The response of paediatric arrhythmias to intravenous and oral flecainide

Flecainide acetate was administered intravenously and orally to 12 consecutive children, aged 1-15 years, presenting with arrhythmias that were life threatening or resistant to conventional medical treatment. Three children had arrhythmias related to Wolff-Parkinson-White syndrome, four had concealed accessory pathways, two had His bundle tachycardia, and three had ventricular tachycardia. Of seven patients who were given flecainide intravenously, four returned to sinus rhythm and in a fifth successful rate control of His bundle tachycardia was achieved. All 12 patients were given the drug orally: in nine it was successful in preventing recurrence of arrhythmia, in one satisfactory rate control was achieved, and in two it was withdrawn because it produced more frequent attacks of tachycardia. No other adverse effects occurred. The efficacy and low toxicity of treatment in this study suggests that flecainide acetate may have an important role in the management of selected paediatric arrhythmias.     

Proarrhythmic effects of the new antiarrhythmic agent flecainide acetate

Flecainide acetate, a new potent class I antiarrhythmic agent, was given to 152 patients (46 orally and 106 intravenously) over a period of 22 months. Seven patients developed proarrhythmic effects. The only conduction abnormalities induced were PR interval prolongation and QRS complex widening, and no patient developed significant sinus bradyarrhythmias; patients with known serious abnormalities of impulse generation or conduction were excluded from this study. Five patients developed ventricular tachycardia or ventricular fibrillation of whom only three had preexisting ventricular arrhythmias. QT and QT_c interval prolongation was observed but was due to QRS complex widening rather than to an increase in the JT interval. A patient with the Wolff-Parkinson-White syndrome had an inducible orthodromic atrioventricular (AV) tachycardia prior to flecainide, but only an antidromic tachycardia was induced after the drug. In one patient flecainide administration resulted in an increase of atrial flutter cycle length which resulted in development of 1:1 AV conduction and overall faster ventricular rate. Two patients who developed ventricular arrhythmias were taking other antiarrhythmic agents, and in this series proarrhythmic effects occurred with both normal and high flecainide concentrations.     

Short- and long-term efficacy and safety of flecainide acetate for supraventricular arrhythmias.

This report summarizes efficacy and safety data on the use of flecainide acetate for supraventricular arrhythmias. For this purpose, 60 original articles were identified by a literature search representing data from 1,835 treatment courses. In 18 trials, flecainide was administered intravenously; in 19, orally; and in 23, both forms of therapy were applied. There were 5 placebo-controlled and 12 comparative studies, whereas data from uncontrolled studies were represented in 43 articles. Short-term flecainide administration terminated atrial fibrillation in 65% of attempts and terminated atrial flutter in 28%. The drug was effective during long-term therapy for atrial fibrillation in 49% of patients, with similar efficacy rates in 11 comparative trials and in 16 uncontrolled studies. In randomized, placebo-controlled studies in patients with paroxysmal atrial fibrillation, flecainide was shown to reduce significantly the number of attacks, to prolong the time between attacks, and to improve quality of life. In patients with atrioventricular (AV) reciprocating tachycardias, acute drug administration was successful in 72%; 83% of patients with AV nodal reentrant tachycardias and 74% exhibiting arrhythmias associated with the Wolff-Parkinson-White syndrome responded acutely. During long-term therapy, efficacy rates were 70%, 78%, and 69%, respectively. Ectopic atrial tachycardia responded in 86% and 95% of patients treated with flecainide acutely or chronically. Data concerning drug-related side effects were available for 1,794 of 1,835 treatment courses (98%). Overall, 352 of 1,794 patients (20%) reported at least one non-cardiac or cardiac adverse experience.(ABSTRACT TRUNCATED AT 250 WORDS)     

Flecainide acetate for resistant arrhythmias in the young: efficacy and pharmacokinetics

