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Jun.08.2022

Acute Coronary Syndromes

Synopsis

Key Points

  • Acute coronary syndromes are several potentially life-threatening conditions associated with acute myocardial ischemia and/or infarction that most commonly result from a sudden decrease in coronary blood flow precipitated by acute thrombosis secondary to a rupture or eroded atherosclerotic coronary plaque
    • Syndromes include ST-elevation myocardial infarction, non–ST-elevation myocardial infarction, and unstable angina
  • Syndromes typically present as retrosternal chest pain that may radiate to the arms, neck, and/or lower jaw; may be accompanied by dyspnea, diaphoresis, nausea, syncope, and fatigue
  • Diagnosis is based on history, physical examination, ECG, and cardiac troponin levels
  • Treatment consists of the following:
    • Initial care includes administration of supplemental oxygen, aspirin, nitrates, IV morphine, a β-blocker (or calcium channel blocker), an ACE inhibitor (or angiotensin receptor blocker), and a statin
    • Antithrombotic therapy is a cornerstone of treatment and is composed of long-term antiplatelet therapy and short-term anticoagulation therapy
    • Therapeutic reperfusion is the treatment of choice in most patients with ST-elevation myocardial infarction
      • Preferred option is percutaneous coronary intervention; alternative treatments include fibrinolytic therapy or coronary artery bypass graft
    • Patients with non–ST-elevation myocardial infarction/unstable angina may be treated using an early invasive strategy (angiography and percutaneous coronary intervention) or an ischemia-guided strategy
      • Early invasive strategy is recommended for patients with uncontrolled pain, arrhythmia, or hypotension, or patients with other risk factors suggesting a high likelihood of further cardiac events
      • Ischemia-guided strategy is recommended for patients assessed as low risk (eg, TIMI score of 1 or less, GRACE score less than 109, troponin levels within the reference range), especially females r1
        • May also be more appropriate for patients in whom other clinical conditions (eg, severe comorbidities) or personal considerations apply
  • Comorbidities that may affect treatment include diabetes, heart failure, and chronic kidney disease
  • Complications include cardiogenic shock, severe heart failure, right ventricular infarction, mechanical complications, electrical complications, pericarditis, thromboemboli, bleeding, and acute kidney injury
  • Prognosis varies based on ST-elevation status; overall, 6-month mortality is 12% to 13%; secondary prevention is key to prognosis r1

Urgent Action

  • Timeliness is essential for the treatment of acute coronary syndromes; time from symptom onset to presentation dictates management strategy, particularly in patients with ST-elevation myocardial infarction in whom reperfusion by percutaneous coronary intervention should be achieved within 120 minutes from first medical contact or fibrinolytic therapy should be started within 30 minutes r2

Pitfalls

  • Failure to institute therapeutic intervention within appropriate time frame
  • Failure to identify and treat life-threatening complications (eg, cardiogenic shock, rupture of cardiac structures, life-threatening ventricular arrhythmias)
  • Failure to consider a cardiac cause of chest pain when gastrointestinal medications relieve pain

Terminology

Clinical Clarification

  • Acute coronary syndromes are several potentially life-threatening conditions associated with acute myocardial ischemia and/or infarction that result from a sudden decrease in coronary blood flow or an increase in myocardial demand that exceeds perfusion r3

Classification

  • Acute coronary syndromes represent a spectrum of disease, including ST-elevation myocardial infarction, non–ST-elevation myocardial infarction, and unstable angina; r3
    • Atherosclerotic coronary artery obstruction is often, but not always, present
    • MINOCA (myocardial infarction in the absence of obstructive coronary artery disease) is found in 5% to 6% of all patients undergoing coronary angiography r4
    • Acute myocardial infarction
      • Acute myocardial injury with clinical evidence of acute myocardial ischemia and detection of rise and/or fall of cardiac troponin values with at least 1 value above the 99th percentile upper reference limit, plus at least 1 of the following:
        • Symptoms of myocardial ischemia
        • New ischemic ECG changes
        • Development of pathologic Q waves
        • Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in pattern consistent with ischemic cause
        • For some types of myocardial infarction, identification of a coronary thrombus by angiography or autopsy
      • There are 2 types of acute myocardial infarction: r5
        • Acute ST-elevation myocardial infarction
          • Transmural ischemia and myocardial necrosis (infarction) associated with release of chemical biomarkers and characterized by ECG changes that include ST-segment elevation or new left bundle branch block, followed by development of pathologic Q waves
        • Acute non–ST-elevation myocardial infarction
          • Myocardial ischemia and necrosis (infarction) associated with the release of chemical biomarkers, but without ECG changes associated with ST-elevation myocardial infarction
    • Unstable angina r3
      • New onset of symptomatic myocardial ischemia or change in pattern of myocardial ischemia (eg, occurring with increasing frequency, duration, or intensity; with less exertion; or at rest)
        • ECG and chemical evidence of acute myocardial necrosis are absent
  • Myocardial infarction (ST-elevation myocardial infarction or non–ST-elevation myocardial infarction) is further classified, by cause, as follows: r5
    • Type 1: spontaneous myocardial infarction
      • Caused by atherothrombotic coronary artery disease and usually precipitated by atherosclerotic plaque disruption (rupture or erosion)
    • Type 2: secondary to ischemic imbalance
      • Condition other than coronary artery disease (eg, coronary artery spasm, coronary embolus, arrhythmia, anemia, hypotension, respiratory failure) creates an imbalance between myocardial oxygen supply and demand
    • Type 3: results in death; biomarkers are unavailable
      • Death in the context of symptoms consistent with myocardial ischemia, but without documented release of chemical biomarkers
    • Type 4a: related to percutaneous coronary intervention
      • Elevated cardiac biomarker levels associated with at least 1 of the following: new ischemic ECG changes, new pathologic Q waves, imaging evidence of new loss of viable myocardium or new regional wall motion abnormality, or angiographic findings demonstrating flow-limiting complication
    • Type 4b: related to stent thrombosis
      • Detected by angiography or autopsy in the context of myocardial ischemia and release of cardiac biomarkers
    • Type 4c: in-stent restenosis, or restenosis after balloon angioplasty in the infarct territory
      • May be the only angiographic explanation when no other culprit lesion or thrombus can be identified
    • Type 5: related to coronary artery bypass grafting
      • Elevation of cardiac biomarker levels associated with new pathologic Q waves or left bundle branch block, angiographically demonstrated coronary artery occlusion, or other imaging showing new loss of myocardium or regional wall motion abnormality

Diagnosis

Clinical Presentation

History

  • Obtaining a thorough history of presenting symptoms, as well as previous similar episodes and known risk factors, is essential
  • Pain c1
    • Usually characterized as substernal pressure or tightness;r6 varies in intensity, but may increase in crescendolike pattern to become very severe, especially in ST-elevation myocardial infarction c2
    • May be bilateral or unilateral, but occurs more commonly on left side
    • May radiate to left or right arm, both arms, neck, or lower jaw r6c3c4c5
    • May be associated with diaphoresis, dyspnea, nausea, vomiting, fatigue, or syncope r6c6c7c8c9c10c11
    • May be precipitated by exertion but may also occur at rest c12c13
    • There is disagreement over the diagnostic significance of relief with nitroglycerin; typical pattern involves prompt relief within several minutes of taking sublingual nitroglycerin c14
    • Duration usually exceeds 10 minutesr3 and may last for hours, especially in ST-elevation myocardial infarctionr7
    • May be absent; may be atypical in nature or distribution
      • Atypical presentations are more common in patients aged 75 years or older, in females, and in patients with diabetes, chronic kidney disease, or dementia r1
    • Characteristics that suggest nonischemic pain include: r1
      • Pleuritic in nature c27
      • Predominantly located in mid or lower abdomen c28c29
      • Localized by fingertip c30
      • Reproducible by palpation or movement c31c32
      • Brief duration (eg, seconds) or continuous for more than 24 hoursr6c33
      • Most severe at onset c34
      • Radiation to legs c35c36
      • Sharp or stabbing quality r6c37c38

Physical examination

  • Findings may be unremarkable, especially with non–ST-elevation myocardial infarction and unstable angina c39
  • Appearance may be pale or diaphoretic; patient may be anxious c40c41c42
  • Heart rate may be within the reference range, low, or rapid c43c44c45
  • Blood pressure may be within the reference range, elevated (owing to pain), or low (owing to cardiogenic shock) c46c47c48
  • Respiratory rate is usually within the reference range, but it may be elevated in patients with extensive infarction and heart failure; Cheyne-Stokes respiration may occur in heart failure or cardiogenic shock c49c50c51
  • Jugular venous distention may indicate heart failure or right ventricular infarction c52
  • Heart tones are often muffled. An S₄ is common; an S₃ may be audible in patients with heart failure, either preexisting or resulting from acute left ventricular dysfunction due to ischemia or infarction c53c54c55
  • A new or worse systolic murmur may indicate papillary muscle ischemia or rupture c56
  • Fine rales may be heard in patients with heart failure or cardiogenic shock c57

