CARDIOVASCULAR SYSTEM

CECEP ARTIKA DIKA

LEARNING ISSUE: ACUTE MYOCARDIAL INFARCTION

NAFISAH BINTI ABDUL HAMID

GROUP 1
CHAPTER 37: ACUTE MYOCARDIAL
INFARCTION, BRAUNWALD HEART
DISEASE
18 MAY 2005

PATHOLOGY
Role of Acute Plaque Change
Gross Pathological Changes
TABLE 37-1 CAUSES OF MYOCARDIAL INFARCTION WITHOUT CORONARY
ATHEROSCLEROSIS
____________________________________________________________________
CORONARY ARTERY DISEASE OTHER THAN ATHEROSCLEROSIS
Arteritis
Leutic
Granulomatous (Takayasu disease)
Polyarteritis nodosa
Mucocutaneous lymph node (Kawasaki) syndrome
Disseminated lupus erythematosus
Rheumatoid arthritis
Ankylosing spondylitis
Trauma to coronary arteries
Laceration
Thrombosis
Iatrogenic
Radiation (radiotherapy for neoplasia)
Coronary mural thickening with metabolic disease or intimal
proliferative disease
Mucopolysaccharidoses (Hurler disease)
Homocystinuria
Fabry disease
Amyloidosis
Juvenile intimal sclerosis (idiopathic arterial calcification of
infancy)
Intimal hyperplasia associated with contraceptive steroids or
with the postpartum period
Pseudoxanthoma elasticum
Coronary fibrosis caused by radiation therapy
Luminal narrowing by other mechanisms
Spasm of coronary arteries (Prinzmetals angina with normal
coronary arteries)
Spasm after nitroglycerin withdrawal
Dissection of the aorta
Dissection of the coronary artery
EMBOLI TO CORONARY ARTERIES
Infective endocarditis
Nonbacterial thrombotic endocarditis
Prolapse of mitral valve
Mural thrombus from left atrium, left ventricle, or pulmonary
veins
Prosthetic valve emboli
Cardiac myxoma
Associated with cardiopulmonary bypass surgery and coronary
arteriography
Paradoxical emboli
Papillary fibroelastoma of the aortic valve (fixed embolus)
Thrombi from intracardiac catheters or guidewires
CONGENITAL CORONARY ARTERY ANOMALIES
Anomalous origin of left coronary from pulmonary artery
Left coronary artery from anterior sinus of Valsalva
Coronary arteriovenous and arteriocameral fistulas
Coronary artery aneurysms
MYOCARDIAL OXYGEN DEMAND-SUPPLY DISPROPORTION
Aortic stenosis, all forms
Incomplete differentiation of the aortic valve
Aortic insufficiency
Carbon monoxide poisoning
Thyrotoxicosis

Prolonged hypotension
HEMATOLOGICAL (IN SITU THROMBOSIS)
Polycythemia vera
Thrombocytosis
Disseminated intravascular coagulation
Hypercoagulability, thrombosis, thrombocytopenic purpura
MISCELLANEOUS
Cocaine abuse
Myocardial contusion
Myocardial infarction with normal coronary arteries
Complication of cardiac catheterization
____________________________________________________________________________
Modified from Cheitlin, M., et al.: Myocardial infarction without athero- sclerosis.
JAMA 231:951, 1975. Copyright 1975, American Medical Association.

ROLE OF ACUTE PLAQUE CHANGE

Slowly accruing high-grade stenoses of epicardial coronaries may progress to complete occlusion but do not
usually precipitate AMI, probably because of the development of a rich collateral network over time. However,
during the natural evolution of atherosclerotic plaques, especially those that are lipid-laden, an abrupt and
catastrophic transition may occur, characterized by plaque rupture and exposure of substances that promote
platelet activation and thrombin generation. The resultant thrombus interrupts blood flow and leads to an
imbalance between oxygen supply and demand and, if this imbalance is severe and persistent, to myocardial
necrosis.
1. COMPOSITION OF PLAQUES.
At autopsy, the atherosclerotic plaque of patients who died of MI is composed:
Primarily of fibrous tissue of varying density and cellularity with superimposed thrombus.
Calcium, lipid-laden foam cells, and extracellular lipid each constitute 5 to 10 per cent of the
remaining area.
The atherosclerotic plaques that are associated with thrombosis and a total occlusion, located in
infarct-related vessels, are generally more complex and irregular than those in vessels not
associated with MI.
Histological studies: these lesions often reveal plaque rupture or fissuring
Platelet-rich thrombi are often associated with the surface of the most advanced
atherosclerotic lesions, called complicated plaques, which are characterized by fibrocalcific
degeneration, deposition of lipid, calcium, fibrous tissue, necrotic debris, extravasated blood, and
a fibrous cap.
Impaired endothelial cell function may contribute to atherogenesis through release of growth
factors.
Luminal narrowing may potentiate platelet activation through augmentation of shear forces.
Young persons with coronary thrombotic events have been described as having a genetic
polymorphism in glycoprotein IIb/IIIa, possibly altering platelet-fibrinogen interactions.
In patients with MI:
Coronary thrombi are usually superimposed on or adjacent to atherosclerotic plaques coronary
arterial thrombi.
Approximately 1 cm in length in most cases,
Adhere to the luminal surface of an artery
Composed of platelets, fibrin, erythrocytes, and leukocytes
The composition of the thrombus may vary at different levels: A white thrombus is composed of
platelets, fibrin, or both, and a red thrombus is composed of erythrocytes, fibrin, platelets, and
leukocytes. Early thrombi are usually small and nonocclusive and are composed almost
exclusively of platelets.
2. PLAQUE FISSURING AND RUPTURE.
The process of plaque fissuring is an area of intense investigation and is likely to be multifactorial:

