Cyclosporine A reduces infarct size

Cyclosporine A reduces infarct sizeand has no detrimental effect of LV

remodeling in STEMI patients

Michel OvizeCardiology Hospital and Inserm U886

Lyon University, France

Previous work by Piot et al. (NEJM 2008)Objective: determine whether cyclosporine A can reduce infarct size in STEMI patients

Direct stenting

Coronary artery occlusion Reperfusion

t0t-10 min

Cyclosporine A (or saline)(2.5 mg/kg, IV bolus)

Day 1-3CK / TnI release

Day 5MRI

Infarct size

STEMI < 12 hrsPCI treatment

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Reduction of cardiac enzymes release by cyclosporine APiot et al. NEJM 2008

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Piot et al. NEJM 2008;359:473-81

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

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

PCI

Coronary artery occlusion Reperfusion

t0t-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

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Control Cyclosporine

Mewton et al. (JACC 2010)

Cyclosporine in acute myocardial infarction

PCI

Coronary artery occlusion Reperfusion

t0t-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

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

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

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

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MRI at 6 months after cyclosporine-treated MI

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Mewton et al. (JACC 2010)

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

Michel OVIZE, MD, PhD