Flecainide

Cardiac dysrhythmias

Typically, flecainide causes ventricular dysrhythmias in patients with structural cardiac abnormalities [ ], but dysrhythmias can occasionally occur in patients with normal cardiac structure.

• A 77-year-old woman with hypertension, diabetes, and persistent atrial fibrillation was given flecainide 100 mg bd after echocardiography showed a ventricle of normal size and thicknesses, with normal systolic function and discrete atrial dilatation [ ]. She was also taking atenolol 50 mg bd. After a week she developed syncope and general weakness. An electrocardiogram showed a broad complex tachycardia and after electrical cardioversion she had a severe bradydysrhythmia, followed by several episodes of self-limited torsade de pointes and two episodes of sustained syncope requiring defibrillation and flecainide was withdrawn. After 48 hours she had a stable narrow complex sinus rhythm.

Flecainide usually does not cause cardiac dysrhythmias in patients with no structural cardiac abnormality, but rare reports do appear, as in this case. In another case episodes of syncope associated with marked QRS widening in a 63-year-old man taking flecainide 100 mg bd were precipitated by hypokalemia due to bendroflumethiazide [ ].

• A 32-year-old man who was taking flecainide 200 mg/day and bisoprolol 5 mg/day for atrial fibrillation developed rapidly worsening nausea and dyspnea [ ]. His systolic blood pressure was 70–85 mmHg and his pulse was irregular. Echocardiography showed no specific acute abnormalities, but the electrocardiogram showed broad complexes and 2:1 heart block. The flecainide concentration was very high at 8.4 μmol/l (usual target range 0.4–2.1).

Flecainide can unmask Brugada syndrome [ ] and has been used in 159 subjects at risk of Brugada syndrome [ ]. The test was positive in 64 cases and negative in 95. The sensitivity and specificity in SCN5A-positive probands and their family members were 77% and 80% respectively. There were no malignant dysrhythmias.

Antidysrhythmic drugs can sometimes cause increased capture threshold of a pacemaker, but this is rarely clinically important. However, flecainide was associated with an abrupt rise in the capture threshold in a 72-year-old man with a VVI pacemaker for sick sinus syndrome, after 15 days of treatment, resulting in ventricular pacing failure; the effect abated 2 days after withdrawal of flecainide acetate [ ].

In the wake of the preliminary and final reports of the Cardiac Arrhythmia Suppression Trial (CAST) [ , ], which showed that there was an increased risk of death among patients who took encainide and flecainide after myocardial infarction, there have been many publications in which the implications of these findings have been thoroughly discussed [ ]. The relative risk of death or cardiac arrest due to dysrhythmias in the treated patients was 2.6 and the relative risk due to all causes was 2.4. The risk of non-fatal cardiac adverse reactions was no different in treated patients from that in those taking placebo and there was no difference between the groups in the use of other drugs.

Although there is a consensus that encainide and flecainide were associated with an increase in the rate of mortality in CAST, there are still some open questions. First, all the patients recruited to CAST had asymptomatic ventricular dysrhythmias after myocardial infarction, and it is not clear whether the results can be extrapolated to other patients. Secondly, the reasons for the increased mortality in the treated patients are not clear: ventricular dysrhythmias and worsening of left ventricular function are both possible. Thirdly, it is not clear whether the results of CAST in patients with asymptomatic ventricular dysrhythmias after myocardial infarction can also be applied to other Class I antidysrhythmic drugs.

The prodysrhythmic effects of flecainide, by prolongation of the QT interval, have been widely discussed [ ]. However, overall, cardiac dysrhythmias are less common with flecainide than with other antidysrhythmic drugs of Class I, and the dysrhythmogenic effects of flecainide in patients with supraventricular dysrhythmias may not be great. When dysrhythmias occur, prolongation of the QT interval is an important mechanism, but in a recent case it was suggested that tachycardia was due to re-entry within the His–Purkinje system [ ]. In another case flecainide reportedly caused a wide-complex tachycardia due to atypical atrial flutter with 1:1 conduction and aberrant QRS complexes [ ]. Although drugs of Class Ic, such as flecainide, can slow atrial and atrioventricular nodal conduction in patients with atrial fibrillation or atrial flutter, they do not alter the refractoriness of the atrioventricular node, and this allows 1:1 atrioventricular conduction as the atrial rate slows. This happens despite prolongation of the PR interval.

