Download Biochemical markers

Treatment of patients with
suspected UA/NSTEMI
2005년 8월 22일
응급의학과 R3 제상모
Definitions
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ACS
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UA
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Occurring for the first time
Accelerating angina, rest angina
NSTEMI
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Clinical syndrome of acute myocardial ischemia
UA/NSTEMI/STEMI
Elevation in biochemical markers
STEMI(ST-segment elevation MI)
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Diagnostic ST elevation on ECG testing
Pathopysiology
Epidemiology
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5-7% of total ED volume in US
6 million patients visit ED per year
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70% prove not to have ACS
3 million patients are hospitalized
0.8 million patients are MI
1.5 million patients are UA/NSTEMI
Chest pain
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Be expert! Both in diagnosis and
recommended management.
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0.4-4% of MI are sent home
Some cases UA/NSTEMI carry a worse
prognosis than STEMI
UA/NSTEMI
UA/NSTEMI
CCU
ED evaluation
Risk stratification
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Historical and physical features
ECG
Cardiac biomarkers
History
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Typical angina
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Risk factors
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Deep, poorly localized chest or arm discomfort
Exertional and relieved with rest or nitrates
Known coronary stenosis greater than 50%
>65 years and male gender
Remember atypical complaints!
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Missed MI are associated
<66 years, female gender, non white race,
normal or nondiagnostic ECGs, diabetes
Physical Examination
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Limited value to rule out ACS
Focus on ACS-related complaints
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Left ventricular failure
Valvular abnormalities
Cardiogenic shock
Clinical Predictors Of AMI Or ACS In
Intermediate-Risk Patients
AMI Odds ratio
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Clinical feature
Chest pain radiation
(Left arm)
(Right arm)
(Both left and right arm)
Nausea or vomiting
Diaphoresis
Exertional pain
Burning/indigestion pain
Crushing/squeezing pain
Relief with nitroglycerin
Pleuritic pain
Tender chest wall
Sharp /stabbing pain
1.5
3.2
7.7
1.8
1.4
3.1
4.0
2.1
0.9
0.5
0.2
0.5
ACS Odds ratio
1.7
2.5
6.0
1.0
1.2
2.5
1.5
0.9
2.0
0.5
0.6
0.8
How useful are clinical features in the diagnosis of acute,
undifferentiated chest pain? Acad Emerg Med 2002 Mar;9(3):203-208.
Electrocardiogram
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Predictive findings
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Reversible ST-segment depression in UA
Symmetric T-wave inversions greater than
0.2mV in the precordial leads(V1 through V4 )
is highly specific for stenosis of the LAD
coronary artery
Less predictive findings
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ST-segment depression less than 0.05mV
T-wave inversion of less than 0.2mV
Existing Q waves
Continuous Multi-Lead ST-segment
Monitoring
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Useful in episodes of silent ischemia
Over 24 hours, silent ischemic episodes were
found 27% of patients with UA
At 30 days, death and MI occurred in 5.7% of
those without episodes and 19.7% of with five of
more episodes
The ACEP clinical policy on chest pain also
supports this technology
Chest X ray
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Most useful in eliminating alternating diagnosis
Routine Laboratiory Studies
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Complete blood count
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Renal fx
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For drug dose reduction
Serum electrolytes
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For r/o underlying anemia
For r/o arrythmogenic abilities
Coagulation studies
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Become less necessary
Biochemical Markers
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Timing of the rise
Elevation
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Return to baseline
Myoglobin within 2-4 hours rapidly
Troponins about 6 hours
one week
CK-MB
about 6 hours
2 days
Large trials found great sensitivity and
specificity of troponins.
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Zimmerman J, Fromm R, Meyer D, et al.
Circulation 1999
(Prospective, multicenter; 955 patients)
Biochemical Markers
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Single isolated troponin measurement
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Current recommendations from ACEP
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Sensitivities of 37-49%
Specipicities of 87%-97%
Measure a first troponin on arrival
Repeat level at least eight hours after
continuous symptom onset.
