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

2000

3000

4000

5000

6000 CK release

Adm.

4h 8h 12h

16h

20h

24h

30h

36h

42h

48h

54h

60h

66h

72h

ControlCsA

(UI/

L)

0

50

100

150

200

250

Control

CsA

Adm.

4h 8h 12h

16h

20h

24h

30h

36h

42h

48h

54h

60h

66h

72h

TnI release

0

1.4.105

10 30 50 70ACS (%)

AU

C (

arb

itra

ry u

nit

s) 1.2.105

1.0.105

0.8.105

0.6.105

0.4.105

0.2.105

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

30

40

50

60

70

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