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Atrial flutter with flecainide-induced 1:1 conduction at a rate <200 b.p.m. at rest: a case report

Abstract Background  Class IC antiarrhythmic drug flecainide is commonly used in the management of atrial arrhythmias and in particular atrial fibrillation (AF). Although previously reported as a potential complication, atrial flutter (AFL) with 1:1 atrioventricular (AV) conduction is rare, with only few cases reported so far, most of which related to physical activity. In all previous reported cases, 1:1 conduction resulted in ventricular rates of >200 b.p.m. Case summary  We report the case of a 60-year-old woman, who presented to our local emergency department with palpitations related to acute onset AF. The patient developed symptomatic 1:1 AFL with a rate of 192 b.p.m., shortly after administration of intravenous flecainide, which spontaneously converted back to AF and subsequently to sinus rhythm, with further administration of amiodarone and beta-blocker. Discussion  The case raises awareness of this rare but potentially life-threatening complication to those using flecainide for pharmacological cardioversion of AF. QRS complex widening can be seen in the context of very rapid ventricular rates, posing additional diagnostic challenge, especially with rates of <200 b.p.m. Prescribing an AV nodal blocking agent, such as a beta-blocker, together with flecainide reduces significantly the risk of 1:1 conduction and should always be considered.


Introduction
Class IC antiarrhythmic drug flecainide is among the most commonly used in the UK for the management of patients with atrial fibrillation (AF), both for the acute pharmacological cardioversion of recentonset AF as well as the prevention of recurrent episodes. 1 Although the possibility to cause pro-arrhythmic effects has been well established, it is generally regarded as a safe drug in patients without structural heart disease. 2

Learning points
• Flecainide can rarely induce atrial flutter with 1:1 atrioventricular (AV) block, which can be life-threatening.
• Recognition can pose a diagnostic challenge, especially with rates <200 b.p.m. and broad QRS complexes. Atrial flutter (AFL) with 1:1 atrioventricular (AV) conduction is an additional arrhythmia-related safety issue associated with flecainide. However, it is regarded rare and there is little awareness of this potentially lethal-should it degenerates into ventricular fibrillation complication. 2,3 Interestingly, in the majority of the reported cases, AFL with 1:1 conduction occurred during physical activity, possibly due to increased sympathetic tone. 3 In all those cases, the heart rate was >200 b.p.m.
1:1 AFL induced by flecainide at rest has only been reported twice in the past 1,3 and to the best of our knowledge, it has never been reported with a rate of <200 b.p.m.

Case presentation
A 60-year-old woman presented to our local emergency department (ED) with a few hours history of palpitations. She had paroxysmal AF for the last 5 years and had been treated in the past with regular flecainide, following previous treatments with intravenous (IV) flecainide in ED. A pill in the pocket approach had been adopted more recently. Additional past medical history included hypothyroidism, anxiety, and gastro-oesophageal reflux disease. There was no history of ischaemic heart disease or angina. Her regular medications included levothyroxine, mirtazapine, and omeprazole. Prior to initiation of flecainide, the electrocardiogram (ECG) demonstrated normal QRS and QTc intervals (Figure 1), which remained normal throughout the course of treatment. Transthoracic echocardiogram ruled out any structural heart disease, being completely normal.
At presentation, the initial ECG demonstrated AF at a rate of 156 b.p.m. (Figure 2). Clinical examination findings were normal and the patient was haemodynamically stable, with blood pressure (BP) of 146/104 mmHg. Blood tests, including full blood count, electrolytes, renal function, C-reactive protein, and coagulation were normal. Thyroid-stimulating hormone was slightly raised with normal free thyroxine (T4). Given the patient had tolerated flecainide well in the past, the emergency physician decided to try pharmacological cardioversion with IV flecainide. Weight was 107 kg, therefore, 150 mg over 10 min were administered (no oral flecainide had been taken). A therapeutic dose of subcutaneous enoxaparin (1.5 mg/kg) was also administered, as she was not anticoagulated (CHA2DS2-VASc score was only 1 for being female). Shortly after the flecainide infusion had finished and with the patient at rest, she developed worsening palpitations associated with chest pain. The cardiac monitor demonstrated a regular tachycardia of 192 b.p.m. with broad QRS complexes and the ECG demonstrated a pattern of 1:1 AFL with QRS complexes of 120 ms ( Figure 3). She remained haemodynamically stable with BP of 128/88 mmHg. While emergency electrical cardioversion was being prepared, the rhythm spontaneously converted into AF at a rate of 160-170 b.p.m. The total duration of 1:1 AFL was 10 min.
Given the anticipated delays in organizing electrical cardioversion in a haemodynamically stable patient and because the patient's chest pain had completely resolved, clinical decision at the time was to proceed with administration of IV amiodarone, beta-blocker, and magnesium (Mg 2þ ), with close monitoring for any further arrhythmias and plan for electrical cardioversion should that failed. The beta-blocker was given to avoid any further 1:1 conduction, by using an AV nodal blocking agent. The use of Mg 2þ has been shown to be effective for rate control and modestly for restoration of sinus rhythm in AF, in conjunction with standard care. 4 Following administration of 600 mg of amiodarone and 10 mg of metoprolol together with 2 g of Mg 2þ , sinus rhythm was restored and the patient felt a lot better. She moved to the coronary care unit for monitoring and was discharged the next day.
At discharge, a small dose of flecainide 50 mg b.i.d., alongside with 1.25 mg of bisoprolol were initiated. Despite CHA2DS2-VASc score being only 1 due to female sex, given multiple previous episodes of paroxysmal AF and in the absence of any bleeding risks, it was decided to commence regular anticoagulation with 60 mg edoxaban. That would also facilitate electrical cardioversion, should AF recurred.
The patient remains asymptomatic at telephonic consultation 1 month after the episode. She will be followed up in clinic, where AF ablation will be discussed, should she remains symptomatic.

