2. STEMI: What’s the Rush? STEMI: What’s the Rush? William Phillips, MD, FACC, FSCAI Director of Cardiology CMMC A PCI Center perspective.

3. NRMI 2: Primary PCI Door-to-Balloon Time vs. Mortality Door-to-Balloon Time (minutes) MV Adjusted Odds of Death P=0.01 P=0.0007P=0.0003 n = 2,230 5,734 6,6164,4612,6275,412

4. Patients Transported by EMS After Calling 9-1-1 Onset of STEMI Symptoms Call 911 Call Fast 9-1-1 EMS Dispatch EMS on-scene Encourage 12-lead ECG Consider prehospital fibrinolytic if capable and EMS-to-needle < 30 min EMS Triage Plan Not PCI Capable Hospital PCI Capable Hospital Interhospital Transfer Hospital Fibrinolysis: Door-to-needle within<30 min EMS transport:EMS to Balloon within 90 min Patient self-transport: Hospital Door-to- Balloon within 90 min EMS transport EMS on scene Within 8 min Dispatch 1 min Patient 5 min after Symptom onset Goals Total ischemic time: Within 120 min* * Golden hour = First 60 min Adapted from Panel A Figure 1 Antman et al. JACC 2004;44:676.

5. ACC/AHA Guidelines for the Management of Patients With ST-Elevation Acute Myocardial Infarction- Focus Emergency Care A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction) Available as full text or executive versions at http://www.acc.org Antman et al. JACC 2004;44:671-719.

6. Achieve Coronary Patency Achieve Coronary Patency Initial Reperfusion Therapy Initial Reperfusion Therapy Defined as the initial strategy employed to restore blood flow to the occluded coronary arteryDefined as the initial strategy employed to restore blood flow to the occluded coronary artery 3 Major Options: 3 Major Options: Pharmacological Reperfusion Pharmacological Reperfusion PCI PCI Acute Surgical Reperfusion Acute Surgical Reperfusion Under both Pharmacological and PCI are listed several lower recommendations & investigational reperfusion strategies Under both Pharmacological and PCI are listed several lower recommendations & investigational reperfusion strategies Class I All patients should undergo rapid evaluation for reperfusion therapy & have a reperfusion strategy implemented promptly after contact with the medical system Antman et al. JACC 2004;44:680.

7. Importance of Early Reperfusion Therapy in STEMI Outcomes Dependent Upon: Time to treatment-TIME IS STILL MUSCLE! Time to treatment-TIME IS STILL MUSCLE! Early and full restoration in coronary blood flow (TIMI 3 flow) Early and full restoration in coronary blood flow (TIMI 3 flow) Sustained restoration of flow (no reinfarction and effective treatment for recurrent ischemia) Sustained restoration of flow (no reinfarction and effective treatment for recurrent ischemia)

8. Comparison of Approved Fibrinolytic Agents Adapted from Table 15, pg 53.Accessed on August 6, 2004 http://www.acc.org/clinical/guidelines/stemi/index.pdf. Streptokinase Alteplase Reteplase Tenecteplase Dose 1.5 MU over Up to 100mg in 10U x 2 30-50mg 30-60 min 90 min (wt-based) each over 2 min based on weight Bolus Admin. No No Yes Yes Antigenic Yes No No No Allergic React Yes No No No Systemic Marked Mild Moderate Minimal Fibrinogen Depletion ~90-min patency 50 75 75? 75 rates (%) TIMI grade 3 flow, % 32 54 60 63

