Acute Coronary Syndromes

ACS: Definition
A spectrum of clinical diagnoses
comprising unstable angina, Non-STEMI,
and STEMI that share similar pathological
features involving intracoronary thrombosis

ACS: Definition

From: Braunwalds Heart Disease

Pathophysiology
atherosclerosis with superimposed coronary thrombosis
Slowly growing high-grade stenoses can progress to complete
occlusion but do not usually precipitate acute STEMI d/t collateral
circulation
During development of plaques, abrupt transition can occur, resulting
in
Platelet activation
Thrombin generation
Thrombus formation
Blood flow occlusion leads to imbalance between supply and demand
and could lead to myocardial necrosis

Stable Angina
Progressive
narrowing of coronary
lumen
Stable fibrous cap

Unstable Angina
Progressive
narrowing
Acute worsening of
coronary lumen due
to thrombus
formation

NSTEMI
Acute worsening of
coronary lumen due to
thrombus formation
Sub-occlusive/
transient coronary
thrombus with
myocardial necrosis

Pathophysiology
STEMI
Minimal prior
narrowing of
coronary lumen
Acute rupture of thin
fibrous cap
Occlusive thrombus
formation
Acute injury pattern
Myocardial necrosis

ACS Evaluation

Angina
Definition: Discomfort in the chest/ choking, that
characteristically comes on with exertion, relieved by rest
and/or NTG

Character
Location

Provoking
Factors

Favors Ischemic
Origin

Against
Ischemic Origin

Constricting
Squeezing
Burning
Heaviness

Dull ache
Knife-like, sharp
Jabs
Pleuritic

Substernal
Anterior thorax
Arms, shoulders
Neck, teeth,
Interscapular

Left submammary area

Left hemithorax

Exertion
Excitement
Cold, meals, stress

Pain after completion

of exercise
Pain with movement

Likelihood that signs & symptoms represent an ACS secondary to CAD

Feature

High

Intermediate

Low

History

Chest or left arm pain or

discomfort as chief
symptom reproducing prior
documented angina
Known history of CAD,
including MI

Chest or left arm pain or

discomfort as chief
symptom
Age > 70
Male gender
Diabetes mellitus

Probable ischemic
symptoms in absence of
the intermediate likelihood
characteristics
Recent cocaine use

Exam

Transient MR, hypotension,

diaphoresis, pulmonary
edema or rales

Extracardiac vascular
disease

Chest discomfort
reproduced by palpation or
respiration

EKG

New or presumably new,

transient ST segment
deviation (0.05mV) or T
wave inversion (0.2mV)
with symptoms

Fixed Q waves
Abnormal ST segments or
T waves not documented to
be new

T wave flattening or
inversion in leads with
dominant R wave
Normal EKG

Cardiac
Marker

Elevated cardiac TnI, TnT

or CK-MB

Normal

Normal

Braundwald 1994 AHCPR Publication No. 94-0602

Chest Pain Classification

Substernal
Exertional
Relieved with rest
Interpretation
Typical Angina: 3 criteria from above
Atypical Angina: 2 criteria from above
Non-Anginal Chest Pain: 1 or less criteria from
above

Classification of Angina
STABLE vs UNSTABLE
CCS Classification for STABLE Angina
I: No symptoms, or angina with strenuous exertion
II: Slight limitation of ordinary physical activity
Walking more than two blocks, climbing more than
one flight of stairs brings on angina
III: Marked limitation of ordinary physical activity
Walking less than two blocks, climbing less than
one flight of stairs
IV: Any physical activity brings on angina; angina at
rest

UA/NSTEMI 9/00

UA/NSTEMI
THREE PRINCIPAL PRESENTATIONS

Rest
Rest Angina*
Angina*

Angina
Angina occurring
occurring at
at rest
rest and
and
prolonged,
prolonged, usually
usually >> 20
20 minutes
minutes

