INTRODUCTION — Myocardial ischemia is one of the more common causes of chest pain (also termed "chest discomfort") in adults. Angina pectoris, or angina for short, is the term used when chest discomfort is thought to be attributable to myocardial ischemia. In patients with myocardial ischemia, chest discomfort is often but not always present, although other associated symptoms with ischemia may be present (such as exertional shortness of breath, nausea, diaphoresis, fatigue). This has been termed "anginal equivalent." Myocardial ischemia in the absence of chest discomfort or another anginal equivalent symptoms is termed "silent ischemia." (See "Silent myocardial ischemia: Epidemiology, diagnosis, treatment, and prognosis".)
For patients with suspected myocardial ischemia, timely diagnosis and treatment is necessary to treat symptoms and possibly also reduce morbidity and mortality. Rapid diagnosis is particularly important in patients with a possible acute coronary syndrome (unstable angina, non-ST elevation myocardial infarction, or ST-elevation myocardial infarction). (See "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department".)
Myocardial ischemia can occur due to fixed epicardial coronary artery ("macrovascular") obstruction, coronary microvascular obstruction (ischemia with no obstructive coronary artery disease [INOCA]), or coronary artery spasm. (See "Microvascular angina: Angina pectoris with normal coronary arteries" and "Vasospastic angina" and "Chronic coronary syndrome: Overview of care", section on 'Introduction'.)
This topic will review the pathophysiology, clinical features, and diagnosis of ischemic chest discomfort due to fixed epicardial coronary artery obstruction. Discussions of other cardiac and noncardiac causes of chest pain, and their clinical presentations, are found elsewhere. Links to those topics are found throughout this topic.
PATHOPHYSIOLOGY OF MYOCARDIAL ISCHEMIA — Myocardial ischemia, and consequently angina, occurs when myocardial oxygen demand exceeds oxygen supply (table 1). Detailed reviews of the pathophysiology of myocardial ischemia are available in the scientific literature [1].
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
Myocardial contractility and wall stress cannot be measured clinically. As a result, 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 functional capacity exceeds 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 affected by a variety of factors including oxygen tension and the hemoglobin concentration; the degree of oxygen unloading from hemoglobin to the tissues, which is related to 2,3 diphosphoglycerate levels; and the coronary artery blood flow delivered to the myocardium. The latter is influenced by:
●Coronary artery diameter and tone (resistance) [2,3].
●Collateral blood flow.
●Perfusion pressure. This is determined by the pressure gradients from the aorta to the coronary arteries. Coronary blood flow from the epicardium to endocardial capillaries is determined by the left ventricular end-diastolic pressure.
●Heart rate, which affects the duration of diastole; importantly, coronary artery flow primarily occurs during diastole. The percent of diastolic time decreases as the heart rate increases. Thus, heart rate is a determining factor for both oxygen demand and supply.
MECHANISMS OF ANGINA — The mechanisms responsible for the sensation of angina are complex and not entirely understood. An important feature is that myocardial ischemia results in the development of acidosis and also reduces the formation of adenosine triphosphate (ATP), the loss of the normal ATP sodium-potassium pump, the loss of myocardial membrane integrity, and the release of chemical substances that stimulate chemosensitive and mechanoreceptive receptors innervated by unmyelinated nerve cells found within cardiac muscle fibers and around the coronary vessels [4]. The substances that are released include lactate, serotonin, bradykinin, histamine, reactive oxygen species, and adenosine [5-7]. In addition, there are substances released from platelets, which often spontaneously aggregate in the area of a coronary artery stenosis, which may also be responsible for myocardial ischemia and angina. These include serotonin, thromboxane A2, and 5-hydroxytyrptamine [8,9].
There is substantial evidence that the primary mediator of angina is adenosine, via stimulation of the A1 adenosine receptor [10-13]. It is also possible that venodilation as a response to ischemia can activate these receptors. The nerve fibers travel along the sympathetic afferent pathways from the heart and enter the sympathetic ganglia in lower cervical and upper thoracic spinal cord (C5-6 and T1-T6). Impulses are then transmitted via the ascending spinothalamic pathways to the medial and lateral thalamus and ultimately activate several areas of the cerebral cortex [4].
