1. Cardioprotective Effects of Postconditioning in Patients Treated with Primary PCI Evaluated with Magnetic Resonance Jacob T Lønborg Niels Vejlstrup, Erik Jørgensen, Steffen Helqvist, Kari Saunamäki, Peter Clemmensen, Lene Holmvang, Marek Treiman, Jan S Jensen, Henning Kelbæk Niels Vejlstrup, Erik Jørgensen, Steffen Helqvist, Kari Saunamäki, Peter Clemmensen, Lene Holmvang, Marek Treiman, Jan S Jensen, Henning Kelbæk, Thomas Engstrøm Department of Cardiology RigshospitaletCopenhagenDenmark

2. POSTCON Copenhagen University Hospital Presenter Disclosure The authors have no disclosures with regard to the conduct of this study

3. POSTCON Copenhagen University Hospital Background Zhao et al., 2003

4. POSTCON Copenhagen University Hospital Background Zhao et al., 2003

5. POSTCON Copenhagen University Hospital Postconditioning has been suggested to reduce myocardial damage during PPCI in patients with ST- segment elevation myocardial infarction (STEMI) However clinical experience is limited Background

6. POSTCON Copenhagen University Hospital Conventional treatment coronary artery ReperfusionOccluded Postconditioning Post- conditioning 30 30 sec30 Balloon inflations - deflations

7. POSTCON Copenhagen University Hospital STEMI - PPCI Randomization Postconditioning Conventional treatment Continue standard treatment Balloon inflation 30 sec / reperfusion 30 sec Continue standard treatment Postconditioning

8. POSTCON Copenhagen University Hospital Patients who presented with symptoms and signs of their first STEMI Chest pain for less than 12 hours TIMI 0-I (range 0-III) in the infarct related artery Major inclusion criteria

9. POSTCON Copenhagen University Hospital Major exclusion criteria History of a previous myocardial infarction Left main stenosis Spontaneous reperfusion before intervention (TIMI II-III) Multivessel disease (any other stenosis > 70%) Cardiogenic shock Stent thrombosis

10. POSTCON Copenhagen University Hospital Endpoints Primary: Infarct size measured with CMR 3 months after the initial procedure (analysis blinded)

11. POSTCON Copenhagen University Hospital Endpoints Secondary: Cardiac death after 1 and 15 months Clinical status after 3 months (angina, heart failure) TLR during hospitalization, after 1 and 15 months Re-infarction during hospitalization, after 1 and 15 months LVEF by CMR

12. POSTCON Copenhagen University Hospital Screened patients 530 Eligible patients 118 Did not meet inclusion criteria 412 - 123 TIMI > 1 before PCI - 64 no myocardial infarction - 44 multiple vessel disease - 39 linguistic problems - 28 duration of symptoms >12 hours - 28 cardiogenic shock - 27 did not meet inclusion criteria - 23 unconsciousness - 17 refused to participate - 12 stentthrombosis - 11 vessel unsuitable for postconditioning - 24 no reason reported 2 deaths 30 lost to CMR - 15 logistic problems - 6 claustrophobia - 3 pacemaker implantation - 3 nephropathy - 3 technical difficulties 86 patients for CMR 116 patients for 3-month clinical follow-up Flow Chart

13. POSTCON Copenhagen University Hospital Mean age (yrs) Male gender (%) Diabetes (%) Hypertension (%) Treatment for hyperlipidemia (%) Current smoker (%) Family history of CAD (%) Previous myocardial infarction (%) Previous PCI (%) Symptom onset to balloon (min) Time to CMR (days) Use of GP IIb/IIIa inhibitor (%) Use of bivalirudin (%) 61 69 7 37 46 61 37 10 7 241 ± 149 83 ± 20 83 7 62 74 7 32 41 49 31 7 8 255 ±196 84 ± 18 83 12 p ns Baseline clinical demography Post- conditioning n = 59 Conventional Treatment n = 59

14. POSTCON Copenhagen University Hospital Mean age (yrs) Male gender (%) Diabetes (%) Hypertension (%) Treatment for hyperlipidemia (%) Current smoker (%) Family history of CAD (%) Previous myocardial infarction (%) Previous PCI (%) Symptom onset to balloon (min) Time to CMR (days) Use of GP IIb/IIIa inhibitor (%) Use of bivalirudin (%) 61 69 7 37 46 61 37 10 7 241 ± 149 83 ± 20 83 7 62 74 7 32 41 49 31 7 8 255 ±196 84 ± 18 83 12 p ns Baseline clinical demography Post- conditioning n = 59 Conventional Treatment n = 59

15. POSTCON Copenhagen University Hospital Mean age (yrs) Male gender (%) Diabetes (%) Hypertension (%) Treatment for hyperlipidemia (%) Current smoker (%) Family history of CAD (%) Previous myocardial infarction (%) Previous PCI (%) Symptom onset to balloon (min) Time to CMR (days) Use of GP IIb/IIIa inhibitor (%) Use of bivalirudin (%) 61 69 7 37 46 61 37 10 7 241 ± 149 83 ± 20 83 7 62 74 7 32 41 49 31 7 8 255 ±196 84 ± 18 83 12 p ns Baseline clinical demography Post- conditioning n = 59 Conventional Treatment n = 59

16. POSTCON Copenhagen University Hospital Mean age (yrs) Male gender (%) Diabetes (%) Hypertension (%) Treatment for hyperlipidemia (%) Current smoker (%) Family history of CAD (%) Previous myocardial infarction (%) Previous PCI (%) Symptom onset to balloon (min) Time to CMR (days) Use of GP IIb/IIIa inhibitor (%) Use of bivalirudin (%) 61 69 7 37 46 61 37 10 7 241 ± 149 83 ± 20 83 7 62 74 7 32 41 49 31 7 8 255 ±196 84 ± 18 83 12 p ns Baseline clinical demography Post- conditioning n = 59 Conventional Treatment n = 59

