Non-ST-Segment Elevation
Acute Coronary Syndromes:
Risk Stratification Based on the ACC/AHA
UA / NSTEMI Guidelines
ED Risk Stratification for Chest Pain
For the past 20 years . . .
In 2002:

Does this patient need
fibrinolytic therapy?

Should this patient get antithrombin and anti-platelet
agents?

Can I safely send this patient
home?
R/O MI
ED  CCU  Cath Lab Risk Stratification for Chest Pain
Three levels of risk stratification are pertinent to the ED:

Low, intermediate, or high risk that ischemic symptoms are a
result of CAD

Low, intermediate, or high risk of short-term death or nonfatal
MI from ACS

Dynamic, ongoing risk-oriented evaluation of low- or
intermediate-risk patients for “conversion” to high-risk status
that is linked to intensity of treatment
Initial Risk Stratification Scheme
Chest Pain
History, Physical
EKG
STEMI
UA/NSTEMI/
High Risk
Mod Risk
Low Risk
Definite
Non-Cardiac
Risk Stratification Tools in the ED
•
History and Physical
•
Standard ECG and Non-standard ECG leads

Cardiac Biomarkers
• Troponin I or T, CK-MB, myoglobin

Predictive Indices / Schemes

Non-Invasive Imaging Studies
 Echocardiogram
 Exercise testing
 Technetium-99m-sestamibi: stress and rest
Initial Evaluation
Risk Stratification (1)
I IIa IIb III
Early risk stratification by symptoms,
physical findings, ECG, cardiac markers
12-lead ECG within 10 min for ongoing pain,
or ASAP if pain has resolved at presentation
Cardiac markers, Troponins and CK-MB, for
initial assessment
Monitoring, repeat ECG and cardiac markers
in 6-12 hours, if initial results normal
Initial Evaluation
Risk Stratification (2)
I IIa IIb III
If <6 hours after symptom onset, add early
myoglobin or CK-MB to troponin
C-reactive protein, other markers of
inflammation
Total CK, SGOT, HBDH, LDH
Clinical Assessment (1)

Rapid, focused evaluation

Decisions based on this evaluation have
substantial clinical and economic consequences

Are the symptoms a manifestation of ACS?
 If so, what is the prognosis?

Identify signs of life-threatening instability

Triage to most appropriate area
 Typically an ED or chest pain unit
Clinical Assessment (2)

Risk status determined in the ED by:







Assessment of anginal symptoms
Careful physical examination
Electrocardiogram
Cardiac biomarkers
CAD risk factors
Illicit drug use
Initial risk stratification assignment drives pace
of subsequent evaluation and treatment
Clinical Assessment (3)

High-risk features apparent in the ED:








Accelerated pattern of angina
Ongoing rest pain > 20 min
Signs of CHF
Hemodynamic instability
Arrhythmias - Atrial or ventricular
Advanced age (> 75 years)
Ischemic ECG changes
Elevated cardiac markers
Electrocardiogram

Carries diagnostic and prognostic value

Especially valuable if captured during pain

ST-segment depression or transient ST-segment
elevation are primary ECG markers of UA/NSTEMI
 75% of patients with + CK-MB do not develop Q waves
 Differentiation between UA and NSTEMI relies upon
positive biomarkers
 Inverted T-waves suggestive of ischemia, particularly
with good chest pain story
Six-Month Mortality by Baseline ECG Findings GUSTO-IIb Results
10%
ST 
% Mortality
8%
ST 
6%
4%
NS ST-Ts
2%
0%
0
30
60
90
120
Days from Randomization
Savonitto, JAMA 1999
150
180
Biomarkers: CK/CKMB

Until recently the principal serum marker used in
evaluation of ACS despite known limitations:
 Low levels in healthy persons limits specificity
 MB band may be elevated in skeletal muscle damage
 Different MB isoforms exist in myocardium (MB2) and
in plasma (MB1), and differentiating assay is not
widely available
Biomarkers: Troponins

