1. Acute Myocardial Infarction: Results from the DHMC Regional Registry Nathaniel Niles, MD Cardiology Grand Rounds January 13, 2005 Dartmouth-Hitchcock Medical Center

2.  Myocardial perfusion perfusion Plaque rupture→ thombotic occlusion of epicardial artery Downstream Infarct zone Thrombolytic Therapy Primary PCI Restore flow to epicardial vessel Current Management Goals for Treating Acute STEMI Treatment goal: prevent death by restoring coronary blood flow High risk of in-hospital death (~10%)

3. “No Flow” “Slow Flow” “Normal Flow” TIMI 0 / TIMI 1 Flow TIMI 0 / TIMI 1 Flow TIMI 2 Flow TIMI 2 Flow TIMI 3 Flow TIMI 3 Flow 9.3% 6.1% 3.7% p<0.0001 vs TIMI 0/1 p<0.0001 vs TIMI 2 p<0.0001 vs TIMI 0/1 p<0.0001 vs TIMI 2 P=0.003 vs TIMI 0/1 Team 2 German GUSTO 1 TAM I 1-7 TIM I 1,4 5,10B TIM I 1,4 5,10B TIM I 1,4 5,10B TIM I 1,4 5,10B TIM I 1,4 5,10B TIM I 1,4 5,10B CM Gibson 1998 in Acute Coronary Syndromes Sample Size of Pooled Analysis: 5,498 0 2 4 6 8 10 12 Epicardial Flow After Thrombolysis and Mortality Outcomes

4. “Time is nature’s way of keeping everything from happening at once” - Woody Allen “Time is muscle” - A. Schwarzenegger

5. 0 25 50 75 100 0306090120150 Reperfusion Strategy and TIMI-3 Flow Rate Time from presentation (min) (30 min angio) (60 min angio)(90 min angio) 210240 TIMI 3 Flow (%) 54% "Door-to- needle" time 30 min t-PA 39% 89% Primary angioplasty 10% spontaneous reperfusion“Door-to-Balloon Time” in DANAMI 2 114 min Lytic Tx gain 1 o PCI gain

6. Reperfusion Strategy and TIMI-3 Flow Rate 0 25 50 75 100 0306090120150 Time from presentation (min) (30 min angio) (60 min angio)(90 min angio) 210240 TIMI 3 Flow (%) 54% "Door-to- needle" time 30 min t-PA 39% 89% Primary angioplasty 10% spontaneous reperfusion“Door-to-Balloon Time” in DANAMI 2 114 min Lytic Tx gain 1 o PCI gain p=0.0002 p=0.0001 Frequency (%) 23 study review vs. p=0.057 p=0.0001 Frequency (%) 5 study review vs. Average Transfer Time = 39 minutes

7. Mortality rates with primary PCI as a function of PCI-related time delay P = 0.006 020406080100 PCI-Related Time Delay (door-to-balloon - door-to-needle) Absolute Risk Difference in Death (%) -5051015 Circle sizes =sample size of the individual study. Solid line=weighted meta-regression. Nallamothu BK, Bates ER. Am J Cardiol. 2003;92:824-6 62 min Benefit Favors PCI Harm Favors Lysis

8. Typical “Door-to- balloon” time for transfer patients Typical “Door-to- balloon” time for transfer patients >200 min Delayed primary angioplasty 0 25 50 75 100 0306090120150 Prolonged Delays→Facilitated PCI Time from presentation (min) (30 min angio) (60 min angio)(90 min angio) 180210 TIMI 3 Flow (%) ½ dose t-PA + abciximab and “facilitated” thrombolysis (TIMI 14) “facilitated PCI”

9. Trials Examining Facilitated PCI after Thrombolysis vs. Thrombolysis alone TrialYearN Thrombolytic Regimen Increased bleeding Conclusions SPEED2000528 Combination Tx No Decreased reinfarction and urgent revasc. TIMI 10B/14B 20011938 Combination Tx No Reduction in Death + Recurrent MI GARCIA-12004500 FD r-PA No Lower post-hospital cardiac events at 30 d. SIAM 3 2003197 FD r-PA No Lower MACE at 6 mos. CAPITAL AMI 2004 170 (high risk) FD TNK No Reduced MACE at 30 d.

