- Clinical science
Acute coronary syndrome (ACS) refers to acute myocardial ischemia and/or infarction due to partial or complete occlusion of a coronary artery. There are three clinical entities grouped under ACS: unstable angina pectoris, non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI). These conditions are often difficult to distinguish from one another based on clinical symptoms alone and require ECG and cardiac biomarker measurement to diagnose. Typical cardiac chest pain is substernal in nature, often described as a feeling of pressure, and is relieved with rest and/or nitrate use. The pain may radiate to the left jaw, neck, epigastrium, upper back, and/or left arm. Additionally, autonomic symptoms such as diaphoresis, nausea, and vomiting are common. ECG and laboratory tests are important diagnostic tools in the initial evaluation. In contrast to angina pectoris, NSTEMI and STEMI are characterized by the destruction of cardiac muscle tissue, which results in elevated cardiac enzymes in the blood (i.e., the elevation of troponin after 3–4 hours). Unlike unstable angina and NSTEMI, STEMI results in specific ECG changes (e.g., ST-segment elevation), which can help to determine the location and stage of the infarct. The need for revascularization with either fibrinolysis or cardiac catheterization should be evaluated immediately, as revascularization significantly affects the prognosis of patients with myocardial infarction. Cardiac catheterization should be performed as soon as possible in STEMI and electively within 2–72 hours in high-risk NSTEMI and/or unstable angina. Medical management of ACS includes anticoagulation, analgesics, and antiplatelet agents. Complications of ACS include congestive heart failure, papillary muscle rupture, arrhythmias, and sudden cardiac death. Subsequent management and secondary prevention of ACS depends on the presence of comorbidities, but most patients should be started on indefinite aspirin and statin therapy.
- Myocardial infarction: myocardial cell death caused by prolonged ischemia 
- Acute coronary syndrome: suspicion or confirmed presence of acute myocardial ischemia and/or myocardial infarction
- Sudden cardiac death (SCD): sudden, unexpected death caused by loss of cardiac function (most commonly due to lethal arrhythmia, e.g., ventricular fibrillation)
|Unstable angina ||Non-ST-segment elevation myocardial infarction (NSTEMI) ||ST-segment elevation myocardial infarction (STEMI) |
|Cardiac biomarkers|| |
|ECG findings|| |
Subtypes of ACS cannot be differentiated based on clinical presentation alone!
- ∼ 1.5 million cases of myocardial infarction per year in the US
- ♂ > ♀ (3:1)
- Risk factors: See .
Epidemiological data refers to the US, unless otherwise specified.
- Most common cause: coronary artery
- Coronary artery dissection
- Coronary artery vasospasm (e.g., Prinzmetal angina, cocaine use)
- Takotsubo cardiomyopathy
- Thrombophilia (e.g., polycythemia vera)
- Coronary artery embolism (e.g., due to prosthetic heart valve, atrial fibrillation)
- Vasculitis (e.g., polyarteritis nodosa, Kawasaki syndrome)
- Myocardial oxygen supply-demand mismatch
ACS is most commonly due to unstable plaque formation and subsequent rupture.
Plaque formation and rupture
- For plaque formation, see principles of coronary heart disease and atherosclerosis.
- Stable atherosclerotic plaque: manifests as stable angina (symptomatic during exertion)
- Unstable plaques are lipid-rich and covered by thin fibrous caps → high risk of rupture
- Inflammatory cells in the plaque (e.g., macrophages) secrete matrix metalloproteinases → breakdown of extracellular matrix → weakening of the fibrous cap → minor stress → rupture of the fibrous cap → exposure of highly thrombogenic lipid core → thrombus formation → coronary artery occlusion
Coronary artery occlusion
- Partial coronary artery occlusion
- Complete coronary artery occlusion
Acute retrosternal chest pain
- Typically described as dull, squeezing pressure and/or tightness
- Commonly radiates to left chest, arm, shoulder, neck, jaw, and/or epigastrium
- Precipitated by exertion or stress
- See also .
- The peak time of occurrence is usually in the morning (8–11 a.m.). 
- Dyspnea (especially with exertion)
- Nausea, vomiting
- Diaphoresis, anxiety
- Dizziness, lightheadedness, syncope
- Acute retrosternal chest pain
- Other findings
- Specific to inferior wall infarction
- Atypical presentation: minimal to no chest pain
ECG should be performed immediately once ACS is suspected, followed by measurement of cardiac biomarkers. Further diagnostic workup (e.g., echocardiography) depends on the results of initial evaluation and further risk stratification (e.g., TIMI score).
