Approach to the patient with suspected angina pectoris

INTRODUCTION AND DEFINITIONS — 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, and fatigue). These symptoms have been termed "anginal equivalent."

The following topics are discussed in detail separately:

●(See "Silent myocardial ischemia: Epidemiology, diagnosis, treatment, and prognosis".)

●(See "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department".)

●(See "Microvascular angina: Angina pectoris with normal coronary arteries" and "Vasospastic angina" and "Chronic coronary syndrome: Overview of care", section on 'Introduction'.)

●(See "Outpatient evaluation of the adult with chest pain".)

●(See "Evaluation of the adult with chest pain in the emergency department".)

PATHOPHYSIOLOGY

●Supply and demand mismatch – 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 [1-3].

•Myocardial oxygen demand – There are four major factors that determine myocardial work and therefore myocardial oxygen demand:

-Heart rate

-Systolic blood pressure (a 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 the following:

-Oxygen tension and the hemoglobin concentration.

-Degree of oxygen unloading from hemoglobin to the tissues, which is related to 2,3 diphosphoglycerate levels.

-Coronary artery blood flow delivered to the myocardium (this is influenced by the following bullets).

-Coronary artery diameter and tone (resistance) [4,5].

-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. Heart rate is a determining factor for both oxygen demand and supply. This affects the duration of diastole given that coronary artery flow occurs virtually only during diastole. The percent of diastolic time decreases as the heart rate increases.

●Molecular basis of angina – The mechanisms responsible for the sensation of angina are complex and not entirely understood.

•Role of acidosis – 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 [6].

•Substances released in ischemia – The substances that are released in patients with ischemia include lactate, bradykinin, histamine, reactive oxygen species, and adenosine [7-9]. In addition, there are substances released from platelets, which often spontaneously aggregate in the area of a coronary artery stenosis, that may also be responsible for myocardial ischemia and angina. These include serotonin, thromboxane A2, and 5-hydroxytyrptamine [10,11].

•Role of adenosine – There is substantial evidence that the primary mediator of angina is adenosine, via stimulation of the A1 adenosine receptor [12-15]. It is also possible that venodilation as a response to ischemia can activate these receptors.

●Neural mechanisms of angina – 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 [6]. Furthermore, stimulation of sensory receptors in different myocardial regions results in the transmission via the same neural pathway [15].

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 [6].

These neural pathways 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 [15]. 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.

Further descriptions of the clinical features of typical angina are discussed in detail separately. (See 'Symptoms' below.)

CONDITIONS CAUSING OR WORSENING ANGINA — 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' above.)

Causes include atherosclerotic epicardial coronary obstruction, microvascular dysfunction, vasospasm, structural heart disease, and noncardiac causes [16-20].  

Specific factors can modify angina symptoms. These include increased adrenergic tone from an increase in myocardial oxygen demand in which there are increased catecholamines or sympathetic tone (eg, in the setting of vigorous exertion or mental stress). The postprandial state can also worsen angina. This results 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) [18]

Tachycardia can contribute to angina by increasing myocardial oxygen demand and decreasing supply from a shortened diastole.

HISTORY

Symptoms — Clinicians should attempt to elicit information about the following characteristics of the discomfort:

●Common quality and descriptions − Angina is usually characterized more as a discomfort rather than pain. The majority of patients with myocardial ischemia will present with classic angina pectoris as the primary clinical manifestation. Classic angina pectoris has been most often described as follows:

•Chest pain

•Pressure or heaviness (elephant sitting on chest)

•Tightness, squeezing, constriction in the center or left of the chest (eg, bra too tight)

•Precipitated by exertion and relieved by rest

Other descriptions of angina are [21]:

•Shortness of breath

•Strangling

•Burning/heart burn

•Fullness

•Band-like sensation

•Knot in the center of the chest

•Lump in throat

•Ache or dullness

•Toothache (when there is radiation to the lower jaw)

However, some patients with myocardial ischemia may present with other angina-equivalent symptoms such as:

•Exertional shortness of breath

•Nausea

•Diaphoresis

•Fatigue without chest discomfort.