Causes and Risk Factors

Causes

  • Coronary thrombosis, precipitated by disruption of atheromatous plaque (most common) c58
  • Other ischemic causes
    • Nonthrombotic causes of partial or complete obstruction to coronary blood flow (eg, embolus, spasm) c59c60c61
    • Other conditions in which myocardial oxygen supply cannot meet demand (eg, arrhythmia, thyrotoxicosis, hypotension, anemia, respiratory failure, overexertion) c62c63c64c65c66c67c68
    • Cocaine and methamphetamine cause acute coronary syndromes through superimposed myocardial demand; cocaine also induces coronary thrombosis, arterial dissection, coronary artery spasm, and direct myocardial toxicity r1c69c70
    • Spontaneous coronary artery dissection r8c71
      • Epicardial coronary artery dissection not associated with atherosclerosis or trauma; not iatrogenic
      • May be a cause of 1% to 4% of acute coronary syndromes cases overall; most common cause of pregnancy-associated myocardial infarction r8
    • Patients with ischemic myocardial infarction but no angiographic obstructive coronary artery disease (at least 50% diameter stenosis in a major epicardial vessel) are described as having MINOCA; prevalence estimated to be about 6% among patients diagnosed with myocardial infarction r4r5

Risk factors and/or associations

Age
  • Uncommon before age 40 years in males and 50 years in females; risk then rises progressively r3c72c73c74c75c76c77c78
  • Average age of first myocardial infarction is 65.6 years in males and 72 years in females r9c79c80
  • Average age of females with spontaneous coronary artery dissection ranges from 45 to 53 years r8c81
Sex
  • More common in males than in females r10c82c83
  • Myocardial infarction with nonobstructive coronary arteries is more common in females r5
  • Spontaneous coronary artery dissection occurs overwhelmingly in females r8c84c85
Genetics
  • Positive family history is associated with increased risk c86c87
Ethnicity/race
  • Recent prevalence data for myocardial infarction in the United States r9
    • Non-Hispanic White population: 4% for males, 2.2% for females c88c89
    • Non-Hispanic Black population: 4% for males, 2.2% for females c90c91
    • Hispanic population: 3.4% for males, 2% for females c92c93
Other risk factors/associations
  • Previous myocardial infarction, angina, or revascularization c94c95c96
  • Use of NSAIDs (except aspirin) or cyclooxygenase-2 inhibitors c97c98
  • Use of antineoplastic or immunosuppressive therapy c99c100
  • Peripheral artery disease c101
  • Cerebrovascular disease c102
  • Other risk factors and associations generally reflect those of coronary artery disease

Diagnostic Procedures

Primary diagnostic tools

  • Primary means of diagnosis are history, physical examination, ECG, and serum biomarkers c113c114
    • Features of history and physical examination that correlate with a high likelihood of acute coronary syndromes include: r11
      • Chest or left arm pain or discomfort that reproduces symptomatic character of previously documented angina
      • Known history of coronary artery disease
      • New mitral regurgitation murmur
      • Hypotension
      • Diaphoresis
      • Rales or pulmonary edema
    • Always consider a cardiac cause of chest pain even if gastrointestinal medications relieve pain
  • All patients with symptoms suggestive of acute coronary syndromes should have a 12-lead ECG performed within 10 minutes of presentation r1
    • If the initial ECG result is not diagnostic and the patient continues to experience symptoms, an ECG should be repeated at 15- to 30-minute intervals within the first hour r1
    • Serial ECG tests are also helpful in following evolution of ischemic process
    • Supplemental leads should be applied if posterior or inferior infarction is suspected and if 12-lead ECG is not diagnostic
    • Normal ECG results do not preclude diagnosis of acute coronary syndromes; normal tracing results are seen in 1% to 6% of cases r1
  • Draw blood from all patients at presentation with symptoms suggestive of acute coronary syndromes to measure cardiac biomarkers r1
    • Cardiac-specific troponin levels (T or I) are highly sensitive and specific; they are the preferred diagnostic biomarker for initial testing c115c116
  • Obtain a chest radiograph for all patients c117
  • Choice of other studies is guided by whether the ECG changes suggest ST-elevation myocardial infarction or non–ST-elevation myocardial infarction/unstable angina; in the latter case, also guided by validated risk assessment tools such as the TIMI score (Thrombolysis in Myocardial Infarction)r12 and the GRACE score (Global Registry of Acute Coronary Events)r13
    • Coronary angiography is recommended for most patients with ST-elevation myocardial infarction or high-risk non–ST-elevation myocardial infarction/unstable angina r1r2
      • Coronary angiography is essential for visualizing the coronary anatomy and distribution and for locating and quantifying intraluminal blockages; in many cases, it can be coupled with therapeutic intervention (reperfusion) r1
      • Immediate coronary angiography (ie, within 90-120 minutes) is recommended when percutaneous intervention is available, such as in: r1
        • ST-elevation myocardial infarction r2
        • Unstable non–ST-elevation myocardial infarction/unstable angina with: r1
          • Refractory ischemic pain
          • Heart failure
          • New or worsening mitral regurgitation
          • Hemodynamic instability
          • Sustained ventricular arrhythmias
      • Early coronary angiography (ie, within 24 hours) is recommended in patients with non–ST-elevation myocardial infarction/unstable angina who are at intermediate or high risk, as follows: r1
        • TIMI score:r14 3 or more
        • GRACE score:r13 more than 140
        • Elevated troponin levels demonstrating rise or fall
        • New ST depression
      • For patients with non–ST-elevation myocardial infarction who are stable, coronary angiography may be delayed or deferred unless a new ischemic event occurs r1
    • Other early imaging studies such as echocardiography and radionuclide testing may be helpful in localizing the area of ischemia or injury, assessing the extent of injury, and evaluating possible alternative diagnoses r5
    • CT angiography or stress testing can be used to further evaluate patients in whom an acute coronary syndrome was initially suspected but whose ECGs and troponin levels are not diagnostic r1c118c119

Laboratory

  • Troponin I or T levels should be obtained at presentation and at 3 to 6 hours after onset of symptoms if using sensitive assays;r1time intervals can be shortened with the use of highly sensitive cardiac troponin assaysr15c120c121
    • Algorithms to include or exclude acute myocardial infarction have been developed for screening of patients presenting with chest pain based on consecutive high-sensitivity troponin levels measured at 0 and either 1, 2, or 3 hours r15r16
    • Both peak level and degree of change are diagnostically important
    • Criteria for a laboratory diagnosis of myocardial necrosis include: r5
      • Troponin I or T levels above the 99th percentile of the upper norm, plus a serial increase or decrease of at least 20% of an elevated level
      • For troponin I or T levels that do not exceed the 99th percentile, a change of 3 standard deviations or more from the initial value is diagnostic
    • Further levels should be obtained if interim symptoms or ECG changes suggest ongoing ischemia
  • Creatine kinase–MB (myocardial band) fraction (formerly the diagnostic biomarker of choice) is not as sensitive as troponin and is not commonly used diagnostically, but because of its shorter half-life, it is sometimes useful in assessing the magnitude of the infarct and in detecting early extension of an infarct before existing troponin elevation has declined r17c122
  • B-type natriuretic hormone measured at presentation or shortly thereafter provides a baseline against which subsequent levels can be compared to gain prognostic information and to help guide therapy r3c123
    • Rise in level of B-type natriuretic hormone is associated with worse prognosis
  • Fasting lipid profile is recommended, preferably within 24 hours of admission, to assess for dyslipidemia r1r2c124

Imaging

  • Obtain a chest radiograph as a baseline for subsequent comparison and to assess for pulmonary vascular congestion r17c125
  • Echocardiography is recommended to evaluate regional and global left ventricular function and to evaluate differential diagnoses r15c126
    • Regional wall motion abnormalities seen on echocardiogram may provide indirect evidence and localization of ischemia or necrosis (eg, in patients with nondiagnostic ECG or in whom cardiac biomarkers were not measured) r2
    • Additionally, echocardiography is often used early during the post–myocardial infarction period to assess left ventricular function, an important prognostic indicator
  • Radionuclide imaging can be used to assess wall motion, but it also reliably detects loss of myocardial tissue viability r15c127
    • Useful means of diagnosing myocardial necrosis when biomarkers have not been measured
    • Can also be used to exclude a diagnosis of myocardial infarction when normal function and viability are demonstrated
  • CT angiography is recommended as a reasonable means of excluding acute coronary syndrome in patients with a low to intermediate likelihood of coronary artery disease and whose ECG and troponin levels are not diagnostic r1r15c128

