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Coronary Artery Disease & Acute Coronary Syndrome — Comprehensive Notes

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PART 1: CORONARY ARTERY DISEASE (CAD) — Overview

Definition

Pathophysiology of Atherosclerosis

1. Endothelial injury: Triggered by hypertension, smoking, dyslipidemia, diabetes, or oxidized LDL
2. Lipid deposition: LDL particles infiltrate the intima and become oxidized
3. Inflammatory response: Monocytes migrate into the intima → differentiate into macrophages → ingest ox-LDL → become foam cells → form the fatty streak
4. Plaque development: Smooth muscle cell migration, collagen deposition → fibrous cap forms over a lipid-rich necrotic core
5. Stable vs. vulnerable plaque:
   • Stable plaque: Thick fibrous cap, small lipid core → causes stable angina by fixed luminal narrowing
   • Vulnerable plaque: Thin fibrous cap, large lipid core, heavy inflammation → prone to rupture

Risk Factors for CAD

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PART 2: ACUTE CORONARY SYNDROME (ACS)

Definition

According to Harrison's Principles of Internal Medicine, 21st Ed. (p. 529): "The term acute coronary syndrome, which encompasses unstable angina, NSTEMI, and STEMI, is in general reserved for ischemia precipitated by acute coronary atherothrombosis."

ACS Spectrum

ACS
├── Unstable Angina (UA)         → No myocardial necrosis (troponin negative)
├── NSTEMI                        → Myocardial necrosis, NO ST elevation on ECG
└── STEMI                         → Myocardial necrosis, ST elevation on ECG

Key Pathophysiologic Event: Plaque Rupture

1. Vulnerable plaque ruptures or erodes
2. Subendothelial collagen and lipid core exposed
3. Platelet adhesion and aggregation → platelet plug
4. Coagulation cascade activated → thrombus formation
5. Thrombus may be:
   • Partial/non-occlusive → UA or NSTEMI
   • Complete/occlusive → STEMI

MI Classification (Harrison's p. 529)

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PART 3: ANGINA PECTORIS

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3A. STABLE ANGINA

Definition

Pathophysiology

• Fixed atherosclerotic plaque causing ≥70% luminal stenosis (or ≥50% in left main)
• During exertion: myocardial O₂ demand ↑ but supply is limited by fixed stenosis
• No plaque rupture, no thrombus

Clinical Features

• Character: Pressure, heaviness, tightness ("like an elephant on my chest")
• Location: Substernal, may radiate to left arm, jaw, neck, shoulder, back
• Duration: 2–10 minutes
• Triggers: Exertion, cold weather, emotional stress, large meals
• Relief: Rest, sublingual nitroglycerin within 5 minutes
• Associated symptoms: Dyspnea, diaphoresis, nausea (less common)

Canadian Cardiovascular Society (CCS) Classification

Diagnosis

• ECG: Often normal at rest; ST depression during episode or stress testing
• Stress ECG (Exercise Tolerance Test): Positive if ≥1 mm ST depression
• Stress echocardiography / Nuclear imaging: Wall motion abnormalities
• Coronary CTA: Non-invasive anatomical assessment
• Coronary angiography: Gold standard for anatomy

Management

• Smoking cessation, weight loss, exercise, BP/glucose/lipid control

• Beta-blockers (first-line): ↓ heart rate and O₂ demand (e.g., metoprolol, atenolol)
• Nitrates: Venodilation → ↓ preload → ↓ wall stress (sublingual for acute, long-acting for prevention)
• Calcium channel blockers: Amlodipine (DHP) or diltiazem/verapamil (non-DHP)
• Ranolazine: Inhibits late sodium current, reduces ischemia without affecting heart rate/BP

• Aspirin 75–100 mg daily: Antiplatelet
• Statins: Plaque stabilization + LDL reduction (target LDL <70 mg/dL in high risk)
• ACE inhibitors: Especially in diabetes, LV dysfunction