T lymphocytes in human atheroma elaborate the cytokine interferon-gamma (IFN-g) that

markedly inhibits the ability of vascular smooth muscle cells to form interstitial collagen in
vulnerable regions of the fibrous cap over an atherosclerotic plaque.
Furthermore, in atherosclerotic plaques prone to rupture, there is an increased rate of formation
of metalloproteinase enzymes such as collagenase, gelatinase, and stromelysin that degrade
components of the protective interstitial matrix.
These proteinases may be elaborated by activated macrophages and mast cells that have been
shown to accumulate in high concentration at the site of atheromatous erosions and plaque
rupture in patients who died of AMI.
Specimens from directional atherectomy reveals a much higher content of macrophages in
patients with unstable angina or AMI compared with patients with chronic stable angina
Stresses induced by intraluminal pressure, coronary vasomotor tone, tachycardia (cyclic
stretching and compression), and disruption of nutrient vessels combine to produce plaque
rupture at the margin of the fibrous cap near an adjacent plaque-free segment of the coronary
artery wall (shoulder region of plaque).
A number of key physiological parameters such as systolic blood pressure, heart rate, blood
viscosity, endogenous tissue plasminogen activator (t-PA) activity, plasminogen activator inhibitor1 (PAI-1) levels, plasma cortisol levels, and plasma epinephrine levels that exhibit circadian
variations act in concert to produce a heightened propensity to plaque rupture and coronary
thrombosis between 6 and 11 A.M., yielding the circadian clustering of AMI and relative resistance
to thrombolytic therapy in the early morning.

3. ACUTE CORONARY SYNDROMES.

When plaque rupture occurs thrombogenic substances is exposedthe coronary

artery lumen may become obstructed by a combination of fibrin, platelet aggregates, and red blood cells.

An adequate collateral network that prevents necrosis from occurring can result in
clinically silent episodes of coronary occlusion.

The rupture of plaques pathophysiological substrate of the acute coronary syndromes

that range from unstable angina through non-Q-wave AMI and Q-wave AMI.

completely occlusive thrombus:

- producing ST elevation on the electrocardiogram and
- ultimately necrosis involving the full or nearly full thickness of the ventricular wall in a zone subtended
by the affected coronary artery (i.e., transmural myocardial infarction
- Q wave development on the ECG).

Less obstructive thrombi:

- and/or those that are constituted by less robust fibrin formation and a greater proportion of platelet
aggregates
- produce the syndromes of unstable angina and
- non-Q-wave AMI,
- ST-segment depression
- and/or T-wave inversion on the ECG.

Relief of transient vasospasm (induced by thromboxane A2 and serotonin released from

activated platelets) or spontaneous lysis and restoration of antegrade flow in the culprit coronary vessel in less
than 20 minutes usually does not result in histological evidence of necrosis, the release of biochemical markers of
necrosis, or persistent changes on the electrocardiogram; the resulting condition is unstable angina .

Episodes of plaque rupture more prolonged and more severe than those producing
unstable angina typically result in release of a biochemical marker of necrosis but a less extensive pattern of
necrosis than is found in patients with ST-elevation MI.

When clinical evidence of necrosis is detected (now possible in a greater number of

patients with sensitive markers such as cardiac-specific troponin T or I)and no pathological Q waves evolve on the
ECG, a diagnosis of non-Q-wave AMI is made, a condition midway between Q-wave infarction and unstable
angina . Often, patients with non-Q-wave MI have a pattern of myocardial necrosis that is less confluent in nature
and more concentrated in the inner third of the ventricular wall because restoration of blood flow prevented the
wavefront of necrosis from extending across the thickness of the ventricular wall.


Some patients with stenotic atherosclerotic lesions experience AMI without evidence of
plaque rupture or superimposed thrombosis.

AMI occurs in clinical circumstances that produce a marked reduction in

myocardial oxygen supply (e.g., prolonged severe vasospasm, as in Prinzmetals variant angina, or
associated with a marked increase in myocardial oxygen demand. These infarcts are located along the
least well perfused inner one-third to one-half of the ventricular wall and often extend beyond the target
territory perfused by a single coronary vessel. The ECG in such patients may show deep T-wave
inversions or diffuse ST-segment depression.
GROSS PATHOLOGICAL CHANGES
On gross inspection, AMI may be divided into two major types:
Transmural infarcts
Subendocardial (nontransmural) infarcts
- myocardial necrosis involves the full thickness
- the necrosis involves the subendocardium, the
(or nearly full thickness) of the ventricular wall
intramural myocardium, or both without extending all
- occlusive coronary thrombosis
the way through the ventricular wall to the epicardium
- localized to the distribution of a single coronary
- occur in the presence of severely narrowed but
artery
still patent coronary arteries.
- histological pattern of necrosis:
- histological pattern of necrosis:
with contraction band injury
with contraction band injury (see below) occurring
almost twice as often in nontransmural
- before their infarction, patients with nontransmural infarcts
have, on average, a more severe stenosis in the infarct-related
coronary artery than do patients suffering from transmural
infarcts
- suggests that a more severe obstruction occurring before
infarction protects against the development of transmural
infarction, perhaps by fostering the development of
collateral circulation.

Gross alterations of the myocardium are difficult to identify until at least 6 to 12 hours have elapsed
following the onset of necrosis
o Histochemical approaches have been used to identify zones of necrosis
o Initially, the myocardium in the affected region may appear pale and slightly swollen.

