Coronary artery disease (CAD) is a condition that is most commonly caused by atherosclerosis and the subsequent reduction in blood supply to the myocardium, resulting in a mismatch between myocardial oxygen supply and demand. Acute retrosternal chest pain (angina) is the cardinal symptom of CAD. Other symptoms include dyspnea, dizziness, anxiety, and nausea. Patients with stable CAD may have stable angina or be asymptomatic, while severe ischemia may lead to , including myocardial infarction (MI). Stable CAD can be diagnosed using cardiac stress testing, nonstress cardiac imaging, and/or coronary catheterization. The management of stable CAD involves secondary prevention of atherosclerosis (e.g., smoking cessation, and treatment of diabetes mellitus, hypertension, and dyslipidemia), antiplatelet agents, (e.g., beta blockers), and, in severe cases, revascularization (e.g., percutaneous transluminal coronary angioplasty).
Coronary artery disease
- Coronary artery disease (CAD): ischemic heart disease due to narrowing or blockage of coronary arteries, most commonly due to atherosclerosis, resulting in a mismatch between myocardial oxygen supply and demand
- Stable CAD: A form of CAD, in which patients are either asymptomatic or have stable or low-risk unstable angina; also used for patients with a history of MI whose symptoms are controlled with treatment.
Chest pain and angina
Preferred terminology for types of chest pain 
- Cardiac chest pain: likely associated with cardiac ischemia based on symptoms (e.g., central, retrosternal, squeezing, exertional).
- Possible cardiac chest pain: may be associated with cardiac ischemia based on symptoms (e.g., stabbing, tearing, ripping, burning).
- Noncardiac chest pain: unlikely associated with cardiac ischemia based on symptoms (e.g., positional, fleeting).
Historical terminology for types of chest pain 
The following terms are no longer recommended for use in the 2021 AHA/ACC chest pain guidelines. 
- Typical angina fulfills all of the following criteria:
- Atypical angina: fulfills only two of the aforementioned criteria
- Nonanginal chest pain: fulfills one or none of the aforementioned criteria
- is the most common cause (see “ ”).
Plaque formation and coronary artery stenosis 
- For plaque formation, see “ .”
- Stable atherosclerotic plaque → vascular stenosis → increased resistance to blood flow in the coronary arteries → decreased myocardial blood flow → oxygen supply-demand mismatch → myocardial ischemia
- The extent of coronary stenosis determines the severity of the oxygen supply-demand mismatch and, thus, the severity of myocardial ischemia.
- Severe ischemia results in myocardial infarction (see “ ”).
- Coronary flow reserve (CFR): the difference between maximum coronary blood flow and coronary flow at rest (a measure of the ability of the coronary capillaries to dilate and increase blood flow to the myocardium).
Myocardial oxygen supply-demand mismatch 
- Definition: mismatch between the amount of oxygen the myocardium receives and the amount it requires
- Factors reducing oxygen supply
- Factors increasing oxygen demand
An increased heart rate reduces oxygen supply and increases oxygen demand.
Effect of vascular stenosis on resistance to blood flow 
- The resistance to blood flow within the coronary arteries is calculated using the Poiseuille equation: R = 8Lη/(πr4), where R = resistance to flow, L = length of the vessel, η = viscosity of blood, and r = radius of the vessel.
- Provided the length of the vessel and viscosity of blood remain constant; , the degree of resistance can be calculated using the simplified formula: R ≈ 1/r4
Vascular stenosis increases vascular resistance significantly. For example, a 50% reduction in radius results in a 16-fold increase in resistance: R ≈ 1/(0.5 x r)4 = [1/(0.5 x r)]4 = (2/r)4 = 16/r4.
Myocardial ischemia 
Reversible ischemia: Tissue is ischemic but not irreversibly dead and, therefore, still potentially salvageable.
- Myocardial stunning: acutely ischemic myocardial segments with transiently impaired but completely reversible contractility
- Hibernating myocardium: a state in which myocardial tissue has persistently impaired contractility due to repetitive or persistent ischemia
- Irreversible ischemia: tissue necrosis (myocardial scars)
Coronary steal syndrome
- Definition: a phenomenon of vasodilator-induced alteration of coronary blood flow in patients with coronary atherosclerosis resulting in myocardial ischemia and symptoms of angina
- Long-standing CAD requires maximal coronary arterial dilation distal to the stenosis to maintain normal myocardial function.