• PCI (Percutaneous Coronary Intervention): Balloon + stent for 1–2 vessel disease
• CABG (Coronary Artery Bypass Grafting): Preferred for left main, 3-vessel disease, or diabetes

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3B. UNSTABLE ANGINA (UA)

Definition

Pathophysiology

• Plaque rupture with partial, non-occlusive thrombus
• Transient reduction in coronary flow → ischemia without necrosis

Clinical Features — "ACS Triad" of Presentations

1. Rest angina: Chest pain at rest, lasting >20 minutes
2. New-onset angina: Angina of CCS Class III or IV severity, onset within 2 months
3. Crescendo angina: Previously stable angina becoming more frequent, longer, or less responsive to nitrates

Key Difference from Stable Angina

TIMI Risk Score for UA/NSTEMI (0–7 points)

• Age ≥65
• ≥3 CAD risk factors
• Known CAD (stenosis ≥50%)
• Aspirin use in past 7 days
• ≥2 anginal events in 24 h
• ST deviation ≥0.5 mm
• Positive cardiac biomarker

Score 0–2: low risk; 3–4: intermediate; 5–7: high risk

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3C. VARIANT ANGINA (Prinzmetal's Angina)

Definition

Pathophysiology

• Focal, reversible spasm of an epicardial coronary artery
• Mechanisms: Endothelial dysfunction, hyperreactivity of vascular smooth muscle, autonomic imbalance (vagal hyperactivity overnight), cocaine use
• Triggers: Cold, smoking, cocaine, hyperventilation, ergot alkaloids

Clinical Features

• Chest pain at rest, typically in the early morning hours (2–6 AM)
• Cyclic, predictable pattern
• Syncope or arrhythmias may accompany episodes (due to complete ischemia)
• Age: younger patients, often with fewer traditional CAD risk factors

ECG During Episode

• Transient ST elevation (hallmark — unlike stable angina) → returns to baseline when spasm resolves
• May cause ventricular arrhythmias or AV block during episode

Diagnosis

• Holter monitor: Captures transient ST elevations
• Provocative testing: Ergonovine or acetylcholine challenge during catheterization → induces vasospasm (rarely used)
• Coronary angiography: May show normal coronaries or mild atherosclerosis

Management

• Calcium channel blockers (first-line): Amlodipine, diltiazem, verapamil — prevent vasospasm
• Long-acting nitrates: Adjunctive
• Avoid triggers: Smoking, cocaine, ergotamines
• Beta-blockers: CONTRAINDICATED (may worsen vasospasm via unopposed alpha activity)

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PART 4: MYOCARDIAL INFARCTION (MI)

Definition

General Pathophysiology

1. Complete or near-complete coronary occlusion → cessation of blood flow
2. Within 20 minutes: Irreversible ischemic cell death begins (subendocardium)
3. Wavefront of necrosis progresses from subendocardium → subepicardium over 4–6 hours
4. Without reperfusion: full-thickness (transmural) necrosis

Zones of Myocardial Infarction

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PART 5: STEMI — ST-Elevation Myocardial Infarction

Definition

According to Harrison's (p. 7562): "The 12-lead ECG is a pivotal diagnostic and triage tool… permitting distinction of those patients presenting with ST-segment elevation from those presenting without ST-segment elevation."

Coronary Artery Territories

Clinical Presentation

• Chest pain: Severe, crushing, substernal, >20–30 minutes, NOT relieved by nitrates
• Radiation to jaw, left arm, neck, back
• Diaphoresis (cold, clammy sweat)
• Nausea/vomiting
• Dyspnea
• Sense of impending doom
• Silent MI: Especially in diabetics and elderly (no pain, only fatigue/dyspnea)

ECG Evolution of STEMI

• ST elevation ≥2 mm in ≥2 contiguous precordial leads
• ST elevation ≥1 mm in ≥2 contiguous limb leads
• New LBBB (treat as STEMI equivalent)

Biomarkers

Troponin is the gold standard biomarker — most sensitive and specific for myocardial necrosis.