18 to 36 hours after the onset of the infarct: the myocardium is tan or reddish purple (due to trapped
erythrocytes), with a serofibrinous exudate evident on the epicardium in transmural infarcts.

Changes persist for approximately 48 hours; the infarct then turns gray, and fine yellow lines, secondary to
neutrophilic infiltration, appear at its periphery.

This zone gradually widens and during the next few days extends throughout the infarct.

8 to 10 days following infarction: the thickness of the cardiac wall in the area of the infarct is reduced as
necrotic muscle is removed by mononuclear cells.

The cut surface of an infarct of this age is yellow, surrounded by a reddish purple band of granulation tissue
that extends through the necrotic tissue by 3 to 4 weeks

Next 2 to 3 months, the infarcted area gradually acquires a gelatinous, ground-glass, gray appearance,
eventually converting into a shrunken, thin, firm scar, which whitens and firms progressively with time, this
o

process begins at the periphery of the infarct and gradually moves centrally. The endocardium below the
infarct increases in thickness and becomes gray and opaque.
Histological and Ultrastructural Changes

1.
2.
3.
4.
5.

ELECTRON MICROSCOPY
LIGHT MICROSCOPY.
ligation of a coronary artery, noted within 20 minutes
some infarcts a pattern of wavy myocardial fibers
consist of reduction in the size and number of
may be seen 1 to 3 hours after onset, especially at the
glycogen granules, intracellular edema, and
periphery of the infarct
swelling and distortion of the transverse tubular

After 8 hours, edema of the interstitium becomes

system, the sarcoplasmic reticulum, and the
evident, as do increased fatty deposits in the muscle fibers, along
mitochondria
with infiltration of neutrophilic
after 60 minutes of occlusion myocardial cell polymorphonuclear leukocytes and red blood cells.
swelling, mitochondrial abnormalities such as
Muscle cell nuclei become pyknotic and then
swelling and internal disruption, and
undergo karyolysis, and small blood vessels undergo
development of amorphous, flocculent
necrosis.
aggregation and margination of nuclear

24 hours: there is clumping of the cytoplasm and loss

chromatin, and relaxation of myofibrils.
of cross striations, with appearance of focal

20 minutes to 2 hours of ischemia, changes in hyalinization and irregular cross-bands in the involved
some cells become irreversible, and there is
myocardial fibers. The nuclei become pyknotic and
progression of these alterations; additional changes
sometimes even disappear. The myocardial capillaries in the
include indistinct tight junctions at the intercalated discs, involved region dilate, and polymorphonuclear
swollen sacs of the sarcoplasmic reticulum at the level leukocytes accumulate, first at the periphery and then in the center
of the A band, greatly enlarged mitochondria with few
of the infarct.
cristae, thinning and fractionation of

first 3 days: the interstitial tissue becomes edematous

myofilaments, disappearance of the heterochromatin,
and red blood cells may extravasate
rarefaction of the euchromatin and peripheral

4th day after infarction, removal of necrotic

aggregation of chromatin in the nucleus,
fibers by macrophages begins, again commencing at the
disorientation of myofibrils, and clumping of mitochondria. periphery.Later, lymphocytes, macrophages, and

Cells irreversibly damaged by ischemia are usually

fibroblasts infiltrate between myocytes, which become
swollen, with an enlarged sarcoplasmic space; the
fragmented.
sarcolemma may peel off the cells, defects in the

At 8 days: the necrotic muscle fibers have

plasma membrane may appear, and the
become dissolved
mitochondria are fragmented. The swollen

10 days: the number of polymorphonuclear

mitochondria obtained from ischemic myocardium
leukocytes is reduced, and granulation tissue first
contain deposits of calcium
appears at the periphery. In growth of blood vessels and
phosphate and amorphous matrix densities. Many
fibroblasts continues, along with removal of necrotic
of these changes become more intense when blood flow
is cells, until the fourth to sixth week following
muscle
restored.
infarction, by which time much of the necrotic
myocardium has been removed.

This process continues along with

increasing collagenization of the infarcted area. By the
sixth week, the infarcted area has usually been converted into a
firm connective tissue scar with interspersed intact muscle
fibers
PATTERN OF MYOCARDIAL NECROSIS
COAGULATION NECROSIS.

results from severe, persistent ischemia and is usually present in the central region of
infarcts, which results in the arrest of muscle cells in the relaxed state and the passive stretching of ischemic
muscle cells.

On light microscopy the myofibrils are stretched, many with nuclear pyknosis, vascular
congestion, and healing by phagocytosis of necrotic muscle cells. There is evidence of mitochondrial damage with
prominent amorphous (flocculent) densities but no calcification.

NECROSIS WITH CONTRACTION BANDS.

Also termed contraction band necrosis or coagulative myocytolysis, results primarily from severe
ischemia followed by reflow.

Caused by increased Ca++ influx into dying cells, resulting in the arrest of cells in the contracted
state.

It is seen in the periphery of large infarcts and is present to a greater extent in nontransmural than
in transmural infarcts.

The entire infarct may show this form of necrosis when reperfusion occurs experimentally or by
surgery Although patches of contraction band necrosis are found after successful reperfusion by thrombolytic
therapy their presence in a large segment of the infarcts of patients who did not receive such therapy suggests
that reperfusion through spontaneous thrombolysis or the release of spasm or both have occurred.

It is characterized by hypercontracted myofibrils with contraction bands and mitochondrial

damage, frequently with calcification, marked vascular congestion, and healing by lysis of muscle cells
MYOCYTOLYSIS.

Severe prolonged ischemia can cause myocyte vacuolization, often termed myocytolysis.

