Pathophysiology and diagnosis of ischemic chest
pain
Patients presenting with chest pain often undergo a thorough evaluation to
assess the possible presence of anginal pain due to coronary ischemia. A
careful history and physical examination is critical to accurately establish
the diagnosis of angina pectoris and to exclude other causes of chest pain,
such as musculoskeletal problems. (
See
"Enhancing the precision for identification of acute coronary ischemia in
the emergency department").
A clinical diagnosis of angina pectoris has a 90 percent predictive accuracy
for the presence of coronary disease, although based on Bayesian principles,
this does depend upon the prevalence of coronary disease in the population, ie,
men versus women, young versus old, etc [
1,2].
This is equal to or perhaps greater than the diagnostic accuracy of exercise
testing [
3,4].
This card will review the underlying pathophysiology of angina and the
characteristic clinical features of this disorder.
This card will review the pathophysiology, clinical manifestations, and
differential diagnosis of ischemic chest pain. The uses of
electrocardiography, blood tests, and echocardiography in the acute evaluation
of this complaint are discussed separately. (
See
"Electrocardiogram in myocardial ischemia and infarction",
see
"Diagnosis of acute myocardial infarction with biomarkers of cardiac
injury-I", and
see
"Transthoracic echocardiography for the evaluation of chest pain in the
emergency department").
PATHOPHYSIOLOGY OF ANGINA ！ Angina is
caused by myocardial ischemia which occurs whenever myocardial oxygen demand
exceeds oxygen supply. An understanding of the pathophysiology of angina first
requires a brief review of the determinants of oxygen demand and supply.
Myocardial oxygen demand ！ There are four
major factors that determine myocardial work and therefore myocardial oxygen
demand:
• Heart rate
• Systolic blood pressure (the clinical marker of
afterload)
• Myocardial wall tension or stress (the product
of ventricular end-diastolic volume or preload and myocardial muscle mass)
• Myocardial contractility
Clinical conditions associated with an increase in oxygen demand must affect
one or more of these parameters. Examples include increased catecholamines, as
with vigorous exertion or mental stress [
5],
tachycardia of any etiology, hypertension, and left ventricular hypertrophy.
Myocardial oxygen demands are estimated clinically by the multiplication
product (also called the double product) of the heart rate and the systolic
blood pressure. Individuals reproducibly experience angina during exercise
testing when asked to exceed a well defined angina threshold or absolute
double product value.
Myocardial oxygen supply ！ The major
determinants of oxygen supply are the oxygen carrying capacity of the blood,
which is determined by oxygen tension and hemoglobin level; the degree of
oxygen unloading from hemoglobin to the tissues, which is related to 2,3
diphosphoglycerate levels; and the coronary artery blood flow, which is
influenced by the following factors:
• Coronary artery diameter and vessel tone
(resistance) [
6,7]
• Collateral flow
• Perfusion pressure, which is determined by the
pressure gradients from the aorta to the coronary artery to the left
ventricular end-diastolic pressure (since flow is from epicardium to
endocardium).
• Heart rate and diastolic period (since coronary
artery flow occurs primarily during diastole).
Any clinical setting or pathologic situation which results in a reduction in
myocardial oxygen supply can cause ischemia. The most frequent cause is
coronary atherosclerosis, but others include coronary artery vasospasm,
fibrosis, and embolism. In addition, stimulation of the esophagus by acid can
cause coronary artery vasoconstriction and a reduction in coronary blood flow
via a neural cardioesophageal reflex [
8].
Angina can also occur after eating. Postprandial angina results from a
redistribution of blood flow, away from territories supplied by severely
stenosed coronary arteries and to those supplied by less diseased or normal
arteries [
9].
This may be due to sympathetic activation from food ingestion and
norepinephrine-induced
vasoconstriction in diseased vessels.
HISTORY ！ The patient with angina often has
a fairly typical history. However, there is marked heterogeneity of responses
to stimuli that can produce ischemia such as mental stress, exercise, and
other factors of daily life [
10].
Nevertheless, the following features of the chest pain should be addressed [
11,12]:
• Quality of the chest pain ！ Angina is often
characterized more as a discomfort than pain, and may be difficult to
describe. Terms frequently used by patients include squeezing, tightness,
pressure, constriction, strangling, burning, heart burn, fullness in the
chest, band-like sensation, knot in the center of the chest, lump in throat,
ache, heavy weight on chest (elephant sitting on chest), like a bra too tight,
and toothache (when there is radiation to the lower jaw). In some cases, the
patient cannot qualify the nature of the discomfort, but places his or her
fist in the center of the chest, known as the "Levine sign."