Functional testing

  • ECG r5c129
    • Always compare ECG with a previous tracing if available
    • If inferior myocardial infarction is suspected, apply right-sided leads V4R, V5R, and V6R and posterior leads V7 to V9, in addition to traditional leads
    • ECG patterns
      • New ST-segment elevation at the J point of 2 contiguous leads, persisting for 20 minutes or longer, suggests ST-elevation myocardial infarction r5
        • Cut point of 1 mm or greater in all leads other than V2 and V3, where the following cut points apply: r5
          • 2 mm or greater in males aged 40 years or older
          • 2.5 mm or greater in males younger than 40 years
          • 1.5 mm or greater in females regardless of age
        • May be preceded by hyperacute T waves
        • Reciprocal ST-segment depression may be observed
      • New horizontal or down-sloping ST-segment depression and T-wave changes suggest non–ST-elevation acute coronary syndrome r5
        • Criteria are as follows:
          • 0.5 mm or greater ST-segment depression in 2 contiguous leads and/or T-wave inversion 0.1 mV or higher in 2 contiguous leads with prominent R wave or R/S ratio greater than 1 r5
    • Other findings that commonly accompany myocardial ischemia include conduction delays, arrhythmias, and decrease in amplitude of precordial R waves (compared with previous tracings)
    • Left bundle branch blocks may obscure typical findings of infarction
    • An acute coronary syndrome is not excluded by a normal ECG result or a result in which the criteria are not fully met
    • Pseudonormalization may occur during the evolution of an acute coronary syndrome as ST-segment depression transitions to ST-segment elevation

Procedures

Cardiac catheterization with angiography r11r17c130c131
General explanation
  • Catheters are placed percutaneously in peripheral blood vessels and advanced into central circulation
  • Measures intravascular pressure, oxygen saturation in the heart and great vessels, and cardiac contractility and function
  • Angiography delineates anatomic structures and coronary artery patency
  • Usually performed under light sedation
Indication
  • Myocardial infarction
  • Unstable angina
  • Chest pain thought to have cardiac origin
  • Abnormal cardiac stress test results
Contraindications
  • No absolute contraindications
  • Relative contraindications
    • Contrast material allergy
    • Hemodynamic instability
    • Severe, uncontrolled hypertension
    • Severe anemia
    • Uncompensated congestive heart failure
Interpretation of results
  • Angiography shows anatomy of coronary vessels and presence and degree of coronary artery obstruction
    • Patients with myocardial infarction but no angiographically obstructive coronary artery disease (50% or larger diameter stenosis in a major epicardial vessel) meet diagnostic criteria for MINOCA r5
  • Left ventricular ejection fraction, an important prognostic indicator, can be calculated
  • Wall motion and contractility can be assessed
  • Valvular function can be assessed and valvular regurgitation quantified, if present

Other diagnostic tools

  • Risk assessment stratification
    • TIMI score r12r14c132
      • Used to stratify risk in patients with non–ST-elevation myocardial infarction/unstable angina to determine disposition (ICU versus other settings) and to identify high-risk patients who will benefit from aggressive antithrombotic and early invasive management (versus ischemia-guided or noninvasive medical management)
      • 1 point is tabulated for each of the following criteria:
        • Age 65 years or older r12
        • 3 or more risk factors for coronary artery disease r12
        • Prior coronary stenosis of 50% or more r12
        • ST deviation
        • 2 or more anginal events in prior 24 hours r12
        • Use of aspirin in prior 7 days r12
        • Elevated cardiac biomarker levels
      • Scores correlate with risk of all-cause mortality, new or recurrent myocardial infarction, or requirement for urgent revascularization
        • Score of 0 or 1: 4.7% r12
        • Score of 2: 8.3% r12
        • Score of 3: 13.2% r12
        • Score of 4: 19.9% r12
        • Score of 5: 26.2% r12
        • Score of 6 or 7: 40.9% r12
    • GRACE score r13r18c133
      • More complex instrument that likewise predicts mortality based on points assigned for Killip class, systolic blood pressure, heart rate, serum creatinine level, cardiac arrest at admission, ST-segment deviation, and cardiac enzyme levels; the point total can be matched to the mortality risk on a published nomogramr18
      • Can be used for risk stratification of patients with either ST-elevation myocardial infarction or non–ST-elevation myocardial infarction/unstable angina

Differential Diagnosis

Most common

  • Life-threatening cardiopulmonary conditions should be considered immediately
    • Pulmonary embolism c134d1
      • Presents with chest pain, dyspnea, tachypnea, and hypoxia; tachycardia, ST abnormalities on ECG, and elevated cardiac troponin levels 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
      • Multidetector-row CT angiography is diagnostic for pulmonary embolism; shows a thrombus or thrombi in pulmonary vessels
    • Dissecting aortic aneurysm c135d2
      • 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 d3
      • Pain is characterized as tearing or ripping
      • Murmur of aortic insufficiency may be audible; pulses may be asymmetrical
      • CT with contrast enhancement is diagnostic for dissecting aortic aneurysm
  • Other cardiac conditions
    • Pericarditis c136d4
      • Presents as pleuritic precordial or retrosternal pain that may radiate to the back, neck, and left shoulder/arm; ECG often shows PR-segment depression and ST-segment elevation; troponin levels may be elevated
      • Pain is worse on inspiration, in supine position, during swallowing, and during movement; pain is improved when the patient is seated and leaning forward. A pericardial friction rub is sometimes heard on auscultation
      • Echocardiography is the diagnostic study of choice, usually demonstrating effusion with or without thickening of the pericardium
    • Mitral valve prolapse c137d5
      • May present with palpitations, fatigue, syncope, and orthostatic hypotension
      • A midsystolic click and systolic murmur may be audible
      • Echocardiography is diagnostic, showing prolapsing valve with or without valve thickening
    • Takotsubo cardiomyopathy c138
      • Transient cardiac syndrome involving left ventricular apical akinesis
      • Produces chest pain, ST elevation, and sometimes elevated cardiac enzyme levels
      • Usually brought on by intense emotional (eg, bereavement) or physical stress; exact cause is unknown
      • Most patients are postmenopausal females
      • Diagnosis is confirmed by coronary angiogram showing normal coronary artery anatomy and left ventricular apical ballooning
  • Noncardiac conditions
    • Cholecystitis c139d6
      • 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; troponin levels are not elevated
      • Right upper quadrant ultrasonography is usually diagnostic, showing an inflamed gallbladder; stones and ductal dilatation may be evident
    • Pancreatitis c140d7
      • 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 the pancreas; lipase and amylase levels are elevated
    • Perforated peptic ulcer c141d8
      • Presents with sudden severe epigastric pain; may involve associated hypotension or shock
      • Tenderness to palpation of the upper abdomen, with peritoneal signs
      • Upright chest radiograph finds free air under diaphragm; abdominal CT scan may localize ulcer and perforation
    • Esophageal spasm c142
      • May present with epigastric pain or tightness, which may be relieved by sublingual nitroglycerin
      • May be precipitated by swallowing; associated with dysphagia
      • Diagnosis is confirmed by manometry (which finds premature rapid contractions) or by the appearance of corkscrew esophagus on barium swallow
    • Costochondritis c143
      • May present with severe pain in sternal area
      • Characterized by exacerbation with chest motion (eg, respiration, rotation of torso)
      • Differentiated from acute coronary syndromes by characteristic exacerbation with physical maneuvers and absence of ECG abnormalities
    • Prodromal or early herpes zoster (varicella-zoster infection) c144d9
      • Infection in midthoracic dermatomes can present as excruciating pain that mimics acute coronary syndromes
      • Not associated with dyspnea, ECG changes, or troponin release
      • Diagnosis may not become apparent until lesions appear; distribution and characteristic features (clustered vesicles) of the lesions are usually diagnostic, but polymerase chain reaction test can be used for confirmation

Treatment

Goals

  • Relief of ischemia
  • Prevention of myocardial infarction (or limitation of infarct size)
  • Preservation of left ventricular function
  • Prevention of death

Disposition

Admission criteria

All patients with a confirmed acute coronary syndrome require admission to hospital telemetry unit r1r2

  • Patients with symptoms suggesting an acute coronary syndrome, but without diagnostic ECG changes or elevated troponin levels, may be observed in a telemetry unit, chest pain unit, or emergency department while undergoing serial ECGs, troponin measurements, and other testing r1

For patients with ST-elevation myocardial infarction who present at a facility without the ability to perform percutaneous coronary intervention, transfer to a hospital with appropriate facilities if the transfer can be achieved within first-medical-contact-to-balloon-time window of 90 minutes or less r2

Criteria for ICU admission r1
  • Ongoing ischemic pain
  • Large infarction
  • Uncontrolled arrhythmias
  • Pulmonary edema
  • Hemodynamic instability

Recommendations for specialist referral

  • Consult a cardiologist for all patients with a confirmed acute coronary syndrome
  • Refer patients with symptoms suggestive of myocardial ischemia, but without evidence of an acute coronary syndrome, to a cardiologist

