Which medications in the drug class Antidysrhythmics, III are used in the treatment of Dilated Cardiomyopathy?

Updated: Mar 02, 2021
  • Author: Vinh Q Nguyen, MD, FACC; Chief Editor: Gyanendra K Sharma, MD, FACC, FASE  more...
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Antidysrhythmics, III

Antiarrhythmics are useful in patients with supraventricular and nonsustained ventricular tachycardias. Not all antiarrhythmics are considered safe in patients with structural heart disease. The class III antiarrhythmics amiodarone and dofetilide are favored in these patients for the treatment of supraventricular and ventricular dysrhythmias.

Amiodarone (Cordarone)

Amiodarone is a class III antiarrhythmic agent (K-channel blocker) with class I activity that may inhibit atrioventricular conduction and sinus node function. It prolongs the action potential and refractory period in myocardium and inhibits adrenergic stimulation.

In patients with recent myocardial infarction and congestive heart failure, amiodarone reduces sudden cardiac death but is inferior compared to ICDs.

For patients with heart failure presumed to be resultant from atrial fibrillation, rhythm control should be attempted. Amiodarone is commonly initiated, with cardioversion attempted 1 month later.  Amiodarone is among the most effective antiarrhythmic agents for suppression of atrial fibrillation. In patients with systolic heart failure and atrial fibrillation, rhythm control does not improve mortality, hospitalization for heart failure exacerbation, or stroke as compared to rate control. [Roy D, Talajic M, Nattel S, et al, for the Atrial Fibrillation and Congestive Heart Failure Investigators. Rhythm control versus rate control for atrial fibrillation and heart failure. N Engl J Med. 2008 Jun 19. 358 (25):2667-77.]

Monitoring of pulmonary, thyroid, and liver toxicity while patients are on amiodarone therapy is advised.

Dofetilide (Tikosyn)

Dofetilide is the prototype of a "pure" class III agent. It has been approved by the US Food and Drug Administration (FDA) for maintenance of sinus rhythm after conversion from atrial fibrillation or atrial flutter lasting longer than 1 week. It is also indicated for conversion of atrial fibrillation and atrial flutter to normal sinus rhythm. If patients do not convert within 24 hours of initiation of therapy, electrical cardioversion should be considered.

Torsade de pointes is the only complicating arrhythmia showing dose-response relationship. The prevalence with supraventricular arrhythmia is 0.8%. Majority of torsade de pointes episodes occur within first 3 days of therapy.

Dofetilide has no effect on cardiac output, cardiac index, stroke volume index, or systemic vascular resistance in patients with ventricular tachycardia, mild-to-moderate heart failure, angina, and either normal or reduced left ventricular ejection fraction (LVEF). It does not affect blood pressure.

Dofetilide blocks delayed rectifier current (IKr) and prolongs action potential duration; indeed, even at higher magnitudes, it has no effect upon other depolarizing potassium currents (IKs and IKl). It terminates induced re-entrant tachyarrhythmias (atrial fibrillation/flutter and ventricular tachycardia) and prevents their re-induction. At clinically prescribed concentrations, it has no effect on sodium channels, which are associated with class I effects. Furthermore, no effect is noted on alpha- or beta-adrenergic receptors.

Dofetilide must be initiated with continuous ECG monitoring and monitoring must be continued for more than 12 hours after conversion. Dose must be individualized according to creatinine clearance (CrCl) and QTc (use QT interval if heart rate < 60/min). There is no information on use of this drug for heart rates less than 50 beats per minute.

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