Stephen

W. Smith
Part I

Part 2 is focussed on STEMI

Key references
Myocardial Infarction: Thygesen, K., et al. Universal denition of
myocardial infarction: 2013.
UA/NSTEMI: Anderson, J., et al. ACC/AHA 2014 guidelines for the
management of patients with unstable angina/non-ST-elevation myocardial
infarctionCirculation. 2014;130:e344-e426
STEMI: Antman EM, et al. ACC/AHA guidelines for the management of
patients with ST-elevation myocardial infarction--executive summary. J Am
Coll Cardiol 2004;44(3):671-719.
STEMI update: Antman, EM., et al. 2007 focused update of the ACC/AHA
2004 Guidelines for the Management of Patients With ST-Elevation
Myocardial InfarctionJ Am Coll Cardiol 2008; 51(2):210-247. Available at:
http://content.onlinejacc.org/article.aspx?articleid=1187096
STEMI 2nd update: Kushner FG., et al. 2009 focused updates: ACC/AHA
guidelines for the management of patients with ST-elevation myocardial
infarction J Am Coll Cardiol 2009;54(23):2205-41.
STEMI 3rd update: Antman, EM., et al. 2013 focused update of the ACC/
AHA Guidelines for the Management of Patients With ST-Elevation
Myocardial Infarction. Circulation. 2013;127:529-555
Nice Review, 2009
slightly out of date
Amit Kumar MD and Christopher Cannon, MD

Acute Coronary Syndromes: Diagnosis and

Management, Part I
Mayo Clin Proc 2009 Oct; 84(10): 917938.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755812/

Acute Coronary Syndromes: Diagnosis and
Management, Part II
Mayo Clin Proc 2009 Nov; 84(11): 1021-1036
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2770915/
Non STE-ACS STEMI
The False STEMI NonSTEMI Dichotomy
 STEMI vs. NSTEMI vs. UA
ST Elevation
STEMI vs. PseudoSTEMI
Acute Coronary Occlusion
STEMI (as dened by mm criteria) vs. Subtle ST elevation (NSTEMI)
NSTEMI
Low risk to high risk
Low risk: few comorbidities, pain gone, no ST deviation
(nondiagnostic ECG), low troponin, vitals all normal (stable)
No ECG evidence of major coronary occlusion
High risk: comorbidities, persistent pain, ST deviation (especially
persistent), high troponin, vitals abnormal (unstable), low EF, heart
failure
ECG evidence of occlusion or of multivessel disease
Unstable Angina
Troponin negative (or no rise and/or fall)
Recent Trends, 2011
AJM 124:40
High Risk STEMI vs. High Risk Non STEMI
2010-2011, 1-Year Mortality Data
JACC 62(18):Suppl B69, 2013

STEMI 15.4%
Non STEMI 19.9%
TIMI risk score
Substudy of ESSENCE and TIMI-11b

>/= 2 anginal events in 24 hours

1-2 = low risk, 3-4 = mod risk, 5-7 = high risk

TIMI score risk of 14-day events
Derivation and Validation
(ESSENCE and TIMI 11b trials, 1999)
All patients had at least one of:
CAD, ischemic ECG, + troponin
(no one > 65 had score of zero)
Limitations
Dichotomous
Leaves out
Your contemporary therapy
Invasive therapy
P2Y12 inhibitors, GP IIb-IIIa inhibitors
Shock, BP, pulse, heart failure
Cardiomyopathy, ejection fraction
Level of troponin elevation
Other EKG ndings
BBB, conduction blocks, dysrhythmias
Extent or location of ST elevation or depression
 GRACE in hospital mortality

Grace apps
http:// www. Gracescore.org/WebSite/
Webversion.aspx
If risk of in-hospital death > 3%
then raw score > 140
Add:
STD and + Trop
Add:
HR 120
Killip III
SBP 90
DiagnosZc vs. nondiagnosZc (nonspecic) ECG
MI Diagnosis by Troponin
30% have diagnostic STE
15% have diagnostic ST depression or TW-inversion
45% of ECGs are diagnostic of ACS
Approx 45% abnormal but nondiagnostic ECG
Approx 10% have a normal ECG

Many pseudoinfarction patterns

Pseudo-STEMI
Pseudo-Non-STEMI

Welch RD et al. JAMA 2001;286:1977-1984; Rouan GW. Am J Cardiol 1989;64:1087;

Roe Arch Int Med 165:1630; Converted from CK to troponin
ST Depression, 1999
GUSTO IIb; JACC 2001; 38:64

2 leads with 2 mm ST Depression:

1-year mortality 14% vs. 4% without STD
Non-diagnosZc ECG
high risk paZent, ongoing pain

Consult resources (EKG, consultant)

Pretest prob (known CAD?)
Record posterior leads
Troponin elevated?
Serial ECGs
Stat ECHO
Angiogram
 Diagnosis of MI
1st thru 3rd Universal DeniZons
At least one of:
Symptoms of ischemia
ECG changes indicative of new ischemia
Development of pathologic Q waves
Imaging evidence of new loss of viable myocardium or
new regional wall motion abnormality
At least one Troponin above cuto
Rise and/or fall and due to ischemia
ACS (Type I MI) is a separate decision!
Acute myocardial injury
Type 1 MI, Type 2 MI, other (toxins, myocarditis, etc.)
Ischemic symptoms and elevated Trop
Type I AMI (ACS) vs. Type II AMI vs. other

Sepsis?
Respiratory failure?
Severe hypertension?
Shock?
Pulmonary embolism?
Renal failure and chest wall pain?
CHF/Cardiomyopathy and chest wall pain?
Tachy- or Brady-dysrhythmia?
Abnormal vital signs suggest a dierent primary disorder