Prolonged severe ischemia, which is potentially reversible, causes cloudy swelling, as well as
hydropic, vascular, and fatty degeneration.

Frequently seen at the borders of an infarct as well as in patchy areas of infarction in patients with
chronic ischemic heart disease, myocytolysis is characterized by edema and cell swelling, lysis of myofibrils and
nuclei, no neutrophilic response, and healing by lysis and phagocytosis of necrotic myocytes and ultimately scar
formation.
PATHOPHYSIOLOGY
Left Ventricular Function
Circulatory Regulation
Ventricular Remodeling
Pathophysiology of Other Organ Systems
LEFT VENTRICULAR FUNCTION
Systolic Function
1. Upon interruption of antegrade flow in an epicardial coronary artery, the zone of myocardium supplied by
that vessel immediately loses its ability to shorten and perform contractile work.
2. Four abnormal contraction patterns develop in sequence:
dyssynchrony, i.e., dissociation in the time course of contraction of adjacent segments;
hypokinesis, reduction in the extent of shortening
akinesis, cessation of shortening
dyskinesis, paradoxical expansion, systolic bulging
3. Patients with AMI often also show reduced myocardial contractile function in noninfarcted zones. This
may result from previous obstruction of the coronary artery supplying the noninfarcted region of the
ventricle and loss of collaterals from the freshly occluded infarct related vessel, a condition that has been
termed ischemia at a distance.
4. If a sufficient quantity of myocardium undergoes ischemic injury:

left ventricular pump function becomes depressed;

cardiac output, stroke volume, blood pressure, and peak dP/dt are reduced

end-systolic volume is increased. In fact, the degree to which end-systolic volume increases
is perhaps the most powerful predictor of mortality following AMI.

With the passage of time, edema and cellular infiltration and ultimately fibrosis increase the
stiffness of the infarcted myocardium back to and beyond control values. Increasing stiffness in the
infarcted zone of myocardium improves left ventricular function because it prevents paradoxical
systolic wall motion.
Diastolic Function
Left ventricular diastolic properties are altered in infarcted and ischemic myocardium

an increase but later to a reduction in left ventricular compliance.

CIRCULATORY REGULATION
an anatomical or functional obstruction in the coronary vascular bed

regional myocardial ischemia and, if the ischemia persists, in infarction.

If the infarct is of sufficient size, it depresses overall left ventricular function.

so that left ventricular stroke volume falls filling pressures rise.

left ventricular stroke volume

lowers aortic pressure

reduces coronary perfusion pressure

this condition may intensify myocardial ischemia

initiate a vicious circle.

.
inability of the left ventricle to empty

increased preload

dilates the well-perfused, normally functioning portion of the left ventricle.

This compensatory mechanism tends to restore stroke volume to normal levels, but at the expense of a reduced
ejection fraction.

dilatation of the left ventricle

also ventricular afterload, because Laplaces law dictates that at any given arterial pressure the dilated ventricle
must develop a higher wall tension.

left ventricular stroke volume

myocardial oxygen consumption,

which in turn intensifies myocardial ischemia.

..

When regional myocardial dysfunction is limited and the function of the remainder of the left
ventricle is normal, compensatory mechanisms sustain overall left ventricular function.

Large portion of the left ventricle becomes necrotic, pump failure occurs; i.e., overall left
ventricular function becomes so depressed that the circulation cannot be sustained despite the dilatation of the
remaining viable portion of the ventricle.

VENTRICULAR REMODELING
Ventricular remodeling, a consequence of MI, the changes in left ventricular size, shape, and thickness involving
both the infarcted and the noninfarcted segments of the ventricle.
INFARCT EXPANSION.

An increase in the size of the infarcted segment,

Is defined as acute dilatation and thinning of the area of infarction not explained by additional
myocardial necrosis.

Caused by (1) a combination of slippage between muscle bundles, reducing the number of
myocytes across the infarct wall; (2) disruption of the normal myocardial cells; and (3) tissue loss within the
necrotic zone.
VENTRICULAR DILATATION

Dilatation may be accompanied by a shift of the pressure-volume curve of the left ventricle to the
right, resulting in a larger left ventricular volume at any given diastolic pressure. This global dilatation of the
noninfarct zone may be viewed as a compensatory mechanism that maintains stroke volume in the face of a large
infarction.

This hypertrophy could help to compensate for the functional impairment caused by the infarct
and may be responsible for some of the hemodynamic improvement seen in the months after infarction in some
patients
EFFECTS OF TREATMENT

Acute reperfusion and other measures to restrict the extent of myocardial necrosis limit the
increase in ventricular volume following AMI.

Glucocorticosteroids and nonsteroidal anti-inflammatory agents given early after MI can cause
scar thinning and greater infarct expansion,

ACE inhibitors attenuate ventricular enlargement

PATHOPHYSIOLOGY OF OTHER ORGAN SYSTEMS
PULMONARY
- Changes in pulmonary gas exchange, ventilation, and distribution of perfusion.
inverse relation between pulmonary artery diastolic pressure and arterial oxygen tension