Angina is a discomfort that is referred to the corresponding dermatomes that supply sympathetic afferent nerves to the same segments of the spinal cord as the heart [4]. Furthermore, stimulation of sensory receptors in different myocardial regions results in the transmission via the same neural pathway [13]. These characteristics account for two typical features of angina: It is often a diffuse discomfort felt in the chest, neck, lower jaw, and down the arm (typically the left arm, although some patients experience right arm discomfort). Most patients experience angina in the same distribution, regardless of which area of the myocardium is ischemic [13]. An exception is often post-cardiac surgery, as this may interrupt and alter the neural supply to the heart, which may affect the distribution of angina.
CLINICAL ENTITIES ASSOCIATED WITH MYOCARDIAL ISCHEMIA — As mentioned above, any significant imbalance between myocardial oxygen supply and demand can lead to myocardial ischemia and angina. Patients may have a supply or a demand problem, but many have both. (See 'Pathophysiology of myocardial ischemia' above.)
Decreased supply — In most of the world, atherosclerotic obstruction of one or more coronary arteries (coronary artery disease) is the most common cause of myocardial ischemia. Other clinical conditions associated with a decrease in supply due to disease in one or more coronary arteries include coronary artery vasospasm, coronary microvascular disease, myocardial bridging, fibrosis, embolism, dissection, and arteritis. Left ventricular hypertrophy may result in a reduction in subendocardial blood flow and oxygen supply; this may result in angina. This may be particularly important with the development of arterial hypertension, which may increase left ventricular end-diastolic pressure, resulting in impairment of capillary flow in the subendocardium.
Other examples of inadequate supply include shock (any cause), hypoxemia, anemia, and postprandial angina resulting from a redistribution of blood flow away from territories supplied by severely stenosed coronary arteries to those supplied by less diseased or normal arteries (ie, a steal phenomenon) [14,15].
Increased demand — Clinical conditions associated with an increase in myocardial oxygen demand include any situation in which there are increased catecholamines or sympathetic tone, as with vigorous exertion or mental stress, tachycardia for any reason, hypertension, left ventricular hypertrophy (with hypertensive heart disease or aortic stenosis), and right ventricular hypertrophy (with pulmonary hypertension) [16].
CLINICAL FEATURES — Most patients with myocardial ischemia will present with classic angina pectoris as the primary clinical manifestation. Classic angina pectoris is described as a pressure, heaviness, tightness, or constriction in the center or left of the chest that is precipitated by exertion and relieved by rest. It is generally not described as pain (sharp or dull), or needles and pins.
However, some patients with myocardial ischemia may present with angina-equivalent symptoms such as exertional shortness of breath, nausea, diaphoresis, or fatigue rather than chest discomfort. Patients may also experience ischemic episodes without chest discomfort or anginal equivalent symptoms. (See "Silent myocardial ischemia: Epidemiology, diagnosis, treatment, and prognosis".)
The initial presentation of myocardial ischemia with angina may be one of a stable pattern or an acute coronary syndrome. Patients with recent onset of chest discomfort, episodes of rest chest discomfort, or one or more prolonged episodes (more than 20 minutes), should be evaluated in an acute care facility for the possibility of an acute coronary syndrome. However, every patient has their first episode of chest discomfort so that recent onset is not necessarily an acute coronary syndrome, particularly if the pattern of occurrence is stable and predictable (ie, with exertion). (See "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department".)
History — Elements of the history that are critically important include characteristics of the discomfort, associated symptoms, precipitating factors, and information about social and family history.
Typical qualities of anginal pain — Clinicians should attempt to elicit information about the following characteristics of the discomfort:
●Quality − Angina is usually characterized more as a discomfort rather than pain. 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) [17]. 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."
It is generally not described as sharp, dull-aching, knife-like, stabbing, or pins and needles-like. In a report of patients presenting to the emergency department, "sharp" or "stabbing" pain was a low risk description, particularly when the pain was pleuritic or positional, was fully reproducible by palpation, and the patient had no history of angina or myocardial infarction [18].
