1. Primary Angioplasty and Hemodynamic Support in Cardiogenic Shock Department of Internal Medicine, College of Medicine, Yonsei University Hyuck Moon Kwon, M.D.

2. Epidemiology of Cardiogenic Shock Occurrence of shock STEMINon- STEMI 4.2-7.2% (GUSTO) 2.9% (PURSUIT) Median time from enrollment to shock 9.6h76h Unstable angina 2.1% (PURSUIT) 94h Hasdai et al. JACC 2000;36:687

4. Definition of Cardiogenic Shock SBP 30min-1 hr that is : Unresponsive to fluid administration alone Secondary to cardiac dysfunction, or signs of end-organ hypoperfusion, or CI 15-18mmHg. SBP increase to>90mmHg within 1 hr after administration of inotrophic agents Death within 1 hr of hypotension but met other criteria for cardiogenic shock. ACC clinical data standard JACC 2001;38:2127

5. ACC/AHA Guidelines (1999/2000) for PCI in Cardiogenic Shock Class I recommendation Primary PTCA: within 36 hrs of an acute ST elevation / Q-wave or new LBBB who develop cardiogenic shock are < 75 years old, Revascularization (PCI or CABG) within 18 hrs of onset of shock. J Am Coll Cardiol 1999;34:`904

6. Predictors of Cardiogenic Shock after STEMI Patient’s age - most important SBP HR Killip Class - Hasdai et al,Lancet 2000;356:749

7. Primary Angioplasty in CS E mployed criteria ? GUSTO-1 Selection bias ? SHOCK vs SMASH Randomized controlled study? Time of studies ? Overall mortality: 44% Successful PCI: 33% Unsuccessful PCI: 81%

8. Cardiogenic shock : 7.2% (among 41,021 pts) Overall 30-day mortality : 55% 30-day mortality of CABG group : 29% 30-day mortality of PTCA group : 22% Comparison of 1 yr mortality, PTCA vs no PTCA : the hazard ratio : 0.81(95% CI,0.71-0.94; p<0.005) Limitations : not randomized study. Selection bias. GUSTO-I (Cardiogenic shock subgroup analysis)

9. SHOCK trial : Randomized and controlled study Acute Myocardial Infarction Shock Randomization Emergency RevascularizationInitial medical Stabilization IABP/Pharmacological support Possible prior thrombolysis Emergency early PTCA(60%)/CABG(40%)<= 6 hrs IABP/Pharmacological support Thrombolysis unless absolute Contraindication (63%) Delayed revasc.(25%) >54hr <= 36hr <= 12hr Hochman et al,NEJM 1999;341:625 Primary end point : 30-day mortality Secondary end point : 6 mo. mortality

10. Outcome and Subgroup 30-day mortality Total Age<75yr Age>=75yr 6-mo. mortality Total Age<75yr Age>=75yr ERV 46.7(152) 41.4(128) 75.0(24) 50.3(151) 44.9(127) 79.2(24) Medical Therapy 56.0(150) 56.8(118) 53.1(32) 63.1(149) 65.0(117) 56.3(32) Difference -9.3 -15.4 +21.9 -12.8 -20.1 +22.9 percent(number in subgroup) Relative risk 0.83 0.73 1.41 0.80 0.70 1.41 P-value 0.11 0.01 0.027 0.003 SHOCK Trial : Mortality among Study Patients Hochman et al,NEJM 1999;341:625

11. PCI in the SHOCK Trial Registry (93-97’, n=884) Webb J et al, Am. Heart J.2001;141:964-71 In-hospital mortality: 46.4% in PCI (n=276) vs 78.0% in medically (n=499) MI-PCI: Median 8.8hrs, Shock-PCI: 3.3hrs PCI within 6 hrs of MI 40.2% PCI within 6-12 hrs of MI 50.9% PCI within 12-24 hrs of MI 60.5% PCI within 24hrs of MI 43.9% Pts with PCI: younger, shock earlier, higher LVEF & CI

