Download diagnosing acute coronary syndrome and determining patient risk

REVIEW
DIAGNOSING ACUTE CORONARY SYNDROME
AND DETERMINING PATIENT RISK
—
Edith A. Nutescu, PharmD*
ABSTRACT
Acute coronary syndrome is a form of coronary
artery disease and has a broad range of clinical
presentations. Generally, patients with acute
coronary syndrome are categorized as having
ST-segment elevation myocardial infarction,
non–ST-segment elevation myocardial infarction,
or unstable angina. The findings on the electrocardiogram and other information from a thorough history and clinical examination allow
patients to be stratified according to their risk for
further myocardial damage. Risk stratification
will determine an individual patient’s need for
aggressive cardiac treatment, observation, or
referral. The clinical characteristics that can be
used to determine a patient’s risk of death or a
subsequent cardiac event are reviewed along
with the American College of Cardiology/
American Heart Association guidelines for immediate management after risk stratification.
(Adv Stud Pharm. 2006;3(3):106-111)
*Clinical Associate Professor, Director, Antithrombosis
Center, College of Pharmacy, The University of Illinois at
Chicago, Chicago, Illinois.
Address correspondence to: Edith A. Nutescu, PharmD,
Clinical Associate Professor, Director, Antithrombosis Center,
College of Pharmacy, The University of Illinois at Chicago, 833
South Wood Street, m/c 886, Room 164, Chicago, IL
60612. E-mail: [email protected].
106
cute coronary syndrome (ACS) is a potentially life-threatening manifestation of
coronary artery disease (CAD), which is
the leading cause of death in the United
1
States. The term ACS describes a broad range of clinical presentations. Patients are generally categorized
according to the results of an initial 12-lead electrocardiogram (ECG) as having ST-segment elevation
myocardial infarction (STEMI) or non–ST-segment
elevation myocardial infarction (NSTEMI). Patients
with an initial ECG suggesting NSTEMI may be
experiencing the closely related condition unstable
angina (UA), which is a relatively high-risk intermediate state between stable angina and myocardial infarction. Both conditions are common manifestations of
CAD that present as ACS.2
Persistent ST-segment elevation accompanied by
chest pain usually indicates total coronary occlusion,
resulting in irreversible myocardial damage. This presentation requires immediate reperfusion of the coronary vessel by medical or pharmacologic intervention
to prevent further myocardial damage.3 Patients who
present with chest pain but do not have persistent STsegment elevation are likely suffering from NSTEMI or
UA, both of which are usually caused by partial occlusion of a coronary artery. In these patients, ischemia
and symptoms should be relieved by appropriate pharmacologic therapy, such as aspirin, low–molecularweight heparin or unfractionated heparin, glycoprotein
IIb/IIIa inhibitors, clopidogrel, beta blockers, nitrates,
and statins. All patients should be subsequently monitored by serial ECGs and measurements of serum biomarkers for myocardial necrosis.3
Despite treatment advances, the rates of mortality,
subsequent cardiac events, and hospitalization remain
high for patients who present with ACS.1 The high
rate of poor outcomes in these patients can be at least
partially attributed to the overlapping characteristics of
A
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STEMI and NSTEMI/UA that
complicate the diagnosis upon
initial presentation.2 This article
reviews the various clinical characteristics, the American College
of Cardiology/American Heart
Association (ACC/AHA) risk
stratification guidelines for
patients experiencing ACS, and
treatment implications for
patients with NSTEMI/UA.
Table 1. Likelihood that Acute Coronary Syndrome Symptoms Result from
Coronary Artery Disease
High Risk
Medium Risk
Evaluation
History
Low Risk
Findings
• Chest discomfort or
left arm pain
• Recurrent,
documented angina
• History of coronary
artery disease or
myocardial infarction
• Chest or left arm pain • Probable ischemic
• Age >70
symptoms without
• Male sex
intermediate risk
• Diabetes mellitus
findings
• Recent cocaine use
CLINICAL EVALUATION
Physical examination • New transient mitral
Extracardiac vascular
Chest discomfort on
Typical symptoms of ACS
regurgitation
disease
palpation
include chest pain, referred
• Hypotension
• Diaphoresis
pain, nausea, vomiting, dys• Pulmonary edema or
pnea, diaphoresis, and lightrales
headedness. Although some
patients may not complain of
ECG
• New transient ST
• Fixed Q waves
• T-wave flattening
chest pain, the presence of
deviation
• Pre-existing abnormal • T inversion in leads
• T-wave inversion
ST or T waves
with dominant R
symptoms such as referred pain
with symptoms
waves
that radiates to the shoulder, left
• Normal ECG results
arm, or both arms increases the
likelihood of ACS. Patients preSerum cardiac
Elevated troponin T,
Normal
Normal
senting with the 3 classic sympmarkers
troponin I, or CK-MB
toms of typical angina
ECG = electrocardiogram; CK-MB= creatine kinase, myocardial bound.