Drug efficacy and pharmacokinetics were assessed in 63 patients, aged 5 days to 30 years (mean 8 years), who received flecainide acetate for control of resistant arrhythmias. Doses of flecainide ranged from 59 to 225 mg/m2 body surface area per day (mean 141) in divided doses every 8 to 12 h and serum trough levels ranged from 0.10 to 0.99 micrograms/ml (mean 0.36). Flecainide controlled or partially controlled arrhythmia in 53 (84%) of the 63 patients: 7 of 7 patients who had the permanent form of junctional reciprocating tachycardia, 12 of 13 who had an atrial ectopic tachycardia, 10 of 10 who had ventricular tachycardia and 18 of 25 patients who had reentrant supraventricular tachycardia. Five of seven patients who had the latter arrhythmia were unsuccessfully treated with flecainide. They had Wolff-Parkinson-White syndrome and developed asymptomatic, incessant, slower orthodromic reciprocating tachycardia while receiving the drug. Transient blurred vision was reported in three patients and two patients had transient hyperactivity. No significant hemodynamic side effects were seen in any patient. Twenty-five patients underwent oral pharmacokinetic investigation. Young infants (less than 1 year of age) had a mean plasma elimination half-life (t 1/2) approximating that (11 to 12 h) found in older children and healthy adults; children aged 1 to 12 years had a shorter mean t 1/2 of 8 h. Dosing schedules based on milligrams per square meter body surface area correlated better with plasma flecainide levels than did dosing based on milligrams per kilogram body weight.(ABSTRACT TRUNCATED AT 250 WORDS)     

Conversion of supraventricular arrhythmias to sinus rhythm using flecainide

We evaluated the efficacy of flecainide acetate (given intravenouslyto a maximal dose of2 mg kg^–1 and then orally in a doseof 100 mg b.d. or 100 mg t.d.s.) in the conversion to sinusrhythm of 50 patients exhibiting supraventricular arrhythmias(39 with atrial fibrillation, 6 with atrial flutter, 4 withsupraventricu tachycardia and onewith supraventricular tachycardiain association with the Wolff—Parkinson—White syndrome).Conversion was achieved in 36 patients (72%) (29 cases withatrial fibrillation, 4 cases with supraventricular tachycardia,2 cases with atrial flutter and one case with Wolff—Parkinson–Whitesyndrome), over a mean period of 7.4 ± 9 h. The patientsin which conversion was achieved had arrhythmias which had beenin existence for a shorter time (5.3 ± 9.8 days) thanthose in which conversion was not achieved (16.7 ± 26.2days) (P<0.01). The mean dosage of flecainide used to achieveconversion was 2.5 ± 2.36 mg kg^–1. Flecainide appearsto be an effective agent for the conversion to sinus rhythmof atrial fibrillation and supraventricular tachycardias. Itsefficacy in cases of atrial flutter has not yet been demonstrated.     

Catheter ablation of junctional ectopic tachycardia in children, with preservation of atrioventricular conduction

Summary Background Idiopathic junctional ectopic tachycardia is a rare arrhythmia in children. Several studies have demonstrated that drug therapy is often ineffective and sometimes the only achieved effect is rate control. Early presentation and frequent recurrence are associated with adverse outcome. Patients and methods Three consecutive children, aged 9, 7 and 12 years respectively, underwent radiofrequency catheter ablation for junctional ectopic tachycardia, after having failed antiarrhythmic drug therapy. The entire His bundle was plotted out and marked, using the Localisa navigation system. The arrhythmia was readily and repeatedly inducible using intravenous isoprenaline infusion and the site of earliest retrograde conduction during tachycardia could be assessed. Ablations were performed in sinus rhythm, empirically targeting the site of earliest retrograde conduction during tachycardia. Results This approach was successful in abolishing tachyarrhythmia in the first two patients, in whom the successful ablation site was located superoparaseptally. In the third patient, junctional ectopic tachycardia was inducible, despite abolishing retrograde atrial activation, in a septal location on the tricuspid valve annulus. Further ablations in the superoparaseptal region, closer to the His bundle, were successful in rendering tachyarrhythmia noninducible. Over a median follow-up of 10 months, none of the patients has had recurrence of arrhythmia, despite discontinuing all antiarrhythmic medications. Conclusions Radio frequency catheter ablation of junctional ectopic tachycardia is feasible with preservation of atrioventricular conduction.     