Very useful in diagnosis and prognosis of ACS




Normally not detectable in blood of healthy persons;
cTnI or cTnT can be positive with negative CK-MB =
“minor myocardial damage”
Predictive of MI and death when elevated, independent
of CK-MB levels
Elevated troponins validated as a predictor of enhanced
treatment benefit from aggressive therapies (LMW
heparins, GP IIb/IIIa inhibitors, early invasive strategy)
Troponin as a Marker of Increased Risk in ACS
40%
34%
Death or MI
30%
Troponin +
Troponin -
30%
23%
22%
19%
20%
12%
11%
12%
10%
2%
4%
19%
6%
4%
1%
6%
0%
0%
Hamm
(1992)
FRISC
(1996)
TRIM
(1999)
Pettijohn
(1997)
Hamm
(1997)
Hamm
(1997)
Polanczyk Galvanni
(1998)
(1997)
Long Term Survival and Troponin-T Status
GUSTO-IIa Results
1-Year Mortality Rates:
Troponin-T Positive: 14%
Troponin-T Negative: 5%
100%
Survival
95%
TnT -
90%
p < 0.001
85%
TnT +
80%
0
50
100
150
200
250
Days from Randomization
300
350
Biomarkers: Myoglobin

Utility limited by release kinetics (early) and by lack
of cardiac specificity

Isolated elevation of myoglobin 4-8 hours after pain
onset with a a non-diagnostic ECG must be
supplemented by a more cardiac-specific marker

Sufficiently sensitive that a negative myoglobin 4-8
hours after pain onset is useful in excluding
myocardial necrosis
Integration of Biomarkers with Clinical History

Time since symptom onset should be a factor in
marker selection and in repeat assay strategy

Elevated serum levels of troponins persist for 7-14
days after initial release

Delta values, as close as 2 hours apart, may be
sufficiently sensitive to assist with serial
evaluations

Serial cardiac marker strategy not specified
Serial Cardiac Markers
Serial Testing in 309 Patients with Suspected MI
Sensitivity
Myoglobin
CK-MB (mass)
Troponin T
100%
75%
50%
25%
0%
3
4
5
6
Hours After Symptom Onset
8
12
Winter, Circulation, 1995
Biomarkers: Bedside Testing

Consideration of bedside marker assay recommended
when hospital lab turnaround time > 30-60 minutes

Ready-for-use availability must be balanced against
need for stringent QC and training of ED personnel,
CLIA concerns, political hazards, etc

Prognostic value limited because many assays are
qualitative, not quantitative
“Vein-to-Brain” Reporting Times
for Cardiac Markers - St. Agnes Hospital
Bedside Test (mean=15 mins)
Laboratory Test (mean=128 mins)
"Vein-to Brain"
Reporting Times (mins)
180
160
140
120
100
80
60
40
20
0
Test Type
Christenson R: Md Med 2001 Spring:Suppl:98-103
n = 939
SD = 46.74
Distribution of Reporting Times for
Cardiac Markers - St. Agnes Hospital
284 mins = Latest Reporting Time
95th percentile
(201.3 mins)
75th percentile
(147 mins)
50th percentile
(Median , 117 mins)
Range of Lab Reporting Times
25th
percentile
5th percentile
(85 mins)
(62.6 mins)
40 mins = Earliest Reporting Time
Christenson R: Md Med 2001 Spring:Suppl:98-103
Noninvasive Studies

Guidelines do not consider use of these tests in
the ED setting, although:
 Many EDs now use rest sestamibi scanning in
the risk stratification process
 Stress testing used after patients have “ruled out”

Reality dictates that appropriate provocative
testing often not likely after patient leaves ED
 ED is the “first, last, and best shot” at intervening
in patients with risk concerns
Predictive Indices - Risk Scores in the ED

Combine clinical history, physical exam
findings, ECG signs of ischemia, and cardiac
marker results
 PURSUIT and TIMI Risk Scores

Therapies such as LMW heparin and GP IIb/IIIa
inhibitors have greater benefit in patients with
higher risk scores

Have not been tested prospectively in the ED

Risk scores not specifically recommended by
the ACC/AHA Guidelines
Immediate Management
I IIa IIb III
Classify as non-cardiac, chronic stable angina,
possible ACS, or definite ACS
Evaluate for immediate reperfusion therapy if
definite ACS and ST-segment  present
Pharmacological or exercise stress test, if
possible ACS and serial biomarkers and ECGs
are normal
Admit pts with definite ACS, ongoing pain, 
biomarkers, new ST  or deep T-wave inversion,
abnormal hemodynamics, or (+) stress test
The “Key” to Risk Stratification

Link ongoing evaluation of risk to
changes in intensity of therapy

Develop risk stratification schemes
that reflect capabilities of ED and
needs/preferences of cardiologists

Develop treatment pathways that
provide for independent response of
emergency physicians to
recognition of higher risk levels
The “Rallying Cry” for CRUSADE . . .
A seamless transition of optimal care—diagnostic and
therapeutic—from the ED to the Cardiology Service . . .
. . . starts with a successful risk stratification strategy