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Aug.29.2022

Stable Ischemic Heart Disease

Synopsis

Key Points

  • Stable ischemic heart disease is a clinical syndrome consisting of episodes of reversible mismatch in myocardial oxygen demand and supply related to inadequate blood flow to the myocardium r1
  • Characterized by episodes of angina (ie, retrosternal chest pain or discomfort that may radiate to left arm or jaw) or angina equivalents (eg, dyspnea, faintness, fatigue) r2
  • Usually precipitated by exertion, emotional excitement, or heavy meal, and is often worse in cold weather r3
  • Diagnosis is based on history, physical examination, 12-lead ECG, measurement of serum biochemical markers, and noninvasive testing (eg, exercise ECG testing, exercise or pharmacologic stress testing with functional imaging)
  • Coronary angiography is the gold standard for evaluating the presence of coronary artery disease; it is not routinely indicated to confirm diagnosis in patients with stable angina but may be performed if noninvasive testing suggests high-risk coronary lesions present r3
  • Acute angina symptoms are controlled with sublingual nitroglycerin or short-acting nitrates
  • Manage risk factors for ischemic heart disease using both pharmacologic (eg, aspirin, ACE inhibitors, angiotensin II receptor antagonists, statins) and nonpharmacologic methods, as necessary
  • β-blockers and calcium channel blockers are the first line agents for long-term symptom control. Second line or add-on agents include long-acting nitrates, ranolazine, or ivabradine; none of these agents has been shown to reduce myocardial infarction or ischemic cardiac death
  • Revascularization with either percutaneous coronary intervention or coronary artery bypass graft surgery may be indicated for symptom relief in refractory cases or to improve prognosis in certain patients

Pitfalls

  • Consider acute coronary syndrome in patients presenting with anginal pain lasting more than 15 minutes r4d1
  • Do not administer a nitrate preparation or nitroglycerin in patients who have taken tadalafil in the last 48 hours or sildenafil in the last 24 hours; a suitable time interval for safe administration of nitrates after vardenafil has not been determinedr6r5

Terminology

Clinical Clarification

  • Stable ischemic heart disease is a clinical syndrome consisting of episodes of reversible mismatch in myocardial oxygen demand and supply related to inadequate blood supply to the myocardium, most frequently due to atherosclerotic obstruction within the coronary arteries. Episodes are usually induced by exercise, emotion, or other stress r1
    • Synonymous with chronic coronary artery disease or chronic coronary syndrome
  • Characterized by angina (ie, retrosternal chest pain or discomfort that may radiate to left arm or jaw) or an anginal equivalentr1 (eg, dyspnea, faintness, fatigue); silent ischemia may also occur r2

Classification

  • Classification by mechanism of ischemia, which may occur alone or in combination: r7
    • Fixed or dynamic stenoses of epicardial coronary arteries due to atherosclerotic plaque
    • Focal or diffuse spasm of epicardial coronary arteries in the presence or absence of atherosclerotic plaque
    • Microvascular, or small-vessel, dysfunction
  • Clinical classification of chest pain r7
    • Typical (definite) angina meets all of the following 3 characteristics:
      • Substernal chest discomfort of characteristic quality and duration
      • Provoked by exertion or emotional stress
      • Relieved by rest, nitroglycerin, or both
    • Atypical (probable) angina:
      • Meets 2 of the 3 characteristics of typical angina
    • Noncardiac chest pain
      • Meets 1 or none of the 3 characteristics of typical angina
  • Canadian Cardiovascular Society Angina Classification r7
    • Class I: no limitation of ordinary physical activity; angina with strenuous, rapid, or prolonged exertion only
    • Class II: slight limitation of ordinary physical activity; angina on walking rapidly or uphill, on climbing stairs rapidly, on exertion after meals, in cold weather, when under emotional stress, or only during the first few hours after awakening
    • Class III: marked limitation of ordinary physical activity; angina on walking 1 or 2 level blocks (equivalent to 100-200 m) or 1 flight of stairs at a normal pace under normal conditions
    • Class IV: inability to carry out any physical activity without discomfort; angina at rest

Diagnosis

Clinical Presentation

History

  • Most commonly reported symptom is chest pain that is typically associated with exertion or emotional stress c1c2
    • Characteristically described as a retrosternal chest pain, tightness, heaviness, or pressure c3c4c5c6
      • Pain may radiate to the left arm or shoulder, the lower jaw and teeth, the back between the shoulder blades, or the epigastrium c7c8c9c10c11c12c13
      • May be associated with symptoms such as pain, squeezing, or pressure in the arm, neck, or jaw c14c15c16c17
    • Chest pain may be accompanied by shortness of breath or nonspecific symptoms (eg, fatigue, syncope, nausea, vomiting, restlessness, a sense of impending doom) r7c18c19c20c21c22c23c24
      • These nonspecific symptoms in the absence of classic chest pain symptoms may represent anginal equivalents
    • Common precipitants include walking a certain distance (variable), stair climbing, emotional distress, sexual activity, heavy meal, exposure to cold, or waking up in the morning c25
      • Symptoms appear or become more severe with increased levels of exertion r7
      • Angina threshold may vary from day to day and even during the same day
    • Onset is gradual with increasing intensity over several minutes c26
    • Duration of discomfort is brief; less than 10 minutes in most cases r7c27
      • Resolves quickly (usually within 5 minutes) with rest or administration of nitroglycerin
      • May be reduced with further exercise (walk-through angina) or on subsequent exertion (warm-up angina)
  • Note any history of prior episodes of chest pain or risk factors for or known coronary artery disease c28c29c30
  • Any change in pattern of usual chest pain symptoms, level of exertion required to elicit anginal symptoms, or response to medications used may indicate disease progression

Physical examination

  • Physical examination findings may be unremarkable, particularly if patient is asymptomatic at the time c31
  • Signs of associated conditions may be present, such as:
    • Anemia c32
    • Hypertension c33
    • Decreased peripheral pulses c34
    • Carotid, femoral, or renal artery bruits c35c36c37
    • Elevated jugular vein pressure c38
    • Xanthelasma or xanthoma c39
    • Arrhythmia c40
    • Obesity c41
    • Peripheral edema c42
    • Pulmonary rales c43
  • Cardiac examination findings are often normal c44
    • Signs of underlying cardiac disease may be present (eg, cardiac enlargement or murmur) c45c46
    • During or immediately after an episode of myocardial ischemia, a third (S₃) or fourth (S₄) heart sound may be heard. A systolic murmur of mitral insufficiency may be apparent; however, these signs are rare and nonspecific r3c47c48c49
  • Palpation of the chest does not typically reproduce symptoms.r3Reproducible chest wall pain suggests a musculoskeletal causer5c50

Causes and Risk Factors

Causes

Myocardial ischemia is caused by a transient imbalance between blood supply and demand, most commonly as result of obstruction to coronary blood flow due to atherosclerotic coronary artery disease r2c51
  • Less common mechanisms include: r2
    • Focal or diffuse coronary vasospasm r7c52
    • Reduced coronary flow reserve, such as that seen in the setting of microvascular (small-vessel) disease or in endothelial dysfunction c53