increased pulmonary capillary hydrostatic pressure

interstitial edema, which results in arteriolar and bronchiolar compression


perfusion of poorly ventilated alveoli

Hypoxemia
- Hyperventilation hypocapnia respiratory alkalosis, particularly in restless, anxious patients with pain.
INCREASE IN INTERSTITIAL WATER
- A positive correlation has been demonstrated between pulmonary extravascular (interstitial) water
content, left ventricular filling pressure, and the clinical signs and symptoms of left ventricular failure.
REDUCTION OF VITAL CAPACITY
Virtually all lung volume indice: total lung capacity, functional residual capacity, and residual volume, as well as
vital capacity
REDUCTION OF AFFINITY OF HEMOGLOBIN FOR OXYGEN
PANCREAS.
- Hyperglycemia and impaired glucose tolerance are common in patients with AMI.
ADRENAL MEDULLA
- Excessive secretion of catecholamines produces many of the characteristic signs and symptoms of
AMI.
- plasma and urinary catecholamine levels are highest during the first 24 hours after the onset of chest
pain
- Greatest rise in plasma catecholamine secretion occurring during the first hour after the onset of MI.
- High levels of circulating catecholamines in patients with AMI correlate with the occurrence of serious
arrhythmias and result in an increase in myocardial oxygen consumption, both directly and indirectly,
as a consequence of catecholamine-induced elevation of circulating free fatty acids.
- Circulating catecholamines enhance platelet aggregation; when this occurs in the coronary
microcirculation, the release of the potent vasoconstrictor thromboxane A2 may further impair cardiac
perfusion.
LOCAL MYOCARDIAL AND SYSTEMIC RENIN-ANGIOTENSIN SYSTEM.
Noninfarcted regions of the myocardium appear to exhibit activation of the tissue renin-angiotensin
system with increased angiotensin II production.
Additional potential actions of angiotensin II that have a more negative impact on the infarction process
include release of endothelin, PAI-1, and aldosterone, which may cause vasoconstriction, impaired fibrinolysis,
and increased sodium retention, respectively.
NATRIURETIC PEPTIDES.
The peptides atrial natriuretic factor (ANF) and N-terminal pro-ANF are released from cardiac atria in
response to elevation of atrial pressure.
ADRENAL CORTEX
Plasma and urinary 17-hydroxycorticosteroids and ketosteroids, as well as aldosterone, are also
markedly elevated in patients with AMI.
Concentrations correlate directly with the peak level of serum creatine kinase
Implying that the stress imposed by larger infarcts is associated with greater secretion of adrenal steroids.
THYROID GLAND
Evidence indicates a significant transient decrease in serum triiodothyronine T3
RENAL FUNCTION
Both prerenal azotemia and acute renal failure can complicate the marked reduction of cardiac output that occurs
in cardiogenic shock.
HEMATOLOGICAL FUNCTION

1. PLATELETS
2. Circulating platelets are hyperaggregable in patients with AMI.
Elevated levels of serum fibrinogen degradation products, an end-product of thrombosisas well as release of
distinctive proteins when platelets are activated.
3. LEUKOCYTES.
AMI is usually accompanied by leukocytosis, which is related to the necrotic process.
4. BLOOD VISCOSITY
Increase in blood viscosity also occurs in patients with AMI.
CLINICAL FEATURES
Predisposing Factors
History
Physical Examination
Laboratory Examinations
PREDISPOSING FACTORS
a. Unusually heavy exercise (particularly in fatigued or emotionally stressed patients)
b. respiratory infections,
c. hypoxemia of any cause,
d. pulmonary embolism,
e. hypoglycemia,
f. administration of ergot preparations,
g. use of cocaine,
h. sympathomimetics,
i. serum sickness,
j. allergy, and on rare occasion wasp stings may all be triggers
CIRCADIAN PERIODICITY
A pronounced circadian periodicity for the time of onset of AMI, with peak
incidence of events between 6 A.M. and 12 noon.
Circadian rhythms affect many physiological and biochemical parameters
The early morning hours are associated with rises in plasma catecholamines
and cortisol and increases in platelet aggregability.
HISTORY
a.
PRODROMAL SYMPTOMS.
- Chest discomfort, resembling classic angina pectoris, but it occurs at rest or with less activity than
usual and can therefore be classified as unstable angina.
- A feeling of general malaise or frank exhaustion often accompanies other symptoms preceding
AMI.
b.
NATURE OF THE PAIN
Pain of AMI is variable in intensity; in most patients it is severe and in some instances
intolerable.
The pain is prolonged, usually lasting for more than 30 minutes and frequently for a
number of hours.
The discomfort is described as constricting, crushing, oppressing, or compressing;
often the patient complains of a sensation of a heavy weight or a squeezing in the chest.
Although the discomfort is typically described as a choking, viselike, or heavy pain, it may
also be characterized as a stabbing, knifelike, boring, or burning discomfort.
The pain is usually retrosternal in location, spreading frequently to both sides of the
anterior chest, with predilection for the left side.
Pain radiates down the ulnar aspect of the left arm, producing a tingling sensation in the
left wrist, hand, and fingers.
Some patients note only a dull ache or numbness of the wrists in association with
severe substernal or precordial discomfort.
In some instances, the pain of AMI may begin in the epigastrium and simulate a
variety of abdominal disorders, a fact that often causes MI to be misdiagnosed as indigestion.

10

In other patients the discomfort of AMI radiates to the shoulders, upper extremities,
neck, jaw, and interscapular region, again usually favoring the left side.
In patients with preexisting angina pectoris, the pain of infarction usually resembles that
of angina with respect to location. However, it is generally much more severe, lasts longer, and is not relieved by rest
and nitroglycerin.
In some patients, particularly the elderly, AMI is manifested clinically not by chest pain
but rather by symptoms of acute left ventricular failure and chest tightness or by marked weakness or frank
syncope.
These symptoms may be accompanied by diaphoresis, nausea, and vomiting.The
pain of AMI may have disappeared by the time the physician first encounters the patient (or the patient reaches the
hospital), or it may persist for many hours.
Opiates in particular, morphine usually relieve the pain. Both angina pectoris and the
pain of AMI are thought to arise from nerve endings in ischemic or injured, but not necrotic, myocardium. Thus, in MI,
stimulation of nerve fibers in an ischemic zone of myocardium surrounding the necrotic central area of infarction
probably gives rise to the pain.
Pain often disappears suddenly and completely when blood flow to the infarct territory is
restored.
c.

