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Angina Pectoris - Complete University Exam Guide

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1. Definition

"Angina pectoris is intermittent chest discomfort or pain caused by transient, reversible myocardial ischemia that is insufficient to cause myocyte necrosis." - Robbins & Kumar Basic Pathology

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2. Epidemiology

• Males = ~70% of all angina patients; even higher proportion in those <50 years
• ~10 million Americans live with angina pectoris
• Among adults aged 60-79: ~25% of men, ~16% of women have coronary heart disease
• Women's presentations may differ from men (less typical chest pain; more dyspnea, nausea, fatigue)
• Coronary atherosclerosis can begin before age 20 and progress silently for decades

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3. Pathophysiology

• Heart rate
• Myocardial contractility
• Wall tension (preload + afterload)

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4. Classification of Angina (Three Variants)

A. Stable (Typical) Angina

• Most common form
• Caused by fixed atherosclerotic stenosis of coronary artery (chronic)
• Predictable: occurs with exertion, emotion, cold, large meals - NOT at rest
• Relieved by rest (reduces demand) or nitroglycerin/calcium channel blockers (increase perfusion)
• A reliable, reproducible threshold of exertion triggers the episode

B. Prinzmetal (Variant) Angina

• Caused by coronary artery vasospasm (not fixed stenosis)
• Occurs at rest, often in the early morning hours
• Attacks are unrelated to physical activity, heart rate, or blood pressure
• Can affect both atherosclerotic AND completely normal coronary vessels
• ECG: transient ST-segment elevation (unlike stable angina which shows ST depression)
• Responds promptly to vasodilators (nitroglycerin, calcium channel blockers)
• Associated with: smoking, cocaine use, cold exposure, hyperventilation

C. Unstable Angina

• Increasingly frequent, prolonged (>20 min), or severe chest pain
• Precipitated by progressively lower levels of activity, or occurs at rest
• Pathology: plaque disruption + superimposed thrombosis + distal embolization + vasospasm
• A harbinger of MI - high risk of complete vascular occlusion
• Part of the Acute Coronary Syndrome (ACS) spectrum
• Treated aggressively to prevent irreversible myocardial damage

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5. Clinical Features (History)

• Described as: heaviness, pressure, squeezing, smothering, choking, crushing - rarely as "sharp pain"
• Levine's sign: patient places a clenched fist over the sternum (pathognomonic of ischemic chest discomfort)
• Crescendo-decrescendo pattern - not maximum intensity at onset
• Lasts 2-5 minutes (stable angina)

• Substernal / precordial (behind the sternum)
• Radiates to: left shoulder, both arms (especially ulnar aspect of forearm and hand), jaw, teeth, neck, back, interscapular region, epigastrium
• NOT below the umbilicus or above the mandible
• NOT to trapezius muscles (that pattern = pericarditis)

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6. CCS Grading Scale (Canadian Cardiovascular Society)

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7. Investigations / Workup

• Full blood count (CBC) - rule out anemia
• Fasting lipid profile
• Fasting glucose / HbA1c
• Renal function + electrolytes
• Thyroid function (TSH)
• Resting ECG
• Chest radiograph

• Stable angina at rest: often normal
• During attack: ST-segment depression (subendocardial ischemia), T-wave flattening or inversion
• Prinzmetal angina during attack: ST-segment elevation

• Demonstrates ischemia at a defined workload
• Positive = ≥1 mm horizontal or down-sloping ST depression at 60-80 ms after J-point

• Exercise or pharmacologic stress echocardiography: wall motion abnormalities
• Myocardial perfusion scintigraphy (nuclear stress test - SPECT/PET): perfusion defects at stress that normalize at rest
• CT Coronary Angiography (CTCA): non-invasive assessment of coronary stenosis; CAC (coronary artery calcium) score as adjunct
• Invasive coronary angiography: gold standard for defining coronary anatomy - indicated when revascularization is planned

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8. Management

A. Non-Pharmacological (Lifestyle)

• Smoking cessation (most important modifiable risk factor)
• Weight loss, regular aerobic exercise (cardiac rehabilitation)
• Dietary modification: low saturated fat, Mediterranean diet
• Treat hypertension, diabetes, dyslipidemia
• Stress reduction

B. Pharmacological Treatment

1. Anti-Anginal (Symptom Relief)

• Nitroglycerin (sublingual) - acute attack; onset 1-3 min
  • Mechanism: releases nitric oxide (NO) → activates guanylyl cyclase → ↑cGMP → smooth muscle relaxation → venodilation (↓preload) + mild arteriodilation (↓afterload) → ↓myocardial O₂ demand; may also dilate coronary vessels
  • High first-pass effect: sublingual dose much smaller than oral
  • Toxicity: orthostatic hypotension, reflex tachycardia, headache
  • Contraindicated with PDE-5 inhibitors (sildenafil/tadalafil) - severe synergistic hypotension
• Isosorbide dinitrate (oral/sublingual) - prophylaxis
• Isosorbide mononitrate (oral) - active metabolite; prophylaxis
• Transdermal nitroglycerin - 12-hour nitrate-free interval required to prevent tolerance

