What is Acute Coronary Syndrome (ACS)?

What is Acute Coronary Syndrome?

Acute coronary syndrome (ACS) is a spectrum of acute myocardial ischemic conditions caused by disruption (rupture or erosion) of an unstable coronary artery atherosclerotic plaque with associated partial or complete coronary artery thrombosis, resulting in diminished blood flow to the myocardium. 1

Clinical Spectrum and Classification

ACS encompasses three related clinical conditions that exist along a continuum of severity 1:

• Unstable angina (UA): Transient myocardial ischemia with diminished coronary flow but without significant myonecrosis, characterized by negative cardiac troponin levels 1
• Non-ST-segment elevation myocardial infarction (NSTEMI): Myocardial ischemia with elevated cardiac biomarkers indicating myonecrosis, but without persistent ST-segment elevation on ECG, typically caused by partially occluded coronary artery leading to subendocardial ischemia 1
• ST-segment elevation myocardial infarction (STEMI): Complete coronary artery occlusion with persistent ST-segment elevation (>20 minutes), leading to transmural myocardial ischemia and infarction, accounting for approximately 30% of ACS cases 1, 2

Epidemiology

• In the United States, more than 780,000 persons experience ACS annually, with approximately 70% presenting as NSTE-ACS (unstable angina or NSTEMI) 1
• Worldwide, more than 7 million people are diagnosed with ACS each year 3
• Patients with NSTE-ACS typically have more cardiac and noncardiac comorbidities compared to STEMI patients 1

Pathophysiology

The hallmark mechanism involves a sudden imbalance between myocardial oxygen supply and demand 1:

• Primary mechanism: Atherosclerotic plaque rupture or erosion with exposure of plaque contents to circulation, culminating in activation of the coagulation cascade and subsequent thrombosis 1
• Progressive pathology: Lipid accumulation and inflammation within atherosclerotic plaque leads to plaque instability, followed by rupture or erosion 1
• Thrombotic consequences: When thrombus forms in epicardial coronary vessels, it compromises myocardial blood flow, causing ischemia and eventual myonecrosis 1

Less Common Causes

Beyond atherosclerotic plaque disruption, ACS can result from 1, 2:

• Coronary artery vasospasm (Prinzmetal angina)
• Coronary embolism
• Coronary arteritis
• Spontaneous coronary artery dissection
• Noncoronary causes of supply-demand mismatch (severe anemia, hypotension, hypertension, tachycardia, hypertrophic cardiomyopathy, severe aortic stenosis)
• Nonischemic myocardial injury (myocarditis, cardiac contusion, cardiotoxic drugs)
• Stress (Takotsubo) cardiomyopathy

Initial Diagnostic Approach

The diagnosis and classification of ACS should be based on three key elements 1:

1. Clinical history and symptomatology: Chest discomfort at rest affects approximately 79% of men and 74% of women, described as pressure, tightness, pain, or burning; atypical presentations (isolated dyspnea, epigastric pain, syncope) are more common in elderly, diabetics, and women 2, 3

2. 12-lead electrocardiogram: Must be obtained within 10 minutes of presentation 1, 3

   • STEMI criteria: New or presumed new ST-elevation ≥1 mm in ≥2 anatomically contiguous leads (measured at J-point), or ≥2 mm in men ≥40 years, ≥2.5 mm in men <40 years, and ≥1.5 mm in women regardless of age in leads V2-V3 1
   • NSTE-ACS criteria: New or presumed new horizontal or down-sloping ST-segment depression ≥0.5 mm in ≥2 contiguous leads and/or T-wave inversion >1 mm in ≥2 contiguous leads with prominent R wave or R/S ratio >1, or transient ST-segment elevation 1
   • Important caveat: Many NSTE-ACS patients have nonspecific ST-segment or T-wave changes or normal ECG; absence of electrocardiographic evidence does not exclude ACS 1

3. Cardiac troponin assessment: High-sensitivity troponin measurements are the preferred test to distinguish NSTEMI (elevated troponin) from unstable angina (negative troponin) 1, 3

Dynamic Nature

A critical pitfall to recognize: The pathophysiology of ACS is dynamic, and patients can rapidly progress from one clinical condition (unstable angina → NSTEMI → STEMI) to another during presentation, initial evaluation, and treatment 1. This requires continuous monitoring and serial reassessment.

Classification Under Universal Definition

Under the Universal Definition of Myocardial Infarction, ACS events resulting from atherosclerotic plaque rupture or erosion with subsequent thrombosis are classified as Type 1 MI events 1. This distinguishes them from Type 2 MI (supply-demand mismatch without plaque rupture), spontaneous coronary artery dissection, and MINOCA (MI with nonobstructive coronary artery disease), which are managed differently 1.