Successful treatment of stress-induced therapy refractory ventricular tachycardia with verapamil

A 51-year-old woman was admitted to the hospital for further elucidation of a syncope of unknown origin and exercise-induced tachycardias with broad QRS-complex. The tachycardia was induced by bicycle exercise stress testing, had a frequency of 165/min, showed an inferior axis and left bundle branch block. Organic heart disease was excluded by right and left heart catheterization and selective coronary angiography. A nodoventricular bundle or an atrio-ventricular bundle was excluded by an extensive electrophysiologic study, therefore the documented tachycardia was probably of ventricular origin. However, it was not possible to induce a ventricular tachycardia by programmed ventricular stimulation with up to three extrastimuli even after the infusion of isoprenaline. Sotalol (2 x 160 mg/die) and the combined treatment with mexiletine (2 x 360 mg/die) and disopyramide (2 x 250 mg/die) did not prevent the induction of the tachycardia by exercise testing. The combination of sotalol and flecainide (2 x 100 mg/die) evoked complex ventricular arrhythmias at rest not noted before, and it was therefore withdrawn as well. After all antiarrhythmic drugs were withdrawn verapamil was given in a dose of 3 x 120 mg and this therapy reproduceably prevented the induction of ventricular tachycardia by exercise testing.     

Encainide versus flecainide for chronic atrial and junctional ectopic tachycardia

For treatment of chronic atrial and Junctional ectopic tachycardia, standard antiarrhythmic therapy has been shown to be ineffective in most patients. Both the intravenous efficacy and the oral efficacy of 2 class IC, were studied in 16 patients with atrial ectopic tachycardia and in 3 patients with junctional ectopic tachycardia, using exercise testing, 24-hour long-term electrocardiography and programmed electrical stimulation. All patients had been previously treated unsuccessfully with several antiarrhythmic drugs. In 5 patients, tachycardia was persistent; in the remaining patients, it occurred intermittently for more than 12 hours/day. Intravenous encainide, in doses ranging from 0.3 to 2.0 mg/kg body weight, was given to 5 patients with atrial ectopic tachycardia, and it terminated atrial ectopic tachycardia in all patients. Intravenous flecainide was given to 9 patients, and it terminated atrial tachycardia in 4 and slowed the tachycardia rate in 2. It terminated Junctional tachycardia in 2 patients and slowed tachycardia rate in 1. During a follow-up period of 10 ± 5 months, oral encainide, in dosages between 150 and 225 mg/day, completely suppressed atrial ectopic activity in 4 patients. In the remaining patient, encainide reduced the number of tachycardia episodes markedly but had to be withdrawn because of intolerable side effects. During a 12 ± 11-month (median 6) follow-up, oral flecainide at dosages between 200 and 300 mg/day, completely suppressed ectopic activity in 7 patients and improved symptoms in 5. Only 1 patient failed to respond to oral flecainide. The results of this study indicate that both encainide and flecainide are effective in the treatment of chronic ectopic atrial and junctional tachycardia.     

Intravenous flecainide acetate for the clinical management of paroxysmal tachycardias

Intravenous flecainide acetate (2 mg/kg) was administered to 40 patients undergoing routine electrophysiological evaluation for the investigation of recurrent paroxysmal tachycardias. Ten patients had recurrent atrial flutter, 11 patients had recurrent atrial fibrillation, one of whom also had paroxysmal left atrial tachycardia, and 19 patients had recurrent ventricular tachyarrhythmias (17 with recurrent ventricular tachycardia and 2 with recurrent fascicular tachycardia). Flecainide was administered during tachycardia (over 5 to 10 minutes) to all patients with atrial flutter, to 10 patients with atrial fibrillation, and to 17 patients with ventricular tachyarrhythmias. In the remaining 3 patients with ill-sustained arrhythmias flecainide was administered during sinus rhythm and reinitiation of tachycardia was then attempted. Flecainide restored sinus rhythm in only 2 patients with atrial flutter (20%), in 9 patients with atrial fibrillation (90%), in 12 patients with ventricular tachycardia (80%), and in one of the 2 patients with fasicular tachycardia. Flecainide also successfully terminated the left atrial tachycardia. Two patients experienced proarrhythmic side effects during flecainide administration, one of whom required intervention by cardioversion. Minor dose effects included oral paresthesia, transient drowsiness or dizziness, and occasional visual blurring. Flecainide acetate is an effective antiarrhythmic agent for the acute termination of recent onset paroxysmal atrial and ventricular tachyarrhythmias.     