Elevation fo TnT level was independently
predictive of risk across the entire
spectrum of renal fuction
Biochemical Markers
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Bed side cardiac markers
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Normal ECG
Those with positive troponin can be consulted to cardiology
minutes after arrival
Accuracy is comparable to standard laboratory assays
CK-MB performs less well than the cardiac
troponins in terms of both sensitivity and
specificity
Myoglobin has very high early sensitivity.
CRP elevation in UA/NSTEMI may indicate the
presence of multiple unstable plaques.
BNP is a relaiable predictor of death with ACS
Risk Scores
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7 variables that predicted increasing risk for
mortality (TIMI score)
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Age greater than 65 years
Presence of at least three risk factors for CAD
Prior coronary stenosis of greater than 50%
Use of aspirin within the previous seven days
Presence of ST-segment deviation on admission ECG
At least two anginal episodes in the prior 24 hours
Elevated serum cardiac biomarkers
Risk stratification
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High Likelihood Signs & Symptoms
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History : Chest or left arm discomfort as chief
complaint reproducing prior documented angina;
known history of CAD, including MI
Examination : Transient MR, hypotension, pulmonary
edema or rales
ECG : New ST deviation (> 0.05 mV) or T-wave
inversion (> 0.2 mV) with symptoms
Biochemical markers : Elevated troponin or CK-MB
American College of Cardiology/American Heart Association
Task Force on Practice Guidelines
Risk stratification
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Intermediate Likelihood
 History : Chest or left arm pain or discomfort as
chief symptom; age > 70 years; male sex;
diabetes mellitus
 Examination : Peripheral vascular disease
 ECG : Fixed Q waves; abnormal ST segments not
documented to be new T-wave flattening or
inversion with dominant R waves;
 Biochemical markers : Normal
Risk stratification
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Low Likelihood
 History : Probable ischemic symptoms in absence
of any of the intermediate likelihood characteristics;
recent cocaine use
 Examination : Chest discomfort reproduced by
palpation
 ECG : normal ECG
 Biochemical markers : Normal
Ed treatment
Risk-Based Treatment
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Anti-ischemic agents
Antiplatelet agents
Antithrombotic agents
Common Anti-Anginal Therapies
Oxygen
 Optimize oxygenation in those with or at risk for hypoxemia
 As needed to keep SaO2 > 90%
 Bed rest with continuous ECG monitoring
 Prevent and detect ischemia/arrhythmias
 Bed rest until serum biomarkers negative
 Nitrates
 Coronary dilation, pre- and after-load reduction
 0.4 mg SL q 5 min x3, consider infusion titrated to relieve
symptoms
 Beta-blockers
 Decreased myocardial oxygen consumption
 e.g., metoprolol 5 mg IV q 5 min x3, then 12.5-25.0 mg PO
BID
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Common Anti-Anginal Therapies
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Morphine
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ACE inhibitors
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Analgesia, venodilation, decreased heart rate and
blood pressure
1-5 mg IV
Afterload reduction in those with CHF, possible
myocardial remodeling benefit
Many possible agents; initiate within 24 hours of MI
Calcium-channel blockers
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Decreased myocardial oxygen consumption
Diltiazem 240 mg PO or 10-15 mg IV followed by
infusion
Antiplatelet Therapy
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Aspirin
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Antagonists of platelet ADP receptor
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Initial dose 160-325 mg PO nonenteric, then 75-160
mg PO qd
Clopidogrel (Plavix)
Ticlopidine (Ticlid), for aspirin intolerant
Glycoprotein IIb/IIIa inhibitors
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Eptifibatide (Integrilin)
Abciximab (ReoPro)
Tirofiban (Aggrastat)
For high-risk patients who have not PCI planned!
Antithrombotics
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Unfractionated heparin
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Bolus 60-70 U/kg (max, 5000 U), then 12-15 U/kg/min
IV infusion;
goal aPTT 1.5-2.5x control
Fractionated heparin
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Enoxaparin (Lovenox) 1 mg/kg SC q 12 hours
Early invasive vs. Early conservarive
Treatment
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An early trial, VANQWISH
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RITA3 trial
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Randomized 920 patients with NSTEMI
At one year, 58 deaths in the invasive group, 36 death
in the conservartive group
Randomized 1810 patients with NSETMI
Rates of death or MI were nonsignificantly different
An early invasive strategy has been
recommended in patients with UA/NSTEMI
without serious co-morbidity who have high risk
features.