(substernal pain that occurs on
Adapted with permission from Braunwald et al. Available at http:www.acc.org/clinical/guidelines/unstable/
exertion and is relieved by rest)
unstable.pdf. Accessed March 25, 2006.
have an increased risk of ACS.4
The presence of atypical symptoms does not rule out ACS.
2).2 The prognosis for patients with UA can be judged
However, multiple atypical symptoms may be useful in
5
by the pace of their clinical course, which can predict
identifying patients at low risk for ACS.
their short-term risk for a cardiac event and their
In patients presenting with chest pain, ruling out
chance of surviving an event. Estimating risk for
noncardiac causes is the primary challenge, requiring a
patients with chest pain at rest can help the clinician
thorough initial evaluation including history with risk
determine the appropriate site of care and the approfactor analysis, physical examination, 12-lead ECG,
priate therapy. Patients at the highest risk will likely
and serum cardiac biomarker measurements, such as
benefit from treatment in coronary care units, wherecardiac-specific troponins T and I.2 Table 1 lists the
as patients at lesser risk may be appropriately managed
clinical factors that characterize patients at high, mediin monitored step-down units or as outpatients.
um, and low risk for ACS resulting from CAD.
Likewise, risk stratification will identify those patients
Patients with a history of ACS or persistent chest pain,
who may benefit from more aggressive therapies, such
unstable vital signs, and syncope should be considered
as glycoprotein IIb/IIIa inhibitors.2
at the highest risk. For these patients, immediate transfer to a cardiac monitoring unit or emergency departDIAGNOSTIC ECG MORPHOLOGY
ment is warranted.2
ST-ELEVATION MYOCARDIAL INFARCTION
For patients who are diagnosed with UA, the shortAmong the clinical presentations of ACS, STEMI
term risk of death or a cardiac event can be stratified
is the most urgent because of the risk for progressive
into high-, moderate-, and low-risk categories (Table
2
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myocardial damage. Approximately 25% of patients with an
ACS will present with new or
presumed new ST elevation on
their ECG.6 Normal or nondiagnostic ECGs do not preclude the
presence or emergence of acute
myocardial infarction (AMI).
Therefore, ST deviation should
be interpreted in the larger context of the clinical presentation
and overall ECG characteristics.7
Because patients with STEMI
are at high risk for progressive
myocardial damage, they require
immediate reperfusion therapy
(either percutaneous coronary
intervention or thrombolytic
therapy) to open the occluded
coronary artery.6
Table 2. Short-term Risk Stratification for Death or MI in Patients with
Unstable Angina
Feature
High Risk
Presence of ≥1
symptoms in this column,
without high-risk features
History
Increasing ischemic
symptoms in prior 48
hours
Prior MI, peripheral or
cerebrovascular disease,
CABG, prior aspirin use
Character of pain
Prolonged ongoing
(>20 minutes) rest pain
ANGINA
108
•Resolved but prolonged
(>20 minutes) rest
angina with moderate
or high likelihood of
CAD
Any symptom in
this column without
moderate- or highrisk features
New-onset or
progressive CCS
Class III or IV angina
in the past 2 weeks
without prolonged
(>20 minutes) rest
pain but with
moderate or high
likelihood of CAD
•Rest angina (<20
minutes) or relieved
with rest or sublingual
nitroglycerin
INFARCTION AND UNSTABLE
DIAGNOSTIC SERUM CARDIAC
MARKERS
Table 3 summarizes the
important clinical points for 3
serum cardiac markers that are
crucial for distinguishing
Low Risk
Presence of ≥1
symptoms in this column
NON–ST-ELEVATION MYOCARDIAL
Approximately 75% of
patients with an ACS present
with NSTEMI or UA. Of these
patients, 40% to 60% will be
diagnosed with NSTEMI based
on positive cardiac troponins,
and the rest will have UA. ECG
changes associated with NSTEMI/UA may include such
changes as ST depression or
other ST-segment abnormalities,
T-wave inversion, or the ECG
may be normal. ST depression is
associated with increased mortality, especially when present in ≥2
ECG leads.8 Primary ST depression is not an indication for
thrombolytic therapy.
