Seminar 3
Seminars from internal medicine for the 5th year
Prof. Jiří Horák
ISCHEMIC HEART DISEASE
Ischemia refers to a lack of oxygen due to inadequate perfusion. Ischemic heart disease is a
condition of diverse etiologies, all having in common an imbalance between oxygen supply
and demand.
Etiology and pathophysiology. The most common cause is atherosclerotic disease of
coronary arteries; also arterial thrombi, spasm, and rarely coronary emboli as well as by ostial
narrowing due to luetic aortitis.
Myocardial ischemia can also occur if myocardial oxygen demands are abnormally increased,
as in severe ventricular hypertrophy due to hypertension or aortic stenosis.
A reduction in the oxygen-carrying capacity of the blood, as in extremely severe anemia or in
the presence of carboxyhemoglobin, is a rare cause of myocardial ischemia. Not infrequently,
two or more causes of ischemia will coexist.
The normal coronary circulation is dominated and controlled by the myocardial requirements
for oxygen. This need is met by the heart's ability to vary coronary vascular resistance (and
therefore blood flow) considerably while the myocardium extracts a high and relatively fixed
percentage of oxygen.
CORONARY ATHEROSCLEROSIS
Major risk factors for atherosclerosis. high plasma LDL, low plasma HDL, cigarette smoking,
diabetes mellitus, and hypertension  dysfunction of vascular endothelium and an abnormal
interaction with blood monocytes and platelets  subintimal collections of abnormal fat,
cells, and debris (i.e., atherosclerotic plaques)  segmental reductions in cross-sectional area.
When the luminal area is reduced by more than approximately 80 percent, blood flow at rest
may be reduced, and further minor decreases in the stenotic orifice can reduce coronary flow
dramatically and cause myocardial ischemia.
Severe coronary narrowing and myocardial ischemia are frequently accompanied by the
development of collateral vessels, especially when the narrowing develops gradually. When
well developed, such vessels can provide sufficient blood flow to sustain the viability of the
myocardium at rest but not during conditions of increased demand.
Once severe stenosis of a proximal epicardial artery has reduced the cross-sectional area by
more than approximately 70 percent, the distal resistance vessels (when they function
normally) dilate to reduce vascular resistance and maintain coronary blood flow. A pressure
gradient develops across the proximal stenosis, and poststenotic pressure falls.
RECOGNITION OF ATHEROSCLEROSIS
Angiographic visualization of deformity in the lumen of a vessel remains the best presumptive
test of silent atherosclerosis. Coronary angiography now permits visualization and assessment
of arteries as small as 0.5 mm in diameter.
Functional tests based on pathophysiologic or metabolic effects of a narrowed arterial lumen
often give indirect clues. Assessment of electrocardiographic changes induced after
standardized exercise is a relatively simple noninvasive aid to the diagnosis of coronary
atherosclerosis with significant narrowing. Myocardial perfusion defects demonstrable with
imaging techniques using radionuclides are usually attributable to atherosclerosis.
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Prof. Jiří Horák
Ischemic heart disease (IHD), synonymous with coronary heart disease or arteriosclerotic
heart disease, is the most reliable indicator of atherosclerosis available today. Practically all
patients with myocardial infarction, as defined by electrocardiographic and enzymatic
changes, have coronary atherosclerosis. Rare exceptions are due to congenital anomalies of
the coronary vessels, emboli, or ostial occlusion due to the other types of cardiac or vascular
disease. Cerebrovascular disease (stroke) is a less reliable criterion for the presence of
atherosclerosis. It includes cerebral thrombosis and cerebral hemorrhage. Cerebral
thrombosis, including infarction or softening without evidence of embolus, is usually due to
atherosclerosis. On the other hand, cerebral hemorrhage is most often the result of congenital
aneurysms or of vascular defects peculiar to hypertension and diabetes. Dissections of the
aorta, peripheral vascular disease, thrombosis of other major vessels, and ischemic renal
disease likewise are not used to determine the prevalence of atherosclerosis in a population or
as an index of atherosclerosis elsewhere. Therefore, from an epidemiologic standpoint,
consideration of atherosclerosis focuses on IHD.
PATHOLOGY
Data from necropsies of SCD victims parallel the clinical observations on the prevalence of
coronary heart disease as the major structural etiologic factor. More than 80 percent of SCD
victims have pathologic findings of coronary heart disease, and these commonly include
ruptured atherosclerotic plaques and/or coronary thrombi. The most consistent coronary
artery abnormality is extensive chronic coronary atherosclerosis. Seventy-five percent of the
victims have two or more major vessels with >=75 percent stenosis.
The pathology of the myocardium in SCD reflects the extensive coronary heart disease which
usually precedes the fatal event. As many as 70 to 75 percent of males who die suddenly have
prior myocardial infarctions (MIs), and 20 to 30 percent have recent acute MIs. A high
incidence of left ventricular (LV) hypertrophy coexists with prior MIs. Clinical,
epidemiologic, and experimental data suggest that LV hypertrophy itself predisposes to SCD,
and it is likely that coexistence with prior MI adds additional risk.
PATHOPHYSIOLOGY
Discomfort due to myocardial ischemia occurs when the oxygen supply to the heart is
deficient in relation to the oxygen need. Oxygen consumption is closely related to the
physiologic effort made during contraction, and coronary venous blood is normally much
more desaturated than that draining other areas of the body. As a consequence, the removal of
more oxygen from each unit of blood, which is one of the adjustments commonly utilized by
exercising skeletal muscle, is already employed in the heart in the basal state. Therefore, the
heart must rely primarily on an increase in the coronary blood flow for obtaining additional
oxygen.
The blood flow through the coronary arteries is directly proportional to the pressure gradient
between the aorta and the ventricular myocardium during systole and the ventricular cavity
during diastole but is also proportional to the fourth power of the radius of the coronary
arteries. A relatively slight alteration in coronary luminal diameter below a critical level can
produce a large decrement in coronary flow, provided that other factors remain constant.
Coronary blood flow occurs primarily during diastole, when it is unopposed by systolic
myocardial compression of the coronary vessels.
When the epicardial coronary arteries are narrowed critically (>70 percent stenosis of the
luminal diameter), the intramyocardial coronary arterioles dilate in an effort to maintain total
flow at a level that will avert myocardial ischemia at rest. Further dilatation, which normally
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occurs during exercise, is therefore not possible. Hence any condition in which increased
heart rate, arterial pressure, or myocardial contractility occurs in the presence of coronary
obstruction tends to precipitate anginal attacks by increasing myocardial oxygen needs in the
face of a fixed oxygen supply.
By far the most frequent underlying cause of myocardial ischemia is organic narrowing of the
coronary arteries secondary to coronary atherosclerosis. A dynamic component of increased
coronary vascular resistance, secondary to spasm of the major epicardial vessels (often near
an atherosclerotic plaque) or more frequently to constriction of smaller coronary arterioles, is
present in many, perhaps the majority, of patients with chronic angina pectoris. There is no
evidence that systemic arterial constriction or increased cardiac contractile activity (rise in
heart rate or blood pressure or increase in contractility from liberation of catecholamines or
adrenergic activity) due to emotion can precipitate angina unless there is also organic or
dynamic narrowing of the coronary vessels. Acute thrombosis superimposed on an
atherosclerotic plaque is frequently the cause of unstable angina and acute myocardial
infarction.
Aside from conditions that narrow the lumen of the coronary arteries, the only other frequent
causes of myocardial ischemia are disorders such as valvular aortic stenosis or hypertrophic
cardiomyopathy, which cause a marked disproportion between the coronary perfusion
pressure and the heart's oxygen requirements.
An increase in heart rate is especially harmful in patients with coronary atherosclerosis or
with aortic stenosis, because it both increases myocardial oxygen needs and shortens diastole
relatively more than systole, thereby decreasing the total available perfusion time per minute.
Tachycardia, a decline in arterial pressure, thyrotoxicosis, and diminution in arterial oxygen
content (such as occurs in anemia or arterial hypoxia) are precipitating and aggravating
factors rather than underlying causes of angina.
EFFECTS OF ISCHEMIA
The inadequate oxygenation may cause transient disturbances of the mechanical, biochemical,
and electrical functions of the myocardium. The abrupt development of ischemia usually
affects a segment of left ventricular myocardium with almost instantaneous failure of normal
muscle contraction and relaxation. The relatively poor perfusion of the subendocardium
causes more intense ischemia of this portion of the wall. Ischemia of large segments of the
ventricle will cause transient left ventricular failure, and if the papillary muscles are involved,
mitral regurgitation can complicate this event. When ischemic events are transient, they may
be associated with angina pectoris; if prolonged, they can lead to myocardial necrosis and
scarring with or without the clinical picture of acute myocardial infarction.
When oxygenated, the normal myocardium metabolizes fatty acids and glucose to carbon
dioxide and water. With severe oxygen deprivation, fatty acids cannot be oxidized, and
glucose is broken down to lactate; intracellular pH is reduced as are the myocardial stores of
high-energy phosphates, adenosine triphosphate (ATP), and creatine phosphate. Impaired cell
membrane function leads to potassium leakage and the uptake of sodium by myocytes. The
severity and duration of the imbalance between myocardial oxygen supply and demand will
determine whether the damage is reversible or whether it is permanent, with subsequent
myocardial necrosis.
Ischemia also causes characteristic electrocardiographic changes such as repolarization
abnormalities. Another important consequence of myocardial ischemia is electrical instability,
since this may lead to ventricular tachycardia or ventricular fibrillation. Most patients who die
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suddenly from ischemic heart disease do so as a result of ischemia-induced malignant
ventricular tachyarrhythmias.
CLINICAL MANIFESTATIONS
ASYMPTOMATIC VERSUS SYMPTOMATIC CORONARY ARTERY DISEASE
Coronary atherosclerosis often begins to develop prior to age 20 and is widespread even
among adults who were asymptomatic during life. Before the menopause women develop less
coronary atherosclerosis and have a much lower incidence of the clinical manifestations of
coronary artery disease. This protection is lost progressively after the menopause. When all
age groups are considered, ischemic heart disease is the most common cause of death not only
in men but also in women. Approximately 25 percent of patients who survive acute
myocardial infarction may not reach medical attention, and these patients carry the same
adverse prognosis as those who present with the classic clinical syndrome. Sudden death may
be unheralded and is a common presenting manifestation of ischemic heart disease. Patients
can also present with cardiomegaly and heart failure secondary to ischemic damage of the left
ventricular myocardium that caused no symptoms prior to the development of heart failure;
this condition is referred to as ischemic cardiomyopathy. In contrast to the asymptomatic
phase of ischemic heart disease, the symptomatic phase is characterized by chest discomfort
due to either angina pectoris or acute myocardial infarction. Having entered the symptomatic
phase, the patient may exhibit a stable or progressive course, revert to the asymptomatic stage,
or suddenly die.