9. Reperfusion Choices Step 2: Determine Whether Fibrinolysis or an Invasive Strategy is Preferred Adapted from Figure 3; Antman et al. JACC 2004;44:682. If presentation is less than 3 hours and there is no delay to an invasive strategy, there is no preference for either strategy. Fibrinolysis is generally preferred if: Early presentation (3 hours or less from symptom onset & delay to invasive strategy; see below) Invasive strategy is not an option Catheterization lab occupied/not available Vascular access difficulties Lack of access to a skilled PCI lab- Operator experience > 75 PCI cases per year Team experience >36 PPCI cases per year Delay to invasive strategy Prolonged transport such that the (Door-to Balloon) – (Door-to- needle) time is > 1 HR Medical contact-to- balloon time is > than 90 min (But how much more is too long?) An invasive strategy is generally preferred if: Skilled PCI laboratory available with surgical backup Medical contact-to- balloon time is < than 90 min (Door-to Balloon) – (Door-to- needle time) is < 1 hr High risk from STEMI Cardiogenic shock Killip class greater than or equal to 3 Contraindications to fibrinolysis, including increased risk of bleeding and ICH Late presentation Symptom onset was more than 3 hours ago Diagnosis of STEMI is in doubt

10. CAPTIM Comparison of Angioplasty and Prehospital Thrombolysis in Acute Myocardial Infarction Primary Composite Endpoint- Death, Reinfarction, Disabling Stroke Bonnefoy E, et al. Lancet 2002;360:825-9

11. CAPTIM -1Year Results Sx to Treatment Analysis Touboul P. Presented at: The 18th International Symposium on Thrombolysis and Interventional Therapy in Acute Myocardial Infarction - George Washington University Symposium; November 16, 2002; Chicago, Ill. Sx  2 h 0.0 Death Sx  2 h 5.0 7.5 2.5 Pre-hospital Lysis Primary PCI 2.2 5.7 Death P=0.057 0.0 7.5 10.0 2.5 Pre-hospital Lysis Primary PCI 5.9 3.7 Death P=0.47 5.0 Percent 2.2% absolute Risk Reduction =37% Relative RR (NS)

12. Time Dependence of Reperfusion in STEMI

13. Time from Symptom Onset to Treatment Predicts 1-year Mortality after Primary PCI De Luca et al, Circulation 2004;109:1223-1225 The relative risk of 1-year mortality increases by 7.5% for each 30-minute delay n=1791

14. 74 (77) hospitals in Sweden National registry since 1995 (1992) > 550.000 ICCU-admissions (95%) Annually 60,000 new admissions Annually 20,000 acute MI Follow up by merging with public registries on hospital care and death Over 26,000 patients included. Register of Information and Knowledge about Swedish Heart Intensive care Admissions General information

15. Mortality in relation to therapy and delay 7-day mortality 30-day mortality 1-year mortality 30-day mortality 1-year mortality 30-day mortality 1-year mortality 0,80,6 0,4 2 1,21,5 0,1110 in-hospital thrombolysis betterPCI or PHT better Reperfusion started <=2 h Reperfusion started >2 h Prehospital thrombolysis (PHT) Primary PCI (PCI) Any time Adjusted outcome by Cox regression analysis including 23 variables plus propensity score. JAMA 2006;296:1749

16. Primary PCI vs prehospital in inhospital trombolysis over 5 years – adjusted cumulative 1 year mortality JAMA 2006;296:1749

17. Primary PCI vs trombolysis age-adjusted 1 year mortality in relation to delay time JAMA 2006;296:1749

18. Primary Percutaneous Coronary Intervention Interhospital Transfer for Primary PCI “To achieve optimal results, time from the first hospital door to the balloon inflation in the second hospital should be as short as possible, with a goal of within 90 minutes. Significant reductions in door-to-balloon times might be achieved by directly transporting patients to PCI centers rather than transporting them to the nearest hospital, if interhospital transfer will subsequently be required to obtain primary PCI”. Significant reductions in door-to-balloon times might be achieved by directly transporting patients to PCI centers rather than transporting them to the nearest hospital, if interhospital transfer will subsequently be required to obtain primary PCI”. Antman et al. JACC 2004;44:686.