The following additional characteristics are typically seen:
•Angina is typically gradual in onset and offset, with the intensity of the discomfort increasing and decreasing over several minutes. In contrast, noncardiac pain is often of greatest intensity at its onset and often has an abrupt onset and offset.
•Since angina is a referred discomfort, patients tend to have the same quality of chest discomfort with recurrent ischemic episodes [13]. Generally, it is felt in the same location. The discomfort is generally the same prior to or with a myocardial infarction and is the same quality as prior to revascularization by either surgery (although the location may be different due to disruption of neural innervation of the heart) or percutaneous coronary intervention.
•Angina is a constant discomfort that does not change with respiration or most changes in position (one exception is lying down, which increases venous return). It is also not provoked or worsened with palpation of the chest wall. However, the presence of a change in pain with respiration (or position) or pain elicited by palpation does not exclude angina as the cause.
●Location and radiation − As noted above, angina is a referred pain due to involvement of a neural reflex pathway via the thoracic and cervical nerves. As a result, it is not felt in a specific spot, but is usually a diffuse discomfort that may be difficult to localize.
The patient often indicates the entire chest when asked where the discomfort is felt. Pain that localizes to one small area of the chest is more likely of chest wall or pleural origin rather than visceral.
Angina is referred to the corresponding dermatomes (C5-6 and T1-T6) that supply afferent nerves to the same segments of the spinal cord as the heart. Thus, 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) [19,20]. Radiation to both arms is a stronger predictor of acute myocardial infarction. The location and radiation of angina is usually the same each time. Occasionally, the location and radiation, but not quality, may be different after bypass surgery due to the disruption of the neural innervation of the heart.
Isolated back pain is unusual in patients with angina. However, it may be seen with an aortic dissection that also involves the coronary arteries. (See "Clinical features and diagnosis of acute aortic dissection".)
●Provoking factors − Angina is often elicited by activities and situations that increase myocardial oxygen demand, including physical activity, cold, emotional stress, sexual intercourse, meals, or lying down (which results in an increase in venous return and increase in wall stress) [21-23]. Patients should be questioned about the use of cocaine or other recreational drugs, as they may trigger myocardial ischemia. (See "Clinical manifestations, diagnosis, and management of the cardiovascular complications of cocaine abuse", section on 'Myocardial ischemia/infarction'.)
Postprandial pain is generally considered to be gastrointestinal in origin. However, it may also be anginal, especially in patients with severe ischemia (eg, left main or three vessel coronary disease) [15].
●Timing − Angina occurs more commonly in the morning due to a diurnal increase in sympathetic tone. Enhanced sympathetic activity raises heart rate, blood pressure, vessel tone and resistance (resulting in a reduced vessel diameter that causes any fixed lesion to be more occlusive), and promotes platelet aggregation (resulting in the release of vasoactive substances, such as serotonin and thromboxane A2) [8,9].
●Duration and relief − Classic angina is often relieved with termination of the provoking factor. Angina generally lasts for two to five minutes. It is not a fleeting discomfort, which 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 coronary syndrome, especially myocardial infarction.
Factors that reduce oxygen demand or increase oxygen supply will result in relief of angina. These include cessation of activity or termination of the provoking factor, use of nitroglycerin (which is a venodilator, reducing venous return, and a coronary artery vasodilator that increases coronary blood flow), and sitting up (which reduces venous return and preload).
Relief of chest discomfort with nitroglycerin is not specific for angina, since a similar response may be seen with esophageal spasm or other gastrointestinal problems as nitroglycerin also relaxes smooth muscle. In a review of 459 patients presenting to an emergency department with chest pain, the percentage of patients with relief of chest discomfort with nitroglycerin was similar among those with and without active coronary disease (35 versus 41 percent) [24].
Atypical features — Specific chest pain characteristics can be used to help differentiate cardiac from noncardiac causes (table 2A-B). (See "Outpatient evaluation of the adult with chest pain".)
In two systematic reviews, the following characteristics were found to be more typical of nonischemic chest discomfort [25,26]:
●Pleuritic pain, sharp or knife-like pain related to respiratory movements or cough.