Risk factors and/or associations

Age
  • Prevalence of angina increases with age in both sexes
    • Ranges from 5% to 7% in women aged 45 to 64 years to 10% to 12% in women aged 65 to 84 years r3c54c55
    • Ranges from 4% to 7% in men aged 45 to 64 years to 12% to 14% in men aged 65 to 84 years r3c56c57
Sex
  • In older adults, angina is more prevalent in men than women; however, angina is more prevalent in middle-aged women than in men, possibly owing to the higher prevalence of functional disease (eg, microvascular angina) in women r3c58c59c60c61
Genetics
  • Family history of coronary artery disease is associated with increased risk c62
Ethnicity/race
  • Annual rates of new angina episodes are higher in men who are not Black when compared with Black men aged 65 to 85 years; rates are higher in Black men older than 85 years r5c63c64c65c66c67c68c69c70
  • Rates are higher in Black women compared with other women aged 65 years and older, with the greatest magnitude of difference in those older than 85 years r5c71c72c73c74
Other risk factors/associations
  • Risk factors and associations for coronary artery disease r5
    • Hypertension c75
    • Cigarette smoking c76
    • Diabetes mellitus c77
    • Metabolic syndrome c78
    • Dyslipidemia c79
    • Family history of premature coronary artery disease c80
    • Estrogen deficiency c81
    • Overweight and obesity c82c83
    • Physical inactivity c84
    • Renal insufficiency c85
    • Connective tissue diseases, rheumatoid arthritis c86c87
    • Antineoplastic or immunosuppressive therapy c88c89
    • Peripheral artery disease c90
    • Cerebrovascular disease c91
  • Systemic conditions that increase myocardial oxygen demand or decrease oxygen supply r5
    • Fever c92
    • Severe anemia c93
    • Hyperthyroidism c94
    • Tachycardia c95
    • Hypoglycemia c96
    • Pain c97
    • Stimulant use disorder c98
    • Pneumonia c99
    • Asthma c100
    • Chronic obstructive pulmonary disease c101
    • Pulmonary hypertension c102
    • Interstitial pulmonary fibrosis c103
    • Obstructive sleep apnea c104
    • Sickle cell disease c105
    • Pheochromocytoma c106
    • Polycythemia c107
    • Leukemia c108
    • Thrombocytosis c109
    • Hypergammaglobulinemia c110
    • Anxiety c111
    • Arteriovenous fistulae c112
    • Hypertrophic cardiomyopathy c113
    • Aortic stenosis c114
    • Dilated cardiomyopathy c115
    • Significant coronary obstruction c116
    • Microvascular disease c117

Diagnostic Procedures

Primary diagnostic tools

  • Diagnosis is based on history, physical examination, 12-lead ECG, measurement of serum biochemical markers, and noninvasive testing c118
  • Obtain detailed history regarding location, character, and duration of chest pain; its relationship to exertion and other exacerbating or relieving factors; and presence of cardiovascular risk factors r5r7
  • Obtain resting ECG in all patients at presentation r8c119
  • Laboratory tests should be obtained to identify possible causes of ischemia, cardiovascular risk factors, and associated conditions, as well as to determine prognosis r7
    • CBC, fasting blood glucose level, hemoglobin A1C level, fasting lipid profile, and baseline renal function tests c120c121c122
    • Thyroid function tests, if clinically suspicious for thyroid disease c123
    • Cardiac-specific troponin (T or I) levels, if there is concern for unstable angina (eg, prolonged periods of angina, angina at rest, new-onset moderate to severe angina) or if previously stable ischemic heart disease with rapidly increasing or crescendo angina is suspected c124
      • If troponin level is elevated, proceed with management for non–ST segment elevation acute coronary syndrome d1
    • Brain natriuretic peptide/N-terminal pro–B-type natriuretic peptide in patients with suspected heart failure
  • Chest radiography is not routinely indicated in initial work-up as it does not provide specific diagnostic or prognostic information c125
    • Occasionally useful for assessing patients with suspected heart failure or comorbid pulmonary disease, or to exclude another cause of chest pain in atypical presentations
  • Echocardiography is recommended in most patients to exclude alternative causes of angina, identify regional wall motion abnormalities suggestive of coronary artery disease, measure left ventricular ejection fraction for risk stratification purposes, evaluate diastolic function, and assess for valvular disease r7
  • In patients without a known history of ischemic heart disease, proceed with risk stratification to determine whether pretest probability of ischemic heart disease is sufficient to recommend further testing r5
    • Predictive models have been developed for this purpose based on historic and demographic patient features
      • Pretest likelihood of coronary artery disease in symptomatic patients.Table shows a combination of Diamond-Forrester and Coronary Artery Surgery Study (CASS) data. The values represent the percentage of patients with significant coronary artery disease on catheterization.Data from Fihn et al: 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 126(25):e354-471, 2012; Diamond GA et al: Analysis of probability as an aid in the clinical diagnosis of coronary-artery disease. N Engl J Med. 300:1350-8, 1979; and Chaitman BR et al: Angiographic prevalence of high-risk coronary artery disease in patient subsets (CASS). Circulation. 64:360-7, 1981.
        Age (y)Nonanginal chest pain: men (%)Nonanginal chest pain: women (%)Atypical angina: men (%)Atypical angina: women (%)Typical angina: men (%)Typical angina: women (%)
        30 to 394234127626
        40 to 4913351228755
        50 to 5920765319373
        60 to 69271472519486
    • Consultation with a cardiologist is recommended to determine pretest risk probability
    • Further testing is most useful in patients for whom the cause of chest pain is truly uncertain; that is, pretest probability of ischemic heart disease is intermediate (variably defined as a probability of ischemic heart disease between 20% and 70% or 15% and 85%r3) r5
    • Other factors may be involved in the decision to refer a patient for further testing, such as degree of uncertainty acceptable to physician and patient, likelihood of alternative diagnosis, cost, potential risks of further testing, and benefits and risks of treatment in the absence of additional testing r5
  • If pretest probability of ischemic heart disease is intermediate or greater, consider noninvasive testing (eg, exercise ECG testing, pharmacologic or exercise imaging stress testing)
    • European guidelines recommend the use of either noninvasive functional imaging or anatomical imaging (cardiac CT angiography) as the initial test for diagnosing coronary artery disease; exercise ECG may be considered if imaging tests are not available r7
  • For patients with a low to intermediate pretest probability (variably defined as less than 10% or less than 20%) of obstructive ischemic heart disease, consider cardiac CT angiography; stress testing is less likely to be indicated
  • Coronary angiography is the gold standard for evaluating the presence of coronary artery disease; however, this invasive procedure is not routinely indicated to establish a diagnosis of ischemic heart disease in patients with stable angina r7
    • Early angiography without previous noninvasive testing may be indicated in patients who have a high pretest probability of ischemic heart disease and: r7
      • Symptoms that are severe, unresponsive to medical therapy, or occur at a low level of exercise, or
      • Clinical evaluation suggesting high risk for a cardiac event
    • May have a role in patients with reduced left ventricular ejection fraction less than 50% and typical angina, in those who cannot undergo stress imaging techniques, or people in certain professions, such as pilots (regulatory requirement)
    • Indicated after risk stratification with noninvasive testing to determine options for revascularization if noninvasive testing suggests presence of high-risk coronary lesions and if a revascularization procedure is reasonable based on patient comorbidities and preferences r5
  • Fractional flow reserve, which may be measured as part of coronary angiography or derived via CT angiography, may be used to determine need for percutaneous coronary intervention by measuring pressure difference across stenosis to assess hemodynamic significance r9