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."

Other patients may experience ischemic episodes without chest discomfort or anginal equivalent symptoms. 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 angina-equivalent symptoms.

The following additional characteristics are typically seen and can help distinguish angina from other causes of chest pain:

●Gradual onset and offset – The intensity of the discomfort increases and decreases over several minutes. In contrast, noncardiac pain is often of greatest intensity at its onset and often has an abrupt onset and offset.

●Location – Ischemic episodes are generally felt in the same location [15]. These are characterized by diffuse discomfort that may be difficult to localize; the patient often indicates the entire chest when asked where the discomfort is felt.

Conversely, pain that localizes to one small area of the chest is more likely of chest wall or pleural origin rather than visceral. 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".) .)

●Radiation – Angina often radiates to the shoulders, arms (upper and forearm), wrist, fingers, neck and throat, lower jaw and teeth (but not upper jaw), the upper abdomen (epigastric), and rarely to the back (specifically the interscapular region) [22,23]. Radiation to both arms is a stronger predictor of acute myocardial infarction. Afferent nerves to the same segment of the spinal cord of the heart underlies referral of pain to other areas within the corresponding dermatomes (C5-6 and T1-T6).

For a patient with angina, the radiation of angina is usually the same with each episode. An exception is after bypass surgery, due to the disruption of the neural innervation of the heart.

●Nonpositional and nonreproducible – Angina is a constant discomfort that does not change with respiration or with 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.

●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) [24-26].

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) [18].

●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) [10,11].

●Duration − 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.

●Symptom relief – Classic angina is often relieved with termination of the provoking factor (such as stopping activity) 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 [27,28]. 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) [27].

●Associated symptoms and/or angina equivalents – Angina is often associated with other symptoms. 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. This includes:

•Dyspnea – This 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".)

•Belching.

•Nausea.

•Indigestion.

•Diaphoresis.

•Dizziness.

•Lightheadedness.

•Clamminess.

•Fatigue.

Symptoms commonly associated with noncardiac syndromes — In two systematic reviews, the following characteristics were found to be more prevalent in nonischemic chest discomfort [29,30], and some of these were relatively uncommon in patients with acute ischemia [31]:

●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

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) [32]. 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. (See "Evaluation of the adult with chest pain in the emergency department" and "Outpatient evaluation of the adult with chest pain".)

Medical, social, and family history — Patients may have a medical history pertinent for cardiovascular risk factors and/or other types of vascular disease such as stroke or peripheral vascular diseases. 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 (CAD) are often present in individuals with angina due to CAD. (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 impairs myocardial function, which may result in the following findings on physical examination. All disappear with resolution of the ischemia. Many patients have none of these features. Physical examination features of ischemia are often subtle and difficult to detect even for experienced clinicians.

Vital signs

●Increase in heart rate – Ischemia can raise the heart rate even if the patient is receiving a beta blocker or calcium channel blocker; this 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.

Precordial palpation — 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.

Cardiac auscultation

●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 preexisting murmurs. (See "Auscultation of cardiac murmurs in adults" and "Chronic secondary mitral regurgitation: General management and prognosis".)

DIAGNOSTIC TESTS IN ALL PATIENTS — Although angina is a clinical diagnosis, in most patients, the following tests can help assess, diagnose, and/or exclude unstable and stable angina.

●Electrocardiogram – For patients in whom the history and physical examination raise the possibility of myocardial ischemia as the cause of chest discomfort, an electrocardiogram (ECG) should be obtained.

An ECG 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 ECG may be entirely normal. (See "Electrocardiogram in the diagnosis of myocardial ischemia and infarction", section on 'Unexpected absence of diagnostic findings'.)

●Chest radiograph – 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) – These 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 [33,34].

