Late presentation in Myocardial Infarction - Review of Management

1. STEMI LATE PRESENTER
How to (practically) approach ?
Dr Satyam Rajvanshi
PGIMER & RML Hospital
New Delhi

2. LATE PRESENTERS
(symptom duration more than 12 hours)
• 8.5–40% of STEMI patients are LATE PRESENTERS worldwide
EHJ 2009;30:1322–30
• >30% STEMI patients are LATE PRESENTERS in INDIA
(CREATE registry) Lancet 2008;371:1435–42

3. Why 12 hour limit ?
• No mortality benefit/increased harm (ICH) by fibrinolysis
• Late presenters not included in trials showing superiority of primary PCI
over fibrinolysis
EHJ 2006;27:779–88
(LATE) Lancet 1993;342:759–766
(EMERAS) Lancet 1993;342:767–772

4. FACTORS RELATED TO
NO REPERFUSION THERAPY – 1/3rd patients!
• Age >75 years
• Prior CHF/MI/CABG
• Female gender
• Diabetes
• Pulmonary edema
• Systolic pressure <100 mm Hg
• CIns to PCI/thrombolysis (<3%)
• Spontaneous reperfusion (11%)
• DELAYED PRESENTATION
(GRACE) Lancet 2002;359:373–377
(NRMI) Am Heart J 2008;156:1035-1044

6. “An open IRA may be beneficial,
by preventing LV dilatation and
improving survival by limiting infarct size
and associated deterioration of LV function,
by mechanisms such as -
Prevention of adverse LV remodelling
Electrical stability
Collaterals to remaining viable myocardium”

10. REAL LIFE SCENARIOS

11. Mr. A
54/Male
Smoker
Ongoing chest pain since 14 hours
STE in V2-V6, Intermittent NSVT
98/64
RWMA in LAD territory; Moderate LVSD
Troponin positive

12. Mrs. B
62/Female
Uncontrolled diabetes, Hypertensive, Obese
Ghabraahat with sweating last night 16 hours back – now minimal
Sinus tachycardia, QS in V2-V3, STE in V2-V6
154/88
RWMA in LAD territory; Moderate LVSD
Troponin positive

13. What does the evidence say?
What do the guidelines say?

14. What does the evidence say?
No level A evidence!
What do the guidelines say?
Guidelines vary/unclear
What would you do?

15. SYMPTOMATIC (Severe) / UNSTABLE – Mr. A
Cardiogenic Shock/Severe HF
(SHOCK) JAMA 2001;285:190 –2
Severe Angina
Intermediate or high risk positive pre-discharge stress test
(SWISSI-2) JAMA 2007;297:1985–91
(DANAMI) Circulation 1997;96:748 –55
PCI is CLASS I recommendation
(ACC/AHA STEMI) JACC 2013;61:e78-140
(ESC/EACTS guidelines 2014) EHJ doi:10.1093/eurheartj/ehu278

16. ASYMPTOMATIC (or Mild symptoms) / STABLE
• No level A evidence
• Guidelines vary
Approach is tricky!

17. EVIDENCE for Mrs. B ?

18. JAMA. 2005;293:2865-2872
Am Heart J 2006 Dec;152:1133-9
JAMA. 2009;301:487-488
365 STEMI pts 12-48 hrs after onset
WITHOUT persistent symptoms
Excluded pts in Killip class 3/4
Randomised to PCI/Med Rx
PE – LV infarct size at 10 days by SPECT
SE – Death/MI/Stroke at 30 days
BRAVE-2

19. 365 STEMI pts 12-48 hrs after onset
without persistent symptoms
Excluded pts in Killip class 3/4
Randomised to PCI/Med Rx
PE – LV infarct size at 10 days by SPECT
SE – Death/MI/Stroke at 30 days
LV INFARCT SIZE IN PCI 8% vs. 13% IN MED Rx (p<0.001)
44% of area at risk salvaged by PCI (vs. 23% by Med Rx)
JAMA. 2005;293:2865-2872
Am Heart J 2006 Dec;152:1133-9
JAMA. 2009;301:487-488
BRAVE-2

