cyclosporine A can reduce infarct size in STEMI patients Direct stenting Coronary artery occlusionReperfusion t0t0 t -10 min Cyclosporine A (or saline) (2.5 mg/kg, IV bolus) Day 1-3 CK / TnI release Day 5 MRI Infarct size STEMI < 12 hrs PCI treatment LAD TIMI flow grade 0-1 No visible collaterals

3. 0 1000 2000 3000 4000 5000 6000 CK release Adm. 4h 8h 12h 16h20h 24h 30h 36h42h48h54h 60h 66h72h Control CsA (UI/L) 0 50 100 150 200 250 Control CsA Adm. 4h 8h 12h 16h 20h 24h 30h 36h42h48h 54h 60h 66h72h TnI release 0 1.4.10 5 10305070 ACS (%) AUC (arbitrary units) 1.2.10 5 1.0.10 5 0.8.10 5 0.6.10 5 0.4.10 5 0.2.10 5 control CsA CK release 0 0204060 1.2.10 5 1.0.10 5 0.8.10 5 0.6.10 5 0.4.10 5 0.2.10 5 AUC (arbitrary units) TnI release Reduction of cardiac enzymes release by cyclosporine A Piot et al. NEJM 2008

4. 0 control cyclosporine area of hyperenhancement (g) 10 20 30 40 50 60 70 120 * MRI infarct size (day 5) Piot et al. NEJM 2008;359:473-81

5. Mewton et al. J Am Coll Cardiol 2010;55:1200–5

6. Rationale CsA can reduce infarct size in STEMI patients. It is therefore expected that this protective effect may be associated with a reduced adverse LV remodeling However, experimental evidence indicates that CsA, via anti-hypertrophic mechanisms, may favor an adverse remodeling response of the LV after STEMI We then assessed LV volumes and wall thickness by MRI at 5 days and 6 months after AMI in a population of patients that had received CsA as an adjunct to PCI revascularization

7. PCI Coronary artery occlusionReperfusion t0t0 t -10 min Cyclosporine A or saline Day 5 MRI 6 Month MRI Follow up CMR at 6 months post-MI Mewton et al. JACC 2010

8. * Control Cyclosporine

10. Mewton et al. (JACC 2010) Cyclosporine in acute myocardial infarction

11. PCI Coronary artery occlusionReperfusion t0t0 t -10 min Cyclosporine A Day 5 MRI 6 Month MRI Follow up CMR at 6 months post-MI Mewton et al. J Am Coll Cardiol 2010;55:1200–5

12. There was a significant correlation between left ventricular end-diastolic volume (LVEDV) and infarct size at 6 months (r2=0.40; p<0.05) in the whole group of patients

13. There was a significant correlation between left ventricular end-systolic volume (LVESV) and infarct size at 6 months (r2=0.66; p<0.05) in the whole group of patients

14. There was a significant correlation between left ventricular ejection fraction (LVEF) and infarct size at 6 months (r2=0.72; p<0.05) in both groups of patients

15. * MRI at 6 months after cyclosporine-treated MI * Mewton et al. (JACC 2010)

16. Conclusion Cyclosporine used at the moment of acute myocardial infarction reperfusion reduces infarct size and does not have a detrimental effect of LV remodeling. These results obtained from a limited population of patients must be confirmed by large-scale trials

17. Michel OVIZE, MD, PhD