10. Trials Examining Facilitated PCI vs. Primary PCI TrialYearN Thrombolyti c Regimen Increased bleeding Conclusions PACT1999606 Half dose t-PA t-PANo Better TIMI 3 flow at initial Angio SPEED2000528 FD r-PA, Combo Tx No Better TIMI 3 flow, lower TIMI frame count GARCIA-22004205 FD TNK No Better ST resolution, better TIMI 3 flow, No difference in cardiac function BRAVE2004253 Combination Tx Trend? Better TIMI 3 flow, no difference in infarct size ASSENT 4 Ongoing4000 FD TNK -- FINESSEOngoing3000 Combination Tx --

11. I I IIa IIb III Updated Guidelines (2004) STEMI patients presenting to a facility without prompt primary PCI capability (within 90 minutes) should receive thrombolytic therapy unless contraindicated. (Level of Evidence: A) Facilitated PCI might be performed as a reperfusion strategy in higher-risk patients when PCI is not immediately available and bleeding risk is low. (Level of Evidence: B) If immediately available, primary PCI should be performed in patients with STEMI as quickly as possible (Level of Evidence: A) If the symptom duration is within 3 hours and the expected door-to- balloon time minus the expected door-to-needle time is: ≤ 1 hour, primary PCI is preferred. (Level of Evidence: B) > 1 hour, thrombolytic therapy is preferred. (Level of Evidence: B) Combination therapy for reperfusion and prevention of reinfarction with abciximab and half-dose reteplase or tenecteplase for selected high risk patients at low risk for bleeding. (Level of Evidence: A)

12. Source of Patients Presenting to DHMC Cath Lab for Treatment of STEMI within 24 hours

13. DHMC STEMI Patient Mortality: 2001 Primary PCI vs Transfer Patients Mortality (%) Observed in-hospital in-hospital Transfer Patients Primary PCI Patients TIMI Risk (expected 30 day) Transfer Patients Primary PCI Patients

14. “When you come to a fork in the road, take it” - Yogi Berra

15. Transport to DHMC for potential salvage PCI ASAP Transport to DHMC Cath Lab ASAP Oxygen, ASA, low dose heparin, beta blocker, nitrates, Morphine, 2 IV lines, treat pain, CHF, shock, arrhythmias Non-DHMC Emergency Dept AMI diagnosed >30 min of CP and/or ECG with 1mmST elevation or LBBB Primary Thrombolytic Therapy Full Dose Thrombolytic Alice Peck Day or VA Hospital Administer abciximab Contraindication for Thrombolytic therapy/ abciximab Remote ER and Age < 75 Administer abciximab and ½ Dose Thrombolytic Primary PCI Facilitated PCI Acute ST elevation MI is now on the DHMC “ALWAYS TAKE” list December 2001

16. DHMC STEMI Registry Goals Assess safety and effectiveness of specific novel management strategies (facilitated PCI for transfer patients)Assess safety and effectiveness of specific novel management strategies (facilitated PCI for transfer patients) Monitor regional outcomes over time in order to assess the impact of overall quality improvement effortsMonitor regional outcomes over time in order to assess the impact of overall quality improvement efforts

17. STEMI Database - Case Report Form Emergency RoomEmergency Room Presentation (Hx/PE)Presentation (Hx/PE) ECGsECGs TreatmentTreatment Timing of TreatmentTiming of Treatment Cath LabCath Lab TIMI FlowTIMI Flow Timing of reperfusionTiming of reperfusion InterventionIntervention Extent of CADExtent of CAD Follow-upFollow-up DeathDeath StrokeStroke Recurrent MIRecurrent MI CHFCHF Bleeding ComplicationsBleeding Complications Repeat Revascularization ProceduresRepeat Revascularization Procedures