Treatment Options

Initial treatment in all patients

  • Assess and stabilize airway, breathing, and circulation; resuscitate if needed r19
  • Administer supplemental oxygen if needed to maintain oxygen saturation greater than 90% r1
  • Treat any associated life-threatening arrhythmia according to advanced cardiovascular life support protocols r20r21r22
  • Treat ongoing chest pain with sublingual nitroglycerin: IV nitrates may be used for persistent symptoms;r15 IV morphine may be given for severe discomfort
  • Administer β-blocker, providing there are no contraindications, and statin r1r2
  • Initiate treatment with an ACE inhibitor as soon as the patient is hemodynamically stable r23
  • Antiplatelet therapy is a cornerstone of management; includes aspirin, P2Y₁₂ inhibitors, and/or glycoprotein IIb/IIIa inhibitors r1r2
    • Give aspirin as soon as possible to all patients without contraindications r23
    • A P2Y₁₂ inhibitor (eg, clopidogrel, prasugrel, ticagrelor) is recommended in addition to aspirin r15
      • Pretreatment (prior to coronary angiography) with any P2Y12 inhibitor is contraindicated in patients planned to undergo rapid coronary angiography and intervention r24
    • Glycoprotein IIb/IIIa inhibitors (eptifibatide, tirofiban) may be considered if there is evidence of thrombotic complication or no reflow r15
  • Anticoagulation is recommended at time of diagnosis and during percutaneous coronary interventions r1r2r15
    • Unfractionated heparin is recommended for patients undergoing percutaneous coronary intervention; bivalirudin is an alternative
    • Enoxaparin and fondaparinux are also used in some circumstances

For ST-elevation myocardial infarction r2r25

  • Percutaneous coronary intervention is the preferred reperfusion strategy in patients whose symptom onset was within the past 12 hours r23
    • Reasonable approach in patients with symptom onset within 12 to 24 hours and evidence of ongoing ischemia r2
    • Should be done regardless of time from symptom onset in patients with any of the following:
      • Contraindication to fibrinolysis
      • Cardiogenic shock
      • Severe acute heart failure
  • Fibrinolytic therapy is recommended in patients with symptom onset within the past 12 hours if percutaneous coronary intervention cannot be achieved within 120 minutes of first medical contact; administer fibrinolytic therapy within 30 minutes of hospital arrival r2r23
    • Reasonable approach in patients with symptom onset within 12 to 24 hours who have evidence of ongoing ischemia, large area of myocardium at risk, or hemodynamic compromise r2
  • Urgent coronary artery bypass grafting is recommended for patients whose coronary artery anatomy precludes effective percutaneous coronary intervention and who have ongoing ischemia, severe heart failure, or cardiogenic shock
    • May be considered for patients without cardiogenic shock in whom neither percutaneous coronary intervention nor fibrinolytic therapy is appropriate, and whose symptom onset was within the past 6 hours r2

For non–ST-elevation myocardial infarction or unstable angina

  • 2 treatment approaches may be taken, depending on clinical circumstances and risk assessment
    • Early invasive strategy includes prompt cardiac catheterization and reperfusion r1
      • Immediate intervention is recommended for patients with ongoing ischemic pain, hemodynamic compromise, or electrical instability r15
        • Urgent coronary artery bypass grafting is recommended for such patients whose coronary artery anatomy precludes effective percutaneous coronary intervention r15
      • An early invasive approach within 24 hours of admission is recommended for non–ST-elevation myocardial infarction based on troponin measurements, GRACE risk score more than 140, and development of new ST-segment changes r15
      • Reasonable to postpone catheterization for 24 to 72 hours in stable patients who are not at high risk or in whom other personal or clinical considerations favor delay
    • Conservative management without early coronary angiography r23
      • Ischemia-guided strategy includes routine medical care followed by noninvasive evaluation of stress tolerance, with invasive management reserved for recurrent ischemia or demonstration of low stress tolerance r1
      • Appropriate for patients assessed as low risk (eg, TIMI score of 1 or less, GRACE score less than 109, troponin levels within the reference range), especially females
      • Appropriate for patients in whom other clinical conditions (eg, severe comorbidities) or personal considerations apply

Secondary prevention r23

  • Patients who are treated for myocardial infarction should commence on the following drugs and continue indefinitely (in the absence of any contraindications): r26
    • ACE inhibitor
    • Dual antiplatelet therapy (aspirin plus a second antiplatelet) unless they have a separate indication for anticoagulation r27
      • Continue dual antiplatelet therapy irrespective of the stent type for up to 12 months after a myocardial infarction;r15 continue aspirin alone indefinitely
    • β-blocker
      • Continue indefinitely in people with reduced left ventricular ejection fraction
      • Consider continuing for 12 months after a myocardial infarction for people without reduced left ventricular ejection fraction
        • There is limited contemporary data to support continuing β-blockers beyond 12 months after a myocardial infarction for people without reduced left ventricular ejection fraction; 1 cohort study found continuing β-blocker therapy for 1 year or more after the myocardial infarction was associated with reduced mortality compared to less than 1 year;r28 however, another suggests β-blockers may be discontinued as soon as 3 months post–myocardial infarctionr29
    • High-intensity statin therapy r30
  • These secondary prevention measures are largely directed at atherothrombotic coronary artery disease and may not be appropriate as routine treatment for all patients with MINOCA; treatment should be individualized in these patients depending on underlying mechanism and patient characteristics r4
  • Patients with reduced left ventricular ejection fraction following a myocardial infarction should be considered for an implantable cardioverter defibrillator r23

