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.
CLICK ON THE IMAGE FOR
ENLARGED VIEW:
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 : CLICK
On the
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).
Pathogenesis:
Click on the image:
Commonest cause (at least 90%) is due
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.
Vasospasm,
platelet aggression or both may cause myocardial infarct without
atheroslerosis.
Complete
vessel occlusion may not cause myocardial infarct due to collateral
blood flow.
In the
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.
The time
interval between onset of complete myocardial ischemia and the
initiation of irreversible injury is 20 to 40 minutes.
Sequence of changes:
Grossly :
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Before 6 to 12 hours: No visible lesion is seen.
By 18 to 24 hours: Infarct area becomes pale to
cyanotic.
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.
Microscopic features: Image1
;
Image2;
Image3 ;
Image4;
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
Electron
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
7 days
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.
After 6
weeks, healing is
complete by fibrosis.
Image5;
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Image7
;
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Image10
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 (e.g. 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.
Complications:
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.
3-14 days:
Large infarct: There is softening of dead muscle
(myomalacia cordis) leading to rupture & death.
Site of rupture is ventricular wall, papillary muscle &
interventricular septum.
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
and death.
Clinical
features:
1. Chest pain- 20-30%
does
not
cause chest pain,
common in patients with diabetes mellitus,
hypertension, & in elderly patients.
2. Nausea,
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
fatal arrythmia.
ii) Patients who survive the acute
phase may develop:
- Congestive heart failure
- Cardiac arrythmia
- Left ventricular failure with
pulmonary edema.
- Rupture of ventricular wall,
interventricular septum and papillary muscle
- Thromboembolism.
iii)
10-20% patients
recover with no complication.
iv) Early restoration of blood flow by thrombolysis or
balloon angioplasty provides better prognosis.
Diagnosis:
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.
The classic EKG
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.
The
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.
3) Recently,
the early and late diagnosis of acute myocardial infarction has been
based on elevated serum levels of cardiac troponin. This elevation
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.
For the
diagnosis of acute myocardial infarction even earlier than detectable
by troponin levels, myoglobin can be tested.
Elevated
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.
The
combination of CPK MB and troponin testing can have even higher
sensitivity and is used for the purpose of "ruling out" myocardial
infarction.
Evaluation of a
proposed panel of cardiac markers for the diagnosis of acute
myocardial infarction in patients with atraumatic chest pain.Arch
Pathol Lab Med. 1998 Apr;122(4):320-4.
OBJECTIVE: The
purpose of this study was to evaluate retrospectively the efficacy
of a proposed panel of three cardiac markers (myoglobin, creatine
kinase-MB mass [CK-MB], and cardiac troponin I) in the diagnosis
of acute myocardial infarction (AMI) in patients with atraumatic
chest pain. DESIGN: A total of 110 patients admitted for the
evaluation of atraumatic chest pain were examined. Forty-one of
these patients were diagnosed with AMI. RESULTS: Five of the 41
patients with AMI had abnormally elevated myoglobin levels,
whereas values of CK-MB and/or cardiac troponin I remained
negative. Creatine kinase-MB mass alone had a sensitivity of
92.7%, a specificity of 89.9%, a positive predictive value of
84.4%, and a negative predictive value of 95.0% for the diagnosis
of AMI. Cardiac troponin I alone had a sensitivity of 90.2%, a
specificity of 95.7%, a positive predictive value of 92.5%, and a
negative predictive value of 94.3% for the diagnosis of AMI.
Cardiac troponin I is a more specific marker for the diagnosis of
AMI than CK-MB, particularly in patients with chronic renal
failure who are evaluated for chest pain. The combination of CK-MB
and cardiac troponin I increased the sensitivity to 100% and the
negative predictive value to 100% and had a specificity of 88.4%
and a positive predictive value of 83.7%. The panel was diagnostic
for all patients with AMI within 12 hours after admission.
CONCLUSIONS: Our preliminary results indicate that this panel is
highly effective for evaluation of AMI in patients with atraumatic
chest pain. Elevated myoglobin levels were useful in detecting
patients at high risk for AMI who initially were not detected with
other markers. The combination of CK-MB and cardiac troponin I
provided much higher sensitivity and had a much higher negative
predictive value for the evaluation of AMI than cardiac troponin I
or CK-MB alone. The 100% negative predictive value is particularly
important because it indicates that patients with negative CK-MB
and cardiac troponin I values 12 hours after admission have a
negligible likelihood of AMI.
Stem cell therapy after myocardial infarction:
ready for clinical application?Curr
Opin Mol Ther. 2006 Oct;8(5):396-414.Curr
Opin Mol Ther. 2006 Oct;8(5):396-414
The discovery
of stem cells capable of generating angiogenic or contractile
cells and structures might offer new treatment options for
patients suffering from heart disease. In particular, embryonic
stem cells are considered to have great potential for regenerative
medicine and tissue engineering. Studies suggest that delivery or
mobilization of stem and progenitor cells might improve tissue
perfusion and contractile performance of the damaged heart;
however, the underlying mechanisms are poorly understood. Fusion
or trans-differentiation into cardiomyocytes or vascular cells are
considered rare events of cellular engraftment, and adult stem
cells are now considered as 'regenerator cells', acting via
paracrine effects of cytokines, or by activation of resident stent
cells, thereby supporting the myocardial healing mechanisms after
injury. Administration of autologous hematopoietic stem cells or
mobilization of endogenous stem cells has been shown to be safe
after myocardial infarction or cardiomyopathies, whereas skeletal
myoblasts are considered to be hazardous due to the occurrence of
life-threatening arrhythmias. This review focuses on the use of
adult human stem cells for treating myocardial infarction and
cardiomyopathy, and discusses recent preliminary efficacy data,
which suggest that 'regenerator cells' might have the potential to
improve myocardial perfusion and contractile performance in
patients suffering from myocardial infarction, severe ischemic
heart disease and chronic heart failure.
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SUMMARY OF
PATHOLOGIC FINDINGS:
The anatomic
pathologic diagnosis of acute myocardial infarction at autopsy is
based on gross and microscopic features.
Acute
myocardial infarction up to 12 hours old is associated with minimal
gross pathologic findings.
Over the
period of 12-24 hours following infarction the myocardium manifests
progressive pallor.
During the
period of 2-4 days following infarction, the dead muscle becomes
yellow and softened.
4-10
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.
Coagulation necrosis,
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.
Neutrophilic infiltration
(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
neutrophils.
Infiltration by macrophages,
lymphocytes, eosinophils, fibroblasts and capillaries begins around
the periphery at 3-10 days. |
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