Imaging

  • Echocardiography c126c127
    • A resting transthoracic echocardiogram is recommended in all patients to exclude alternative causes of angina, identify regional wall motion abnormalities suggestive of coronary artery disease, measure left ventricular ejection fraction for risk stratification purposes, evaluate diastolic function, and evaluate presence of significant valvular disease r7
      • Consider in patients with a cardiac murmur on examination, previous myocardial infarction, or symptoms/signs of heart failure
      • May be omitted in very young and healthy patients with a high suspicion of an extracardiac cause of chest pain and in multimorbid patients in whom the result of echocardiography will not influence patient management
  • Noninvasive functional imaging tests
    • Stress test with functional imaging is superior to conventional exercise ECG testing owing to its increased sensitivity in detecting obstructive coronary disease, its ability to quantify and localize areas of ischemia, and its ability to provide diagnostic information in the presence of an abnormal baseline resting electrocardiogram r7
    • Recommended as the initial test in patients with intermediate to high pretest probability of ischemic heart disease and in patients without typical angina symptoms who have a left ventricular ejection fraction less than 50%, if local expertise and availability permit r5r7
      • Also recommended in patients with abnormal baseline ECG findings that prevent accurate interpretation of ECG changes during stress ECG testing
      • Consider in symptomatic patients with previous percutaneous coronary intervention or coronary artery bypass grafting, particularly if evaluating for changes over time in size and location of ischemia
      • Screen patients of childbearing age for possibility of pregnancy or breastfeeding status when considering any testing modality involving possible radiation exposure
    • Exercise stress testing is recommended over pharmacologic testing when possible as it provides a physiologic environment and provides additional physiologic data (ie, exercise time, workload achieved) as well as information about changes in heart rate, blood pressure, and ECG results r3
    • Stress imaging using a pharmacologic stress agent (eg, adenosine, dipyridamole, dobutamine, regadenoson) can be performed in patients who have an inadequate ability to exercise
    • Stress imaging modalities r3
      • Exercise stress echocardiography c128
      • Exercise stress myocardial perfusion imaging (with single photon emission CT) c129
      • Dobutamine stress echocardiography c130c131
      • Dobutamine stress MRI c132c133
      • Vasodilator stress echocardiography c134
      • Vasodilator stress myocardial perfusion imaging (with single photon emission CT) c135
      • Vasodilator stress MRI c136
      • Vasodilator stress myocardial perfusion PET scan c137
  • Cardiac CT angiography and coronary artery calcium scoring c138c139c140
    • Consider CT angiography as an alternative to stress imaging techniques for ruling out ischemic heart disease in patients with low to intermediate pretest probability for ischemic heart disease in whom good image quality can be anticipated r5r7
      • Also consider in patients with an inconclusive exercise ECG or stress imaging test result, those having continued symptoms despite normal exercise ECG findings or stress imaging test results, those with contraindications to stress testing, or those patients who should avoid invasive coronary angiography owing to increased risk r5r7
      • Prescreening is recommended to confirm patients have adequate breath-holding capabilities, have a favorable calcium score and distribution, are not severely obese, and are preferably in sinus rhythm with a heart rate of 65 beats per minute or less (preferably 60 beats per minute or less) r7
      • Cardiac CT angiography techniques and modeling may be used as noninvasive means to derive fractional flow reserve and determine if coronary artery stenosis is hemodynamically significant r10
    • CT also provides measurement of coronary artery calcium score; however, this is not recommended as a standalone test to evaluate ischemia in symptomatic patients
      • Calcium score correlates roughly to total amount of atherosclerosis present in coronary arteries r3
      • Correlation with actual extent of luminal narrowing, or stenosis, is poor
      • A "zero" calcium score does not rule out coronary artery stenosis in symptomatic patients

Functional testing

  • ECG c141
    • A 12-lead ECG is recommended in all patients presenting with symptoms of chest pain concerning for angina or possible anginal equivalent r7
    • Establishes baseline for comparison and has a role in risk stratification
    • Resting ECG findings may be normal, even in patients with a history of severe angina, and do not rule out a diagnosis of ischemia
    • Note findings consistent with ischemic heart disease (eg, prior myocardial infarction, abnormal repolarization pattern)
      • Presence of Q waves, chronic ST segment depression (or other ST-T–wave abnormalities), or poor R-wave progression in the precordial leads may suggest prior myocardial infarction r5
    • Dynamic ST segment changes may be present in the setting of active chest pain due to ischemia
    • Can be diagnostic in patients with coronary vasospasm if characteristic transient ST segment changes are noted at the time of chest pain event and resolve with resolution of pain
    • Associated ECG abnormalities include left ventricular hypertrophy, left or right bundle branch block, preexcitation, arrhythmias, or conduction defects
  • Exercise stress testing c142
    • Exercise ECG is recommended as an alternative to noninvasive imaging tests for establishing a diagnosis in patients with angina symptoms and intermediate pretest probability of coronary artery disease who are able to exercise and have no abnormalities on resting ECG r7
      • Preferred modality; provides additional information about symptoms, heart rate and blood pressure response, presence of arrhythmias, exercise tolerance, and workload achieved, all of which have both diagnostic and prognostic relevance r7
      • Can be used when noninvasive imaging tests are unavailable
      • Less sensitive and specific in female patients r3
      • Performed on treadmill or bicycle using 12-lead ECG monitoring
      • An ECG exercise stress test is considered positive for ischemia when there is greater than or equal to 1 mm (0.1 mV) of horizontal or down-sloping ST segment depression, persisting for at least 0.06 to 0.08 seconds after the J point, in 1 or more ECG leads r3r8r11
      • Inconclusive results can be followed up using alternative stress testing with noninvasive imaging r3
      • Nondiagnostic in patients with resting ECG abnormalities that prevent interpretation of ST segment changes during stress r7
      • Contraindications to exercise stress testing: r12
        • Inability to exercise
        • Ongoing unstable angina
        • Recent (acute) myocardial infarction (less than 48 hours)
        • Decompensated heart failure
        • Acute myocarditis/pericarditis
        • Acute aortic dissection
        • Active endocarditis

Procedures

Cardiac catheterization with coronary angiography c143c144
General explanation
  • A coronary catheter is placed percutaneously in a peripheral blood vessel and advanced into central circulation
    • Femoral or radial arteries are used as access site for coronary angiography
  • Defines coronary artery anatomy and patency
  • Measures intravascular pressure, oxygen saturation in the heart and great vessels, and cardiac contractility and function
  • Coronary pressure-derived fractional flow reserve can be measured for functional assessment of lesion severity in patients with intermediate-grade stenosis without evidence of ischemia in noninvasive testing, or in those with multivessel disease r13
  • Intracoronary imaging (with intravascular ultrasonography or optical coherence tomography) may also be performed in patients being considered for revascularization to establish severity of lesions in the setting of intermediate-grade stenosis or ambiguous findings on angiography r13
  • Usually performed under conscious sedation
Indication r14
  • Myocardial infarction (ST elevation myocardial infarction, non–ST elevation myocardial infarction)
  • Unstable angina
  • Chronic stable angina not controlled by optimal medical therapy
  • Abnormal cardiac stress test result, particularly if findings are high-risk
  • Cardiac arrest
  • New congestive heart failure
  • Before cardiac surgery
Contraindications r15
  • No absolute contraindications
  • Relative contraindications
    • Preexisting renal failure
    • Contrast material allergy (anaphylaxis)
    • Coagulopathy
    • Hemodynamic instability
    • Acute stroke
    • Decompensated congestive heart failure
    • Severe, uncontrolled hypertension
    • Severe anemia
    • Pregnancy
    • Uncooperative patient
    • Active infection, sepsis
Interpretation of results
  • Coronary angiography defines coronary anatomy, including origin, course, length, diameter, and contour of epicardial coronary arteries; presence and severity of coronary artery stenoses; characteristic of obstruction; and presence and extent of any collateral flow
  • Left ventricular ejection fraction, an important prognostic indicator, can be determined
  • Wall motion and contractility can be assessed
  • Valvular function can be assessed and valvular regurgitation quantified, if present

Other diagnostic tools

  • Risk stratification r7c145
    • Identifies patients at high risk for cardiovascular death and myocardial infarction who will benefit from revascularization
    • Conducted in a stepwise fashion based on clinical evaluation, assessment of ventricular function, results of noninvasive testing, and delineation of coronary anatomy
    • Ventricular function
      • Cardiovascular mortality increases as left ventricular ejection fraction declines
        • Left ventricular ejection fraction less than 50% is associated with high risk for cardiovascular death (annual mortality greater than 3%), even without accounting for additional event risk factors r3
    • Exercise stress ECG
      • Duke Treadmill Score combines duration of exercise, severity of ST segment depression or elevation, and development of angina to stratify patients into risk groups r16
        • High risk: cardiovascular mortality greater than 3% per year
        • Intermediate risk: cardiovascular mortality from 1% to 3% per year
        • Low risk: cardiovascular mortality less than 1% per year
    • Cardiovascular imaging findings
      • High risk: r7
        • Area of ischemia greater than 10% on single photon emission CT scan
        • 2 or more segments out of 16 with new perfusion defects or 3 or more dobutamine-induced dysfunctional segments on cardiac MRI
        • 3 or more segments of left ventricle with stress-induced hypokinesia or akinesia on stress echocardiography
      • Intermediate risk: area of ischemia from 1% to 10% or any ischemia less than high risk by cardiovascular magnetic resonance or stress echocardiogram r17
      • Low risk: no ischemia
    • Coronary CT angiography findings r18
      • High risk: significant high-risk lesions (ie, 3-vessel disease with proximal stenosis, left main disease, proximal anterior descending disease)
      • Intermediate risk: significant lesions in large and proximal coronary arteries but not high-risk category
      • Low risk: normal coronary artery or plaques only
    • Invasive coronary angiography findings r11
      • Classified into 1-, 2-, or 3-vessel or left main coronary artery disease on basis of angiography
        • Probability of survival declines progressively with increased number of occluded coronary arteries and presence of severe proximal left anterior descending coronary artery disease r11