Use ECG and clinical presentation to interpret troponin

Troponin level and 42 day mortality
Antman, NEJM 1996;335:1342

Not as important in the era of invasive therapy

Circulation 2014:129:293
MedicaZons 4 groups

STEMI treated with thrombolytics

STEMI treated with PCI
UA/NSTEMI treated invasively (with PCI)
UA/NSTEMI treated conservatively
Medical treatment only
Oxygen

Unnecessary and potentially harmful if oxygen

saturation is 94% or above
Morphine
Associated with higher mortality in UA/NSTEMI
CRUSADE registry, OR 1.41
Nevertheless ACC/AHA class IIa
Do not give unless committed to cath lab
Nitroglycerin
topical NTG is useless (not acceptable for ongoing pain ACC/AHA)
STEMI
All IV NTG mortality benet is from pre-reperfusion era
IV NTG for: hypertension, pulmonary edema
NTG sublingual has little data, probably harmless, maybe benecial
Do not give IV NTG with tPA or TNK-tPA

UA/NSTEMI--IV NTG for:

Ischemic pain (avoid morphine)
Pulmonary Edema
Elevated Blood Pressure

Caution
Sildenal, etc.
Hypotension
Right Ventricular MI
Aspirin:
Most important medicaZon in ACS
STEMI
Mortality: 13.2% vs. 10.7% (ISIS-2), NNT = 40
Recurrent ischemia after lytics: 41% vs. 25 % (NNT = 6)
Roux S et al.

Unstable Angina:
Death/MI: 10.1% vs. 5.0%, NNT = 20
Lewis et al.
Chew it
Dose 165-325mg
not baby 81 mg
not more than 325 mg
Every chest pain patient (except allergy)
Dual anZplatelet therapy (DAPT)
P2Y12 inhibitors, block ADP producZon in platelets
Ticagrelor (also Cangrelor, also Thienopyridines: Clopidogrel, Prasugrel)

STEMI with lytics

Clopidogrel (300 mg) (Clarity trial)
75 mg for those age > 75
Others have higher bleeding risk; 600 mg not studied
STEMI with PCI
Ticagrelor 180 mg, then 90 bid.
Better outcomes (PLATO trial), quicker onset
Safer if patient ultimately needs CABG (shorter-acting)
UA/NSTEMI with PCI
Ticagrelor
UA/NSTEMI without PCI
Ticagrelor
Clopidogrel (in contrast to Zcagrelor)
STEMI with PCI (Ticagrelor preferred)
In ED if institutionally ok (CABG bleeding risk)
Some wait 5 days for CABG
Even if CABG needed early, it is benecial
600 mg preferred, decreases death/MI
STEMI with lytics
300 mg loading dose
COMMIT-75mg, death/re-MI 10.1% vs. 9.2%
CLARITY-300mg, death or re-MI 21.7% vs. 15.0%
UA/NSTEMI with PCI (Ticagrelor preferred)
CURE trial, PCI-CURE, death/MI/revasc 6.4% vs. 4.5%
600 mg better than 300 mg (Cuisset, randomized, 2006)
Indicated for UA/NSTEMI without PCI (CURE)
(Ticagrelor preferred)
Prasugrel in UA/NSTEMI
TRITON TIMI 38
Prasugrel 60/10 mg vs. clopidogrel 300 loading
Prasugrel
Less death/MI/nonfatal stroke (12.1% vs. 9.9%)
more major bleeding (2.4% vs 1.8%)
ACC/AHA: you can use either one
STEMI or NSTEMI
Contraindicated
previous stroke
Prior to angiogram
Heparin + ASA vs. ASA alone
STEMI
With Fibrinolytics
Fibrin specic (tPA, TNK-tPA, Reteplase)
Must give some antithrombotic

Streptokinase
None

PCI
Must give antithrombotic (heparin, enoxaparin, bivalirudin)
NSTEMI
Heparin + ASA vs. ASA alone in UA/NSTEMI
Oler et al., 1996, meta-analysis of 6 trials 2-12 week endpoint
10.4% vs. 7.9% death/MI; RR = 0.67 (0.44-1.02, did not reach
statistical signicance) (NNT = 40)
Heparin vs. LMWH in STEMI
2013 STEMI guidelines
With Thrombolytics
Enoxaparin over unfractionated heparin (UFH)
ASSENT-3, ExTRACT-TIMI 25, CLARITY
Death or Re-infarction improved by 2-4% absolute
NNT = ~30 vs. UFH
30 mg IV loading dose
1 mg/kg sub q bid 15 min later and q 12 hours
Warning: greater bleeding risk w bailout (rescue) PCI
Age > 75 (ASSENT-3 PLUS):
no bolus
0.75 mg/kg sub q q 12 hrs
Regardless of age: if GFR < 30, then 1mg/kg q 24 hrs
UFH: 60 U/kg bolus (max 4000), 12u/kg/hr (max 1000)
Enoxaparin increases risk if rescue PCI needed
With PCI
Do not give LMWH (no enoxaparin)
UFH only, and it is essential
AnZthromboZcs
Heparin (UFH) vs. Enoxaparin

UA/NSTEMI (Non-STE-ACS)
Must treat conrmed Non-STE-ACS with antithrombotic
Conservative (non-invasive) Rx of NSTEMI:
LMWH
Invasive (PCI):
Your interventionalist will have his/her preferred regimen.
Do NOT mix UFH and Enoxaparin, increased bleeding
If only UFH given in cath lab, then must give UFH in ED
STEMI with tPA: must use antithrombotic
Enoxaparin slightly better than UFH
Enox: IV load of 0.3 mg/kg, but not in patients > age 75
STEMI with PCI: must use antithrombotic
 Non-STE ACS (UA/NSTEMI)
without PCI (conservaZve):
LMWH (Enoxaparin or Fondaparinux) Superior to UFH
for NSTEMI

Extra benet only for NSTEMI (+ troponin)