18. STEMI Database Initiated 12/01Initiated 12/01 Cath lab database query of all patients cathed with hx of MI within 24 hrsCath lab database query of all patients cathed with hx of MI within 24 hrs 1/01-12/01 retrospective chart review1/01-12/01 retrospective chart review 1/02-3/04 prospective chart review1/02-3/04 prospective chart review 4/04-7/04 prospective cath lab data entry4/04-7/04 prospective cath lab data entry

19. Safety and Effectiveness of specific novel management strategies: Facilitated PCI in Moderate to High Risk Patients Requiring Hospital Transfer for PCI Presented at: TransCatheter Therapeutics (TCT) Washington, DC September, 2004

20. “Non-Committed Strategy” ± full dose TTx ± GP 2b3a Inhib Transfer/cath as 2° strategy N= 276 (49%) “Facilitated Strategy” ½ dose TTx GP 2b3a Inh Emergent transfer for cath N= 163 (29%) “Primary Strategy” No TTx ± GP 2b3a Inh Emergent cath N= 107 (19%) Clinical history consistent with acute myocardial infarction and ST elevation, LBBB or anterior ST depression consistent with acute posterior MI N=564 Presenting to DHMC or Local Hospital N= 125 (22%) Presenting to Remote Hospital N= 439 (78%) “Non-Committed Strategy” ± TTx ± GP 2b3a Inh Cath as 2° Strategy N= 18 (3%) TIMI Score < 2 N = 22 (4%) TIMI Score ≥ 2 N = 85 (15%) TIMI Score < 2 N = 51 (9%) TIMI Score ≥ 2 N = 112 (20%)

21. Door-to-Balloon Time Time in minutes Reperfusion was delayed on average more than 70 minutes among facilitated PCI strategy patients

22. Pre-Cath Lab Outcomes Facilitated PCI strategy patients arrived at the cath lab in more stable condition

23. Cath Lab Findings and Outcomes Initial TIMI Flow in IRACath Lab Intubation or IABP % of Patients Facilitated Strategy yielded more patent arteries and was associated with less complcated procedures Facilitated Strategy yielded more patent arteries and was associated with less complcated procedures

24. In-hospital Outcomes % of Patients p=0.098 ns p=0.025 ns

25. “Optimal” 1° PCI vs. transfer for facilitated PCI Conclusions: had longer delays before reperfusion (avg. >70 minutes)had longer delays before reperfusion (avg. >70 minutes)But… had no greater likelihood of deterioration pre-cathhad no greater likelihood of deterioration pre-cath were less likely to have ischemia in lab and had less complicated procedureswere less likely to have ischemia in lab and had less complicated procedures had better initial infarct artery flow and overall better clinical outcomeshad better initial infarct artery flow and overall better clinical outcomes tended to have more bleeding problemstended to have more bleeding problemsBut… no increase in ICH no increase in ICH

26. Monitoring Regional Outcomes Over Time Transfer for PCI PatientsTransfer for PCI Patients Primary PCI Patients (DHMC, VAMC, APD)Primary PCI Patients (DHMC, VAMC, APD)

27. DHMC STEMI Transfer Volumes Q1(01)-Q2(04) Number of STEMI Patients

28. AMI Transfer Patients: 01→ 04 In-hospital Mortality % Mortality Year

29. AMI Transfer Patients: 01→ 04 In-hospital MACE* % MACE Year * Death, Recurrent MI, ICH, Repeat revascularization

30. AMI Transfer Patients In-hospital Bleeding Complications % Year

31. Possible Explanations for Improving Outcomes Lower risk patients now transferredLower risk patients now transferred Reduction in delays to reperfusionReduction in delays to reperfusion Volume effect – Improved outcomes with increased volumeVolume effect – Improved outcomes with increased volume Effect of half dose lytic protocolEffect of half dose lytic protocol