New-onset
New-onset Angina
Angina

New-onset
New-onset angina
angina of
of at
at least
least CCS
CCS
Class
Class III
III severity
severity

Increasing
Increasing Angina
Angina

Previously
Previously diagnosed
diagnosed angina
angina that
that has
has
become
become distinctly
distinctly more
more frequent,
frequent,
longer
longer in
in duration,
duration, or
or lower
lower in
in
threshold
threshold (i.e.,
(i.e., increased
increased by
by >> 11 CCS)
CCS)
class
class to
to at
at least
least CCS
CCS Class
Class III
III severity.
severity.

** Pts
Pts with
with NSTEMI
NSTEMI usually
usually present
present with
with angina
angina at
at rest.
rest.
Braunwald
Braunwald
Circulation
Circulation 80:410;
80:410; 1989
1989

Pre-Test Likelihood of CAD

Age (y.)

Nonanginal pain
Men
Women

Atypical angina
Men
Women

Typical angina
Men
Women

30-39

34

12

76

26

40-49

13

51

22

87

55

50-59

20

65

31

93

73

60-69

27

14

72

51

94

86

Diamond and Forrester, NEJM, 1979

Relationship of Rise in Biochemical

Markers to Onset of AMI

Troponin
cTnT (33 kDa) binds to
tropomyosin to complex
molecule to thin filament
cTnI (24kDa) inhibits
actin-myosin interactions
cTnC binds Ca2+
Generally not detectable
in plasma of normal
persons

Troponin
TnT and TnI have different amino acid sequence in cardiac
vs. skeletal muscle
Permits development of cardiac specific antibodies

More sensitive and specific than CKMB

Detects minimal amounts of cardiac necrosis (neg. CKMB)
minor myocardial damage/microinfarction

Elevated in MI (pos. CKMB)

New guidelines suggest troponin is sufficient to dx MI

Other situations assoc. with increased troponin:

CHF
ICU
Renal failure
CVA
Myocarditis/other myocardial injury

TROPONINS T AND I
AS PREDICTORS OF MORTALITY
Cardiac Mortality
6.9
6.9

Total
Total Mortality
6.4
6.4

77
66

5.0
5.0

55
44
33
22

3.3
3.3
2.0
2.0

1.7
1.7

11
00
PTS
1993
PTS 1993

Trop.
Neg
Trop. Neg
No. Trials

1057
1057
Pos
Pos

RR
RR

1641
1641

792
792

Neg
Neg

Pos
Pos

RR
RR

Prognostic Significance of Cardiac Troponin

N Engl J Med 1997;337:1648-53

Risk Stratification of Patients with ACS in ER

US/NSTEMI Rx

Management of UA/NSTEMI

8 medication
Oxygen
ASA , clopidogrel
Anticoagulant: UFH, LMWH
Nitrates for pain
Nitropatch 0.4 mg/hr x 12 hours daily
IV NTG

Beta-blocker
Metoprolol 25-50 mg PO BID

+ Calcium channel blocker

ACEI for secondary prevention
Statin
Investigations:
Serial cardiac enzymes
Definitive in-hospital risk stratification.

Platelet Inhibitors in the ACS

A platelet GpIIb/IIIa receptor antagonist
should be administered, in addition to ASA
and UFH, to patients with continuing
ischemia or with other high risk features
Level of the evidence: A
ACC/AHA Guideline Circulation 2000;102:1193-1209

DEATH OR MI AT 30 DAYS
18

Placebo

16.7

GP IIb-IIIa Inhibitor

Percent of Patients

14.1

14

11.6

10.9

10.2

10.1
9

10

5.9
4.8

3.6
1.8

2
0

3.9

EPIC

CAPTURE

EPILOG

EPISTENT PRISM-PLUS PURSUIT

ACC Slide

ANTIPLATELET Rx
Class I
Definite ACS with continuing
Possible ACS Likely/Definite ACS Ischemia or Other High-Risk
Features or planned PCI
Aspirin