- 12-lead ECG is the best initial test if ACS is suspected.
- Dynamic changes require serial ECG evaluation.
- Compare to prior ECGs (if available).
ECG changes in STEMI 
- Acute stage: myocardial damage ongoing
Intermediate stage: myocardial necrosis present
- Absence of R wave
- T-wave inversions
- Pathological Q waves
Chronic stage: permanent scarring
- Persistent, broad, and deep Q waves
- Often incomplete recovery of R waves
- Permanent T wave inversion is possible.
An acute left bundle branch block accompanied by symptoms of acute coronary syndrome is also considered an ST-elevation myocardial infarction (STEMI) because ST elevations cannot be adequately assessed in the setting of an LBBB.
- No ST elevations present
- Nonspecific changes may be present.
Localization of the myocardial infarct on ECG 
|ECG leads affected||Infarct location||Vessel involved |
|V1–V6|| || |
|V1–V2|| || |
|V3–V4|| || |
|I, aVL|| || |
|II, III, aVF|| |
Infarction of the anterior wall is caused by obstruction of the LAD or its branches. Depending on the extent of anterior wall infarction, it results in ECG changes in the anterior wall leads (V1–6) and/or I and aVL. Infarction of the inferior wall is caused by obstruction of the LCX or RCA or their branches, and ECG changes are seen in leads II, III, and aVF.
Cardiac biomarkers 
|Troponin T/I|| |
∼ 1 h
|CK-MB||∼ 4–9 h||12–24 h||2–3 days|
|* The values rise, reach a certain maximum, and normalize in the span of hours or days following the onset of myocardial infarction or its symptoms. Values and time references may vary based on the precise laboratory methods employed.|
Serum troponin T is the most important cardiac-specific marker and may be measured 3–4 hours after the onset of myocardial infarction. CK-MB values correlate with the size of the infarct, reach a maximum after approximately 12–24 hours, and normalize after only 2–3 days, making CK-MB a good marker for evaluating reinfarction.
Additional findings 
- Elevated inflammatory markers: ↑ WBC, CRP
- Elevated BNP: especially in heart failure
- Elevated LDH
- Elevated AST (SGOT)
- Best test for definitive diagnosis of acute coronary occlusion
- Can be used for concurrent intervention (e.g., ; with stent placement)
- Can identify site and degree of vessel occlusion
- Indications include
- Transthoracic echocardiogram
- Cardiac CT
TIMI score for unstable angina/NSTEMI 
- Method for calculating the risk of mortality in patients with unstable angina or NSTEMI
- Can be used to determine recommended therapeutic regimen and timing for revascularization
- An increasing score is associated with a higher risk of mortality, new or recurrent myocardial infarction, and need for urgent revascularization (e.g., progression of unstable angina to STEMI)
- Risk score ≥ 3
|Age ≥ 65 years||1|
|Known CAD (prior stenosis > 50%)||1|
|Two or more episodes of severe angina in the last < 24 hours||1|
|ASA use in the last 7 days||1|
|ST deviation (≥ 0.5 mm)||1|
|Elevated cardiac biomarkers||1|
|Time interval post-infarction||Histopathological findings|
| || |
2 weeks to several months
| || |
- See “Ischemia” in .
- Mechanism: blood flow restored → damaged myocytes release reactive oxygen species (ROS); → mitochondrial permeability transition pores are formed → cell swelling → cell death → Ca2+ entry into the cytosol → hypercontraction of myocytes → contraction band necrosis and increase in infarct size 
- Microscopic findings: neutrophilic infiltration, capillary obstruction, and contraction band necrosis of the myocardium
Differential diagnosis of chest pain
- Musculoskeletal: costochondritis
- Dermatological: herpes zoster
- Stimulant drug use (e.g., cocaine)
- For more information, see “Differential diagnoses” of .
- Cardiac causes
- Noncardiac causes
- Early repolarization
- Brugada syndrome
- Pulmonary embolism
- Tricyclic antidepressant use
- Poor ECG lead placement
The differential diagnoses listed here are not exhaustive.
All patients 
- Serial 12-lead ECG
- Continuous cardiac monitoring
- Serial serum troponin measurement
- Sublingual or intravenous nitrate (nitroglycerin or ISDN)
- Morphine IV or SC (3–5 mg)
- Beta blocker
- Statins: early initiation of high-intensity ; (such as atorvastatin 80 mg; ) regardless of baseline cholesterol, LDL, and HDL levels
- Loop diuretic (e.g., furosemide) if the patient has flash pulmonary edema or features of heart failure
- Supportive care
Primary interventions of MI treatment include “MONA”: Morphine, Oxygen, Nitroglycerin, and Aspirin. But remember: Morphine, oxygen, and nitroglycerine are not necessarily indicated for every patient (see indications above).