Moderate Risk
Clinical findings
•Pulmonary edema,
Age >70 years
likely from ischemia
•New or worsening
mitral regurgitation
murmur
•S3 or new worsening rales
•Hypotension,
bradycardia,
tachycardia
•Age >75 years
ECG
•Angina at rest with
transient ST-segment
changes >0.05 mV
•Bundle-branch block,
new or presumed new
•Sustained ventricular
tachycardia
Cardiac markers
Elevated troponin T or I
(>0.1 ng/mL)
•T-wave inversions >0.2
mV
•Pathological Q waves
Slightly elevated
troponin T or I
(<0.1 ng/mL)
Normal or
unchanged ECG
during an episode
of chest discomfort
Normal
MI = myocardial infarction; CABG = coronary artery bypass graft; CAD = coronary artery disease;
ECG = electrocardiogram.
Adapted with permission from Braunwald et al. Available at http:www.acc.org/clinical/guidelines/unstable/
unstable.pdf. Accessed March 25, 2006.2
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NSTEMI from UA. Creatine kinase
Table 3. Serum Cardiac Markers for Acute Myocardial Infarction
(CK) is an enzyme found in many
body organs and striated muscle. CK
*Positive
*Negative
may be elevated in cardiac and noncarHours to First
Hours to Peak
Predictive
Predictive
diac conditions; therefore, it is sensitive
Protein Marker
Positive Test
Level
Value %
Value %
or specific for detecting myocardial
Creatine kinase
3–8
12–24
30
99
injury.4 The more cardiac-specific CK
Creatine kinase-MB
4–6
12–24
73
99
isoenzyme CK-MB replaced CK testTroponin I and T
4–10
8–28
72
98
ing, but because it is also found in
skeletal muscle and the blood of
*Measured by serial assays
Adapted with permission from Achar et al. Am Fam Physician. 2005;72(1):119-126.
healthy patients, it also lacks sensitivity
for detecting cardiac necrosis. CK-MB
is helpful in the early diagnosis of AMI
because CK-MB is typically detectable
in the blood earlier than other cardiac
markers.2 Although CK-MB isoform
risk of poor outcomes in patients with ACS.2 Further
assays are not yet widely available, 1 large study sugresearch is needed to determine whether these markers
gested that CK-MB isoform analysis has sensitivity
will have utility in risk stratification algorithms.
and specificity of approximately 95% six hours after
symptom onset.9
RISK STRATIFICATION AND TREATMENT IMPLICATIONS
The isoforms of cardiac troponins, troponin T and
Patient history, physical examination, and laboratroponin I, are specific to cardiac muscle and, theretory assessment are key for detecting the presence of
fore, are the most reliable indicators of cardiac damcardiovascular disease risk factors. The degree of carage.10 Because of their high sensitivity and specificity
diovascular risk attributable to these risk factors is profor even small amounts of myocardial injury, the ACC
portional to their severity and duration. Because the
and the European Society of Cardiology now recomincidence of cardiac events increases with age, is highmend the use of cardiac troponins as the preferred bioer in men than in women (and affects men at an earlimarker for diagnosing MI.3 The presence of normal
er age), and is higher in people with a family history of
CK-MB and elevated cardiac troponins typically indiheart disease, the AHA has identified age, male sex,
cates minor myocardial damage or microinfarction.
and heredity as the major nonmodifiable cardiovascuHowever, elevation in both of these markers indicates
lar risk factors. Similarly, the AHA has identified
AMI.4 The level of serum troponins correlates with the
smoking, high cholesterol, hypertension, physical
risk of death and subsequent cardiac events. Patients
inactivity, excess body fat, and diabetes as the major
with high troponin levels will require the most urgent
modifiable risk factors for coronary disease.14 The presintervention, whereas patients with low troponin levence of traditional risk factors should be taken into
els may be monitored as outpatients.11,12 In patients
account when determining the prognosis of patients
with negative cardiac markers collected within 6 hours
who present with ACS.
of chest pain onset, another sample should be analyzed
The estimation of risk level for patients with ACS
over the next 8 to 24 hours.
depends on multiple variables and cannot be reduced
Elevated levels of other biochemical markers, such
to a simple algorithm. Nevertheless, an assessment of
as highly sensitive C-reactive protein (hs-CRP) and
prognosis often determines the pace of initial evaluafibrinogen, have been observed in patients with
tion and treatment strategies. There is a strong relaischemic chest pain.13 Although data supporting the
tionship between ischemia caused by CAD and poor
routine measurement of these markers are unavailable,
prognosis. Therefore, determining the likelihood of
they may provide supportive diagnostic information.
