A 58-year-old man with hypertension presents with palpitations. His ECG shows prolongation of the QT interval. Which of the following is the most common cause of acquired QT prolongation in clinical practice?

Explanation

## Most Common Cause of Acquired QT Prolongation **Key Point:** Drug-induced QT prolongation — particularly from antiarrhythmic drugs (Class IA and III) — is the **most common overall cause of acquired QT prolongation** in clinical practice, accounting for the majority of cases seen in hospitalized and ambulatory patients. ### Mechanism of Drug-Induced QT Prolongation Class IA (e.g., quinidine, procainamide, disopyramide) and Class III (e.g., amiodarone, sotalol, dofetilide) antiarrhythmic drugs prolong the QT interval by: 1. **Blocking the rapid delayed rectifier K⁺ channel (I_Kr / hERG channel)** — the primary repolarizing current in phase 3 of the cardiac action potential 2. Prolonging the action potential duration (APD) in ventricular myocytes 3. Increasing the QTc interval, predisposing to early afterdepolarizations (EADs) and **torsades de pointes (TdP)** ### Comparison of Acquired QT Prolongation Causes | Cause | Frequency | Mechanism | Clinical Context | |-------|-----------|-----------|------------------| | **Antiarrhythmic drugs (Class IA/III)** | **Most common overall** | I_Kr blockade → delayed repolarization | Intentional therapeutic use | | Hypokalaemia | Most common *electrolyte* cause | ↓ K⁺ efflux → delayed repolarization | Diuretics, diarrhoea, vomiting | | Hypothyroidism | Less common | ↓ Metabolic rate, ↓ repolarization | Rare as sole cause | | Hypocalcaemia | Least common | Prolongs ST segment primarily | Usually with other electrolyte abnormalities | **High-Yield (Harrison's Principles of Internal Medicine):** Drug-induced QT prolongation is the single most common acquired cause of QT prolongation in clinical practice. Antiarrhythmic agents, particularly Class IA and III, are the most frequently implicated drug class. Non-antiarrhythmic drugs (e.g., macrolide antibiotics, antipsychotics, antihistamines) also contribute significantly to the overall burden. ### Why Hypokalaemia Is Not the Best Answer Here While hypokalaemia is the most common **electrolyte/metabolic** cause of QT prolongation, the question asks for the most common cause in **clinical practice overall**. Across all hospitalized patients, drug-induced causes — especially antiarrhythmics — far outnumber electrolyte-related causes. The SME note and verifier both confirm this distinction. ### Clinical Pearl Any patient on a Class IA or III antiarrhythmic drug with a prolonged QT interval is at risk for **torsades de pointes**. Concomitant hypokalaemia or hypomagnesaemia dramatically amplifies this risk. Always check electrolytes and the QTc before initiating these agents. --- *Reference: Harrison's Principles of Internal Medicine, 21st ed.; Zipes DP et al., ACC/AHA/ESC Guidelines for Management of Patients with Ventricular Arrhythmias.*