Differential Diagnosis

Most common

  • Cardiovascular conditions
    • Acute coronary syndromes d1
      • Include unstable or crescendo angina, non–ST elevation myocardial infarction, and ST elevation myocardial infarction c146c147c148
        • Typically present as retrosternal chest pain that may radiate to arms, neck, or lower jaw; may be accompanied by dyspnea, diaphoresis, nausea, syncope, or fatigue
      • Diagnosis is based on history, physical examination, ECG findings, and serum cardiac troponin levels
        • Consider acute coronary syndrome in patients presenting with anginal pain lasting more than 15 minutes r4
        • New ST segment elevation at the J point in 2 contiguous leads, persisting for 20 minutes or longer, suggests ST elevation myocardial infarction and is a medical emergency r19
        • New horizontal or down-sloping ST segment depression and T wave changes suggest non–ST elevation acute coronary syndrome
        • Unstable or crescendo angina lacks the ECG and biochemical evidence for acute myocardial necrosis but has at least 1 of the following features:
          • Occurs at rest or with minimal exertion
          • Lasts at least 20 minutes if not treated with nitroglycerin
          • Severe and new onset (within the past month)
          • Occurs in a crescendo pattern that has progressed and is more severe, prolonged, or frequent than before
    • Pulmonary embolism c149d2
      • Sudden obstruction of a portion of the pulmonary arterial vasculature, usually by embolization of a lower extremity or pelvic thrombus
      • Presents with chest pain, dyspnea, tachypnea, and hypoxia. Tachycardia and ST abnormalities on ECG, as well as an elevated cardiac troponin level, may be present
      • Chest pain is usually pleuritic; dyspnea is usually prominent and may be overwhelming; edema, tenderness, or a palpable "cord" may be present in 1 or both lower extremities, which should raise suspicion for deep vein thrombosis
      • Multidetector-row CT angiography is diagnostic for pulmonary embolism; identifies thrombus or thrombi in pulmonary vessels
    • Thoracic aortic dissection c150
      • Presents with sudden, severe chest pain that may radiate to the back. May be associated with hypotension or diaphoresis; nonspecific ECG changes and elevated cardiac troponin levels may be present
      • Pain may be characterized as tearing or ripping
      • A murmur of aortic insufficiency may be audible when the dissection extends into the aortic root; brachial or radial pulses may be asymmetrical
      • CT with contrast enhancement is diagnostic for thoracic aortic dissection. Alternate imaging modalities include MRI and transesophageal echocardiogram
    • Pericarditis (acute) c151d3
      • Inflammation of the pericardium with or without pericardial effusion
      • Typically presents as pleuritic precordial or retrosternal pain that may radiate to the back, neck, left shoulder, or arm
      • ECG often shows PR segment depression and diffuse ST segment elevation; troponin levels may be elevated
      • Pain is worse on inspiration, when supine, during swallowing, and during movement; pain is improved when seated and leaning forward
      • A pericardial friction rub is sometimes heard on auscultation
      • Echocardiography is the initial diagnostic study of choice, frequently demonstrating pericardial effusion with or without pericardial thickening
  • Noncardiac conditions
    • Cholecystitis (acute) c152d4
      • Inflammation of the gallbladder; most commonly resulting from obstruction of cystic duct by an impacted gallstone
      • Presents with epigastric pain that may be poorly localized at first, mimicking anginal pain
      • Nausea and vomiting are often prominent, and there is tenderness to palpation in the right upper quadrant
      • Right upper quadrant ultrasonography is usually diagnostic, showing an inflamed gallbladder; stones and ductal dilation may be evident
    • Pancreatitis (acute) c153d5
      • Sudden onset of pancreatic parenchymal inflammation with a disease course that can range from mild to severe
      • Presents with epigastric pain, often with radiation to the back; pain may be severe
      • Tenderness to palpation of the upper abdomen, sometimes with rebound tenderness
      • Abdominal CT or ultrasonography shows inflammation of pancreas; lipase and amylase levels are elevated
    • Peptic ulcer disease c154d6
      • Development of ulcerations in the stomach or duodenum owing to an imbalance between mucosal protective factors and various mucosal-damaging mechanisms
      • Presents with recurrent chest or epigastric pain
      • Pain is rarely related to exertion and may be improved by eating
      • May have tenderness to palpation of the upper abdomen
      • Diagnosis is confirmed on upper gastrointestinal endoscopy
    • Esophageal spasm c155
      • May present with epigastric pain or tightness, which may be relieved by sublingual nitroglycerin
      • May be precipitated by swallowing; associated with dysphagia
      • Pain is rarely related to exertion
      • Sublingual nitroglycerin and certain calcium channel blockers used to treat angina can occasionally alleviate pain due to esophageal reflux or spasm
      • Diagnosis is confirmed by manometry, which reveals premature rapid contractions, or by appearance of "corkscrew" esophagus on barium swallow
    • Costochondritis c156
      • Inflammation of costochondral junctions of ribs or chondrosternal joints
      • May present with severe pain in the sternal area
      • Characterized by exacerbation with chest motion (eg, respiration, rotation of the torso)
      • Differentiated by characteristic exacerbation with physical maneuvers and absence of ECG abnormalities

Treatment

Goals

  • Eliminate ischemic symptoms
  • Prevent major cardiac events such as myocardial infarction, heart failure, and death

Disposition

Admission criteria

Patients with symptoms suggestive of acute coronary syndrome with or without diagnostic ECG changes or elevated troponin levels

Patients with chest pain associated with hemodynamic instability or congestive heart failure

Criteria for ICU admission
  • Ongoing or refractory ischemic pain, uncontrolled arrhythmias, pulmonary edema, or hemodynamic instability

Recommendations for specialist referral

  • Consult with cardiologist for patients with symptoms suggestive of myocardial ischemia or abnormal functional testing results r4

Treatment Options

Identify and treat conditions that contribute to or complicate ischemic heart disease

Modify risk factors for ischemic heart disease to reduce risk of myocardial infarction and cardiovascular death; use both pharmacologic and nonpharmacologic methods as necessary

  • Daily low-dose aspirin is recommended in all patients with evidence of coronary artery disease r4r5
    • Clopidogrel is indicated as an alternative in case of aspirin intolerance
    • In patients at moderate or high risk of ischemic events and no increased risk of bleeding, addition of a second antiplatelet agent (eg, clopidogrel, prasugrel, ticagrelor) for long-term secondary prevention may be considered r7
    • In patients who have undergone coronary revascularization with stent placement, dual antiplatelet therapy consisting of low-dose aspirin plus antithrombotic agent should be given, typically for at least 1 month (bare metal stent) or at least 6 months (drug-eluting stent); however, a shorter duration of therapy may be considered in those at high risk or life-threatening bleeding risk, given the low risk of stent thrombosis after 1 to 3 months r20
    • Long-term therapy with ticagrelor in addition to aspirin may be beneficial in patients with diabetes who are at high risk for cardiovascular events and low risk for bleeding r21r22
  • Statins are recommended in all patients to reduce risk of myocardial infarction and ischemic stroke, regardless of baseline LDL-C levels r5r23
    • Use high-intensity statin therapy for patients who are aged 75 years or younger
      • For patients who are at very high risk, use maximally tolerated statin therapy plus ezetimibe
        • Very-high-risk patients include those with a history of multiple major atherosclerotic cardiovascular disease events (eg, acute coronary syndrome, myocardial infarction or ischemic stroke, symptomatic peripheral artery disease) or 1 major atherosclerotic cardiovascular disease event and multiple high-risk conditions
      • Consider a PCSK9 inhibitor in patients who are at very high risk and are taking maximally tolerated LDL-C–lowering medication if either of the following exists:
        • LDL-C level is 70 mg/dL or higher, or
        • Non–HDL-C level is 100 mg/dL or higher
    • Use moderate-intensity statin therapy if patient cannot receive high-intensity therapy
    • In patients older than 75 years, initiate either moderate- or high-intensity statin therapy after considering potential reduction in risk, adverse effects and interactions, and overall prognosis
  • Low-dose colchicine
    • Long-term low-dose colchicine is an effective agent for secondary prevention of chronic coronary disease; however, it is not currently part of standard therapy r24
    • Colchicine, added to standard therapy, may reduce the risk of cardiovascular death, myocardial infarction, ischemic stroke, and need for revascularization in patients with chronic coronary disease r25r26r27
    • Gastrointestinal adverse effects are common; contraindicated in patients with renal or hepatic impairment r24r25
  • Antihypertensive drug therapy, in addition to lifestyle modification, is recommended for patients with blood pressure of 130/80 mm Hg or higher r28
    • Aim for blood pressure target lower than 130/80 mm Hg
    • First line therapy should consist of medications such as ACE inhibitors (or angiotensin II receptor blockers) and β-blockers as required for other indications below
    • Add thiazide diuretics, dihydropyridine calcium channel blockers, or mineralocorticoid receptor antagonists if first line agents fail to control hypertension
  • ACE inhibitors (or angiotensin II receptor blockers) are recommended for patients who also have heart failure, hypertension, chronic kidney disease, or diabetes r11
  • Proton pump inhibitors are recommended for patients on aspirin, dual antiplatelet therapy, or oral anticoagulants who are at risk of gastrointestinal bleeding r7
  • β-blockers are recommended for patients with left ventricular dysfunction or systolic heart failure; consider in patients with previous ST elevation myocardial infarction r7

