A Case of Flecainide Toxicity

Introduction

Flecainide acetate, first available in 1982, is a class Ic antiarrhythmic and sodium channel blocker used for treatment of supraventricular arrhythmia. After the CAST trial, flecainide’s safety profile was re-established in atrial fibrillation patients without significant left ventricular dysfunction or coronary heart disease.¹ 

Flecainide acts on cardiac conduction, and its toxicity is manifested by a 50% increase in QRS duration or 30% prolongation in PR interval, especially at rapid heart rates. Signs of intoxication are difficult to discern, owing to its nonspecific presentation. 

An under-recognized complication of flecainide use is its transformation of the cardiac rhythm from atrial fibrillation to flutter, more so in cases of toxicity.

Case Report

A 78-year-old female who underwent recent pacemaker implantation for sick sinus syndrome and has a long history of atrial fibrillation, presented to the ER with nausea and dizziness of one week duration. Her past medical history included osteoarthritis and longstanding atrial fibrillation, which was refractory to catheter ablation including pulmonary vein isolation. Medications included warfarin, flecainide 150 mg BID, and carvedilol. 

Clinical examination revealed BP of 128/72 mmHg and heart rate of 108 bpm. The rest of the physical examination was within normal limits. Telemetry at admission showed a wide complex tachycardia. This was immediately followed by a 12-lead EKG, which showed wide paced complex tachycardia with a QRS duration of 240 ms (Figure 1).

Further evaluation was undertaken with a basic metabolic panel, which was notable for a mild elevation in creatinine. Pacemaker interrogation upon admission showed atrial flutter with atrial sensing and ventricular pacing with a widened QRS of 240 msec (Figure 2). Flecainide was discontinued in view of suspected flecainide toxicity, and a flecainide level was sent out. Aggressive hydration was then initiated.

Within 10 hours of admission, QRS duration narrowed significantly, and further decreases in QRS interval were noted with the passage of time. The patient’s symptoms of nausea and dizziness gradually resolved, and her atrial flutter converted back to atrial fibrillation (Figure 3). Renal insufficiency resolved with hydration. Flecainide level came back elevated at 1.23 (0.20-1.00 mcg/ml).

A second pacemaker interrogation after hospital discharge showed atrial fibrillation with ventricular paced rhythm and QRS duration of 160 ms, which is likely her baseline. Retrospectively, the QRS duration during her hospitalization demonstrated a 50% increase from her baseline.  

Discussion

Flecainide toxicity can occur secondary to chronic ingestion and may be precipitated even by mild renal failure, as seen in this case, since the majority of the flecainide is excreted by the kidneys. The half-life of flecainide is about 20 hours. Maximal therapeutic effect has been observed at levels of 0.2-1.0 mcg/mL. Plasma levels above 0.7-1 mcg/mL are associated with higher adverse effects. Extracardiac effects include dizziness and visual disturbances. 

A high degree of suspicion for flecainide toxicity is required when the patient’s initial presentation is nonspecific. Early diagnosis and treatment prevents fatality. Treatment includes increasing the excretion of flecainide, with symptomatic support and administration of sodium bicarbonate in severe cases, which reverses the effect of sodium channel blockade. 

Conclusion

Flecainide is indicated for atrial fibrillation with no structural heart disease. Conduction disturbances begin with widening of the QRS complex, which is an early sign of flecainide toxicity as evidenced in this case.

Ventricular proarrhythmia has been described, but it is not always a manifestation of flecainide toxicity. Toxicity is manifested at levels >1 mcg/mL due to its proarrhythmic effect because it promotes reentry in ventricular tissue. This occurs due to rate-dependent blockade of rapid sodium channels, slowing phase 0 of the cardiac action potential, and some inhibition of the slow calcium channel. PR prolongation is also an early manifestation of flecainide toxicity, which could not be determined in this patient due to her presentation in atrial flutter with ventricular pacing. 

A clinically important but infrequent consequence of flecainide toxicity is its organization of atrial fibrillation into atrial flutter, as seen in this case. With the resolution of the toxicity, the atrial flutter gradually converted back to atrial fibrillation.

Early recognition, discontinuation of the drug, and aggressively hydrating the patient enabled rapid resolution of symptoms, narrowing of the widened QRS complex, and clinical stability for discharge home.

Disclosures: The authors have no conflicts of interest to report regarding the content herein.   

References

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