QT prolongation and torsades de pointes

Pathophysiology - The Long & Winding QT

• QT Interval: Represents the duration of the ventricular myocyte action potential (AP), from initial depolarization to complete repolarization.
• Core Defect: Prolongation of AP Phase 3 (ventricular repolarization).
  • Primarily due to blockade of the delayed rectifier potassium current ($I_{Kr}$).
  • This ↓ K⁺ efflux lengthens repolarization time, stretching the QT interval.
• Trigger for TdP: This prolonged plateau can lead to early afterdepolarizations (EADs), which can initiate polymorphic ventricular tachycardia if they reach threshold.

⭐ Congenital Long QT Syndromes often result from mutations in genes encoding cardiac potassium (e.g., KCNH2) or sodium channels, impairing repolarization.

Etiologies - The Usual Suspects

• QTc Interval Thresholds: Prolonged if > 450 ms (males) or > 470 ms (females). High risk for TdP if > 500 ms.

• Medications (Most Common Cause)

  • 📌 Mnemonic: ABCDE
  • Antiarrhythmics: Class IA (Quinidine, Procainamide), Class III (Amiodarone, Sotalol, Dofetilide)
  • Biotics (Antibiotics): Macrolides (Erythromycin, Azithromycin), Fluoroquinolones
  • Cychotics (Antipsychotics): Haloperidol, Ziprasidone, other atypical antipsychotics
  • Depressants (Antidepressants): TCAs (Amitriptyline), SSRIs (Citalopram)
  • Emetics (Antiemetics): Ondansetron (5-HT3 antagonists)
  • Others: Azole antifungals (e.g., Fluconazole)

• Electrolyte Disturbances

  • ↓ K⁺ (Hypokalemia)
  • ↓ Mg²⁺ (Hypomagnesemia)
  • ↓ Ca²⁺ (Hypocalcemia)

• Other Causes

  • Congenital Long QT Syndrome (e.g., Romano-Ward, Jervell and Lange-Nielsen)
  • Bradycardia, Hypothyroidism

⭐ Exam Favorite: Citalopram carries a dose-dependent risk of QT prolongation. The FDA recommends a maximum dose of 40 mg/day (20 mg/day in patients >60 years, or with hepatic impairment).

Diagnosis - ECG Tells the Tale

• ECG is key: Look for a prolonged QT interval, corrected for heart rate (QTc).
  • Bazett's Formula: $QTc = QT / \sqrt{RR}$
  • Thresholds: QTc > 450 ms in males, > 470 ms in females.
• Torsades de Pointes (TdP): A specific polymorphic ventricular tachycardia.
  • ECG shows rapid, irregular, QRS complexes twisting around the isoelectric baseline.

⭐ Exam Favorite: TdP is often initiated by a "short-long-short" R-R interval sequence, where a PVC follows a long pause.

Management - Taming the Twisting Storm

• Immediate Actions: Discontinue all QT-prolonging agents. Correct electrolyte imbalances, especially hypokalemia and hypomagnesemia.

⭐ IV magnesium is the first-line therapy for TdP regardless of the patient's baseline magnesium level; it stabilizes the cardiac membrane.

High‑Yield Points - ⚡ Biggest Takeaways

• QT prolongation is a major risk factor for Torsades de Pointes (TdP), a life-threatening polymorphic ventricular tachycardia.
• Key drug classes include Class IA/III antiarrhythmics, macrolides, fluoroquinolones, antipsychotics, and -azole antifungals.
• Hypokalemia and hypomagnesemia are critical co-factors that significantly increase TdP risk.
• The first-line treatment for TdP is immediate IV magnesium sulfate, which stabilizes the cardiac membrane.
• Always discontinue the offending drug and correct underlying electrolyte imbalances.
• ECG shows characteristic twisting QRS complexes around the isoelectric line.