Control acute angina symptoms with sublingual nitroglycerin or short-acting nitrates

  • These agents dilate epicardial coronary arteries, thereby increasing coronary blood flow r29
  • Most patients with angina are prescribed sublingual nitroglycerin tablets or nitroglycerin spray for home use (unless contraindicated) r4r30
    • Most patients have pain relief within 5 minutes of taking 1 or 2 doses 5 minutes apart; instruct patients to seek emergency medical care if pain is not relieved after 3 doses (maximum dosage) in a 15-minute span or sooner if pain is worsening
    • Both products may be used prophylactically 5 to 10 minutes before planned activity to prevent effort-induced angina; duration of effect is 30 to 40 minutes
  • These rapid-acting formulations of nitroglycerin provide immediate relief of angina symptoms at the onset of an episode or prevent onset in situations in which it is likely to occur r7
  • Isosorbide dinitrate (short-acting) and isosorbide mononitrate (long-acting) are longer-acting nitrate formulations r7
    • Hemodynamic and antianginal effects persist for several hours, conferring longer angina prevention than sublingual nitroglycerin
    • Onset of antianginal action is slower than with sublingual nitroglycerin
  • Short-acting nitrates may cause hypotension and should be taken when patients are sitting or supine; headache is a common adverse effect
  • Do not administer a nitrate preparation or nitroglycerin in patients who have taken tadalafil in the last 48 hours or sildenafil in the last 24 hours given risk of severe hypotension; a suitable time interval for safe administration of nitrates after vardenafil has not been determinedr6r5

Institute long-term symptom control

  • β-blockers, calcium channel blockers, long-acting nitrates, ranolazine, and ivabradine appear to be equally effective at managing symptoms in patients with stable ischemic heart disease but have not been shown to reduce myocardial infarction or ischemic cardiac death in this population r2
  • Available agents decrease severity, duration, or frequency of angina, usually increasing exercise performance and time to onset of ST segment depression r29
  • β-blockers and calcium channel blockers are considered first line agents r2
    • β-blockers r5
      • Recommended as initial agents to relieve symptoms in most patients r4r5
      • Lower resting heart rate and limit heart rate rises during exercise, keeping myocardial oxygen demand below angina-producing threshold r29
      • Long-term treatment is well tolerated and reduces ischemic burden and threshold in patients with stable ischemic heart disease r5
      • Use of β-blockers in patients post–myocardial infarction and those with heart failure is associated with reduced mortality and reinfarction r2
    • Calcium channel blockers
      • Recommended as alternative first line therapy for symptom relief if adverse effects or contraindications limit use of β-blockers r5
      • All classes of calcium channel blockers are effective coronary vasodilatorsr29 and reduce anginal episodes, increase exercise duration, and reduce use of sublingual nitroglycerin in patients with effort-induced angina r5
        • In addition, nondihydropyridine calcium channel blockers (ie, diltiazem, verapamil) lower myocardial oxygen demand by lowering heart rate and depressing myocardial contractilityr29 and are generally preferred
          • In general, avoid nondihydropyridine calcium channel blockers in patients with heart failure with reduced ejection fraction owing to the drug's negative inotropic effect
        • Dihydropyridine calcium channel blockers (eg, nifedipine, amlodipine) are more suitable for patients with cardiac conduction defects such as sick sinus syndrome, sinus bradycardia, or significant arteriovenous conduction disturbances r5
    • Combination of nondihydropyridine calcium channel blocker and β-blocker may be used in selected patients with close monitoring for excessive bradycardia or signs of heart failure r7
  • Second line or add-on agents include long-acting nitrates, ranolazine, and ivabradine r2
    • Effective alternatives to first line agents r3
    • Used as monotherapy if first line agents are contraindicated or cause unacceptable adverse effects
    • Long-acting nitrate preparations can be prescribed as an add-on to β-blockers or calcium channel blockers when those medications alone are not effective in preventing angina r5
      • Formulations include nitroglycerin transdermal patch, oral isosorbide dinitrate, and oral isosorbide mononitrate r29
      • It is recommended to maintain a daily nitrate-free interval of 10 to 14 hours to avoid development of nitrate tolerance r5
    • Ranolazine or ivabradine may be used as part of combination therapy with β-blockers or calcium channel blockers when β-blockers or calcium channel blockers alone are not effective r7
    • Trimetazidine and nicorandil are alternative agents that are available in Europe but not the United States r7

Consider revascularization by percutaneous catheter–based techniques or coronary artery bypass graft

  • Decision regarding revascularization is complex and dependent on many patient and anatomic factors, including presence of significant obstructive coronary artery stenosis, amount of related ischemia, and expected benefit in terms of prognosis or symptom relief r3
    • Perform when there is clear evidence of potential to improve patient health status and/or survival
    • Decision to perform surgical or percutaneous revascularization depends on complexity of coronary anatomy according to SYNTAX score, surgical risk based on Society of Thoracic Surgeons risk score, and patient preference r8r31r32
  • Survival advantages for revascularization by coronary artery bypass graft have been well-established in patients with 50% or greater stenosis of the left main coronary artery r3
    • Revascularization provides better symptom reliefr3 but has not been shown to be superior to optimal medical therapy alone in terms of survival in patients with stable angina (excluding those with significant left main coronary artery disease), including those considered high-risk based on stress testing r2
  • European guidelines recommend revascularization to improve survival in patients with left main stenosis greater than 50%, any proximal left anterior descending artery stenosis greater than 50%, 2- to 3-vessel disease with stenosis greater than 50% and impaired left ventricular function or heart failure, last remaining patent vessel with greater than 50% stenosis, or large area of ischemic myocardium demonstrated by functional testing or abnormal fractional flow reserve r3r13
    • Revascularization to improve symptoms is recommended in patients who have hemodynamically significant coronary stenosis in the presence of limiting angina or angina equivalent that is unresponsive to optimal medical therapy r13
  • US guidelines recommend coronary artery bypass graft in preference to percutaneous coronary intervention to improve survival in patients with left main coronary artery stenosis greater than 50%, with 3-vessel coronary artery disease with or without proximal left anterior descending involvement, and with proximal left anterior descending stenosis plus significant stenosis in 1 other vessel r33
    • Percutaneous coronary intervention is a reasonable option to improve survival in selected patients with low to medium anatomic complexity of coronary artery disease or left main disease that is equally suitable for coronary artery bypass graft or percutaneous coronary intervention r33
    • Either coronary artery bypass graft or percutaneous coronary intervention is recommended for symptom improvement in patients with refractory angina despite optimal medical therapy and significant coronary artery stenosis that is amenable to revascularization r33
    • Either coronary artery bypass graft or percutaneous coronary intervention are recommended over medical therapy alone to lower the risk of adverse events such as cardiac death, myocardial infarction, or urgent revascularization in patients with multivessel coronary artery disease r33

