Myocardial infarction may occur at any
age but frequency rises with increasing age.
Women are remarkably protected against
myocardial infarction during reproductive life.
Myocardial infarct is the ischemic
necrosis of an area of myocardium.
This is a section of the subepicardial
myocardium from an autopsy case of a 71 year old Asian male. The
features are those of acute myocardial infarction showing neutrophilic
infiltrate along with areas of necrosis, diffuse interstitial edema
and pale myocytes with fading nuclei and decreased striations.
Sudden Cardiac Death
basis of morphology, pathogenesis and clinical significance, there are
two types of infarct.
1. Transmural infarct-
This is the infarction of the full thickness of the ventricular wall,
usually caused by severe coronary atherosclerosis, worsened by acute
plaque disruption and superimposed occlusive thrombosis.
2. Subendothelial infarct-
This is limited to the inner one third to one half of the ventricular
wall (an area of diminished perfusion).
Commonest cause (at least 90%)
to coronary atherosclerosis with occluding thrombus.
Occlusion is typically seen in the proximal 2 cm
of the left anterior descending and left circumflex arteries and in the proximal and distal thirds of
the right coronary artery.
platelet aggression or both may cause myocardial infarct without
vessel occlusion may not cause myocardial infarct due to collateral
absence of sudden death, thrombi may be lysed spontaneously or with
fibrinolytic treatment, or vasospasm may relax, thereby reestablishing
blood flow and thus spare some myocardium from necrosis.
interval between onset of complete myocardial ischemia and the
initiation of irreversible injury is 20 to 40 minutes.
Sequence of changes:
Before 6 to 12 hours: No visible lesion is seen.
By 18 to 24 hours: Infarct area becomes pale to
In the first week: The infarct area becomes
progressively more sharply defined, yellow and softened.
By the 7 to 10 days, circumference of the
infarct area becomes hyperemic, and progressively expands.
By the 6 weeks, fibrous scar is well established.
Within 1 hour,
of ischemic injury, there is intercellular edema and “wavy fibers” may
be present at the periphery of the infarct. These are noncontrctile
dead fibers, stretched by the adjacent viable contracting myocytes
microscopy shows reversible changes (swelling of mitochondria
& endoplasmic reticulum and relaxation of myofibrils).
Histochemically, there is loss of
oxidative enzyme & fall of glycogen.
In 12 to 72
hours, there is infiltration of neutrophils with progressive
coagulative necrosis of myocytes. Dead myocytes become
hypereosinophilic with loss of nuclei.
Between 3 and
after onset, dead myocytes begin to disintegrate and are
removed by macrophages and enzyme proteolysis. There is proliferation
of fibroblasts with formation of granulation tissue, which
progressively replaces necrotic tissue.
weeks, healing is complete by
Contraction band necrosis:
Contraction band necrosis, characterized by hypereosinophilic
transverse bands of precipitated myofibrils in dead myocytes is
usually seen at the edge of an infarct or with reperfusion (Example: with thrombolytic therapy).
Reperfusion of an infarct:
Reperfusion of an infarct is also associated with more hemorrhage,
less acute inflammation, less limitation of the acute inflammation to
the periphery in the first few days, reactive stromal cells, more
macrophage infiltration earlier and a more patchy distribution of
necrosis, especially around the periphery.
It depends on the size and location
of the lesion.
Within minutes to 3
days of onset:
1. Arrythmias : i) ventricular fibrillation ; ii)
block of A-V bundles and its branches causing acute heart failure.
2. Cardiogenic shock (usually in large infarct) causing
acute heart failure.
3. Thrombotic complication- mural thrombus over infarct
area or atrial thrombus, causing embolism to brain, kidney etc.
4. Rupture of heart.
Large infarct: There is softening of dead muscle
(myomalacia cordis) leading to rupture & death.
Site of rupture is ventricular wall, papillary muscle &
5. Acute fibrinous or hemorrhagic pericarditis -
over infarct area.