Moderate hypothermia in the management of resistant automatic tachycardias in children.

BACKGROUND--Automatic focus tachycardias are often resistant to electrical and pharmacological treatment. Moderate systemic hypothermia (32-34 degrees C) may reduce the tachycardia rate in children with His bundle tachycardia after cardiac surgery. METHODS--The case notes of seven children with automatic focus tachycardias treated with hypothermia were reviewed. Six had His bundle tachycardia after cardiac surgery and one had ectopic atrial tachycardia; all had signs of low cardiac output. RESULTS--Hypothermia led to a reduction in heart rate in all patients (from 211 (28) (mean (SD] to 146 (5) beats/minute, p less than 0.001), with rises in systolic blood pressure (from 74 (14) mm Hg to 97 (10) mm Hg, p less than 0.01) and hourly urine output (from 0.5 (0.4) ml/kg to 4.6 (2.8) ml/kg, p less than 0.02). No direct adverse effects were noted. The arrhythmia did not resolve in three children, who died (two with His bundle tachycardia after Fontan procedures and one with ectopic atrial tachycardia); the other four regained sinus rhythm which was maintained at follow up of 3-13 (mean 9) months. CONCLUSIONS--Moderate systemic hypothermia led to slowing of the arrhythmia rate and an improvement in cardiac output in patients with resistant automatic focus tachycardias. It can be used to improve the haemodynamic condition while other measures of arrhythmia control are being pursued or until spontaneous recovery of normal rhythm.     

Moderate hypothermia in the management of resistant automatic tachycardias in children

BACKGROUND--Automatic focus tachycardias are often resistant to electrical and pharmacological treatment. Moderate systemic hypothermia (32-34 degrees C) may reduce the tachycardia rate in children with His bundle tachycardia after cardiac surgery. METHODS--The case notes of seven children with automatic focus tachycardias treated with hypothermia were reviewed. Six had His bundle tachycardia after cardiac surgery and one had ectopic atrial tachycardia; all had signs of low cardiac output. RESULTS--Hypothermia led to a reduction in heart rate in all patients (from 211 (28) (mean (SD] to 146 (5) beats/minute, p less than 0.001), with rises in systolic blood pressure (from 74 (14) mm Hg to 97 (10) mm Hg, p less than 0.01) and hourly urine output (from 0.5 (0.4) ml/kg to 4.6 (2.8) ml/kg, p less than 0.02). No direct adverse effects were noted. The arrhythmia did not resolve in three children, who died (two with His bundle tachycardia after Fontan procedures and one with ectopic atrial tachycardia); the other four regained sinus rhythm which was maintained at follow up of 3-13 (mean 9) months. CONCLUSIONS--Moderate systemic hypothermia led to slowing of the arrhythmia rate and an improvement in cardiac output in patients with resistant automatic focus tachycardias. It can be used to improve the haemodynamic condition while other measures of arrhythmia control are being pursued or until spontaneous recovery of normal rhythm.     

Inefficacy and proarrhythmic effects of flecainide and encainide for sustained ventricular tachycardia and ventricular fibrillation

OBJECTIVE: To assess the efficacy of encainide and flecainide in treating patients with sustained ventricular arrhythmias. DESIGN: Patients were treated with encainide or flecainide. Efficacy was assessed by comparing the results of programmed ventricular stimulation while patients received therapy with the results while they were drug free. SETTING: The electrophysiology laboratory of the University of California at San Francisco. PATIENTS: Forty-nine patients with spontaneous or inducible sustained ventricular tachycardia or ventricular fibrillation for whom treatment with at least one class IA antiarrhythmic agent had failed. INTERVENTIONS: Patients were treated with encainide, 35 to 50 mg three or four times daily, or flecainide, 100 to 200 mg twice daily. RESULTS: Arrhythmia worsened early in 5 of 16 patients receiving encainide and 3 of 33 patients receiving flecainide. Patients with poor left ventricular function were more likely to exhibit proarrhythmia (P = 0.02). Nine of eleven patients receiving encainide and 23 of 28 patients receiving flecainide who had repeat programmed ventricular stimulation while receiving drug therapy still had inducible, poorly tolerated ventricular tachycardia. CONCLUSION: Encainide and flecainide have a low efficacy rate and a high incidence of worsening of arrhythmia in patients with sustained ventricular arrhythmias, particularly when this condition is associated with poor left ventricular function.     