Not for unstable angina (- troponin)
ESSENCE, TIMI 11b, A to Z trials:
Many Non-PCI patients
Favor enoxaparin
ESSENCE: NEJM 1997;337:447
TIMI 11b: Circulation 1999a: 100:1602
ESSENCE and TIMI 11b did not use GPIs or P2Y12 inhibitor
A to Z did not use P2Y12 inhibitor
JAMA. 2004;292(1):55
Heparin vs. Enox in Non-STE-ACS with PCI

LMWH Possibly better than unfractionated heparin

(NNT = 100) (meta-analysis, Murphy, 2007)
Or not better at all (Petersen, 2004)
However, this data is skewed by the poorly done
SYNERGY trial.(Mahaey, 2005; Ferguson, 2004)
SYNERGY: UFH vs. Enoxaparin
PCI patients receiving a GP IIb-IIIa inhibitor
62% with clopidogrel 75mg
Nevertheless, most authors consider them equivalent
Synergy: 30 Day Outcomes
ASA, clopidogrel 62%, GPI
Heparin vs. enoxaparin

Ferguson JJ et al. JAMA 2004: 292(1):45-54

Synergy: 30 Day Outcomes
ASA, clopid, GPI
Heparin vs. enoxaparin
Consistent Therapy Group
More on Enoxaparin
In the cath lab
If > 8 hours since dose, 0.3 mg/kg boost
Monitor anti Xa activity
Contraindicated in renal failure
Dosing of heparin/enoxaparin
Overdosing of heparin is major cause of bleeding
Heparin in UA/NSTEMI
Loading dose: 60U/kg (max 4000)
Maintenance: 12U/kg/hr (max 1000)
Heparin in STEMI with PCI: 50-70 U/kg
Heparin in STEMI with Lytics:
same as UA/NSTEMI
Enoxaparin:
loading dose: 1mg/kg subQ;
maintenance: 1mg/kg q 12 hours (q 24 if GFR < 30)
Add 0.3 mg/kg after 8 hours for PCI
For STEMI: also load 30mg IV
Other LMWH
Fondaparinux (very little anti-IIa activity)
Use only if no PCI conservative therapy
Better than Enoxaparin for this
Increased risk of catheter thrombosis with PCI
If already given, PCI needs added anti-IIa drug (UFH)
Dalteparin
No advantage
Bivalirudin vs. Heparin + GP IIb-IIIa inhibitor
Safety benet? Its complicated

With lytics for STEMI No!

Not studied with (TNK) tPA
With PCI for STEMI
Previously: thought better than Heparin
(HORIZONS-AMI, 2008)
All received clopidogrel 600 (60%) or 300 (35%)

Death: (2.9 vs. 2.0%), major bleeding: (8.5% vs. 5.1%)

Recent trials: No better than heparin + GPI, more recent:
HEAT-PPCI (Shahad et al. Lancet 2014 384:1849)
MATRIX (Valgimigli M. NEJM 2015;373(11):997)
With PCI for NonSTEMI - (ACUITY, 2006)
Formerly recommended
New study shows no better than UFH;
MATRIX (Valgimigli M. NEJM 2015;373(11):997)
Glycoprotein IIB/IIIA inhibitors (GPIs)
Abciximab (Reopro), EpZbaZde (Integrilin), Tiroban (Aggrastat)

--Rare in ED
--For patients who need dual antiplatelet therapy (DAP) and cannot or did not get
P2Y12 inhibitor
b/o CABG risk rare, especially with ticagrelor over clopidogrel

STEMI with lytics do not give (GUSTO-V)

STEMI with PCI
Class IIa, but only at time of PCI, by interventionalist
Not if bivalirudin is used
UA/NSTEMI with PCI:
Only at time of PCI by interventionalist
not upstream in the ED
Class I: If not adequately pretreated with P2Y12 inhibitor
UA/NSTEMI without PCI:
Class IIa: If adequately pretreated with P2Y12 inhibitor
Do not give abciximab (GUSTO-VI-ACS)
GPIs: UA/NSTEMI with PCI
With heparin or Enoxaparin
3-5% decrease in death/MI (NNT = 20-35)
(Boersma, 1999)
These studies without clopidogrel or stenting
With clopidogrel
Death/MI/revasc 28.0% vs. 23.3% (NNT = 22)
Death/MI 15.3% vs. 11.6% for those with elevated trop
Bivalirudin
Without GPI: As good as UFH with GPI (Less bleeding)
Must give clopidogrel
 UpstreamGPIs: NSTEMI with PCI
(Giugliano, 2009) This arZcle is worth looking at

UA/NSTEMI
Antithrombotic + ASA + clopidogrel 300/600
Randomized to:
ED upstream eptibatide or
Provisional eptibatide only after angiogram, if needed
N=9492. 9.3% vs. 10.0% death/MI/recurrent ischemia (p=.2)
Results almost signicant for each of these groups:
1-Had positive trop (84% in each group)
2-Had time to randomization < 4 hours (1/3 of each group)
3-Had unfractionated heparin (vs. enoxaparin)
How about a patient who has + trop, immediate treatment, and UFH?
Beta Blockers-
almost all supporZng randomized data from pre-reperfusion era
All ACS
Oral within 24 hours (metoprolol 50 mg)
Unless contraindicated
Signs of CHF
Signs of low output (BP, tachy, anterior MI)
Risk of cardiogenic shock
Age > 70, SBP < 120, HR > 110 or < 60, long symptom duration
PR > 0.24, heart block, asthma?
IV: hypertension, without one of the contraindications
5 mg IV q 5 min x 3, followed by 50 mg po
STEMI
STEMI with lytics, BB vs. placebo (COMMIT, Chen, 2005)
No better: more cardiogenic shock, less V b
IV BB: Class IIa (reasonable without above contraindications)
No data to show it is important to give in the ED for STEMI.
May be useful in NSTEMI patients with HTN and no contraindications
GPIs: UA/NSTEMI
When no PCI
Unstable Angina
No abciximab (GUSTO-IV-ACS)
Eptibatide or Tiroban also out of favor now
NSTEMI, conservative management
Eptibatide or Tiroban (not abciximab!)
When in ED?
Rarely
Patient not amenable to angiogram/PCI but is high risk and
needs maximal antiplatelet therapy and not at high risk of
bleeding, especially if cannot get P2Y12 inhibitor.
ST depression (ACS)
reperfusion therapy (lyIcs, emergent PCI)