12. Final TIMI flow grade after PCI and in-hospital mortality rates in SHOCK Registry patients with pump(Lt.or Rt.ventricular) failure. (P< 0.001). ( Webb J et al, Am. Heart J.2001;141:964-71) 0 20 40 60 80 100 0 or 1(n=35) 3(n=111) 85.7% 50.0% In-hospital mortality(%) 33.3% 2(n=24) Final TIMI Flow Grade

13. Angiographic success and in-hospital mortality rates in SHOCK Registry patients with pump failure. Success is defined as residual stenosis<50% and final TIMI flow grade of 2 or 3(P< 0.001). ( Webb J et al, Am. Heart J.2001;141:964-71) 0 20 40 60 80 100 Unsuccessful(n=40) Successful(n=119) 82.5% 36.1% In-hospital mortality(%)

14. Region ANC Europe AB USA P value Hospital mortality(%) 58 65 79 39 < 0.0001 ERV(%) 25 31 46 57 <0.0001 Stent use 25 80 53 80 0.0019 GPIIbIIIa Inhibitor 5 15 9 26 0.0005 Global Use of Revascularization for Pts. in Cardiogenic Shock: Global registry of Acute Coronary Events (GRACE, 99-00’, n=535) ANC: Australia/New Zealand/Canada, AB: Argentina/brazil Dauerman et al, Am J cardiol 2001;88(suppl 5A) The most powerful predictor of in–hospital survival : PCI with stenting (n=535, odds ratio, 5.8 ; 95% confidence interval, 3.3-10.4)

15. Long-term Results after acute PCI in AMI with shock 12-months survival rate 47% SHOCK trial 60% Ajani et al. AJC 2001;87:633 80% Ammann et al. Int J of cardiology 2002;82:127 Early prediction - ERV with stenting & anti-PLT !!

16. Beneficial effect of GP IIb/IIIa receptor blockers in patients undergoing primary PCI/Stenting in CS: 1-month mortality (n=74) 19 vs 41% Antoniucci D et al. Am J Cardiol. 2001;88:5A In hospital mortality (n=323) 26.4 vs 34.4% Moscucci M et al. JACC. 2002;39:330A Glycoprotein IIb/IIIa inhibitors

17. Hemodynamic Support in Cardiogenic Shock

18. IABP in Cardiogenic Shock Diastolic inflation - Augmentation of DBP Systolic Deflation - Afterload Reduction Contraindicated in severe Aortic regurgitation ! -Increases diastolic coronary arterial perfusion - Reduce LV wall stress - Decrease myocardial oxygen demand - Increase in cardiac output

19. IABP as an an adjunctive treatment to revascularization in GUSTO-I trial, a trend towards lower 30-day and 1 -year mortality rates. (Anderson et al. JACC 1997;30:708-715) (Barron et al,Am heart J 2001;141:933-939) IABP in Cardiogenic Shock complicating AMI SHOCK trial : IABP used in 86% National Registry of MI-2 IABP in 7268/23180 (31%): Thrombolytic therapy with IABP :49 vs 67 % Primary angioplasty with IABP :47 vs 45 %

20. Conclusion Prevention is the best policy: identification of pre-shock state followed by preventing deterioration into cardiogenic shock. Strategy of ERV: PTCA/CABG accompanied with IABP support. for > 75yrs old,invasive strategy on case by case basis. TIMI flow after PCI was strongly associated with in-hospital mortality rate.

22. Thrombolytic therapy The outcome of cardiogenic shock is closely linked to the patency of the culprit coronary arteries Thrombolytic therapy has decreased the occurrence of shock among patients with persistent STEMI. The GUSTO-I : t-PA is more efficacious than streptokinase in preventing shock.

23. Thrombolysis in cardiogenic shock Results have been disappointing Cause : ? limited efficacy of lytics in the setting of low perfusion pressure. GISSI-I Study Mortality of thrombolysis(streptokinase) group = 69.9% Mortality of. control group = 70.1% -David Hasdai et al,Lancet 2000;356:753