What is the etiology, epidemiology, pathophysiology, clinical manifestations, diagnostics, and management of Acute Coronary Syndrome (ACS) ST-Elevation Myocardial Infarction (STEMI)?

Acute Coronary Syndrome (ACS) - ST-Elevation Myocardial Infarction (STEMI)

1. Etiology

STEMI results from complete coronary artery occlusion, most commonly caused by atherosclerotic plaque rupture or erosion with subsequent thrombotic occlusion. 1

• Plaque disruption is the primary mechanism, where a vulnerable atherosclerotic plaque with a weakened fibrous cap ruptures, exposing procoagulant material that triggers thrombogenesis and complete vessel occlusion 1
• Coronary thrombosis forms at the site of plaque disruption, leading to complete coronary artery obstruction and transmural myocardial ischemia 1
• Less common causes include coronary vasospasm (Prinzmetal angina), coronary embolism, coronary arteritis, aortic dissection involving coronary ostia, and cocaine-induced vasospasm 1
• Supply-demand mismatch can occur with severe anemia, hypotension, tachycardia, hypertrophic cardiomyopathy, or severe aortic stenosis superimposed on fixed coronary stenosis 1

2. Epidemiology and Risk

STEMI accounts for approximately 30% of all acute coronary syndromes, with an estimated 7 million cases worldwide annually and over 1 million hospitalizations in the United States. 2

Age and Gender Distribution

• Average age at first STEMI is 65.8 years for men and 70.4 years for women 1
• Women comprise 43% of all ACS patients across all age groups 1
• Elderly patients and women are more likely to present with atypical symptoms and non-diagnostic ECGs 3

Risk Factors

• Traditional cardiovascular risk factors include older age, male gender, family history of coronary artery disease, diabetes mellitus, hyperlipidemia, hypertension, and smoking 1
• Prior cardiovascular disease including previous MI, known coronary artery disease, peripheral arterial disease, or carotid artery disease significantly increases risk 1
• Precipitating conditions such as anemia, infection, inflammation, fever, and metabolic or thyroid disorders can trigger STEMI in patients with underlying coronary disease 1

Mortality Trends

• Pre-coronary care unit era mortality averaged 25-30% 1
• Pre-reperfusion era (mid-1980s) showed 16% in-hospital mortality 1
• Current mortality with modern reperfusion therapy is 4-7% in clinical trials, though registry studies show higher real-world mortality rates 1, 4
• Primary PCI reduces mortality from 9% to 7% when performed within 120 minutes 2

3. Pathophysiology

STEMI pathophysiology centers on the sudden imbalance between myocardial oxygen supply and demand caused by complete coronary artery occlusion, resulting in transmural myocardial necrosis. 1

Atherogenesis and Plaque Formation

• Progressive atherosclerosis evolves from normal artery → extracellular lipid accumulation in subintima → fibrofatty plaque → vulnerable plaque with thin fibrous cap and procoagulant expression 1
• Plaque vulnerability is characterized by large lipid core, thin fibrous cap, inflammatory cell infiltration, and weakening of the protective fibrous layer 1

Acute Thrombotic Occlusion

• Fibrous cap disruption exposes thrombogenic material, triggering platelet adhesion, activation, and aggregation 1
• Thrombus propagation leads to complete coronary occlusion, distinguishing STEMI from NSTE-ACS where occlusion is partial or intermittent 1, 2
• Coronary vasospasm may contribute to or exacerbate the occlusion 1

Myocardial Injury Cascade

• Transmural ischemia begins within minutes of complete occlusion, affecting the full thickness of myocardium supplied by the occluded artery 1
• Irreversible injury starts within 20-40 minutes of complete occlusion if not reperfused 1
• Infarct size correlates directly with duration of occlusion and extent of collateral circulation 1, 5
• Autonomic activation produces pallor, sweating, and hemodynamic changes including hypotension or narrow pulse pressure 1

Complications

• Mechanical complications include papillary muscle rupture causing acute mitral regurgitation, ventricular septal rupture, and free wall rupture 1
• Electrical instability manifests as ventricular arrhythmias and conduction disturbances 1
• Ventricular dysfunction ranges from regional wall motion abnormalities to cardiogenic shock 1

4. Clinical Manifestations

The hallmark presentation is persistent chest discomfort lasting 10-20 minutes or more that does not fully respond to nitroglycerin, though approximately 40% of men and 48% of women present with atypical symptoms. 1, 2