32. DHMC STEMI: Mean TIMI Risk Score Q1(01)-Q2(04) TIMI Risk Score * * Composite of advanced age, CV risk factors, hypotension, tachycardia, high Killip class, low body weight, anterior MI location, delay in Tx high Killip class, low body weight, anterior MI location, delay in Tx

33. DHMC STEMI: Mean Door-to-Balloon time Q1(01)-Q2(04) Door-to-Balloon time (min) Quarter

34. DHMC STEMI Transfer Volumes Q1(01)-Q2(04) Number of STEMI Patients

35. AMI Transfer Patients: By Intended Dose In-hospital Mortality % Mortality Lytic Dose Strategy p<0.04 p<0.0009 p=ns

36. AMI Transfer Patients: By Intended Dose TIMI Risk Score Average TIMI Risk Score Lytic Dose Strategy p<0.06 p=0.007 p=ns

37. AMI Transfer Patients: By Intended Dose Reperfusion and “Facilitated” Course Persistant CP or ST elevation TIMI 3 Flow on Initial Angio Cath Lab IABP or Intubation Clinical Deterioration Pre-Cath No lytic given Half dose lytic Full dose lytic

38. AMI Transfer Patients: By Intended Dose Door-to-Balloon Time Door-to-Balloon Time (min) Lytic Dose Strategy p=0.0023 p=0.0001 p=0.0164

39. AMI Transfer Patients: 01→ 04 In-hospital Mortality by Treatment strategy % Mortality Year

40. Monitoring Outcomes Over Time Transfer for PCI Patients Outcomes are improvingOutcomes are improving Explanation of improvement is unclear:Explanation of improvement is unclear: Half-dose lytic regimenHalf-dose lytic regimen Expedited care in half-dose groupExpedited care in half-dose group Non-specific improvement (“Hawthorne effect”)Non-specific improvement (“Hawthorne effect”) Still Room for improvementStill Room for improvement Faster transfersFaster transfers Better regimens (reduce bleeding)Better regimens (reduce bleeding)

41. Oxygen, ASA, heparin, beta blocker, nitrates, Morphine, 2 IV lines, treat pain, CHF, shock, arrhythmias Oxygen, ASA, heparin, beta blocker, nitrates, Morphine, 2 IV lines, treat pain, CHF, shock, arrhythmias After hour or weekends (technician not on site) Page Cardiology fellow on call Administer abciximab unless contraindication or significant cautions Weekday hours Call 5-7783, Notify “charge-person” Administer abciximab unless contraindication or significant cautions No Cath lab ready Cath lab ready DHMC Emergency Dept AMI diagnosed: >30 min of CP and/or ECG with 1mmST elevation or LBBB DHMC Emergency Dept AMI diagnosed: >30 min of CP and/or ECG with 1mmST elevation or LBBB Consent and transport to Catheterization Lab on Call

42. Non-transfer STEMI Patients (Presenting to DHMC, VAMC, APD) Q1(01)-Q2(04) Number of STEMI Patients

43. STEMI Patients presenting to DHMC, VAMC, APD n=112 Not initially admitted to or transferred to DHMC Time to Cath Lab table ≥ 10 hrs PCI not attempted n=109 n=98 n=93 True 1° PCI strategy True 1° PCI

44. 1° PCI Strategy Patients Years Actual In-hospital Mortality (%) TIMI Risk Score

45. 1° PCI Patients (with PCI actually attempted) Year Grouping Actual In-hospital Mortality (%) TIMI Risk Score

46. 1° PCI Strategy Patients Table Time and Mortality Door-to-Table Time Actual In- hospital Mortality (%) TIMI Risk Score Pre-Cath Shock or Intubation

