A 42-year-old man comes to the clinic due to recurrent palpitations. After initial evaluation, he is diagnosed with paroxysmal atrial fibrillation. Echocardiography shows normal left ventricular function and no valvular disease. He is initiated on medication therapy. Two weeks later, the patient undergoes a treadmill exercise test. During the test, his heart rate increases from 75/min to 165/min and QRS complex duration increases from 0.09 seconds to 0.13 seconds. Which of the following medications is most likely responsible for the observed findings?

Question

A 42-year-old man comes to the clinic due to recurrent palpitations.  After initial evaluation, he is diagnosed with paroxysmal atrial fibrillation.  Echocardiography shows normal left ventricular function and no valvular disease.  He is initiated on medication therapy.  Two weeks later, the patient undergoes a treadmill exercise test.  During the test, his heart rate increases from 75/min to 165/min and QRS complex duration increases from 0.09 seconds to 0.13 seconds.  Which of the following medications is most likely responsible for the observed findings?

Quizplus · Accepted Answer

11ec25c8_d337_a9cb_bc81_7fbede417c11_MD0003_00 Class I antiarrhythmic drugs act by blocking sodium channels and inhibiting the initial depolarization phase (phase 0) of the ventricular action potential. Flecainide and propafenone are class IC antiarrhythmic drugs that are occasionally used for rhythm control of atrial fibrillation (for maintenance of sinus rhythm) in patients with structurally normal hearts. These drugs have the slowest rate of drug binding and dissociation from the sodium channel receptor. action potential Under normal circumstances, flecainide does not cause any significant prolongation of the QRS duration or QT interval; however, in patients with rapid heart rates, the drug has less time to dissociate from sodium channels, leading to a higher number of blocked channels, which results in a progressive decrease in impulse conduction and widening of the QRS complex. This phenomenon is termed use dependence and is seen most frequently with class IC antiarrhythmic agents (less commonly with class IA drugs and rarely with class IB drugs). It is the primary mechanism behind their efficacy against supraventricular arrhythmias. (Choices A and E) Dihydropyridine calcium channel blockers (eg, amlodipine, nifedipine) do not have a significant effect on the cardiac conduction system. Nondihydropyridine calcium channel blockers (eg, verapamil, diltiazem) have antiarrhythmic properties via blockade of L-type calcium channels in the sinoatrial and atrioventricular (AV) nodes. These drugs also exhibit use dependence, but they cause prolongation of the PR interval with no effect on QRS complex duration. (Choices B and D) Digoxin is not typically used as an antiarrhythmic agent and, in fact, has proarrhythmic properties in many settings. Due to its ability to increase vagal tone at the AV node, digoxin is sometimes used as a rate control agent for atrial fibrillation. Beta blockers (eg, metoprolol) inhibit sympathetic activity to the heart, allowing for both antiarrhythmic and rate control properties. Due to their slowing of conduction through the AV node, they are commonly used for rate control of atrial fibrillation. Slowing of conduction through the AV node prolongs the PR interval but has no effect on QRS complex duration. Educational objective: Use dependence refers to enhanced pharmacologic effects of a drug during rapid heart rates and is seen with class IC (eg, flecainide), and, to a lesser extent, class IA antiarrhythmic agents. These agents cause a progressive increase in sodium channel inhibition (ie, progressive decrease in impulse conduction) with faster heart rates, leading to an increase in QRS complex duration. References: Old and new antiarrhythmic drugs for converting and maintaining sinus rhythm in atrial fibrillation: comparative efficacy and results of trials. (http://www.ncbi.nlm.nih.gov/pubmed/12670638) Flecainide associated torsade de pointes: a potential case of reverse use dependence. (http://www.ncbi.nlm.nih.gov/pubmed/24523805)

A 42-Year-Old Man Comes to the Clinic Due to Recurrent