●Echocardiogram – The echocardiogram can aid in the diagnosis of angina pectoris. If there is regional wall dysfunction, this may point to ischemia and angina as a diagnosis. On the other hand, if there is global left ventricular dysfunction, myocarditis (usually not associated with atherosclerotic coronary artery disease [CAD]) or severe three-vessel CAD may underlie symptoms. Specific echocardiographic patterns can also raise suspicion for stress cardiomyopathy (eg, apical ballooning). Other pertinent echocardiographic findings for nonatherosclerotic causes of ischemia and angina are left ventricular hypertrophy, hypertrophic cardiomyopathy, and valvular disease (eg, aortic or mitral stenosis).

EVALUATION OF SUSPECTED UNSTABLE ANGINA — The initial presentation of myocardial ischemia with angina may be a stable pattern or unstable (including acute coronary syndrome).

If the patient has one or more of the following symptoms, we strongly consider having them promptly evaluated in an acute care facility for the possibility of acute coronary syndrome:

●Recent onset of chest discomfort

●One or more prolonged episodes (more than 20 minutes)

●Chest discomfort occurring with less exertion and/or at rest compared with prior episodes of stable angina

If the patient has recent-onset chest pain in a pattern of occurrence that is stable and predictable (ie, with exertion), evaluation may not need to be as rapid and can sometimes be performed electively. (See "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department".)

EVALUATION OF SUSPECTED STABLE ANGINA — In the patient with suspected stable angina (based on initial diagnostic tests, the history, and physical examination), our initial diagnostic workup depends on if the patient has known coronary artery disease (CAD). Our diagnostic approach broadly agrees with the approach to diagnosis made in the 2021 American College of Cardiology/American Heart Association Joint Committee Guideline for the Evaluation and Diagnosis of Chest Pain [35].

Patient without known coronary artery disease — In patients with no known CAD presenting with suspected stable angina, diagnostic testing is based on pretest probability of obstructive CAD.

Pretest probability

Definition and role of pretest probability — Pretest probability refers to the initial probability that a patient’s symptoms represent obstructive CAD prior to undergoing the diagnostic test and is based upon the patient’s age, sex, symptom characteristics, and clinical history, including standard cardiac risk factors.

Our approach to diagnostic testing varies with the pretest probability, which strongly influences post-test likelihood of disease (figure 1). Thus, clinical estimation of pretest probability based on data from large cohort studies is essential prior to determining whether diagnostic testing (ie, stress testing) is needed and the optimal initial testing modality.  

Estimating pretest probability — Several studies with varying methodologies have contributed to estimation of the pretest probability of coronary heart disease [35,36]. More recently, both the United States [35] and European guidelines [36] have developed and endorsed pretest probability estimates. Pretest probability estimates typically include one or more of the following categories:

●Age and sex

●Symptom type (ie, more or less likely to be cardiac, dyspnea, etc)

In general, pretest probability increases with age, while women with the same symptoms are less likely to have obstructive CAD than men of the same age [37-40].

A recent analysis also suggests that the presence of traditional atherosclerotic risk factors added to the accuracy of pretest probability [41].

A provider can estimate their patient’s pretest probability by using tables that categorize the pretest probability based on age, sex, symptom type, and other risk factors [35,36]. We consider a pretest probability of <10 percent as low, 10 to 90 percent as intermediate, and ≥90 percent as high. In general, noninvasive testing is most useful in patients in the intermediate-risk category.

Study populations were pooled in order to estimate the pretest probability; the pooled studies are described below [41]:

●The Promise Trial – The PROMISE trial, a pragmatic randomized comparative effectiveness study, randomly assigned 4415 patients to testing through coronary computed tomographic angiography (CCTA) from 10,003 originally enrolled subjects [42]. Patients with known CAD, acute presentation, or contraindications for CCTA were excluded. Obstructive CAD was defined as any CCTA-defined luminal narrowing ≥50 percent.