Suppression of resistant ventricular arrhythmias by twice daily dosing with flecainide

Flecainide acetate is a new antiarrhythmic agent whose pharmacokinetics have suggested that effective therapy could be achieved with twice daily dosing. The antiarrhythmic and electrocardiographic effects of flecainide were evaluated in 11 patients with chronic ventricular ectopic beats. Nine patients had been resistant or intolerant to at least three antiarrhythmic agents and eight had recurrent nonsustained ventricular tachycardia. The antiarrhythmic efficacy of increasing doses of flecainide was determined by comparison with results during administration of a placebo 2 days before and 3 days after increasing doses of flecainide. All 11 patients had an antiarrhythmic response with a mean 97 percent (range 88 to 100) rate of suppression of ventricular ectopic beats and mean 100 percent rate of suppression of ventricular tachycardia with a mean daily dose of 410 mg (range 200 to 600) of flecainide. Effective therapy was accompanied by lengthening of the P-R (+ 29 percent), QRS (+ 27 percent) and Q-Tc (+ 11 percent) intervals. These changes were not associated with a deterioration in exercise tolerance or a reduction in ejection fraction (0.52 ± 0.08 with placebo, 0.53 ± 0.12 with flecainide) as assessed with two dimensional echocardiography. Increasing doses of flecainide were associated with progressive prolongation of the ventricular ectopic coupling interval before suppression of ventricular ectopic beats. During the placebo washout period after multiple oral doses, the terminal (postabsorptive) phase plasma half-life of flecainide was found to range from 13 to 27 hours (mean 20.3). The minimal effective plasma levels of flecainide (resulting in greater than 90 percent suppression of ventricular etopic beats) ranged from 245 to 980 ng/ml (mean 631). Adverse effects during the inpatient evaluation were limited to blurring of vision in three patients, which resolved with smaller but still effective doses.

Suppression of ventricular ectopic beats at a mean rate of 95 percent continued during outpatient therapy. During a mean of 12 months of outpatient follow-up in nine patients, regularly scheduled evaluation of ambulatory arrhythmia frequency continued to document suppression of arrhythmia. Outpatient follow-up occurred monthly for the first 6 months and every 2nd month thereafter. In three patients it was necessary to administer flecainide every 8 hours because blurring of vision occurred at the time of peak plasma levels when the drug was administered every 12 hours. Flecainide was highly effective in suppressing ventricular arrhythmias when administered twice daily.     

Use of flecainide acetate for refractory junctional tachycardias in children with the Wolff-Parkinson-White syndrome

The response of sustained supraventricular tachycardia to intravenous and oral flecainide acetate was investigated in 5 children, aged 5.5 to 11.5 years, who had tachycardias associated with Wolff-Parkinson-White syndrome. All children had failed to respond to at least 2 conventional agents. The effect of flecainide was studied using intracardiac techniques. Intravenous flecainide terminated tachycardia in all 5 patients. After drug infusion, slow, sustained tachycardia could be initiated in 1 patient. With oral treatment, slow, sustained tachycardia was started in 2 children and nonsustained in 2. One child had no inducible tachycardias. In 4 of 5 patients, long-term treatment has reduced the frequency of episodes and the drug is well tolerated. Thus, flecainide may be used to terminate and suppress junctional tachycardias in children who have failed to respond to conventional therapy.     

