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
LAD TIMI flow grade 0-1No visible collaterals
0
1000
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6000 CK release
Adm.
4h 8h 12h
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54h
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66h
72h
ControlCsA
(UI/
L)
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Control
CsA
Adm.
4h 8h 12h
16h
20h
24h
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48h
54h
60h
66h
72h
TnI release
0
1.4.105
10 30 50 70ACS (%)
AU
C (
arb
itra
ry u
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s) 1.2.105
1.0.105
0.8.105
0.6.105
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controlCsA
CK release
00 20 40 60
1.2.105
1.0.105
0.8.105
0.6.105
0.4.105
0.2.105
AU
C (
arb
itra
ry u
nit
s)
TnI release
Reduction of cardiac enzymes release by cyclosporine APiot et al. NEJM 2008
0control cyclosporine
area
of
hyp
eren
han
cem
ent
(g)
10
20
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120
*
MRI infarct size (day 5)
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
*
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
*
MRI at 6 months after cyclosporine-treated MI
*
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
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