Typical Chest Pain Characteristics

• Quality: Pressure, tightness, squeezing, heaviness, or burning sensation in the chest 1
• Location: Retrosternal or precordial, may be epigastric or interscapular 1
• Radiation: Neck, lower jaw, left arm, or both arms 1
• Duration: Typically >20 minutes and persistent, unlike stable angina 1
• Nitroglycerin response: Incomplete or no relief, distinguishing it from stable angina 1

Atypical Presentations

• Non-chest symptoms include isolated dyspnea (79% of men and 74% of women with chest discomfort, but many present with dyspnea alone or combined with chest pain) 2
• Elderly patients commonly present with fatigue, dyspnea, faintness, or syncope rather than chest pain 1
• Diabetic patients may have minimal or absent pain due to autonomic neuropathy 3
• Women are more likely to present with atypical symptoms including nausea, vomiting, and fatigue 3

Associated Symptoms

• Autonomic symptoms: Pallor, diaphoresis, nausea, vomiting 1
• Anxiety: Sense of impending doom 1
• Dyspnea: May indicate heart failure or extensive ischemia 1

Physical Examination Findings

• Vital signs: Hypotension, narrow pulse pressure, tachycardia or bradycardia 1
• Cardiac auscultation: Third heart sound (S3), fourth heart sound (S4), systolic murmur of acute mitral regurgitation 1
• Pulmonary findings: Basal rales indicating pulmonary edema 1
• Peripheral signs: Irregular pulse, jugular venous distension 1
• Normal examination: Frequently unremarkable, especially early in presentation 1

Red Flags for Alternative Diagnoses

• Blood pressure discrepancy between arms or upper/lower limbs suggests aortic dissection 1
• Friction rub suggests pericarditis 1
• Pain reproduced by palpation suggests musculoskeletal etiology 1

5. Diagnostics

A 12-lead ECG must be obtained and interpreted by a trained clinician within 10 minutes of presentation, as it is the primary tool for distinguishing STEMI from other ACS. 1, 6

Electrocardiographic Criteria for STEMI

• ST-segment elevation ≥1 mm (0.1 mV) in two or more contiguous leads, or new or presumed new left bundle branch block in the appropriate clinical context 1
• Posterior STEMI presents with ST-segment depression in anterior leads (V1-V3); posterior leads (V7-V9) should be obtained showing ST elevation 1
• Right ventricular infarction: V4R lead shows ST elevation in inferior STEMI 1

Cardiac Biomarkers

• High-sensitivity cardiac troponin (hs-cTn) should be measured as soon as possible upon presentation 1
• Repeat measurement at 1-2 hours for hs-cTn or 3-6 hours for conventional troponin if initial value is nondiagnostic 1
• Do not delay reperfusion for troponin results in patients with diagnostic ECG changes 1
• Troponin elevation confirms myocardial necrosis but should not delay treatment when ECG shows STEMI 1

Additional Laboratory Tests

• Initial blood work: Creatinine, hemoglobin, hematocrit, platelet count, blood glucose, INR (if on anticoagulation) 3
• Results availability: Troponin should be available within 60 minutes 3

Echocardiography

• Urgent indication: Cardiogenic shock, hemodynamic instability, or suspected mechanical complications 1
• Point-of-care ultrasound: May be performed by trained clinicians for immediate assessment 1
• Regional wall motion abnormalities: Confirm ischemic territory and assess ventricular function 1
• Should not delay reperfusion: Unless it would immediately change management 1

Serial ECG Monitoring

• Continuous monitoring: All STEMI patients require continuous ECG monitoring with defibrillation capability 6, 3
• Repeat ECGs: If initial ECG is equivocal, obtain repeated recordings and compare with previous ECGs 1
• Additional leads: V7-V8 for posterior infarction, V4R for right ventricular involvement 1

Risk Stratification

• Clinical assessment: History of coronary disease, hemodynamic status, heart failure signs, arrhythmias 1
• ECG findings: Number of leads with ST elevation, magnitude of ST elevation, presence of reciprocal changes 1
• Not applicable for immediate management: Risk scores are less relevant in STEMI as all patients require immediate reperfusion 6

6. Management

Primary percutaneous coronary intervention (PCI) within 90-120 minutes of first medical contact is the definitive reperfusion strategy for all STEMI patients presenting within 12 hours of symptom onset. 6, 2

Immediate Pre-Hospital and Emergency Department Actions

Initial Stabilization

• Continuous cardiac monitoring with defibrillator capability and defibrillator patches placed 6, 3
• Intravenous access established immediately 1
• Oxygen therapy: Only if oxygen saturation <90% or respiratory distress (routine oxygen not recommended, Class III evidence) 6