20. BRAVE-2
365 STEMI pts 12-48 hrs after onset
without persistent symptoms
Excluded pts in Killip class 3/4
Randomised to PCI/Med Rx
PE – LV infarct size at 10 days by SPECT
SE – Death/MI/Stroke at 30 days
LV INFARCT SIZE IN PCI 8% vs. 13% IN MED Rx (p<0.001)
44% of area at risk salvaged by PCI (vs. 23% by Med Rx)
JAMA. 2005;293:2865-2872
Am Heart J 2006 Dec;152:1133-9
JAMA. 2009;301:487-488
4-YEAR MORTALITY
Reduced by 45%!

21. Am J Cardiol 2011;107:501-8

22. Am J Cardiol 2011;107:501-8
Polish registry – Real world ACS pts
>2000 pts between 12-24 hrs
after symptom onset
Excluded pts in Killip class 3/4
910 treated by PCI
vs
1126 by Med Rx
PE – 12 mo All-cause mortality

23. Am J Cardiol 2011;107:501-8
Polish registry
Selected pts presenting after 12 hrs of
symptom onset
Excluded pts in Killip class 3/4 (Revasc is
recommended)
910 treated invasively
vs
1126 conservatively
PE – 12 mo All-cause mortality

24. Am J Cardiol 2011;107:501-8
Polish registry
Selected pts presenting after 12 hrs of
symptom onset
Excluded pts in Killip class 3/4 (Revasc is
recommended)
910 treated invasively
vs
1126 conservatively
PE – 12 mo All-cause mortality

25. So far so good..
BUT
What about
these?

26. N Engl J Med 2006;355:2395-407

27. N Engl J Med 2006;355:2395-407
>2166 pts
between 3-28 days after symptom onset
with
LVEF<50% and/or
Proximal large vessel occlusion
Excluded pts in Killip class 3/4, LM/TVD
PE – Death/MI/Class IV HF

28. N Engl J Med 2006;355:2395-407
>2166 pts
between 3-28 days after symptom onset
with
LVEF<50% and/or
Proximal large vessel occlusion
Excluded pts in Killip class 3/4, LM/TVD
PE – Death/MI/Class IV HF

29. N Engl J Med 2006;355:2395-407
>2166 pts
between 3-28 days after symptom onset
with
LVEF<50% and/or
Proximal large vessel occlusion
Excluded pts in Killip class 3/4, LM/TVD
PE – Death/MI/Class IV HF

30. OAT long term 7 year follow-up. Circulation 2011;124:1-9
>2166 pts
between 3-28 days after symptom onset
with
LVEF<50% and/or
Proximal large vessel occlusion
Excluded pts in Killip class 3/4, LM/TVD
PE – Death/MI/Class IV HF
No mortality benefit by PCI vs. OMT
But Angina significantly less at 7 yrs
Repeat revascularization significantly less at 7 yrs

31. OAT early enrolled subgroup. EHJ 2009;30:183-191
>2166 pts
between 3-28 days after symptom onset
with
LVEF<50% and/or
Proximal large vessel occlusion
Excluded pts in Killip class 3/4, LM/TVD
PE – Death/MI/Class IV HF
No mortality benefit by PCI vs. OMT
Even in pts treated <3 days or <7 days from onset

32. Beyond 12 hrs of STEMI
Can myocardium no longer be
salvaged ?
Is OAT the end of the road for Occluded IRA ?

33. OAT major critics!!
• Long exclusion list – OAT not representative of real life ACS population
(LMCAD, TVD, Severe angina/HF, Unstable Arrhythmias, Renal dysfunction)
Enrollment extremely slow and prematurely interrupted –
Avg. only 2 patients per centre per year!
Cath Cardiovasc Interv 2008;71:772-781
• Median time to revascularization – 8 days post STEMI
Too late for benefit? Maybe earlier is better
N Engl J Med 2006;355:2395-407