Drug therapy

  • Nitrates
    • Nitroglycerin r1r2c145
      • Initial route is sublingual; IV administration is indicated if ischemic pain persists after 3 sublingual doses
      • Sublingual
        • Nitroglycerin Sublingual tablet; Adults: 1 tablet (300 mcg, 400 mcg, or 600 mcg) SL, dissolved under the tongue or in buccal pouch at attack onset; may repeat with 1 tablet every 5 minutes PRN for up to 3 tablets. If chest pain persists after 3 tablets, prompt medical attention should be sought. Guidelines suggest patients with persistent chest pain following 1 dose, should seek prompt medical attention. May use prophylactically 5 to 10 minutes before participating in activities that may precipitate an acute attack.
      • IV
        • Nitroglycerin Solution for injection; Adults: 5 mcg/minute continuous IV infusion, initially. Titrate by 5 mcg/minute every 3 to 5 minutes to clinical response, or a dose of 20 mcg/minute. May further titrate by 10 mcg/minute, and if the desired effect is still not achieved, by 20 mcg/minute. Max titration: 20 mcg/minute every 3 to 5 minutes. Usual dose range: 5 to 100 mcg/minute. Max: 200 mcg/minute.
  • Analgesia
    • Morphine r1r2c146
      • Morphine Sulfate Solution for injection; Adults: Initially, 2 to 5 mg IV every 5 to 30 minutes PRN for pain; some patients may require maintenance doses of 4 to 8 mg IV every 4 to 6 hours.
      • Monitor blood pressure and respiratory rate
  • Antiplatelet drugs
    • Aspirin r1r2c147
      • Provides analgesia and reduces platelet aggregation to inhibit thrombus formation
      • Aspirin Oral tablet; Adults: 160 mg to 325 mg PO non-enteric coated tablet, chewed and swallowed immediately, regardless of concomitant fibrinolytic therapy. Maintenance: 75 mg to 162 mg PO once daily.
      • Recommended maintenance dose of aspirin is 81 mg for indefinite period
      • Avoid other NSAIDs
    • P2Y₁₂ inhibitors r31r32r33c148
      • Reduce platelet aggregation by blocking the P2Y₁₂ adenosine diphosphate receptor on platelets, which reduces thrombus formation, increases bleeding time, and reduces blood viscosity
      • For patients with ST-elevation myocardial infarction undergoing percutaneous coronary intervention, prasugrel or ticagrelor is preferred over clopidogrel; cangrelor may be an option for patients who are unable to take an oral P2Y₁₂ inhibitor r25
      • Prasugrel c149c150
        • FDA-approved for patients with acute coronary syndromes undergoing percutaneous coronary intervention; not FDA-approved for medical management of acute coronary syndromes
        • Recommended in patients who are proceeding to percutaneous coronary intervention if there are no contraindications r15
        • Prasugrel is preferred over ticagrelor in patients with non–ST-elevation myocardial infarction who undergo percutaneous coronary intervention r15
        • Not recommended for patients older than 75 years
        • Greater antiplatelet effect with significant reduction in risk of thrombotic events compared with clopidogrel or ticagrelor; greater risk of bleeding compared with clopidogrel or ticagrelor r34
        • In elderly or low-weight patients, a reduced dose of prasugrel compared with the standard dose of ticagrelor is associated with maintained anti-ischemic efficacy while protecting against excess risk for bleeding r35
        • Prasugrel Oral tablet; Adults and Geriatric Adults less than 75 years of age and weighing less than 60 kg: 60 mg PO as a loading dose, then consider a lower maintenance dose of 5 mg PO once daily. Optimal duration of therapy is not known. Also give aspirin 75 mg/day to 325 mg/day PO.
        • Prasugrel Oral tablet; Adults and Geriatric Adults less than 75 years of age and weighing 60 kg or more: 60 mg PO as a loading dose, then 10 mg PO once daily. The optimal duration of therapy is not known. Also give aspirin 75 mg/day to 325 mg/day PO.
        • Prasugrel Oral tablet; Geriatric 75 years or older: Use in this population is generally not recommended, except in high-risk patients with a past history of myocardial infarction or diabetes, where studies have demonstrated benefit is greater than risk. In such patients, if weight is 60 kg or more: 60 mg PO as a loading dose, then 10 mg PO once daily. If weight is less than 60 kg: 60 mg PO as a loading dose, then consider a lower maintenance dose of 5 mg PO once daily. The optimal duration of therapy is not known. All patients should also take aspirin 75 mg/day to 325 mg/day PO.
        • Discontinue 7 days before elective coronary artery bypass graft surgery r1
      • Ticagrelor c151
        • Compared with clopidogrel
          • Greater antiplatelet effect with significant reduction in risk of thrombotic events compared with clopidogrel r36
          • Greater risk of bleeding compared with clopidogrel r37
          • Positive mortality benefit has been observed in non–ST-elevation myocardial infarction/unstable angina patients r1
        • Compared with prasugrel
          • Less myonecrosis was observed after percutaneous coronary intervention r38
          • In elderly or low-weight patients, a reduced dose of prasugrel compared with the standard dose of ticagrelor is associated with maintained anti-ischemic efficacy while protecting against excess risk for bleeding r35
        • Recommended, in the absence of contraindications, for all patients at moderate to high risk of ischemic events (eg, elevated cardiac troponin levels), regardless of initial treatment strategy and including those pretreated with clopidogrel (which should be discontinued when ticagrelor is started) r15
        • Ticagrelor Oral tablet; Adults: 180 mg PO loading dose plus aspirin (usually 325 mg PO) then, beginning 12 hours after loading dose, 90 mg PO twice daily plus aspirin 75 to 100 mg (i.e., 81 mg) PO once daily for 1 year. After 1 year, 60 mg PO twice daily and continue aspirin maintenance dose. Avoid maintenance doses of aspirin above 100 mg/day.
        • Discontinue 5 days before elective coronary artery bypass graft surgery and 24 hours before urgent coronary artery bypass graft surgery
      • Cangrelor c152
        • Reduced intraprocedural stent thrombosis compared with clopidogrel r39
        • Cangrelor Solution for injection; Adults: 30 mcg/kg single dose IV bolus followed immediately by 4 mcg/kg/minute continuous IV infusion. The bolus should be administered prior to PCI and the maintenance infusion should be continued for at least 2 hours or for the duration of PCI, whichever is longer. An oral P2Y12 platelet inhibitor (e.g., either ticagrelor, prasugrel or clopidogrel) should be administered to maintain platelet inhibition; choose one to administer. Prasugrel 60 mg PO or clopridogrel 600 mg PO may be administered after discontinuation of the cangrelor infusion. Do not administer prasugrel or clopidogrel prior to discontinuation of cangrelor. Ticagrelor 180 mg PO may be administered at any time during or immediately after discontinuation of cangrelor infusion.
      • Clopidogrel c153
        • For percutaneous coronary intervention
          • Clopidogrel Bisulfate Oral tablet; Adults: 300 or 600 mg PO once, within 24 hours and if more than 24 hours since fibrinolytic, respectively, followed by 75 mg PO once daily for at least 6 months in patients receiving a drug-eluting stent and at least 1 month in patients receiving a bare metal stent.
        • For medical management
          • Standard therapy for acute coronary syndromes before introduction of newer agents; relatively high rate of atherothrombotic events compared with newer agents, which conversely increase bleeding risk r36
          • Recommended for patients who cannot receive ticagrelor or prasugrel or who require oral anticoagulation r15
          • A 2020 trial suggested that, in patients aged 70 years or older presenting with non–ST-elevation acute coronary syndrome, clopidogrel is a favorable alternative, causing fewer bleeding events without an increase in the combined end point of all-cause death, myocardial infarction, stroke, and bleeding r40
          • Discontinue 5 days before elective coronary artery bypass graft surgery or 24 hours before urgent coronary artery bypass graft surgery r1
          • Clopidogrel Bisulfate Oral tablet; Adults: 300 mg PO once, followed by 75 mg PO once daily for up to 12 months.
    • Glycoprotein IIb/IIIa inhibitors c154
      • Reduced platelet aggregation through interruption of the final common pathway of fibrinogen-mediated cross-linkage of platelets; platelet counts need to be monitored during therapy
      • Used as bailout therapy when there is angiographic evidence of a large thrombus, slow or absent reperfusion, or other thrombotic complication; evidence is lacking r15r25
      • Eptifibatide c155
        • Eptifibatide Solution for injection; Adults: 180 mcg/kg (Max: 22.6 mg) IV bolus, followed by 2 mcg/kg/minute continuous IV infusion. Max: 15 mg/hour. Double-bolus eptifibatide (180 mcg/kg IV 10 minutes after first bolus) at the time of PCI in patients with intermediate/high-risk features is recommended. Continue the infusion until hospital discharge or initiation of CABG surgery, for up to 72 hours. If a patient is to undergo PCI, continue the infusion until hospital discharge or for up to 18 to 24 hours after the procedure, whichever comes first, allowing for up to 96 hours of therapy.
        • Discontinue 2 to 4 hours before coronary artery bypass graft surgery r1
      • Tirofiban r1c156
        • Tirofiban Hydrochloride Solution for injection; Adults: 25 mcg/kg IV within 5 minutes followed by 0.15 mcg/kg/minute for up to 18 to 24 hours at time of primary PCI. Discontinue at least 2 to 4 hours prior to urgent CABG.
  • Anticoagulants c157
    • Choice of anticoagulant depends on timing of percutaneous intervention and individual thrombosis and bleeding risk
    • Parenteral agents used during initial management of acute coronary syndromes in combination with antiplatelet drugs
      • Unfractionated heparin c158
        • Indirect thrombin inhibitor
        • For ST-elevation myocardial infarction r2
          • Heparin Sodium (Porcine) Solution for injection; Adults: 60 units/kg IV bolus (Max: 4,000 units) given simultaneously with initial dose of thrombolytic therapy followed by heparin 12 units/kg/hour (Max: 1,000 units/hour) adjusted to keep the aPTT 1.5 to 2 times control (50 to 70 seconds) for 48 hours. All AMI patients without contraindications and who are not receiving heparin for another reason should receive not less than low-dose heparin (7,500 units subcutaneous every 12 hours) or LMWH until ambulation.
        • For non–ST-elevation myocardial infarction/unstable angina r1
          • Heparin Sodium (Porcine) Solution for injection; Adults: 60 units/kg (Max: 5,000 units) IV, then 12 units/kg/hour (Max: 1,000 units/hour) continuous IV infusion, initially. Titrate dose to target coagulation parameter to maintain therapeutic anticoagulation for 48 hours or until PCI performed.
      • Enoxaparin c159
        • Indirect thrombin inhibitor
        • More effective anticoagulant than unfractionated heparin, but carries a higher risk of bleeding r11r17
        • Enoxaparin Sodium (Porcine) Solution for injection; Adults: 1 mg/kg subcutaneous q12h with concurrent aspirin for at least 48 hours and until stable. Invasive strategies (e.g., PCI) are recommended; continue LMWH until PCI. In patients undergoing PCI, if last dose of enoxaparin was <= 8h before PCI, do not give additional anticoagulant treatment. If enoxaparin was given 8—12 hours before PCI, give enoxaparin 0.3 mg/kg IV or heparin prior to PCI; if enoxaparin was given >=12 hours before PCI, administer standard anticoagulant treatment during PCI.
        • Guidelines list as an option for non–ST-elevation myocardial infarction/unstable anginar1 but not for ST-elevation myocardial infarctionr2
      • Fondaparinux c160