OTHER SYMPTOMS.
Nausea and vomiting
Complains of diarrhea or a violent urge to evacuate the bowels during the

acute phase of MI.

Feelings of profound weakness, dizziness, palpitations, cold perspiration, and a

sense of impending doom

Differential Diagnosis
Ischemic discomfort
- never radiates to the
trapezius ridge

Pericardial pain
- radiates to the trapezius
ridge

Pleural pain
- sharp, knife-like, and
aggravated in a cyclical
fashion by each breath

Pulmonary embolism
- pain laterally in the chest,
is often pleuritic in nature,
and may be associated with
hemoptysis.
- The pain due to acute
dissection of the aorta is usually
localized in the center of the
chest, is extremely severe and
described by the patient as a
ripping or tearing
sensation, is at its
maximal intensity shortly after
onset, persists for many
hours, and often radiates to the
back or the lower extremities.

SILENT MI AND ATYPICAL PRESENTATION

Unrecognized or silent infarction occurs more commonly in patients without antecedent angina
pectoris and in patients with diabetes and hypertension.

In an analysis of atypical presentations of AMI, Bean lists the following: (1) congestive heart
failure beginning de novo or worsening of established failure; (2) classic angina pectoris without a particularly
severe or prolonged attack; (3) atypical location of the pain; (4) central nervous system manifestations,
resembling those of stroke, secondary to a sharp reduction in cardiac output in a patient with cerebral
arteriosclerosis; (5) apprehension and nervousness; (6) sudden mania or psychosis; (7) syncope; (8)
overwhelming weakness; (9) acute indigestion; and (10) peripheral embolization.
PHYSICAL EXAMINATION
GENERAL APPEARANCE

anxious and in considerable distress

Restless and move about in an effort to find a comfortable position.

11


massage or clutch their chests and frequently describe their pain with a clenched fist held
against the sternum (the Levine sign, named after Dr. Samuel A. Levine).

In patients with left ventricular failure and sympathetic stimulation, cold perspiration and
skin pallor may be evident; they typically sit or are propped up in bed, gasping for breath.

Between breaths, they may complain of chest discomfort or a feeling of suffocation. Cough
productive of frothy, pink, or blood-streaked sputum is common.

Patients in cardiogenic shock often lie listlessly, making few if any spontaneous movements.
The skin is cool and clammy, with a bluish or mottled color over the extremities, and there is marked facial pallor
with severe cyanosis of the lips and nailbeds.

Depending on the degree of cerebral perfusion, the patient in shock may converse normally or
may evidence confusion and disorientation.
HEART RATE

Vary from a marked bradycardia to a rapid regular or irregular tachycardia, depending on the
underlying rhythm and the degree of left ventricular failure.

Most commonly, the pulse is rapid and regular initially (sinus tachycardia at 100 to 110 beats/
min), slowing as the patients pain and anxiety are relieved; BLOOD PRESSURE
BLOOD PRESSURE.

Majority of patients with uncomplicated AMI are normotensive, although the reduced stroke volume
accompanying the tachycardia may cause declines in systolic and pulse pressures and elevation of diastolic
pressure.

Among previously normotensive patients, a hypertensive response occasionally is seen during the first
few hours, with the arterial pressure exceeding 160/90 mm Hg, presumably as a consequence of adrenergic
discharge secondary to pain and agitation.

In patients with massive infarction, arterial pressure falls acutely, owing to left ventricular dysfunction and
venous pooling secondary to administration of morphine or nitrates or both; as recovery occurs, the arterial
pressure tends to return to preinfarction levels.
of the Trendelenburg position. Other patients who are initially only slightly hypotensive may demonstrate gradually
TEMPERATURE AND RESPIRATION

Most patients with extensive AMI develop fever, a nonspecific response to tissue necrosis, within
24 to 48 hours of the onset of infarction.

Body temperature often begins to rise within 4 to 8 hours after the onset of infarction, and rectal
temperature may reach 101 to 102F.

Fever usually resolves by the fifth or sixth day following infarction.

Respiratory rate may be slightly elevated soon after the development of an AMI; in patients without heart
failure, it results from anxiety and pain because it returns to normal with treatment of physical and psychological
discomfort.

In patients with left ventricular failure, the respiratory rate correlates with the severity of failure; patients
with pulmonary edema may have respiratory rates exceeding 40 per minute.
JUGULAR VENOUS PULSE.

patients with AMI and cardiogenic shock, the jugular venous pressure is usually elevated.

right ventricular infarction, marked jugular venous distention

CAROTID PULSE

Palpation clue to the left ventricular stroke volume; a small pulse suggests a reduced stroke
volume, whereas a sharp, brief upstroke is often observed in patients with mitral regurgitation or ruptured
ventricular septum with a left-to-right shunt.

Pulsus alternans reflects severe left ventricular dysfunction.

THE CHEST.

Moist rales are audible in patients who develop left ventricular failure and/or a reduction of left
ventricular compliance with AMI.

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Diffuse wheezing may be present in patients with severe left ventricular failure.

