A 50-year-old man has recurrent episodes of paroxysmal atrial fibrillation accompanied by uncomfortable palpitations and chest pressure. Echocardiogram reveals normal biventricular function and no significant valvular disease. Coronary angiography reveals no obstructive coronary artery disease. The patient is started on medication to reduce his symptoms. Two weeks later, he is seen in the emergency department for lightheadedness, weakness, and presyncope. ECG reveals sinus bradycardia at a rate of 53/min with QTc prolongation (508 msec). Telemetry monitoring reveals a short episode of self-resolved torsades de pointes. Which of the following medications was most likely used to treat this patient's palpitations?

Question

A 50-year-old man has recurrent episodes of paroxysmal atrial fibrillation accompanied by uncomfortable palpitations and chest pressure.  Echocardiogram reveals normal biventricular function and no significant valvular disease.  Coronary angiography reveals no obstructive coronary artery disease.  The patient is started on medication to reduce his symptoms.  Two weeks later, he is seen in the emergency department for lightheadedness, weakness, and presyncope.  ECG reveals sinus bradycardia at a rate of 53/min with QTc prolongation (508 msec).  Telemetry monitoring reveals a short episode of self-resolved torsades de pointes.  Which of the following medications was most likely used to treat this patient's palpitations?

Quizplus · Accepted Answer

11ec160b_3b7a_fd7d_9249_49c0398d9092_MD0001_00 Paroxysmal atrial fibrillation is usually treated with rate or rhythm control strategies. Rate control uses AV nodal-blocking drugs (beta blockers, calcium channel blockers) to prevent rapid ventricular response, whereas rhythm control attempts to maintain sinus rhythm with antiarrhythmic drugs (eg, sotalol, flecainide, amiodarone). The QT interval represents both ventricular depolarization and repolarization (total duration of ventricular action potential). However, ventricular depolarization normally contributes only a small amount of time to the interval, and in practice, the QT interval is primarily used as a measure of ventricular repolarization. Class III antiarrhythmics (eg, sotalol, amiodarone, dofetilide) predominantly block potassium channels and inhibit outward repolarizing currents during phase 3 of the cardiomyocyte action potential. This leads to increased action potential duration and QT interval prolongation, which predisposes to the development of polymorphic ventricular tachycardia (torsades de pointes [TdP]). Amiodarone has a lesser proarrhythmic effect than other class III drugs; therefore, TdP is less frequently observed with amiodarone than with sotalol. (Choice A) Diltiazem is a class IV antiarrhythmic drug (calcium channel blocker) that inhibits L-type calcium channels during phase 2 (cardiomyocyte action potential) and phase 0 (nodal action potential) depolarization. It slows the sinus rate, prolongs conduction through the AV node, and depresses myocardial contractility (negative inotropic effect) but does not prolong the QT interval. (Choice B) Metoprolol is a class II antiarrhythmic drug that is a selective beta-1 receptor antagonist. It acts as a negative inotropic and chronotropic agent by decreasing myocardial contractility and heart rate. Unlike sotalol, beta blockers do not have any potassium channel-blocking properties and do not prolong the QT interval. (Choice C) Mexiletine is a class IB antiarrhythmic drug that blocks sodium channels, inhibiting the initial depolarization phase (phase 0) of the cardiomyocyte action potential. It is occasionally used to maintain sinus rhythm in patients with paroxysmal symptomatic atrial fibrillation, but it does not prolong the QT interval. (Choice D) Ranolazine is an antianginal agent and exerts its effect by inhibiting the late phase of inward sodium channels in ischemic cardiac myocytes. It also blocks potassium channels and causes a dose-dependent increase in QT interval; however, TdP has not been reported in ranolazine use. Educational objective: Sotalol has both beta adrenergic-blocking and class III antiarrhythmic (K+ channel-blocking) properties and is occasionally used in treatment of atrial fibrillation. Major side effects of sotalol include bradycardia, proarrhythmia, and most commonly torsades de pointes due to QT interval prolongation. __________ References: Drug-induced arrhythmia: pharmacogenomic prescribing? (http://www.ncbi.nlm.nih.gov/pubmed/23091201)

A 50-Year-Old Man Has Recurrent Episodes of Paroxysmal Atrial Fibrillation