Coronary artery disease

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 acute coronary syndrome, 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, antianginal medication (e.g., beta blockers), and, in severe cases, revascularization (e.g., percutaneous transluminal coronary angioplasty).

This article provides an overview of CAD as well as diagnostic and treatment options for patients with stable CAD. Atherosclerosis and acute coronary syndrome (including MI) are discussed in separate articles.

• 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. ^[1]
• The lifetime risk of coronary artery disease at age 50 is approx. 50% for men and 40% for women. ^[2]

Epidemiological data refers to the US, unless otherwise specified.

• Atherosclerosis is the most common cause (see “Risk factors for atherosclerosis”).

Plaque formation and coronary artery stenosis ^[3][4]

• For plaque formation, see “Pathogenesis of atherosclerosis.”
• 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 “Acute coronary syndrome”).
• 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).
  • In healthy individuals, the CFR can be up to 4 times higher on exertion than at rest.
  • CFR is reduced in individuals with CAD due to vascular stenosis and reduced vascular compliance.

Myocardial oxygen supply-demand mismatch ^[5]

• Definition: mismatch between the amount of oxygen the myocardium receives and the amount it requires
• Factors reducing oxygen supply
  • Coronary atherosclerosis and sequelae, including:
    • Rupture of an unstable atherosclerotic plaque (most common cause)
    • Thrombosis
    • Stenosis
  • Vasospasms
  • ↑ Heart rate
  • Anemia
• Factors increasing oxygen demand
  • ↑ Heart rate
  • ↑ Afterload
  • Anemia

An increased heart rate reduces oxygen supply and increases oxygen demand.

Effect of vascular stenosis on resistance to blood flow ^[6]

• 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 ^[5]

• 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
    • Partially or completely reversible when adequate oxygen supply is restored (e.g., after angioplasty or coronary artery bypass grafting)
    • Seen in angina pectoris, left ventricular dysfunction, and/or heart failure
• 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
• Pathomechanism
  • 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.
• Clinical relevance
  • Coronary steal is the underlying mechanism of pharmacological stress testing.
  • 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

Coronary steal syndrome should not be confused with coronary-subclavian steal syndrome.

Chronic ischemic heart disease

• Definition: progressive heart failure that occurs after many years of chronic ischemic damage to the myocardium

Angina

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
  • Pain may radiate to the left arm, neck, jaw, epigastric region, or back.
  • Pain is not affected by body position or respiration.
  • No chest wall tenderness
  • May gradually increase in intensity
  • May present as gastrointestinal discomfort
  • May be absent, especially in geriatric and diabetic patients. ^[7]
• Dyspnea
• Dizziness, palpitations
• Restlessness, anxiety
• Autonomic symptoms (e.g., diaphoresis, nausea, vomiting, syncope)

Stable angina

• 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

Vasospastic angina

Description

• 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 ^[8]

Epidemiology ^[9]

• Highest prevalence in the Japanese population (especially young women)
• Average age of onset: 50 years

Etiology

• 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) ^[10]
• Common atherosclerotic risk factors (except smoking) do not apply to vasospastic angina.

Diagnosis ^[11][12]

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. ^[12]

• Initial testing ^[12][13]
  • Resting ECG: Obtain during an acute anginal attack.
  • Consider Holter monitor in patients with: ^[13]
    • No ischemic changes documented on resting ECG
    • Syncope or bradyarrhythmias ^[12][13]
  • Exercise stress test
    • Consider if ischemic changes have not been identified using other methods.
    • Approx. one-third of patients with vasospastic angina show no ST segment changes during an exercise stress test. ^[12]
• Cardiac biomarkers
  • Measure serial troponin I and/or troponin T levels during periods of acute chest pain (i.e., at arrival and 1–6 hours later) if acute coronary syndrome is suspected (see also “Complications”).
  • Serial troponin levels are unlikely to be elevated in patients with transient ischemic changes. ^[8][14]
• Advanced testing ^[11][12]
  • Coronary angiography: commonly indicated in vasospastic angina with ST-segment elevation to rule out underlying coronary artery stenosis
  • Coronary artery spasm provocation testing ^[11][12]
    • 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 ^[8]
    • 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. ^[11]