• Propranolol (non-selective), metoprolol, atenolol (β1-selective - preferred if asthma risk)
• Mechanism: block β-adrenoceptors → ↓heart rate, ↓contractility, ↓blood pressure → ↓myocardial O₂ demand; especially effective during exercise/stress
• Reduces anginal episodes AND improves mortality post-MI
• Toxicity: bronchospasm (avoid in asthma), bradycardia, AV block, acute heart failure, fatigue
• Do NOT abruptly stop - risk of rebound angina and MI

• Verapamil, diltiazem (non-dihydropyridines): ↓heart rate + ↓contractility + coronary vasodilation
• Amlodipine, nifedipine (dihydropyridines): predominantly vasodilators
• Drug of choice for Prinzmetal angina (coronary vasospasm)
• Useful when beta-blockers are contraindicated
• Toxicity: verapamil/diltiazem - bradycardia, AV block, constipation; nifedipine - peripheral edema, reflex tachycardia

• Blocks late sodium current → ↓intracellular calcium overload → ↓O₂ demand
• Useful add-on without affecting heart rate or blood pressure
• Toxicity: QT prolongation, constipation, dizziness

2. Anti-Atherosclerotic / Cardioprotective

• Aspirin (75-100 mg daily) - all patients with stable angina, lifelong
• Clopidogrel - alternative if aspirin-intolerant; combined with aspirin post-PCI (dual antiplatelet therapy)

• High-intensity statin (atorvastatin 40-80 mg, rosuvastatin 20-40 mg) for all patients with IHD
• LDL target: <1.4 mmol/L (<55 mg/dL) with >50% reduction

• Recommended in angina with: hypertension, LV dysfunction, diabetes, CKD
• Reduce MI risk and cardiovascular mortality

C. Revascularization

• Balloon angioplasty + drug-eluting stent (DES)
• Preferred for 1-2 vessel disease, focal lesions
• Requires dual antiplatelet therapy (DAPT) post-procedure

• Grafts (saphenous vein or internal mammary artery) bypass stenotic segments
• Preferred for: left main disease, 3-vessel disease, diabetes with multivessel disease, poor LV function
• Relieves angina and improves survival in high-risk groups

• Persistent symptoms despite optimal medical therapy
• High-risk anatomy (left main, proximal LAD stenosis)
• Evidence of large area of viable ischemic myocardium

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9. Key Distinctions (Exam Table)

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10. Complications

• Progression to unstable angina → NSTEMI → STEMI
• Sudden cardiac death (ventricular fibrillation during ischemic episode)
• Heart failure (ischemic cardiomyopathy from repeated ischemic episodes)
• Arrhythmias
• Reduced quality of life, exercise intolerance

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11. Differentials to Exclude

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Summary Mnemonics

• Provocation: exertion, cold, stress
• Quality: squeezing, pressure, heaviness
• Radiation: left arm, jaw, neck
• Severity/associated Symptoms: Levine sign, diaphoresis
• Time: 2-5 min (stable), >20 min (unstable)

• A - Aspirin + ACE inhibitor
• B - Beta-blocker
• C - Calcium channel blocker + Cholesterol (statin)
• D - Diet + risk factor modification
• E - Exercise + revascularization if indicated

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Unstable Angina - Complete University Exam Guide

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1. Definition & Position in the ACS Spectrum

Stable Angina → UNSTABLE ANGINA → NSTEMI → STEMI
              ← No ST elevation (NSTE-ACS) →

• UA vs NSTEMI: Same mechanism, same ECG pattern - differentiated only by biomarkers
  • UA: troponin negative
  • NSTEMI: troponin positive (myocyte necrosis has occurred)
• UA vs STEMI: UA has partial coronary occlusion; STEMI has complete occlusion

"The patient with unstable angina has cardiac chest pain that is new, worsening, or occurring at rest, without serologic evidence of myocyte necrosis - that is, no elevation of troponin or CK-MB." - Goldman-Cecil Medicine

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2. Also Known As

• Preinfarction angina
• Crescendo angina / accelerating angina
• Intermediate coronary syndrome
• Pre-occlusive syndrome
• Acute coronary insufficiency

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3. Pathophysiology

Step-by-Step Sequence:

• A lipid-rich atherosclerotic plaque with a thin fibrous cap becomes unstable
• Inflammation (macrophages, T-lymphocytes) degrades the cap through metalloproteinase release

• Sudden rupture of the fibrous cap exposes the lipid core and subendothelial collagen to circulating blood

• Circulating platelets bind exposed subendothelium via von Willebrand factor and collagen
• Activated platelets:
  • Change shape (discoid → stellate) - ↑ surface area for thrombin formation
  • Release thromboxane A2, serotonin, ADP, fibrinogen, vWF from granules
  • Upregulate glycoprotein IIb/IIIa receptors - bind fibrinogen → platelet aggregation
  • Cause focal vasoconstriction

• Partial, non-occlusive thrombus forms on the disrupted plaque
• The thrombus is dynamic - it can grow, fragment (causing distal microembolization), or lyse
• Results in reduced but not completely abolished coronary flow