Drug therapy

  • Rapid-acting nitrates r11
    • Nitroglycerin sublingual tablets c157
      • Nitroglycerin Sublingual tablet; Adults: 300 to 600 mcg SL 5 to 10 minutes before participating in activities that may precipitate an acute attack or at the onset of an attack; may repeat dose every 5 minutes as needed. Max: 3 tablets/15-minute period. If chest pain persists after 3 tablets in a 15-minute period, prompt medical attention should be sought.
    • Nitroglycerin spray c158
      • Nitroglycerin Sublingual/Translingual spray; Adults: 400 or 800 mcg on or under the tongue 5 to 10 minutes before participating in activities that may precipitate an acute attack or at the onset of an attack; may repeat 400 mcg every 5 minutes as needed. Max: 1,200 mcg/15-minute period. If chest pain persists after 1,200 mcg in a 15-minute period, prompt medical attention should be sought.
  • Short-acting nitrates
    • Isosorbide dinitrate c159
      • Isosorbide Dinitrate Oral tablet; Adults: 5 to 20 mg PO 2 to 3 times daily, initially. Increase dose as needed. Usual dose: 10 to 40 mg PO 2 to 3 times daily. Dose range: 10 to 480 mg/day. A daily dose-free interval of 14 hours or more is recommended to minimize tolerance.
    • Nitroglycerin topical ointment (2%) c160
      • Nitroglycerin Topical ointment; Adults: 7.5 mg (0.5 inch) topically twice daily every 6 hours, initially. May double dose in persons tolerating but failing to respond. Max: 30 mg/dose.
  • Long-acting nitrates r11
    • Isosorbide mononitrate c161
      • Immediate release
        • Isosorbide Mononitrate Oral tablet; Adults: 20 mg PO twice daily, initially, with doses given 7 hours apart. May consider 5 mg PO twice daily, initially, in persons with small stature; increase dose to at least 10 mg PO twice daily by day 2 to 3.
      • Extended release
        • Isosorbide Mononitrate Oral tablet, extended-release; Adults: 30 or 60 mg PO once daily, initially. May increase dose to 120 mg PO once daily after several days. Max: 240 mg/day, rarely needed.
    • Transdermal patch c162
      • Nitroglycerin Transdermal patch - 24 hour; Adults: 0.2 to 0.4 mg/hour transdermally for 12 to 14 hours daily with a 10 to 12 hours daily patch-off period, initially. Adjust dose based on symptoms and adverse effects. Dose range: 0.1 to 0.8 mg/hour.
  • β-blockers r11
    • Bisoprolol c163
      • Bisoprolol Fumarate Oral tablet; Adults: 5 to 20 mg PO once daily.
    • Carvedilol c164
      • Carvedilol Oral tablet; Adults: 25 to 50 mg PO twice daily.
    • Metoprolol succinate c165
      • Metoprolol Succinate Oral tablet, extended-release; Adults: 100 mg PO once daily, initially. Gradually increase the dose weekly until desired clinical response is achieved or pronounced slowing of heart rate. Max: 400 mg/day. To discontinue, decrease dose gradually over 1 to 2 weeks.
    • Metoprolol tartrate c166
      • Metoprolol Tartrate Oral tablet; Adults: 50 mg PO twice daily, initially. Gradually increase the dose weekly until desired clinical response is achieved or pronounced slowing of heart rate. Usual dose: 100 to 400 mg/day.
  • Calcium channel blockers r11
    • Nondihydropyridine calcium channel blockers
      • Verapamil
        • Verapamil Hydrochloride Oral tablet; Adults: 40 to 120 mg PO 3 times daily. Usual dose: 80 to 120 mg PO 3 times daily. Adjust dose daily or weekly until desired clinical response is achieved.
      • Diltiazem
        • Immediate release
          • Diltiazem Hydrochloride Oral tablet; Adults: 30 mg PO 4 times daily, initially. Gradually increase the dose every 1 to 2 days until desired clinical response is achieved. Usual dose: 180 to 360 mg/day in 3 to 4 divided doses.
        • Extended release
          • Diltiazem Hydrochloride Oral capsule, extended release 24 hour; Adults: 120 to 180 mg PO once daily, initially. Increase the dose every 7 to 14 days until desired clinical response is achieved. Max: 540 mg/day.
    • Dihydropyridine calcium channel blockers
      • Amlodipine
        • Amlodipine Besylate Oral tablet; Adults: 5 to 10 mg PO once daily. Usual dose: 10 mg PO once daily.
      • Nifedipine
        • Nifedipine Oral tablet, extended-release; Adults: 30 or 60 mg PO once daily, initially. Increase the dose every 7 to 14 days until desired clinical response is achieved. Usual Max: 90 mg/day. Max: 120 mg/day.
  • Other antianginal agents
    • Ranolazine c167
      • Ranolazine Oral tablet, extended-release; Adults: 500 mg PO twice daily. May increase dose to 1,000 mg PO twice daily if needed. Max: 1,000 mg PO twice daily. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
    • Ivabradine c168
      • Ivabradine Oral tablet; Adults 75 years or more: 2.5 mg PO twice daily, initially. Adjust the dose after 3 to 4 weeks and thereafter as needed based on heart rate and tolerability. Max: 7.5 mg PO twice daily. Discontinue therapy if no improvement in angina symptoms within 3 months and consider discontinuing therapy if there is only limited symptomatic response and no clinically relevant decrease in resting heart rate within 3 months.
      • Ivabradine Oral tablet; Adults 18 to 74 years: 5 mg PO twice daily, initially. Adjust the dose after 3 to 4 weeks and thereafter as needed based on heart rate and tolerability. Max: 7.5 mg PO twice daily. Discontinue therapy if no improvement in angina symptoms within 3 months and consider discontinuing therapy if there is only limited symptomatic response and no clinically relevant decrease in resting heart rate within 3 months.
  • Antiplatelet drugs r7
    • Aspirin c169
      • Aspirin Oral tablet; Adults: 75 to 162 mg PO once daily indefinitely.
    • Clopidogrel c170
      • Clopidogrel Bisulfate Oral tablet; Adults: 75 mg PO once daily.
    • Prasugrel c171
      • Prasugrel Oral tablet; Adults weighing less than 60 kg: 60 mg PO loading dose, then 5 mg PO once daily in combination with aspirin.
      • Prasugrel Oral tablet; Adults weighing 60 kg or more: 60 mg PO loading dose, then 10 mg PO once daily in combination with aspirin.
    • Ticagrelor c172
      • Ticagrelor Oral tablet; Adults: 180 mg PO loading dose, then 90 mg PO twice daily in combination with low-dose aspirin. Reduce dose to 60 mg PO twice daily in combination with low-dose aspirin after 1 year.
  • ACE inhibitors
    • Lisinopril c173c174c175c176
      • Lisinopril Oral tablet; Adults: 10 mg PO once daily, initially. May increase dose if further control is needed. Usual dose range: 10 to 40 mg/day. Max: 80 mg/day.
    • Ramipril c177c178c179c180
      • Ramipril Oral capsule; Adults: 2.5 mg PO once daily, initially. May increase dose if further control is needed. Usual dose: 2.5 to 20 mg/day in 1 to 2 divided doses.
  • Angiotensin II receptor blockers
    • Irbesartan c181c182c183c184
      • Irbesartan Oral tablet; Adults: 150 mg PO once daily, initially. May increase dose to 300 mg PO once daily if further control is needed.
    • Losartan c185c186c187c188
      • Losartan Potassium Oral tablet; Adults: 50 mg PO once daily, initially. May increase dose to 100 mg/day in 1 to 2 divided doses if further control is needed.
    • Telmisartan c189c190c191c192
      • Telmisartan Oral tablet; Adults: 40 mg PO once daily, initially. May increase dose if further control is needed. Dose range: 20 to 80 mg/day.
  • Statins
    • Atorvastatin c193
      • Atorvastatin Calcium Oral tablet; Adults: 10 to 20 mg PO once daily. May start at 40 mg once daily for greater than 45% LDL-reduction. Range: 10 to 80 mg once daily.
    • Pitavastatin c194
      • Pitavastatin Calcium Oral tablet; Adults: 2 mg PO once daily. Analyze lipid concentrations 4 weeks after initiation or dosage titration. Max: 4 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
    • Pravastatin
      • Pravastatin Sodium Oral tablet; Adults: 40 to 80 mg PO once daily. Max: 80 mg/day. Assess LDL-C 4 to 12 weeks after initiation or dose adjustment; adjust dosage as needed. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
    • Rosuvastatin c195
      • Rosuvastatin Calcium Oral tablet; Adults: 10 mg PO once daily; 5 mg once daily may be used for less aggressive LDL-reduction, patients with CrCl less than 30 mL/minute, higher risk for myopathy, or for Asian patients. Dose range: 5 to 40 mg once daily. Consider 20 mg once daily for marked hypercholesterolemia (LDL more than 190 mg/dL). Reserve 40 mg/day for insufficient response; 40 mg/day has been associated with higher risk of myopathy. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
    • Simvastatin c196
      • Simvastatin Oral tablet; Adults: Initially, 10 to 20 mg PO at bedtime. In patients with CHD, risk factors for CHD, or familial homozygous hypercholesterolemia, starting dose is 40 mg PO once daily in the evening. Usual dosage range: 5 to 40 mg/day PO. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Only use 80 mg in patients who have been taking 80 mg chronically without myopathy.
  • Nonstatin lipid-lowering agents
    • Ezetimibe r23c197
      • Ezetimibe Oral tablet; Adults: 10 mg PO once daily.
    • Proprotein convertase subtilisin/kexin type 9 (PCSK9) serine protease inhibitors
      • Evolocumab r34c198
        • Evolocumab Solution for injection; Adults: 140 mg subcutaneously every 2 weeks or 420 mg subcutaneously once monthly.
      • Alirocumab r35c199
        • Alirocumab Solution for injection; Adults: 75 mg subcutaneously every 2 weeks or 300 mg subcutaneously every 4 weeks. Measure LDL-C prior to next dose for persons receiving 300 mg subcutaneously every 4 weeks and otherwise as clinically appropriate. May adjust dose to 150 mg subcutaneously every 2 weeks for inadequate LDL-C response.
  • Colchicine
    • Colchicine Oral tablet; Adults: 0.5 mg PO once daily. Optimal duration is not defined.