ACC Slide

Aspirin
Aspirin
+
+
Subcutaneous LMWH
IV heparin
+
or
IV heparin
IV platelet GP IIb/IIIa antagonist

Other Antiplatelet Agents: Clopidogrel

Primary efficacy endpoints in the CURE trial
Endpoint

Clopidogrel Placebo

Relative
risk

p value

CV
death/MI/stroke

9.3%

11.4%

0.80

<0.001

CV
death/MI/stroke/
refractory
ischemia

16.4%

18.8%

0.86

<0.001

The CURE Investigators. N Engl J Med 2001;345: 494-502.

Role at this point in combination with 2b3a inhibitor

unclear: a useful option in ASA allergic pt

Effect of Clopidogrel in ACS: the CURE trial

In Hospital Risk Stratification with

ACS: Principles
Spectrum of risk
Features associated with poor prognosis
(high probability of short term MI, etc.)
EKG features: dynamic ST depression
Cardiac markers: increased troponin

Risk stratification refers to identifying

patients at risk

Strategies for Risk Stratification

Non-invasive
EST
Sensitivity 70%
Specificity 70%

MIBI scan
Sensitivity 86-90%
Specificity 90%

Invasive
Diagnostic coronary angiography

Exercise Stress Testing

Positive response: horizontal 1mm ST depression and
symptoms
High risk response:
Deep ST depression
Poor exercise tolerance: unable to exercise past stage 2 (<6
mins)
Exercise induced hypotension and dysrhythmias

Uninterpretable:
LBBB
Digoxin
LVH

Contra-indications:

Severe Aortic stenosis

Aortic dissection
MI/ACS within 24 h
PE

Angiography

Gold standard
Defines anatomy: 1VD, 2VD, 3VD, LM
Assesses LV function
Guides treatment: PCI, CABG or medical therapy

Indications

UA/post MI with ongoing pain, ST depresssion

Hemodynamic instability
CHF, ventricular arrhythmias
Previous PCI, CABG
High risk non-invasive test
Emerging as the strategy of choice for initial evaluation of most
ACS with elevated troponins or EKG changes
Based on FRISC II, TACTICS trials

Strategy needs to be individualized.

Angiography

Indications for Invasive Risk

Stratification Strategy in UA/NSTEMI
Class I

Recurrent ischemia at rest despite medical Rx

Elevated troponin I or T
New ST depression
High risk findings on non-invasive testing
Depressed LV function
Hemodynamic instability
Sustained VT
PCI within 6 months
Prior CABG

In the absence of the above, either non-invasive or

invasive strategy can be followed.
ACC/AHA Guidelines for Management of UA/NSTEMI 2002

SUMMARY: ER Evaluation of

Patient with Chest Pain

NO

Symptoms
Suggestive of
Cardiac Origin?
YES

Consider
Alternative
Diagnosis
Stable

Unstable

Early Risk Stratification in ER

SUMMARY: Management of UA/NSTEMI

Prolonged CP (>20 minutes
or ongoing), plus:
EKG:
Transient ST changes
Sustained ST depr.
Deep T wave inv. (>5
leads)
Biochemical markers:
Troponin/CKMB
abnormal
Recurrent ischemia
AMI in last 4 weeks
Hemodynamic compromise

ASA + heparin/LMWH
GP IIb/IIIa
Early cardiac cath

INTERM. RISK
(4-8%)
No high risk features but >=1
of:
Ongoing chest pain
Crescendo angina
Borderline positive
troponin I (0.4-2.0)
Previous intervention:
PCI or CABG
Increased baseline risk
(DM, elderly)

ASA + clopidogrel
UFH or LMWH
Cardiac cath lab

LOW RISK
(<2%)
No high or
intermediated features
Chest pain, single
episode, exertional
EKG: normal or
nonspecific or
unchanged
May include previous
hx of CAD or risk
factors

