Acute coronary syndrome

Acute coronary syndrome (ACS) is the clinical manifestation of myocardial infarct and commonly the default working diagnosis in patients with new-onset chest pain suspected to be of cardiac ischemic origin. Clinical findings (e.g., onset and characteristics of pain, patient history) in combination with ECG and troponin are the mainstays of diagnosis. Based on ECG findings, patients are categorized into those with ST-elevation (STE-ACS) or non-ST-elevation ACS (NSTE-ACS). Depending on serum levels of cardiac troponin (cTn), NSTE-ACS can be categorized as NSTEMI or unstable angina (UA). STE-ACS patients require immediate revascularization therapy. The timing and necessity of revascularization therapy in NSTE-ACS is determined based on multiple risk factors. All ACS patients receive dual antiplatelet therapy and initially anticoagulation. Adjunctive therapy (e.g., beta blockers, oxygen) helps reduce symptoms and can have a positive impact on mortality.

This article concerns the initial management of ACS patients. See “Myocardial infarction” for more details regarding, e.g., histopathology and long-term management.

• Acute coronary syndrome (ACS): the suspicion or confirmed presence of acute myocardial ischemia ^[1][2]
• Acute coronary syndrome may be further classified into the following categories:
  • NSTE-ACS: acute coronary syndrome manifesting without ST-elevations on ECG
    • NSTEMI: positive myocardial injury biomarkers
    • Unstable angina: absence of detectable myocardial injury biomarkers
  • STE-ACS: acute coronary syndrome manifesting with ST-elevations on ECG
• See “Myocardial infarction” for more definitions.

Subtypes of ACS cannot be differentiated based on clinical presentation alone.

• Classic presentation ^[4][5]
  • Acute retrosternal chest pain
    • Typical: dull, squeezing pressure and/or tightness
    • Commonly radiates to left chest, arm, shoulder, neck, jaw, and/or epigastrium
    • Precipitated by exertion or stress
    • Symptom relief after administration of nitrates is not a diagnostic criterion for cardiac ischemia. ^[2]
    • The peak time of occurrence is usually in the morning.
    • See also “Angina.”
  • Dyspnea (especially with exertion)
  • Pallor
  • Nausea, vomiting
  • Diaphoresis, anxiety
  • Dizziness, lightheadedness, syncope
• Other findings
  • Tachycardia, arrhythmias
  • Symptoms of CHF (e.g., orthopnea, pulmonary edema) or cardiogenic shock (e.g., hypotension, tachycardia, cold extremities)
  • New heart murmur on auscultation (e.g., new S₄)
• Atypical presentations: more likely in elderly, diabetic individuals, and women ^[2][6]
  • Stabbing, sharp chest pain
  • No or minimal chest pain
    • ”Silent MI” without chest pain is more common in patients with diabetes, as a result of polyneuropathy.
  • Autonomic symptoms (e.g., nausea, diaphoresis)
• More common in inferior wall infarction
  • Epigastric pain
  • Bradycardia
  • Clinical triad in right ventricular infarction: hypotension, elevated jugular venous pressure, clear lung fields ^[1]

Classically, it has been taught that STEMI manifests with more severe symptoms than NSTEMI, but this is not always the case.

Approach ^[1][2][6][7]

• ECG: should be performed immediately once ACS is suspected or considered as differential diagnosis.
  • ST-elevations present: immediate revascularization therapy, preferably PCI (see “Management of STEMI”)
  • No ST-elevations present (i.e., NSTE-ACS): management strategy is guided by ECG findings, troponin levels, clinical features, and risk factors.
• Cardiac troponin levels: Measure as soon as possible and repeat after 1–6 hours.
• Consider bedside TTE if the diagnosis is unclear.

Patients suspected of having STE-ACS should be evaluated immediately for revascularization therapy.

12-lead ECG ^[1][2]

• Indicated for every patient with suspected ACS (best initial test) within 10 minutes of presentation ^[2]
• Findings: should always be interpreted in the context of clinical findings and patient history
  • ECG changes in STEMI
  • ECG changes in NSTEMI/unstable angina
• Repeat every 15–30 minutes in the first hour (especially if the first ECG is inconclusive or symptoms recur or change in quality)
• Compare with previous ECGs (if available).

ECG findings can change within minutes and ST elevations can appear or disappear.

Cardiac troponin ^[2][7]

• Indication: obtain troponin T/I in every patient with suspected ACS ^[2][8]
• Timing
  • At arrival and after 1–6 hours
  • Repeat if symptoms or ECG changes occur.
  • Consider repeat after 72 hours as a marker of infarct size.
• Findings: should always be interpreted in combination with clinical findings.
  • STEMI: usually elevated
  • NSTEMI: elevation above the 99^thpercentile
  • Unstable angina: usually normal
  • See “Cardiac biomarkers” for more information.