Nondrug and supportive care

Smoking cessation r36c200d4

Nutrition c201

  • Modify nutrition counseling based on individual patient factors (eg, lipid profile, blood pressure, required caloric intake, alcohol intake)
  • Emphasize intake of vegetables, fruits, nuts, whole grains, lean vegetable or animal protein, and fish r37
  • Minimize intake of trans fats, red meat and processed red meats, refined carbohydrates, and sweetened beverages r37

Weight management r36c202

  • BMI goal is 18.5 to 24.9 kg/m²; waist circumference goal is less than 89 cm for females and less than 102 cm for males
  • If weight loss is required, initial weight loss goal should be 5% to 10% below baseline

Physical activity c203

  • Before discharge from acute care setting, provide patient with instructions on specific activity recommendations (eg, lifting, stair climbing, housework, yard work, sexual activity)
  • Goal is 30 to 60 minutes of moderate intensity aerobic activity for 5 to 7 days per week; supplement with 2 days of resistance training r36
  • Counsel patients to report exercise-associated symptoms

Prevention of infectious diseases r38

  • Pneumococcal vaccine is recommended for high-risk patients who have cardiovascular disease and are older than 65 years c204
  • Yearly influenza vaccine is recommended for patients with cardiovascular disease r8c205
    • Influenza vaccination in patients with high-risk coronary heart disease has been shown to lower the risk of all-cause death and cardiovascular death r39
Procedures
Percutaneous coronary intervention c206
General explanation
  • Invasive therapeutic technique in which a catheter is guided via the radial artery (preferred) or femoral artery to the stenosed or occluded coronary artery (or arteries) for the purpose of alleviating lesion(s) and revascularizing myocardial tissue
  • Techniques include:
    • Percutaneous transluminal coronary angioplasty (balloon dilation) r40c207
    • Intracoronary stenting r40
      • Bare metal stent c208
      • Drug-eluting stent c209
        • Thought to reduce restenosis and improve clinical outcomes; typically first line approach r41
    • Atheroablative technologies (eg, atherectomy) r40c210
  • Currently, 80% to 85% of percutaneous coronary interventions involve balloon dilation and coronary stenting r42
Indication
  • Decision regarding revascularization in stable ischemic heart disease is complex and dependent on many patient and anatomic factors, including presence of significant obstructive coronary artery stenosis, amount of related ischemia, and expected benefit in terms of prognosis and/or symptom relief
  • Revascularization may be indicated in patients with flow-limiting coronary stenoses and symptoms that persist despite optimal medical therapy and/or potential for improvement of prognosis
  • A multidisciplinary (heart team) approach to revascularization decisions is recommended when optimal revascularization strategy is not straightforward
    • Both an interventional cardiologist and a cardiac surgeon should review patient's medical condition and coronary anatomy, determine whether percutaneous coronary intervention and/or coronary artery bypass graft are technically feasible and reasonable, and discuss revascularization options with the patient before selecting a treatment strategy
  • Refer to published guidelines, including those from the American College of Cardiology (2017) or the European Society of Cardiology and European Association for Cardio-Thoracic Surgery (2018), for detailed indications r13r14
Contraindications
  • Percutaneous coronary intervention to improve survival should not be performed in stable patients with significant (greater than 50% diameter stenosis) unprotected left main coronary artery disease who have anatomy unfavorable to this intervention and who are good candidates for coronary artery bypass graft (preferred approach) r33
  • May not be appropriate for patients with certain comorbidities (eg, chronic kidney disease, diabetes) in whom coronary artery bypass graft surgery is associated with better outcomes among patients with an acceptable surgical risk
  • Percutaneous coronary intervention with coronary stenting (ie, bare metal or drug-eluting stents) should not be performed if the patient is not likely to be able to tolerate and comply with dual antiplatelet therapy for the duration of treatment appropriate to the type of stent implanted r33
Complications
  • Myocardial infarction
  • Arrhythmia
  • Stroke
  • Reaction to contrast material
  • Vascular perforation or dissection
  • Emergent coronary artery bypass graft
  • Death
Coronary artery bypass graft surgery c211c212c213
General explanation
  • Open surgical procedure in which an artery (ie, internal mammary artery) or a vein (ie, saphenous vein) is grafted around the occluded portion of the coronary artery or arteries for the purpose of revascularizing the affected myocardial tissue r43
Indication
  • Decision regarding revascularization in stable ischemic heart disease is complex and dependent on many patient and anatomic factors, including presence of significant obstructive coronary artery stenosis, amount of related ischemia, and expected benefit in terms of prognosis and/or symptom relief
  • Revascularization may be indicated in patients with flow-limiting coronary stenoses and symptoms that persist despite medical treatment
  • Coronary artery bypass graft is indicated to improve survival in patients with significant (greater than 50% diameter stenosis) left main coronary artery stenosis, 3-vessel coronary artery disease with or without proximal left anterior descending coronary artery involvement, and proximal left anterior descending coronary artery stenosis plus significant stenosis in 1 other vessel r33
  • Coronary artery bypass graft surgery may be preferred over percutaneous coronary intervention in patients with certain comorbidities (eg, chronic kidney disease, diabetes)
  • A multidisciplinary (heart team) approach to revascularization decisions is recommended when the optimal revascularization strategy is not straightforward
    • Both an interventional cardiologist and a cardiac surgeon review patient's medical condition and coronary anatomy, determine whether percutaneous coronary intervention and/or coronary artery bypass graft are technically feasible and reasonable, and discuss revascularization options with the patient before selecting a treatment strategy
  • Refer to published guidelines, including those from the American College of Cardiology (2017), American College of Cardiology/American Heart Association/ for Cardiovascular Angiography and Interventions (2021), or the European Society of Cardiology and European Association for Cardio-Thoracic Surgery (2018), for detailed indications r13r14r33
Complications
  • Myocardial infarction
  • Arrhythmia
  • Neurologic abnormalities
  • Stroke
  • Renal dysfunction
  • Sternal infection
  • Death