34. OAT major critics!!
• Cardiac mortality gradually increased as LVEF decreased below 40%
OAT population only 21% had LVEF <40%
• IRA was RCA in 49%
N Engl J Med 2006;355:2395-407

35. OAT impact on
practice! – Too small
For late occluded IRA -
Even after OAT publication &
change in guidelines
Almost no change in practice
even in US
Arch Intern Med 2011;171:1636-1643

36. Late myocardial salvage
EHJ 2009;30:1322–30

37. EHJ 2009;30:1322–30
396 STEMI pts 30 min-72 hours after
symptom onset
SPECT-MPI performed acutely before PCI
after 30 days
PE – LV infarct size at 30 days
SE – Percentage of area at risk salvaged
at 30 days

38. EHJ 2009;30:1322–30
396 STEMI pts 30 min-72 hours after
symptom onset
SPECT-MPI performed acutely before PCI
after 30 days
PE – LV infarct size at 30 days
SE – Percentage of area at risk salvaged
at 30 days
LV Infarct Size was larger in late presenters – as expected
But percentage area salvaged by PCI - 53% in late presenters
(vs. 66% in early presenters)
Salvaged area 44% even in OCCLUDED IRA
(vs. 71% in open IRA)

39. EHJ 2006;27:1900-1907

40. EHJ 2006;27:1900-1907
12 hour time limit is arbitrary for primary PCI!

41. 5 RCTs; 648 hemodynamically stable pts >12 hours to 6 weeks post MI
With totally occluded IRA
Cath Cardiovasc Interv 2008;71:772-781

42. 5 RCTs; 648 hemodynamically stable pts >12 hours to 6 weeks post MI
With totally occluded IRA
Cath Cardiovasc Interv 2008;71:772-781

43. Beyond 12 hrs of STEMI
Can we reduce MACE ?
YES, WE CAN!

44. 10 RCTs; 3560 hemodynamically stable pts >12 hours to 60 days post MI
JACC 2008;51:956-64

45. JACC 2008;51:956-64

46. JACC 2008;51:956-64
10 studies; 3560 hemodynamically stable pts >12 hours to 60 days post MI

48. What are the guidelines?

49. ACC/AHA STEMI 2013
JACC 2013;61:e78-140

50. ESC Revascularization 2014
ESC/EACTS guidelines 2014
EHJ doi:10.1093/eurheartj/ehu278

51. • Shall we revascularize without stress testing ?
• Are all STABLE late presenters same ?
• Are there ‘EARLY’ LATE PRESENTERS and ‘LATE’ LATE PRESENTERS ?
• What about silent ischemia ?
Post fibrinolysis - Routine CAG strategy is better than ischemia guided strategy
• Sensitivity/Specificity of viability tests ?

52. A practical CONCLUSION

53. • No simple and specific guideline to manage patients when they present
late to ER
• 12 hour limit is arbitrary
• Substantial myocardial salvage is possible even in occluded IRA

54. • A practical approach
• Unstable patient – Revascularization
(Symptoms/Hemodynamics/Electrical)

55. • A practical approach
• Stable patient presenting <72 hrs – CAG with intent for revascularization
(Mild or No Symptoms / Stable Hemodynamics)

56. • A practical approach
• Stable patient presenting <72 hrs – CAG with intent for revascularization
(Mild or No Symptoms / Stable Hemodynamics)
• Significant lesion IRA – Revascularize
• Occluded IRA – Revascularize - ‘OPEN ARTERY HYPOTHESIS’
<72 hours Excluded from the OAT trial!

57. • A practical approach
• Stable patient presenting >72 hrs – Stress / Viability testing
(Mild or No Symptoms / Stable Hemodynamics)

58. • A practical approach
• Stable patient presenting >72 hrs – Stress / Viability testing
(Mild or No Symptoms / Stable Hemodynamics)
Positive test – CAG with intent for revascularization
• Significant lesion IRA – Revascularize
• Occluded IRA – Revascularize - ‘OPEN ARTERY HYPOTHESIS’