- In CAD, the affected coronary artery is maximally dilated distal to the stenosis to compensate for the reduced blood flow .
- If a vasodilator (e.g., dipyridamole) is administered, the subsequent vasodilation of healthy vessels causes these to “steal” blood from the stenotic blood vessels, resulting in poststenotic myocardial ischemia.
- Coronary steal is the underlying mechanism of .
- Administration of vasodilators (e.g., dipyridamole) → coronary vasodilation → decreased hydrostatic pressure in the normal coronary arteries → blood shunting back to well-perfused myocardium → decreased flow to the ischemic myocardium → myocardial ischemia downstream to the pathologically dilated vessels → angina pectoris and/or ECG changes
- Paroxysmal attacks of retrosternal chest discomfort, tightness, or pressure due to myocardial ischemia.
- Most commonly occurs in individuals with coronary heart disease.
- Triggers include exertion or stress, which results in increased myocardial oxygen demand.
- Angina is the cardinal symptom of CAD.
- Patients with CAD usually become symptomatic when the degree of coronary stenosis reaches ≥ 70%.
- Typically retrosternal chest pain or pressure
- Symptoms are reproducible/predictable and severity, frequency, and threshold for reproduction of symptoms do not change.
- Symptoms often subside within minutes with rest or after administration of nitroglycerin
- Common triggers include physical/mental stress or exposure to cold
Anginal equivalents 
- Definition: A symptom of cardiac ischemia (other than chest pain) that is associated with exertion or stress, or relieved by short-acting nitrates or rest.
- Possible manifestations
The following recommendations are consistent with the 2012 and 2013 American Heart Association (AHA) guidelines for the management of stable ischemic heart disease (IHD) and the 2021 AHA chest pain guidelines. They focus on patients with chronic stable angina and no history of CAD. For patients with acute symptoms, see “Diagnostics” in “Acute coronary syndrome.” 
Symptomatic patients without known CAD 
- Clinical evaluation
- Resting ECG: indicated for all patients
Additional evaluation 
Perform the following according to the : 
- Obvious noncardiac cause : No cardiac testing required
- Intermediate to high
Further diagnostic testing: Tailor additional testing decisions to individual patients. 
- Additional noninvasive cardiac testing : preferred for most patients
- Invasive coronary angiography (gold standard): usually reserved for specific clinical scenarios
Additional diagnostic testing is not routinely recommended for patients with a low pretest probability of obstructive CAD. 
- Diagnostic testing may be indicated for in select patients.
- The U.S. Preventive Services Task Force does not recommend screening asymptomatic adults with low ASCVD risk using resting ECG or exercise ECG. 
Resting ECG 
- Best initial test for chest pain
- Usually normal in stable angina
- Findings that suggest previous MI or unstable angina: These typically necessitate further workup (see “ ”).
- Uninterpretable ECG: one that does not allow identification of stress-induced ischemic changes, typically due to preexisting abnormalities that affect interpretability, such as: 
Pretest probability of obstructive CAD by age, sex, and symptoms
- The following is one of several possible methods suggested in the 2021 AHA guidelines for estimating the pretest probability of obstructive CAD based on age, sex, and symptoms. 
- Patients with obvious noncardiac chest pain and reassuring ECG do not require cardiac testing or calculation of pretest probability of CAD. 
|Pretest probability of obstructive CAD causing suspected cardiac symptoms |
|Chest pain||Dyspnea||Chest pain||Dyspnea|
Other factors that independently increase PTP 
Further cardiac testing
- Noninvasive testing
- Invasive testing: coronary angiography
Cardiac stress testing 
- The goal is to detect evidence of stress-induced ischemia.
- Heart rate is monitored throughout the study 
- 12-lead ECG is used for monitoring throughout the study.
- Chronic stable angina: most useful for risk stratification in patients with an intermediate-to-high .
- Provocation of arrhythmia
- Evaluation of patients who experience other exertional symptoms (e.g., palpitations, syncope)
- Risk assessment for patients who are due to undergo cardiac revascularization
Types of stress induction
- (e.g., treadmill or bicycle): first-line 
- vasodilator or inotropic medication): alternative in patients unable to exercise  (e.g.,
Modalities and diagnostic endpoints
|Evidence of stress-induced ischemia|
|(e.g., SPECT, PET)|
General criteria for test termination
- A diagnostic endpoint is reached (preferred). 
