STEMI LATE PRESENTER

How to (practically) approach ?

Dr Satyam Rajvanshi
PGIMER & RML Hospital
New Delhi
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

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
FACTORS RELATED TO
rd
NO REPERFUSION THERAPY – 1/3 patients!
• Age >75 years
• Prior CHF/MI/CABG
• DELAYED PRESENTATION
• Female gender
• Diabetes

• Pulmonary edema
• Systolic pressure <100 mm Hg
(GRACE) Lancet 2002;359:373–377
• CIns to PCI/thrombolysis (<3%)
(NRMI) Am Heart J 2008;156:1035-1044
• Spontaneous reperfusion (11%)
“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”
REAL LIFE SCENARIOS
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
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
What does the evidence say?

What do the guidelines say?

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

What would you do?

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
ASYMPTOMATIC (or Mild symptoms) / STABLE
• No level A evidence
• Guidelines vary

Approach is tricky!
EVIDENCE for Mrs. B ?
 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

JAMA. 2005;293:2865-2872
SE – Death/MI/Stroke at 30 days
Am Heart J 2006 Dec;152:1133-9
JAMA. 2009;301:487-488
 BRAVE-2
365 STEMI pts 12-48 hrs after onset
without persistent symptoms
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)
Excluded pts in Killip class 3/4

Randomised to PCI/Med Rx

PE – LV infarct size at 10 days by SPECT

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

Randomised to PCI/Med Rx

PE – LV infarct size at 10 days by SPECT

JAMA. 2005;293:2865-2872
SE – Death/MI/Stroke at 30 days
Am Heart J 2006 Dec;152:1133-9
JAMA. 2009;301:487-488
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 Am J Cardiol 2011;107:501-8

PE – 12 mo All-cause mortality
 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
Am J Cardiol 2011;107:501-8
PE – 12 mo All-cause mortality
 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
Am J Cardiol 2011;107:501-8
PE – 12 mo All-cause mortality
So far so good..
BUT
What about
these?
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

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

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

N Engl J Med 2006;355:2395-407

 >2166 pts
between 3-28 days after symptom onset
with
LVEF<50% and/orNo mortality benefit by PCI vs. OMT
Proximal large vessel occlusion
But Angina significantly less at 7 yrs
Repeat revascularization significantly less at 7 yrs
Excluded pts in Killip class 3/4, LM/TVD

PE – Death/MI/Class IV HF

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
No mortality benefit by PCI vs. OMT
Proximal large vessel occlusion
Even in pts treated <3 days or <7 days from onset
Excluded pts in Killip class 3/4, LM/TVD

PE – Death/MI/Class IV HF

OAT early enrolled subgroup. EHJ 2009;30:183-191

Beyond 12 hrs of STEMI

Can myocardium no longer be

salvaged ?
Is OAT the end of the road for Occluded IRA ?
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

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

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

Late myocardial salvage

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
EHJ 2009;30:1322–30
at 30 days
 396 STEMI pts 30 min-72 hours after
symptom onset
LV Infarct Size was larger in late presenters – as expected
SPECT-MPI performed acutely before PCI
But percentage area salvaged by PCI - 53% in late presenters
after 30 days
(vs. 66% in early presenters)
PE – LV infarct size at 30 days
Salvaged area 44% even in OCCLUDED IRA
SE – Percentage of area at risk salvaged
(vs.2009;30:1322–30
EHJ 71% in open IRA)
at 30 days
EHJ 2006;27:1900-1907
12 hour time limit is arbitrary for primary PCI!

EHJ 2006;27:1900-1907
5 RCTs; 648 hemodynamically stable pts >12 hours to 6 weeks post MI
With totally occluded IRA

Cath Cardiovasc Interv 2008;71:772-781

5 RCTs; 648 hemodynamically stable pts >12 hours to 6 weeks post MI
With totally occluded IRA

Cath Cardiovasc Interv 2008;71:772-781

Beyond 12 hrs of STEMI

Can we reduce MACE ?

YES, WE CAN!
10 RCTs; 3560 hemodynamically stable pts >12 hours to 60 days post MI

JACC 2008;51:956-64
JACC 2008;51:956-64
 JACC 2008;51:956-64

10 studies; 3560 hemodynamically stable pts >12 hours to 60 days post MI

What are the guidelines?
ACC/AHA STEMI 2013
JACC 2013;61:e78-140
ESC Revascularization 2014
ESC/EACTS guidelines 2014
EHJ doi:10.1093/eurheartj/ehu278
• 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 ?

A practical CONCLUSION
• 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

• A practical approach

• Unstable patient – Revascularization

(Symptoms/Hemodynamics/Electrical)
• A practical approach

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

• Stable patient presenting >72 hrs – Stress / Viability testing

(Mild or No Symptoms / Stable Hemodynamics)
• 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’