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-Ts
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
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