●Primary or sole location in the mid 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 into the lower extremities or above the mandible.
However, some patients with an acute coronary syndrome present with atypical types of chest pain. In one study, acute ischemia was diagnosed in 22 percent of patients who presented with sharp or stabbing pain and 13 percent who presented with pleuritic-type pain [18].
In addition, some patients who appear to have a noncardiac cause of chest pain have other serious conditions including acute aortic dissection, pulmonary embolism, tension pneumothorax, myocarditis, perforating peptic ulcer, and esophageal rupture (table 2A-B) [27]. It is essential to consider these alternate diagnoses to avoid potentially dangerous errors in management, such as the administration of thrombolytic therapy to a patient with an aortic dissection.
Associated symptoms — Angina is often associated with other symptoms. Dyspnea is a common anginal equivalent, and its presence is associated with a higher cardiovascular death rate compared with patients with typical angina. Dyspnea in the setting of angina may reflect pulmonary congestion due to an elevation in left ventricular end diastolic pressure related to failure of the myocardium to relax normally in diastole (as relaxation or lusitropy is energy dependent). The resulting diastolic "stiffness" or diastolic dysfunction results in an increase in left ventricular end diastolic pressure, left atrial pressure, and pulmonary venous pressure, which is transmitted to the pulmonary vessels. (See "Heart failure with preserved ejection fraction: Clinical manifestations and diagnosis".)
Other symptoms may include belching, nausea, indigestion, diaphoresis, dizziness, lightheadedness, clamminess, and fatigue. These have been referred to as "angina equivalent" symptoms and appear to be more common in women compared with men. However, these symptoms may be seen with other etiologies for chest pain, especially gastrointestinal causes.
It is common for patients with diabetes mellitus, who often have autonomic (sympathetic) dysfunction, to experience "silent ischemia" or best termed "discomfortless ischemia." (see "Silent myocardial ischemia: Epidemiology, diagnosis, treatment, and prognosis"). They may also present with anginal equivalent symptoms.
Social and family history — Many patients who are ultimately diagnosed with myocardial ischemia have key pieces of information in the social and family histories. For example, risk factors for coronary artery disease are often present in individuals with angina due to coronary artery disease. (See "Overview of established risk factors for cardiovascular disease", section on 'Established risk factors for atherosclerotic CVD'.)
The family history may reveal members with premature cardiovascular disease or hypertrophic cardiomyopathy. (See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation".)
Physical examination — Ischemia can produce impairment in myocardial function, which may result in the following findings on physical examination. All disappear with resolution of the ischemia. Some patients have none of these features.
Increase in heart rate — Ischemia can raise the heart rate 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 ischemia.
Elevation in blood pressure — Ischemia often causes a hypertensive blood pressure response. The elevation in blood pressure is induced by both sympathetic activation in response to ischemia and stimulation of the left anterior descending coronary artery chemoreceptor. This chemoreceptor is stimulated by serotonin secreted as a result of platelet aggregation, which often occurs in association with angina.
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. (See "Auscultation of heart sounds".)
New/changed murmurs — Impaired myocardial function may result in a new mitral regurgitation murmur, which appears to be due to papillary muscle dysfunction causing apical tethering or tenting of the leaflets, or changes in the intensity or timing of pre-existing murmurs. (See "Auscultation of cardiac murmurs in adults" and "Management and prognosis of chronic secondary mitral regurgitation".)
Precordial pulsation — Palpation of the chest wall may reveal abnormal pulsations that correlate with transient left ventricular dysfunction. An area of dyskinesis may develop, especially at the apex of the left ventricle or at the anterior axillary line (location of the left ventricular wall), reflecting disease of the left anterior descending coronary artery. (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 lead to a transient right ventricular heave or sternal pulsation.
Laboratory tests — For patients in whom the history and physical examination raise the possibility of myocardial ischemia as the cause of chest discomfort, an electrocardiogram should be obtained. An electrocardiogram obtained when the chest discomfort is present will often show J point and ST-segment depression, which indicates subendocardial ischemia. When the patient is asymptomatic, the electrocardiogram may be entirely normal. (See "Electrocardiogram in the diagnosis of myocardial ischemia and infarction", section on 'Unexpected absence of diagnostic findings'.)