●Danish Study – This observational study included 3903 patients with stable CAD and a normal ejection fraction referred to noninvasive testing or invasive coronary angiography [43]. Obstructive CAD was defined either by noninvasive (stress ECG, stress echocardiography, CCTA [at least >50 stenosis], or myocardial perfusion imaging) or invasive coronary angiography with ≥70 percent stenosis or fractional flow reserve <0.8).

●CONFIRM Study – The CONFIRM] Study included a total of 19,703 consecutive adult patients referred for CCTA [44]. After exclusion of subjects with known CAD, acute coronary syndrome, young people (<30 years old), and those without sufficient characterizing information, 14,048 subjects were analyzed for prevalence of CCTA-defined obstructive CAD.

Low (<10 percent) pretest probability — In patients without known CAD who have suspected angina and a low pretest probability of obstructive CAD (<10 percent), we generally perform no further testing; in these individuals, the probability of a false positive test is high (figure 1) [38]. However, if there is still suspicion that the patient’s symptoms could be due to angina from obstructive CAD, the following tests can provide additional information that can help exclude obstructive CAD:

●Exercise treadmill test – This test is preferred in patients who have adequate exercise capacity and no significant resting ECG abnormalities. A negative test can accurately rule out obstructive CAD. (See "Exercise ECG testing: Performing the test and interpreting the ECG results".)

●Coronary artery calcium scan – The absence of coronary artery calcification makes the diagnosis of obstructive CAD highly unlikely, whereas its presence increases the probability of this diagnosis. (See "Coronary artery calcium scoring (CAC): Overview and clinical utilization".)

Intermediate/high (≥10 percent) pretest probability

Choice of test — We evaluate patients with an intermediate or high probability of angina for obstructive CAD with a stress test (usually with imaging) or CCTA. These tests have high posttest probability when a patient’s pretest probability of obstructive CAD is at least intermediate (figure 1) [38].

●Stress test with imaging – This includes either exercise or pharmacologic stress testing. The most common imaging modalities are nuclear or echocardiographic; some centers perform magnetic resonance imaging. The selection of specific stress test modalities is discussed separately. (See "Stress testing for the diagnosis of obstructive coronary heart disease", section on 'Test selection'.)

An exercise treadmill test can also be performed but has lower accuracy than stress tests with imaging. Also, the presence of any resting ECG abnormalities can decrease the diagnostic accuracy of an exercise treadmill test. (See "Stress testing for the diagnosis of obstructive coronary heart disease".)

Among patients with equivocal or nondiagnostic noninvasive test results, a CCTA is an alternative to invasive coronary angiography [36].

●CCTA – This is a computed tomography scan with intravenous contrast that can visualize filling defects in the coronary arteries; these defects reflect stenoses. The degree of stenosis is quantified by the percentage that it occupies the arterial lumen (image 1). Other aspects of CCTA are discussed in detail separately. (See "Clinical use of coronary computed tomographic angiography".)

Among patients with stable chest pain who are at an intermediate risk of obstructive CAD, CCTA was shown to be a safe and appropriate first diagnostic test compared with invasive angiography. In a pragmatic randomized trial, 3561 such patients were randomly assigned to CCTA or invasive angiography as the initial diagnostic test [45]. Patients were followed for 3.5 years for development of cardiovascular outcomes (including cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) and secondary outcomes (procedure-related complications and angina). Cardiovascular events were similar in the CCTA versus invasive angiography groups (2.1 versus 3 percent; hazard ratio [HR] 0.70; 95% CI 0.46-1.07). Procedure-related complications were less frequent in the CCTA group (0.5 versus 1.9 percent; HR 0.26; 95% CI 0.13-0.55). The frequency of angina during the last four weeks of the study was similar (8.8 versus 7.5 percent; odds ratio 1.17; 95% CI 0.92-1.48).

CCTA is also a useful test for risk stratification of future atherosclerotic cardiovascular disease events. In approximately 2000 patients referred for CCTA, the presence of CAD, including the extent of nonobstructive (<50 percent stenosis) plaque, was superior to clinical risk factors and validated risk scores at discriminating future cardiovascular disease events [46].