CHRONIC STABLE ANGINA PECTORIS
This episodic clinical syndrome is due to transient myocardial ischemia. Males constitute
approximately 70% of all patients with angina pectoris and an even greater fraction of those
younger than 50 years of age. The typical patient with angina is a 50- to 60-year-old man or
65- to 75-year-old woman who seeks medical help for troublesome or frightening chest
discomfort, usually described as heaviness, pressure, squeezing, smothering, or choking and
only rarely as frank pain. When the patient is asked to localize the sensation, he or she will
typically press on the sternum, sometimes with a clenched fist, to indicate a squeezing,
central, substernal discomfort. This symptom is usually crescendo-decrescendo in nature and
lasts 1 to 5 min. Angina can radiate to the left shoulder and to both arms, and especially to the
ulnar surfaces of the forearm and hand. It can also arise in or radiate to the back, neck, jaw,
teeth, and epigastrium.
Although episodes of angina are typically caused by exertion (e.g., exercise, hurrying, or
sexual activity) or emotion (e.g., stress, anger, fright, or frustration) and are relieved by rest,
they may also occur at rest and at night while the patient is recumbent (angina decubitus). The
patient may be awakened at night distressed by typical chest discomfort and dyspnea. The
pathophysiology of nocturnal angina is analogous to that of paroxysmal nocturnal dyspnea,
i.e., the expansion of the intrathoracic blood volume that occurs with recumbency causes an
increase in cardiac size and myocardial oxygen demand that lead to ischemia and transient left
ventricular failure.
The threshold for the development of angina pectoris varies from person to person and may
vary by time of day and emotional state. A patient may report symptoms upon minor exertion
in the morning (a short walk or shaving) yet by midday may be capable of much greater effort
without symptoms. Angina may be precipitated by unfamiliar tasks, a heavy meal, or
exposure to cold.
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A positive family history of ischemic heart disease, diabetes, hyperlipidemia, hypertension,
cigarette smoking, and other risk factors for coronary atherosclerosis.
In variant (Prinzmetal's) angina, the chest discomfort characteristically occurs at rest or
awakens the patient from sleep. It may be accompanied by palpitations or severe shortness of
breath, explosive in onset, severe, and frightening. It may also be brought on by effort,
although the workload at which it is precipitated usually varies considerably. Variant angina
is caused by focal spasm of proximal epicardial coronary arteries; in approximately threefourths of the patients atherosclerotic coronary artery obstruction is present, in which case the
vasospasm occurs near the stenotic lesion.
Physical examination is often normal. The patient's general appearance may reveal signs of
risk factors associated with coronary atherosclerosis such as xanthelasma or diabetic skin
lesions. There may also be signs of anemia, thyroid disease, and nicotine stains on the
fingertips from cigarette smoking. Palpation can reveal thickened or absent peripheral arteries,
signs of cardiac enlargement, and abnormal contraction of the cardiac impulse (left ventricular
akinesia or dyskinesia). Examination of the fundi may reveal increased light reflexes and
arteriovenous nicking as evidence of hypertension (an important risk factor for ischemic heart
disease), while auscultation can uncover arterial bruits, a third and/or fourth heart sound, and,
if acute ischemia or previous infarction has impaired papillary muscle function, a late apical
systolic murmur due to mitral regurgitation.
Laboratory examination. The urine should be examined for evidence of diabetes mellitus and
renal disease. Examination of the blood should include measurements of lipids (cholesterol-total, low density, and high density), glucose, creatinine, hematocrit, and, if indicated based
on the physical examination, thyroid function. A chest x-ray is important, since it may show
the consequences of ischemic heart disease, i.e., cardiac enlargement, ventricular aneurysm,
or signs of heart failure. Calcification of the coronary arteries can sometimes be identified on
chest fluoroscopy.
Electrocardiogram. A normal ECG does not exclude the diagnosis of ischemic heart disease.
A 12-lead ECG recorded at rest is normal in about half the patients with typical angina
pectoris, but there may be signs of an old myocardial infarction. Serial tracings are particulary
useful to look for past or evolving myocardial infarction. Although repolarization
abnormalities, i.e., T-wave and ST-segment changes and intraventricular conduction
disturbances at rest, are suggestive of ischemic heart disease, they are nonspecific, since they
can also occur in pericardial, myocardial, and valvular heart disease or with anxiety, changes
in posture, drugs, or esophageal disease. Typical ST-segment and T-wave changes that
accompany episodes of angina pectoris and disappear thereafter are more specific. The most
characteristic changes include displacement of the ST segment. The ST segment is usually
depressed during angina but may be elevated--sometimes strikingly so--as in the early stages
of myocardial infarction and in Prinzmetal's angina.
PROGNOSIS
The principal prognostic indicators in patients with ischemic heart disease are the functional
state of the left ventricle, the location and severity of coronary artery narrowing, and the
severity or activity of myocardial ischemia.
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Prof. Jiří Horák
On cardiac catheterization, elevations in left ventricular end-diastolic pressure and ventricular
volume and a reduced ejection fraction are the most important signs of left ventricular
dysfunction and are associated with a poor prognosis.
Patients with chest discomfort but normal left ventricular function and normal coronary
arteries have an excellent prognosis. In patients with normal left ventricular function and mild
angina but with critical stenoses (>=70 percent luminal diameter) of one, two, or three
epicardial coronary arteries, the 5-year mortality rates are approximately 2, 8, and 11 percent,
respectively. Obstructive lesions of the proximal left anterior descending coronary artery are
associated with a greater risk than are lesions of the right or left circumflex coronary artery,
since the former vessel usually perfuses a greater quantity of myocardium. Critical stenosis of
the left main coronary artery is associated with a mortality of about 15 percent per year.
How the exercise tolerance test affects the probability of coronary artery disease. The beforetest probability of coronary artery disease (CAD) will be modified by the result of the exercise
electrocardiogram to yield an after-test probability of CAD. Note that the finding of <1 mm of
ST-segment depression will reduce the probability of CAD, whereas >=1 mm of ST-segment
depression will increase the probability. For example, if a patient with a before-test
probability of CAD of 90 percent (about that of a middle-aged man with typical anginal
symptoms) had 2 to 2.49 mm on ST-segment depression on exercise testing, the after-test
probability of CAD would be 99.5 percent. In contrast, the same exercise test result in a
patient with 30 percent before-test probability of CAD (about that of a patient with atypical
anginal symptoms) would yield an after-test probability of about 90 percent. In an
asymptomatic patient, with a before-test probability of about 5 percent, the same exercise test
result would yield an after-test probability of 53 percent. Thus the same test yields different
after-test probabilities in patients with different before-test probabilities.
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Approximate probability of coronary artery disease before and after noninvasive testing of a
patient with typical (A) and atypical (B) angina pectoris. The percentages demonstrate how
the sequential use of an exercise electrocardiogram and an exercise thallium test may affect
the probability of coronary artery disease.
MANAGEMENT
Each patient must be evaluated individually with respect to life patterns, risk factors, control
of symptoms, and prevention of damage to left ventricular myocardium. The management
plan should consist of:
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1) explanation and reassurance,
2) reduction of risk factors (secondary prevention): The discontinuance of cigarette
smoking is vital. The risk of coronary events is low when the total plasma cholesterol
is less than 200 mg/100 mL, intermediate when it is 200 to 240 mg/100 mL, and
abnormally increased when the plasma cholesterol is over 240 mg/100 mL. Ideal
weight should be attained and maintained. Aggravating factors (e.g., endocrine
disorders, hypertension, and drugs such as glucocorticoids) should be treated and
eliminated when possible. Diabetes mellitus and hypertension, when present, should
be treated. The administration of estrogen to postmenopausal women appears to
provide significant protection with a reduction in coronary events. Nevertheless, there
is a modest increase in the occurrence of some malignancies and therefore therapy
should be individualized.
3) treatment of coexisting conditions capable of aggravating angina (hypertension,
anemia and hyperthyroidism).
4) sensible adaptations of activities to minimize anginal attacks. Patients must appreciate
the diurnal variation in their tolerance of certain activities and should reduce their
energy requirements in the morning and immediately after meals. It may be necessary
to recommend a change in employment to avoid physical stress.
5) a program of drug therapy:
 Nitrates act by causing systemic venodilation, thereby reducing myocardial wall
tension and oxygen requirements, as well as by dilating the epicardial coronary vessels
and increasing blood flow in collateral vessels. Nitroglycerin is administered
sublingually in tablets of 0.4 or 0.6 mg. Patients with angina should be instructed to
take the medication both to relieve an attack and also in anticipation of stress (exercise
or emotional). Headache and a pulsating feeling in the head are the most common side
effects of nitroglycerin. If relief is not achieved after the first dose of nitroglycerin, a
second or third dose may be given at 5-min intervals. If discomfort continues despite
treatment, the patient should consult a physician or report promptly to a hospital
emergency room for evaluation of possible unstable angina or acute myocardial
infarction. None of the long-acting nitrates is as effective as sublingual nitroglycerin
for the acute relief of angina. These preparations can be swallowed, chewed, or
administered as a patch or paste by the transdermal route. They can provide effective
plasma levels for up to 24 h, but the therapeutic response is highly variable. Useful
preparations include isosorbide dinitrate (10 to 40 mg PO tid), nitroglycerin ointment
(0.5 to 2.0 inches qid), or sustained-release transdermal patches (5 to 25 mg/d). Longacting nitrates are relatively safe and can be used together with intermittent sublingual
nitroglycerin to relieve discomfort and prevent attacks of angina.
 Beta-adrenoceptor blockers reduce myocardial oxygen demand by inhibiting the
increases in heart rate and myocardial contractility caused by adrenergic activity. Beta
blockage reduces these variables most strikingly during exercise while causing only
small reductions in heart rate, cardiac output, and arterial pressure at rest. Propranolol
is usually administered in an initial dose of 20 to 40 mg four times a day and is
increased as tolerated to 320 mg per day in divided doses. Long-acting beta-blocking
drugs (atenolol, 50 to 100 mg/d, and nadolol, 40 to 80 mg/d) offer the advantage of
once-a-day dosage.
 The therapeutic aims include relief of angina and ischemia. These drugs can also
reduce mortality and reinfarction when given to patients after myocardial infarction.
Side effects: fatigue, impotence, cold extremities, intermittent claudication, and
bradycardia. They can worsen disturbed cardiac conduction, left ventricular failure,
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and bronchial asthma or intensify the hypoglycemia produced by oral hypoglycemic
agents and insulin.
Calcium antagonists: verapamil (80 to 120 mg tid), diltiazem (30 to 90 mg qid) and
other calcium antagonists are all coronary vasodilators that produce variable and dosedependent reductions in myocardial oxygen demand, contractility, and arterial
pressure. These combined pharmacologic effects are advantageous and make these
agents quite effective in the treatment of angina pectoris. Verapamil and diltiazem
may produce symptomatic disturbances in cardiac conduction and bradyarrhythmias,
exert negative inotropic actions, and are more likely to worsen left ventricular failure,
particularly when used in combination with beta blockers in patients with underlying
left ventricular dysfunction. Careful individual titration of dose is essential with these
potent combinations. Variant (Prinzmetal's) angina responds particularly well to
calcium antagonists, supplemented when necessary by nitrates. The calcium
antagonists are now formulated as long-acting preparations including nifedipine (30 to
90 mg once daily), diltiazem (60 to 120 mg twice daily), and verapamil (180 to 240
mg once daily). Verapamil should not be combined with beta-adrenoreceptor blocking
drugs because of the combined effects on heart rate and contractility
Aspirin is an irreversible inhibitor of platelet cyclooxygenase activity. Chronic
administration of 100 to 325 mg orally per day has been shown to reduce coronary
events in asymptomatic adult men, patients with asymptomatic ischemia after
myocardial infarction, patients with chronic stable angina, and patients who have
survived unstable angina and myocardial infarction. Administration of this drug
should be considered in all patients with coronary artery disease in the absence of side
effects such as gastrointestinal bleeding, allergy, or dyspepsia.