ASA
No heparin
Observe/outpt tests

*30 day rate of death or MI

HIGH RISK
(12-30%)*

STEMI
WHO defn: 2 of
characteristic chest pain
ECG changes ST elevation
Biochemical changes

ACC + ESC
Rise and fall of biochemical marker (Tn, CK-MB) +
one of

ischemic symptoms
development of pathological Q waves
ECG changes suggestive of ischemia
Coronary angiography

STEMI
More than 1 million MIs per year in US
Fatal in 1/3 of pts, of death occurs within
1 hr of symptoms (arrhythmias)

Symptoms
prolonged pain > 30 min usually
constricting, crushing, or compressing; heaviness or
squeezing
can be choking, burning, knife-like
retrosternal, radiating to L>R side of chest, ulnar sides of
arms L>R, shoulder, upper extremity, jaw, neck,
interscapular region sometimes epigastric
pain usually implies ischemia
other sx

nausea/vomiting more common in inferior MI

weakness
dizziness
palpitation
cold perspiration
sense of impending doom

STEMI
Pre-hospital care
EMS

Dispatch, first response, EMS ambulance

AED to first responders
Relief of pain to reduce sympathetic tone
Rapid transfer to hospital

Prehosp fibrinolysis
Some evidence suggesting improved mortality

STEMI
ER Management
Early recognition
Ischemic type chest pain
ECG signs

ECG monitor rhythm

IV access
O2
Reperfusion strategy will depend on

Time since symptoms

Risk assoc with STEMI
Risk of lytics
Time required for PCI

Time to Rx

STEMI - Acute Rx
ASA
Block formation of thromboxane A2 in platelets by blocking cox
Chew 160-325 mg to allow for buccal absorption

Pain control
Try to decrease sympathetic activity
Analgesics
Nitrates
Coronary vasodilation, decrease preload by increasing venous
capacitance
Avoid if suspect RV infarct

Beta blockers

Reduce HR, decrease myocardial oxygen demand

Reduce pain
Reduce the need for analgesics
Reduce infarct size

Oxygen

STEMI - Reperfusion
Time is muscle
Increased mortality with delay in reperfusion
regardless of strategy
Less time:

Recovery of LV systolic fxn

Improved diastolic dysfxn
Reduced mortality
Post ischemic contractile dysfxn can occur after
reperfusion
Myocardial stunning

STEMI - Lytics
Benefits

Recanalize thrombotic occlusion

Restores coronary flow
Reduce infarct size
Improves myocardial function
Improves survival
May result in microvascualr damage and
reperfusion injury
STR strong predictor of reperfusion

STEMI - lytics
GISSI first trial to demonstrate benefit of
streptokinase
Other fibrinolytics
Alteplase (t-PA)
GUSTO I

Reteplace (rtPA)
GUSTO III (equivalence)

Tenecteplase (TNK)
ASSENT II (equiv with t-PA)

Evidence for Fibrinolysis: GISSI

n >11,000
ARR: 2%
RRR: 18%

Circ. 1998

Comparison of Thrombolytics:
GUSTO

n=>41,000
ARR 0.9%
RRR 12.5%

NEJM, 1993

ASSENT 2
N= 16949
Design: non-inferiority
Trend toward decrease in
bleeding
Improve ease of use with
Bolus infusion
Combination with heparin
IV

Lancet 1999; 354: 716-22

Time to Rx

Efficacy of Thrombolysis: Subgroups

n=56,800

Fibrinolytic
Therapy
Trialists Group.
Lancet, 1988

Choosing a Fibrinolytic
Patients in whom t-PA is proven superior to SK:
Age < 75
Anterior MI, presenting within 4 hours
High risk/extensive MI at other site within 4 hours
Cardiogenic shock
Previous SK exposure
TNK = rtPA > tPA
Easy administration
Lower chance of med error
Less non-cerebral bleeds
Patients in whom SK appears to be equivalent to t-PA:
Inferior, posterior or lateral MI
MI at any site after 6 hours
Age > 75 years