Cough with hemoptysis, suggesting pulmonary embolism with infarction, may also occur. In 1967
Killip proposed a prognostic classification scheme based on the presence and severity of rales detected in
patients presenting with AMI. Class I patients are free of rales and a third heart sound. Class II patients have
rales but to only a mildmoderate degree (< 50 per cent of lung fields) and may or may not have an S3. Patients in
Class III have rales in more than half of each lung field and frequently have pulmonary edema. Finally, Class IV
patients are in cardiogenic shock.
Cardiac Examination
PALPATION

Palpation of the precordium may yield normal findings,

Patients with transmural AMI it more commonly reveals a presystolic pulsation, reflecting a
vigorous left atrial contraction filling a ventricle with reduced compliance.

Presence of left ventricular systolic dysfunction, an outward movement of the left ventricle may be
palpated in early diastole, coincident with a third heart sound.

Patients with longstanding hypertension or previous infarction with left ventricular hypertrophy
often demonstrate a laterally displaced, sustained apical impulse.
AUSCULTATION

The heart sounds, particularly the first sound, are frequently muffled and occasionally inaudible
immediately after the infarct, and their intensity increases during convalescence.

A soft first heart sound may also reflect prolongation of the P-R interval.

Patients with marked ventricular dysfunction and/or left bundle branch block may have
paradoxical splitting of the second heart sound).

Patients with postinfarction angina may also develop a transient, paradoxically split second heart
sound during anginal episodes.

A fourth heart sound is almost universally present in patients in sinus rhythm with AMI and is
usually best heard between the left sternal border and the apex. This sound reflects the atrial contribution to
ventricular filling and is particularly prominent in AMI patients due to a reduction in left ventricular compliance and

elevation of left ventricular end-diastolic pressure, even in the absence of left ventricular systolic
dysfunction. This finding is of limited diagnostic value because it is commonly audible in most patients with
chronic ischemic heart disease and is recordable, although not often audible, in many normal subjects older than
45 years.

A third heart sound in AMI usually reflects severe left ventricular dysfunction with elevated
ventricular filling pressure. It is caused by rapid deceleration of transmitral blood flow during protodiastolic filling of
the left ventricle with resultant oscillations of the cardiohemic system (i.e., myocardium and stream of blood
flowing from left atrium to left ventricle)

Systolic murmurs, transient or persistent, are commonly audible in patients with AMI and
generally result from mitral regurgitation secondary to dysfunction of the mitral valve apparatus (papillary muscle
dysfunction, left ventricular dilatation).

A new, prominent apical holosystolic murmur, accompanied by a thrill, may represent rupture of a
head of a papillary muscle The findings in rupture of the interventricular septum are similar, although the murmur
and thrill are usually most prominent along the left sternal border and may be audible at the right sternal border as
well.

Pericardial friction rubs are audible in 6 to 30 per cent of all patients with AMI and in a higher
percentage
Other Findings
FUNDI.
Hypertension, diabetes, and generalized atherosclerosis commonly accompany AMI, and because these
conditions may produce characteristic changes in the fundus, a careful funduscopic examination may provide
information concerning the underlying vascular status; this is particularly useful in patients unable to provide a
detailed history.

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ABDOMEN.
As already noted, in patients with AMI, particularly in an inferior location with diaphragmatic irritation, the pain may
be localized to the epigastrium or the right upper quadrant. Pain in the abdomen associated with nausea,
vomiting, restlessness, and even abdominal distention is often interpreted by patients as. Right heart failure,
characterized by hepatomegaly and a positive abdominojugular reflux, is unusual in patients with acute left
ventricular infarction but does occur in patients with severe and prolonged left ventricular failure or right ventricular
infarction.
EXTREMITIES.
Coronary atherosclerosis is often associated with systemic atherosclerosis, and it is therefore common for
patients with AMI to have a history of intermittent claudication and to demonstrate physical findings of peripheral
vascular disease. Thus, diminished peripheral arterial pulses, loss of hair, and atrophic skin in the lower
extremities are noted frequently in patients with coronary artery disease. Peripheral edema is a manifestation of
right ventricular failure and, like congestive hepatomegaly, is unusual in patients with acute left ventricular
infarction. Cyanosis of the nailbeds is common in patients with severe left ventricular failure and is particularly
striking in patients with cardiogenic shock.
NEUROPSYCHIATRIC FINDINGS
Neurological examination is normal unless the patient has suffered cerebral embolism secondary to a mural
thrombus.
LABORATORY EXAMINATIONS
Serum Markers of Cardiac Damage
The World Health Organization (WHO) criteria for the diagnosis of AMI require that at least two of the
following three elements be present:
- a history of ischemic-type chest discomfort,
- evolutionary changes on serially obtained ECG tracings
- a rise and fall in serum cardiac markers.
Finally, the assay methodology should be inexpensive and easy to perform:
CREATINE KINASE (CK)
- Serum CK activity exceeds the normal range within 4 to 8 hours following the onset of AMI and declines to
normal within 2 to 3 days.

CK ISOENZYMES

Three isoenzymes of CK (MM, BB, and MB) have been identified by electrophoresis.

Extracts of brain and kidney contain predominantly the BB isoenzyme, skeletal muscle contains
principally MM but does contain some MB (1 to 3 per cent), and both MM and MB isoenzymes are present in
cardiac muscle.
.
CK ISOFORMS
MYOGLOBIN
CARDIAC-SPECIFIC TROPONINS.
LACTIC DEHYDROGENASE (LDH).
The activity of this enzyme exceeds the normal range by 24 to 48 hours after the onset of AMI
- reaches a peak 3 to 6 days after the onset of pain,
- and returns to normal levels 8 to 14 days after the infarction
- increases diagnostic accuracy because the heart contains principally LDH1.
OTHER SERUM CARDIAC MARKERS
- serum glutamic oxaloacetic acid transferase (SGOT) now generally referred to as aspartate aminotransferase
(AST).