6) mechanical revascularization.
UNSTABLE ANGINA PECTORIS
1. patients with new onset (<2 months) angina that is severe and/or frequent (>=3
episodes per day);
2. patients with accelerating angina, i.e., those with chronic stable angina who develop
angina that is distinctly more frequent, severe, prolonged, or precipitated by less
exertion than previously;
3. those with angina at rest.
Unstable angina, particularly when it is characterized by rest pain or occurs in the
postinfarction state, carries an adverse prognosis, with significant risk of acute myocardial
infarction or the development of intractable chronic stable angina.
When unstable angina is accompanied by objective electrocardiographic evidence of transient
myocardial ischemia (ST-segment changes and/or T-wave inversions during episodes of chest
pain), it is almost always associated with critical stenoses in one or more major epicardial
coronary arteries. The atherosclerotic lesions may have a complicated morphology, with
evidence of superimposed thrombosis in approximately 25 to 60 percent of cases. Segmental
spasm in the vicinity of atherosclerotic plaques may also play a role in the development of
unstable angina.
MANAGEMENT
 The patient should be admitted promptly to the hospital for observation, further
diagnosis, and treatment.
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Identify and treat concomitant conditions that can intensify ischemia, such as
uncontrolled tachycardia, hypertension and diabetes mellitus, cardiomegaly, heart
failure, arrhythmias, thyrotoxicosis, and any acute febrile illness. Acute myocardial
infarction should be ruled out by means of serial ECGs and measurements of plasma
cardiac enzyme activity.
Continuous electrocardiographic monitoring should be carried out and the patients
should receive reassurance and sedation.
Thrombus formation frequently complicates this condition. Therefore, intravenous
heparin should be given for 3 to 5 days to maintain the partial thromboplastin time at 2
to 2.5 times control, together with or followed by oral aspirin at a dose of 325 mg/d.
Beta-adrenoceptor blocking drugs and calcium antagonists should be administered, but
with caution and an awareness of the possible side effects discussed above. Dosages
must be titrated to avoid bradycardia, heart failure, and hypotension.
Nitroglycerin should be given by the sublingual route as needed for symptoms. In
addition, intravenous nitroglycerin is quite effective, although it requires continuous
monitoring of arterial pressure. It is begun at a dosage of 10 g/min and is raised in 5ug/min increments to a level at which chest pain is abolished but systolic arterial
pressure is maintained or reduced only slightly and other side effects are avoided.
The majority of patients improve with such treatment. However, if angina and/or
electrocardiographic evidence of ischemia do not diminish within 24 to 48 h of the
comprehensive treatment described above in patients with no obvious contraindications for
revascularization, then cardiac catheterization and coronary arteriography should be
performed. If the anatomy is suitable, PTCA can be performed with surgical standby. PTCA
in this condition, particularly in the presence of thrombus, is attended by increased risk of
acute closure and ischemia. If angioplasty cannot be done, coronary artery bypass grafting
should be considered to relieve symptoms and myocardial ischemia and as a means of
preventing myocardial damage. If the patient's symptoms and signs are controlled on medical
therapy, a diagnostic exercise ECG should be obtained near the time of hospital discharge. If
there is evidence of severe myocardial ischemia, serious consideration should be given to
catheterization and revascularization. It should be recognized that severe coronary artery
disease is often present in patients with unstable angina who respond to medical therapy.
Many patients in whom the unstable state is controlled are left with severe chronic stable
angina and ultimately require mechanical revascularization.
ACUTE MYOCARDIAL INFARCTION
In the United States, approximately 1.5 million myocardial infarctions occur each year.
Mortality with acute infarction is approximately 30%, with more than half of the deaths
occurring before the stricken individual reaches the hospital. An additional 5 to 10 percent of
survivors die in the first year following myocardial infarction and the number of myocardial
infarctions each year in the United States has remained largely unchanged since the early
1970s.
Thrombotic occlusion of a coronary artery previously narrowed by atherosclerosis 
myocardial infarction.
Factors such as cigarette smoking, hypertension, and lipid accumulation  vascular injury.
In the majority of cases, infarction occurs when an atherosclerotic plaque fissures, ruptures, or
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ulcerates, and, with conditions favoring thrombogenesis (factors which may be local or
systemic), a mural thrombus forms leading to coronary artery occlusion.
The amount of myocardial damage caused by coronary occlusion depends upon the territory
supplied by the affected vessel, whether or not the vessel becomes totally occluded, native
factors which can produce early spontaneous lysis of the occlusive thrombus, the quantity of
blood supplied by collateral vessels to the affected tissue, and the demand for oxygen of the
myocardium whose blood supply has been suddenly limited.
Patients at increased risk of developing acute myocardial infarction include those with
unstable angina, multiple coronary risk factors and Prinzmetal's variant angina. Less common
etiologic factors include hypercoagulability, coronary emboli, collagen vascular disease, and
cocaine abuse.
CLINICAL PRESENTATION
In roughly one-half of cases no precipitating factor appears to be present. In other cases,
triggers such as physical exercise, emotional stress, and medical or surgical illnesses can often
be identified. A higher frequency of onset occurs in the morning within a few hours of
awakening. Pain is the most common presenting complaint. The pain of myocardial infarction
is deep and visceral; adjectives commonly used to describe it are heavy, squeezing, and
crushing. It is similar in character to the discomfort of angina pectoris but is usually more
severe and lasts longer. Typically the pain involves the central portion of the chest and/or
epigastrium, and in about 30 percent of cases it radiates to the arms. Less common sites of
radiation include the abdomen, back, lower jaw, and neck. The location of the pain beneath
the xiphoid and patients' denial that they may be suffering a heart attack are chiefly
responsible for the mistaken diagnosis of indigestion. The pain of myocardial infarction may
radiate as high as the occipital area but not below the umbilicus. The pain is often
accompanied by weakness, sweating, nausea, vomiting, giddiness, and anxiety. The
discomfort usually commences with the patient at rest. When the pain begins during a period
of exertion, in contrast to angina pectoris, it does not usually subside with cessation of
activity. Approximately one-half of patients with myocardial infarction exhibit the prodrome
of unstable angina.
A minimum of 15 to 20 percent of myocardial infarcts are painless. The incidence of painless
infarcts is greater in women and patients with diabetes mellitus, and it increases with age. In
the elderly, myocardial infarction may present as sudden-onset breathlessness, which may
progress to pulmonary edema. Other less common presentations, with or without pain, include
sudden loss of consciousness, a confusional state, a sensation of profound weakness, the
appearance of an arrhythmia, evidence of peripheral embolism, or merely an unexplained
drop in arterial pressure. The pain of myocardial infarction can be similar to pain from acute
pericarditis, pulmonary embolism, acute aortic dissection, or costochondritis. These
conditions should be considered in the differential diagnosis.
PHYSICAL FINDINGS
Most patients are anxious and restless.
Pallor is common and is often associated with perspiration and coolness of the extremities.
The combination of substernal chest pain persistent for more than 30 min and diaphoresis
strongly suggests acute myocardial infarction.
Within the first hour of infarction about one-fourth of patients with anterior infarction have
manifestations of sympathetic nervous system hyperactivity (tachycardia and/or
hypertension), and up to one-half with inferior infarction show evidence of parasympathetic
hyperactivity (bradycardia and/or hypotension).
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The precordium is usually quiet, and the apical impulse may be difficult to palpate. In about
one-fourth of patients with anterior wall infarction, an abnormal systolic pulsation caused by
dyskinetic bulging of infarcted myocardium develops in the periapical area within the first
days of the illness. Other physical signs: fourth (S4) and third (S3) heart sounds, decreased
intensity of heart sounds, and, rarely, paradoxical splitting of the second heart sound. A
transient apical systolic murmur, presumably due to mitral regurgitation secondary to
papillary muscle dysfunction during acute infarction, may be midsystolic or late systolic in
timing.
A pericardial friction rub is heard in many patients with transmural myocardial infarction at
some time in their course if they are examined frequently. Jugular venous distention occurs
commonly in patients with right ventricular infarction. The carotid pulse is often decreased in
volume, reflecting reduced stroke volume. Temperature elevations up to 38 degC may be
observed during the first week following acute myocardial infarction; however, a temperature
exceeding 38 degC should prompt a search for other causes. The arterial pressure is variable;
in most patients with transmural infarction systolic pressure declines approximately 10 to 15
mmHg from the preinfarction state.
LABORATORY FINDINGS
The nonspecific reaction to myocardial injury is associated with polymorphonuclear
leukocytosis, which appears within a few hours after the onset of pain, persists for 3 to 7 days,
and often reaches levels of 12,000 to 15,000 leukocytes per microliter. The erythrocyte
sedimentation rate rises more slowly than the white blood cell count, peaking during the first
week, and sometimes remaining elevated for 1 or 2 weeks.
The electrocardiographic manifestations: transmural infarction is often present if the
electrocardiogram demonstrates Q waves or loss of R waves; nontransmural infarction may be
present if the electrocardiogram shows only transient ST-segment and sustained T-wave
changes.
Serum enzymes are released in large quantities into the blood from necrotic heart muscle
following myocardial infarction. The rate of liberation of specific enzymes differs following
infarction, and the temporal pattern of enzyme release is of diagnostic importance. Creatine
phosphokinase (CK) rises within 8 to 24 h and generally returns to normal by 48 to 72 h,
except in the case of large infarctions, when CK clearance is delayed. Lactic dehydrogenase
(LDH) rises later (24 to 48 h) and remains elevated for as long as 7 to 14 days. The serum
aminotransferase enzymes AST and ALT (previously designated SGOT and SGPT) were
utilized in the diagnosis of myocardial infarction for many years but have fallen out of favor.
The MB isoenzyme of CK has the advantage over CK and LDH in that it is not present in
significant concentrations in extracardiac tissue and therefore is more specific. CK-MB
isoenzymes are particularly useful when skeletal muscle and/or brain damage are suspected
since both of these tissues contain large quantities of the CK enzyme but none of the MB
isoenzyme.
Cardiac surgery, myocarditis, and electrical cardioversion often result in elevation of serum
levels of MB isoenzyme.
Cardiac-specific troponin T and cardiac-specific troponin I are now the preferred biochemical
markers of AMI.