• Syncope occurred in a patient whose QRS complex duration was prolonged [ ].

• In a 67-year-old woman taking flecainide 150 mg bd, widening of the QRS complex occurred during exercise; the effect did not occur at rest or with a dose of 50 mg bd [ ].

• A 68-year-old woman developed flecainide-induced syncope due to torsade de pointes, before the onset of which her QT _c interval reached 680 ms without a change in the QRS duration [ ]. None of the usual triggers were found and she was taking no other drugs.

• A baby developed a supraventricular tachycardia in utero at 38 weeks and was delivered by cesarian section [ ]. Flecainide 2 mg/kg was given postnatally and 48 hours later, after four doses had been given, a broad-complex tachycardia developed. Flecainide was withdrawn, but 4 hours later ventricular fibrillation developed. After resuscitation a re-entrant supraventricular tachycardia was treated with digoxin and amiodarone.

In the second case the serum flecainide concentration 24 hours after the last dose was 630 ng/ml, and since flecainide has a half-life of about 12 hours in children [ ] this suggest that the flecainide concentration at the time of the ventricular fibrillation was probably quite high.

Sodium channel blockers have been used to improve muscle strength and relaxation in myotonic dystrophy. However, myotonic dystrophy is associated with cardiac abnormalities and 30% of deaths are attributable to cardiac causes, mainly dysrhythmias.

• A 41-year-old woman with myotonic dystrophy developed a ventricular tachycardia while talking flecainide [ ]. When flecainide was withdrawn ventricular tachycardia could not be induced.

The authors recommended careful cardiac assessment, risk stratification, and consideration of high-risk patients for electrophysiological studies, especially if considering use of a class I antidsysrhythmic drug.

Hypokalemia can increase the risk of torsade de pointes with flecainide, as with other antidysrhythmic drugs.

• Torsade pointes has been attributed to mosapride (which is related to cisapride) and flecainide in a 68-year-old man with a plasma potassium concentration of 3.2 mmol/l and prolongation of the QT _c interval from 0.48 to 0.56 seconds [ ]. His plasma flecainide concentration was just above the target range at 1013 ng/ml, but the mosapride concentration was not reported.

The authors speculated that mosapride may have inhibited the metabolism of flecainide by CYP2D6.

In a retrospective analysis of 24 patients who developed atrial flutter while taking flecainide (n = 12) or propafenone (n = 12), the electrocardiogram was classified as typical atrial flutter in 13 cases, atypical atrial flutter in eight, or coarse atrial fibrillation in three [ ]. Counterclockwise atrial flutter was the predominant dysrhythmia. The acute results of ablation suggested that the flutter circuit was located in the right atrium and that the isthmus was involved in the re-entry mechanism. There was better long-term control of recurrent atrial fibrillation in patients with typical atrial flutter (85%) compared with atypical atrial flutter (50%). The authors suggested that patients who develop coarse drug-induced atrial fibrillation may not be candidates for ablation.

Flecainide can cause changes of the Brugada syndrome on the electrocardiogram, and another case has been reported in a 70-year-old man [ ].

Cardioversion

In 24 patients with atrial fibrillation who underwent elective transvenous cardioversion for atrial fibrillation, flecainide reduced the energy requirements for further defibrillation after induction of atrial fibrillation by atrial pacing [ ]. There were no ventricular dysrhythmias, but transient bradycardia requiring ventricular pacing occurred in two patients. Two patients had transient asymptomatic hypotension after flecainide and one reported transient dizziness and some light-headedness.

Antidysrhythmic drugs increase the pacing threshold, but failure to capture is a rare consequence. It has, however, been reported twice with flecainide [ , ].

Electrocardiographic changes

ST segment elevation in leads II, III, and aVf, resembling an acute inferior myocardial infarction, have been reported with oral flecainide [ ]. Brugada syndrome is partial right bundle branch block with ST segment elevation in the right precordial leads of the electrocardiogram; it is due to an abnormality of sodium channels and occurs in 0.05–0.1% of the population; some cases are inherited [ ]. Flecainide can bring out Brugada-type changes on the electrocardiogram [ ].

Hypotension

Flecainide has been reported to cause acute hypotension after intravenous administration [ ].