ST depression refractory to medical treatment

Immediate cath, with PCI if indicated
ST depression
Not an indication for Thrombolytics
2 Exceptions (2013 STEMI guidelines):
Exception #1:
Severe diuse ST depression, with STE in aVR
Exception #2:
Right precordial ST depression (V1-V4 primarily)
Posterior STEMI
PCI vs. medical therapy in Non STE-ACS
PCI best if any of these high risk features:

High risk, any one of:

NonSTEMI (Acute MI, Positive troponin)
Positive ECG
Recurrent ischemia
High GRACE score > 140

Lower death/MI/angina/hospitalization
41.3% vs. 32. 5%, NNT = 11)

(Cannon, 2001, Mehta, 2005)

ConservaZve Stragegy
Timing of PCI for UA/NSTEMI
Immediate, Emergency
Refractory Ischemia
Ongoing ischemic chest pain and/or
Refractory ST depression
Unstable (pulmonary edema, shock, dysrhythmias, etc.)
Non-Emergent
Higher mortality if > 24 hours, even for lower risk patients
(Sorajja, 2010; JACC 55(14):1416)
Mehta, TIMACS, NEJM 2009
> 24 hours ok if:
Not high risk
GRACE score >140
Correlates to in-hospital mortality of 3%
Mean 16 vs. 52 hours
Other meds

Calcium channel blockers

HTN with contraindication to Beta Blockers
Atrial brillation with RVR, Prinzmetals angina
At discharge
ASA, Statin, clopidogrel
Beta Blockers if no contraindications
ACE for CHF or EF < 40% (if no contraindications)
ARB if no ACE
 ThrombolyZcs in Non-STEMI?
STEMI
ST Depression:
Posterior STEMI, STE in aVR
Patient must have no absolute contraindications
Consider relative contraindications
TNK-tPA (tenecteplase)
Best if you regularly give lytics for STEMI
We use Alteplase (tPA)
Because it is used for stroke
Rarely give lytics for STEMI (use PCI)
Fewer medication errors
Treatment Summary: UA/NSTEMI
Aspirin 162-325 mg
P2Y12 inhibitor: Ticagrelor 180 mg, immediately
Beta blocker/nitrates as needed for pain, elevated BP
UFH, or Enoxaparin (bivalirudin?)
GP IIb/IIIa inhibitor upstream rarely (not with bivalirudin):
Those not getting P2Y12 and hi risk (ST depression, positive troponin)
Early Invasive Strategy
Emergent for refractory ischemia, instability
ASAP for high risk (GRACE > 140)
Other NSTEMI (+ Trop): within 36 hours
Consider Conservative Strategy
Negative Troponin (unstable angina) and other low risk features
No ST Depression, No Recurrent Ischemia, Normal stress test, EF > 40%,
absence of other high risk features.

ICTUS trial (Lancet 369(9564):827, 10 March 2007 suggests that low risk
NSTEMI patients may do well with conservative approach.
UA/NSTEMI
50 yo with CP
No h/o CAD
Substernal pressure x 2 hours, not otherwise
explained, Resolved
Not stabbing, not pleuritic, not reproducible, not
positional, not seconds only, not localized to
ngertip
Exam neg, smokes, BP 160/90, pulse 70
Initial Troponin = 0.012 ng/ml (< 99%-ile)
TIMI score: zero
ACS? Treatment? Workup? Discharge?
Aspirin and discharge if 2nd troponin < 99% 1-2 = low risk, 3-4 = mod risk,
See lecture on Ischemic Chest Pain 5-7 = high risk
50 yo with CP
No h/o CAD
Substernal pressure x 2 hours, not otherwise
explained, Resolved
Not stabbing, not pleuritic, not reproducible, not
positional, not seconds only, not localized to
ngertip
Exam neg, smokes, +FHx, BP 160/90, pulse 70
Takes aspirin for primary prevention
Initial Troponin = 0.012 ng/ml (< 99%-ile)
TIMI score: 2
ACS? Treatment? Workup? 1-2 = low risk, 3-4 = mod risk,
Admit, ASA, ticagrelor 5-7 = high risk
50 yo with CP
Substernal pressure x 2 hours last night, not otherwise
explained
Resolved, recurred, and resolved again.
Not stabbing, not pleuritic, not reproducible, not
positional, not seconds only, not localized to ngertip
++ h/o CAD, takes aspirin
Exam neg, smokes, +FHx, BP 160/90, pulse 70
Initial Troponin = 0.015
TIMI score: 4
ACS? Treatment? Workup?
Admit, ASA, ticagrelor, anti-coagulant? 1-2 = low risk, 3-4 = mod risk,
GRACE score < 140 5-7 = high risk
50 yo with CP
Substernal pressure x 2 hours last night, not otherwise
explained
Resolved, recurred and resolved again.
Not stabbing, not pleuritic, not reproducible, not
positional, not seconds only, not localized to ngertip
++ h/o CAD, takes aspirin
Exam neg, smokes, +FHx, BP 160/90, pulse 70
Initial Troponin = 2.1 ng/ml
TIMI score: 5
ACS? Treatment? Workup?
GRACE score < 140 1-2 = low risk, 3-4 = mod risk,
ASA, ticagrelor, anticoagulant, will get PCI 5-7 = high risk
50 yo male with CP

Substernal CP not otherwise explained, Resolved

1 risk factor (smokes)
Exam neg, BP 120/70, pulse 70
Initial Troponin < 0.012 ng/ml
ACS? Treatment? Workup?
Wellens, high risk LAD lesion
TIMI score low, but ECG risk high
Full medical therapy in ED: ASA, ticagrelor, Hep, ?GPI
Continuous 12-lead monitoring
Angio/PCI next available
50 yo male with CP

Substernal CP not otherwise explained. Resolved.

