CORONARY ARTERY 3.2.

Non‐ST‐Segment Elevation Myocardial

Infarction (NSTEMI)
DISEASE (CAD) A rise in troponin, per se, is diagnostic of
myocardial necrosis but is not sufficient to define
1. Atherosclerosis myocardial infarction (MI), which is myocardial
necrosis secondary to myocardial ischemia.
2. Definitions and Classification Additional clinical, ECG, or echocardiographic
Persons with atherosclerosis of epicardial coronary evidence of ischemia is needed to define MI.
arteries and/or microcirculation may be In fact, MI is defined as a troponin
asymptomatic or present with angina pectoris on elevation above the 99th percentile of the reference
effort or develop an acute coronary syndrome limit (~0.03 ng/ml, depending on the assay) with a
(ACS). Chronic stable angina is the initial rise and/or fall pattern, along with any one of the
manifestation of CAD in approximately 50% of all following four features: (i) angina; (ii) ST‐T
patients with CAD. Stable coronary artery disease abnormalities, new LBBB, or new Q waves on
may be detected following a diagnostic ischaemia ECG; (iii) new wall motion abnormality on
test or diagnosed after presentation with an ACS. imaging; (iv) intracoronary thrombus on
ACS refers to an acute imbalance of myocardial angiography. NSTEMI is defined as MI without
oxygen supply and demand due to progressive or persistent (>20 min) ST‐segment elevation.
abrupt flow-limiting coronary stenosis and/or high- Isolated myocardial necrosis is common in
output or increased afterload states. ACS include critically ill patients and manifests as a troponin
myocardial infarction with ST segment elevation or rise, sometimes with a rise and fall pattern, but
new LBBB (STEMI), and non-ST elevation frequently no other MI features. Also, troponin I
myocardial infarction (NSTEMI) that is diagnosed usually remains <1 ng/ml in the absence of
by enzyme rise. Unstable angina is diagnosed when underlying CAD.
there are new or worsening symptoms of A rise or fall in troponin is necessary to
ischaemia, and ischaemic ECG changes such as ST define MI. A fluctuating troponin or a mild,
segment depressions and T-wave inversion, with chronically elevated but stable troponin may be
normal biomarkers. It is now evident that a large seen in chronic heart failure, myocarditis, severe
majority of patients with clinical manifestations of left ventricular hypertrophy, or advanced kidney
myocardial ischaemia, with rest pain but without disease. While having a prognostic value, this
elevated troponins by a commercially available stable troponin rise is not diagnostic of MI.
assay, and therefore considered to have UA, have Different cutoffs have been used to define a
an elevation of circulating troponins measured by a relevant troponin change, but, in general, a troponin
high-sensitivity assay and could therefore be that rises above the 99th percentile with a rise or
classified as NSTEMI. fall of >50–80% is characteristic of MI (ACC
The spectrum of ischaemic heart disease is guidelines use a less specific cutoff of 20%; 50–
presented in Figure 27.1 . 80% cutoff is more applicable to low troponin
levels <0.1 ng/ml).
3. TYPES OF ACUTE CORONARY
SYNDROME (ACS) Definition
3.1. Unstable Angina Non-ST elevation acute coronary syndromes refer
Unstable angina is defined as any of the following to a spectrum of conditions due to acute ischaemia
clinical presentations, with or without ECG that is sufficiently severe and prolonged to cause
evidence of ischemia and with a normal troponin: myocardial damage that results in the release of a
 Crescendo angina: angina that increases in biomarker of myocardial necrosis into the
frequency, intensity, or duration, often circulation, but without causing ST elevation or
requiring a more frequent use of nitroglycerin new LBBB.
 New‐onset (<2 months) severe angina, Unstable angina (UA) is a clinical term
occurring during normal activities performed that denotes rest angina (usually lasting >20
at a normal pace minutes), new-onset (within the past 2 months and,
 Rest angina at least, Canadian Cardiovascular Society III in
 Angina occurring within 2 weeks after a severity), and increasing angina (in severity and
myocardial infarction (post‐infarction angina) frequency). Its diagnostic hallmark was lack of
enzyme rise, but in the era of high-sensitivity
assays the term is rather obsolete. Variant angina
(Prinzmetal’s angina, periodic angina) denotes