47. 1° PCI Strategy Patients: ER to Cath Lab Cath Lab Readiness “Ideal” (weekday 7 AM to 5 PM) “Suboptimal” (after hours or on weekend) Target <45 min. <75 min. Mean 89 min. 142 min. Median 83 min. 108 min. Median Tabletop-to-balloon time = 38 min. Median Door-to-balloon time (ideal readiness) = 122 min. Door-to-Table Time

48. Times Over Time “Ideal” (Weekdays 7 AM to 5 PM) “Suboptimal” (After hours and Weekends)

49. 1° PCI Strategy Patients Early GP 2b3a inhibitor use and Mortality GP 2b3a Inhibitor Initiation Actual In- hospital Mortality (%) TIMI Risk Score Infarct Vessel Patency (%)

50. 1° PCI Strategy Patients Early GP 2b3a inhibitor Use Over Time % p=0.01

51. n=3n=17n=34 1° PCI Strategy Patients Early GP 2b3a inhibitor Choice and Outcomes

52. Monitoring Outcomes Over Time Primary PCI Patients Outcomes of patients actually receiving PCI are stable despite increasing risk over timeOutcomes of patients actually receiving PCI are stable despite increasing risk over time Time intervals - process is too slowTime intervals - process is too slow getting to the cath labgetting to the cath lab in the cath labin the cath lab GP 2b3a Inhibitors – appear to be effectiveGP 2b3a Inhibitors – appear to be effective may improved patency but not TIMI 3 flowmay improved patency but not TIMI 3 flow our utilization is increasingour utilization is increasing agent of choice?agent of choice?

53. DHMC STEMI Registry Conclusions useful in assessing the safety and efficacy of novel management strategiesuseful in assessing the safety and efficacy of novel management strategies useful in assessing the impact of new protocols over timeuseful in assessing the impact of new protocols over time May be useful for providing benchmark data to individual institutions for QA/QCIMay be useful for providing benchmark data to individual institutions for QA/QCI

54. DHMC STEMI Registry Limitations Enrollment bias - cath lab enrollment will miss patients who are not sent to the cath lab emergentlyEnrollment bias - cath lab enrollment will miss patients who are not sent to the cath lab emergently Patients admitted to the initial hospital rather than transferred acutelyPatients admitted to the initial hospital rather than transferred acutely Patients in whom the decision is made not to cathPatients in whom the decision is made not to cath Patients who decline transfer and/or cathPatients who decline transfer and/or cath Patients who die before they get to cath labPatients who die before they get to cath lab

55. DHMC STEMI Registry Next Steps ER enrollment of all STEMI patients in the regionER enrollment of all STEMI patients in the region Web-based, secure, registry interfaceWeb-based, secure, registry interface On-line decision supportOn-line decision support Risk assessment toolsRisk assessment tools GuidelinesGuidelines Treatment protocolsTreatment protocols Regular feedback to participating ERs/hospitalsRegular feedback to participating ERs/hospitals STEMI patient outcomes overall and by treatment strategySTEMI patient outcomes overall and by treatment strategy Process metrics (e.g. time intervals)Process metrics (e.g. time intervals) Partnership in process improvementPartnership in process improvement Novel treatment regimensNovel treatment regimens Transfer delay reductionTransfer delay reduction Pre-hospital triage??Pre-hospital triage??

56. Other Nest Steps – WritingOther Nest Steps – Writing “Writing is easy, all you have to do is stare at a blank sheet of paper until droplets of blood begin to form on your forehead” - anonymous

57. Questions?

58. The Throw Backs (Patients Not Receiving PCI at Acute Procedure) Incidence per Year %

59. Throw back Mortality vs TIMI Risk In-hospital Mortality TIMI Risk Score

60. Throw Backs Components of TIMI Risk

61. All STEMI Patients PCI Attempted Acutely 89% No PCI Attempted Acutely 11% CABG 1.5% 1.5% No CABG 98.5%CABG38% 62% 62% Mortality18.1%Mortality31.4%Mortality5.1%Mortality25%