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1
Question:

A 56-year-old man comes to the emergency department due to palpitations and lightheadedness over the last 2 hours.  He has a history of hypertension but no other cardiac conditions and never before had similar symptoms.  The patient drinks 1 to 2 alcoholic beverages daily but does not smoke cigarettes or use illicit drugs.  Blood pressure is 132/76 mm Hg and pulse is 116/min and irregular.  Cardiopulmonary examination is normal, except for tachycardia.  Resting ECG shows atrial fibrillation.  The patient undergoes transesophageal echocardiography, which reveals normal cardiac anatomy and no intracardiac thrombi.  Electrical cardioversion is performed.  After the intervention, sinus rhythm is restored, and amiodarone therapy is begun to maintain normal sinus rhythm.  Which of the following cardiac electrophysiologic changes are most likely to occur in this patient due to the medication?

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Explanation:

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ECG effects of antiarrhythmic drugs

PR interval
(prolonged via Ca2+
channel inhibition or
sympathetic blockade)

QRS duration
(prolonged via Na+
channel inhibition)

QT interval
(prolonged via K+
channel inhibition)

Class IA
(eg, procainamide)

Class IB
(eg, lidocaine)

Class IC
(eg, flecainide)

Class II
(eg, metoprolol)

Amiodarone

Sotalol

Other class III
(eg, dofetilide)

Class IV
(eg, verapamil)

Amiodarone is a commonly used antiarrhythmic drug with wide-ranging antiarrhythmic effects and corresponding ECG manifestations.  It primarily functions as a class III antiarrhythmic by inhibiting the rapid component of the delayed rectifier potassium current, which is responsible for ventricular repolarization.  This prolongs action potential duration and the effective refractory period, suppressing electrical foci that stimulate atrial and ventricular arrhythmias.  It also prolongs the QT interval on ECG, which increases the risk of torsade de pointes; however, compared to other class III antiarrhythmics (eg, dofetilide, ibutilide), the risk of torsade de pointes with amiodarone is low.

Amiodarone also has the following effects:

  • Class I effect: Amiodarone somewhat inhibits the fast sodium channels responsible for cardiomyocyte depolarization (phase 0).  This slows ventricular depolarization to suppress arrhythmogenic foci, and it prolongs QRS complex duration on ECG.

  • Class II and IV effects: Amiodarone has beta-blocking properties that inhibit sympathetic stimulation of the conduction system.  The drug also inhibits the slow L-type calcium channels responsible for depolarization of the sinus node and atrioventricular node.  Both effects prolong the refractory period of the conduction system to suppress arrhythmogenic foci and in doing so contribute to a decreased sinus rate (ie, slowed heart rate) and a prolonged PR interval on ECG.

(Choice A)  Both class II (ie, beta blockers) and class IV (ie, nondihydropyridine calcium channel blockers) antiarrhythmics slow the sinus rate and prolong the PR interval, but have no effect on QRS duration or the QT interval.

(Choices C, D, and E)  Class I antiarrhythmics inhibit fast sodium channels to slow depolarization and prolong QRS duration.  However, the effects of class IB antiarrhythmics (eg, lidocaine) occur only at rapid heart rates, and no change in QRS duration is seen on resting ECG.  Class IA antiarrhythmics (eg, procainamide) also inhibit the delayed rectifier potassium current to prolong the QT interval.

Educational objective:
Amiodarone primarily functions as a class III antiarrhythmic, inhibiting the delayed rectifier potassium current to slow ventricular repolarization and prolong the QT interval.  It also inhibits fast sodium channels (class I effect) to slow ventricular depolarization and prolong QRS complex duration.  Beta blockade (class II effect) and inhibition of slow L-type calcium channels (class IV effect) slow conduction in the sinus node and atrioventricular node causing decreased sinus rate and a prolonged PR interval.