Angina is typically gradual in onset as the intensity of the discomfort
increases over several minutes. In contrast, noncardiac pain is often of
greatest intensity at its onset.
Angina is a constant discomfort which does not change with respiration or
position. It is generally not described as sharp, dull-aching, knife-like,
stabbing, or pins and needles-like.
• Location ！ Angina is not felt in one specific
spot, but rather is a diffuse discomfort that may be difficult to localize.
The patient often indicates the entire chest, rather than a specific area,
when asked where the discomfort is felt.
• Radiation ！ Angina often radiates to other
parts of the body including the upper abdomen (epigastric), shoulders, arms
(upper and forearm), wrist, fingers, neck and throat, lower jaw and teeth (but
not upper jaw), and rarely to the back (specifically the interscapular region)
[
12,13].
• Associated symptoms ！ Angina is often
associated with other symptoms. The most common is shortness of breath, which
may reflect mild pulmonary congestion resulting from ischemia-mediated
diastolic dysfunction [
13,14].
Other symptoms may include belching, nausea, indigestion, diaphoresis,
dizziness, lightheadedness, clamminess, and fatigue.
• Provoking factors ！ Angina is often elicited
by activities and situations which increase myocardial oxygen demand,
including physical activity, cold, emotional stress, sexual intercourse,
meals, or lying down [
15,16,17].
It has been strongly recommended that patients also be questioned about
cocaine
use [
18,19,20].
As an example, one study of 3946 patients with a acute myocardial infarction
found that one percent had used
cocaine
within the prior year; the risk of a myocardial infarction was increased 23.7
times over baseline in the 60 minutes after
cocaine
use [
21].
• Timing ！ Angina occurs more commonly in the
morning due to a morning diurnal increase in sympathetic tone. Enhanced
sympathetic activity raises heart rate, blood pressure, vessel tone and
resistance (resulting in a reduced vessel diameter which causes any fixed
lesion to be more occlusive), and platelet aggregability.
• Duration of symptoms ！ Angina generally lasts
for two to five minutes. It is not a fleeting discomfort, that lasts only for
a few seconds or less than a minute, and it generally does not last for 20 to
30 minutes, unless the patient is experiencing an acute myocardial infarction.
• Relief of discomfort ！ Factors that reduce
oxygen demand or increase oxygen supply will result in relief of angina. These
include cessation of activity (the patient generally has the feeling that he
needs to stop what he is doing), use of
nitroglycerin,
sitting up (which reduces venous return and preload), Valsalva maneuver, and
carotid sinus pressure [
22,23].
PHYSICAL EXAMINATION ！ Ischemia can produce
myocardial function abnormalities which may result in the following findings
on physical examination:
• Increase in heart rate ！ Ischemia can raise
the heart rate which may occur even if the patient is receiving a beta blocker
or calcium channel blocker. The increase in heart rate is induced by reflex
sympathetic nervous system activation as a response to discomfort.
Stimulation of a chemoreceptor located in the area of the proximal left
anterior descending (LAD) artery results in activation of the sympathetic
nervous system. This receptor binds vasoactive amines, in particular serotonin,
which is found in high levels in platelets and is released during platelet
aggregation. Platelets are known to spontaneously aggregate at the site of an
atheroma, causing further obstruction to blood flow and, therefore, additional
ischemia.
• Elevation in blood pressure ！ Ischemia often
causes a hypertensive response. The elevation in blood pressure is induced by
both sympathetic activation in response and stimulation of the LAD
chemoreceptor.
• New heart sounds ！ Ischemia-induced
myocardial dysfunction can lead to changes in the normal heart sounds. The
second heart sound may become paradoxically split due to delayed relaxation of
the left ventricular myocardium and delayed closure of the aortic valve. There
may also be a third or fourth heart sound. These changes are typically
transient and disappear upon resolution of ischemia.
• New murmurs ！ Impaired myocardial function
may result in a new mitral regurgitation murmur (which may be due in part to
transient papillary muscle dysfunction) or changes in preexisting murmurs. (
See
"Auscultation of cardiac murmurs-I").