Treatment ^[12][15]

• General recommendations
  • Smoking cessation
  • Avoid beta-blockers (particularly nonselective beta blockers) , and other agents that induce vasoconstriction, such as: ^[13][15]
    • Triptans
    • High-dose aspirin (> 325 mg) ^[13][15]
    • Certain chemotherapeutic agents
    • Alcohol and recreational drugs
  • Atherosclerotic risk factor modification, as appropriate (see “Prevention”) ^[8]
• Pharmacotherapy: The goal is to prevent spasms and arrhythmias, and to improve symptoms during acute attacks. ^[12][13]
  • First-line therapy: calcium channel blockers, e.g., verapamil , diltiazem , or nifedipine ^[12]
  • Alternatively:
    • Long-acting nitrates: e.g., isosorbide dinitrate
    • Combination therapy for symptom control: nitrates with up to two CCBs from different classes ^[12]
• Additional pharmacotherapy
  • Short-acting nitrates: e.g., nitroglycerin
    • May be used during acute attacks
    • Patients should seek medical attention if pain persists after three doses of nitroglycerin taken over 15 minutes.
  • Statins: e.g., fluvastatin can further prevent coronary artery spasm when added to CCB treatment. ^[8][16]
  • Alpha blockers: The addition of prazosin to CCBs or long-acting nitrates may reduce episodes of spasm. ^[8][15]
  • Magnesium supplementation may help to prevent spasms. ^[8][13][17]

Prognosis

• 5-year survival rate is > 90% (with treatment). ^[18]
• 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 “Risk stratification for ACS.” ^[19][20]

Approach ^[19]

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
  • Determine the pretest probability of CAD.
  • Assess the patient for traditional ASCVD risk factors.
  • Take a history of recurrent angina episodes and characterize the nature of the pain.
  • Findings from a physical examination may be normal. Look for signs of:
    • Atherosclerotic vascular disease
    • Congestive heart failure
    • Valvular heart diseases
• 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. ^[21]
    • 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
  • May be indicated preoperatively (see “Preoperative cardiac assessment”)
  • The U.S. Preventive Services Task Force does not recommend screening asymptomatic adults with low ASCVD risk using resting ECG or exercise ECG. ^[22]

Resting ECG ^[19]

• 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 “Acute coronary syndrome”).
  • ST-segment depression
  • T-wave inversion or T-wave flattening
• Uninterpretable ECG: on that does not allow identification of stress-induced ischemic changes, typically due to preexisting abnormalities that affect interpretability, such as: ^[20][21]
  • Resting ST depression ≥ 0.1 mV (1 mm)
  • Complete LBBB
  • Digoxin use
  • Preexcitation (e.g., WPW)
  • Ventricular paced rhythm
  • LVH

Resting ECG results are usually normal in patients with stable CAD.

This is one of several possible methods for estimating the pretest probability of CAD. See also “Chest pain” and “Risk stratification of ACS” for approaches to in patients with acute symptoms.

• Pretest probability of CAD takes the following into consideration:
  • The patient's age and sex
  • Type of chest pain ^[20]
    • Typical angina fulfills all of the following criteria:
      • Retrosternal chest pain of characteristic nature and duration (e.g., transient retrosternal pressure)
      • Provoked by exertion or emotional stress
      • Relieved by rest and/or nitroglycerin
    • 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”).

Decision algorithm ^[19][20][21]

• Consider specialist consultation for decisions regarding further diagnostic testing.
• Indications and choice of testing are determined by the following:
  • Pretest probability of CAD
  • The patient's ability to exercise ^[19]
  • ECG interpretability
  • Contraindications to specific testing modalities
  • Test availability
• For patients with a low or very low probability of CAD further testing should be considered on an individual basis.

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. ^[20]

Noninvasive testing

Cardiac stress testing ^{[19][20][24][25][26]}

The goal is to detect evidence of stress-induced ischemia.