Exam neg, 1 risk factor, BP 140/80, pulse 70; trop 2.1 ng/mL.
TIMI score: trop pos, Q-wave V2 (old MI) = 2 (low risk)
positive trop, so will get angiography
ASA, ticagrelor
Heparin or Enoxaparin
Beta blocker IV (metoprolol 5 mg IV x 3, 50 mg po)
IV NTG if pain recurs
Immediate cath if pain recurs and cannot be controlled
70 yo female with CP

Substernal CP not otherwise explained. Resolved after 3 sl NTG

Exam neg, 3 risk factors, takes ASA, BP 150/70, pulse 70, rst trop neg
TIMI score: age, 3 risks, ASA, ST deviation = 4 (moderate)
Troponin 0.789 ng/mL, now TIMI score = 5
ASA, ticagrelor
Heparin or Enoxaparin
BB (metoprolol, 5 mg IV x 3, 50 mg po)
IV NTG if pain recurs
GRACE risk: 3% -- Cath urgent (not emergent and not delayed)
Immediate cath if pain recurs and cannot be controlled
70 y/o woman with CP

3 hours of substernal CP/SOB, Ongoing, Known CAD, 3 risk factors

Exam: few rales, BP 95/70, pulse 90, 1st Trop negative
TIMI = age, risks, CAD, ASA, STD = 5 (will have + trop = 6, high risk)
ASA, ticagrelor? (reasonable probability of CABG)
Heparin
Upstream GPI only in consultation with interventionalist, if no ticagrelor
Beta Blocker?
IV NTG?
Morphine?
Timing of PCI?
70 yo female with CP

3 hours of Substernal CP/SOB, Ongoing, Known CAD

Exam: few rales and B-lines, 3 risk factors, BP 180/100, pulse 90, 1st Troponin negative
TIMI = age, risks, CAD, ASA, STD = 5 (will have + trop = 6, high risk)
IV NTG?
ASA, ..how about Ticagrelor? (reasonable probability of CABG)
Heparin
Upstream GPI only in consultation with interventionalist, if no ticagrelor
Beta blocker?
No: even though BP is high, there is pulmonary edema
Morphine?
Timing of PCI?
UA, 74 yo with CAD
CABG x 2, DM, HTN, hyperlipidemia, previous LAD occlusions, on ASA
Decreased EF, 110/70, HR = 65
CP on and o all day, lasting max 30 minutes and relieved by NTG
ECG 1853, initial trop neg.
TIMI: age, CAD, risks, ASA, severe angina = 5; GRACE risk 2%
(26% 14-day risk of death/MI/revasc)
Rx actually given: ASA only
Then two negative troponins
EKG unchanged from last
Unstable Angina conZnued
Sudden recurrent CP, ECG 2250
Rapidly developed shock and arrest
Resuscitated
Cath lab: LAD and Circ occlusion (Left main equivalent)
Ultimately died
When to anZcoagulate empirically?
i.e., if EKG and trop negaZve

When it is highly likely to be signicant ACS

High TIMI or GRACE score
High risk patient
Older age, Old MI, low EF, rales, lower BP, higher HR,
higher Cr, more risk factors, more abnormal EKG
So if you want some eect
P2Y12 inhibitor
Flash pulmonary edema, 280/150
Improved with NTG
No repeat ECG in the Stab room
Initiated by HTN (EKG with severe LVH)? or
Initiated by Ischemia?
ECG in CCU
LAD occlusion
CP, known severe CAD
Not amenable to revascularizaIon

ASA
clopidogrel or ticagrelor
Enoxaparin better than UFH
If Trop and/or EKG positive
ESSENCE and TIMI 11b
Fondaparinux better yet.
End of Part I -- NSTEMI
Part 2 - STEMI
ST-ElevaIon MI 2016: Primary Treatment OpIons
Thrombolytics (TNK-tPA or tPA, tenecteplase or alteplase):
Aspirin 165-325mg
Clopidogrel 300 mg, 75 mg for those > 75 yrs
Enoxaparin (1mg/kg sub q, preceded by 30 mg IV load)
Age > 75, no load, use 0.75 mg/kg
May increase bleeding in rescue PCI
UFH acceptable, dose 60 U/Kg (max 4000), 12 U/kg/hr (max 1000)
Avoid Upstream Beta blockers unless hypertensive
Not with: CHF, bradycardia, hypotension, anterior MI
No NTG drip, control HTN with beta blockers
Percutaneous Coronary Intervention
ASA
Unfractionated heparin (dose 50-70 U/kg)
Enoxaparin in some institutions
Ticagrelor 180 mg
GP IIb/IIIa inhibitor, only by interventionalist
Generally avoid Beta blockers in the ED
NTG (only for severe hypertension/pulm edema)
NO NTG if hypotension, RVMI, Sildenal etc.
Reperfusion therapy is underuIlized*
Commonly due to diculty in ECG
interpretation**
**Barron 1997
**Hirvonen 1998

**Krumholz 1997

*Eagle 2002

(28% of eligible patients did not receive)

Lambert 2010 (22%) (JAMA 303:2148)

IndicaZons for brinolyZcs
Coronary occlusion (ST elevaIon MI)
Many denitions, Subjective interpretation best
Best mm criteria:
1 mm 2 consecutive limb leads
2 mm in V2 and V3, 1.5 mm for women, 2.5 for men< 40 yrs
ACEP
1 mm in 2 cons leads not due to non-MI condition
LBBB with + Modied Sgarbossa criteria
ST depression of:
True posterior MI (max V1-V3)
Severe diuse subendocardial ischemia
Not for other ST depression, T-wave inversion
(class III)
Aspirin:
Most important medicaZon in Cardiology