The choice between CCTA and stress testing is guided by test availability and patient characteristics such as exercise capacity and presence or absence of resting ECG abnormalities. For example, a CCTA is preferable in those <65 years of age and in those who are not on optimal primary preventive therapies for atherosclerotic coronary artery disease; stress testing may be preferred in those ≥65 years of age (who have a higher likelihood of ischemia and coronary artery calcification that may obscure the lumen of the coronary artery in terms of quantifying obstructive coronary disease). Stress testing may also be preferred in those with risk of contrast-induced kidney injury. (See "Contrast-associated and contrast-induced acute kidney injury: Clinical features, diagnosis, and management".)

Finding of nonobstructive coronary artery disease (<50 percent) and/or no ischemia — Nonobstructive CAD <50 percent can only be determined on CCTA or diagnostic angiography (these lesions will not usually be evident on stress testing).

For individuals with nonobstructive CAD and intermediate lesions (30 to 50 percent), we perform a CT with fractional flow reserve (FFR) assessment to assess for hemodynamic significance to one or more coronary lesions. An FFR <0.8 would indicate a hemodynamically significant lesion. (See "Clinical use of coronary artery pressure flow measurements" and "Clinical use of coronary computed tomographic angiography", section on 'CT-FFR'.)

If significant CAD is ruled out (ie, not visualized with CCTA and/or there is no ischemia on stress testing), we consider alternative diagnoses, including:

●Ischemia with nonobstructed coronary arteries – The evaluation of these conditions (eg, microvascular disease, vasospastic angina) is discussed separately. (See "Microvascular angina: Angina pectoris with normal coronary arteries" and "Vasospastic angina" and "Myocardial infarction or ischemia with no obstructive coronary atherosclerosis".)

●Noncardiac causes of chest pain – The workup for noncardiac causes of chest pain (eg, musculoskeletal, gastrointestinal) is described in detail separately. (See "Outpatient evaluation of the adult with chest pain".)

Finding of obstructive coronary artery disease (≥50 percent stenosis) — If obstructive CAD is detected (≥50 percent stenosis on CCTA and/or ischemia is seen on stress testing), the subsequent management differs depending on whether or not high-risk features are present.

High-risk features — High-risk features include one or more the following:

●Obstructive three-vessel CAD on CCTA.

●Left main coronary artery stenosis ≥50 percent on CCTA.

●Findings on the ECG or imaging portion of stress testing that are reflective of left main or three-vessel obstructive CAD (eg, reversible large anterior wall defect, multiple reversible defects, ischemia occurring at a low heart rate, extensive stress-induced wall motion abnormalities, and transient ischemic dilatation). (See "Exercise ECG testing: Performing the test and interpreting the ECG results", section on 'ST segment elevation'.)

If high-risk features are present, we further investigate with invasive coronary angiography. This is discussed in detail separately. (See "Revascularization in patients with stable coronary artery disease: Coronary artery bypass graft surgery versus percutaneous coronary intervention".)

Non-high-risk features — In these patients, we generally treat the non-high-risk obstructive CAD and reassess symptoms in regular follow-up. If there are persistent angina symptoms after adequate treatment, we pursue invasive angiography to confirm the diagnosis and to further guide therapy. If there is hemodynamically significant stenosis, revascularization is sometimes indicated. This is discussed in detail separately. (See "Chronic coronary syndrome: Indications for revascularization", section on 'Relief of angina'.)

If there are no hemodynamically significant lesions, we explore noncardiac causes and treat as indicated. We may also pursue evaluation for ischemia with nonobstructive coronary arteries, particularly if symptoms continue with no other identified cause. (See "Myocardial infarction or ischemia with no obstructive coronary atherosclerosis".)

Patients with coronary artery disease

General measures in all patients — In patients with known CAD and angina symptoms, we intensify antianginal therapy and reassess. If patients have a resolution of symptoms, no additional diagnostic workup is needed. In this case, we perform routine follow-up with assessment of symptoms.