• Description
  • Heart rate is monitored throughout the study ^[27]
    • Estimated maximum heart rate = 220 – age (in years)
    • Target heart rate = 85% of the maximum heart rate
  • 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.
• Options
  • Cardiac exercise stress test (e.g., treadmill or bicycle): first-line test ^[21][26]
  • Cardiac pharmacological stress test (e.g., vasodilator or inotropic medication): alternative in patients unable to exercise ^[20]
• Indications ^[28]
  • 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:
      • High pretest probability: A negative result cannot rule out ischemic heart disease.
      • Low pretest probability: Positive results are often false positives.
  • Other indications
    • 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
• General criteria for test termination can include the following:
  • A diagnostic endpoint is reached (preferred). ^[21][27][28]
  • 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
  • ECG
    • Downsloping ST depression or horizontal ST depression of ≥ 0.1 mV (1 mm) at peak exercise intensity
    • ST elevation of ≥ 0.1 mV; (1 mm) in leads with no preexisting Q waves (except in V1 or aVR) : considered to be a high-risk ECG finding consistent with acute coronary syndrome
  • Echocardiography
    • Changes in global left ventricular function during or after stress
    • New or worsening wall motion abnormalities
  • Radionuclide myocardial perfusion imaging: decreased myocardial perfusion after stress
  • CMR: new wall motion abnormality or perfusion abnormality
• Test preparation
  • 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. ^[28]

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). ^[28]

Nonstress cardiac imaging ^[19]

• Coronary CT angiography (CCTA): can visualize anatomic CAD ^[29]
  • Indications
    • Patients with contraindications to cardiac stress testing
    • Patients who have previously had a cardiac stress test with:
      • Persistent symptoms and no abnormalities detected during previous tests
      • Inconclusive cardiac stress test results
  • Supportive findings ^[30]
    • Calcified or noncalcified plaques
    • The degree and extent of coronary stenosis can be measured and is usually reported using CAD-RADS.
• Coronary artery calcium (CAC) scoring: measures the amount of calcification in the coronary arteries ^[20]
  • Rarely used to assess for CAD in symptomatic patients; usually reserved for asymptomatic patients (see “Diagnostics” in “Lipid disorders”)
  • Consider in patients with a low pretest probability of CAD to rule out the disease.

Invasive testing (coronary angiography) ^[19][31]

• Indications
  • 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: ^[32]
      • ST elevation during cardiac stress testing
      • Perfusion abnormalities involving 10% of the myocardium after stress
      • Significant coronary artery stenosis on CCTA
      • Inducible wall motion abnormalities
    • 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., acute coronary syndrome and certain valvular diseases (see “Cardiac catheterization”)
• Uses
  • Direct visualization of coronary arteries
  • To determine the feasibility of direct therapeutic intervention using percutaneous coronary intervention (see “Treatment” below)
  • Cardiac catheterization can provide information on several parameters; (e.g., coronary blood flow; , pressure within heart chambers, cardiac output, oxygen saturation). ^[33]
• Supportive findings: ^[19]
  • 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:
    • ≥ 50% narrowing of the LMCA
    • ≥ 70% narrowing of other coronary arteries, e.g., RCA, LCx, LAD

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.

See “Differential diagnosis of chest pain.”

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. ^[19][31]

Approach ^[19]

The goal of treatment is to reduce cardiovascular morbidity and mortality, improve ischemic symptoms, and maintain quality of life.

• All patients: pharmacotherapy for CAD
  • Start secondary prevention of CAD, i.e., antiplatelet agents, statins, and management of comorbidities.
  • Start antianginal medication.
• Select patients: revascularization
  • Not routinely recommended for stable CAD
  • Techniques
    • Percutaneous coronary intervention (PCI)
    • Coronary artery bypass grafting (CABG)

All patients with CAD should receive education on risk factor reduction, as well as treatment with antiplatelet agents and antianginal medications

Pharmacotherapy for CAD

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.

Antianginal drugs

• 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) ^[34]
• Third-line agent: Consider ranolazine if beta-blockers, CCBs, and nitrates are ineffective or not tolerated. ^[19]

Overview of pharmacotherapeutic agents for CAD

Beta blockers are used both to reduce the risk of MI and death (secondary prevention) and for symptom relief (antianginal treatment) in patients with CAD.

Revascularization for stable CAD ^[19][32]

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 “Acute coronary syndrome” for revascularization indications of patients with acute symptoms.