Discussion
Atrial flutter is categorized into typical and atypical form. Typical AFL is a MACRO-reentry tachycardia. The mechanism is that of a large re-entrant circuit contained in the right atrium (RA), with passive activation of the left atrium. The activation wave front goes downward in the RA free wall, travels through the cavotricuspid isthmus, spreads upward in the septal wall, and crosses the crista terminalis to complete the re-entrant circuit. Depending on the direction of the re-entrant circuit, typical AFL is further sub-divided into counter clockwise (the commonest) and clockwise AFL. The term atypical AFL is used to describe rapid atrial tachycardias with ECG patterns differing from the forms of typical AFL and circuit configuration different from the typical RA flutter circuit, even if they have an ECG pattern similar to typical flutter. The precise mechanism of atypical flutter can only be determined by electrophysiological studies. 5,6 The re-entrant circuit present in AFL causes a repeated loop of electrical activity to depolarize the atrium at a rate of 250-350 b.p.m. Atrial flutter usually occurs with some degree of AV block, most commonly 2:1, giving ventricular rates of $150 b.p.m. However, uncommonly, it occurs without AV block, i.e. with 1:1 AV conduction. This can result in extremely high ventricular rates of up to 320 b.p.m.      and although very rare to happen spontaneously, it has the potential to occur more frequently by the use of cardio-depressant drugs, such as flecainide. 7 This has been named in the past 'Class IC Atrial Flutter', as it can also be seen with other Class IC antiarrhythmic agents. 8 Flecainide slows down atrial conduction, reducing the flutter rate by $1/3. 9 That, together with its infrequent capability of 'organizing' AF into AFL can give rise in AFL with 1:1 conduction, resulting in very high ventricular rates, which can potentially degenerate into lifethreatening arrhythmias and cause death. 1,3 Thus, 1:1 AFL is a very serious complication of flecainide. The incidence is believed to be 3.5-5.0%, according to some old reports based on small registry data. 10 Tables 1 and 2 show indications for use of flecainide in AF, together with potential adverse effects, contraindications, dosing, success rate, and other important considerations. 2,11,12 It is important to emphasize that concomitant use of flecainide with an AV nodal blocking agent, such as a beta-blocker, reduces significantly the incidence of 1:1 conduction. 2,11,12 Another important point to remember is that given the high ventricular rates, it is common to see a pattern of aberrant ventricular depolarization, which produces a regular broad complex tachycardia and can be mistaken for ventricular tachycardia (VT), further complicating the diagnosis. In our case, the presence of what looked like P waves before each QRS complex directed us towards 1:1 AFL, rather than VT, despite the fact that we would normally expect a ventricular rate of much >192 b.p.m. We believe that flecainide slowed the atrial rate quite significantly and therefore, allowed such a ventricular rate.
In our opinion, our case presents several important learning points to the reader and raises awareness of a rare and under-recognized complication of flecainide, which should be considered by all those using this or other Class IC antiarrhythmic drugs, for the treatment of AF.

Lead author biography
Dr Sotirios Dardas is a cardiology specialty trainee in the East Midlands Deanery in the UK. His aspiration is a career in interventional cardiology with a special interest in structural interventions.

Supplementary material
Supplementary material is available at European Heart Journal -Case Reports online.
Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data.

Consent:
The authors confirm that written consent for submission and publication of this case report including images and associated text has been obtained from the patient in line with COPE guidance.