The ECG is a cornerstone in the diagnosis of acute and chronic ischemic heart disease. The
findings depend on several key factors: the nature of the process [reversible (i.e., ischemia)
versus irreversible (i.e., infarction)], the duration (acute versus chronic), extent (transmural
versus subendocardial), and localization (anterior versus inferoposterior), as well as the
presence of other underlying abnormalities (ventricular hypertrophy, conduction defects).
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Ischemia exerts complex time-dependent effects on the electrical properties of myocardial
cells. Severe, acute ischemia lowers the resting membrane potential and shortens the duration
of the action potential. Such changes cause a voltage gradient between normal and ischemic
zones. As a consequence, current flows between these regions. These so-called currents of
injury are represented on the surface ECG by deviation of the ST segment. When the acute
ischemia is transmural, the ST vector is usually shifted in the direction of the outer
(epicardial) layers, producing ST elevations and sometimes, in the earliest stages of ischemia,
tall, positive so-called hyperacute T waves over the ischemic zone. With ischemia confined
primarily to the subendocardium, the ST vector typically shifts toward the subendocardium
and ventricular cavity so that overlying (e.g., anterior precordial) leads show ST-segment
depression (with ST elevation in lead aVR). Multiple factors affect the amplitude of acute
ischemic ST deviations. Profound ST elevation or depression in multiple leads usually
indicates very severe ischemia. Complete resolution of ST elevation promptly following
thrombolytic therapy is a relatively specific, though not sensitive, marker of successful
reperfusion.
The ECG leads are more helpful in localizing regions of Q wave than non-Q wave ischemia.
For example, acute anterior wall ischemia leading to Q wave infarction is reflected by ST
elevations or increased T-wave positivity in one or more of the precordial leads (V1 to V6)
and leads I and aVL. Anteroseptal ischemia produces these changes in leads V1 to V3, apical
or lateral ischemia in leads V4 to V6. Inferior wall ischemia produces changes in leads II, III,
and aVF. Posterior wall ischemia may be indirectly recognized by reciprocal ST depressions
in leads V1 to V3. Prominent reciprocal ST depressions in these leads also occur with certain
inferior wall infarcts, particularly those with posterior or lateral wall extension. Right
ventricular ischemia usually produces ST elevations in right-sided chest leads. When ischemic
ST elevations occur as the earliest sign of acute infarction, they are typically followed within
a period ranging from hours to days by evolving T-wave inversions and often by Q waves
occurring in the same lead distribution. (T-wave inversions due to evolving or chronic
ischemia correlate with prolongation of repolarization and are often associated with QT
lengthening.) Reversible transmural ischemia, e.g., due to coronary vasospasm (Prinzmetal's
variant angina), may cause transient ST-segment elevations without development of Q waves.
Depending on the severity and duration of such ischemia, the ST elevations may either
resolve completely within minutes or be followed by T-wave inversions that persist for hours
or even days. Patients with ischemic chest pain who present with deep T-wave inversions in
multiple precordial leads (e.g., V1 to V4) with or without cardiac enzyme elevations typically
have severe obstruction in the left anterior descending coronary artery system. In contrast,
patients whose baseline ECG already shows abnormal T-wave inversions may develop Twave normalization (pseudonormalization) during episodes of acute transmural ischemia.
With infarction, depolarization (QRS) changes often accompany repolarization (ST-T)
abnormalities. Necrosis of sufficient myocardial tissue may lead to decreased R-wave
amplitude or frank abnormal Q waves in the anterior or inferior leads. Previously, abnormal Q
waves were considered to be markers of transmural myocardial infarction, while
subendocardial infarcts were thought not to produce Q waves. Infarcts are more appropriately
classified as "Q-wave" or "non-Q-wave". Loss of depolarization forces due to posterior or
lateral infarction may cause reciprocal increases in R-wave amplitude in leads V1 and V2
without diagnostic Q waves in any of the conventional leads. Atrial infarction may be
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associated with PR-segment deviations due to an atrial current of injury, changes in P-wave
morphology, or atrial arrhythmias. In the weeks and months following infarction, these ECG
changes may persist or begin to resolve. Complete normalization of the ECG following Qwave infarction is uncommon but may occur, particularly with smaller infarcts. In contrast,
persistent ST-segment elevations several weeks or more after a Q-wave infarct usually
correlate with a severe underlying wall motion disorder (akinetic or dyskinetic zone),
although not necessarily a frank ventricular aneurysm.
ECG changes due to ischemia may occur spontaneously or may be provoked by various
exercise protocols (stress electrocardiography). In patients with severe ischemic heart disease,
exercise testing is most likely to elicit signs of subendocardial ischemia (horizontal or
downsloping ST depression in multiple leads). ST-segment elevation during exercise is most
often observed after a Q-wave infarct. This repolarization change does not necessarily
indicate active ischemia but correlates strongly with the presence of an underlying ventricular
wall motion abnormality. However, in patients without prior infarction, transient ST-segment
elevation with exercise is a reliable sign of transmural ischemia.
The ECG has important limitations in both sensitivity and specificity in the diagnosis of
ischemic heart disease.
Cardiac imaging. Acute infarct scintigraphy ("hot-spot" imaging) is carried out with an
infarct-avid imaging agent such as [99mTc]stannous pyrophosphate. Scans are usually
positive 2 to 5 days after infarction, particularly in patients with transmural infarcts; although
they aid in localizing infarcts and provide a measure of infarct size, these scans are less
sensitive than CK determination for making the diagnosis of myocardial infarction.
Myocardial perfusion imaging with thallium 201 or technetium 99m Sesta-Mibi, which are
distributed in proportion to myocardial blood flow and concentrated by viable myocardium,
reveals a defect ("cold spot") in most patients during the first few hours after development of
a transmural infarct. However, since it is not possible to distinguish acute infarcts from
chronic scars, perfusion scanning, although extremely sensitive, is not specific for the
diagnosis of acute myocardial infarction. Through sequential [99mTc]Sesta-Mibi imaging
(e.g., before and after thrombolysis) the area of myocardium at risk may be estimated;
likewise, sequential scanning may permit assessment of the area of successful reperfusion and
comparison of infarct size (late) with the area at risk (early).
Two-dimensional echocardiography can also be of value in patients with acute myocardial
infarction. Abnormalities of wall motion are almost universally present. In the emergency
room setting, the early use of echocardiography can aid in management decisions such as
whether or not thrombolytic agents should be administered. Echocardiographic estimation of
left ventricular function is relatively accurate and can be useful prognostically.
MANAGEMENT
The prognosis in acute myocardial infarction is largely related to the occurrence of two
general classes of complications: (1) electrical (arrhythmias) and (2) mechanical ("pump
failure"). Ventricular fibrillation is the most common form of arrhythmic death in acute
myocardial infarction. The vast majority of deaths due to ventricular fibrillation occur within
the first 24 h of the onset of symptoms, and of these deaths, over half occur in the first hour.
Most out-of-hospital deaths from myocardial infarction are due to ventricular fibrillation. It
may occur without warning symptoms or arrhythmias. Over the last 30 years, with careful
monitoring and prompt attention to arrhythmias, the in-hospital mortality for acute myocardial
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infarction has been reduced from about 30 to between 10 and 15 percent, and death from inhospital ventricular arrhythmia is now unusual.
Pump failure is now the primary cause of in-hospital death from acute myocardial infarction.
The extent of ischemic necrosis correlates well with the degree of pump failure and with
mortality, both early, i.e., within 10 days of infarction, and later as well.
The principal objectives of management of the patient with myocardial infarction are to
prevent death from arrhythmia and to minimize the mass of infarcted tissue.
CORONARY CARE UNITS
These have resulted in improved care of patients with myocardial infarction, reduction in
mortality rates, and major increases in knowledge about myocardial infarction.
Patients should be admitted to these units early in their illness when they may expect to derive
maximum benefit from the care provided.
REPERFUSION
Thrombolysis. Early reperfusion of ischemic myocardium can potentially salvage tissue
before it becomes irreversibly injured. Since most infarctions are caused by a relatively
sudden thrombotic occlusion overlying an atherosclerotic plaque in a major epicardial
coronary vessel, recent attention has been appropriately directed at techniques to
pharmacologically or mechanically recanalize the "culprit" vessel. The thrombolytic agents
streptokinase, anisoylated plasminogen streptokinase activator complex (APSAC), and tissue
plasminogen activator (tPA) have been approved by the Federal Drug Administration for
intravenous use in the setting of acute myocardial infarction.
Institution of therapy remains of benefit in many patients seen 3 to 6 h after the onset of
infarction, and some benefit appears possible up to 12 h.
tPA is more effective than streptokinase or APSAC at restoring coronary artery flow, and has
a small edge in improving survival as well. The current recommended total dose of tPA is 100
mg, beginning with a 5 to 10 mg bolus followed by 60 mg intravenously over the first hour,
followed by 20 mg each in the second and third hours.
Streptokinase is administered as 1.5 million units intravenously over 1 h. APSAC has the
benefit of being administered as a single dose of 30 mg over 2 to 5 min, making it an ideal
agent when given out of the hospital. Anticoagulant and platelet regimens appear to aid in
establishing and maintaining vessel patency, and aspirin has been shown to lower mortality
when given with thrombolytic therapy. Recent studies suggest that 160 to 325 mg of aspirin
and 5000 units of I.V. heparin should be given with the institution of thrombolytic therapy.
This should be followed by 325 mg of aspirin daily and a continuous infusion of heparin for 2
to 5 days.
Clear contraindications to the use of thrombolytic agents include a history of cerebrovascular
accident, a recent (within 2 weeks) invasive or surgical procedure (or prolonged
cardiopulmonary resuscitation), marked hypertension (systolic arterial pressure greater than
180 mmHg and/or diastolic pressure greater than 100 mmHg) at any time during the acute
presentation, and active peptic ulcer disease.
Allergic reactions to streptokinase or APSAC occur in approximately 2 percent of cases.
Hemorrhage is the most frequent and potentially the most serious complication. Hemorrhagic
stroke is the most serious complication and occurs in approximately 0.4 percent of cases. This
rate increases with advancing age, with patients greater than 70 years of age experiencing
roughly twice the rate of intracranial hemorrhage as those less than 65 years of age.
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Primary percutaneous transluminal coronary angioplasty. Primary PTCA without preceding
thrombolysis is also effective in restoring perfusion in acute myocardial infarction. It has the
advantages of being applicable to patients with contraindications to thrombolytic therapy; it
appears to be more effective than thrombolysis in opening occluded coronary arteries and may
be associated with a somewhat better clinical outcome.
The early administration of nitrates and beta blockers, with or without thrombolytic therapy,
appears to be of benefit.
ROUTINE TREATMENT OF THE PATIENT WITH MYOCARDIAL INFARCTION
ANALGESIA. One of the important initial therapeutic objectives is the relief of pain.