• Indications
  • High-risk anatomic lesions involving multiple or critical vessels, such as:
    • Complex CAD
    • 3-vessel disease
    • LMCA stenosis without patent bypass grafts
    • Proximal LAD stenosis PLUS 2-vessel disease or 1-vessel disease
  • High-risk physiological conditions, such as:
    • LVEF < 50%
    • Prior sudden cardiac arrest with suspected ischemia-induced VT
  • Activity-limiting symptoms due to any significant coronary artery stenosis that persist:
    • Despite optimal medical treatment
    • OR due to contraindications to pharmacotherapy
• Options
  • CABG is generally preferred in patients with:
    • > 50% LMCA stenosis without patent bypass grafts
    • Complex CAD or three-vessel disease PLUS low surgical risk
    • Multivessel disease with either proximal LAD stenosis or concomitant diabetes mellitus ^[31]
    • LV dysfunction
  • PCI : may be preferred in select patients

• Prognostic factors
  • Left ventricular function: increased mortality if EF < 50% ^[40]
  • Involvement of left main coronary artery or involvement of more than one vessel is associated with a worse prognosis
• Stable angina
  • Annual mortality rate: up to 5% ^[19]
  • 25% of patients will develop acute MI within the first 5 years. ^[41]
  • High-grade stenosis is associated with an unfavorable prognosis.

Primary prevention of CAD

Similar to other atherosclerotic cardiovascular diseases: See “ASVCD prevention.”

Secondary prevention of CAD

• Lifestyle modifications
  • Smoking cessation
  • Increased physical activity
• Lifelong antiplatelet therapy with aspirin or clopidogrel
• Treatment of comorbidities
  • Hypertension
    • Target BP in hypertension: < 130/80 mm Hg ^[36]
    • First-line treatment: beta blockers
    • Alternative: ACE inhibitors or angiotensin receptor blockers (ARBs), especially in patients post MI
  • Diabetes mellitus
    • Individualized glycemic goals (e.g., HbA1c < 7%)
    • Consider the use of antihyperglycemics with known protective cardiovascular effects in patients with T2DM. ^[42]
• Lipid-lowering therapy
  • Moderate- or high-intensity statin therapy
  • Consider second-line lipid-lower therapy if there is a poor response to statin monotherapy.
  • See “Guidelines for lipid-lowering therapy in adults.”