• Released platelet products (thromboxane, serotonin) and endothelial dysfunction cause additional coronary vasospasm, worsening ischemia

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4. Classification / Types of UA (Braunwald Classification)

By Clinical Circumstances:

By Clinical Context:

Formal Operational Definitions (used in practice):

1. Rest angina: Angina at rest, lasting >20 min, occurring within 1 week of presentation
2. New-onset angina: New angina of at least CCS class II severity, within 2 months
3. Crescendo (progressive) angina: Known stable angina that has increased by ≥1 CCS class to at least class III severity within 2 months

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5. Clinical Features

• Substernal pressure, heaviness, squeezing - Levine's sign
• Radiates to left arm, jaw, neck, back
• Lasts >20 minutes (unlike stable angina which resolves in 2-5 min)
• NOT relieved by rest alone
• NOT fully relieved by nitroglycerin (unlike stable angina)
• May occur at rest, at night, or with minimal activity
• Accelerating: more frequent attacks, triggered by less and less exertion

• Dyspnea, diaphoresis, nausea, vomiting, syncope, palpitations
• Silent ischemia - no pain at all (common in diabetic neuropathy)

• S4 gallop (reduced LV compliance)
• Transient mitral regurgitation murmur (papillary muscle ischemia)
• Signs of heart failure if LV dysfunction (S3, crackles, elevated JVP)

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6. Risk Stratification

TIMI Risk Score for UA/NSTEMI (7 variables, 1 point each):

• Score 0-2: Low risk (~4-8% event rate)
• Score 3-4: Intermediate risk (~13-19%)
• Score 5-7: High risk (~26-41%)

GRACE Score (Global Registry of Acute Coronary Events):

CRUSADE Score: Estimates bleeding risk with intensive therapy (key variables: female sex, older age, renal insufficiency, low weight, anemia, diabetes).

High-Risk Features Requiring Urgent Admission:

• Age >70 years
• Prior history of CAD or revascularization
• Ongoing chest pain >20 minutes
• ECG changes: ST depression ≥0.5 mm in ≥2 contiguous leads, new T-wave inversions, new LBBB
• Elevated cardiac biomarkers (troponin → reclassifies as NSTEMI)
• Hemodynamic instability (hypotension, signs of shock)
• Developing heart failure

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7. Investigations

ECG (within 10 minutes of arrival - mandatory):

• May be normal in up to 30-40% of cases
• ST-segment depression (≥0.5-1 mm horizontal or downsloping) - most common
• T-wave inversion or pseudonormalization
• Transient ST changes that resolve with symptom relief are highly specific
• Compare to prior ECG - subtle new changes matter

Cardiac Biomarkers (serial measurements):

Other investigations:

• Chest radiograph: Heart size, pulmonary edema, aortic knuckle
• Echocardiogram: Regional wall motion abnormalities, LV function, valve assessment
• CBC, CMP, lipid panel, BNP (risk assessment and comorbidities)

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8. Management

Immediate Goals (the "3 Ps"):

1. Prevent thrombus propagation
2. Prevent recurrent ischemia (O2 supply-demand balance)
3. Prevent progression to MI and death

A. Initial Emergency Management (MONA + H)

B. Antiplatelet Therapy (Dual Antiplatelet - DAPT)

• Mechanism: irreversibly inhibits COX-1 → ↓ TXA2 synthesis → ↓ platelet aggregation

C. Antithrombotic (Anticoagulant) Therapy

D. Beta-Blockers

• Start within 24 hours if no contraindications (acute HF, bradycardia, hypotension, severe bronchospasm)
• Reduce HR, BP, contractility → ↓ myocardial O2 demand
• Metoprolol (oral/IV) is most commonly used
• Do NOT give if: cardiogenic shock, severe bradycardia, high-degree AV block, active bronchospasm

E. Glycoprotein IIb/IIIa Inhibitors

F. Other Drugs

• Statins (high-intensity): atorvastatin 40-80 mg immediately - plaque stabilization, anti-inflammatory, LDL lowering
• ACE inhibitors: If LV dysfunction, hypertension, or diabetes
• Calcium channel blockers: If beta-blockers contraindicated; not first-line in UA (no proven mortality benefit alone)
• Morphine sulfate: For pain unresponsive to anti-ischemic therapy

G. Revascularization Strategy

• Ongoing refractory chest pain despite maximal medical therapy
• Hemodynamic instability / cardiogenic shock
• Life-threatening arrhythmias
• Signs of acute heart failure

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9. ECG Changes - Visual Summary

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10. UA vs. NSTEMI vs. STEMI Comparison

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11. Prognosis and Complications

• Progression to NSTEMI or STEMI (complete occlusion)
• Sudden cardiac death (VF/VT from ischemia)
• Cardiogenic shock (severe LV dysfunction)
• Acute mitral regurgitation (papillary muscle ischemia/rupture)
• Ventricular septal defect (rare, in context of STEMI)
• Recurrent ischemia post-discharge

• 20-40% reduction in recurrent ischemia and MI
• ~10% reduction in mortality
• ~18-month postponement of recurrent MI or death

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12. Secondary Prevention (Long-Term After UA)

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13. Quick Exam Summary Table

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