Acute Coronary Syndromes — Part 1: Definitions, Pathophysiology & Initial Evaluation

1. The Acute Coronary Syndrome Spectrum

1.1 Overview

Acute coronary syndromes (ACS) encompass a spectrum of clinical presentations resulting from acute myocardial ischemia, unified by a common pathophysiology — disruption of a coronary atherosclerotic plaque with superimposed thrombosis, leading to reduction or cessation of myocardial blood flow. The ACS spectrum is classified into three categories based on ECG findings and biomarker status:^{1 2}

1.2 Key Distinctions

• STEMI requires emergent reperfusion therapy (primary PCI or fibrinolysis) and is a time-critical diagnosis. The ECG is the primary diagnostic tool.¹
• NSTEMI is distinguished from UA solely by the presence of elevated cardiac troponin, indicating myocardial necrosis. Both require urgent risk stratification and consideration of invasive management.²
• Unstable Angina has become less commonly diagnosed in the era of high-sensitivity troponin assays, as many patients previously classified as UA are now reclassified as NSTEMI due to detection of smaller degrees of myocardial necrosis.³
• The distinction between STEMI and NSTEMI/UA is made at the time of initial ECG and determines the immediate management pathway. Biomarker results should never delay reperfusion in suspected STEMI.¹

2. Fourth Universal Definition of Myocardial Infarction

The international expert consensus document published in 2018 by the joint cardiology task force provides the current standard definitions for myocardial infarction and myocardial injury.⁴

2.1 Myocardial Injury vs. Myocardial Infarction

Myocardial injury is defined as detection of an elevated cardiac troponin value above the 99th percentile upper reference limit (URL). Injury is considered acute if there is a rise and/or fall of troponin values.

Myocardial infarction is a specific subset of myocardial injury in which the acute injury occurs in a clinical context consistent with acute myocardial ischemia. The diagnosis of MI requires:⁴

Detection of a rise and/or fall of cardiac troponin (cTn) with at least one value above the 99th percentile URL AND at least one of the following:

1. Symptoms of acute myocardial ischemia
2. New ischemic ECG changes
3. Development of pathological Q waves
4. Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with an ischemic etiology
5. Identification of a coronary thrombus by angiography or autopsy (not for Types 2 or 3)

2.2 Five Types of Myocardial Infarction

2.3 Type 2 MI — Differential and Clinical Significance

Type 2 MI is frequently encountered in the ED and must be differentiated from Type 1 MI, as the management differs fundamentally. Common triggers of supply-demand mismatch include:⁴

Key clinical point: Type 2 MI treatment is directed at correcting the underlying supply-demand mismatch, not routine ACS pharmacotherapy. However, patients with known coronary artery disease who develop Type 2 MI may benefit from some ACS therapies on a case-by-case basis.⁴

3. Pathophysiology of Acute Coronary Syndromes

3.1 Plaque Rupture

The most common mechanism of Type 1 MI, accounting for approximately 60-70% of fatal coronary thrombi. Plaque rupture involves disruption of a thin fibrous cap (typically < 65 micrometers) overlying a lipid-rich necrotic core, exposing thrombogenic material to the bloodstream. Key features of the “vulnerable plaque”:⁵

• Thin-cap fibroatheroma (TCFA) with fibrous cap < 65 micrometers
• Large lipid-rich necrotic core (> 40% of plaque area)
• Increased macrophage infiltration and inflammatory activity
• Reduced smooth muscle cell density in the cap
• Positive (outward) remodeling
• Neovascularization from the vasa vasorum

3.2 Plaque Erosion

Accounts for approximately 25-35% of ACS events. The fibrous cap remains intact, but endothelial denudation or dysfunction leads to superimposed thrombosis. Plaque erosion is more common in:⁵

• Younger patients (especially women < 50 years)
• Smokers
• Patients with less severe underlying stenosis
• Plaques rich in proteoglycans and smooth muscle cells rather than lipid

3.3 Other Mechanisms

3.4 Thrombosis Cascade in ACS

Following plaque disruption, the thrombotic cascade proceeds through two overlapping phases:

1. Primary hemostasis: Platelet adhesion (via GP Ib/IX/V binding to von Willebrand factor on exposed collagen) → platelet activation (via ADP, thromboxane A2, thrombin) → platelet aggregation (via GP IIb/IIIa binding to fibrinogen)
2. Secondary hemostasis: Tissue factor exposure activates the coagulation cascade → thrombin generation → fibrin formation → stabilized fibrin-platelet thrombus