Morphine is an extremely effective analgesic for the pain associated with myocardial
infarction. However, it may reduce sympathetically mediated arteriolar and venous
constriction. The resultant venous pooling may produce a reduction in cardiac output and
arterial pressure. Morphine also has a vagotonic effect and may cause bradycardia or
advanced degrees of heart block, particularly in patients with posteroinferior infarction. These
side effects of morphine usually respond to atropine (0.5 mg intravenously). Morphine is
routinely administered by repetitive (every 5 min) intravenous injection of small doses of drug
(2 to 4 mg) rather than by administration of a larger quantity by the subcutaneous route, by
which absorption may be unpredictable. Meperidine hydrochloride or hydromorphone
hydrochloride may be effectively employed in place of morphine.
Prior to administering morphine, sublingual nitroglycerin can be given safely to most patients
with myocardial infarction. As long as hypotension does not occur, up to three 0.4-mg doses
should be administered at about 5-min intervals. In addition to diminishing or abolishing chest
discomfort, this form of therapy, may be capable of both decreasing myocardial oxygen
demand (by lowering preload) and increasing myocardial oxygen supply (by dilating infarctrelated coronary vessels or collateral vessels).
However, therapy with nitrates should be avoided in patients who present with a low systolic
arterial pressure (<100 mmHg).
Intravenous beta blockers are also useful in the control of the pain of acute myocardial
infarction. These drugs have been shown to control pain effectively in some patients,
presumably by diminishing ischemia consequent to lowering myocardial oxygen demand.
More importantly, there is some evidence that intravenous beta blockers reduce in-hospital
mortality.
OXYGEN. The routine use of oxygen is supported by the observation that the arterial PO2 is
reduced in many patients with myocardial infarction and that oxygen inhalation reduces the
area of ischemic injury in experimental animals. Oxygen should be administered by face mask
or nasal prongs for the first day or two after infarction.
ACTIVITY. Factors which increase the work of the heart during the initial hours of infarction
may increase the size of the infarct. Circumstances in which heart size, cardiac output, or
myocardial contractility are increased should be avoided. 6 to 8 weeks are required for
complete healing, i.e., replacement of the infarcted myocardium by scar tissue. The purpose
of a graded increase in physical activity is to provide the most favorable possible
circumstances for this healing.
Most patients with myocardial infarction should be admitted to a coronary care unit and
remain there until clinical stability has been demonstrated (usually 1 to 3 days). A catheter
should be introduced into a peripheral vein. The patient should be in bed most of the day, with
one or two periods of 15 to 30 min in a bedside chair. The patient should be bathed but may
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eat unassisted. By the third or fourth day the patient with an uncomplicated course should be
spending at least 30 to 60 min in a chair twice a day.
Standing and gradual ambulation are usually begun between the second and fourth days post
infarction in patients with uncomplicated myocardial infarction. Ambulation is progressively
increased, eventually including walks about the hospital floor.
The total duration of hospitalization in uncomplicated cases is usually 6 to 11 days.
If ischemia occurs at rest, or if ischemia and/or hypotension occur during limited exercise,
coronary arteriography should be carried out, except in the very elderly or in those for whom
contraindications to invasive procedures exist. If a large quantity of viable myocardium,
perfused by critically narrowed vessel(s), is found at angiography, then revascularization
(either by angioplasty or by operation) may be required.
The remainder of the convalescent phase of myocardial infarction may be accomplished at
home. From 2 to 6 weeks, the patient should be encouraged to increase activity by walking
about the house and outdoors in good weather. Patients should still spend 8 to 10 h in bed
each night. Additional rest periods in the morning and afternoon may be advisable for selected
patients. Normal sexual activity may be resumed during this period.
From 6 to 8 weeks onward, the physician must regulate the patient's activity on the basis of
his or her exercise tolerance. It is during this period of increasing activity that the patient may
become aware of profound fatigue. Postural hypotension may still be a problem. Most patients
will be able to return to work after 12 weeks, and many patients much earlier. If not
performed earlier, a maximal exercise test is frequently performed after 6 to 8 weeks or prior
to returning to work. A trend toward earlier ambulation, hospital discharge, and resumption of
full activity for patients recuperating from acute myocardial infarction has developed in recent
years.
DIET. During the first 4 or 5 days, a low-calorie diet divided into multiple small feedings is
preferred. If heart failure is present, sodium intake should be restricted.
BOWELS. Bed rest of 3 to 5 days and the effect of the narcotics utilized for the relief of pain
often lead to constipation. A bedside commode, rather than a bed pan, a diet rich in bulk, and
the routine use of a stool softener are recommended. If the patient remains constipated despite
these measures, a laxative can be safely used.
SEDATION. Most patients require sedation during hospitalization in order to withstand the
period of enforced inactivity with tranquility. Diazepam, 5 mg, oxazepam, 15 to 30 mg, or
lorazepam, 0.5 to 2 mg, given three or four times daily, is usually effective. An additional
dose of any of the above medications may be given at night to ensure adequate sleep.
ANTICOAGULANTS AND ANTIPLATELET AGENTS. At the time of thrombolytic
therapy, unless contraindications exist, most patients with possible or probable myocardial
infarction should be started on aspirin, 160 or 325 mg daily. Patients with acute myocardial
infarction not undergoing thrombolytic therapy should also generally receive aspirin.
Additionally, in order to prevent venous thrombosis in patients not treated with thrombolytic
therapy, either intravenous heparin or small subcutaneous doses of heparin (5000 units every
8 to 12 h) should be employed as well.
Controversy persists about the use of oral anticoagulants once the patient is out of the
intensive care area. Warfarin should be used for patients with congestive heart failure which
persists for more than 3 to 4 days or for those with large anterior infarctions in whom the risk
of developing a left ventricular thrombus is greater. The indication for anticoagulation as
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prophylaxis against arterial embolism increases with the extent of infarction. The appropriate
duration of therapy is unknown, but probably should be carried out for 3 to 6 months.
Evidence suggests that warfarin lowers late mortality and the incidence of reinfarction after an
acute myocardial infarction.
BETA-ADRENOCEPTOR BLOCKERS. The chronic routine use of oral beta-adrenoceptor
blockers for at least 2 years following acute myocardial infarction is supported by wellconducted placebo-controlled trials which have convincingly demonstrated reductions in total
mortality, sudden death, and in some instances, reinfarction rate. For patients presenting with
the clear picture of a hyperdynamic state, in the absence of contraindications such as
congestive heart failure, hypotension, bradycardia, atrioventricular block, or a history of
asthma, an intravenous dose of a beta blocker such as metoprolol may be given (5 mg every 5
to 10 min for a total dose of 15 mg, stopping between doses if any complications arise). This
is usually followed by an oral dose regimen of metoprolol (50 to 100 mg bid). Later in the
hospital course, a long-acting beta blocker, such as atenolol (50 to 100 mg qd) can be
prescribed. Beta blocker therapy is probably indicated for most patients after myocardial
infarction, except those for whom its use is specifically contraindicated.
ANGIOTENSIN CONVERTING ENZYME INHIBITORS. The administration of
angiotensin-converting enzyme (ACE) inhibitors can now be recommended for improvement
in mortality as well as for prevention of heart failure and recurrent myocardial infarction.
ACE inhibitors should be prescribed within 24 h to all patients with AMI and overt congestive
heart failure.
Magnesium appears to have favorable effects on cardiac arrhythmias, coronary blood flow,
platelet aggregation, as well as myocardial metabolism. The early use of intravenous
magnesium (8 mmol MgSO4 over 15 min, followed by 65 mmol over the next 24 h)
significantly reduces serious arrhythmias and total mortality after myocardial infarction.
As noted earlier, nitrates (intravenous or oral) may be useful in the relief of pain associated
with acute myocardial infarction. Favorable effects on the ischemic process and ventricular
remodeling (see below) has led many physicians to routinely use intravenous nitroglycerin (5
to 10 ug/min initial dose and up to 200 ug/min as long as hemodynamic stability is
maintained) for the first 24 to 48 h after the onset of infarction.
Complications
Ventricular premature systoles. Pharmacologic therapy is now reserved for patients with
sustained or symptomatic ventricular arrhythmias. Prophylactic antiarrhythmic therapy (either
intravenous lidocaine early or oral agents later), in the absence of clinically important
ventricular tachyarrhythmias, is contraindicated as such therapy may actually increase late
mortality. Beta-adrenoceptor blocking agents are effective in abolishing ventricular ectopic
activity in infarction patients and in the prevention of ventricular fibrillation. They should be
used routinely in patients without contraindications. In addition, hypokalemia is a risk factor
for ventricular fibrillation in patients with acute myocardial infarction, and the serum
potassium concentration should be adjusted to approximately 4.5 mmol/L.
Ventricular tachycardia and ventricular fibrillation. Sustained ventricular tachycardia is
treated first with lidocaine, and if it cannot be terminated by one or two 50- to 100-mg doses,
electroconversion should be employed. Electroshock is used immediately in patients with
ventricular fibrillation, or when ventricular tachycardia causes hemodynamic deterioration. If
fibrillation has persisted for more than a few seconds, the first shock may be unsuccessful,
and in this situation it is advisable to administer closed-chest massage and mouth-to-mouth
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respiration before attempting electroconversion again. Improvement of oxygenation and
perfusion increase the likelihood of successful defibrillation.
Long-term survival is good (generally better than 90 percent at 1 year) in patients with
primary ventricular fibrillation, i.e., ventricular fibrillation resulting as a primary response to
acute ischemia and not associated with predisposing factors such as congestive heart failure,
shock, bundle branch block, or ventricular aneurysm. This prognosis is in sharp contrast to
that for patients who develop ventricular fibrillation secondary to severe pump failure. In
patients who develop ventricular tachycardia or ventricular fibrillation late in their hospital
course, the mortality in 1 year may be as high as 85 percent.
Supraventricular arrhythmias. Sinus tachycardia is the most common arrhythmia of this type.
If it occurs secondary to other causes (such as anemia, fever, heart failure, or a metabolic
derangement), the primary problem should be treated first. However, if sinus tachycardia
appears to be due to sympathetic overstimulation, such as is seen as part of a hyperdynamic
state, then treatment with a relatively short acting beta blocker such as propranolol should be
considered. Other common arrhythmias in this group are junctional rhythm and tachycardia,
atrial tachycardia, atrial flutter, and atrial fibrillation. These rhythm disturbances are often
secondary to left ventricular failure. The administration of digoxin is usually the treatment of
choice for supraventricular arrhythmias if heart failure is present. If heart failure is absent,
verapamil is an ideal alternative, as this agent may also help control ischemia. If the abnormal
rhythm persists for more than 2 h with a ventricular rate in excess of 120 beats per minute, or
at any time when tachycardia induces heart failure, shock, or ischemia (as manifested by
recurrent pain or ECG changes), electroshock should be utilized.
Sinus bradycardia. Treatment of sinus bradycardia is indicated if hemodynamic compromise
results from the slow heart rate. Elevation of the legs and/or the foot of the bed is frequently
helpful in the treatment of sinus bradycardia. Atropine is the most useful drug for increasing
heart rate and should be given intravenously in doses of 0.5 mg initially. If the rate remains
below 60 beats per minute, additional doses of 0.2 mg, up to a total of 2.0 mg, may be given
in divided doses. Persistent bradycardia (<40 beats per minute) despite atropine may be
treated with electrical pacing.