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angina that usually occurs spontaneously and is In this case, ischemia is related to severely
characterized by transient ST-segment elevation increased O2 demands (demand/supply mismatch).
that spontaneously resolves or resolves with The patient may have underlying CAD but the
nitrates without progression to STEMI. coronary plaques are stable without acute rupture
or thrombosis. Conversely, the patient may not
have any underlying CAD, in which case troponin I
3.3. ST‐Segment Elevation Myocardial usually remains <0.5–1 ng/ml. Acute
Infarction (STEMI) antithrombotic therapy is not warranted.
STEMI is defined as a combination of ischemic
symptoms and persistent, ischemic ST‐segment In the absence of clinical or ECG features of MI,
elevation. For practical purposes, ischemic the troponin rise is not even called MI.
symptoms with ongoing ST‐segment elevation of
any duration are considered STEMI and treated as C. Coronary vasospasm
such. The diagnosis may be retrospectively It was initially hypothesized by Prinzmetal and
changed to NSTEMI if ST elevation quickly then demonstrated in a large series that vasospasm
resolves without reperfusion therapy, in <20 and vasospastic angina (Prinzmetal) often occur in
minutes. patients with significant CAD at the site of a
significant atherosclerotic obstruction. In one
Unstable angina and NSTEMI are grouped together series, 90% of patients with vasospastic angina had
as non‐ST‐segment elevation ACS (NSTE‐ACS). significant, single‐ or multivessel CAD. Most
However, it must be noted that unstable angina has frequently, CAD was not only significant but
a much better prognosis than NSTEMI, and unstable. In fact, a ruptured plaque is frequently
particularly that many patients labeled as unstable accompanied by vasospasm, as the activated
angina do not actually have ACS. In fact, in the platelets and leukocytes release vasoconstrictors.
current era of highly sensitive troponin assays, a About 20% of these patients with underlying CAD
true ACS is often accompanied by a troponin rise. go on to develop a large MI, while >25% develop
Unstable angina is, thus, a “vanishing” entity. severe ventricular arrhythmias or paroxysmal AV
block with syncope.
4. MECHANISMS OF ACS
A. True ACS is usually due to plaque rupture APPROACH TO CHEST PAIN,
or erosion that promotes platelet LIKELIHOOD OF ACS, RISK
aggregation (spontaneous or type 1 MI). STRATIFICATION OF ACS
This is followed by thrombus formation and Only 25% of patients presenting with chest pain are
microembolization of platelet aggregates. In eventually diagnosed with ACS. On the other hand,
NSTEMI, the thrombus is most often a platelet‐rich ~5% of patients discharged home with a presumed
non‐occlusive thrombus. This contrasts with non‐cardiac chest pain are eventually diagnosed
STEMI, which is due to an occlusive thrombus rich with ACS, and the ECG is normal in 20–37% of
in platelets and fibrin. Also, NSTEMI usually has patients with ACS.
greater collateral flow to the infarct zone than Consider the following approach in patients
STEMI. presenting with acute or recent chest pain.
As a result of the diffuse inflammation and
alteration of platelet aggregability, multiple plaque A. Assess the likelihood of ACS (Table 1.1)
ruptures are seen in ~30–80% of ACS cases,
although only one is usually considered the culprit Table 1. ACS likelihood.
in ACS. This shows the importance of medical
therapy to “cool down” the diffuse process, and High likelihood
explains the high risk of ACS recurrence within the  Elevated troponin or ST‐T abnormalities
following year even if the culprit plaque is stented. that are definitely ischemic
Occasionally, a ruptured plaque or, more  Prior history of CAD or MI with typical
angina or symptoms similar to prior MI
commonly, an eroded plaque may lead to
 S3, new MR murmura
microembolization of platelets and thrombi and
 Chest pain with signs of new HF (and
impaired coronary flow without any residual,
without malignant HTN that could account
angiographically significant lesion or thrombus.
for both pain and HF)
 Typical angina is reproduced or worsened
B. Secondary unstable angina and NSTEMI by exertion. In vasospasm, angina may
(type 2 MI).