If patients have persistent symptoms, the subsequent diagnostic workup depends on whether or not the patient has a history of obstructive CAD.

Known nonobstructive coronary artery disease (<50 percent stenosis in ≥1 coronary artery) — In these patients with epicardial atherosclerotic coronary disease occupying <50 percent of the coronary lumen, we evaluate for the presence of ischemia and hemodynamically significant stenoses with either a CCTA (with or without fractional flow reserve testing) or stress test, preferably with imaging. (See "Clinical use of coronary computed tomographic angiography" and "Clinical use of coronary artery pressure flow measurements" and "Stress testing for the diagnosis of obstructive coronary heart disease".)

No evidence of ischemia — If the FFR-CT is ≥0.8 and/or there is no ischemia on stress testing, we consider other causes of chest pain aside from epicardial atherosclerotic coronary artery disease, including:

●Ischemia with nonobstructed coronary arteries – The evaluation of these conditions (eg, microvascular disease, vasospastic angina) is discussed separately. (See "Microvascular angina: Angina pectoris with normal coronary arteries" and "Vasospastic angina" and "Myocardial infarction or ischemia with no obstructive coronary atherosclerosis".)

●Noncardiac causes of chest pain – The workup for noncardiac causes of chest pain (eg, musculoskeletal, gastrointestinal, etc) is described in detail separately. (See "Outpatient evaluation of the adult with chest pain".)

●Other cardiac causes of chest pain – Other causes including left ventricular hypertrophy, hypertrophic cardiomyopathy, valvular disease should be evaluated.

Evidence of ischemia — If FFR-CT <0.8 is seen on CCTA or ischemia is noted on stress testing, the diagnosis of stable angina from epicardial atherosclerotic obstructive CAD is likely. Further diagnostic evaluation is detailed below. (See 'Known obstructive coronary artery disease (≥50 percent stenosis)' below.)

Known obstructive coronary artery disease (≥50 percent stenosis) — The diagnostic workup of stable angina in patients with obstructive CAD depends on the presence of high-risk coronary artery anatomy (ie, obstructive three-vessel CAD or left main coronary artery stenosis ≥50 percent on CCTA) and/or symptoms that substantially limit activity or quality of life despite maximal anginal therapy.

High-risk anatomy or limiting symptoms — In these individuals, the diagnosis of stable angina is likely and the presence of high-risk anatomy and/or limiting symptoms require accurate diagnosis and, if appropriate, invasive therapies such as revascularization.

Therefore, we further evaluate with invasive angiography with FFR to better characterize anatomy and lesion severity. We further pursue invasive cardiac catheterization in order to better assess coronary anatomy, lesion severity, and to guide therapy. This is discussed in detail separately. (See "Clinical use of coronary artery pressure flow measurements" and "Revascularization in patients with stable coronary artery disease: Coronary artery bypass graft surgery versus percutaneous coronary intervention" and "Chronic coronary syndrome: Overview of care".)

No high-risk anatomy and no limiting symptoms — In these individuals, we next pursue stress test with imaging to further evaluate for obstructive CAD. Any further evaluation depends on the presence and severity of ischemia seen on stress testing.

Moderate to severe ischemia — In these patients, symptoms are likely the result of stable angina. We further evaluate with invasive angiography with FFR or instantaneous wave free-ratio to better characterize anatomy and lesion hemodynamic severity. This evaluation can help guide treatment. This is discussed in detail separately. (See "Clinical use of coronary artery pressure flow measurements" and "Revascularization in patients with stable coronary artery disease: Coronary artery bypass graft surgery versus percutaneous coronary intervention".)

Mild ischemia — If there is evidence of mild ischemia on stress testing, we assume the patient’s symptoms are likely the result of mild angina. No further immediate diagnostic evaluation is necessary. We next treat stable angina and reevaluate with regular follow-up. The treatment of stable angina is discussed separately. (See "Chronic coronary syndrome: Overview of care".)