Transthoracic echocardiography (TTE) ^[1][2][7][8]

TTE is generally not necessary and should not delay reperfusion therapy. However, it may be a helpful study in patients with atypical symptoms or if the diagnosis is unclear.

• Indications include:
  • Cardiogenic shock
  • Infarct-like symptoms but inconclusive ECG findings
  • Evaluation for complications of myocardial infarction
• Findings
  • Wall motion abnormalities
  • Decreased LV function ^[1]
  • Signs of different conditions that cause chest pain (see “Differential diagnoses of chest pain”)

Imaging should not delay treatment of ACS.

• Several scoring systems are available to help identify low-risk patients, facilitate disposition (e.g., necessity of ICU admission), and guide timing of PCI in patients with chest pain.
• Risk stratification tools are not a substitute for clinical judgment.
• Should not be used for patients suspected of having STEMI

Risk stratification tools are not appropriate in the setting of STEMI; patients suspected of having STEMI should be evaluated immediately for revascularization.

GRACE score for risk of mortality in ACS ^[2][9][10]

• Based on the Global Registry of Acute Coronary Events (GRACE)
• May be used to inform management and disposition (e.g., ICU admission, timing of intervention in NSTE-ACS).
• Incorporates different criteria to estimate risk of mortality in patients with ACS, including:
  • Patient age
  • Vital signs
  • Cardiac and renal function
  • Cardiac arrest on presentation
  • ECG findings
  • Troponin levels

HEART score ^[11]

• The HEART score is an acronym of its components: history, ECG, age, risk factors, and troponin values.
• Risk assessment for major adverse cardiovascular events (MACE) in patients with chest pain presenting to the emergency department
  • Can be integrated into decision pathways for early discharge
  • Potentially reduces hospital admissions of low-risk patients
  • Should not be used in patients with STEMI or those who are hemodynamically unstable

TIMI score for NSTE-ACS ^[2][15][16]

• Estimates the risk of mortality, new or recurrent myocardial infarction, or the need for urgent revascularization in patients with NSTE-ACS
• Can help determine the therapeutic regimen and timing for revascularization.

Patients with STEMI require immediate revascularization and should be identified as soon as possible.; ECG findings can change over time and with fluctuations in symptoms, which is why the diagnosis of STEMI should not be excluded based on a single ECG. Percutaneous coronary intervention (PCI) within 90 minutes of first medical contact (FMC) is the treatment of choice. Intravenous fibrinolytics are an alternative if PCI can not be performed within 120 minutes and no contraindications are present.

ECG changes in STEMI ^{[1][6][8][17]}

• Definition: significant ST elevation in two contiguous leads
• Specific criteria: elevation measured at the J point in reference to the onset of the Q wave
  • In all leads except V₂ and V₃: ≥ 1 mm (≥ 0.1 mV)
  • In V₂ and V₃: depends on patient's sex and age
    • Men < 40 years: ≥ 2.5 mm (≥ 0.25 mV)
    • Men ≥ 40 years: ≥ 2.0 mm (≥ 0.2 mV)
    • Women of any age: ≥ 1.5 mm (≥ 0.15 mV)
  • The criteria are valid only in the absence of left ventricular hypertrophy and LBBB.
• Additional considerations
  • ECG findings may change over time (see “Timeline of ECG changes in STEMI”)
  • Hyperacute T waves can be present without ST elevations in the very early stages of ischemia.
  • If inferior myocardial infarction is suspected, investigate for signs of right ventricular involvement (see “Localization of myocardial infarct on ECG”)

Any patient with ST elevations on ECG requires immediate evaluation for urgent revascularization. The administration of other therapies should not delay care.

Classical timeline of ECG changes in STEMI

• Acute stage: myocardial damage ongoing
  • Hyperacute T waves (peaked T wave)
  • ST elevations in two contiguous leads with reciprocal ST depressions
• Intermediate stage: myocardial necrosis present
  • Absence of R wave
  • T-wave inversions
  • Pathological Q waves
    • Duration ≥ 0.04 seconds
    • Amplitude ≥ ¼ of the R wave or ≥ 0.1 mV
    • Any Q wave in leads V1–3
• Chronic stage: permanent scarring
  • Persistent, broad, and deep Q waves
  • Often incomplete recovery of R waves
  • Permanent T-wave inversion is possible.

The sequence of ECG changes over several hours to days: hyperacute T wave → ST elevation → pathological Q wave → T-wave inversion → ST normalization → T-wave normalization

Assessment of ST elevations in the presence of left bundle branch block (LBBB) can be difficult. If clinical suspicion for myocardial ischemia is high, patients with this constellation should be managed like patients with STEMI.