This pathophysiology provides the rationale for dual antiplatelet therapy (blocking platelet activation and aggregation) and anticoagulation (inhibiting thrombin generation) in ACS management.^{1 2}

4. Initial Emergency Department Evaluation

4.1 Prehospital Care

• 12-lead ECG: Should be acquired in the field within 10 minutes of EMS contact for patients with symptoms suggestive of ACS¹
• Prehospital STEMI activation: When field ECG demonstrates STEMI, the receiving cardiac catheterization laboratory should be activated while in transit to minimize door-to-balloon time
• Aspirin: Chewable aspirin 162-325 mg should be administered as soon as ACS is suspected (unless true aspirin allergy)¹
• Nitroglycerin: Sublingual nitroglycerin 0.4 mg every 5 minutes (up to 3 doses) for ongoing chest pain; avoid if systolic BP < 90 mmHg, severe aortic stenosis, or recent phosphodiesterase-5 inhibitor use (sildenafil/vardenafil within 24 hours; tadalafil within 48 hours)¹
• Transport destination: Patients with STEMI should be transported directly to a PCI-capable facility when the anticipated first medical contact-to-device time is ≤ 120 minutes¹

4.2 Focused History

The initial history should be rapidly obtained and should include:⁶

4.3 Physical Examination

The physical examination in suspected ACS serves three purposes: (1) identify hemodynamic compromise, (2) detect complications, and (3) evaluate for alternative diagnoses.^{1 2}

4.4 Killip Classification

The Killip classification is assessed on initial presentation and provides important prognostic information:¹

4.5 Differential Diagnosis of Acute Chest Pain

5. The 12-Lead ECG in Acute Coronary Syndromes

5.1 ECG Acquisition Standards

• A 12-lead ECG must be acquired and interpreted within 10 minutes of ED arrival for any patient with symptoms suggestive of ACS^{1 7}
• If the initial ECG is non-diagnostic but clinical suspicion remains high, serial ECGs should be obtained at 15-30 minute intervals during the first 1-2 hours⁶
• Right-sided leads (V3R, V4R) should be obtained when inferior STEMI is identified to assess for right ventricular involvement¹
• Posterior leads (V7, V8, V9) should be obtained when there is ST depression in V1-V3 (suspected posterior MI) or when clinical suspicion for ACS is high despite a non-diagnostic standard 12-lead ECG¹

5.2 STEMI Criteria — ST-Segment Elevation

The diagnosis of STEMI requires new ST elevation at the J point in at least two contiguous leads meeting the following voltage criteria:^{1 4}

5.3 STEMI Localization by ECG Leads

5.4 STEMI Equivalents

These ECG patterns represent acute coronary occlusion (or near-occlusion) requiring emergent reperfusion despite not meeting classic STEMI voltage criteria. Recognition of these patterns is critical and should trigger the same time-urgent response as STEMI.^{7 8}

5.4.1 De Winter Pattern

• Description: Tall, symmetric, peaked T waves with 1-3 mm upsloping ST depression at the J point in precordial leads (V1-V6), often with subtle ST elevation in aVR
• Significance: Represents acute LAD occlusion equivalent to anterior STEMI; present in approximately 2% of acute LAD occlusions
• Management: Emergent catheterization/PCI (treat as STEMI equivalent)⁸
• Key distinguishing features: The ST depression is upsloping (not horizontal or downsloping as in typical subendocardial ischemia), and the T waves are tall, symmetric, and hyperacute

5.4.2 Wellens Syndrome

• Description: Biphasic (Type A) or deeply inverted (Type B) T waves in V2-V3, occurring during a pain-free interval in patients with recent anginal symptoms
• Pattern A: Biphasic T waves (initially positive, then negative) in V2-V3 — ~25% of cases
• Pattern B: Deep, symmetric T-wave inversions in V2-V3 (may extend to V1-V6) — ~75% of cases
• Significance: Indicates critical proximal LAD stenosis with high risk of imminent extensive anterior MI
• Management: Avoid stress testing (high risk of precipitating infarction). Refer for cardiac catheterization. These patients require revascularization, not a stress test.⁸
• Key ECG criteria: Minimal or no ST elevation, no precordial Q waves, preserved R-wave progression, normal or minimally elevated troponin at time of ECG (the pattern appears during reperfusion/pain-free intervals)