Atrioventricular and intraventricular conduction disturbances. The in-hospital mortality rate
of patients with complete AV block in association with anterior infarction is markedly higher
(60 to 75%) than that of patients who develop AV block with inferior infarction (25 to 40%),
and the risk of subsequent death in those who survive to leave the hospital is also increased in
the former group. This difference is related to the fact that heart block in inferior infarction is
usually caused by AV nodal ischemia. The AV node is a small discrete structure, and thus a
small amount of ischemia or necrosis can result in AV nodal dysfunction. In anterior wall
infarction, heart block is usually related to ischemic malfunction of all three fascicles of the
conduction system and thus commonly results only from extensive myocardial necrosis.
Electrical pacing provides an effective means of increasing the heart rate of patients with
bradycardia due to AV block.
HEART FAILURE
Some degree of transient impairment of left ventricular function occurs in over half of
patients with myocardial infarction. The most common clinical signs are pulmonary rales and
S3 and S4 gallop rhythms. Pulmonary congestion is also frequently seen on the chest
roentgenogram.
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The management of heart failure in association with myocardial infarction:
Diuretic agents are extremely effective since they diminish pulmonary congestion in the
presence of systolic and/or diastolic heart failure. A fall in left ventricular filling pressure and
an improvement in orthopnea and dyspnea follow the intravenous administration of
furosemide. Nitrates in various forms may be used to decrease preload and congestive
symptoms. Oral isosorbide dinitrate, topical nitroglycerin ointment, or intravenous
nitroglycerin, all have the advantage over a diuretic of lowering preload through
venodilatation without decreasing the total plasma volume. Additionally, nitrates may
improve ventricular compliance if concurrent ischemia is present, since ischemia causes an
elevation of left ventricular filling pressure.
ACE inhibitors are ideal, esp. in the long-term use.
Ventricular remodeling. Soon after myocardial infarction, the left ventricle begins to dilate.
Acutely, this occurs as the result of expansion of the infarct. Later, lengthening of the
noninfarcted segments occurs as well. Overall chamber enlargement is related to the size of
the infarction, with greater degrees of dilatation causing more marked hemodynamic
impairment, more frequent heart failure, and a poorer prognosis as well. Progressive dilatation
and its clinical consequences may be attenuated by afterload-reducing therapy such as
vasodilatation induced by an ACE inhibitor.
Cardiogenic shock. It is useful to consider cardiogenic shock as a form of severe left
ventricular failure. This syndrome is characterized by marked hypotension with systolic
arterial pressure <80 mmHg and a marked reduction of cardiac index [<1.8 (L/min)m2] in the
face of elevated left ventricular filling (pulmonary capillary wedge) pressure >18 mmHg.
Hypotension alone is not a basis for the diagnosis of cardiogenic shock, because many
patients who make an uneventful recovery will have serious hypotension (systolic pressure
<80 mmHg) for several hours. Cardiogenic shock is generally associated with a mortality rate
of >70 percent.
Pathophysiology of pump failure
Marked reduction in the quantity of contracting myocardium → cardiogenic shock. The initial
insult results in a decrease in arterial pressure and hence in coronary blood flow. The
reduction in coronary perfusion pressure and myocardial blood flow further impairs
myocardial function and may increase the size of the myocardial infarction. Arrhythmias and
metabolic acidosis also contribute to this deterioration because they are the result of
inadequate perfusion. It is this positive feedback loop which accounts for the high mortality
rate associated with the shock syndrome.
Treatment of pump failure
All patients with shock should have continuous monitoring of arterial pressure and of left
ventricular filling pressure (as reflected in the pulmonary capillary wedge pressure measured
with a pulmonary artery balloon catheter) as well as frequent determinations of cardiac
output. When pulmonary edema coexists, endotracheal intubation may be necessary to ensure
oxygenation. The relief of pain is important, as some vasodepressor reflex activity may be a
response to severe pain. However, narcotics should be used cautiously in view of their
propensity to lower arterial pressure.
Attempt to maintain coronary perfusion by raising the arterial blood pressure with
vasopressors, intraaortic balloon counterpulsation, and manipulation of blood volume to a
level that ensures an optimum left ventricular filling pressure (approximately 20 mmHg). The
latter may require either infusion of crystalloid or diuresis.
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In patients seen within the first 4 to 8 h of the onset of infarction, reperfusion by thrombolytic
therapy and/or PTCA may improve left ventricular function dramatically, thereby interrupting
the cycle of hemodynamic deterioration.
Hypovolemia
Hypovolemia may be secondary to previous diuretic use, to reduced fluid intake during the
early stages of the illness, and/or to vomiting associated with pain or medications.
Consequently, hypovolemia should be identified and corrected in patients with acute
myocardial infarction and hypotension. The optimal left ventricular filling or pulmonary
artery wedge pressure may vary considerably among different patients (generally at
approximately 20 mmHg). Central venous pressure reflects right rather than left ventricular
filling pressure and is an inadequate guide for adjustment of blood volume, since left
ventricular function is almost always affected much more adversely than right ventricular
function in acute myocardial infarction.
Vasopressors
Isoproterenol is a sympathomimetic amine which is now rarely used in the treatment of shock
due to myocardial infarction. Although this agent increases contractility, it also produces
peripheral vasodilatation and increases heart rate. The resultant increase in myocardial oxygen
consumption and reduction of coronary perfusion pressure may extend the area of ischemic
injury. Norepinephrine is a potent alpha-adrenergic agent with powerful vasoconstrictive
properties which also possesses beta-adrenergic activity and therefore enhances contractility.
Because the increase in afterload and contractility associated with its use causes a marked
increase in myocardial oxygen consumption, it should be reserved for desperate situations or
for patients with cardiogenic shock and lowered systemic vascular resistance. It should be
started at 2 to 4 ug/min. If pressure cannot be maintained with a dosage of 15 ug/min, it is
unlikely that a further increase will be beneficial.
Dopamine is useful in many patients with power failure. At low doses [2 to 10 (ug/kg)/min]
the drug has positive chronotropic and inotropic effects as a consequence of beta receptor
stimulation. At higher doses, a vasoconstrictive effect results from alpha receptor stimulation.
At lower doses dopamine [<=2 (ug/kg)/min] also has the unique effect of dilating the renal
and splanchnic vascular beds and apparently has little effect on myocardial oxygen
consumption. Intravenous dopamine is started at an infusion rate of 2 to 5 (ug/kg)/min with
increments in dosage every 2 to 5 min up to a maximum of 20 to 50 (ug/kg)/min. Systolic
arterial blood pressure should be maintained at approximately 90 mmHg.
Dobutamine is a synthetic sympathomimetic amine with positive inotropic action and minimal
positive chronotropic or peripheral vasoconstrictive activity in the usual dosage range of 2.5
to 10 (ug/kg)/min. It should not be employed when a vasoconstrictor effect is required.
However, in patients with less profound degrees of hypotension, dobutamine may be an
extremely useful agent, particularly if positive chronotropy is to be avoided.
Amrinone is a positive inotropic agent without catecholamine structure or activity. It
resembles dobutamine in its pharmacologic activity, although it has a more potent
vasodilating action. Initially a loading dose of 0.75 mg/kg is given over 2 to 3 min. If
effective, this is followed by an infusion of 5 to 10 (ug/kg)/min, followed if necessary 30 min
later by an additional bolus of 0.75 mg/kg. If necessary, the dose may then be increased up to
15 (ug/kg)/min for short periods.
Cardiac glycosides
Controlled studies have failed to demonstrate significant beneficial effects of cardiac
glycoside therapy in the early phases (0 to 48 h) of acute myocardial infarction.
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Aortic counterpulsation
In cardiogenic shock mechanical assistance with an intraaortic balloon pumping system
capable of augmenting both diastolic pressure and cardiac output can provide circulatory
support. A sausage-shaped balloon at the end of a catheter is introduced percutaneously into
the aorta via the femoral artery, and the balloon is automatically inflated during early diastole,
thereby enhancing both coronary blood flow and peripheral perfusion. The balloon collapses
in early systole, thereby reducing the afterload against which left ventricular ejection takes
place. Improvement in hemodynamic status has been observed with balloon pumping in a
large number of patients, but, in the absence of early revascularization, long-term survival
following this mode of therapy in patients with cardiogenic shock is still disappointing. The
balloon counterpulsation system may best be reserved for patients whose condition merits
mechanical (surgery or angioplasty) intervention (e.g., patients with continuing ischemia,
ventricular septal rupture, or mitral regurgitation) and in whom a successful result is likely to
result in the reversal of cardiogenic shock. Intraaortic balloon pumping is contraindicated if
aortic regurgitation is present or if aortic dissection is possible or suspected.
MITRAL REGURGITATION. The reported incidence of apical systolic murmurs of mitral
regurgitation during the first few days after the onset of a myocardial infarction varies widely
(10 to 50 percent of patients) depending on the population studied and the acumen of the
observers. In the first hours of infarction, mitral regurgitation can be demonstrated
angiographically in approximately 15 percent of patients but is audible in only about onetenth of those with positive angiograms. Whether audible or angiographically demonstrated,
mitral regurgitation is of hemodynamic importance in only a minority of these patients.
The most common cause of mitral regurgitation following myocardial infarction is
dysfunction of the papillary muscles of the left ventricle due to ischemia or infarction.
CARDIAC RUPTURE
Myocardial rupture is a dramatic complication of myocardial infarction most likely to occur
during the first week after the onset of symptoms; its frequency increases with the age of the
patient. The clinical presentation may often be that of a sudden disappearance of the pulse,
blood pressure, and consciousness while the electrocardiogram continues to show sinus
rhythm (apparent electromechanical dissociation). The myocardium continues to contract, but
forward flow is not maintained as blood escapes into the pericardium. Cardiac tamponade
ensues, and closed-chest massage is ineffective. This condition is almost universally fatal.
SEPTAL PERFORATION
The pathogenesis of perforation of the ventricular septum is similar to that of external rupture
of the myocardium, but the therapeutic potential is greater. Patients with ventricular septal
rupture present with severe heart failure in association with the sudden appearance of a
pansystolic murmur, often accompanied by a parasternal thrill. It is often impossible to
differentiate this condition from rupture of a papillary muscle with resultant mitral
regurgitation, and a tall v wave in the pulmonary capillary wedge pressure in both conditions
further complicates the differentiation. The diagnosis can be established by the demonstration
of a left-to-right shunt (i.e., an oxygen step-up at the level of the right ventricle) by limited
cardiac catheterization performed at the bedside using a flow-directed balloon catheter. Color
flow Doppler echocardiography can be extremely useful for making this diagnosis at the
bedside. Rupture of the ventricular septum is amenable to immediate surgical treatment, albeit
at a significant risk, but this form of therapy is ordinarily indicated on an urgent basis in
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patients whose condition cannot be stabilized rapidly. A prolonged period of hemodynamic
compromise may produce end-organ damage and other complications that can be avoided by
early intervention including nitroprusside infusion and intraaortic balloon counterpulsation.