1. Kochanek KD, Murphy S, Xu J, Arias E. Mortality in the United States, 2016.. NCHS Data Brief. 2017 : p.1-8.
2. Lloyd-Jones DM, Leip EP, Larson MG, et al. Prediction of Lifetime Risk for Cardiovascular Disease by Risk Factor Burden at 50 Years of Age. Circulation. 2006; 113 (6): p.791-798. doi: 10.1161/circulationaha.105.548206 . | Open in Read by QxMD
3. Kolli KK, Arif I, Peelukhana SV, et al. Diagnostic performance of pressure drop coefficient in relation to fractional flow reserve and coronary flow reserve. J Invasive Cardiol. 2014; 26 (5): p.188-195.
4. Pijls NHJ, Van Gelder B, Van der Voort P. Fractional Flow Reserve: A Useful Index to Evaluate the Influence of an Epicardial Coronary Stenosis on Myocardial Blood Flow. Circulation. 1995; 92 : p.3183-3193. doi: 10.1161/01.CIR.92.11.3183 . | Open in Read by QxMD
5. Physiology, Myocardial Oxygen Demand.
6. Determinants of Resistance to Flow (Poiseuille's Equation). http://www.cvphysiology.com/Hemodynamics/H003. Updated: August 12, 2017. Accessed: April 16, 2018.
7. Zunaira Gul, Amgad N. Makaryus.. Silent Myocardial Ischemia. StatPearls. 2020 .
8. E. A. Amsterdam, N. K. Wenger, R. G. Brindis, D. E. Casey Jr., T. G. Ganiats, D. R. Holmes Jr., A. S. Jaffe, H. Jneid, R. F. Kelly, M. C. Kontos, G. N. Levine, P. R. Liebson, D. Mukherjee, E. D. Peterson, M. S. Sabatine, R. W. Smalling, S. J. Zieman. 2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes. Journal of the American College of Cardiology. 2014 . doi: 10.1016/j.jacc.2014.09.017 . | Open in Read by QxMD
9. Mary Rodriguez Ziccardi; Jason D. Hatcher.. Prinzmetal Angina. StatPearls. 2020 .
10. Kathryn Buchanan Keller, Louis Lemberg. Prinzmetal's angina. American Journal of Critical Care. 2004 .
11. Beltrame JF, Crea F, Kaski JC, et al. International standardization of diagnostic criteria for vasospastic angina. Eur Heart J. 2017; 38 (33): p.2565-2568. doi: 10.1093/eurheartj/ehv351 . | Open in Read by QxMD
12. Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction. Circulation. 2007; 116 (7): p.e148-304. doi: 10.1161/circulationaha.107.181940 . | Open in Read by QxMD
13. Slavich M, Patel RS. Coronary artery spasm: Current knowledge and residual uncertainties. IJC Heart & Vasculature. 2016; 10 : p.47-53. doi: 10.1016/j.ijcha.2016.01.003 . | Open in Read by QxMD
14. Roffi M, Patrono C, Collet J-P, et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2015; 37 (3): p.267-315. doi: 10.1093/eurheartj/ehv320 . | Open in Read by QxMD
15. Harris JR, Hale GM, Dasari TW, Schwier NC. Pharmacotherapy of Vasospastic Angina. J Cardiovasc Pharmacol Ther. 2016; 21 (5): p.439-451. doi: 10.1177/1074248416640161 . | Open in Read by QxMD
16. Yasue H, Mizuno Y, Harada E, et al. Effects of a 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitor, Fluvastatin, on Coronary Spasm After Withdrawal of Calcium-Channel Blockers. J Am Coll Cardiol. 2008; 51 (18): p.1742-1748. doi: 10.1016/j.jacc.2007.12.049 . | Open in Read by QxMD
17. Stern S, Bayes de Luna A. Coronary Artery Spasm. Circulation. 2009; 119 (18): p.2531-2534. doi: 10.1161/circulationaha.108.843474 . | Open in Read by QxMD
18. Walling A, Waters DD, Miller DD, Roy D, Pelletier GB, Théroux P. Long-term prognosis of patients with variant angina.. Circulation. 1987 .
19. Stephan D Fihn, Julius M Gardin, Jonathan Abrams, Kathleen Berra, James C Blankenship, Apostolos P Dallas, Pamela S Douglas, etal.. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease. Circulation. 2012 . doi: 10.1161/CIR.0b013e318277d6a0 . | Open in Read by QxMD
20. Wolk MJ, Bailey SR, Doherty JU, et al. ACCF/AHA/ASE/ASNC/HFSA/HRS/SCAI/SCCT/SCMR/STS 2013 Multimodality Appropriate Use Criteria for the Detection and Risk Assessment of Stable Ischemic Heart Disease. J Am Coll Cardiol. 2014; 63 (4): p.380-406. doi: 10.1016/j.jacc.2013.11.009 . | Open in Read by QxMD
21. Gibbons RJ, Balady GJ, Beasley JW, et al. ACC/AHA Guidelines for Exercise Testing. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Exercise Testing).. J Am Coll Cardiol. 1997; 30 (1): p.260-311. doi: 10.1016/s0735-1097(97)00150-2 . | Open in Read by QxMD