5.4.3 Posterior STEMI (Isolated Posterior MI)

• Standard 12-lead clues: ST depression in V1-V3 with tall, broad R waves in V1-V2 (R/S ratio > 1), upright T waves in V1-V3
• Posterior leads: ST elevation ≥ 0.5 mm in V7-V9 confirms the diagnosis
• Significance: Represents acute occlusion of the LCx or PDA; occurs in approximately 3-11% of all acute MI; frequently missed because the standard 12-lead ECG does not directly record posterior electrical activity¹
• Management: Emergent reperfusion (same as STEMI). The international cardiology guidelines committee and the emergency cardiology expert panel both recommend posterior lead acquisition in any patient with ST depression isolated to V1-V3^{1 7}

5.4.4 Sgarbossa Criteria (STEMI in the Setting of Left Bundle Branch Block)

In patients with LBBB, the expected baseline ST-T changes make STEMI diagnosis challenging. The modified Sgarbossa criteria (Smith modification) improve diagnostic accuracy:⁹

Interpretation:

• Original Sgarbossa: Score ≥ 3 is highly specific (approximately 90%) for STEMI in LBBB, but sensitivity is low (~36%)
• Modified Sgarbossa (Smith): Replacing the absolute 5 mm criterion with the proportional 0.25 ratio improves sensitivity to approximately 91% while maintaining specificity around 90%⁹
• Clinical application: New or presumably new LBBB alone is no longer considered a STEMI equivalent per updated guidelines. The presence of ischemic symptoms PLUS positive modified Sgarbossa criteria should trigger emergent reperfusion.⁷

5.4.5 Sgarbossa Criteria in Ventricular Paced Rhythm

The same modified Sgarbossa criteria can be applied to patients with ventricular paced rhythms (which produce an LBBB-like pattern). The concordance/discordance rules are identical:⁹

• Concordant ST elevation ≥ 1 mm: highly specific for acute MI
• Concordant ST depression ≥ 1 mm in V1-V3: highly specific for acute MI
• Excessive discordant ST elevation (ST/S ratio ≥ 0.25): sensitive and specific

5.4.6 Isolated ST Elevation in aVR

• Pattern: ST elevation in aVR ≥ 1 mm with diffuse ST depression in multiple other leads (≥ 6 leads)
• Significance: Suggests left main coronary artery (LMCA) occlusion or severe three-vessel disease with diffuse subendocardial ischemia
• Clinical context: The degree of ST elevation in aVR relative to ST elevation in V1 may help differentiate LMCA (aVR > V1) from proximal LAD (V1 > aVR) occlusion
• Management: Emergent cardiology consultation and catheterization; these patients are at extremely high risk for cardiogenic shock and cardiac arrest⁷

6. Right Ventricular Myocardial Infarction

6.1 Epidemiology and Pathophysiology

Right ventricular (RV) infarction occurs in approximately 30-50% of inferior STEMIs and results from occlusion of the proximal RCA (before the RV marginal branches). Isolated RV infarction is rare. The hemodynamic consequences are distinct from LV infarction and require specific management.^{1 10}

6.2 Diagnosis

6.3 Hemodynamic Consequences

The infarcted RV is unable to generate adequate preload for the LV. Cardiac output becomes highly preload-dependent. Key hemodynamic features:

• Elevated right atrial pressure (RAP) with RAP/PCWP ratio ≥ 0.8
• Low or normal pulmonary capillary wedge pressure (PCWP)
• Low cardiac output
• Equalization of diastolic pressures (RAP ≈ RV diastolic pressure ≈ PCWP) — may mimic constrictive pericarditis or tamponade

6.4 Management Principles for RV Infarction

7. ECG Pitfalls and Special Considerations

7.1 Conditions That May Mimic STEMI on ECG

7.2 Normal-ECG ACS

Approximately 1-6% of patients with acute MI have a completely normal initial ECG. Therefore:⁶

• A normal ECG does not exclude ACS
• Serial ECGs and troponin testing are essential when clinical suspicion is present
• Clinical risk stratification tools (HEART score) should be applied to guide disposition

7.3 Dynamic ECG Changes

Serial ECG monitoring may reveal evolving changes not present on the initial tracing. Key dynamic patterns include:

• Intermittent ST elevation (suggesting intermittent occlusion/reperfusion)
• Progressive ST depression or T-wave inversions
• New conduction abnormalities (new LBBB, fascicular blocks, AV block)
• Resolution of ST elevation (may indicate spontaneous reperfusion — important for timing of intervention)

References