19. Barriers to Interhospital Transfer for PPCI Distance Distance Weather! Weather! Road conditions Road conditions Ambulance and/or helicopter availability Ambulance and/or helicopter availability Economics Economics EMTALA regulations EMTALA regulations Lack of a well-rehearsed transfer protocol by a committed team with ongoing QI reviews Lack of a well-rehearsed transfer protocol by a committed team with ongoing QI reviews

20. Criteria for Level 1 Heart Attack Center 24/7 Cardiac cath lab 24/7 Cardiac cath lab 24/7 Cardiovascular surgery 24/7 Cardiovascular surgery Comprehensive interventional team Comprehensive interventional team >200 interventional Pts/yr >200 interventional Pts/yr >36 PPCI/yr >36 PPCI/yr >75 PCI/interventional Cardiologist >75 PCI/interventional Cardiologist Standardized protocols at referral and receiving hospitals Standardized protocols at referral and receiving hospitals Transfer agreements in place Transfer agreements in place Education and training programs Education and training programs Quality Assurance ongoing Quality Assurance ongoing Henry, et al, JACC vol.47: April 4, 2006, 1339-45

21. Achieving Rapid Treatment

22. Summary: Selection of the Optimal Reperfusion Options for the STEMI Patient: 2004 Full Dose Fibrinolytic Monotherapy if… Door to balloon (D-B) > 90 min (?how much greater) Door to balloon (D-B) > 90 min (?how much greater) Lack of access to skilled PCI center Lack of access to skilled PCI center (D-B) – (D-N) > 1 h (D-B) – (D-N) > 1 h < 3 h from symptom onset < 3 h from symptom onset (TNK—62% TIMI 3 flow) (TNK—62% TIMI 3 flow) Full Dose Fibrinolytic Monotherapy if… Door to balloon (D-B) > 90 min (?how much greater) Door to balloon (D-B) > 90 min (?how much greater) Lack of access to skilled PCI center Lack of access to skilled PCI center (D-B) – (D-N) > 1 h (D-B) – (D-N) > 1 h < 3 h from symptom onset < 3 h from symptom onset (TNK—62% TIMI 3 flow) (TNK—62% TIMI 3 flow) Invasive Strategy if… Cardiogenic shock (age < 75) Cardiogenic shock (age < 75) Bleeding risk Bleeding risk Diagnosis in doubt (pericarditis/aneurysm) Diagnosis in doubt (pericarditis/aneurysm) Door to balloon < 90 min Door to balloon < 90 min Symptoms > 2-3 h Symptoms > 2-3 h Lytic failure or post lysis Lytic failure or post lysis Skilled PCI center available, defined by: Skilled PCI center available, defined by: Operator experience > 75 cases/yr Team experience > 36 primary PCI/yr Age > 75 Age > 75 (90+% TIMI 3 flow) (90+% TIMI 3 flow) Invasive Strategy if… Cardiogenic shock (age < 75) Cardiogenic shock (age < 75) Bleeding risk Bleeding risk Diagnosis in doubt (pericarditis/aneurysm) Diagnosis in doubt (pericarditis/aneurysm) Door to balloon < 90 min Door to balloon < 90 min Symptoms > 2-3 h Symptoms > 2-3 h Lytic failure or post lysis Lytic failure or post lysis Skilled PCI center available, defined by: Skilled PCI center available, defined by: Operator experience > 75 cases/yr Team experience > 36 primary PCI/yr Age > 75 Age > 75 (90+% TIMI 3 flow) (90+% TIMI 3 flow)

23. Technical Aspects of PPCI Direct to Cath Lab (meet patient at door…consent & history enroute to lab). Confirm diagnosis and appropriateness. Direct to Cath Lab (meet patient at door…consent & history enroute to lab). Confirm diagnosis and appropriateness. Rapid prep (if not done by sending hospital) Rapid prep (if not done by sending hospital) Adjunctive pharmocotherapy? Adjunctive pharmocotherapy? Careful vascular access (goal is one stick…Ultrasound guidance?) Careful vascular access (goal is one stick…Ultrasound guidance?) Angiographic preferences: Infarct artery first? Angiographic preferences: Infarct artery first? Cross, Dotter, Assess, Inflate, ?Thrombectomy, Stent (?not DES) Cross, Dotter, Assess, Inflate, ?Thrombectomy, Stent (?not DES) LV gram at end if stable, LVEDP at least. LV gram at end if stable, LVEDP at least.

24. The end….of the beginning. Knowing is not enough, we must apply. Willing is not enough, we must do. Goethe Goethe