1. Francone M, Bucciarelli-Ducci C*, Carbone I, Canali E, Scardala R, Calabrese F, Sardella G, Mancone M, Catalano C, Fedele F, Passariello R, Bogaert J** and Agati L Impact Of Primary Coronary Angioplasty Delay On Myocardial Salvage, Infarct Size And Microvascular Damage in Patients with ST-Elevation Myocardial Infarction: Insight From Cardiovascular Magnetic Resonance *Royal Brompton Hospital, National Heart and Lung Institute, Imperial College London, United Kingdom **Leuven University, Belgium Umberto I Hospital, University “La Sapienza”, Rome, Italy

2. Time is muscle De Luca, Circulation 2004 Background

3. Challenges Background What happens to the muscle? How to recognize salvageable myocardium? How much salvageable myocardium is there?

4. Background Kim RJ et al, Circulation 1999 Aletras AH et al, Circulation 2006 Rochitte C et al, Circulation 1998 MICROVASCULAR DAMAGE MYOCARDIAL NECROSIS MYOCARDIUM AT RISK

5. Aims of the Study 1.To investigate the correlation between the extent and the nature of myocardial damage in relation to different time-to- reperfusion intervals 2.To investigate the relationship between time-to-reperfusion intervals, myocardial damage and subsequent LV remodeling

6. Study Protocol n=70 STEMI, primary PCI ≤90min n=19 >90-150min n=17 >150-360min n=17 >360min n=17 Time-to-reperfusion

7. CMR Protocol Cine 6 months3±2 days

8. CMR Protocol 3±2 days T2 wT1 w gadolinium increased signal intensity (myocardial edema) Myocardium at risk increased signal intensityreduced signal intensity Infarct SizeMicrovascular Obstruction

9. Results: Myocardium at Risk Myocardial Edema (% LV) Time to reperfusion (min) p=0.37

10. Results: Infarct Size Infarct Size (% LV) Time to reperfusion (min) p=0.005 * * p=0.002

11. Myocardium at Risk – Infarct size Time to reperfusion (min)

12. Myocardial Salvage (%) Time to reperfusion (min) p=0.003 * * p=0.001

13. Microvascular Obstruction MVO (% LV) Time to reperfusion (min) p=0.04 * * p=0.001

14. EDV: Baseline ≤90 min>90-150 min>150-360 min>360 min Time to reperfusion (min) EDV (ml) p=0.03

15. EDV: Baseline vs 6 Months ≤90 min>90-150 min>150-360 min>360 min Time to reperfusion (min) EDV (ml) p=0.002 p=0.005 p=0.05 p=0.003 Baseline 6 months

16. ESV: Baseline ≤90 min>90-150 min>150-360 min>360 min Time to reperfusion (min) ESV (ml) p=0.02

17. ESV: Baseline vs 6 Months ≤90 min>90-150 min>150-360 min>360 min Time to reperfusion (min) ESV (ml) p=0.003 p=0.006 p=0.001 p=0.06 Baseline 6 months

18. EF: Baseline ≤90 min>90-150 min>150-360 min>360 min Time to reperfusion (min) EF (%) p=0.06

19. EF: Baseline vs 6 Months ≤90 min>90-150 min>150-360 min>360 min Time to reperfusion (min) EF (%) p=0.04 p=ns p=0.04 Baseline 6 months

20. LAD Infarctions ≤90 min>90-150 min>150-360 min>360 min Time to reperfusion (min) * MVO Myocardium at Risk Infarct Size

21. Non-LAD Infarctions ≤90 min>90-150 min>150-360 min>360 min Time to reperfusion (min) * MVO Myocardium at Risk Infarct Size

22. Conclusions-1  First in-vivo, clinical, non invasive evaluation of the consequences of early and delayed coronary reperfusion on myocardial damage

23. Conclusions-2  Time is muscle Longer time-to-reperfusion (>360min) Less salvaged myocardium Larger infarct size and more MVO LV remodeling  Myocardial salvage, infarct size and MVO by CMR surrogate endpoints for clinical trials assessing the efficacy of reperfusion strategies