CAD will aid in estimating prognosis in addition to
Elevated fibrinogen, for example, indicates coagulaselecting the site of care and initial therapy.2 As a clintion cascade activity and is associated with increased
ical presentation, NSTEMI/UA shares characteristics
risk for poor outcomes in patients with ACS.2
with several lower and higher risk conditions, such as
Similarly, elevated hs-CRP is associated with increased
severe chronic stable angina and STEMI.
4
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The Thrombolysis in Myocardial Infarction
(TIMI) risk score is a validated, arithmetic tool to predict a patient’s risk of death and cardiac ischemic
events when they present with NSTEMI/UA.2 The
TIMI risk score is calculated from the sum of variables
that are easily attained during the initial evaluation
(Table 4). Using the TIMI score system, Antman et al
showed that as the TIMI score increased in the study
population, the risk of death, MI, or recurrent
ischemia requiring urgent revascularization increased
significantly (Figure).15 Patients with the lowest scores
upon presentation were at nearly 5% risk for reaching
the composite endpoint (ie, death, new or recurrent
MI, or revascularization), whereas patients with the
highest number of factors upon presentation were at
nearly 41% risk for the endpoint. The TIMI risk score
can guide clinicians as they plan further evaluations
and treatment by providing a reliable prognostic
assessment for individual patients. Patients at progressively higher risk have been shown to benefit from
newer therapies, such as low–molecular-weight
heparin or glycoprotein IIb/IIIa inhibitors, in addition
to an early invasive strategy, such as percutaneous
coronary intervention.16-18 Therefore, the TIMI risk
score may be useful in identifying patients who would
benefit from these newer therapies.2 The use of the
TIMI risk score, in combination with the information
gathered from the physical examination, medical history, ECG, and cardiac biomarkers, can be used to
assess the risk of mortality and other major adverse
cardiac events. Such a risk assessment can then be used
to determine the aggressiveness of evaluation and therapy. In addition to appropriate pharmacological therapy, patients at higher risk are typically treated with an
early invasive approach consisting of coronary angiography followed by percutaneous coronary intervention, if appropriate.2 A less aggressive approach is often
appropriate in patients deemed to be at lower risk.
CONCLUSIONS
In patients with chest pain, differentiating between
cardiac and noncardiac causes represents a major challenge. Similarly, determining the immediate risk for
patients with ACS requires a thorough clinical evaluation. Patients with ST elevation on their initial ECGs
are at significant risk of progressive myocardial damage
and require urgent revascularization. For patients who
do not have ST elevation, other factors, such as medical
history, physical examination, and cardiac biomarkers,
110
Table 4. TIMI Risk Score for NSTEMI/UA
Factor
Point Value
Age >65
≥3 CAD risk factors
Prior coronary stenosis =50%
ST deviation at presentation
≥2 anginal events in past 24 hours
Aspirin use in prior 7 days
Elevated serum cardiac markers
1
1
1
1
1
1
1
Total of 7
TIMI = Thrombolysis in Myocardial Infarction; NSTEMI/UA = non–ST-segment elevation myocardial infarction/unstable angina; CAD= coronary
artery disease.
Adapted with permission from Antman et al. JAMA. 2000;284(7):835-842.15
Figure. TIMI Risk for Death, MI, or Urgent
Revascularization
TIMI= Thrombolysis in Myocardial Infarction; MI= myocardial infarction.
P <.001 for trend.
Adapted with permission from Antman et al. JAMA.2000;284:835-842.15
are used to help identify those patients at higher risk
who are likely to benefit from aggressive therapies. The
cardiac troponins T and I are the gold standard for
determining the presence and extent of myocardial
damage. A risk stratification method that uses easily
obtained information, such as the TIMI risk score, can
help identify those patients who are at the greatest risk
for poor outcomes. Therefore, risk stratification is
essential to determining an appropriate management
strategy and may prove to be a factor in reducing the
high rates of mortality associated with ACS.
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