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.
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 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 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.
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
three-fourths 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.
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 before-test
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.
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:
Side effects: fatigue, impotence, cold extremities, intermittent claudication, and bradycardia. They can worsen disturbed cardiac conduction, left ventricular failure, and bronchial asthma or intensify the hypoglycemia produced by oral hypoglycemic agents and insulin.
UNSTABLE ANGINA PECTORIS
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 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 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).
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).
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 T-wave 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 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 Q-wave 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
infarction has been reduced from about 30 to between 10 and 15 percent,
and death from in-hospital 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.
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 infarct-related 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 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 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 well-conducted 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.
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 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.
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.
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.
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.
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.
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.
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 one-tenth 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 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
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
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. 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
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
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 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
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 computer-derived
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.
Indications
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 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.
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.