Ventricular aneurysm
The term ventricular aneurysm is usually used to describe dyskinesis or local expansile
paradoxical wall motion. Normally functioning myocardial fibers must shorten more if stroke
volume and cardiac output are to be maintained in patients with ventricular aneurysm, and if
they are unable to do so, overall ventricular function is impaired. Aneurysms are composed of
scar tissue and neither predispose to nor are associated with cardiac rupture.
The complications of left ventricular aneurysm do not usually occur for weeks to months
following myocardial infarction; they include congestive heart failure, arterial embolism, and
ventricular arrhythmias. Apical aneurysms are the most common and the most easily detected
by clinical examination. The physical finding of greatest value is a double, diffuse, or
displaced apical impulse. The electrocardiographic finding of ST-segment elevation at rest is
present in precordial leads in 25 percent of patients with either apical or anterior aneurysms.
Ventricular aneurysms are readily detectable by two-dimensional echocardiography, which
may also reveal a mural thrombus within an aneurysm. Rarely, myocardial rupture may be
contained by a local area of pericardium, along with organizing thrombus and hematoma.
Over time this pseudoaneurysm enlarges, maintaining communication with the left ventricular
cavity via a narrow neck. Because spontaneous rupture of a pseudoaneurysm often occurs, if
recognized, it should be surgically repaired.
Right ventricular infarction
Approximately one-third of patients with inferoposterior infarction demonstrate at least a
minor degree of right ventricular necrosis. An occasional patient with inferoposterior left
ventricular infarction also has extensive right ventricular myocardial infarction, and rarely
patients present with infarction limited to the right ventricle. These patients often present with
signs of severe right ventricular failure (jugular venous distention, hepatomegaly) with or
without hypotension. ST-segment elevations of the right-sided precordial electrocardiographic
leads, particularly lead V4R, are present in the majority of patients with right ventricular
infarction. Radionuclide ventriculography and two-dimensional echocardiography are also
sensitive in the detection of right ventricular dysfunction associated with acute myocardial
infarction. Catheterization of the right side of the heart often reveals a distinctive
hemodynamic pattern resembling cardiac tamponade or constrictive pericarditis. Volume
expansion is often successful in treating low cardiac output and hypotension associated with
extensive right ventricular infarction.
Postinfarction ischemia and extension
Recurrent angina develops in approximately 25 percent of patients hospitalized for acute
myocardial infarction. This percentage is even higher in patients undergoing successful
thrombolysis. Since recurrent or persistent ischemia often heralds extension of the original
infarct and is associated with a doubling of risk following acute myocardial infarction,
patients with these symptoms should be considered for prompt coronary arteriography and
mechanical revascularization.
Thromboembolism
Clinically apparent thromboembolism complicates acute myocardial infarction in
approximately 10 percent of cases, but embolic lesions are found in 45 percent of patients in
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necropsy series, suggesting that thromboembolism is often clinically silent.
Thromboembolism is considered to be at least an important contributing cause of death in 25
percent of infarct patients who die following admission to the hospital. Arterial emboli
originate from left ventricular mural thrombi, while most pulmonary emboli arise in the leg
veins. Thromboembolism most commonly occurs in association with large infarcts in the
presence of heart failure. Thromboembolism occurs extremely commonly in patients with
echocardiographic evidence of a left ventricular thrombus, but only rarely if a thrombus is not
present on the echocardiogram. Although well-controlled trials do not exist, the incidence of
embolization appears to be decreased by anticoagulation.
Pericarditis
Pericardial friction rubs and/or pericardial pain are frequently encountered in patients with
acute transmural myocardial infarction. This complication can usually be managed with
aspirin (650 mg qid). It is important to diagnose the chest pain of pericarditis accurately, since
failure to appreciate it may lead to the erroneous diagnosis of recurrent ischemic pain and/or
infarct extension with resultant inappropriate use of anticoagulants, nitrates, beta blockers, or
coronary arteriography. The possibility exists that anticoagulants can cause tamponade in the
presence of acute pericarditis, thus their use is contraindicated in patients with pericarditis
Post-myocardial infarction syndrome--Dressler's syndrome
This syndrome, characterized by fever and pleuropericardial chest pain, is thought to be due
to an autoimmune pericarditis, pleuritis, and/or pneumonitis. It may begin from a few days to
6 weeks after myocardial infarction. The occurrence of Dressler's syndrome may be
etiologically related to the early use of anticoagulants and appears to have decreased markedly
in the last decade as long-term anticoagulants are used less frequently in acute myocardial
infarction. The syndrome usually responds promptly to therapy with salicylates. On occasion,
glucocorticoids may be required to relieve discomfort of an unusual, refractory nature.
Effusions associated with Dressler's syndrome may become hemorrhagic if anticoagulants are
administered.
ASYMPTOMATIC (SILENT) ISCHEMIA
Obstructive coronary artery disease, acute myocardial infarction, and transient myocardial
ischemia are frequently asymptomatic. During continuous ambulatory electrocardiographic
monitoring, the majority of ambulatory patients with typical chronic stable angina are found
to have objective evidence of myocardial ischemia (ST-segment depression) during episodes
of chest discomfort while they are active outside the hospital, but many of these patients also
appear to have more frequent episodes of asymptomatic ischemia. Longitudinal studies have
demonstrated an increased incidence of coronary events (sudden death, myocardial infarction,
and angina) in asymptomatic patients with positive exercise tests. In addition, patients with
asymptomatic ischemia after suffering a myocardial infarction are at far greater risk for a
second coronary event.
MANAGEMENT of patients with asymptomatic ischemia must be individualized. Consider
the following: (1) the degree of positivity of the exercise test, particularly the stage of exercise
at which electrocardiographic signs of ischemia appear, the magnitude and number of the
perfusion defect(s) on thallium scintigraphy, and the change in left ventricular ejection
fraction which occurs during ischemia and/or during exercise on radionuclide
ventriculography; (2) the electrocardiographic leads showing a positive response, with
changes in the anterior precordial leads indicating a less favorable prognosis than changes in
the inferior leads; and (3) the patient's age, occupation, and general medical condition.
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Patients with evidence of severe ischemia on noninvasive testing should undergo coronary
arteriography. Asymptomatic patients with silent ischemia, three-vessel coronary artery
disease, and impaired left ventricular function may be considered appropriate candidates for
coronary artery bypass surgery.
The chronic administration of aspirin to patients with asymptomatic ischemia after myocardial
infarction has been shown to reduce adverse coronary events. While the incidence of
asymptomatic ischemia can be reduced by treatment with beta blockers, calcium channel
antagonists, and long-acting nitrates, it is not clear whether this is necessary or desirable in
patients who have not suffered a myocardial infarction. Beta-adrenoceptor blockade begun 7
to 35 days after acute myocardial infarction improves survival
Coronary arteriography
This invasive diagnostic method outlines the coronary anatomy and can be used to detect
important evidence of coronary atherosclerosis or to exclude this condition. By this means,
one can assess the severity of obstructive lesions and when combined with left ventricular
angiocardiography can evaluate both global and regional function of the left ventricle.
Coronary arteriography is indicated in
1) patients with chronic stable or unstable angina pectoris who are severely symptomatic
despite medical therapy and who are being considered for revascularization, i.e.,
percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery;
2) patients with troublesome symptoms that present diagnostic difficulties in whom there is
need to confirm or rule out the diagnosis of coronary artery disease; and
3) patients suspected of having left main stem or three-vessel coronary artery disease based
on signs of severe ischemia on noninvasive testing, regardless of the presence or severity
of symptoms.
SUDDEN CARDIAC DEATH
ETIOLOGY, INITIATING EVENTS, AND CLINICAL EPIDEMIOLOGY
Extensive epidemiologic studies have identified populations at high risk for SCD. In addition,
a large body of pathologic data provides information on the underlying structural
abnormalities in victims of SCD, and clinical/physiologic studies have begun to identify a
group of transient functional factors which may convert a long-standing underlying structural
abnormality from a stable to an unstable state. This information is developing into an
understanding of the causes and mechanisms of SCD.
Cardiac disorders constitute the most common causes of sudden natural death. After an initial
peak incidence of sudden death between birth and 6 months of age (the sudden infant death
syndrome), the incidence of sudden death falls abruptly and then increases to a second peak in
the age range of 45 to 75 years. Moreover, increasing age is a powerful risk factor for sudden
cardiac death. It follows that the proportion of cardiac causes among all sudden natural
deaths increases dramatically with advancing years. From 1 to 13 years of age, only one of
five sudden natural deaths is due to cardiac causes. Between 14 and 21 years of age, the
proportion increases to 30 percent, and then to 88 percent in the middle-aged and elderly.
Men and women have very different susceptibilities to SCD, and the gender differences
decrease with advancing age. The overall male/female ratio is approximately 4:1, but in the
45- to 64-year-old age group, the male SCD excess is nearly 7:1. It falls to approximately 2:1
in the 65- to 74-year-old age group. The difference in risk for SCD parallels the risks for other
manifestations of coronary heart disease in men and women. As the gap for other
manifestations of coronary heart disease closes in the seventh and eighth decades of life, the
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excess risk of SCD narrows. Despite the lower incidence in women, the classic coronary risk
factors still operate in the proportionately smaller subgroup of women--cigarette smoking,
diabetes, hyperlipidemia, hypertension.
Hereditary factors contribute to the risk of SCD, but largely in a nonspecific manner: They
represent expressions of the hereditary predisposition to coronary heart disease.
Coronary atherosclerotic heart disease is the most common structural abnormality associated
with SCD. Up to 80 percent of all SCDs in the United States are due to the consequences of
coronary atherosclerosis. The cardiomyopathies (dilated and hypertrophic) account for
another 10 to 15 percent of SCDs, and all the remaining diverse etiologies cause only 5 to 10
percent of these events. The relative role of various factors contributing to the initiation of
cardiac arrest has not been quantitated as well as the structural basis. Transient ischemia in the
previously scarred or hypertrophied heart, hemodynamic and fluid and electrolyte
disturbances, fluctuations in autonomic nervous system activity, and transient
electrophysiologic changes caused by drugs or other chemicals (e.g., proarrhythmia) have all
been implicated as mechanisms responsible for transition from electrophysiologic stability to
instability. In addition, spontaneous reperfusion of ischemic myocardium, caused by
vasomotor changes in the coronary vasculature and/or spontaneous thrombolysis, may cause
transient electrophysiologic instability and arrhythmias.
MYOCARDIAL PERFUSION IMAGING
The potassium analogue thallium 201, cyclotron-produced with a half-life of 72 h, is the most
commonly used agent to assess myocardial perfusion. Its active uptake by normal myocardial
cells is proportional to regional blood flow. Areas of myocardial necrosis, fibrosis, and
ischemia show reduced thallium accumulation ("cold spots") on images obtained soon after
injection. Following its initial accumulation within cells, however, thallium 201 continues to
exchange with the systemic pool. After several hours, equilibration occurs; viable myocardial
cells having intact membrane function contain nearly equal concentrations.
Thallium 201 scintigraphy is used most commonly to detect exercise-induced ischemia.