STEMI
Mortality: 13.2% vs. 10.7% (ISIS-2), NNT = 40
Every chest pain patient (except allergy)
Dual anZplatelet therapy (DAPT)
P2Y12 inhibitors, block ADP producZon in platelets

Clopidogrel, Prasugrel, Ticagrelor

STEMI with lytics

Clopidogrel (300 mg) (Clarity trial)
75 mg for those age > 75
Others have higher bleeding risk; 600 mg not studied
STEMI with PCI
Ticagrelor 180 mg, then 90 bid.
Better outcomes (PLATO trial), quicker onset
Safer if patient ultimately needs CABG (shorter-acting)
UA/NSTEMI with PCI
Ticagrelor
UA/NSTEMI without PCI
Ticagrelor
Clopidogrel
STEMI with PCI
In ED if institutionally ok (CABG bleeding risk)
Wait 5 days for CABG
600 mg preferred, decreases death/MI
STEMI with lytics
300 mg loading dose
COMMIT-75mg, death/re-MI 10.1% vs. 9.2%
CLARITY-300mg, death or re-MI 21.7% vs. 15.0%
UA/NSTEMI with PCI
CURE trial, PCI-CURE, death/MI/revasc 6.4% vs. 4.5%
600 mg better than 300 mg (Cuisset, randomized, 2006)
Indicated for UA/NSTEMI without PCI (CURE)
Heparin vs. LMWH in STEMI
2013 STEMI guidelines
With Thrombolytics
Enoxaparin > unfractionated heparin (UFH)
ASSENT-3, ExTRACT-TIMI 25, CLARITY
Death or Re-infarction improved by 2-4% absolute
NNT = ~30 vs. UFH
30 mg IV loading dose
1 mg/kg sub q bid 15 min later and q 12 hours
Warning: greater bleeding risk w bailout (rescue) PCI
Age > 75 (ASSENT-3 PLUS):
no bolus
0.75 mg/kg subq q 12 hrs
Regardless of age: if GFR < 30, then 1 mg/kg q 24 hrs
UFH: 60 U/kg bolus (max 4000), 12u/kg/hr (max 1000)
With PCI
Do not give LMWH (no enoxaparin)
UFH only, and it is essential
LyZcs?
LyZcs?
New LBBB
5-10% of patients with chest pain and LBBB or new
LBBB have MI as diagnosed by biomarkers
Even lower percent have coronary occlusion
Clinicians do not follow ACC/AHA guidelines
ACC/AHA says to consider Sgarbossa criteria
Use Smith Modied Sgarbossa
(this is not on the boards)
Modied Sgarbossa PosiZve
ProporZonally Excessive Discordant ST ElevaZon
STEMI: PCI vs. brinolyZcs
PCI is beker
Survival correlates with TIMI-3 ow
TIMI 3 ow:
Lytics 55%
PCI 90%
Both are better with newer adjuncts
Lytics:
Enoxaparin, clopidogrel, rescue PCI
Routine transfer for immediate angio
(Cantor, NEJM 360:2705, 2009)
PCI with stent:
Better stents, thrombectomy?
P2Y12 inhibitors, GPI
PCI especially preferred
Skilled PCI Lab available
Per year: 75 PCIs, 36 primary PCIs by team
Signicant diagnostic uncertainty
Contraindications to lytics
Cardiogenic shock
Age > 75
FMC to PCI < 120 minutes
> 2-4 hours since onset, unless very acute ECG
Large T-wave
Height of ST segments
Well formed Q-waves

FMC = rst medical contact

 Lower
acuteness

Higher
acuteness
Assess Time and Risk
lyZcs vs. PCI
Signicant diagnostic uncertainty
Contraindications to lytics
Cardiogenic shock
> 4 hours since onset, unless very acute ECG

Time of Onset of symptoms

Acuteness of ECG
Risk of STEMI
Risk of Fibrinolysis
Time required for transport to skilled PCI lab
Fibrinolysis generally preferred
Early presentaIon and

Invasive Strategy not an option

No cath lab, or it is occupied
Vascular access diculty
Delay to invasive strategy
Prolonged transport
DTBT DTNT > 60-90 minutes
Depends on acuity
DTBT > 90 minutes, FMC to BT > 120 minutes
ThrombolyZc choice
tPA (alteplase) and TNK-tPA (tenecteplase) equivalent
(ASSENT-2, 1999)
TNK requires only one bolus
TNK more brin specic
Lower bleeding rates (ASSENT-2) with TNK
4.66% vs. 5.94% non cerebral bleeding
ICH same
Alteplase tPA is the only one used for stroke and PE
thats why we only use alteplase
Streptokinase inferior (GUSTO-1), inexpensive
Elderly (> 75) and thrombolyZcs
not a contraindicaZon

3300 patients of age > 75 year

within 12 hours of symptom onset
ST elevation or bundle branch block
Randomized to thrombolytic or placebo
35-day mortality was reduced from 29.4% to 26.0% (p =
0.03), or 34 lives saved per 1000 treated.
White HD. Thrombolytic therapy in the elderly. Lancet 2000;
356:2028-2030.
DuraZon of symptoms
< 2 hours, lytics excellent
>12 hours, lytics contraindicated
Unless high acuteness on ECG
> 12 hours
PCI indicated even without symptoms if persistent
chest pain
 Major ContraindicaZons-FibrinolyZcs

Absolute contraindications
Hx of hemorrhagic stroke or known cerebral aneurysm
Active, serious, non-compressible bleeding
Cerebral infarct within 3 months (except within 4.5 hours)
Known intracranial neoplasm or vascular lesion
Cranial or spinal surgery within 14 days
Major relative contraindications
Persistent HTN > 180/110
Cerebral infarct within 3-6 months
Symptomatic gastrointestinal bleed within 14 days
Significant head trauma 10-14 days, or major head injury within 3 months
(Do a head CT scan prior to treatment)
Major surgery or trauma within 2 weeks
Signicant Bleeding Concerns
ThrombolyZcs