Oral flecainide is effective in management of refractory tachycardia in infants

BackgroundPropranolol and digoxin have been used as first line drugs for treatment of supraventricular tachycardia (SVT) in infants. Flecainide and other drugs have been effective as a second line treatment for controlling refractory SVT.Material and methodsThis is a prospective study without randomization and control. The inclusion criteria were: infants (≤12 months) with tachyarrhythmia who failed to respond to first line drugs. Patients having post-surgical arrhythmias were excluded from the study.ResultsA total of 8 infants were treated with flecainide for refractory tachyarrhythmia's. Diagnosis on electrocardiogram (ECG) was atrioventricular reentry tachycardia (AVRT) in 5, atrial ectopic tachycardia (AET) in 2, a combination of AVRT and atrioventricular nodal reentry tachycardia (AVNRT) in 1. All patients had failed trial of antiarrhythmic drugs prior to presentation: digoxin and propranolol in 7, amiodarone in 3, cardioversion in 1. Flecainide (80–130 mg/m² orally) resulted in termination of the tachycardia in all 8 patients. Acute pharmacological termination of arrhythmia occurred with oral flecainide loading in 1 and temporarily with intravenous esmolol loading in 1 patient. Adjuvant therapy in form of propranolol was used in 5 and digoxin in 2. There were no side effects noted. Four episodes of recurrence were noted in 3 patients over 2 years, all of which responded to dose increase. Mean follow up time is 24.75 months.ConclusionThis small case series indicates that flecainide is an effective antiarrhythmic agent, free of side effects and when used orally is capable of terminating and controlling relatively resistant supraventricular tachycardia in children.     

Occurrence of exercise-induced and spontaneous wide complex tachycardia during therapy with flecainide for complex ventricular arrhythmias: a probable proarrhythmic effect

Flecainide acetate, a new antiarrhythmic agent, possesses favorable pharmacokinetic and hemodynamic properties and demonstrates highly favorable antiarrhythmic activity in patients with ventricular arrhythmias. However, the proarrhythmic potential of flecainide deserves further evaluation. In 7 (13%) of 55 consecutive patients treated with oral flecainide, 200 to 600 mg/day, for complex ventricular arrhythmias (including sustained ventricular tachycardia in 14), we observed the appearance of new or more sustained exercise-induced (five patients) or spontaneous (two patients) wide complex tachycardia. The mechanism of wide complex tachycardia appeared to be ventricular tachycardia in all seven. In our series, episodes were self-remitting or successfully treated. In four patients, wide complex tachycardia did not recur during exercise testing during alternative antiarrhythmic therapy (three patients) or no antiarrhythmic therapy (one patient). These observations raise the possibility of flecainide-related proarrhythmia, manifested as an increased propensity to exercise (activity)-induced wide complex tachycardia, which was not reliably predicted by results of Holter recordings or programmed electrical stimulation. Patients with complex ventricular arrhythmias beginning long-term treatment with oral flecainide should be considered for treadmill exercise testing together with ambulatory monitoring as part of the initial assessment of drug efficacy.     

Efficacy and safety of flecainide acetate for atrial tachycardia or fibrillation

Thirty-nine patients with symptomatic ectopic atrial tachycardia (9 paroxysmal, of which 5 were incessant) and atrial fibrillation (AF) (25 paroxysmal, 5 chronic) were treated with oral flecainide acetate (100 to 400 mg/day). Thirty-two patients had organic heart disease (16 coronary artery disease, 6 valvular, 10 cardiomyopathy, 7 primary electrical abnormality). Previous antiarrhythmic trials consisted of 0 to 5 drugs (mean 2.2). Of 39 patients with atrial tachycardia or AF, a complete response (no recurrent symptomatic atrial arrhythmia) was achieved in 22 (56%), a partial response (more than 95% reduction in arrhythmia occurrence) in 3 (8%) and no response in 14 (36%). Left atrial size, ejection fraction, underlying heart disease, duration of symptoms before treatment and drug levels were not useful for predicting clinical response. Therefore, during the follow-up period of 5.4 +/- 6.7 months (range 4 weeks to 2.5 years), flecainide had a complete or partial effect in 25 patients (64%). Complete or partial responses were noted in 8 of 9 patients (90%) with ectopic atrial tachycardia and 17 of 30 (57%) with AF. In 14 patients with concurrent ventricular arrhythmias, a significant reduction in episodes of nonsustained ventricular tachycardia was also achieved. Treatment was discontinued in 8 patients (20%) because of cardiac adverse reactions, including pulmonary edema and ventricular or atrial proarrhythmic response. Thus, oral flecainide acetate is effective therapy for some patients with ectopic atrial tachycardia or AF.     

