A Case of Flecainide Toxicity and Its Complications
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EP LAB DIGEST. 2024;24(6):1,12-13.
We present a case that explores the intricate interplay between therapeutic benefits and toxic effects of flecainide, emphasizing the importance of vigilant monitoring and precise dosing in clinical settings. Through a comprehensive examination of the patient’s medical history, clinical presentation, and relevant diagnostic findings, this case aims to enhance our understanding of flecainide toxicity, ultimately contributing to improved patient outcomes and refined clinical management strategies.
Case Presentation
An 81-year-old male with atrial fibrillation (AF) on flecainide, sinus node dysfunction with a dual chamber pacemaker, heart failure with recovered
ejection fraction, and chronic kidney disease (CKD) presented to the emergency department (ED) after a syncopal episode.
Several days prior to his presentation, he noticed increasing rates on his ambulatory monitoring device and an irregular rhythm concerning for AF. After contacting his electrophysiologist, his flecainide was increased from 100 mg twice daily to 150 mg twice daily. Following the medication titration, he reported worsening fatigue and noted ensuing poor oral intake of both food and liquids due to nausea. On the day of his presentation, he sustained a witnessed collapse without prodromal symptoms and was promptly brought to the ED for clinical assessment.
Upon presentation to the ED, he was hemodynamically stable, but his electrocardiogram (ECG) demonstrated a regular, wide complex tachycardia (Figure 1). His presenting rhythm was interpreted in the ED as ventricular tachycardia (VT), prompting treatment with amiodarone; however, cardioversion was deferred.
Initial labs at that time were notable for a creatinine of 2.1 mg/dL (eGFR 31), increased from a baseline of 1.6 mg/dL (eGFR 43), and a pH of 7.35.
Further rhythm review on serial ECGs showed varying frontal axes with a broad QRS (Figure 2). Device interrogation demonstrated an AS-VS rhythm consistent with a supraventricular tachycardia (SVT) with aberrancy as the culprit arrhythmia (Figure 3) corresponding to the approximate time of the initial ECG. On further review of the interrogation, several episodes of nonsustained VT as well as a prolonged episode of VT were observed earlier in the day (Figure 4). This prolonged episode of VT was thought to be temporally consistent with the presenting syncopal episode. Flecainide toxicity was suspected, and a drawn level was elevated at 1.06 mcg/mL (normal <1.0 mcg/ml). Given high suspicion for flecainide toxicity, the amiodarone infusion was thus discontinued. Medical toxicology was consulted and a NaHCO₃ drip was initiated with a target alkaline pH of 7.45-7.55.
Approximately 24 hours after his last dose of flecainide, his SVT resolved and the QRS narrowed back to baseline. Lipid emulsion therapies, which had been initially considered, were thus deferred given quick recovery.
Discussion
Flecainide, a class 1c lipophilic antiarrhythmic agent, delays phase 0 depolarization by binding open-state sodium channels to cause slowing of
conduction and has proven to be an effective medication for termination of atrial arrhythmias.2 However, flecainide has atrial and ventricular proarrhythmic potential even at usual prescribed doses, particularly in patients with underlying CAD or structural heart disease. These proarrhythmic manifestations can manifest as bradyarrhythmias, QRS widening, and tachyarrhythmias (particularly VT). The proposed mechanism is thought to be due to nonuniform conduction slowing and prolonging of the ventricular myocyte refractory period.3-5
The mainstay of medical therapy for flecainide toxicity has been the use of a high-dose sodium bicarbonate infusion to offset the cardiotoxic effects of the drug by inducing a high-dose sodium load along with serum alkalinization.5 This is thought to result in increased electrostatic repulsion, thereby decreasing flecainide binding capacity to facilitate dissociation from the Na-channel binding sites.6 This therapy alone has been shown to rescue patients from even life-threatening overdoses, as it did in this patient’s case. Alternative treatment options include intravenous lipid emulsion therapy to sequester the lipophilic drug and decrease receptor binding, antiarrhythmics, transvenous pacing, and extracorporeal membrane oxygenation for hemodynamic support.6
Flecainide toxicity has a high mortality (approximately 10%-22.5%) associated with overdose. The duration of QRS interval and QTc are thought to
be prognostic in terms of risk of hemodynamic collapse and lethal arrhythmias. Requirement for mechanical circulatory support is more common in patients with QRS >200 ms.4 Thus, monitoring for flecainide toxicity via ECG after dose adjustments is an important consideration in clinical management. Although not feasible in all practice settings, it may be reasonable to obtain flecainide levels during outpatient visits, especially after dose adjustments in at-risk patients. Additionally, although flecainide is predominately metabolized by the liver, there is a significant renal contribution to its elimination. Levels even slightly above the upper limit of normal can be associated with clinical toxicity and arrhythmogenic manifestations.1
Close retrospective review of our patient’s history and risk factors raised several concerns regarding selection of flecainide as a safe agent. Classically, trainees are taught about the Cardiac Arrhythmia Suppression Trial (CAST), which demonstrated that the use of encainide or flecainide to treat asymptomatic or mildly symptomatic ventricular arrhythmias in patients with left ventricular dysfunction after MI carries a risk of excess mortality.1 On review of this patient’s angiograms, he was found to have a mild-moderate degree of coronary stenosis; in reviewing his echocardiograms, he was found to have previously had a reduced ejection fraction, although this had recovered in recent years. Although outside the scope of MI, given the advent and frequent clinical utilization of cardiac computed tomography and evolution of various stress modalities (PET, MPI, SPECT), this raises the question as to what degree plaque stenosis or flow-limiting coronary disease should be considered to preclude initiation of class Ic antiarrhythmics.
Summary
We demonstrate the intricate challenges associated with flecainide toxicity, particularly in patients with multiple comorbidities and complex cardiac history. Higher doses of antiarrhythmics, including flecainide, should be used sparingly in the elderly population given the higher risk of developing side effects. Flecainide, while effective in managing AF, demands meticulous dosing and continuous monitoring due to its narrow therapeutic window. The presented case underscores the potential proarrhythmic manifestations of flecainide, including wide complex tachycardias, emphasizing the need for prompt recognition and intervention.
Though rare, flecainide toxicity can lead to life-threatening complications, necessitating a multidisciplinary approach for optimal management. Ultimately, this case contributes to our understanding of flecainide toxicity and encourages a thoughtful reassessment of its appropriateness in specific patient populations.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest, and report no conflicts of interest regarding the content herein.
References
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2. Roden DM, Woosley RL. Drug therapy. Flecainide. N Engl J Med. 1986;315(1):36-41. doi:10.1056/NEJM198607033150106
3. Brugada J, Boersma L, Kirchhof C, Allessie M. Proarrhythmic effects of flecainide. Experimental evidence for increased susceptibility to reentrant arrhythmias. Circulation. 1991;84(4):1808-1818. doi:10.1161/01.cir.84.4.1808
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5. Vu NM, Hill TE, Summers MR, Vranian MN, Faulx MD. Management of life-threatening flecainide overdose: a case report and review of the literature. HeartRhythm Case Rep. 2015;2(3):228-231. doi:10.1016/j.hrcr.2015.12.013
6. Di Grande A, Giuffrida C, Narbone G, et al. Management of sodium-channel blocker poisoning: the role of hypertonic sodium salts. Eur Rev Med Pharmacol Sci. 2010;14(1):25-30.
