What are the causes of Torsades de Pointes (TdP), a polymorphic ventricular tachycardia?

From the Guidelines

Torsades de Pointes (TdP) is primarily caused by prolongation of the QT interval on an electrocardiogram, which increases the risk of this potentially fatal ventricular tachyarrhythmia, with the most common causes including medications that prolong the QT interval, electrolyte abnormalities, and congenital long QT syndromes. The causes of TdP can be multifactorial, involving various mechanisms that ultimately lead to delayed ventricular repolarization.

Medications

Medications that prolong the QT interval are a major cause of TdP, including:

• Certain antiarrhythmics (amiodarone, sotalol, procainamide) 1
• Antipsychotics (haloperidol, quetiapine) 1
• Antibiotics (macrolides like azithromycin, fluoroquinolones like levofloxacin) 1
• Antiemetics (ondansetron) 1

Electrolyte Abnormalities

Electrolyte abnormalities, particularly:

• Hypokalemia
• Hypomagnesemia
• Hypocalcemia, can also precipitate TdP 1

Congenital Long QT Syndromes

Congenital long QT syndromes are another significant cause of TdP, often triggered by factors such as:

• Bradycardia
• Stress
• Exercise 1

Other Contributing Factors

Other contributing factors include:

• Structural heart disease
• Female gender
• Advanced age
• Renal or hepatic dysfunction
• Concomitant use of multiple QT-prolonging medications 1

Underlying Mechanism

The underlying mechanism involves delayed ventricular repolarization, which creates an environment for early afterdepolarizations that can trigger this distinctive "twisting of the points" arrhythmia 1

Immediate Management

Immediate management includes:

• Correcting electrolytes
• Discontinuing offending medications
• Administering magnesium sulfate 1-2g IV over 5-10 minutes, even if magnesium levels are normal 1

From the FDA Drug Label

Ventricular Arrhythmia Sotalol AF can cause serious ventricular arrhythmias, primarily Torsade de Pointes (TdP) type ventricular tachycardia, a polymorphic ventricular tachycardia associated with QT interval prolongation. QT interval prolongation is directly related to the dose of Sotalol AF Factors such as reduced creatinine clearance, gender (female) and larger doses increase the risk of TdP.

The causes of Torsades de Pointes (TdP) include:

• QT interval prolongation, which is directly related to the dose of Sotalol AF 2
• Reduced creatinine clearance 2
• Gender (female) 2
• Larger doses of Sotalol AF 2
• Other risk factors such as history of cardiomegaly or congestive heart failure, and history of sustained ventricular tachycardia 2
• Concomitant use of other drugs that prolong the QT interval, such as antiarrhythmics, phenothiazines, bepridil, tricyclic antidepressants, and certain oral macrolides 2
• Hypokalemia, hypomagnesemia, and hypocalcemia 3

From the Research

Causes of Torsades de Pointes (TdP)

The causes of Torsades de Pointes (TdP), a polymorphic ventricular tachycardia, can be attributed to various factors, including:

• Congenital syndromes, such as genetic mutations in genes that control expression of potassium and sodium channels 4
• Acquired factors, including:
  • Drug-induced QT prolongation, particularly with antiarrhythmic agents like quinidine, sotalol, dofetilide, and ibutilide 5, 4
  • Electrolyte imbalances, such as hypokalemia, hypomagnesemia, or both 5, 6
  • Slow heart rate, induced by sinus bradycardia or heart block 5
  • Cardiac disease 7
• Other factors, including:
  • Abnormalities of ventricular repolarization, with prolongation of the QTU interval and variable deformations of the TU waves 6
  • Pause-dependent torsades, such as paroxysmal bradycardia 6
  • Potassium and magnesium deficiencies 6

Underlying Mechanisms

The underlying mechanisms of TdP involve:

• Reentry and afterdepolarization-induced activity 6
• Genetic factors causing abnormalities of the G-proteins, potassium currents, or adrenergic receptors 6
• Delayed ventricular repolarization, as evidenced by QT interval prolongation on the surface electrocardiogram 7