Acute Coronary Syndrome (non-ST-

Segment Elevation Myocardial infarction

and unstable Angina , ST elevation
Myocardial Infarction)

Dr.M.Gholipour
Cardiologist
Faculty members of Guilan University of Medical Sciences
 Patients with ischemic heart disease fall into two large groups: patients with
chronic coronary artery disease (CAD) who most commonly present with stable
angina and patients with acute coronary syndromes (ACSs).

 These include patients with acute myocardial infarction with ST-segment elevation
(STEMI) on their presenting electrocardiogram and those with non-ST-segment
elevation acute coronary syndrome (NSTE-ACS). The latter include patients with
non-ST-segment elevation myocardial infarction (NSTEMI), who, by definition,
have evidence of myocyte necrosis, and those with unstable angina (UA), who
do not.
 The relative incidence of
NSTEMI compared to STEMI
appears to be increasing .
Every year in the United
States, approximately 1.1
million patients are admitted
to hospitals with NSTE-ACS as
compared with ~300,000
patients with acute STEMI.
Women comprise more than
one-third of patients with
NSTE-ACS, but less than one-
fourth of patients with
STEMI.
 PATHOPHYSIOLOGY
 NSTE-ACS is most commonly caused by an imbalance between oxygen supply and
oxygen demand resulting from a partially occluding thrombus forming on a disrupted
atherothrombotic coronary plaque or on eroded coronary artery endothelium.

 Severe ischemia or myocardial necrosis may occur consequent to the reduction of

coronary blood flow caused by the thrombus and by downstream embolization of
platelet aggregates and/or atherosclerotic debris.

 Other causes of NSTE-ACS include:

 (1)dynamic obstruction (e.g., coronary spasm, as in Prinzmetal’s variant angina

 (2) severe mechanical obstruction due to progressive coronary atherosclerosis; and
 (3) increased myocardial oxygen demand produced by conditions such as fever,
tachycardia, and thyrotoxicosis in the presence of fixed epicardial coronary
obstruction. More than one of these processes may be involved.
Activation of the coagulation cascade and platelets plays a central role in the formation
of thrombus following plaque rupture/erosion.

1) The first step in thrombus formation is vascular injury or endothelial dysfunction,

which causes adhesion of platelets to the arterial wall via binding of platelet
glycoprotein (GP) Ib to subendothelial von Willebrand factor.

2) Exposure of platelets to subendothelial collagen and/or circulating thrombin causes

platelet activation which induces platelets to change shape and results in degranulation
with release of adenosine diphosphate ADP) and thromboxane A2 (TxA2)—which in turn
causes further platelet activation and expression of platelet glycoprotein GP IIb/IIIa

In parallel, tissue factor expressed within the lipid-rich core of atherosclerotic plaque, when
exposed to circulating blood, activates the coagulation cascade. A complex of tissue factor and
coagulation factors VIIa and Va leads to the formation of activated factor X (factor Xa), which in
turn amplifies the production of activated factor IIa (thrombin).

The cascade proceeds with thrombin-induced conver-sion of fibrinogen to fibrin. The platelet
and coagulation systems converge in that thrombin is also a potent platelet activator.
3) Platlet GP IIb/IIIa binds circulating fibrinogen, thereby causing platelet aggregation
and ultimately producing a platelet-fibrin thrombus, portions of which may embolize
distally and cause myocardial necrosis.
Coronary artery anatomy
The thrombus transforms a region
of plaque narrowing to one of
severe or complete occlusion, and
the impaired blood flow causes a
marked imbalance between
myocardial oxygen supply and
demand.
Infarctions can be described pathologically by the extent of necrosis they produce within
the myocardial wall.
Transmural infarcts span the entire thickness of the myocardium and result from total,
prolonged occlusion of an epicardial coronary artery.

subendocardial infarcts exclusively involve the innermost layers of the myocardium. The
subendocardium is particularly susceptible to ischemia because it is the zone subjected
to the highest pressure from the ventricular chamber, has few collateral connections that
supply it, and is perfused by vessels that must pass through layers of contracting
myocardium.
 CLINICAL PRESENTATION

Diagnosis
The diagnosis of NSTE-ACS is based largely on the clinical presentation.
Typically, chest discomfort is severe and has three features:
(1) it occurs at rest (or with minimal exertion), lasting >10 minutes
(2) it is of relatively recent onset (i.e., within the prior 2 weeks); and/or
(3) it occurs with a crescendo pattern (i.e., distinctly more severe, prolonged, or
frequent than previous episodes).

The diagnosis of NSTEMI is established if a patient with these clinical features

develops evidence of myocardial necrosis, as reflected in abnormally elevated
levels of biomarkers of cardiac necrosis
History and Physical Examination
The chest discomfort, often severe enough to be described as frank pain, is
typically located in the substernal region or sometimes in the epigastrium,
and radiates to the left arm, left shoulder, and/or neck.

Anginal “equivalents” such as dyspnea, epigastric discomfort, nausea, or weakness

may occur instead of chest pain and appear to be more frequent in women,
the elderly, and patients with diabetes mellitus.