- A target heart rate threshold is achieved (i.e., if no diagnostic endpoint is reached)
- Significant cardiac arrhythmia
- Technical issues with patient monitoring
- Patient request
- Hold methylxanthines (e.g., caffeine, aminophylline) for 12 hours prior to testing (no need to hold for dobutamine testing).
- Hold dipyridamole for 48 hours prior to adenosine and regadenoson stress tests.
- Beta blockers, CCBs, and nitrates can affect diagnostic value and may be held prior to testing at the treating clinician's discretion. 
|Comparison of cardiac stress tests |
|Test characteristics||Cardiac exercise stress test||Cardiac pharmacological stress test|
Typical modalities 
|Specific criteria for test termination||Clinical|
Achievement of 85% of the patient's estimated maximum heart rate, no exaggerated BP response, and no ST-segment abnormalities during exercise stress testing confer a low probability of CAD (i.e., a normal test). 
Cardiac anatomic testing 
Coronary CT angiography (CCTA): can visualize anatomic CAD 
- Supportive findings 
- Coronary artery calcium (CAC) scoring: measures the amount of calcification in the coronary arteries 
Coronary angiography 
- Chronic stable angina
- Contraindications for or inability to perform noninvasive testing
- High clinical suspicion for CAD and ambiguous results on noninvasive testing
- Abnormal results from noninvasive testing, such as: 
- Persistent symptoms of angina despite appropriate therapy
- Initial testing for survivors of sudden cardiac arrest
- Consider as initial testing for patients with signs of heart failure.
- Other indications: e.g., and certain (see “ ”)
- Chronic stable angina
- Direct visualization of coronary arteries
- To determine the feasibility of direct therapeutic intervention using (see “Treatment” below)
- Cardiac catheterization can provide information on several parameters; (e.g., coronary blood flow; , pressure within heart chambers, cardiac output, oxygen saturation). 
Supportive findings: 
- The extent of the disease is reported as either the number of involved vessels (1, 2, or 3 vessels) or involvement of the left main coronary artery (LMCA).
- Significant coronary artery stenosis is usually defined as one of the following:
Patients with acute chest pain and other concerning clinical findings (e.g., hypotension) or ECG changes that are suggestive of acute coronary syndrome (e.g., new heart blocks or arrhythmias) should undergo cardiac catheterization.
The differential diagnoses listed here are not exhaustive.
The following recommendations are consistent with the 2012, 2014, and 2021 American Heart Association (AHA) guidelines on the management of patients with stable IHD and coronary artery revascularization. 
- All patients: pharmacotherapy for CAD
- Select patients: revascularization
Pharmacotherapy for CAD has two main therapeutic goals, secondary prevention for CAD and symptomatic relief with antianginal treatment. Specific indications and potential effects should be taken into account before prescribing the different drug classes.
- Goal: : reduction of myocardial oxygen demand (MVO2)
- First-line agent: beta blockers
Second-line agents: CCBs, nitrates, ranolazine
- Consider as initial monotherapy for patients with contraindications to beta blockers (e.g., vasospastic angina).
- Consider as combination therapy; with beta blockers to improve symptom control , e.g., a beta blocker PLUS a nitrate, dihydropyridine CCB , OR ranolazine.
- CCB (nondihydropyridine) PLUS a nitrate (nondihydropyridine CCBs such as verapamil have a similar effect to beta blockers on cardiac conduction) 
- Third-line agent: Consider if beta-blockers, CCBs, and nitrates are ineffective or not tolerated. 
|Effects of antianginal medications|
|Parameters that impact MVO2||Beta blockers||Nitrates||Combination of a beta blocker and a nitrate|
|Heart rate||↓|| |
|Unchanged or slightly ↓|
|Inotropy (contractility)||↓||↑ (reflectory)||Unchanged|
|End-diastolic volume||Unchanged or ↑||↓||Unchanged or slightly ↓|
|Overall effect on MVO2||↓||↓||↓↓|
Overview of pharmacotherapeutic agents for CAD
|Pharmacotherapy for CAD |
|Therapeutic goal||Drug class||Example agents||Specific indications and effects|
|Secondary prevention||Antiplatelet agents|| |
|ACEIs or ARBs|
|Secondary prevention and antianginal treatment||Beta blockers|| |
|Antianginal treatment||CCBs|| |
|Metabolic modulators|| || |
Revascularization for stable CAD 
Decisions regarding revascularization are complex and should be made with a multidisciplinary team of specialists (e.g., interventional cardiologists, cardiac surgeons) on an individual basis. See “” for revascularization indications of patients with acute symptoms.