The following recommendations are generally consistent with the 2013 AHA/ACC guidelines for the management of STE-ACS. ^[1]

"Time is muscle": Revascularization should occur as soon as possible in patients with STEMI! All other interventions can wait!

Immediate revascularization ^[1]

Emergency coronary angiography with PCI ^[1]

• Indication: preferred method of revascularization in patients suspected of having STEMI
  • STEMI and STEMI equivalents
  • LBBB with positive modified Sgarbossa criteria
  • LBBB or RBBB with strong clinical suspicion of myocardial ischemia
• Procedure: balloon dilatation with stent implantation (see “Cardiac catheterization”)
• First medical contact (FMC) to PCI time
  • Ideally ≤ 90 minutes.
  • Should not exceed 120 minutes

Fibrinolytic therapy in STEMI ^[1]

• Indications (in STEMI and STEMI equivalents, if all of the following apply):
  • PCI cannot be performed ≤ 120 minutes after FMC.
  • Symptom onset
    • ≤ 12 hours
    • OR 12–24 hours with clinical signs of ongoing ischemia (PCI is even more preferable in this context)
  • No contraindications to fibrinolysis present
• Timing: within < 30 minutes of patient arrival at the hospital
• Contraindications
  • If > 24 hours after symptom onset
  • See “Contraindications for fibrinolysis in STEMI and STEMI-equivalents.”
• Regimens (one of the following)
  • Tenecteplase
  • Alteplase
  • Reteplase
  • Streptokinase
• Postfibrinolysis: Check TIMI coronary grade flow and transfer to a facility with PCI capabilities.

PCI should be performed even if lysis is successful.

Streptokinase is nonfibrin-specific and highly antigenic. It is contraindicated within 6 months of previous exposure to streptokinase.

Other

• Coronary artery bypass grafting: Not routinely recommended for acute STEMI ^[1]
  • Consider in the following cases:
    • Coronary anatomy poorly suited to PCI
    • After unsuccessful PCI
    • STEMI occurring at the time of surgical repair of a mechanical defect

Antiplatelet therapy and anticoagulation in STEMI ^[1]

• Timing: Therapy should be initiated without delaying revascularization.

For patients < 120 min away from a PCI-capable facility

• Immediate cardiology consult and evaluation for emergency revascularization (code STEMI)
• Transfer to cath lab for angiography.
• Start antiplatelets and anticoagulation (see “Antiplatelet therapy and anticoagulation in STEMI”).
  • Aspirin
  • ADP receptor inhibitor (can also be given at time of PCI)
  • Start anticoagulation with UFH, bivalirudin, or fondaparinux.
  • Consider glycoprotein (GP) IIb/IIIa receptor antagonist.

For patients > 120 min away from a PCI-capable facility and symptom onset < 12 hours

• Immediate cardiology consult (code STEMI), even if no PCI is available
• Check for contraindications to fibrinolysis (see “Contraindications for fibrinolysis in STEMI and STEMI-equivalents”).
• If no absolute contraindications present: Administer fibrinolytic (see “Fibrinolytic therapy in STEMI”).
• Start antiplatelets and anticoagulation (see “Antiplatelet therapy and anticoagulation in STEMI”).
  • Aspirin (as soon as possible)
  • ADP receptor inhibitor: clopidogrel
  • Start anticoagulation with UFH, enoxaparin, or fondaparinux.
• Postfibrinolysis: Check TIMI coronary grade flow.
• Transfer to a PCI-capable facility.

For all patients with STEMI

• Adjunctive medical therapy for ACS
  • Supplemental oxygen as needed: target SpO₂ > 90%
  • Nitroglycerin for patients with ongoing chest pain or hypertension
  • Analgesia with morphine only for patients with very strong pain.
  • High-intensity statin
  • Consider a beta blocker if there are no contraindications.
  • Consider an ACE inhibitor if there are no contraindications.
• Order continuous telemetry, serial ECG, and serum troponins every 4–6 hours.
• Consider ICU level of care

Patients with NSTE-ACS are classified based on the presence (NSTEMI) or absence (UA) of significantly elevated cardiac troponin (cTn) levels. A key element of management is to assess the necessity for and timing of PCI (fibrinolytics are not indicated in NSTE-ACS). Hemodynamically unstable patients and those with intractable angina require immediate PCI (i.e., the are managed like STEMI patients). Multiple risk scores (e.g., HEART, TIMI, GRACE) can help to determine an adequate strategy but are no substitute for individual clinical judgment. Dual antiplatelet therapy and anticoagulation is indicated initially and the preferred regimens vary based on patient risk factors and timing of revascularization. Some low-risk NSTE-ACS patients can be managed conservatively.