        • Factor Xa inhibitor c161
        • Used in combination with another anticoagulant in the setting of percutaneous coronary intervention owing to increased risk of catheter thrombosis
        • For ST-elevation myocardial infarction
          • Fondaparinux Sodium Solution for injection; Adults: Regimen suggested by OASIS-6 study. If no indication for heparin, give 2.5 mg subcutaneously once daily for 8 days or until hospital discharge; in patients with an indication for heparin (PCI, fibrinolysis, or receiving antithrombotics), give 2.5 mg IV† then 24 hours later begin 2.5 mg subcutaneously once daily for up to 7 days or until hospital discharge. Compared to heparin, fondaparinux reduces mortality without increasing the risk of bleeding in patients with STEMI not undergoing primary PCI.
        • For non–ST-elevation myocardial infarction/unstable angina
          • Fondaparinux Sodium Solution for injection; Adults: 2.5 mg subcutaneously once daily for 8 days or until hospital discharge; fondaparinux has been shown to be noninferior to enoxaparin with a decreased incidence of bleeding and death.
      • Bivalirudin c162
        • Direct thrombin inhibitor
        • Used only for patients undergoing percutaneous coronary intervention
        • Compared to heparin: r41
          • No significant difference in composite end point of death from any cause, myocardial infarction, or major bleeding at 180 days
          • No significant difference in the secondary end point of stent thrombosis
        • May be considered as an alternative for patients with contraindications to unfractionated heparin (ie, heparin-induced thrombocytopenia) who need anticoagulation r1
        • For ST-elevation myocardial infarction r2
          • Bivalirudin Solution for injection; Adults: 0.75 mg/kg IV bolus followed by 1.75 mg/kg/hour continuous IV infusion for duration of procedure. Perform ACT 5 minutes after bolus; may give additional 0.3 mg/kg IV bolus if needed.
        • For non–ST-elevation myocardial infarction/unstable angina
          • Dosing before percutaneous coronary intervention or diagnostic angiography r1
            • Bivalirudin Solution for injection; Adults: 0.1 mg/kg IV bolus followed by 0.25 mg/kg/hour continuous IV infusion until diagnostic angiography or PCI.
  • Fibrinolytics
    • Pharmacologic reperfusion strategy indicated for patients with ST-elevation myocardial infarction and symptom onset within the past 12 hours for whom the time from first medical contact to anticipated time of percutaneous coronary intervention is 120 minutes or more c163
    • Administer within 30 minutes of hospital arrival
    • Streptokinase c164
      • Streptokinase Solution for injection; Adults: 1,500,000 International Units by IV infusion within 60 minutes.
    • Alteplase c165
      • Alteplase Solution for injection; Adults weighing 67 kg or less: 15 mg IV bolus, followed by 0.75 mg/kg IV over next 30 minutes, and then 0.5 mg/kg IV over the next 60 minutes.
      • Alteplase Solution for injection; Adults weighing more than 67 kg: 15 mg IV bolus, followed by 50 mg IV over next 30 minutes, and then 35 mg IV over the next 60 minutes.
    • Reteplase c166
      • Reteplase (Recombinant) Solution for injection; Adults: 10 units IV over 2 minutes followed by a second dose of 10 units IV 30 minutes after first dose.
    • Tenecteplase c167
      • Tenecteplase Solution for injection; Adults: Administer single bolus dose of 30 to 50 mg IV over 5 seconds based on patient weight (30 mg for less than 60 kg; 35 mg for 60 to 69 kg; 40 mg for 70 to 79 kg; 45 mg for 80 to 89 kg; or 50 mg for 90 kg or greater). Safety and efficacy have been primarily studied in AMI patients receiving aspirin and heparin. In the efficacy and safety trial, ASSENT 2, use of glycoprotein IIb/IIIa inhibitors was discouraged for the first 24 hours following randomization. Tenecteplase has been used with enoxaparin as an alternative to unfractionated heparin.
  • β-blockers
    • Initiate oral β-blockers within 24 hours of presentation and continue indefinitely r1r2
    • IV β-blockers may be administered initially in patients with ST-elevation myocardial infarction who are hypertensive or who have ongoing ischemia; do not administer in patients at risk for shock r2
    • Preferred oral agents for patients with stabilized heart failure and reduced systolic function include metoprolol succinate, carvedilol, and bisoprolol r1
      • Metoprolol c168
        • Immediate-release dosing
          • Metoprolol Tartrate Oral tablet; Adults: 50 mg PO every 6 hours for 48 hours starting 15 minutes after the last IV dose. If the patient did not tolerate the full IV dose, initiate at 25 mg PO. The maintenance dose is 50 to 100 mg PO twice daily. In patients who were not candidates for metoprolol during the acute phase of the myocardial infarction, start 100 mg PO twice daily as soon as the patient is stable and without contraindications for use.
        • Once-daily dosing
          • Metoprolol Succinate Oral tablet, extended-release; Adults: Initially, 25 mg PO once daily in patients with NYHA class II heart failure or 12.5 mg PO once daily in patients with more severe heart failure. Double the dose every 2 weeks as tolerated, up to target dosage of 200 mg PO once daily.
      • Carvedilol c169
        • Carvedilol Oral tablet; Adults: Initially, 6.25 mg PO twice daily for 3 to 10 days. If tolerated (stable heart rate and blood pressure, minimal fluid retention), increase to 12.5 mg twice daily. Gradually titrate to target 25 mg twice daily, as tolerated. Max: 50 mg/day. If indicated, a lower starting dose of 3.125 mg PO twice daily may be used.
      • Bisoprolol c170
        • Bisoprolol Fumarate Oral tablet; Adults: Initially, 1.25 mg PO once daily for 48 hours, then 2.5 mg PO once daily for first month, then 5 mg PO once daily. Max: 10 mg PO once daily.
  • Calcium channel blockers
    • Alternative to β-blockers for patients in whom β-blockers are contraindicated or not tolerated; used as an adjunct to β-blockers if the patient has continuing or recurrent ischemic symptoms r1r2
    • Verapamil and diltiazem are preferred nondihydropyridine calcium channel blockers; do not administer immediate-release nifedipine without concurrent use of a β-blocker r1
      • Verapamil c171
        • Verapamil Hydrochloride Oral tablet; Adults: Initially, 80 to 120 mg PO every 8 hours. May increase up to 480 mg/day, administered in 3 to 4 divided doses.
        • Verapamil Hydrochloride Oral tablet; Geriatric: Use lower initial adult dose (e.g., 40 mg PO every 8 hours).
      • Diltiazem c172
        • Diltiazem Hydrochloride Oral tablet; Adults: Initially, 30 to 60 mg PO 4 times per day. Increase up to 360 mg/day in 3 to 4 divided doses. Individual patients may respond to higher doses up to 480 mg/day.
  • ACE inhibitors
    • Initiate ACE inhibitors within 24 hours of presentation and continue indefinitely, especially in patients with the following: r1r2
      • Pulmonary congestion c173
      • Heart failure c174
      • Anterior ST-elevation myocardial infarction c175
      • Left ventricular ejection fraction of 40% or less c176
      • Diabetes c177
      • Stable chronic kidney disease c178
    • Lisinopril c179
      • Lisinopril Oral tablet; Adults who are hemodynamically stable: Begin within 24 hours of symptom onset. Administer one 5 mg PO dose, followed by 5 mg PO after 24 hours, 10 mg PO after 48 hours, and then 10 mg PO once daily. If no complications or LV dysfunction by 6 weeks after AMI, ACEI can be stopped.
      • Lisinopril Oral tablet; Adults who develop low systolic blood pressure (<= 120 mmHg) either prior to therapy or during the first three days of therapy after the infarct: Begin within 24 hours of symptom onset. If hypotensive, start with 2.5 mg/day PO. If not hypotensive, 5 mg PO once daily may be given (reduce to 2.5 mg/day if needed). If SBP falls below 90 mm Hg for more than 1 hour, discontinue lisinopril.
      • Lisinopril Oral tablet; Geriatric: Start at the low end of adult dosage range.
    • Captopril c180
      • Captopril Oral tablet; Adults: 6.25 mg PO initially, followed 2 hours later with 12.5 mg PO, followed 10—12 hours later with 25 mg PO. Thereafter, 50 mg PO bid.
      • Captopril Oral tablet; Geriatric: See adult dosage. Initiate at low end of adult dosage range.
    • Ramipril c181
      • Ramipril Oral tablet; Adults: Initially, 1.25 mg to 2.5 mg PO once or twice daily. Increase dose as tolerated, adjusting to clinical response of patient up to Max: 10 mg/day.
    • Trandolapril c182
      • Trandolapril Oral tablet; Adults: Initially, 1 mg PO once daily. Increase dose as tolerated, adjusting to the clinical response of the patient up to 4 mg/day.
  • Angiotensin receptor blockers
    • Alternative to ACE inhibitors for patients in whom ACE inhibitors are contraindicated or not tolerated r1r2
    • Valsartan c183
      • As effective as captopril (ACE inhibitor), but do not use these 2 agents together r11
      • Valsartan Oral tablet; Adults: 20 mg PO twice daily initially, started as early as 12 hours after a MI. May titrate within 7 days to 40 mg PO twice daily. Subsequently, titrate to target maintenance dose of 160 mg PO twice daily as tolerated. Consider dose reduction if hypotension or renal dysfunction occurs.
    • Losartan (off-label indication) c184
      • Losartan Potassium Oral tablet; Adults: Initially, 25 to 50 mg PO once daily. Increase dose as tolerated, adjusting to clinical response of patient up to Max: 50 to 150 mg/day.
  • Aldosterone antagonists
    • Indicated as an adjunct for patients already on a β-blocker and an ACE inhibitor (or angiotensin receptor blocker) who have a left ventricular ejection fraction of 40% or less, diabetes, or heart failure r1
    • Spironolactone is a nonspecific aldosterone receptor antagonist and is associated with progestogenic and androgenic effects (eg, gynecomastia, erectile dysfunction, menstrual irregularities, hirsutism, mastalgia); eplerenone has lower affinity for androgen, progesterone, and glucocorticoid receptors and thus a lower incidence of these adverse effects.
    • Eplerenone c185
      • Eplerenone Oral tablet; Adults: Initially, 25 mg PO once daily. Increase dosage to 50 mg PO once daily as tolerated within 4 weeks. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Monitor serum potassium at baseline, within first week, and at 1 month after dosage initiation or adjustments; monitor more frequently in at-risk patients. If serum potassium 5.5 mEq/L or more, decrease dosage. Hold if serum potassium 6 mEq/L or more; may restart at 25 mg PO every other day once serum potassium less than 5.5 mEq/L.
    • Spironolactone c186
      • Spironolactone Oral tablet; Adults: Initially, 12.5 to 25 mg PO once daily. May reduce dosage to 25 mg PO every other day if hyperkalemia occurs with 25 mg PO once daily. May increase dosage to 50 mg/day, if clinically indicated and lower dose tolerated.
  • Statins
    • Initiate (or continue) high-intensity statin therapy in all patients who do not have contraindications r1r2
    • It is recommended to start high-intensity statin therapy as early as possible, unless contraindicated, and to continue it as long-term maintenance r15
    • Atorvastatin and rosuvastatin are the only 2 statins with high-intensity therapy dosing. Atorvastatin 40 to 80 mg daily or rosuvastatin 20 to 40 mg daily is considered high-intensity dose. r30
    • Atorvastatin c187
      • 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.
    • Rosuvastatin c188
      • Rosuvastatin Calcium Oral tablet; Adults: Usual starting dose is 10 to 20 mg PO daily, with range of 5 to 40 mg PO daily. For Asian patients, consider starting dose of 5 mg once daily. JUPITER study used 20 mg PO once daily. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Nondrug and supportive care