The physical examination resembles that in patients with stable angina and may
be unremarkable. If the patient has a large area of myocardial ischemia or a large
NSTEMI, the physical findings can include diaphoresis; pale, cool skin; sinus
tachycardia; a third and/or fourth heart sound; basilar rales; and, sometimes,
hypotension.
Electrocardiogram
ST-segment depression occurs in 20 to 25% of patients; it may be transient
in patients without biomarker evidence of myocardial necrosis, but may be
persistent for several days in NSTEMI. The ECG aids in both diagnosis and
prognosis. ST segment elevation ≥1 mm in ≥2 contiguous leads is required for
the diagnosis of STEMI. ST segment depression as little as 0.5 mm is suggestive
of ischemia. T wave inversions of at least 2 mm can also indicate ischemia but
are less specific
Completely normal findings on an ECG do not exclude the possibility of ACS;
the risk for acute MI is approx-imately 4% in patients with a history of CAD and
2% in those with no such history

Patients with normal or nearly normal findings on an ECG, however, have a

better prognosis than do those with clearly abnormal ECGs at initial evaluation.

normal ECG has a negative pre-dictive value of 80% to 90%, regardless of

whether the patient was expe-riencing chest pain at the time that the ECG was
obtained.
Diffuse ST- segment elevation and PR- segment depression suggest
pericarditis.
Right- axis deviation, right bundle branch block, T wave inversions in leads V1
to V4, and an S wave in lead I and Q wave and T wave inver-sions in lead III
suggest Pulmonary emboli
 Chest Radiography

A chest radiograph is typically obtained for all patients with chest pain.
It is usually nondiagnostic in patients with ACS but can show pulmonary edema
secondary to ischemia- induced diastolic or systolic dysfunction.

It is more useful for diagnosing or suggesting other disor-ders; for example, it

may show a widened mediastinum or aortic knob in patients with aortic
dissection.
The chest radiograph is generally normal in PE but can show atelectasis, an
elevated hemidiaphragm, a pleural effusion, or more rarely, a Hampton hump or
Westermark sign. The chest radiograph can reveal pneumonia or pneumothorax. 
Cardiac Biomarkers
Patients with NSTEMI have elevated biomarkers of necrosis, such as cardiac troponin I or T, which
are specific, sensitive, and the preferred markers of myocardial necrosis.
The MB isoform of creatine kinase (CK-MB) is a less sensitive alternative.

Elevated levels of these markers distinguish patients with NSTEMI from those with UA.
There is a characteristic temporal rise and fall of the plasma concentration of these markers and
a direct relationship between the degree of elevation and mortality

However, in patients without a clear clinical history of myocardial ischemia, minor cardiac troponin
(cTn) elevations have been reported and can be caused by congestive heart failure, myocarditis, or
pulmonary embolism, or using highsensitivity assays, they may occur in ostensibly normal subjects.

Thus, in patients with an unclear history, small elevations of cTn, especially if they are persistent,
may not be diagnostic of an ACS. With more widespread measurement of troponin, especially
using high-sensitivity assays, an increasing fraction of patients with NSTEACS are found to have
NSTEMI, whereas the fraction of patients with UA is dwindling.
Type 2 MI occurs when there is clinical evidence of myocardial ischemia and an
elevated biomarker of necrosis, but in the setting of
stable coronary disease with either reduced myocardial oxygen supply (e.g.,
hypotension, vasospasm, severe anemia) or
increased myocardial oxygen demand (e.g., hypertensive crisis, tachycardia, critical
aortic stenosis, severe hypertrophic cardiomyopathy, extreme exercise).
Other patients may have an elevated troponin but without evidence of acute
ischemia; this is termed “myocardial injury,” and may be seen in direct
myocyte injury, such as in myocarditis, myocardial contusion, or cardioversion or
defibrillation.
Sepsis and acute viral infections including that due to SARS- CoV2 can precipitate
type 2 MI.
Myocardial injury can also occur in right ventricular strain as in PE, in other causes
of acute pulmonary hypertension, or in cases of catechol excess such as in sepsis,
stroke, or subarachnoid hemorrhage or other critical illness. Patients with renal
disease can have stable but elevated levels of cardiac troponins.
DIAGNOSTIC
EVALUATION In addition to the clinical examination, three major noninvasive tools are
used in the evaluation of NSTEMI-ACS: the electrocardiogram (ECG), cardiac
biomarkers, and stress testing. CCTA is an additional emerging option
The goals are to: (1) recognize or exclude myocardial infarction (MI)

using cardiac biomarkers, preferably cTn(2) detect rest ischemia (using serial or
continuous ECGs); and (3) detect significant coronary obstruction at rest with CCTA and
myocardial ischemia using stress testing .