No ischemia — We consider other causes of chest pain aside from atherosclerotic CAD. (See 'No evidence of ischemia' above.)

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".)

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 5^th to 6^th 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 10^th to 12^th 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

●Pathophysiology – Myocardial ischemia is one of the more common causes of chest discomfort in adults. Angina pectoris is chest discomfort thought to be attributable to myocardial ischemia; it is often caused by a mismatch between oxygen supply and demand in the heart. (See 'Pathophysiology' above.)

●Conditions causing angina – Several conditions cause angina symptoms. (See 'Conditions causing or worsening angina' above.)

●History – Angina is usually characterized as a discomfort rather than pain. The majority of patients with myocardial ischemia will present with classic angina pectoris symptoms such as chest discomfort as the primary clinical manifestation; however, anginal-equivalent symptoms are also possible. Gathering a social and family history is important. (See 'History' above.)

●Physical examination – Some patients will have an increase in heart rate and blood pressure, other specific findings on cardiac auscultation (eg, S3 or S4), and palpation (transient ventricular heave). These go away when the angina is not present. (See 'Physical examination' above.)

●Diagnostic tests in all patients – An electrocardiogram (ECG), chest radiograph, and cardiac biomarker testing may be useful as initial tests. (See 'Diagnostic tests in all patients' above.)

●Evaluation of suspected unstable angina – Patients with recent onset of 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. (See "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department".)

●Evaluation of suspected stable angina

•Patients without known coronary artery disease (CAD) – In these patients, our diagnostic approach is based on our estimation of a patient’s pretest probability of obstructive CAD. (See 'Pretest probability' above.)

-Low estimated pretest probability – In these patients, no further diagnostic testing is needed.

-Intermediate or high pretest probability – In these patients, we perform stress test with imaging or coronary computed tomography imaging (CCTA). (See 'Patient without known coronary artery disease' above.)

If there is no CAD or nonobstructive CAD, we consider evaluation for noncardiac causes of chest pain and ischemia with nonobstructive CAD. (See 'Finding of nonobstructive coronary artery disease (<50 percent) and/or no ischemia' above.)

If obstructive CAD is present, we determine if there are high-risk features; if so, we perform invasive angiography to further evaluate and decide treatment. (See 'High-risk features' above.)

If there is no evidence of high-risk features, we make a presumptive diagnosis of angina from epicardial CAD, and no further diagnostic workup is needed. (See 'Non-high-risk features' above.)

•Patients with CAD – We intensify antianginal therapy and then reassess. The subsequent evaluation depends on whether or not the patient has known obstructive CAD (≥50 percent stenosis). (See 'Patients with coronary artery disease' above.)

-Nonobstructive CAD – We evaluate for the presence of ischemia and hemodynamically significant stenoses with either a coronary computed tomographic angiography (CCTA; with or without fractional flow reserve [FFR] testing) or stress test with imaging. (See "Clinical use of coronary computed tomographic angiography" and "Clinical use of coronary artery pressure flow measurements" and "Stress testing for the diagnosis of obstructive coronary heart disease".)

If there is no evidence for ischemia from epicardial atherosclerotic disease, we evaluate for other diagnoses, including noncardiac causes of chest pain and ischemia without obstructive CAD. (See 'No evidence of ischemia' above.)

If ischemia is present, the diagnosis of stable angina is likely. We further pursue invasive cardiac catheterization to assess coronary anatomy, lesion severity, and to guide therapy. (See 'Evidence of ischemia' above.)

-Obstructive CAD – The diagnostic workup of stable angina in these patients depends on whether high-risk coronary artery anatomy (ie, obstructive three-vessel CAD or left main coronary artery stenosis ≥50 percent on CCTA) and/or symptoms that substantially limit activity or quality of life despite maximal anginal therapy are present. (See 'Known obstructive coronary artery disease (≥50 percent stenosis)' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff thank Dr. Philip Podrid for his past contributions as an author to this topic review.