Initial supportive care includes oxygen therapy; therapeutic reperfusion includes coronary revascularization procedures (percutaneous coronary intervention or coronary artery bypass graft surgery) r1r2c189

  • Oxygen therapy c190
    • Provide supplemental oxygen to patients who have arterial oxygen saturation of less than 90%, respiratory distress, or other evidence of hypoxemia r1

Risk reduction strategies for secondary prevention

  • Cardiac rehabilitation c191
    • Refer all patients with acute coronary syndromes to a comprehensive outpatient cardiovascular rehabilitation program, either upon hospital discharge or at first follow-up office visit r1
    • Alternatively, a home-based cardiac rehabilitation program may be sufficient for low-risk patients
    • Aerobic exercise can begin 1 to 2 weeks after discharge for patients who have undergone percutaneous coronary intervention or coronary artery bypass graft surgery r1
    • Resistance exercise can begin 2 to 4 weeks after starting aerobic exercise r1
  • Smoking cessation r26c192d10
    • Advise all patients to avoid exposure to tobacco smoke, including secondhand smoke; those who use tobacco should be advised to quit at each contact
      • Provide assistance in quitting through referral to a smoking cessation program and/or prescribing pharmacotherapy (eg, bupropion, varenicline)
  • Nutrition c193
    • Modify nutrition counseling based on individual patient factors (eg, lipid profile, blood pressure, required caloric intake, alcohol intake)
    • Diets should emphasize nonstarchy vegetables, minimize added sugars and refined grains, and avoid highly processed foods; these diets are inherently relatively low in cholesterol r42r43r44
      • Mediterranean diet is often recommended; however, a 2019 Cochrane review found paucity of evidence for secondary prevention r45
      • DASH diet (Dietary Approaches to Stop Hypertension) is also recommended to reduce cardiovascular risk c194
    • Minimize intake of processed meats, refined carbohydrates, and sweetened beverages r42
    • Decrease intake of sodium, alcohol, and substitute healthy fats for saturated and trans fats r26c195c196c197c198c199
  • Weight management c200
    • BMI goal is 18.5 to 24.9 kg/m²; waist circumference goal is less than 89 cm for females, less than 102 cm for males r26
    • If weight loss is required, initial weight loss goal should be 5% to 10% below baseline r26c201
  • Physical activity
    • Before discharge from the acute care setting, provide the patient with instructions on specific activity recommendations (eg, lifting, stair climbing, housework, yardwork, sexual activity) c202
    • Perform risk assessment, including physical activity history and exercise test, before recommending exercise plan c203c204
    • Goal is 150 minutes of moderate-intensity aerobic activity per week (eg, 30-60 minutes on 5 days); supplement with resistance training at least twice per week r26r43
    • Counsel patients to report exercise-associated symptoms
  • Prevention of infectious diseases r1
    • Pneumococcal vaccine is recommended for high-risk patients with cardiovascular disease and age older than 65 years c205
    • Yearly influenza vaccine is recommended for patients with cardiovascular disease c206
Procedures
Percutaneous coronary intervention c207
General explanation
  • Invasive therapeutic technique in which a catheter is guided via the radial artery (preferred) or femoral artery to the stenosed/occluded coronary artery (or arteries) for the purpose of alleviating the lesion(s) and revascularizing the myocardial tissue
    • Radial approach is preferredr15r46 over femoral, because radial approach is associated with a consistent reduction in mortality and major bleeding complications for ST-elevation myocardial infarctionr47 and non–ST-elevation myocardial infarction/unstable anginar37
  • May be done on culprit lesion only or in multivessel form
    • Complete revascularization with percutaneous coronary intervention during the index hospital admission is recommended for patients with acute ST-elevation myocardial infarction and multivessel coronary artery disease who are hemodynamically stable r23
      • Multivessel intervention has been shown to be safe; reduces rate of subsequent major cardiac events r48
    • Culprit lesion only is the favored approach in patients with multivessel disease who have cardiogenic shock; subsequent intervention in noninfarct arteries may be performed as a planned, staged procedure r2r23
  • Techniques include:
    • Percutaneous transluminal coronary angioplasty (balloon dilation) r11c208
    • Intracoronary stenting r11c209
      • Bare metal stent c210
        • Risk of restenosis due to smooth muscle hyperplasia
        • May be used for patients who may not be able to tolerate 1 year of dual antiplatelet therapy with aspirin and a P2Y₁₂ inhibitor r49
      • Drug-eluting stent r11c211
        • Coated with sirolimus, everolimus, or paclitaxel to reduce the risk of restenosis due to smooth muscle hyperplasia
        • Sirolimus and paclitaxel have been compared and found to be equally effective in reducing stent thrombosis r49
        • Requires at least 1 year of antiplatelet therapy with a P2Y₁₂ inhibitor r49
    • Atheroablative technologies, such as atherectomy r11c212
  • Currently, 80% to 85% of percutaneous coronary interventions involve balloon dilation and coronary stenting r17
Indication
  • ST-elevation myocardial infarction r2r23
    • Ischemic symptoms less than 12 hours in duration
    • Minimal time-to-treatment delays
      • Percutaneous coronary intervention can be delivered within 120 minutes of the time when fibrinolysis could have been given
    • More than 12 hours after the onset of symptoms with evidence of continuing myocardial ischemia or cardiogenic shock
  • Non–ST-elevation myocardial infarction r1r23
    • Intermediate or higher risk of adverse cardiovascular events (predicted 6‑month mortality above 3.0%) and no contraindications to angiography (such as active bleeding or comorbidity)
    • Low risk of adverse cardiovascular events (predicted 6‑month mortality 3.0% or less) with recurring ischemia demonstrated by ischemia testing or symptoms
    • Benefit of early invasive strategy with coronary angiography is less certain
Contraindications
  • May not be appropriate for patients with certain comorbidities (eg, diabetes), in whom coronary artery bypass graft surgery is associated with better outcomes (among those with acceptable surgical risk) r50
Coronary artery bypass graft surgery c213
General explanation
  • Open surgical procedure in which a piece of artery (eg, internal mammary artery) or vein (eg, saphenous) is grafted around the occluded portion of the coronary artery or arteries for the purpose of revascularizing the affected myocardial tissue r51
Indication
  • ST-elevation myocardial infarction r2
    • Urgent coronary artery bypass graft surgery is indicated in patients with coronary anatomy not amenable to percutaneous coronary intervention who have cardiogenic shock, severe heart failure, ongoing or recurrent ischemia, or other high-risk characteristics
    • Emergency coronary artery bypass graft surgery within 6 hours of symptom onset in patients who did not have cardiogenic shock and who are not candidates for alternative reperfusion strategies (percutaneous coronary intervention or fibrinolysis)
  • Non–ST-elevation myocardial infarction r1
    • Emergency coronary artery bypass graft surgery is reasonable for those who have failed percutaneous coronary intervention, with continuing ischemia, hemodynamic compromise, or threatened arterial occlusion with significant myocardium at risk, and are appropriate candidates for surgery r50
Contraindications
  • Potential for excess mortality when performed early after ST-elevation myocardial infarction r1