Management of STEMI — "TIME IS MUSCLE"

Immediate (First 10 Minutes — "MONA" + antiplatelet)

• M — Morphine IV (for pain, but use with caution — may mask symptoms, associated with worse outcomes)
• O — Oxygen (only if SpO₂ <90%)
• N — Nitroglycerin sublingual (avoid if hypotension, RV infarct, or PDE-5 inhibitor use)
• A — Aspirin 300 mg loading dose (chew, immediately)
• P2Y₁₂ inhibitor: Ticagrelor 180 mg or Clopidogrel 600 mg (dual antiplatelet therapy — DAPT)

Reperfusion Strategy (MOST CRITICAL)

• Door-to-balloon time: ≤90 minutes
• Stent placement at site of occlusion
• Superior to thrombolysis if performed timely

• Door-to-needle time: ≤30 minutes
• Agents: Alteplase (tPA), Tenecteplase, Streptokinase
• Contraindications: Prior intracranial hemorrhage, recent stroke (<3 months), active bleeding, aortic dissection

Anti-coagulation

• Unfractionated heparin (UFH) or low molecular weight heparin (LMWH) (enoxaparin)
• Bivalirudin: Alternative in PCI setting

Post-MI Long-Term Management ("ABCDE" + statins)

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PART 6: NSTEMI — Non-ST-Elevation Myocardial Infarction

Definition

Pathophysiology

• Plaque rupture → partial thrombus → non-occlusive obstruction
• Subendocardium (most vulnerable zone — farthest from epicardial vessels) becomes necrotic
• Full-thickness necrosis less common (unlike STEMI)

ECG Findings in NSTEMI

• ST depression (most common) — leads facing the ischemic zone
• T-wave inversion or flattening
• No ST elevation (if ST elevation is present → reclassify as STEMI)
• No pathological Q waves typically (no transmural necrosis)

UA vs. NSTEMI — Key Distinction

This distinction is made retrospectively after biomarker results return — both are managed as ACS.

Management of UA/NSTEMI

Risk Stratification (Guides urgency of invasive strategy)

• GRACE score: Most widely used (age, HR, BP, creatinine, Killip class, cardiac arrest, ST deviation, troponin)
• TIMI score: As described above

Antiplatelet & Anticoagulation

• Aspirin 300 mg loading → 75 mg daily
• P2Y₁₂ inhibitor: Ticagrelor (preferred) or Clopidogrel
• Anticoagulant: Fondaparinux (preferred), LMWH (enoxaparin), or UFH
• GPIIb/IIIa inhibitors (e.g., eptifibatide): High-risk patients going to PCI

Invasive Strategy (Coronary Angiography + PCI)

Anti-ischemic Therapy

• Beta-blockers: Oral, within 24 hours if no contraindications
• Nitrates: IV for ongoing pain
• Calcium channel blockers: If beta-blockers contraindicated

Long-term Management

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PART 7: COMPLICATIONS OF MI

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PART 8: KILLIP CLASSIFICATION (Heart Failure in MI)

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PART 9: SUMMARY COMPARISON TABLE

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PART 10: CLINICAL PEARLS

• ST elevation = Emergency: Every minute of delay in STEMI reperfusion = ~1,700 myocardial cells lost per heartbeat
• Right ventricular infarction (inferior STEMI): Avoid nitrates and diuretics — RV preload-dependent; treat with IV fluids + early reperfusion
• Posterior MI: ST depression in V1–V3 with dominant R waves → get V7–V9 leads
• Diabetics and elderly: May present with atypical symptoms (silent MI, fatigue, dyspnea, nausea without chest pain)
• Cocaine-induced MI: Can cause vasospasm (Type 2 MI) or atherothrombosis; treat with nitrates + CCBs; avoid beta-blockers (risk of unopposed alpha vasoconstriction)
• Wellens' syndrome: T-wave changes in V2–V3 (biphasic or deep inversion) = critical LAD stenosis — patient at high risk of anterior STEMI; avoid stress testing

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