Signicant considerations
Warfarin use in the presence of minor bleeding
Signicant bleeding diathesis
(INR > 4.0); RR = 2.15, CI: 1.1-4.2
CPR chest compressions with evidence of injury
Non-compressible vessel puncture (do not use subclavian)
Femoral access in patient who needs a central line and who may
need thrombolytics
LyZcs: Minor Bleeding Concerns
CPR chest compressions < 10 min, with no physical
evidence of injury
Warfarin use with INR < 4.0
Minor bleeding (e.g. occult blood in stool).
Routine heme testing of stool is not required
Inconsequential
Active menstruation
Diabetic retinopathy
History of previous MI
History of stent or angioplasty
History of CABG
Time to treatment
Door to balloon time standard 90 minutes
60 should be easy in work hours
Door to needle time standard 30 minutes
15 should be easy if EKG easy
Check contraindications and go.
Door to EKG 10 minutes
STEMI systems, STEMI Receiving center
Prehospital triage system
Prehospital activation--Parallel processing
Transmit
Paramedic decision
Plan for backup thrombolytics
Transport to PCI capable hospital
Need not be CABG capable
Emergency Physician activation
QA real time data feedback, hospital-based CQI
Single call to central operator
Expect sta to arrive in 20 minutes
Importance of prehospital ECG
Importance of prehospital ECG
FibrinolyZcs eecZve early
Speed and Magnitude of Patency

1. Thick line = lytics

2. Thin solid line = angioplasty with 120 minute DBT
3. Thin dotted line = angioplasty with DBT of 75 minutes

Gibson CM. Ann Intern Med. 1999;130:841-847.

 Angioplasty/StenZng vs. LyZcs
Stenting plus P2Y12 inhibitor +/- GPI
Superior to thrombolytic therapy for STEMI for symptom
duration > 2 hours
Higher TIMI 3 ow
Less re-infarction
Lower mortality
True only if:
DTBT DTNT + 90 minutes, FMC to BT < 120 minutes
However: if < 2 hrs of Sxs (2.2% versus 5.7%, P=0.058)
Fibrinolytics better (rescue angioplasty in 26%)
DTBT DTNT + 60 minutes; FMC to BT > 90 minutes
Risk of bleeding higher, but overall outcome better
Steg PG. Circulation 2003; 108:2851; ACC/AHA guidelines

PCI always preferred for

Age > 75
Diagnosis uncertain
Contraindications to lytics
Hemodynamically Unstable (Cardiogenic Shock)
Facilitated PCI; lyZcs followed by PCI
ASSENT- 4 (2006), FINESSE (2008)
Lancet 2006;367:569-78; NEJM 2008;358(21):2205-17

ASSENT-4: STEMI < 6 hours

Anticipated PCI delay of at least one hour
ASA
Randomized to
PCI or
Full dose tenecteplase (TNK-tPA) followed by PCI
No heparin or clopidogrel in TNK group
Study halted
More bleeding and ischemic events in TNK-tPA group
FINESSE also showed no signicant dierence
Do NOT facilitate PCI with thrombolytics
Compare to TRANSFER-AMI (Cantor 2009)
ASSENT-4
tPA is prothromboZc

Median time from Sx to TNK: 2.6 h

Median time from TNK to PCI: 104 min (82, 135)
No clopidogrel with TNK
No heparin infusion with TNK
No GPI for PCI in TNK group [except bailout (10%)]
After PCI: TNK group
50% heparin
13% GPI
FINESSE
Reasons for failure of facilitated PCI

First 2 hours are most important

Importance of time to treatment not as critical for PCI
as for thrombolysis
Benet hard to show except in high risk patients
Dicult to improve on PCI and abciximab adjunct
TRANSFER-AMI
Cantor et al. (2009)
High risk STEMI
In patients for whom PCI cannot be timely
All patients received:
ASA, Hep or enoxaparin, clopidogrel 300 in 80-90%, TNK-tPA
Randomized to: early transfer/PCI vs. delayed transfer/PCI
If non-transfer patient does not have ST resolution at 60-90 minutes,
then transferred for Rescue PCI
Cath median 2.8 hours after randomization vs. 32.5 hours
Transfer better outcome
(death/re-MI/recurrent ischemia/CHF/shock: 17% vs. 11%, p=.004)
Death:
3.4% vs. 4.5% (p=NS)
Some dierences from ASSENT-4:
102 min vs. 168 min.
Clopidogrel given
Heparin (or enoxaparin) given
Transfer, again:
Armstrong et al., NEJM 368:1379 2013
PaZents presenZng within 3 hours of symptom onset
unable to undergo PCI within 1 hour
If DBT minus DTNT < 60 min, transfer without lytics
If DBT minus DTNT > 60 min, randomized to:
a) TNK tPA
+ transfer for PCI [emergent PCI (rescue) if no reperfusion,
otherwise 6-24 hours)]
dose for patients > age 75 or
b) Transfer for immediate PCI without TNK.
c) Enoxaparin and clopidogrel
Endpoint: death, shock, CHF, re-infarction at 30 days
12.4% in lytics group; 14.3% inPCI group (P = 0.21)
1.0% intracranial bleed in TNK group. 0.2% in PCI group.
Facilitated PCI
with full dose lyIcs not recommended
Routine Early PCI after thrombolytics vs. Selective PCI

Verheugt FW. N Engl J Med 2009;360:2779-2781.