Patients with a low likelihood of ischemia are usually managed with an emergency department–
based critical pathway (which, in some institutions, is carried out in a “chest pain unit”)
Evaluation of such patients includes clinical monitoring for recurrent ischemic discomfort
and continuous monitoring of ECGs and cardiac markers, typically obtained at baseline and at
1-3 h after presentation. If new elevations in cardiac markers or ST-T-wave changes on the ECG
are noted, the patient should be admitted to the hospital. Patients who remain pain free with
negative markers may proceed to stress testing to determine the presence of ischemia or CCTA to
detect coronary luminal obstruction
RISK STRATIFICATION
Patients with documented NSTE-ACS exhibit a wide spectrum of early (30 days) risk of death, ranging from
1 to 10%, and a recurrent ACS rate of 5 to 15% during the first year.
Assessment of risk can be accomplished by clinical risk scoring systems such as that developed from the
Thrombolysis in Myocardial Infarction (TIMI) Trials, which includes seven independent risk factors
TREATMENT
non-St-SegMent eleVation acute coronary SyndroMe (non-St-SegMent
eleVation Myocardial infarction and unStaBle angina)

Medical Treatment

Patients should be placed at bed rest with continuous ECG monitoring for ST-segment
deviation and cardiac arrhythmias. Ambulation is permitted if the patient shows no
recurrence of ischemia (symptoms or ECG changes) and does not develop an elevation of
a biomarker of necrosis for 12–24 h. Medical therapy involves simultaneous anti-ischemic
and antithrombotic treatments and consideration of coronary revascularization.
ANTI-ISCHEMIC TREATMENT
To provide relief and prevention of recurrence of chest pain, initial treatment should include bed rest,
nitrates, beta adrenergic blockers, and inhaled oxygen in the presence of hypoxemia.
PRINZMETAL’S VARIANT ANGINA In
1959 Prinzmetal et al. described a syndrome of
severe ischemic pain that usually occurs at rest
and is associated with transient ST-segment
elevation. Prinzmetal’s variant angina (PVA) is
caused by focal spasm of an epicardial coronary
artery, leading to severe transient myocardial
ischemia and occasionally infarction. The cause of the
spasm is not well defined, but it may be related to
hypercontractility of vascular smooth muscle due to
adrenergic vasoconstrictors, leukotrienes, or
serotonin. For reasons that are not clear, the
prevalence of PVA has decreased substantially during
the past few decades
 Clinical and Angiographic Manifestations

 Patients with PVA are generally younger and have fewer coronary risk factors (with the
exception of cigarette smoking) than do patients with NSTE-ACS. Cardiac examination is usually
unremarkable in the absence of ischemia.

 The clinical diagnosis of PVA is made by the detection of transient ST-segment elevation with
rest pain. Many patients also exhibit multiple episodes of asymptomatic ST-segment elevation
(silent ischemia). Small elevations of troponin may occur in patients with prolonged attacks.

 Coronary angiography demonstrates transient coronary spasm as the diagnostic hallmark of

PVA. Atherosclerotic plaques in at least one proximal coronary artery occur in about half of
patients, and in these patients, spasm usually occurs within 1 cm of the plaque.

 Focal spasm is most common in the right coronary artery, and it may occur at one or more sites
in one artery or in multiple arteries simultaneously. Hyperventilation or intracoronary
acetylcholine has been used to provoke focal coronary stenosis on angiography or to provoke
rest angina with ST-segment elevation to establish the diagnosis.
TREATMENT
PrinzMetal’S Variant angina Nitrates and calcium channel blockers are the main therapeutic
agents. Aspirin may actually increase the severity of ischemic episodes, possibly as a result of
the sensitivity of coronary tone to modest changes in the synthesis of prostacyclin. The
response to beta blockers is variable. Coronary revascularization may be helpful in patients who
also have discrete, flow-limiting, proximal fixed obstructive lesions.

Prognosis Many patients with PVA pass through an acute, active phase, with frequent episodes
of angina and cardiac events during the first 6 months after presentation.
Survival at 5 years is excellent (~90–95%). Patients with no or mild fixed coronary obstruction
tend to experience a more benign course than do patients with associated severe obstructive
lesions. Nonfatal MI occurs in up to 20% of patients by 5 years.
Patients with PVA who develop serious arrhythmias during spontaneous episodes of pain are at
a higher risk for sudden cardiac death. In most patients who survive an infarction or the
initial 3- to 6-month period of frequent episodes, there is a tendency for symptoms and cardiac
events to diminish over time.
Primary Percutaneous Coronary Intervention

An alternative to fibrinolytic therapy in patients with acute STEMI is immediate cardiac

catheterization and PCI of the lesion responsible for the infarction.

This approach is termed primary PCI and involves angioplasty, and usually stenting, of the
culprit vessel.

Primary PCI is a very effective method for reestablishing coronary perfusion and, in clinical
trials performed at highly experienced medical centers, has achieved optimal fl ow in the
infarct related artery in more than 95% of patients.

Compared with fibrinolytic therapy, primary PCI leads to greater survival with lower rates of
reinfarction and bleeding. Therefore, primary PCI is usually the preferred reperfusion
approach in acute STEMI, if the procedure can be performed by an experienced operator
in a rapid fashion (within 90 minutes of hospital presentation).