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 (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
- Angina: chest pain caused by myocardial ischemia (necrosis of myocytes has not yet occurred) due to narrowing (e.g., thrombus) or spasm (e.g., Prinzmetal angina) of the coronary artery
- Stable angina: a type of angina that occurs upon exertion, mental stress, and/or exposure to cold and usually subsides within 20 minutes of rest or after administration of nitroglycerin
- 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.
- CAD is the leading cause of death in the US and worldwide. 
- The lifetime risk of coronary artery disease at age 50 is approx. 50% for men and 40% for women. 
Epidemiological data refers to the US, unless otherwise specified.
- 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
- Typically retrosternal chest pain or pressure
- Dizziness, palpitations
- Restlessness, anxiety
- Autonomic symptoms (e.g., diaphoresis, nausea, vomiting, syncope)
- Symptoms are reproducible/predictable
- Symptoms often subside within minutes with rest or after administration of nitroglycerin
- Common triggers include mental/physical stress or exposure to cold
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.
This approach is consistent with 2012 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) Task Force guidelines on the diagnosis of patients with stable ischemic heart disease (IHD), as well as the 2013 ACCF/AHA appropriate use criteria for the detection and risk assessment of stable IHD. Recommendations focus on patients with chronic stable angina. For patients with acute symptoms, see “ .” 
Clinical assessment of symptomatic patients to predict the probability of CAD is used to help determine the need for further diagnostic tests and guide the selection of the best initial diagnostic test.
- Perform an initial clinical evaluation
Perform diagnostic testing
- Resting ECG: in all patients being evaluated for CAD
- Further diagnostic testing: The decision to perform additional tests and the type of test should be tailored to the patient. 
- Noninvasive diagnostic testing : preferred for most patients
- Invasive coronary angiography (gold standard): usually reserved for specific clinical scenarios
- Diagnostic testing for CAD in asymptomatic patients
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 CAD takes the following into consideration:
- The patient's age and sex
Type of chest pain 
- 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
- The likelihood of an alternate diagnosis that explains the symptoms (see “Differential diagnoses of chest pain”).
|Determining pretest probability of CAD |
|Estimated PTP||Clinical presentation|
|Very low (< 5%)|| |
|High (> 90%)|| |
|Other factors that independently increase PTP |
Further diagnostic testing
Decision algorithm 
- Consider specialist consultation for decisions regarding further diagnostic testing.
- Indications and choice of testing are determined by the following:
- For patients with a low or very low probability of CAD further testing should be considered on an individual basis.
|Approach to further diagnostics based on PTP of CAD |
|PTP||Able to exercise with interpretable ECG||Unable to exercise or uninterpretable ECG|
|Very low (< 5%)|| |
|Low (5–10%)|| || |
|Intermediate (10–90%)|| |
|High (> 90%)|
|For patients able to exercise with an uninterpretable ECG (regardless of PTP): Consider with imaging, e.g., echocardiography, or myocardial perfusion imaging|
Cardiac stress testing is most useful for patients with an intermediate pretest probability of CAD; ischemic changes during testing allow for reclassification of patients into a high probability of CAD, while a normal test makes the probability of CAD low.
Further diagnostic testing may be unnecessary in individuals with a very low pretest probability of CAD. 
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.
- Other modalities, e.g., echocardiography,; myocardial perfusion imaging, are used to detect signs of ischemia in some patients, e.g., those with an uninterpretable ECG.
- See “Comparison of cardiac stress tests” for details.
- Chronic stable angina
- Most useful for risk stratification in patients with an intermediate pretest probability of CAD
- Consider the following limitations of cardiac stress testing in patients with a low or high pretest probability of CAD:
- Other indications
- Chronic stable angina
General criteria for test termination can include the following:
- 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
- See “Comparison of cardiac stress tests” for specific criteria for test termination.
Diagnostic endpoints: evidence of stress-induced ischemia
- Changes in global left ventricular function during or after stress
- New or worsening
- myocardial perfusion after stress : decreased
- perfusion abnormality : new or
- 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|
|Procedure|| || |
|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). 
Nonstress cardiac imaging 
Coronary CT angiography (CCTA): can visualize anatomic CAD 
- Supportive findings 
- Coronary artery calcium (CAC) scoring: measures the amount of calcification in the coronary arteries 
Invasive testing ( )
- 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 ACCF/AHA Task Force guidelines on the management of patients with stable IHD, and with its 2014 focused update. 
- 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.
- 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
- One-Minute Telegram 39-2021-3/3: Should patient age alter interpretation of coronary artery calcium?
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