6.1 Acute Coronary Syndromes & Myocardial Infarction

Acute coronary syndromes (ACS) encompass a spectrum of myocardial ischaemia ranging from unstable angina (UA) and non-ST-elevation myocardial infarction (NSTEMI) to transmural ST-elevation myocardial infarction (STEMI). Mastery of the pathophysiological distinctions, electrocardiographic diagnostic thresholds, evidence-based pharmacotherapy, and post-infarction mechanical complications is essential for MRCP(UK) Part 1.

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1. Pathophysiology & Universal Definition of Myocardial Infarction

Plaque Rupture vs. Plaque Erosion

Coronary atherothrombosis arises from two distinct histopathological mechanisms:

• Plaque Rupture (~70% of fatal MIs): Classically features a thin fibrous cap (<65 μm), large necrotic lipid core, and heavy macrophage infiltration. Degradation of the extracellular matrix by matrix metalloproteinases precipitates cap disruption, exposing thrombogenic core contents (tissue factor, type I collagen) to circulating platelets. Platelet activation occurs via glycoprotein VI and GP Ib-IX-V, followed by cross-linking of glycoprotein IIb/IIIa receptors by fibrinogen. This produces an occlusive red (fibrin- and erythrocyte-rich) thrombus, most commonly causing STEMI.
• Plaque Erosion (~30% of MIs): Characterized by a thick fibrous cap rich in extracellular matrix (hyaluranan, proteoglycans) and vascular smooth muscle cells, devoid of a large lipid core. Endothelial denudation and neutrophil extracellular traps (NETs) trigger platelet activation, yielding a non-occlusive white (platelet-rich) thrombus. Plaque erosion is increasingly recognized in premenopausal women, younger individuals, and active smokers, typically presenting as NSTEMI.

Fourth Universal Definition of Myocardial Infarction

The consensus definition requires myocardial injury—evidenced by a rise and/or fall of cardiac troponin (cTnI or cTnT) with at least one value above the 99th percentile upper reference limit (URL)—occurring in the setting of acute myocardial ischaemia, substantiated by at least one of:

1. Symptoms of acute myocardial ischaemia (e.g., retrosternal crushing pain, diaphoresis, nausea).
2. New ischaemic ECG changes (ST-segment deviations or T-wave inversions).
3. Development of pathological Q waves.
4. Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality (RWMA) in an ischaemic distribution.
5. Identification of an intraluminal coronary thrombus by angiography or autopsy.

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2. Electrocardiographic Diagnosis: STEMI, Posterior MI & RV Infarction

Standard ST-Elevation Cut-offs

ST elevation must be measured at the J-point in at least two contiguous leads:

• Leads V2–V3:
  • Men < 40 years: $\ge 2.5\text{ mm}$ ($0.25\text{ mV}$)
  • Men $\ge 40$ years: $\ge 2.0\text{ mm}$ ($0.20\text{ mV}$)
  • Women (any age): $\ge 1.5\text{ mm}$ ($0.15\text{ mV}$)
• All other leads (Limb leads I, II, III, aVF, aVL and precordial V1, V4–V6): $\ge 1.0\text{ mm}$ ($0.10\text{ mV}$) regardless of sex or age.
• Reciprocal ST depression: Strongly corroborates STEMI (e.g., ST depression in leads I and aVL during acute inferior STEMI, or leads II, III, aVF during anterior STEMI).

Posterior Myocardial Infarction

Occlusion of the left circumflex (LCx) or distal right coronary artery (RCA) causes transmural ischaemia of the posterior basal LV wall. Standard 12-lead ECG does not directly view the posterior wall:

• Indirect changes in V1–V3: Horizontal ST depression, tall upright broad R waves ($R/S \text{ ratio} > 1$), and prominent upright T waves (the inverted mirror image of anterior transmural STEMI).
• Posterior Leads (V7–V9): Electrode V7 at the posterior axillary line, V8 at the mid-scapular line, and V9 at the left paraspinal border (all in the 5th intercostal space). Diagnostic threshold: ST elevation $\ge 0.5\text{ mm}$ ($0.05\text{ mV}$) confirms acute posterior STEMI and mandates immediate reperfusion.

Right Ventricular Infarction

Right ventricular involvement occurs in 30–50% of inferior STEMIs due to proximal occlusion of a dominant RCA (before the acute marginal branches).