Bleeding complications with Lytics

Major bleeding 0.5-2%
Minor bleeding: 10-20 %
Intracranial hemorrhage: 0.5-2%
Management:
D/C thrombolytic
Cryoprecipitate (fibrinogen enriched)
If heparin, give protamine sulfate

Indications for Primary PCI

Class I
Alternative to thrombolytic if performed in a timely fashion by skilled
individuals
Patients within 36 hours of AMI, with cardiogenic shock, <75 years
Class IIa
Contraindication to thrombolysis
Class IIb
NSTEMI within 12 hours, with less than TIMI II flow in infarct related
artery
Class III
Elective PCI of non-IRA at time of AMI
Beyond 12 hours of symptoms, no evidence of ischemia
Successful thrombolysis

From ACC/AHA Guidelines, 2000

STEMI -PCI
Meta analyis shows improved clinical
endpoints favoring PCI
Factors to consider

Time to treatment
Risk of STEMI
Cardiogenic shock
Kilip class >= II
Risk of bleeding
Time to transport to skilled PCI center

STEMI Other Rx
ASA
ISIS-2

Thienpyridines
Clopidogrel
CLARITY

Ticlopidine
Inhibit binding to adenosine diphosphate receptor

GPIIb/IIIa inhibitors
Abciximab
Tirofiban
Eptifibatide

GUSTO V
rtPA vs 1/2rtPA and abciximab
similar efficace endpoints but increased bleeds with IIb/IIIa

ASA: ISIS 2
n > 17, 000

Lancet, 1988

STEMI Other Rx
Heparin
reduces reinfarction, stroke, PE
reduces mortality in pts receiving lytic

LMWH
ASSENT III showed benefit over UFH in pts
receiving TNK

Others
Bivalirudin (HITT)

Post- STEMI Rx
BB
ACEi

Prevents ventricular remodeling

Improved hemodynamics
Reduces CHF
Selected population: (long-term, started day 3-16)
SAVE
AIRE
TRACE

Unselected pop (short term, started early)

GISSI 3
SMILE
ISIS-4
CCS-1

Post- STEMI Rx
ARB
OPTIMAAL (losartan)
VALIANT (valsartan)

Aldasterone antagonists
EPHESUS (acute MI, LV dysfxn, HF)
Reduction in mortality

Statins
PROVE-IT

Mechanical Complications of MI
Variable

VSD

Free Wall
Rupture

Papillary
Muscle Rupture

Age

63

69

65

Days, post MI

3-5

3-6

3-5

Anterior MI

66%

50%

25%

New Murmur

90%

25%

50%

Thrill

Yes

No

Rare

Previous MI

25%

25%

30%

Echo:

VSD

Pericardial
Effusion

Flail leaflet
MR

O2 step-up
RA-RV

Equalization of
diastolic press.

Prominent Vwave

90%
50%

90%
?

90%
40-90%

PA catheter:
Mortality:
Medical
Surgical

Other Complications
Arrhythmias
Electrical instability

VPB
VT
VF
AIVR

Pump failure/inc symp drive

Sinus tachy
AFib/Flutter
SVT

Brady/conduction
Sinus brady
Junctional escape
AVB

Other Complications
Recurrent chest pain
Distinguish reinfarction from recurrent
ischemia from non-ischemic chest pain

Pericarditis
LV aneurysm

Risk Stratification
survival after STEMI depends on
LV fxn
Stress/pharma Echo, PET

Residual potentially ischemic myocardium

Submaximal ETT

Susceptibility to vent arrhythmias

Risk Stratification

Discharge Planning
usually 5 days post STEMI
counseling
ambulation but avoid heavy lifting
graded activity (symptom limited)
Rehabilitation

Questions