22. Curry SJ, Krist AH, et al. Screening for Cardiovascular Disease Risk With Electrocardiography. JAMA. 2018; 319 (22): p.2308-2314. doi: 10.1001/jama.2018.6848 . | Open in Read by QxMD
23. Fihn SD, Blankenship JC, Alexander KP, et al. 2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease. J Am Coll Cardiol. 2014; 64 (18): p.1929-1949. doi: 10.1016/j.jacc.2014.07.017 . | Open in Read by QxMD
24. Asirvatham S, Sebastian C, Thadani U. Choosing the Most Appropriate Treatment for Stable Angina. Drug Saf. 1998; 19 (1): p.23-44. doi: 10.2165/00002018-199819010-00003 . | Open in Read by QxMD
25. Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease, 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction, 2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes, and 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery. Circulation. 2016; 134 (10): p.e123-55. doi: 10.1161/cir.0000000000000404 . | Open in Read by QxMD
26. Whelton, PK, Carey, RM et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. Hypertension. 2017; 71 (6): p.e13–e115. doi: 10.1161/hyp.0000000000000065 . | Open in Read by QxMD
27. Ohman EM. Chronic Stable Angina. N Engl J Med. 2016; 374 (12): p.1167-1176. doi: 10.1056/nejmcp1502240 . | Open in Read by QxMD
28. Rosano GMC, Vitale C, Volterrani M. Pharmacological Management of Chronic Stable Angina: Focus on Ranolazine. Cardiovasc Drugs Ther. 2016; 30 (4): p.393-398. doi: 10.1007/s10557-016-6674-1 . | Open in Read by QxMD
29. Lee L, Horowitz J, Frenneaux M. Metabolic manipulation in ischaemic heart disease, a novel approach to treatment.. European Heart Journal. 2004 .
30. Patel MR, Calhoon JH, Dehmer GJ, et al. ACC/AATS/AHA/ASE/ASNC/SCAI/SCCT/STS 2017 Appropriate Use Criteria for Coronary Revascularization in Patients With Stable Ischemic Heart Disease. J Am Coll Cardiol. 2017; 69 (17): p.2212-2241. doi: 10.1016/j.jacc.2017.02.001 . | Open in Read by QxMD
31. Connie W. Tsao, MD, MPH, Asya Lyass, PhD, and Ramachandran S. Vasan, MD. Prognosis of Adults with Borderline Left Ventricular Ejection Fraction. JACC. Heart failure. 2016 .
32. Clinical Outcomes of Patients With Stable Angina.
33. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease. J Am Coll Cardiol. 2019; 74 (10): p.e177-e232. doi: 10.1016/j.jacc.2019.03.010 . | Open in Read by QxMD
34. Exercise Stress Testing. https://www.aafp.org/afp/2017/0901/p293.html. Updated: September 1, 2017. Accessed: January 20, 2020.
35. Henzlova MJ, Duvall WL, Einstein AJ, Travin MI, Verberne HJ. ASNC imaging guidelines for SPECT nuclear cardiology procedures: Stress, protocols, and tracers. Journal of Nuclear Cardiology. 2016; 23 (3): p.606-639. doi: 10.1007/s12350-015-0387-x . | Open in Read by QxMD
36. Fletcher GF, Ades PA, Kligfield P, et al. Exercise Standards for Testing and Training. Circulation. 2013; 128 (8): p.873-934. doi: 10.1161/cir.0b013e31829b5b44 . | Open in Read by QxMD
37. Garner KK, Pomeroy W, Arnold JJ. Exercise Stress Testing: Indications and Common Questions.. Am Fam Physician. 2017; 96 (5): p.293-299.
38. Fletcher GF, Balady GJ, Amsterdam EA, et al. Exercise Standards for Testing and Training. Circulation. 2001; 104 (14): p.1694-1740. doi: 10.1161/hc3901.095960 . | Open in Read by QxMD
39. Hill J. ABC of clinical electrocardiography: Exercise tolerance testing. BMJ. 2002; 324 (7345): p.1084-1087. doi: 10.1136/bmj.324.7345.1084 . | Open in Read by QxMD
40. Taylor AJ, Cerqueira M, Hodgson JM, et al. ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 Appropriate Use Criteria for Cardiac Computed Tomography. J Am Coll Cardiol. 2010; 56 (22): p.1864-1894. doi: 10.1016/j.jacc.2010.07.005 . | Open in Read by QxMD
41. Cury RC, Abbara S, Achenbach S, et al. Coronary Artery Disease - Reporting and Data System (CAD-RADS). JACC: Cardiovasc Imaging. 2016; 9 (9): p.1099-1113. doi: 10.1016/j.jcmg.2016.05.005 . | Open in Read by QxMD
42. Bashore TM, Balter S, Barac A, et al. 2012 American College of Cardiology Foundation/Society for Cardiovascular Angiography and Interventions Expert Consensus Document on Cardiac Catheterization Laboratory Standards Update. J Am Coll Cardiol. 2012; 59 (24): p.2221-2305. doi: 10.1016/j.jacc.2012.02.010 . | Open in Read by QxMD