A chest radiograph is often ordered but is not likely to confirm or refute the diagnosis of myocardial ischemia. Generally, the radiography is performed to screen for other causes of chest pain (eg, enlarged aorta, broken rib). (See "Outpatient evaluation of the adult with chest pain", section on 'Indications for chest radiograph'.)
Cardiac biomarkers (eg, troponin) are often obtained in patients with angina. They are unlikely to be elevated in patients with intermittent and relatively brief angina episodes. However, they may be useful when the anginal episode is more prolonged and for prognostication. If high-sensitivity troponin assays are used, low levels of troponin are often detected in patients experiencing stable angina. Increased high-sensitivity troponin levels are associated with adverse outcomes [28,29]. (See "Troponin testing: Clinical use", section on 'Diagnosis of acute MI'.)
DIAGNOSIS — The diagnosis of myocardial ischemia can often be made with a high likelihood based on the history, physical examination, and electrocardiogram. Such patients have classic angina (see 'Clinical features' above), either a normal physical examination or features consistent with myocardial ischemia (see 'Physical examination' above), and an electrocardiogram that is normal in the absence of ongoing ischemia.
For example, in the patient with classic angina and multiple risk factors for coronary artery disease, the diagnosis is highly likely.
For some patients, additional testing is necessary to secure the diagnosis with certainty. Testing, particularly stress testing, is of value when the history is not completely consistent with angina or in a high-risk patient with symptoms that are atypical for ischemia.
We perform some type of stress testing in most patients for the purpose of prognosis. (See "Prognostic features of stress testing in patients with known or suspected coronary disease".)
Differential diagnosis — Discussions of other cardiac and noncardiac causes of chest pain, and their clinical presentations, are found elsewhere. (See "Outpatient evaluation of the adult with chest pain" and "Evaluation of the adult with chest pain in the emergency department".)
RECOMMENDATIONS OF OTHERS — We broadly agree with the approach to diagnosis made in the 2014 American College of Cardiology Foundation/American Heart Association/American College of Physicians/American Association for Thoracic Surgery/Preventive Cardiovascular Nurses Association/Society for Cardiovascular Angiography and Interventions/Society for Thoracic Surgeons focused update of an earlier guideline for the diagnosis and management of patients with stable ischemic heart disease [30,31].
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Chest pain (The Basics)")
●Beyond the Basics topic (see "Patient education: Chest pain (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Myocardial ischemia is one of the more common causes of chest discomfort in adults. Angina pectoris, or angina for short, is the term used when chest discomfort is thought to be attributable to myocardial ischemia.
●The patient with angina often has a fairly typical history (table 3) (see 'History' above):
•Angina is usually characterized more as a discomfort (pressure, squeezing, constriction, choking, burning, tightness, knot in throat or chest) rather than pain (sharp, stabbing, pins and needles-like).
•Angina is typically gradual in onset and offset. Once present, it is constant and does not change with position or respiration.
•Angina is not felt in a specific spot, but is usually a diffuse discomfort that may be difficult to localize.
•Angina is usually elicited by activities and situations that increase myocardial oxygen demand.
•Angina generally lasts for two to five minutes.
•Angina is often associated with other symptoms; the most common are shortness of breath, nausea, and diaphoresis.
●Myocardial ischemia may be accompanied by a normal cardiovascular examination or the following (see 'Physical examination' above):
•Tachycardia
•Hypertension
•New and potentially abnormal heart sounds and murmurs or changes in a pre-existing murmur.
●The diagnosis of myocardial ischemia can often be made with a high degree of certainty based on the history, physical examination, and electrocardiogram. Such patients have classic angina, either a normal physical examination or features consistent with myocardial ischemia, and an electrocardiogram that is normal in the absence of ongoing ischemia. Some patients may require stress testing for the purpose of diagnosis, but in most cases it is performed for prognostic reasons. (See 'Diagnosis' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff thank Dr. Philip Podrid for his past contributions as an author to this topic review.