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- Other promising serum cardiac markers that are under development include heart fatty acid binding proteins
(hFABP), myosin light chains (MLC), myosin heavy chains (MHC), and glycogen phosphorylase isoenzyme BB
(GPBB). These markers offer the potential for earlier diagnosis (hFABP, GPBB) and a longer diagnostic window
(MLC, MHC), but their relative roles compared with traditional markers such as CK-MB and newer markers such
as CK-MB isoforms, cTnT, or cTnI remain to be defined. Carbonic anhydrase III is a protein found only in skeletal
muscle and not cardiac muscle. With injury to skeletal muscle it is released in a fixed relationship to myoglobin,
and therefore the ratio of myoglobin to carbonic anhydrase III may be a useful means of excluding a cardiac
source of myoglobin elevation.
SERUM LIPIDS.
HEMATOLOGICAL MANIFESTATIONS.
The elevation of the white blood count usually develops within 2 hours after the onset of chest pain,
reaches a peak 2 to 4 days following infarction, and returns to normal in 1 week
The erythrocyte sedimentation rate (ESR) is usually normal during the first day or two after infarction,
even though fever and leukocytosis may be present.
It then rises to a peak on the fourth or fifth day and may remain elevated for several weeks. The increase
in the ESR is secondary to elevated plasma alpha2 globulin fibrinogen

The hematocrit often increases during the first few days following infarction as a consequence of
hemoconcentration.
Electrocardiographic Findings
1. Q-WAVE AND NON-Q-WAVE INFARCTION
2. .ISCHEMIA AT A DISTANCE.
3. RIGHT VENTRICULAR INFARCTION.
- ST-segment elevation in right precordial leads (V1, V3RV6R)
4. ATRIAL INFARCTION.
- The most common electrocardiographic patterns are depression or elevation of the PR segment, alterations in
the contour of the P wave, and abnormal atrial rhythms, including atrial flutter, atrial fibrillation, wandering atrial
pacemaker, and AV nodal rhythm.
Imaging
1. ROENTGENOGRAPHY.
Two findings are common: signs of left ventricular failure and cardiomegaly., significant temporal
discrepancies may occur because of what have been termed diagnostic lags and post-therapeutic lags.
Echocardiography
1. TWO-DIMENSIONAL ECHOCARDIOGRAPHY

Ideal for the assessment of patients with AMI hospitalized in the coronary care unit or even in
the emergency department before admission.

Echocardiography is also useful in evaluating patients with chest pain and a nondiagnostic
ECG who are suspected of having an aortic dissection.
2. DOPPLER ECHOCARDIOGRAPHY
This technique allows for assessment of blood flow in the cardiac chambers and across cardiac valves. Used in
conjunction with two-dimensional echocardiography, it is helpful in detecting and assessing the severity of mitral
or tricuspid regurgitation following AMI.Identification of the site of acute ventricular septal rupture, as well as
quantification of shunt flow across the resulting defect, is also possible.
Other Imaging Modalities
1. COMPUTED TOMOGRAPHY (CT)
This technique can provide useful cross-sectional information in patients with MI. In addition to the assessment of
cavity dimensions and wall thickness, left ventricular aneurysms may be detected, and, of particular importance in

15

AMI, intracardiac thrombi can be identified. Although cardiac CT is a less convenient technique, it probably is
more sensitive for thrombus detection than is echocardiography
2. MAGNETIC RESONANCE IMAGING (MRI)
MRI techniques are capable of early recognition of MI and of providing an assessment of the severity of the
ischemic insult. This modality holds much promise because of its ability to assess perfusion of infarcted and
noninfarcted tissue as well as of reperfused myocardium; to identify areas of jeopardized but not infarcted
myocardium; to identify myocardial edema, fibrosis, wall thinning, and hypertrophy; to assess ventricular chamber
size and segmental wall motion; and to identify the temporal transition between ischemia and infarction.
3. NUCLEAR IMAGING.
Radionuclide angiography, perfusion imaging, infarct-avid scintigraphy, and positron-emission tomography have
been used to evaluate patients with AMI. Nuclear cardiac imaging techniques can be useful for detecting AMI
assessing infarct size, collateral flow, and jeopardized myocardium; determining the effects of the infarct on
ventricular function; and establishing prognosis of patients with AMI.
Estimation of Infarct Size
1.
ELECTROCARDIOGRAPHY.

formal sizing of infarcts by ECG technique is not necessary in most patients

The duration of ischemia time as estimated from continuous ST segment monitoring is correlated
with infarct size, the ratio of infarct size to area at risk, and the extent of regional wall motion abnormality
observed at 7 days and 30 days after AMI.
2.
SERUM CARDIAC MARKER METHODS
Account for the quantity of the marker lost from the myocardium, its volume of distribution, and its release ratio.
3.
NONINVASIVE IMAGING TECHNIQUES.
Echocardiography, radionuclide scintigraphy, CT scanning, and have all been utilized for the clinical and
experimental assessment of infarct size. Infarct-avid scintigraphy and myocardial perfusion imaging have
been used to quantify infarct size. Estimation of infarct size by quantitative tomographic 99mTc-sestamibi
imaging appears to be less limited by ventricular geometry and can distinguish small infarcts and ischemia from
infarcted myocardium more readily than other noninvasive methods. Contrast-enhanced MRI imaging has been
helpful in demonstrating the regional heterogeneity of infarction patterns in patients with persistently occluded
infarct arteries versus those with successfully reperfused vessels.

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