What substances can cause electrical alternans in a patient with a history of cardiac disease?

Substances Causing Electrical Alternans

QT-Prolonging Drugs and Torsade de Pointes

The most clinically significant substances causing electrical alternans are QT-prolonging drugs that induce macroscopic T-wave alternans as a harbinger of Torsade de Pointes, including Class III antiarrhythmics (sotalol, dofetilide), Class Ia antiarrhythmics (quinidine, disopyramide, procainamide), macrolide antibiotics (erythromycin, clarithromycin, azithromycin), fluoroquinolones, and certain antipsychotics. 1

Class III Antiarrhythmic Agents

• Sotalol causes dose-dependent QT prolongation and T-wave alternans, with Torsade de Pointes incidence of 4% in sustained ventricular tachycardia patients and 0.6% in atrial fibrillation patients 2
• Risk increases dramatically when QTc exceeds 500 ms (10.8% incidence of Torsade de Pointes) or when QTc change from baseline exceeds 130 ms (7.1% incidence) 2
• Dofetilide caused Torsade de Pointes in 3.3% of heart failure patients during the first 72 hours of therapy 1
• Amiodarone is notably less likely to cause Torsade de Pointes compared to other QT-prolonging antiarrhythmics, despite causing QT prolongation 1, 3

Class Ia Antiarrhythmic Agents

• Quinidine, disopyramide, and procainamide prolong QT interval and are specifically contraindicated as concomitant therapy with other QT-prolonging agents 1, 2
• These agents should be withheld for at least three half-lives before initiating other QT-prolonging drugs 2

Antibiotics

• Erythromycin can cause extreme QT prolongation (QTc up to 730 ms) with macroscopic T-wave alternans preceding cardiac arrest 1
• Azithromycin significantly increases risk of death and cardiac arrhythmia, particularly in women 1
• Clarithromycin (metabolized by CYP3A4) increases risk of polymorphic ventricular tachycardia and cardiac death 1
• Fluoroquinolones are known to cause QTc prolongation and can precipitate Torsade de Pointes, especially when combined with amiodarone 1, 3

Psychotropic Medications

• Tricyclic antidepressants produce QRS prolongation and can create a Brugada syndrome-like ECG pattern through sodium channel blockade 1
• Phenothiazines (particularly thioridazine) and haloperidol produce marked QT prolongation and Torsade de Pointes 1, 2

Sodium Channel Blocking Drugs

• Flecainide and propafenone can provoke more frequent and difficult-to-cardiovert episodes of sustained ventricular tachycardia 1
• These agents increased mortality in post-myocardial infarction patients in the CAST trial 1
• Cocaine produces toxicity through sodium channel blockade mechanisms 1

Digitalis Glycosides

• Digoxin causes enhanced atrial, junctional, or ventricular automaticity often combined with AV block 1
• Toad venom and foxglove tea produce clinical toxicity resembling digoxin 1

Chemotherapeutic Agents

• Anthracyclines (doxorubicin) cause dose-dependent cardiotoxicity with increased risk of lethal arrhythmias at higher cumulative doses 1
• 5-fluorouracil may cause ventricular fibrillation due to coronary spasm 1

Critical ECG Warning Signs

Macroscopic T-wave alternans is the most critical ECG harbinger of impending Torsade de Pointes and requires immediate intervention. 1

• QTc prolongation >500 ms (except with amiodarone or verapamil) 1
• Marked QT-U prolongation and distortion after a pause 1
• Onset of ventricular ectopy and couplets 1
• Episodes of polymorphic ventricular tachycardia initiated with short-long-short R-R cycle sequence 1

Management Algorithm

1. Immediate recognition: Discontinue the offending drug immediately upon detection of macroscopic T-wave alternans or QTc >500 ms 1
2. Administer intravenous magnesium sulfate regardless of serum magnesium levels 1
3. Correct electrolyte abnormalities: Replete potassium to 4.5-5 mEq/L 1
4. Prevent bradycardia and long pauses with temporary pacing if necessary 1
5. Consider isoproterenol to increase heart rate and shorten ventricular action potential duration 1

Common Pitfalls

• Female gender is an independent risk factor for drug-induced Torsade de Pointes 1
• Patients with left ventricular hypertrophy (wall thickness >1.4 cm) are at particular risk with sotalol, flecainide, and propafenone 1
• Congestive heart failure history increases risk of serious proarrhythmia to 7% with sustained ventricular tachycardia 2
• Drug-drug interactions via CYP3A4 inhibition can precipitate alternans (e.g., amiodarone with other QT-prolonging agents) 3
• Unrecognized hyperkalaemia from combination of renin-angiotensin system inhibitors and co-trimoxazole increases sudden death risk 1