Thallium is injected intravenously at peak exercise, and images are obtained 5 to 10 minutes
later in several projections using either planar imaging or single photon emission computed
tomography (SPECT). The images may be analyzed qualitatively or quantitatively using
computer algorithms. Normal scans show relatively homogeneous distribution of activity,
while those of patients with infarction or ischemia typically demonstrate one or more "cold
spots." Because of continued exchange of thallium between viable cells and the systemic
pool, however, most initial defects due to ischemia "fill in" on repeat imaging several hours
later. Some, however, require up to 24 h for redistribution or are best identified following
reinjection of thallium 4 h after exercise, but areas of infarction demonstrate persistent
reduction of uptake.
Compared with routine exercise electrocardiography, exercise thallium scintigraphy increases
the sensitivity for detection of coronary disease from approximately 60 to 80 percent and
increases specificity slightly from about 80 to 90 percent. It is most useful in patients with
atypical chest pain in whom the exercise ECG is nondiagnostic or uninterpretable due to
baseline ST abnormalities, left bundle branch block, ventricular hypertrophy, or drug and
electrolyte effects; in patients who fail to achieve 85 percent of predicted maximal heart rate;
and in patients with a high likelihood of a false-positive exercise ECG study. Thallium
scanning improves localization of ischemia and provides prognostic information, since the
presence and number of redistributing defects correlate with the incidence of future cardiac
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events. Thallium scintigraphy also has been used to detect ischemia during spontaneous pain,
pacing, and adenosine- and dipyridamole-induced coronary vasodilation. Dipyridamole
thallium imaging appears to be as sensitive and specific as exercise thallium scintigraphy for
detection of ischemic heart disease. It should be considered for patients unable to exercise,
including those with peripheral vascular disease who have an increased risk of cardiac
morbidity and mortality with vascular surgery.
Serial thallium 201 scintigrams obtained in the 45 degree(s) LAO projection in a patient
undergoing exercise testing for evaluation of chest pain. The immediate postexercise image
(left) demonstrates decreased perfusion of the septum. The 1- and 2-h delayed images (middle
and right) demonstrate "filling in" of the defect, reflecting redistribution. The computerderived time-activity curves (bottom) confirm the significant reduction in initial counts in the
septum, relative to the posterolateral wall, and demonstrate near equalization of activity by 2
h. S = septum; PL = posterolateral wall.
PERCUTANEOUS TRANSLUMINAL CORONARY ANGIOPLASTY
PTCA is a widely used method to achieve revascularization of the myocardium in patients
with symptomatic ischemic heart disease and suitable stenoses of epicardial coronary arteries.
Whereas patients with stenosis of the left main coronary artery and those with three-vessel
coronary artery disease who require revascularization are best treated with coronary artery
bypass surgery, PTCA is widely employed in patients with symptoms and evidence of
ischemia due to stenoses of one or two vessels, and even selected patients with three-vessel
disease, and may offer many advantages over surgery.
After a flexible guidewire is advanced into a coronary artery and across the stenosis to be
dilated, a miniature balloon catheter is advanced over the guidewire and into the stenosis
followed by repeated inflations until the stenosis is decreased or relieved.
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Indications
 angina pectoris, stable or unstable, which should be accompanied by evidence of ischemia
in an exercise test. This symptom should be sufficiently severe to warrant the
consideration of bypass graft surgery. PTCA is more effective than medical therapy for
the relief of angina in patients with single-vessel coronary artery disease. The value of this
procedure in improving outcome has not been established, and therefore it is not generally
indicted in asymptomatic or mildly symptomatic patients.
 to dilate stenoses in native coronary arteries and in bypass grafts in patients who have
recurrent angina following coronary artery surgery. This is an important indication when
the technical difficulties and the increased mortality that accompanies reoperation are
considered.
 in patients with recent total occlusion (within 3 months) of a coronary artery and severe
angina; in this group the primary success rate is decreased to approximately 50 percent.
Efficacy
Primary success, i.e., adequate dilation with relief of angina, is achieved in 85 to 90 percent of
cases. Recurrent stenosis of the dilated vessels occurs in 20 to 40 percent of cases within 6
months of the procedure, and angina will recur within 6 to 12 months in 25 percent of cases.
This recurrence of symptoms and restenosis is more common in patients with diabetes
mellitus, unstable angina, incomplete dilation of the stenosis, dilation of the left anterior
descending coronary artery, and stenoses containing thrombi. Dilation of arteries which are
totally occluded and of stenotic or occluded vein grafts also exhibit a high incidence of
restenosis. It is usual clinical practice to administer aspirin and a calcium channel antagonist
for months after the procedure. Although aspirin may help prevent acute coronary thrombosis
during and immediately following PTCA, there are no controlled clinical trials that have
demonstrated that these medications or any other can clearly reduce the incidence of
restenosis.
If patients do not develop restenosis or angina within the first year after angioplasty, the
prognosis for maintaining improvement over the subsequent 4 years is excellent. If restenosis
occurs, PTCA can be repeated with the same success and risk, but the likelihood of restenosis
increases with the third or subsequent attempt.
Between 30 and 50 percent of patients with symptomatic coronary artery disease who require
revascularization can be treated by PTCA and need not undergo coronary artery bypass
surgery. Successful angioplasty is less invasive and expensive than coronary artery surgery,
usually requires only two days in the hospital, and permits considerable savings in the cost of
care. Successful PTCA also allows earlier return to work and the resumption of an active life.
CORONARY ARTERY BYPASS GRAFTING
In this procedure, a section of a vein (usually the saphenous) is used to form a connection
between the aorta and the coronary artery distal to the obstructive lesion. Alternatively,
anastomosis of one or both of the internal mammary arteries to the coronary artery distal to
the obstructive lesion may be employed.
1 The operation is relatively safe, with mortality rates less than 1 percent when the procedure
is performed by an experienced surgical team in patients without serious comorbid disease
and normal left ventricular function.
2 Intraoperative and postoperative mortality increases with the degree of ventricular
dysfunction, comorbidities, and surgical inexperience. The effectiveness and risk of coronary
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artery bypass grafting vary widely depending on case selection and the skill and experience of
the surgical team, so that the latter must be taken into account when a patient is being
considered as a candidate for this procedure.
3 Occlusion of vein grafts is observed in 10 to 20 percent during the first postoperative year,
and the incidence is approximately 2 percent per year during 5- to 7-year follow-up and 5
percent per year thereafter. Long-term patency rates are considerably higher for internal
mammary artery implantations; in patients with left anterior descending coronary artery
obstruction, survival is better when coronary bypass involves the internal mammary artery
rather than a saphenous vein.
4 Angina is abolished or greatly reduced in approximately 85 percent of patients following
complete revascularization. Although this is usually associated with graft patency and
restoration of blood flow, the pain may also have been alleviated as a result of infarction of
the ischemic segment or a placebo effect.
5 Coronary artery bypass grafting does not appear to reduce the incidence of myocardial
infarction in patients with chronic ischemic heart disease; perioperative myocardial infarction
occurs in 5 to 10 percent of cases, but in most instances these infarcts are small.
6 Mortality is reduced by operation in patients with stenosis of the left main coronary artery
as well as in patients with three-vessel coronary artery disease and impaired left ventricular
function. However, there is no evidence that coronary artery bypass surgery improves survival
in patients with one- or two-vessel disease who have chronic stable angina and normal left
ventricular function or in patients with one-vessel disease and impaired left ventricular
function.
DIFFERENTIAL DIAGNOSIS OF CHEST DISCOMFORT
The key issue in the evaluation of the patient with is to distinguish potentially life-threatening
conditions such as coronary artery disease, aortic dissection, and pulmonary embolism from
other causes of chest discomfort. Even patients who have brief episodes of pain and are
otherwise in apparently excellent health may have intermittent myocardial ischemia or even
recurrent pulmonary emboli.
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The chest discomfort of myocardial ischemia is angina pectoris. Myocardial ischemia
from coronary atherosclerosis is more common in patients who have
hypercholesterolemia, diabetes mellitus, hypertension, obesity, or who smoke. Toxins,
including cocaine ingestion or withdrawal of chronic exposure to nitroglycerin, can cause
sufficient coronary vasoconstriction to result in myocardial ischemia, and cocaine also can
cause myocardial infarction.
Myocardial infarction
The chest discomfort from myocardial ischemia that is caused by aortic stenosis,
hypertrophic cardiomyopathy, and nonatherosclerotic causes of coronary artery disease is
generally similar to that of angina pectoris from coronary atherosclerosis.
Pericarditis can cause pain in several locations.
Patients with marked right ventricular hypertension may have exertional pain which is
quite similar to that of angina. This discomfort probably results from relative ischemia of
the right ventricle brought about by the increased oxygen needs and by the elevated
intramural resistance, with reduction of the normally large systolic pressure gradient
which perfuses this chamber.
The pain due to acute dissection of the aorta or to an expanding aortic aneurysm results
from stimulation of nerve endings in the adventitia. The pain usually begins abruptly,
reaches an extremely severe peak rapidly, is felt in the center of the chest and/or in the
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back depending on the site of the dissection, lasts for hours, and requires unusually large
amounts of analgesics for relief.
The pain resulting from pulmonary embolism may resemble that of acute myocardial
infarction, and in massive embolism it is located substernally. In patients with smaller
emboli, the pain is located more laterally, is pleuritic in nature, and may be associated
with hemoptysis.
Pleural pain from fibrinous pleurisy or any pneumonic process is very common.
Substernal discomfort also frequently occurs in the presence of tracheobronchitis; it is
commonly described as a burning sensation accentuated by coughing.
The pain of mediastinal emphysema may be intense and sharp and may radiate from the
substernal region to the shoulders; often a distinct crepitus is heard.
The pain associated with mediastinitis and mediastinal tumors usually resembles that of
pleuritis but is more likely to be maximal in the substernal region.
The several abdominal disorders which may at times mimic anginal pain may usually be
suspected from the history.
PROGNOSIS
The principal prognostic indicators in patients with ischemic heart disease are the functional
state of the left ventricle, the location and severity of coronary artery narrowing, and the
severity or activity of myocardial ischemia. Angina pectoris of recent onset, unstable angina,
angina which is unresponsive or poorly responsive to medical therapy or is accompanied by
symptoms of congestive heart failure all indicate an increased risk for adverse coronary
events. The same is true for the physical signs of heart failure, episodes of pulmonary edema,
or roentgenographic evidence of cardiac enlargement. An abnormal resting ECG or positive
evidence of myocardial ischemia during a stress test also indicate increased risk. Most
importantly, the following signs during noninvasive testing indicate a high risk for coronary
events: a strongly positive exercise test showing onset of myocardial ischemia at low
workloads, large or multiple perfusion defects or increased lung uptake during stress thallium
scanning, a decrease in left ventricular ejection fraction during exercise on radionuclide
ventriculography, and hypotension with ischemia during stress testing.
Obstructive lesions of the proximal left anterior descending coronary artery are associated
with a greater risk than are lesions of the right or left circumflex coronary artery, since the
former vessel usually perfuses a greater quantity of myocardium. Critical stenosis of the left
main coronary artery is associated with a mortality of about 15 percent per year.
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