Comorbidities

  • Diabetes c214
    • Use β-blockers with caution
      • Vasodilating β-blockers (carvedilol, labetalol, nebivolol) may be preferable as these have fewer metabolic effects in patients with type 2 diabetes r44
    • Sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists are the recommended oral antihyperglycemic agents in patients with type 2 diabetes, as these have been shown to reduce major adverse cardiac events and hospitalization from heart failure r7r44
    • Ranolazine has glucose-lowering effect, particularly in patients with poorly controlled type 2 diabetes r44
  • Heart failure r5c215
    • β-blockers may simultaneously confer a symptomatic benefit for patients with angina and a mortality benefit for patients with heart failure
      • Use with caution and only in patients in a compensated state owing to the negative inotropic effect
      • Metoprolol succinate, carvedilol, and bisoprolol are FDA approved for patients with congestive heart failure
    • In general, avoid nondihydropyridine calcium channel blockers in patients with heart failure with reduced ejection fraction owing to the drug's negative inotropic effect
  • Hypertension r28c216
    • Antihypertensive drug therapy, in addition to lifestyle modification, is recommended for patients with blood pressure of 130/80 mm Hg or higher
    • Aim for blood pressure target lower than 130/80 mm Hg
    • First line therapy should consist of medications such as ACE inhibitors (or angiotensin II receptor blockers) and β-blockers as required for other indications
    • Add thiazide diuretics, dihydropyridine calcium channel blockers, or mineralocorticoid receptor antagonists if first line agents fail to control hypertension
  • Atrial fibrillation c217
    • Use of aspirin in combination with oral anticoagulant therapy for atrial fibrillation increases risk for major bleeding compared to either agent alone with no additional reduction in risk of stroke or cardiovascular events in patients with stable ischemic heart disease r45r46
    • For patients that meet criteria for anticoagulation (CHADS VASc score greater than or equal to 2) monotherapy with either warfarin (INR target of 2-3) or a direct-acting oral anticoagulant is recommended r46r47
  • Peripheral vascular disease c218
    • Mild peripheral vascular disease: there is no contraindication for use of β-blockers or calcium channel blockers
    • Severe peripheral vascular disease and pain during rest: calcium channel blockers are preferred; avoid β-blockers
  • Bradyarrhythmias r5c219
    • Use β-blockers with caution in patients with significant bradyarrhythmias
    • Use diltiazem and verapamil (ie, nondihydropyridine calcium channel blockers) with caution in patients with significant bradyarrhythmias
    • Exercise caution when using concomitant β-blockers and heart rate–limiting calcium channel blockers (ie, diltiazem, verapamil) owing to their combined effects impairing conduction across the atrioventricular node; this is a frequent cause of hospitalization in older adult patients
  • Ischemic dilated cardiomyopathy c220
    • Calcium channel blockers may relieve angina, although they have not been found to confer a mortality benefit in this population
    • In general, avoid nondihydropyridine calcium channel blockers in patients with heart failure with reduced ejection fraction owing to the drug's negative inotropic effect r5
  • Asthma c221
    • Avoid β-blockers owing to their potential exacerbation of bronchospasm in patients prone to wheezing and bronchoconstriction r48r49
  • Migraine c222
    • β-blockers and calcium channel blockers may be beneficial r50
    • Nitrates may worsen headaches
  • Use of amphetamines and/or cocaine r51c223c224d7
    • β-blockers may allow unopposed α-adrenergic effects of these drugs, which may lead to significant vasospasm
    • Consider using calcium channel blockers

Special populations

  • Patients with vasospastic (Prinzmetal) angina r7
    • Calcium channel blockers and long-acting nitrates are first line agents for preventive treatment
    • All patients should also achieve optimal coronary risk factor control, in particular through smoking cessation and aspirin
  • Patients with refractory angina
    • Defined as symptoms caused by established reversible ischemia that last for at least 3 months and are not controlled by escalating medical therapy, bypass grafting, or percutaneous coronary intervention
    • Certain patients may be candidates for novel treatments such as: r7
      • Enhanced external counterpulsation r11
      • Coronary sinus constriction
      • Spinal cord stimulation

Monitoring

  • During the first year of medical therapy, follow-up evaluations every 4 to 6 months are recommended. After the first year of therapy, evaluations every 6 to 12 months are recommended if the patient is stable r5c225c226
    • Follow-up evaluation r52
      • Assessment of symptoms and clinical function
      • Monitoring of cardiac risk factors
      • Assessment of the adequacy of and adherence to recommended lifestyle changes and medical therapy
      • Surveillance for complications of stable ischemic heart disease, including heart failure and arrhythmias
    • Resting 12-lead ECG is indicated at least annually in patients with stable ischemic heart disease, as well as at the time of any clinical change c227
    • In patients not known to have diabetes mellitus, measure fasting blood glucose every 3 years to detect new-onset diabetes mellitus c228
    • In patients with established diabetes mellitus, measure glycosylated hemoglobin at least annually to assess glycemic control
    • Obtain a lipid profile annually c229
    • Obtain measurements of hemoglobin, thyroid function, serum electrolytes, and renal function annually or as prompted by clinical findings c230c231c232c233
    • Standard exercise ECG, imaging stress tests, or coronary CT angiography are not routinely indicated as part of follow-up assessment in patients with stable ischemic heart disease with no change in clinical status or with worsening of symptoms r52c234c235c236
    • Assessment of left ventricular ejection fraction and segmental wall motion by echocardiography or radionuclide imaging is recommended for patients with new or worsening heart failure or evidence of interval myocardial infarction by history or ECG r52c237c238c239c240c241c242
    • Echocardiography to assess left ventricular function, valvular status, and cardiac dimensions, and noninvasive stress imaging to assess for silent ischemia may be considered for asymptomatic patients every 3 to 5 years r7
  • Patients who have undergone revascularization with either percutaneous coronary intervention or coronary artery bypass graft within 6 months should be monitored according to the percutaneous coronary intervention and coronary artery bypass graft guidelines r33
  • Patients with stable ischemic heart disease who have accelerating symptoms or decreasing functional capacity require prompt reassessment

Complications and Prognosis

Complications

  • Myocardial infarction c243
  • Left ventricular dysfunction and failure c244c245
  • Arrhythmias c246
  • Death c247

Prognosis

  • Prognosis is worse in patients with microvascular disease, severe proximal left anterior descending artery disease, 2-vessel disease, left main coronary artery disease, and 3-vessel disease who have reduced left ventricular function and/or diabetes r4r53
  • Patients with poor exercise capacity and those with evidence of severe ischemia at low workload are at higher risk of mortality r4r53
  • Prognosis is also influenced by age and coexisting medical conditions such as heart failure, cerebrovascular disease, diabetes mellitus, and chronic kidney disease r5
    • Smoking, hypertension, dyslipidemia, family history of premature coronary artery disease, obesity, and sedentary lifestyle confer a greater risk of complications
    • Depression, stress, and poor social support also have been demonstrated to be strongly and independently associated with increased mortality

Screening and Prevention

Screening

At-risk populations

  • Patients with severe hypercholesterolemia (LDL-C levels of 190 mg/dL or higher), adults with diabetes, and adults aged 40 to 75 years r23

Screening tests

  • Screen to identify candidates who may benefit from lifestyle or pharmacologic interventions (lipid-lowering therapy) aimed at reducing cardiovascular risk r23
    • Evaluate adults without preexisting atherosclerotic cardiovascular disease every 4 to 6 years with tests that measure traditional cardiovascular risk factors
      • Fasting blood glucose (or other assessment of diabetes) c248
      • Total and HDL-C c249c250
      • Blood pressure c251
      • Question regarding tobacco use c252
    • Based on these, estimate 10-year cardiovascular risk using the ASCVD Risk Predictor Plus r23r54r55
  • Coronary artery calcium score is the best imaging measure of risk in asymptomatic patients r56
    • Consider CT coronary artery calcium scoring in asymptomatic patients with an intermediate or high risk of coronary artery disease
    • Not usually indicated in asymptomatic patients with low risk of coronary artery disease
  • CT angiogram of the coronary arteries is an alternative for imaging asymptomatic patient with a high risk of coronary artery disease r56

Prevention

  • Control modifiable risk factors for coronary artery disease such as:
  • Specific prevention recommendations are available in a clinical practice guideline from the American College of Cardiology/American Heart Association r37
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