• Findings ^[2]
  • No ST elevations present
  • Nonspecific signs of ischemia may be present, including:
    • ST depression, especially if horizontal or downsloping
    • Transient ST deviations ≥ 0.5 mm (≥ 0.05 mV) in symptomatic patients at rest
    • T-wave inversions of ≥ 2 mm (≥ 0.2 mV) in V₁–V₆
• Additional considerations
  • Normal ECG may be seen in up to 15% of patients with NSTEMI. ^[2][25]
  • Be wary of STEMI-equivalent ECG findings (e.g., signs of posterior myocardial infarction) and repeat ECGs if inconclusive.

To identify STEMI or STEMI-equivalent ECG findings, repeat ECGs if the initial one is inconclusive or any changes in symptoms occur.

The following recommendations are generally consistent with the 2014 AHA/ACC guidelines for the management of NSTE-ACS. ^[2]

Risk-dependent timing of revascularization ^[2][7]

• Management of NSTE-ACS depends on a patient's mortality risk (e.g., TIMI score), clinical findings, and the availability of resources.
• Invasive strategy for NSTE-ACS (very high- to intermediate-risk patients): coronary angiography within 2–72 hours
• Ischemia-guided strategy for NSTE-ACS (in stable, low-risk patients): Further testing (e.g., exercise ECG, stress echocardiography) is used to evaluate the need for coronary angiography.

Patients with NSTEMI who have unstable hemodynamics, intractable angina, suspected posterior infarction, and/or left main-vessel occlusion require urgent PCI (< 2 hours), even if no ST elevations are present. ^[1][2][6]

Fibrinolytic therapy is not indicated in patients with unstable angina or NSTEMI.

Antiplatelet therapy and anticoagulation in NSTE-ACS ^[2]

• Evaluate for very-high risk factors requiring urgent coronary angiography : If present, follow STEMI checklist. ^[2]
• Start antiplatelet therapy and anticoagulation.
  • Aspirin
  • ADP receptor inhibitor: ticagrelor or clopidogrel
  • Anticoagulation with UFH, enoxaparin, bivalirudin, or fondaparinux
• Calculate TIMI score and GRACE score.
• Cardiology consult for discussion of strategy (see “Risk-dependent timing of revascularization in NSTE-ACS”)
• Adjunctive medical therapy for ACS
  • Supplemental oxygen as needed: target SpO₂ > 90%
  • Nitroglycerin for patients with ongoing chest pain or hypertension
  • Analgesia with morphine only for patients with very strong pain
  • High-intensity statin
  • Consider beta blocker if no contraindications.
  • Consider ACE inhibitor if no contraindications.
• Order continuous telemetry, serial ECG, and serum troponins every 3–6 hours.
• Transfer to cardiac telemetry floor or (cardiac) ICU.

Monitoring

• Continuous cardiac monitoring
• Serial 12-lead ECG every 15–30 minutes for the first hour
• Serial serum troponin measurement (every 1–6 hours)

Adjunct medical therapy in ACS ^[1][2]

Acute medical treatment in ACS includes “MONA”: Morphine, Oxygen, Nitroglycerin, and Aspirin. But remember: Morphine, oxygen, and nitroglycerine are not necessarily indicated for every patient (see “Indications”).

Supportive measures

• Oxygen therapy for patients with:
  • Cyanosis
  • Severe dyspnea
  • SpO₂ < 90%
• Fluid management: see “Management of acute heart failure.”
  • Intravenous fluids (e.g., normal saline)
    • Consider for inferior myocardial infarction causing RV dysfunction
    • Increasing the preload optimizes left and right ventricular filling and reduces hemodynamic instability.
  • Loop diuretic (e.g., furosemide ): consider for patients with pulmonary edema, acute heart failure

Subsequent measures

• See “Prevention of myocardial infarction.”
• See “Coronary artery surgery.”

See “Differential diagnoses of chest pain.”

Differential diagnoses of increased troponin ^[7]

• Cardiovascular causes
  • Myocarditis
  • Decompensated congestive heart failure
  • Pulmonary embolism
  • Cardiac arrhythmia, tachycardia
  • Aortic dissection
  • Hypertensive emergencies
  • Structural heart disease
  • Myocardial drug toxicity (e.g., doxorubicin)
  • Cardiac trauma (including iatrogenic/periprocedural)
  • Takotsubo cardiomyopathy
  • Stroke
• Noncardiovascular causes
  • Renal failure
  • Critical illness (e.g., sepsis)
  • Hypothyroidism or hyperthyroidism

Differential diagnoses of ST elevations on ECG ^[1]

• Early repolarization
• LBBB
• Brugada syndrome
• Myocarditis
• Pericarditis
• Pulmonary embolism
• Hyperkalemia
• Tricyclic antidepressant use
• Poor ECG lead placement

The differential diagnoses listed here are not exhaustive.

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