Chapter 8  ·  Module 1

Cardiac Electrophysiology and the Vaughan Williams Classification

Action potential phases, arrhythmia mechanisms, and the four-class antiarrhythmic framework

The Cardiac Action Potential — Five Phases

Phase 0

Rapid Depolarization

Fast sodium channels open; large inward sodium current

Class I target

Phase 1

Early Repolarization

Sodium channels inactivate; brief outward potassium current

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Phase 2

Plateau

Inward calcium current balanced by outward potassium; triggers contraction

Class IV target

Phase 3

Rapid Repolarization

Outward potassium current dominant; calcium current declines

Class III target

Phase 4

Resting Potential

Stable in working muscle; spontaneous in nodal cells (If, Ca)

Class II target

Mechanisms of Arrhythmogenesis

Abnormal Automaticity

Non-pacemaker cells acquire spontaneous phase 4 depolarization

Triggers: ischemia, catecholamine excess, hypokalemia, digitalis toxicity

Class II suppresses

Triggered Activity

EADs (phases 2–3): bradycardia, hypokalemia, QT-prolonging drugs → torsades de pointes

DADs (phase 4): calcium overload, rapid rates, digitalis toxicity

Mg for EADs · Beta-blockers for DADs

Re-entry

Requires: closed circuit + unidirectional block + slow conduction

Most supraventricular tachycardias and ventricular tachycardia in structural disease

Class I or III terminates

The Vaughan Williams Classification

Class Mechanism Prototype Drugs ECG Effect Key Caution
Ia Sodium channel block (intermediate kinetics); also prolongs repolarization Quinidine, procainamide, disopyramide Wide QRS + prolonged QT Torsades de pointes risk
Ib Sodium channel block (rapid kinetics); shortens action potential duration Lidocaine, mexiletine Minimal at rest Ischemia-selective; ineffective in atrial tissue
Ic Sodium channel block (slow kinetics); profound conduction slowing Flecainide, propafenone Wide QRS Contraindicated in structural heart disease (Cardiac Arrhythmia Suppression Trial)
II Beta-adrenergic receptor blockade; reduce phase 4 slope, slow atrioventricular node Metoprolol, atenolol, propranolol Prolonged PR Bradycardia, atrioventricular block, bronchospasm
III Potassium channel block; prolong action potential duration and effective refractory period Amiodarone, sotalol, dofetilide, ibutilide Prolonged QT Torsades de pointes; amiodarone multi-organ toxicity
IV Calcium channel block (L-type); slow atrioventricular nodal conduction Verapamil, diltiazem Prolonged PR Contraindicated in ventricular tachycardia; negative inotropy

Agents Outside the Vaughan Williams Framework

Unclassified

Adenosine

  • Adenosine receptor agonist → atrioventricular nodal block
  • Half-life under 10 seconds
  • First-line for supraventricular tachycardia termination
  • Contraindicated in Wolff-Parkinson-White with atrial fibrillation

Unclassified

Digoxin

  • Increases vagal tone; inhibits sodium-potassium pump
  • Rate control in atrial fibrillation
  • Narrow therapeutic index
  • Toxicity: ectopy plus atrioventricular block

Unclassified

Magnesium Sulfate

  • Suppresses early afterdepolarization-driven oscillations
  • First-line for torsades de pointes
  • Effective regardless of serum magnesium level
  • Also used in digoxin toxicity and refractory ventricular fibrillation

Core Principle

Every antiarrhythmic drug can also cause arrhythmias. Proarrhythmia is inherent to altering cardiac electrophysiology. Structural heart disease constrains drug selection: Class Ic agents are contraindicated when myocardial scarring is present. Class III agents carry QT prolongation and torsades de pointes risk, greatest at slow heart rates (reverse use-dependence). Rational prescribing requires weighing arrhythmia risk against drug risk for every patient.