A 45-year-old man who was recently started on medication for paroxysmal atrial fibrillation undergoes stress ECG testing. The patient exercises on a treadmill for 9 minutes and reaches 98% of age-predicted maximal heart rate without chest pain or ST-segment changes. His pre-test resting QRS complex duration is 95 msec (normal: 80-120 msec) and corrected QT (QTc) interval duration is 410 msec (normal <440 msec). ECG findings recorded at his maximally achieved heart rate show a QRS complex duration of 125 msec and QTc interval duration of 400 msec. Based on the patient's test results, which of the following medications is most likely being used to treat his atrial fibrillation?
Show Explanatory Sources
The QRS complex duration is typically slightly reduced during exercise in response to the increase in cardiac conduction velocity that accompanies faster heart rates. However, this patient's QRS duration is normal at rest and prolonged at near-maximal heart rate. This suggests that the drug used to treat his atrial fibrillation lengthens the QRS duration in a rate-dependent manner, which is consistent with a drug exhibiting strong use-dependence such as flecainide.
Flecainide is a class 1C antiarrhythmic that is typically used to treat supraventricular tachycardias such as those caused by atrial fibrillation. Class 1C antiarrhythmics bind to the fast sodium channels responsible for phase 0 depolarization of cardiac myocytes, blocking the inward sodium current. This prolongs the QRS duration with little effect on total action potential or QT interval duration. Class 1C drugs are the slowest of the class 1 agents to dissociate from the sodium channel, and do so primarily during diastole. This results in a phenomenon known as use-dependence, in which their sodium-blocking effects intensify as the heart rate increases due to less time for the medication to dissociate from the receptor.
(Choice A) Selective β1 blockers such as atenolol do not significantly affect QRS duration. However, their use during exercise ECG testing can limit the maximal heart rate that is achieved.
(Choice B) Digoxin can cause false-positive ST-segment depression during exercise ECG testing as well as lower the maximal achievable heart rate. It does not significantly affect QRS duration.
(Choice C) Dofetilide is a class III antiarrhythmic drug that blocks the outward potassium current during repolarization. As a result, it increases the QT interval duration but does not affect QRS duration. Class III agents demonstrate reverse use-dependence (the slower the heart rate, the more the QT interval is prolonged).
(Choice E) Verapamil (a class IV antiarrhythmic) is a calcium channel blocker that slows sinoatrial and atrioventricular nodal conduction. It also increases coronary blood flow and reduces myocardial oxygen demand, which can mask ischemia during stress testing. Verapamil does not affect QRS duration.
Educational objective:
Class 1C antiarrhythmics such as flecainide are potent sodium channel blockers that have increased effect at faster heart rates (use-dependence). This makes them more effective at treating tachyarrhythmias, but can also cause prolonged QRS duration (a proarrhythmic effect) at higher heart rates.