Revascularization is the most important step in the management of acute STEMI and initiation of further therapies (e.g., DAPT, anticoagulation) should not delay this step in management.
Emergent coronary angiography: with percutaneous coronary intervention (PCI)
- Preferred method of revascularization
- Balloon dilatation with stent implantation (see )
- Ideally, door-to-PCI time should be < 90 minutes. It should not exceed 120 minutes.
Thrombolytic therapy: tPA, reteplase, or streptokinase
- Symptom onset was within the past 3–12 hours
- Should be administered within < 30 minutes of patient arrival to the hospital
- Contraindicated if > 24 hours after symptom onset
- PCI should be performed even if lysis is successful.
- Coronary artery bypass grafting
- Dual antiplatelet therapy: start as soon as possible
- GP IIb/IIIa receptor antagonist: (e.g., eptifibatide or tirofiban): should be considered in precatheterization setting
"Time is muscle": Revascularization should occur as soon as possible in patients with STEMI!
- Dual antiplatelet therapy: start as soon as possible
Immediate vs. delayed revascularization
- The indication for and timing of revascularization depends on the mortality risk (e.g., TIMI score).
- In patients with therapy-resistant chest pain, a TIMI score ≥ 3, ↑ troponin, and/or ST changes > 1 mm
- See “Prevention” below.
- Secondary prophylaxis: See , ; , and .
- See .
0–24 hours post-infarction
Sudden cardiac death
- The most common underlying cause in elderly individuals is acute coronary syndrome (∼ 70% of cases). 
- The most common cause is ventricular arrhythmia.
- Acute left heart failure: : death of affected myocardium → absence of myocardial contraction→ pulmonary edema
- Cardiogenic shock
1–3 days post-infarction
- Early infarct-associated pericarditis
3–14 days post-infarction
Papillary muscle rupture
- Usually occurs 2–7 days after myocardial infarction
- Can lead to acute mitral regurgitation
- Rupture of the posteromedial papillary muscle due to occlusion of the posterior descending artery is most common.
- Clinical features
Ventricular septal rupture
- Usually occurs 3–5 days after myocardial infarction
- Due to structural degradation by macrophages
- Most commonly due to LAD infarction (septal arteries arise from LAD)
- Clinical features
- Treatment: emergency surgery and revascularization (often via CABG)
Left ventricular free wall rupture
- Usually occurs 5–14 days after myocardial infarction
- Greatest risk during macrophage-mediated removal of necrotic tissue
- Clinical features: chest pain, dyspnea, signs of cardiac tamponade (e.g., Beck triad)
2 weeks to months post-infarction
Atrial and ventricular aneurysms
- Clinical features
- Diagnosis: echocardiography
- Treatment: anticoagulation, possibly surgery
Postmyocardial infarction syndrome (Dressler syndrome): pericarditis occurring 2–10 weeks post-MI without an infective cause
- Thought to be due to circulating antibodies against cardiac muscle cells (autoimmune etiology)
- Clinical features
- Treatment: aspirin, acetaminophen
- Complications (rare): hemopericardium, pericardial tamponade
- Arrhythmias (e.g., AV block)
- Congestive heart failure (e.g., ischemic cardiomyopathy)
We list the most important complications. The selection is not exhaustive.
Primary prevention 
- Treatment/avoidance of modifiable risk factors for atherosclerosis (e.g., smoking cessation, treatment of hypertension, etc.)
- Healthy, plant-based diet 
- Regular physical activity and exercise
- Low-dose aspirin is beneficial for certain high-risk groups. The choice to prescribe it should be made on an individual basis.
Secondary prevention 
- Lifestyle modification and treatment of modifiable risk factors (see “Primary prevention” above and )
- Lifelong low-dose aspirin 75–100 mg/day
- DAPT with the addition of an ADP receptor inhibitor (e.g., prasugrel, ticagrelor, or clopidogrel) is recommended for 12 months for all patients who have undergone PCI.
- Glycoprotein IIb/IIIa antagonists (e.g., abciximab) may be considered but are not used routinely.
- Beta blockers: Unless contraindicated, all patients should be started on a beta blocker, which has been shown to confer a mortality benefit.
- Statin: All patients should be started on a high-intensity statin (e.g., atorvastatin).
- An aldosterone antagonist and ACE inhibitor/ARB are recommended for all patients with ischemic cardiomyopathy and an LV ejection fraction < 40% or symptoms of heart failure.