17. POSTCON Copenhagen University Hospital Baseline angiographic results Number of Diseased vessels (%) 1 Vessel Disease 2 Vessel Disease 3 Vessel Disease Infarct related artery (%) LAD RCA LCX / PDA / PLA/ OM / D TIMI 0-I before procedure Visible thrombus (%) 78 15 7 44 47 8 100 75 83 14 3 39 42 19 100 83 ns p Post- conditioning n = 59 Conventional Treatment n = 59

18. POSTCON Copenhagen University Hospital Baseline angiographic results Number of Diseased vessels (%) 1 Vessel Disease 2 Vessel Disease 3 Vessel Disease Infarct related artery (%) LAD RCA LCX / PDA / PLA/ OM / D TIMI 0-I before procedure Visible thrombus (%) 78 15 7 44 47 8 100 75 83 14 3 39 42 19 100 83 ns p Post- conditioning n = 59 Conventional Treatment n = 59

19. POSTCON Copenhagen University Hospital Baseline angiographic results Number of Diseased vessels (%) 1 Vessel Disease 2 Vessel Disease 3 Vessel Disease Infarct related artery (%) LAD RCA LCX / PDA / PLA/ OM / D TIMI 0-I before procedure Visible thrombus (%) 78 15 7 44 47 8 100 75 83 14 3 39 42 19 100 83 ns p Post- conditioning n = 59 Conventional Treatment n = 59

20. POSTCON Copenhagen University Hospital Baseline angiographic characteristics Number of Diseased vessels (%) 1 Vessel Disease 2 Vessel Disease 3 Vessel Disease Infarct related artery (%) LAD RCA LCX / PDA / PLA/ OM / D TIMI 0-I before procedure Visible thrombus (%) 78 15 7 44 47 8 100 75 83 14 3 39 42 19 100 83 ns p Post- conditioning n = 59 Conventional Treatment n = 59

21. POSTCON Copenhagen University Hospital Procedural Results Type of stent (%) None BMS DES Number of stents (%) 0 1 2 3 Diameter of final balloon, mm Length of stented segment, mm Max deployment pressure, mmHg Thrombectomy (%) TIMI grade III after procedure (%) 15 6 78 15 71 12 2 3.3 19.6 17.6 10 95 17 12 69 17 68 14 2 3.3 18.1 16.2 14 88 ns p Post- conditioning n = 59 Conventional Treatment n = 59

22. POSTCON Copenhagen University Hospital Procedural Results Type of stent (%) None BMS DES Number of stents (%) 0 1 2 3 Diameter of final balloon, mm Length of stented segment, mm Max deployment pressure, mmHg Thrombectomy (%) TIMI grade III after procedure (%) 15 6 78 15 71 12 2 3.3 19.6 17.6 10 95 17 12 69 17 68 14 2 3.3 18.1 16.2 14 88 ns p Post- conditioning n = 59 Conventional Treatment n = 59

23. POSTCON Copenhagen University Hospital Procedural Results Type of stent (%) None BMS DES Number of stents (%) 0 1 2 3 Diameter of final balloon, mm Length of stented segment, mm Max deployment pressure, mmHg Thrombectomy (%) TIMI grade III after procedure (%) 15 6 78 15 71 12 2 3.3 19.6 17.6 10 95 17 12 69 17 68 14 2 3.3 18.1 16.2 14 88 ns p Post- conditioning n = 59 Conventional Treatment n = 59

24. POSTCON Copenhagen University Hospital CMR – late enhancement

25. POSTCON Copenhagen University Hospital CMR – late enhancement = Infarct mass = LV mass Infarct (%) = Infarct mass / LV mass

26. POSTCON Copenhagen University Hospital CMR – The wavefront phenomenon Myocardium at risk Final infarct 40 minutes 3 hours96 hours

27. POSTCON Copenhagen University Hospital CMR – Area At Risk Ortiz-Pérez et al., 2007 1432 5876 Apex Basis = Infarct = None-infarct AAR-ESA = Infarct / (none-infarct + Infarct)

28. POSTCON Copenhagen University Hospital p=0.987 p=0.037 p=0.007 Results - CMR

29. POSTCON Copenhagen University Hospital Results - CMR Lønborg et al., 2010

30. POSTCON Copenhagen University Hospital Infarct size Results - CMR

31. POSTCON Copenhagen University Hospital Infarct size Results - CMR p=0.213 - interaction test

32. POSTCON Copenhagen University Hospital p=0.705 Infarct size - interaction test Results - CMR AAR = Area At Risk

33. POSTCON Copenhagen University Hospital Heart failure p=0.048 Angina pectoris p=0.362 Clinical outcome at 3 months 7

34. POSTCON Copenhagen University Hospital Myocardial infarction, n (%) STEMI NSTEMI Stent thrombosis, n (%) Pacemaker, n (%) PCI on target vessel, n (%) CABG, n (%) Death, n (%) 0 (0) 3 (5) 0 (0) 1 (2) 0 (0) 2 (3) 0 (0) 1 (2) 2 (3) 1 (2) 0 (0) ns p Post- conditioning n = 59 Conventional Treatment n = 59 Clinical outcome at 3 months

35. POSTCON Copenhagen University Hospital Postconditioning reduces infarct size in patients with STEMI Postconditioning improves functional class in patients with STEMI The treatment is independently effective for all Areas At Risk Postconditioning should be tested in larger clinical trials Conclusion