Unstable Angina

A 50-year-old male presents to the emergency department with acute chest pain that began 30 minutes ago. The pain is sudden, substernal, tight, and crushing, severe in intensity, and radiates to the left arm, jaw, and neck. It is not relieved by rest and is associated with shortness of breath, diaphoresis, nausea, and vomiting. He has a history of hypertension, diabetes mellitus, and hyperlipidemia, with poor medication compliance, and is an active smoker who drinks alcohol occasionally. On examination, he appears anxious and diaphoretic. His vital signs show a blood pressure of 130/90 mmHg, pulse rate of 98 beats/min, respiratory rate of 18 breaths/min, oxygen saturation of 92% on room air, and temperature of 97.9°F. Cardiovascular examination may reveal an S4 gallop. Electrocardiography demonstrates ST-segment depression in the anterior leads (V1–V4) with T-wave inversion, consistent with subendocardial ischemia. Initial high-sensitivity cardiac troponin is negative, and repeat measurements at 1–3 hours remain negative, making myocardial necrosis unlikely. Echocardiography shows no significant regional wall motion abnormalities. Diagnosis?

Diagnosis is Unstable Angina (Non–ST-Elevation Acute Coronary Syndrome without myocardial necrosis).

1. Definition

1. Unstable angina is a form of acute coronary syndrome (ACS) characterized by myocardial ischemia without biochemical evidence of myocardial necrosis.
2. It results from transient reduction in coronary blood flow.
3. It typically presents as:
• Angina at rest
• New-onset severe angina
• Crescendo (worsening) angina
4. It represents a high-risk pre-infarction state with potential progression to NSTEMI or STEMI.

2. Etiology

1. Rupture or erosion of atherosclerotic plaque with non-occlusive thrombus (most common)
2. Coronary artery vasospasm (Prinzmetal angina)
3. Coronary microvascular dysfunction
4. Oxygen supply–demand mismatch due to:
• Tachycardia
• Anemia
• Fever
• Thyrotoxicosis
5. Cocaine or stimulant-induced vasoconstriction

3. Pathophysiology

1. Atherosclerotic plaque becomes unstable and ruptures
2. Exposure of subendothelial collagen → platelet adhesion and activation
3. Formation of a platelet-rich thrombus (white thrombus typical of ACS)
4. Partial occlusion of coronary artery → reduced coronary perfusion
5. Results in subendocardial ischemia (most vulnerable region)
6. No sustained occlusion → no myocardial necrosis (troponin negative)
7. Associated with inflammatory activation (↑ CRP, cytokines)

4. Clinical Features

4.1 Classic Features

1. Chest pain at rest or minimal exertion
2. Crescendo angina (increasing frequency, severity, duration)
3. Prolonged chest pain (>20 minutes)
4. Incomplete relief with nitrates

4.2 Additional Features

1. Radiation to left arm, jaw, neck, or back
2. Shortness of breath
3. Diaphoresis
4. Nausea and vomiting
5. Dizziness or presyncope

4.3 High-Risk Features

1. Ongoing or recurrent chest pain
2. Hemodynamic instability
3. Signs of heart failure (S3, rales)
4. Dynamic ECG changes
5. Refractory angina despite medical therapy

5. Diagnosis

5.1 Electrocardiography

1. ST-segment depression (≥0.5 mm)
2. T-wave inversion
3. Transient ischemic changes
4. May be normal or nonspecific

5.2 Cardiac Biomarkers

1. High-sensitivity troponins negative on serial testing (0 and 1–3 hours)
2. Absence of myocardial necrosis distinguishes UA from NSTEMI

5.3 Echocardiography

1. May be normal
2. May show transient regional wall motion abnormalities
3. Helps exclude alternative diagnoses

5.4 Risk Stratification

TIMI Score (UA/NSTEMI)

1. Age ≥ 65 years
2. ≥ 3 CAD risk factors
3. Known coronary stenosis ≥ 50%
4. Aspirin use in last 7 days
5. ≥ 2 anginal episodes in 24 hours
6. ST deviation ≥ 0.5 mm
7. Elevated cardiac biomarkers (indicates NSTEMI within ACS spectrum)

GRACE Score

1. Used for mortality risk prediction
2. Guides invasive vs conservative strategy

5.5 Definitive Investigation

1. Coronary angiography (gold standard)

6. Management

6.1 Initial Step

1. Rapid assessment of hemodynamic stability and risk
2. Continuous cardiac monitoring

6.2 Immediate Medical Therapy (ACS Protocol)

1. Aspirin (loading dose 162–325 mg)
2. P2Y12 inhibitor (clopidogrel/ticagrelor)
3. Anticoagulation (UFH, LMWH, or fondaparinux)
4. Nitrates (sublingual/IV)
5. Beta-blockers (if no contraindications: hypotension, acute HF, bradycardia)
6. High-intensity statins (e.g., atorvastatin 80 mg)

6.3 Oxygen Therapy

1. Administer only if SpO₂ < 90% or respiratory distress

6.4 Adjunctive Therapy

1. ACE inhibitors/ARBs (especially in diabetes, LV dysfunction)
2. Proton pump inhibitors if high bleeding risk
3. Consider ranolazine for refractory angina

6.5 Risk-Based Strategy

1. Very high risk → Immediate angiography (<2 hours)
2. High risk (TIMI ≥ 3 or high GRACE score) → Early invasive strategy (<24 hours)
3. Low risk → Conservative management + stress testing

6.6 Definitive Management

1. Percutaneous coronary intervention (PCI)
2. Coronary artery bypass grafting (CABG) if indicated

6.7 Secondary Prevention

1. Smoking cessation
2. Lipid control (LDL <70 mg/dL)
3. Blood pressure and diabetes control
4. Lifestyle modification and cardiac rehabilitation

7. Important Clinical Rule

1. Thrombolytics are contraindicated in unstable angina and NSTEMI
2. Thrombolytics are indicated only in STEMI when PCI is not immediately available

8. Key Clinical Insight

1. Chest pain + ST depression = subendocardial ischemia
2. Negative serial troponins distinguish unstable angina from NSTEMI
3. Always treat initially as acute coronary syndrome (ACS)
4. UA and NSTEMI differ only by presence of myocardial necrosis (troponin elevation)
5. Early recognition prevents progression to myocardial infarction

9. Exam Level Pearls

1. Negative troponin distinguishes unstable angina from NSTEMI
2. Subendocardial ischemia causes ST depression
3. Normal ECG does not exclude unstable angina
4. Always treat as acute coronary syndrome initially
5. Early intervention prevents myocardial infarction