Torsades de pointes

A 55-year-old woman with a history of depression presents to the emergency department after an episode of syncope. She reports lightheadedness and palpitations before transient loss of consciousness, followed by spontaneous recovery. She was recently treated for a urinary tract infection with ciprofloxacin and is taking citalopram. On examination, findings are unremarkable. Vital signs show blood pressure 100/60 mm Hg, pulse 55/min, respiratory rate 18/min, oxygen saturation 98% on room air, and temperature 97.9°F. ECG shows a prolonged QT interval with QTc >500 ms and polymorphic ventricular tachycardia with twisting of the QRS complexes around the isoelectric line. Diagnosis?

Diagnosis is Torsades de pointes.

1. Definition

Torsades de pointes is a form of polymorphic ventricular tachycardia that occurs in the setting of a prolonged QT interval, characterized by cyclic variation in QRS amplitude and axis that appears to twist around the isoelectric line.

2. Pathophysiology

1.      Prolonged ventricular repolarization increases action potential duration and the QT interval

2.      In acquired drug-induced cases, a common mechanism is inhibition of the rapid delayed rectifier potassium current (IKr)

3.      Prolonged repolarization promotes early afterdepolarizations

4.      Early afterdepolarizations can produce triggered ventricular activity, initiating polymorphic ventricular tachycardia

5.      Torsades de pointes is often pause-dependent and may follow a short-long-short sequence

3. Etiology

3.1 Acquired Causes

1.      QT-prolonging drugs

o    Antiarrhythmics, particularly class IA and some class III agents

o    Antibiotics, including macrolides and some fluoroquinolones such as ciprofloxacin

o    Antidepressants, including citalopram and certain tricyclic antidepressants

o    Antipsychotics

o    Antiemetics, such as ondansetron

o    Methadone

2.      Electrolyte abnormalities

o    Hypokalemia

o    Hypomagnesemia

o    Hypocalcemia

3.      Bradycardia

4.      Additional risk factors include:

o    Female sex

o    Structural heart disease

o    Renal or hepatic dysfunction

o    Use of multiple QT-prolonging drugs

3.2 Congenital Causes

1.      Congenital long QT syndrome

o    Romano-Ward syndrome

o    Jervell and Lange-Nielsen syndrome, associated with congenital sensorineural hearing loss

4. Clinical Features

1.      Palpitations

2.      Lightheadedness or dizziness

3.      Syncope

4.      Episodes may terminate spontaneously and recur

5.      May deteriorate into ventricular fibrillation and sudden cardiac death

5. ECG Findings

1.      Prolonged QT interval

2.      QTc >500 ms is associated with a substantially increased risk of Torsades de pointes

3.      Polymorphic ventricular tachycardia

4.      Characteristic twisting of QRS complexes around the isoelectric line

5.      Episodes may be preceded by a short-long-short sequence

6. Management

6.1 Immediate Measures

1.      Discontinue offending QT-prolonging drugs

2.      Correct reversible causes and electrolyte abnormalities

o    Correct hypokalemia

o    Correct hypomagnesemia

o    Correct hypocalcemia

3.      Consider maintaining serum potassium at approximately 4.5 to 5.0 mmol/L

4.      Continuous cardiac monitoring

6.2 Hemodynamically Unstable, Sustained, or Pulseless Torsades de Pointes

1.      Immediate high-energy unsynchronized defibrillation

o    Polymorphic ventricular tachycardia cannot be reliably synchronized

2.      If pulseless, initiate CPR and standard cardiac arrest management

6.3 Recurrent or Self-Terminating Torsades de Pointes

1.      Intravenous magnesium sulfate, 2 g IV, is first-line therapy

2.      Magnesium is effective even when the serum magnesium level is normal

3.      A repeat 2 g IV dose may be considered if episodes persist or recur

6.4 Refractory or Recurrent Acquired Torsades de Pointes

1.      Increase the heart rate to shorten the QT interval and prevent pauses

2.      Temporary overdrive pacing may be used

3.      Isoproterenol may be used for recurrent acquired, pause-dependent Torsades de pointes

4.      Avoid isoproterenol in congenital long QT syndrome and acute coronary syndrome

7. Special Considerations

1.      Avoid or discontinue QT-prolonging medications whenever possible

2.      Correct electrolyte abnormalities and consider maintaining potassium at approximately 4.5 to 5.0 mmol/L

3.      Avoid combinations of QT-prolonging drugs, particularly in patients with additional risk factors

4.      In congenital long QT syndrome, beta-blockers, particularly nadolol or propranolol, are important long-term therapy

5.      ICD therapy may be indicated in selected patients with congenital long QT syndrome or persistent high arrhythmic risk

6.      An ICD is generally not indicated solely for an isolated reversible episode of drug-induced Torsades de pointes, but ICD decisions should be individualized after cardiac arrest or when residual arrhythmic risk remains

8. Key Clinical Insight

Syncope + QTc >500 ms + polymorphic ventricular tachycardia with twisting QRS complexes + QT-prolonging medications + bradycardia = Torsades de pointes

In this patient, citalopram and ciprofloxacin can both contribute to QT prolongation, while female sex and bradycardia provide additional risk factors for acquired Torsades de pointes.

References

1.      Zeppenfeld K, Tfelt-Hansen J, de Riva M, et al. 2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Heart J. 2022;43(40):3997-4126. doi:10.1093/eurheartj/ehac262. PMID: 36017572.

2.      Drew BJ, Ackerman MJ, Funk M, et al. Prevention of torsade de pointes in hospital settings: a scientific statement from the American Heart Association and the American College of Cardiology Foundation. Circulation. 2010;121(8):1047-1060. doi:10.1161/CIRCULATIONAHA.109.192704. PMID: 20142454.

3.      Panchal AR, Bartos JA, Cabañas JG, et al. Part 3: Adult Basic and Advanced Life Support: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2020;142(16 Suppl 2):S366-S468. doi:10.1161/CIR.0000000000000916. PMID: 33081529.