Comorbidities r1

  • Hypertension c214c215
    • In patients with increased cardiovascular risk (including stable ischemic heart disease), reduction of systolic blood pressure to less than 130/80 mm Hg has been shown to reduce cardiovascular disease complications by 25% and all-cause mortality by 27% r52r53
    • In adults who have had a myocardial infarction or acute coronary syndrome, it is reasonable to continue β-blockers as long-term therapy for hypertension r53
  • Dyslipidemia c216c217
    • Targeting specific lipid levels is controversial; use of intensive statin therapy, without specific goal direction, is recommended in all patients who can tolerate it r30
    • Reduce LDL-C by at least 50% with high-intensity statin therapy or maximally tolerated statin therapy r30
      • In very-high-risk atherosclerotic cardiovascular disease, use an LDL-C threshold of 70 mg/dL to consider addition of nonstatins to statin therapy
      • Very high risk includes:
        • History of at least multiple major atherosclerotic cardiovascular events or history of 1 major atherosclerotic cardiovascular event and multiple high-risk conditions
      • Reasonable to add ezetimibe to maximally tolerated statin therapy when LDL-C level remains at 70 mg/dL or higher
      • Patients at very high risk whose LDL-C level remains at 70 mg/dL or higher on maximally tolerated statin and ezetimibe therapy, adding a PCSK9 inhibitor is reasonable, although long-term safety (longer than 3 years) is uncertain
  • Diabetes c218
    • Aggressively control blood glucose levels and maintain at 180 mg/dL or less while avoiding hypoglycemia r1
    • Most patients with type 2 diabetes and coronary artery disease should be treated with an oral glucose-lowering agent proven to reduce major cardiovascular events and/or cardiovascular mortality, either a sodium-glucose cotransporter 2 inhibitor or a glucagonlike peptide 1 receptor agonist r54
    • Strongest evidence for cardiovascular benefit has been demonstrated with liraglutide, dulaglutide, semaglutide, empagliflozin, dapagliflozin, and canagliflozin r54
    • May be commenced at during admission, or at discharge or outpatient follow-up
  • Heart failure c219
    • May complicate diagnosis, because troponin levels may be elevated owing to acute heart failure
    • Base revascularization strategy on the extent of coronary artery disease, cardiac lesions, left ventricular dysfunction, and prior revascularization r1
    • In the presence of a large area of ischemia or significant heart failure, a percutaneous ventricular assist device or an intra-aortic balloon pump may be needed during surgical intervention r1
  • Chronic kidney disease c220
    • Adjust pharmacotherapy dosages according to creatinine clearance in patients with chronic kidney disease
    • Provide adequate hydration to patients undergoing angiography r1

Special populations

  • Older patients (aged 75 years or older) r1
    • Adjust pharmacotherapy dosages according to weight and/or creatinine clearance in older patients
    • Tailor care to consider patient preferences and goals, functional and cognitive status, comorbidities, drug interactions, and life expectancy
    • Survival advantage associated with an early invasive strategy in patients with non–ST-elevation myocardial infarction is also seen in patients aged 80 years and older r55
  • Females r1
    • Consider adjusting antiplatelet and anticoagulant dosages according to weight and/or creatinine clearance to reduce the risk of bleeding
    • Pregnant patients may undergo myocardial revascularization if ischemia-guided therapy is ineffective
    • Do not use an early invasive strategy to manage females with non–ST-elevation myocardial infarction/unstable angina and low-risk assessment (eg, low TIMI score, troponin levels within the reference range), because risk of harm outweighs likely benefit r1
  • Patients acutely intoxicated with cocaine or methamphetamine r1
    • β-blockers are contraindicated owing to risk of coronary spasm
    • Benzodiazepines may be used alone or with nitroglycerin to manage hypertension and tachycardia associated with cocaine or methamphetamine intoxication

Monitoring

  • Perform noninvasive testing for ischemia before discharge in patients with ST-elevation myocardial infarction who have not had coronary angiography,r2 and consider it in other patients to evaluate exercise tolerance (eg, in patients with uncorrected noninfarct stenoses)r1c221c222
  • Measure left ventricular function before discharge in all patients with acute coronary syndromes, if measurement was not obtained earlier in hospital stay r1r2c223
  • Postdischarge management includes monitoring for recurrent symptoms and adjustment of medications based on clinical and laboratory parameters
    • During the first year, outpatient follow-up is recommended every 4 to 6 months; thereafter, 6- to 12-month intervals are reasonable for stable disease r56c224c225
  • At each follow-up visit, ask patients about interval symptoms of ischemia, heart failure, and arrhythmias and perform a focused cardiovascular examination c226
  • Monitor patients for adherence to an optimal medical regimen c227
  • Testing
    • Obtain serial LDL-C measurements 4 to 12 weeks from start of treatment; results should show 50% reduction r30c228c229
      • Monitor every 3 to 12 months thereafter if expected response is achieved
    • In patients who are not known to have diabetes, obtain hemoglobin A1C measurement every 3 years r56c230
    • Measure hemoglobin level, thyroid function, renal function, and serum electrolyte levels yearly r56c231c232c233c234
    • ECG may be considered in asymptomatic patients on a yearly basis; done as needed in patients experiencing new or worsening cardiac symptoms r56c235
    • Stress testing at intervals of 1 to 2 years may be appropriate in patients with prior evidence of silent ischemia or in patients who are felt to be at high risk for recurrent ischemia; the need for routine testing in other patients is not established r56
      • Stress testing
        • ECG evaluation during stress (pharmacologically or exercise-induced) used to detect ischemia and estimate prognosis
          • Treadmill stress test is the preferred method c236
            • Used in patients who can exercise and whose ECG is free of ST changes at rest, which might affect interpretation
            • An imaging modality (ie, single-photon emission CT with a radioactive tracer, echocardiography) may be added for patients whose ECG results have ST changes at rest that might affect interpretation
          • Pharmacologic stress test with imaging (ie, single-photon emission CT with a radioactive tracer, echocardiography) is performed in patients whose physical limitations preclude exercise; pharmacologic agents may include adenosine, dipyridamole, or dobutamine c237
        • Can be used to evaluate patients with nondiagnostic ECG and biomarker levels within the reference range, in the absence of ongoing pain or signs of heart failure
        • Indicated to evaluate exercise tolerance in low- and intermediate-risk patients with non–ST-elevation acute coronary syndromes who have been symptom free while at rest for 12 to 24 hours r1
          • Performed before hospital discharge or within 72 hours after discharge on an outpatient basis
        • Indicated to identify residual risk for ischemia before discharge of patients with ST-elevation myocardial infarction who have not had coronary angiography r2
        • Contraindicated in patients with evidence of active ischemia or left ventricular dysfunction
    • Echocardiography is often used early during the post–myocardial infarction period to assess left ventricular function (ejection fraction), an important prognostic indicator c238
      • Patients whose left ventricular ejection fraction is 40% or less initially should undergo serial testing at least 40 days later to assess risk of arrhythmia and potential indications for implantable defibrillator r2

Complications and Prognosis

Complications

  • Electrical complications c239
    • Ventricular arrhythmias c240
      • Ventricular tachycardia c241
      • Ventricular fibrillation c242d11
    • Supraventricular arrhythmias c243
      • Atrial fibrillation c244d12
      • Atrial flutter c245
      • Other supraventricular tachyarrhythmias c246
    • Bradyarrhythmias c247
      • Atrioventricular block c248
      • Bundle branch block c249
  • Complications of left ventricular function c250
  • Other mechanical complications
    • Mitral regurgitation c253d14
    • Ventricular septal rupture c254
    • Left ventricular free-wall rupture c255
    • Left ventricular aneurysm c256
  • Pericarditis c257
  • Thromboembolic complications, including stroke c258c259d15
  • Acute kidney injury c260d16
  • Complications due to medications
    • Bleeding, including gastrointestinal and cerebral (eg, anticoagulants, antiplatelet agents, fibrinolytics)
    • Refractory hypotension (calcium channel blockers)

Prognosis

  • Overall 6-month mortality for acute coronary syndromes is 12% to 13% r10
    • In-hospital mortality rate for ST-elevation myocardial infarction is approximately 5% to 6% r2
    • 1-year mortality rate for ST-elevation myocardial infarction is approximately 7% to 18% r2
  • Number of leads showing ST depression and the magnitude of ST depression are indicative of the extent of ischemia and correlate with prognosis r15
  • Secondary prevention represents an essential aspect of reducing the risk for further ischemic events and improving long-term outcomes r10

Screening and Prevention

Screening

At-risk populations

Screening tests

  • Global risk tools are used to estimate risk of experiencing a coronary heart disease event over a specific period (often 10 years) r42
    • For adults aged 40 to 75 years, assess traditional cardiovascular risk factors routinely; for adults aged 20 to 39 years, it is reasonable to assess traditional risk factors at least every 4 to 6 years r42
      • American Heart Association's web-based calculatorr57c355
      • Framingham Risk Score r42c356
      • Systematic Coronary Risk Evaluation r42r58c357
    • Risk categories include the following: low (less than 5%), borderline (5% to less than 7.5%), intermediate (7.5% or higher to less than 20%), or high (20% or higher) 10-year risk r42
    • Decisions about specific interventions (eg, statin treatment and its intensity) are based on this category
    • For patients with intermediate predicted risk or for select adults with borderline predicted risk, coronary artery calcium measurement can be a useful tool in refining risk assessment for statin therapy c358

Prevention

  • Prevention of acute coronary syndromes hinges on control of modifiable cardiovascular risk factors (accounts for 80% of risk), such as: r59
  • In a randomized trial involving patients with chronic coronary disease, the risk of cardiovascular events was significantly lower among those who received 0.5 mg of colchicine once daily than among those who received placebo; most patients were already receiving proven secondary prevention therapies r60
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