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 occur only at rest or at night without an  Elevated troponin (NSTEMI). Any
exertional component troponin elevation (e.g., 0.05 ng/ml)
 Severe distress, deep fatigue, diaphoresis, or in a patient with chest pain and no
severe nausea during pain is concerning for other obvious cardiac or systemic
angina (the latter symptoms may occur insult (HF, critical illness) implies
without pain and are called “angina high‐risk ACS.
equivalents”). Jaw radiation is concerning
 Ischemic ECG changes (especially
for angina
new, dynamic ST depression ≥0.5
mm or transient ST elevation)
Intermediate likelihood
 PAD, age >70, diabetesb  Hemodynamic instability, electrical
instability (VT), or HF (S3,
In the absence of the above features, pulmonary edema, ischemic MR)
the following suggests a low ACS likelihood  Angina at rest or minimal exertion
(the 3 Ps) that is persistent/refractory, or
 Chest pain that is Positional or reproduced recurrent despite the initial
with certain chest/arm movements antithrombotic and anti‐ischemic
 Pleuritic pain (↑ with inspiration or cough: therapies. In patients with negative
suggests pleural or pericardial pain, or ECG/troponin, clinical features are
costochondritis) used to decide whether the persistent
 Palpable pain localized at a fingertip area chest pain is a true angina or not.
and fully reproduced with palpationc  EF <40%
 Pain >30–60 min with consistently negative  Prior PCI <6–12 months (time frame
markers.
of restenosis), or prior CABG
 Very brief pain <15 s
 TIMI risk score ≥3*
a
A new MR murmur in a patient with chest pain is
considered ischemic MR until proven otherwise.
While diabetes is associated with a higher
b
Traditional risk factors are only weakly predictive
risk of adverse outcomes in ACS, it does
of the likelihood of ACS.25 Once ACS is
not, per se, dictate early coronary
otherwise diagnosed, diabetes and PAD do
angiography. Coronary angiography is
predict a higher ACS risk.
rather dictated by the above features. As
c
True angina and PE pain may seem reproducible
stated in the 2014 ACC guidelines:
with palpation, as the chest wall is hypersensitive
“decisions to perform stress testing,
in those conditions. A combination of multiple
angiography, and revascularization should
low‐likelihood features (e.g., reproducible pain
be similar in patients with and without
that is also positional and sharp), rather than a
diabetes mellitus (class I).”
sole reliance on pain reproducibility, better
defines the low‐likelihood group.26,27
The TIMI risk score is used in ACS once
the diagnosis of ACS is established or is
B. Assess for other serious causes of chest pain
highly likely. The score should not be
at least clinically, by chest X‐ray and by ECG
used for the diagnosis of ACS; it has a
(always think of pulmonary embolism, aortic
prognostic rather than a diagnostic value.
dissection, and pericarditis).
Also, this score is one risk stratifier out of
many. An elevated troponin may be
C. The patient with a probable ACS should
associated with a TIMI risk score of only
be risk stratified into a high‐ or low‐risk
1, yet still implies a high‐risk ACS. In the
category
right setting, even a mild troponin rise
1. High‐risk ACS. Any of the following
(e.g., 0.05 ng/ml) implies a high‐risk
features implies a high risk of major
ACS.
adverse coronary events (mortality, MI, or
need for urgent revascularization within
Table 2. Cardiovascular Disease Risk Factors
30 days), and justifies early coronary
angiography and a more aggressive Non- Modifiable Contributing
antithrombotic strategy. These high‐risk modifiable Factors Factors
features should only be sought after (Fixed)
establishing that ACS is highly probable: Factors
• Heredity • High • Stress

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 • Race blood • Inflammatory
• Gender pressure markers
• Age • Elevated • Psychosocial
serum factors
cholesterol • Alcohol
levels intake
• Tobacco
use
• Diabetes
• Physical
inactivity
• Obesity
• Metabolic
syndrome
1. Non‐ST‐Segment Elevation Acute Coronary
Syndrome
Box 1. Clinical Spectrum of Atherosclerotic
Coronary Artery Disease.
 Subclinical symptoms or asymptomatic
 Stable angina
 Unstable angina
 Acute myocardial infarction
 Acute pulmonary edema
 Sudden death

Prevalence
Coronary heart disease is one of the most common
health disorders in modern life, accounting for
nearly one-third of all deaths. It may be silent or
may manifest as angina, acute coronary syndromes
or sudden death. It is already a major cause of
disability, and the World Health Organization has Daftar Pustaka
estimated that it will be by far the major health 1. Katritsis DG, Gersh BJ, and Camm AJ. (2016)
burden worldwide within the next two decades. Clinical Cardiology: Current Practice
Guidelines, Updated Edition. Oxford
University Press
Table 3. CLINICAL MANIFESTATIONS OF
CORONARY ARTERY DISEASE

Vessel Blood Flow Clinical

Architecture Manifestation
Early plaque Unobstructed Asymptomatic
Critical Blood flow Stable angina
coronary limited
artery stenosis during
>70% exertion
Unstable Platelet Unstable angina
plaque rupture thrombus
begins to form
and spasm
limits blood
flow at rest
Unstable Transient or Non–ST-segment
platelet incomplete elevation
thrombus on vessel (subendocardial)
ruptured occlusion myocardial
plaque (lysis occurs) infarction
Platelet Complete ST-segment
thrombus on vessel elevation
ruptured occlusion (no (transmural)
plaque lysis) myocardial
infarction