Summary:
When to use ThrombolyIcs
Your hospital does not have PCI
Your door to their balloon time > 90-120 min
STEMI guidelines say: FMC to BT > 120 minutes
50% of transfer patients get PCI within 120 minutes.
When drive time > 30 min, 43% get FMC to DBT of < 120 min
Give thrombolytics, then transfer.
No contraindication to immediate PCI for pt who received lytics.
Your Cath lab is occupied: 2 patients, one cath lab
Assess Benet and Risk for each patient
Duration of MI
Short duration: very acute respond well to lytics
Long duration: emergent reperfusion less critical
Large MI (anterior): benet of PCI is greater
Cardiogenic shock: PCI over lytics is critical
Contraindications to thrombolytics
Choice of Reperfusion Strategy
Transport Time Time since onset of Symptoms
DTBT - DTNT
< 2 hours > 2 hours
< 30 minutes (HCMC) PCI PCI
30 60 minutes Consider Lytics PCI
> 60 minutes Lytics Lytics or PCI
All lytic patients should be transferred to PCI capable facility

Widimsky P (PRAGUE-2). Eur HT J 2003;24:94 Pts randomized <

3h from symptom onset: lytics had same mortality as transfer for
PCI
Steg PG (CAPTIM) Circ 108:2851. Prehospital lytics lower mortality
than PCI if randomized < 2 hours since symptom onset..
50 year old with 13 hours of severe, heavy, chest pain,
PCI not an opZon.
Prehospital thrombolysis for Sxs < 2 hours?
Vs. PCI

Prehospital studies done in Europe

Physicians on ambulances
Mortality
2.2% (lytics) vs. 5.7% (PCI), (p=.058) (Steg et al. 2003)
Mean time to PCI 150 minutes
Prehospital transport times > 60 minutes
Must be done with transmission of ECG
 50 yo male with CP

Duration of pain (2, 3, 4 hours, important?). Bleeding risks. 110/60, P 90, no pulm edema,
no ventricular dysrhythmias. DTNT = 15 min. Do you need to know much else?

Your door to their balloon time > 75-90 min

TNK-tPA
ASA
Enoxaparin 30 mg IV, 1 mg/kg sq Door to their balloon time < 75-90 min
or UFH ASA
300 mg clopidogrel Heparin (Enox?)
No beta blockers Ticagrelor 180 mg
No GPI No BB
No IV NTG IV NTG if hypertension, w or w/o pulm
Transfer edema
Cardiac Arrest, shock, lungs clear
Right Ventricular MI
do RV ECG in inferior MI

High short term mortality (30-60% with shock)

Good long term mortality if survive
Only with RCA (inferior MI). Do R sided ECG with inferior MI.
Fluids, avoid NTG
Avoid excessive uids
Norepinephrine
Who needs urgent cath?
1. ST elevaZon
2. ACS and denite ongoing ischemia
3. ComplicaZons

STEMI
Refractory ST depression
Ongoing ischemic chest pain
Cardiogenic shock
Pulmonary edema
Ventricular dysrhythmias with ischemia
Pulmonary Edema
ACS
Not due to uid overload
May be hypertensive (NTG)
Valve
Mitral: afterload reduction
Aortic regurg: afterload reduction
Aortic Stenosis: tough
HTN
High dose IV and sublingual NTG
Chronic CHF
Fluid overload +/- ischemia
Furosemide
Cardiogenic Shock
Big trouble
Pulmonary edema and shock/hypotension
Etiology in ACS
Poor pump function
Valve (Mitral)
Also VSD and myocardial rupture
Tachycardias/bradycardias
Cardiogenic Shock (mortality 40-60%)
EP can do these things
Echo to assess
RV and LV pump/tamponade
mitral valve/papillary muscle?
Arterial line, Intubation and Paralysis
Correct dysrhythmias
Fluids
Afterload reduction for mitral regurgitation
Get artery open now
PCI best, but lytics before transfer
No evidence of benet of pressors (level of evidence C)
Increase blood pressure
Increase ischemia
Intra aortic balloon pump
ECMO (extracorporeal life support?)
Refractory VT (electrical storm)

K > 4.0
Mg > 2.0
Amiodarone? Esmolol?
Open the artery
AV conducZon disturbances in STEMI
--Use of transvenous pacer
--both anterior and non-anterior MI
--Class I: should be done
IIa: reasonable
IIb: may be considered
III: should not be done
AVB No block 1st degree Mobitz I 2nd Mobitz II 2nd
BBB AVB degree block degree block
Old BBB III IIb IIb IIa
New BBB IIb IIa IIa I
Fascicular IIb IIa IIa I
block + RBBB
Alternating I I I I
RBBB/LBBB
Thanks for listening
When to get stat echo vs. bedside
You better be an expert to rule out a wall motion
abnormality!
Few of us are
That said, if youre ruling out a STEMI
If: very high quality image
If: very good shortening and movement
Then:
Lower probability of occlusion of large epicardial
HTN as eZology
3 essenZals to troponin assay

Level of detection (LoD)

the value that is dierent than zero
99% reference (99% of normals are < this level)
20% coecient of variation (20 % CV)
Troponin
SensiIve biomarker for myocardial injury
Elevated in many disease states
60% of true positive trops not ACS
ACS: levels rise and fall
Most other pathologies: steady state
Elevated troponin of any etiology (ACS or not)
Associated with higher mortality
Chronically elevated troponins
Bad prognosis
Not indication to be in ED or be admitted
Old rst generaZon assays
(very few sIll in marketplace):

Troponin only detectable if abnormally high

Few normal subjects had measurable values
+ troponin was pathology
Error: applying this old thinking to new test
The troponin is + (measurable), therefore we
have to worry.
Present assay
(Ortho Clinical DiagnosZcs Vitros ES)

LoD = 0.012
99% reference = 0.034
10% CV at 0.034 (same as 99% ref)
Troponin detectable in 20% of normals (no disease of any kind)
Cuto of 0.012: specicity for ACS = 50%, PPV = ~ 20%
Cuto of 0.034: specicity for ACS = 77-81%, PPV = ~ 40%
Most have serious disease but not ACS
Add 30% rise: specicity 90%, PPV 60%
Best sensitivity and specicity: Delta trop of > 30% and:
Initial trop > 0.034 or
Followup trop > 0.034