- High-risk anatomic lesions involving multiple or critical vessels, such as:
- High-risk physiological conditions, such as:
Activity-limiting symptoms due to any that persist:
- Despite optimal medical treatment
- OR due to contraindications to pharmacotherapy
The choice of revascularization technique should take into account patient preference, coronary anatomy, left ventricular function, prior history of revascularization, and the presence of concomitant chronic conditions.
Revascularization is harmful in patients who do not meet anatomical or physiological criteria for intervention.
- Prognostic factors
- Stable angina
Similar to other atherosclerotic cardiovascular diseases: See “ .”
Secondary prevention of CAD
- Smoking cessation
- Increased physical activity
- Lifelong antiplatelet therapy with aspirin or clopidogrel
Treatment of comorbidities
- Diabetes mellitus
- Lipid-lowering therapy
Subtypes and variants
- Angina caused by transient coronary spasms (usually due to spasms occurring close to areas of coronary stenosis)
- Not affected by exertion (may also occur at rest)
- Typically occurs early in the morning 
- Highest prevalence in the Japanese population (especially young women)
- Average age of onset: 50 years
- Cigarette smoking; use of stimulants (e.g., cocaine, amphetamines), alcohol, or triptans
- Stress, hyperventilation, exposure to cold
- Associated with other vasospastic disorders (e.g., Raynaud phenomenon, migraine headaches) 
- Common atherosclerotic risk factors (except smoking) do not apply to vasospastic angina.
The goal of diagnostic testing is to detect transient ischemic changes and/or coronary artery spasm during anginal episodes, as well as concomitant coronary artery stenosis. Specialist consultation is advised. 
Initial testing 
- Resting ECG: Obtain during an acute anginal attack.
- Consider in patients with: 
Advanced testing 
- Coronary angiography: commonly indicated in vasospastic angina with ST-segment elevation to rule out underlying coronary artery stenosis
Coronary artery spasm provocation testing 
- Usually only performed to help inform a diagnosis or treatment decision when further information is required after completion of other tests
- Not recommended for patients with severe coronary artery stenosis or advanced heart failure 
- Spasms are usually induced pharmacologically.
- Nitrates and calcium channel blockers (CCBs) should be held before testing.
- Noninvasive coronary artery spasm provocation testing is not advised. 
|Diagnostic criteria for vasospastic angina |
|Typical clinical features|
|Transient ischemic ECG changes|
|Coronary spasm on angiography|
Noninvasive bedside coronary artery spasm provocation testing can lead to significant adverse effects and even death. Provocative testing to diagnose vasospastic angina should only be attempted by a specialist, and usually only during coronary angiography. 
- Smoking cessation
- Avoid beta-blockers (particularly nonselective beta blockers) , and other agents that induce vasoconstriction, such as: 
- Atherosclerotic risk factor modification, as appropriate (see “Prevention”) 
- Pharmacotherapy: The goal is to prevent spasms and arrhythmias, and to improve symptoms during acute attacks. 
- Short-acting nitrates: e.g., nitroglycerin
- Statins: e.g., fluvastatin can further prevent coronary artery spasm when added to CCB treatment. 
- Alpha blockers: The addition of prazosin to CCBs or long-acting nitrates may reduce episodes of spasm. 
- Magnesium supplementation may help to prevent spasms. 
- May occur with prolonged spasms or in patients with concomitant coronary artery stenosis
- See “ .”
- AV block: A pacemaker may be required (see “ ”).
- and : An may be required.
- 5-year survival rate is > 90% (with treatment). 
- The persistence of symptoms is common.
- One-Minute Telegram 58-2022-2/3: 2022 USPSTF recommendations on statins for primary ASCVD prevention
- One-Minute Telegram 51-2022-1/3: Is all chest pain created equal?
- One-Minute Telegram 39-2021-3/3: Should patient age alter interpretation of coronary artery calcium?
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