• Precordial movements ！ Palpation of the chest
wall may reveal abnormal pulsations which correlate with transient left
ventricular dysfunction. An area of dyskinesis may develop, especially at the
apex of the left ventricle. This abnormal movement reflects disease of the
LAD. (
See
"Examination of the precordial pulsation")
Palpation of the left anterior chest wall at the anterior axillary line may
reveal an abnormal tapping in systole, which reflects the presence of an area
of dyskinetic contraction or aneurysm. Transient right ventricular dysfunction
may also manifest as a transient right ventricular heave or sternal pulsation.
EVALUATION OF CHEST PAIN IN THE EMERGENCY
DEPARTMENT ！ The first step in the evaluation of patients with chest
pain is the exclusion of coronary ischemia as the cause. Despite the
availability of a number of tests, the Working Group on Evaluation of
Technologies for Identifying Acute Cardiac Ischemia in the Emergency Room has
concluded that, with the exception of the 12-lead ECG, which should be
considered a standard of care, there is no additional testing that can be
broadly applied for general use [
24].
Before embarking upon any algorithm or diagnostic pathway, the responsible
health care provider (physician or trained other health care provider), must
take the totality of evidence and place the individual in one of four
classifications [
25]:
• Definite ACI ！ Substernal discomfort
precipitated by exertion, with a typical radiation to the shoulder, jaw or
inner aspect of the arm relieved by rest or
nitroglycerin
in less than 10 minutes
• Probable ACI ！ Has most of the features of
definite angina but may not be entirely typical in some aspects
• Probably not ACI ！ Defined as an atypical
overall pattern of chest pain that does not fit the description of definite
angina
• Definitely not ACI ！ A questionable history
of chest pain that is unrelated to activity, appears to be clearly of
noncardiac origin and is not relieved by
nitroglycerin
This proposed schema is an adaptation of the characterization of angina that
was used so successfully in the Coronary Artery Surgery Study (CASS) more than
20 years ago [
25].
Of 18,844 men who were entered into the CASS Registry following coronary
angiography, 46 percent were classified as having definite angina, 29 percent
probable angina, 9 percent probably not angina, and 2 percent definitely not
angina. For the 6,097 women enrolled, the comparable numbers were 28, 35, 25,
and 4 percent, respectively [
25].
Combining all patients with probably not and definitely not angina as
nonischemic pain was subsequently shown to have a powerful discriminatory
function in identifying those individuals without angiographically proven
coronary disease and a negative stress test [
26].
(
See
"Evaluation of suspected acute coronary ischemia in the emergency
department").
DIFFERENTIAL DIAGNOSIS ！ There are a number
of conditions which can produce chest pain that may be mimic or be confused
with angina pectoris (
show
table 2A-2B).
• Other cardiac disorders ！ Pericarditis,
myocarditis, atrial arrhythmias, pulmonary hypertension, mitral valve prolapse.
(
See
"Evaluation and management of acute pericarditis").
• Intrathoracic diseases ！ Pulmonary embolism,
pleuritis, mediastinitis, pneumonia.
• Esophageal disorders ！ Spasm, reflux,
esophagitis, esophageal motility disorders [
8,27,28].
(
See
"Chest pain of esophageal origin").
• Gastrointestinal diseases ！ Gallbladder
disease (cholecystitis, cholelithiasis), gastritis, peptic and duodenal ulcer,
distension of colon (splenic flexure), pancreatitis [
29].
• Musculoskeletal conditions ！ Costochondritis,
Tietze's syndrome, radiculopathy, chest wall trauma, herpes zoster and
postherpetic syndrome, rib fracture, rheumatic diseases (rheumatoid arthritis,
ankylosing spondylitis), fibromyalgia [
30].
(
See
"Major causes of musculoskeletal chest pain").
• Functional ！ Da Costa's syndrome (hyperkinetic
heart syndrome) [
31,32].
The characteristics of the chest pain in these disorders, including location,
duration, and precipitating and relieving factors, are summarized in Table 2 (
show
table 2A-2B). Practice guidelines have identified the following
characteristics of nonischemic chest discomfort [
18]:
• Pleuritic pain sharp or knife-like pain related
to respiratory movements or cough
• Primary or sole location in the mild or lower
abdominal region
• Any discomfort localized with one finger
• Any discomfort reproduced by movement or
palpation
• Constant pain lasting for days
• Fleeting pains lasting for a few seconds or
less
• Pain radiating in to the lower extremities or
above the mandible