Thrombolysis
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Don’t do it!
Increse the risk of MI in UA/NSTEMI
Expose patients to significant cost and
bleeding resk
Only to patients with STEMI who meet
standard AHA inclusion criteria
Disposition
Disposition
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Noncardiac causes
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Chronic stable angina
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Appropriate treatment
Exit
Definite ACS
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Stable patients with UA/NSTEMI who have recurrent
symptom, and/or ST segment deviations, or elevated
cardiac markers should be admitted
Hemodynamic instability or recurrent ischemic pain
warrant addmision to CCU
Disposition
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Possible ACS
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High risk group
 Hospitalization
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Moderate risk group
Repeat ECG and biomarkers
 Noninvasive stress testing before discharge or shortly
thereafter
Low risk group
 Immediate ED stress testing
 Repeat ECG and biomarkers
 Noninvasive stress testing before discharge or shortly
thereafter
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Chest pain observation units
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ED-based chest pain evaluation centers
Become common
Strict protocol to rapidly rule out cardiac
ischemia
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Reduce hospital charges over 60%(500-1500$ per
patient)
Decrease time in the hospital by 10-40 hours per
patient
Reduce the rates of missed AMI from 4% to 0.4%
Chest pain center 가 없으면?
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Consider outpatient provocative testing rather
than admission
Hamm et al. NEJM.
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773 patients who had acute chest pain for less than
12hours without ST segment elevation
Bed side measurement of TnT and TnI
Another sample taken at least six hours after the onset
of pain
Only 1 with negative TnT had a cardiac event within
two weeks after discharge
EM physician can safely discharge patients home
for urgent outpatient stress testing by using ECG
and troponin level at least six hours after pain
Chest pain observation units
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Erlanger chest pain evaluating protocol
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Erlanger medical center, University of Tenessee
College of Medicine
1-year period, from Jan to Dec 1999
2,074 patients with chest pain
Serial ECG monitor, 2-hour serum marker,
selective nuclear stress testing
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179 patients with AMI,
26 patients with recent AMI(decreasing curve of CKMB)
327 patients with with 30-day ACS
Provocative Testing
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Graded Exercise Testing
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Simplest and least expensive form
Sensitivity are low as 70%
Normal test has a strong negative predictive value
Eligible patient
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Symptom-free
Normal ECG
Be able to either walk on a treadmill or ride a bicycle to
achieve 70-85% predicted maximal heart rate(220-age)
Provocative Testing
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Immediate stress testing in the ED
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Kirk et al.
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Time- and cost-effective
212 low-risk patients, without evaluation biomarker
None of the patients discharged from the ED had
mortality at 30-day follow-up
Amsterdam et al.
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1000 low-risk patients with no evidence of
hemodynamic instability, arrhythmias, or ECG signs of
ischemia
They found that immediate exercise testing are safe
and accurate
Provocative Testing
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Stress echocardiography
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For patients with poor exercise tolerance
Dobutamine chemically drive the heart rate
Inducible wall motion abnormalities are hall marker of
critical CAD
Sensitivities over 85% for normal or non-diagnostinc
ECGs
Low-risk patients with negative stress echocardiogram
have a less than 1% rate for AMI and cardiac death in
the subsequent year
Limitation
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Cost, Operator dependence
Provocative Testing
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Myocardial perfusion imaging
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Sensitivities for ACS greater than 90%
Quantify infarct size
Predict the need for revascularization
Drawback
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After injection, patients must to be moved to a
radioisotope-approved area
Cost. $1000-$1600 per study
Reference
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Evidence-Based Risk Stratification Of Patients
With Suspected UA/NSTEMI, Emergency
medicine practice, April 2004.
Chest Pain: Diagnostic Strategies To Save Lives,
Time, And Money In The ED, Emergency
medicine practice, June 2003.
ACLS for experienced providers, AHA, 2003.
Marx: Rosen's Emergency Medicine: Concepts
and Clinical Practice, 5th ed