Symptom Management

• Morphine sulfate 4-8 mg IV with additional 2 mg doses at 5-15 minute intervals for pain control and anxiety reduction 6, 7
• Nitroglycerin sublingual or IV for ongoing chest pain, unless contraindicated (hypotension, right ventricular infarction, recent phosphodiesterase inhibitor use) 7

Immediate Antiplatelet Therapy

• Aspirin 150-325 mg oral (or IV if unable to swallow) administered immediately 6, 8
• P2Y12 inhibitor (prasugrel or ticagrelor preferred over clopidogrel) given before or at time of PCI 6, 8
• Clopidogrel 300-600 mg loading dose if prasugrel or ticagrelor unavailable 8

Anticoagulation

• Unfractionated heparin as weight-adjusted IV bolus followed by infusion for primary PCI 6
• Low molecular weight heparin (enoxaparin) is at least as effective as unfractionated heparin 9, 7

Reperfusion Strategy Selection

Primary PCI (Preferred Strategy)

• Timing: Perform within 90-120 minutes of first medical contact if PCI-capable facility available 6, 2
• Superiority: Reduces mortality and reinfarction beyond fibrinolysis, especially when performed within 90 minutes 10, 2
• All STEMI patients: Indicated for symptoms <12 hours duration 6
• Glycoprotein IIb/IIIa inhibitors: Should be used in association with PCI in high-risk patients 9

Fibrinolytic Therapy (When PCI Not Available Within 120 Minutes)

• Indication: If primary PCI cannot be performed within 120 minutes of STEMI diagnosis 6, 2
• Timing: Most effective within 3 hours of symptom onset (equally efficient as PCI in this window) 7
• Agents: Fibrin-specific agents preferred (alteplase, reteplase, or tenecteplase at full dose for age <75 years; half dose for age ≥75 years) 2
• Alternative: Streptokinase at full dose if cost is a consideration 2
• Pre-hospital administration: Preferably initiated in pre-hospital setting 6
• Mandatory transfer: All patients receiving fibrinolysis must be transferred to PCI-capable center immediately after fibrinolysis 6
• Rescue PCI: Perform within 24 hours, or emergently if heart failure/shock develops 6

Post-Reperfusion Management

Immediate Post-Procedure Care

• Continuous monitoring: ECG monitoring for arrhythmias and recurrent ischemia 6
• Vital signs: Regular assessment 3
• Emergency angiography: Immediately if heart failure or cardiogenic shock develops (Class I, Level A evidence) 6

Dual Antiplatelet Therapy (DAPT)

• Duration: Continue aspirin 75-100 mg plus ticagrelor or prasugrel (or clopidogrel if unavailable/contraindicated) for 12 months unless excessive bleeding risk 6
• Strength of evidence: Class I, Level A 6

Gastrointestinal Protection

• Proton pump inhibitor (PPI): Recommended in combination with DAPT for patients at high risk of gastrointestinal bleeding (Class I, Level B evidence) 6

Secondary Prevention (Initiated During Hospitalization)

• Beta-blockers: For all patients without contraindications 1, 6
• ACE inhibitors: For all patients, especially those with anterior MI, heart failure, or LVEF <40% 1, 9
• Statins: High-intensity statin therapy for cholesterol lowering 1, 9
• Smoking cessation: Imperative for all patients 9
• Blood pressure control: Tight control to target 9
• Diabetes management: Optimal glycemic control 9

Special Considerations

High-Risk Features Requiring Immediate Intervention

• Refractory angina despite medical therapy 3
• Hemodynamic instability or cardiogenic shock 1, 3
• Life-threatening ventricular arrhythmias 3
• Mechanical complications: Acute mitral regurgitation, ventricular septal rupture, free wall rupture 1

Atypical Presentations

• ST elevation without chest pain: Treat as true STEMI requiring immediate reperfusion; absence of chest pain does not change urgency or management approach 6
• Elderly and diabetic patients: Maintain high index of suspicion despite atypical symptoms 3

Common Pitfalls to Avoid

• Delaying reperfusion for additional diagnostic testing unless it immediately changes management 1
• Waiting for troponin results when ECG shows diagnostic ST elevation 1
• Routine oxygen administration in patients with adequate saturation (Class III recommendation) 6
• Underestimating posterior or right ventricular MI: Obtain additional ECG leads when suspected 1
• Failing to transfer post-fibrinolysis patients to PCI-capable centers 6