• ECG Confirmation: Right-sided precordial lead V4R (5th right intercostal space, midclavicular line) demonstrates ST elevation $\ge 1.0\text{ mm}$.
• Haemodynamic Profile: The ischaemic RV fails to pump forward volume, leading to elevated right atrial pressure and diminished LV filling. The patient presents with the classic triad of hypotension, clear lung fields, and raised jugular venous pressure (Kussmaul's sign).
• Therapeutic Rules: The RV is strictly preload-dependent. Nitrates, diuretics, morphine, and beta-blockers are strictly contraindicated; their administration causes catastrophic precipitous hypotension. Management demands urgent primary PCI and aggressive volume loading with intravenous crystalloids (500–1000 mL boluses of $0.9%$ saline). If hypoperfusion persists despite volume expansion, inotropic support with dobutamine is initiated.

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3. Reperfusion Strategies & Evidence-Based Pharmacology

Reperfusion Pathways in STEMI

• Primary PCI: Reperfusion strategy of choice if wire crossing can be achieved within 120 minutes of STEMI diagnosis (door-to-balloon time $< 90\text{ minutes}$ in PCI centres; $< 120\text{ minutes}$ if transferred from a non-PCI centre).
• Intravenous Fibrinolysis: Indicated when anticipated delay to primary PCI exceeds 120 minutes. Fibrin-specific agents (tenecteplase weight-adjusted bolus, alteplase, or reteplase) must be administered within 10 minutes of STEMI diagnosis ("needle time"). Absolute contraindications: prior intracranial haemorrhage, ischaemic stroke within 6 months, known central nervous system neoplasm/AVM, active internal bleeding, or suspected aortic dissection.
• Pharmacoinvasive Strategy: Following fibrinolysis, transfer all patients immediately to a PCI centre:
  • Rescue PCI: Indicated for failed fibrinolysis ($< 50%$ ST-segment resolution in the lead with maximum ST elevation at 60–90 minutes, ongoing ischaemia, or haemodynamic instability).
  • Routine Angiography: Performed within 2–24 hours after successful fibrinolysis.

Dual Antiplatelet Therapy (DAPT) & Anticoagulation

• Aspirin: Loading dose 300 mg chewed/oral, followed by 75 mg once daily indefinitely.
• Potent P2Y12 Inhibitors:
  • Ticagrelor: 180 mg loading dose, then 90 mg twice daily. Direct, reversible P2Y12 receptor antagonist. Associated with transient dyspnoea and asymptomatic ventricular pauses.
  • Prasugrel: 60 mg loading dose, then 10 mg once daily. Irreversible prodrug thienopyridine with faster, more potent platelet inhibition. Superior to ticagrelor in ACS undergoing PCI (ISAR-REACT 5 trial). Contraindications: Prior stroke or transient ischaemic attack (TIA) due to fatal intracranial bleed risk. Dose reduction to 5 mg daily if age $\ge 75$ years or weight $< 60\text{ kg}$.
  • Clopidogrel: 300–600 mg load, 75 mg daily. Reserved for patients requiring triple therapy (concurrent oral anticoagulation), high bleeding risk, or when newer agents are contraindicated.
• Anticoagulation:
  • Primary PCI: Unfractionated heparin (UFH; 70–100 IU/kg IV adjusted by ACT) or bivalirudin (direct thrombin inhibitor).
  • NSTEMI / Non-invasive: Fondaparinux (2.5 mg SC daily, selective factor Xa inhibitor) offers the lowest bleeding profile; during PCI, a bolus of UFH is required to prevent catheter-induced thrombosis.

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4. NSTEMI Risk Stratification & Invasive Strategy Timing

NSTEMI and UA require immediate risk stratification using validated clinical risk scores:

• GRACE 2.0 Score: Calculates 6-month in-hospital and post-discharge mortality based on 8 variables: age, heart rate, systolic blood pressure, serum creatinine, Killip class, cardiac arrest at admission, ST-segment deviation, and elevated cardiac biomarkers.
• Invasive Timing (ESC / NICE Guidelines):
  1. Immediate Invasive Strategy ($< 2\text{ hours}$): Hemodynamic instability or cardiogenic shock, recurrent/refractory angina despite medical therapy, life-threatening ventricular arrhythmias, mechanical complications, or acute heart failure due to myocardial ischaemia.
  2. Early Invasive Strategy ($< 24\text{ hours}$): High-risk patients with a GRACE score $> 140$, dynamic ST- or T-wave changes, or transient ST elevation.
  3. Selective Invasive Strategy: Low-risk patients (GRACE score $\le 140$ without recurrent ischaemia) undergo outpatient non-invasive functional imaging (stress echocardiography, cardiac MRI, or CT coronary angiography).

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5. Mechanical Complications of Acute Myocardial Infarction

Mechanical complications develop predominantly 3 to 7 days post-MI (bimodal peak: $< 24\text{ hours}$ and day 3–5) during peak macrophage-mediated phagocytosis and necrotic myocardial thinning before mature collagen scar formation.