After weeks or months:
6. Chronic heart failure
7. Cardiac aneurysm, which may rupture producing hemopericardium
1. Chest pain- 20-30%
cause chest pain,
common in patients with diabetes mellitus,
hypertension, & in elderly patients.
diaphoresis and dyspnea.
Fate of the patient:
In hospitalized patients (where
angiography, echocardiography and perfusion scintigraphy are
available) usual fate are:
i) About 25 % of patients dye of cardiogenic shock or
ii) Patients who survive the acute
phase may develop:
- Congestive heart failure
- Cardiac arrythmia
- Left ventricular failure with
- Rupture of ventricular wall,
interventricular septum and papillary muscle
recover with no complication.
iv) Early restoration of blood flow by thrombolysis or
balloon angioplasty provides better prognosis.
It is based on symptoms, electrocardiographic change and
serum elevation of myocardial enzymes (creatine kinase-MB isoenzyme)
or other proteins (troponin I, troponin T or myoglobin), that leak out
of dead cells.
findings: ST segment elevation, followed by T wave inversion and Q waves, are
associated with transmural infarction. ST segment depression and
T wave inversion are associated with subendocardial infarction.
laboratory diagnosis of myocardial infarction:
1) This has been based on elevation of creatine phosphokinase (CPK),
with an MB fraction >5% of the total CPK or a relative index >3 (if
the MB fraction is measured in mass units instead of activity units).
The elevation of CPK begins around 8 hours after the onset of
infarction, peaks around 18 hours and ends around 48 hours.
2) The late
diagnosis of myocardial infarction can be based on elevation of
lactate dehydrogenase (LDH), with an LDH-1 fraction >40% of the total LDH or LDH-1/LDH-2 ratio >1, because this peaks around 5 days.
the early and late diagnosis of acute myocardial infarction has been
based on elevated serum levels of cardiac troponin.
begins around 4 hours after the onset of infarction and lasts longer
than LDH; this test has a sensitivity similar to CPK-MB fraction and
better than LDH.
diagnosis of acute myocardial infarction even earlier than detectable
by troponin levels, myoglobin can be tested.
levels of myoglobin can be detected around 2 hours after the onset of
infarction, but this has only about 60% specificity for the heart.
A new type of
test being evaluated for the diagnosis of acute myocardial infarction
is CPK MB isoform assay, which has a 96% sensitivity and 93%
specificity for infarction within 6 hours of onset of chest pain.
combination of CPK MB and troponin testing can have even higher
sensitivity and is used for the purpose of "ruling out" myocardial
Summary of pathologic findings:
pathologic diagnosis of acute myocardial infarction at autopsy is
based on gross and microscopic features.
myocardial infarction up to 12 hours old is associated with minimal
gross pathologic findings.
period of 12-24 hours following infarction the myocardium manifests
period of 2-4 days following infarction, the dead muscle becomes
yellow and softened.
days following infarction it develops a hyperemic border and a
softened yellow shrunken depressed center.
Thin wavy myocytes are the
earliest light microscopic finding of acute myocardial infarction.
It is visible one hour
following the onset of infarction.
characterized by hypereosinophilia and nuclear pyknosis, followed by
karyorrhexis, karyolysis, total loss of nuclei and loss of cytoplasmic
cross-striations, is generally first visible in the period from 4-12
hours following infarction.
Necrotic myocytes may retain
their striations for a long time.
(acute inflammation), edema and hemorrhage are also first visible at
4-12 hours but generally closer to 12 hours.
Acute inflammation is
generally present in a narrow band of the periphery at 24 hours, in a
broad band of the periphery at 48 hours and tends to be maximal around
72 hours, with extensive basophilic debris from degenerating
Infiltration by macrophages,
lymphocytes, eosinophils, fibroblasts and capillaries begins around
the periphery at 3-10 days.