Clinical electrophysiologic effects of flecainide acetate

Summary Flecainide acetate depresses the rate of depolarization of action potential (V_max), the so-called membrane stablizing action. In the intact heart it has a unique profile of substantial effect on conduction with modest effect on refractoriness. After intravenous administration, clinical electrophysiologic studies show that conduction through atrial myocardium, atrioventricular (AV) node, His-Purkinje system, and ventricular myocardium is depressed, the most prominent effect being on the His-Purkinje system. Refractorines of the normal atrial and AV nodal myocardium is not prolonged while that of the ventricular muscle is slightly increased. Atrial fibrillation (60% to 70%), atrial tachycardia (90% to 100%), and nodal and AV tachycardia (80% to 90%) are generally terminated, while flutter is usually slowed, but in a small proportion of patients (10% to 20%) might be terminated by the intravenous use of flecainide acetate. This drug has also been shown to be effective in terminating stable ventricular tachycardia (70%). However, it appears to be slightly less effective in suppressing inducibility of ventricular arrhythmias. Administered orally, flecainide is very effective in decreasing ventricular ectopic activity (80% to 95%) and nonsustained ventricular tachycardia. Thus, flecainide has a wide range of antiarrhythmic properties, making it a useful agent in the management of a variety of supraventricular and ventricular arrhythmias. In a small proportion of patients, however, its use can lead to apparent arrhythmogenic effects, the most dangerous being exacerbation of ventricular tachycardia.     

Clinical and electrophysiologic assessment of oral flecainide acetate for recurrent ventricular tachycardia: Evidence for exacerbation of electrical instability

Four patients with recurrent, symptomatic ventricular tachycardia (VT) refractory to conventional antiarrhythmic agents were given flecainide acetate to control arrhythmias. Ventricular stimulation studies were performed in all patients before and 1 to 2 weeks after initiation of oral flecainide therapy. Before flecainide, all patients had easily inducible VT that was morphologically identical to their spontaneously occurring arrhythmia. Flecainide increased the mean PR interval (from 0.17 to 0.23 second), mean QRS duration (from 0.08 to 0.12 second) and mean ventricular effective refractory period (from 235 to 270 ms). Mean corrected QT interval did not change (0.51 second).In 2 patients, VT could not be induced during follow-up stimulation studies. One patient has been treated successfully for 10 months, with no clinically apparent episodes of VT. One patient had recurrent nonsustained VT and was withdrawn from the study as a treatment failure after 6 months of therapy. Two patients had inducible, polymorphous VT that degenerated into ventricular fibrillation that required 2 countershocks before the successful restoration of sinus rhythm. One of these patients had VT stimulation by atrial pacing at a cycle length of 320 ms in the postflecainide electrophysiologic study. VT was not inducible by atrial pacing during this patient's preflecainide study.Thus, sustained oral flecainide administration may precipitate serious electrical instability in susceptible patients, and ventricular stimulation studies and other clinical variables may be useful in selecting patients with recurrent VT who may benefit or may be endangered by oral flecainide therapy.     

Electrophysiologic and antiarrhythmic actions of bepridil : Comparison with verapamil and ajmaline for atrioventricular reentrant tachycardia

Bepridil (2 mg/kg intravenously) was given to 20 patients with atrioventricular (AV) reentrant tachycardia and its effects were compared with those of verapamil (0.15 mg/kg intravenously) in 8 patients and ajmaline (0.75 mg/kg intravenously) in 12. After baseline electrophysiologic measurements, the drugs were given during sustained AV reentrant tachycardia (8 patients had dual AV nodal pathways and 12 had an accessory AV pathway). Verapamil terminated AV reentrant tachycardia in 7 patients and bepridil terminated it in 6. In 8 of the patients who received ajmaline, AV reentrant tachycardia was terminated and in 6 of this group bepridil did so. Bepridil was more successful in terminating AV reentrant tachycardia in those with dual AV nodal pathways than in those with an accessory AV pathway. Bepridil slowed sinus rate by 10% (p <0.0001), whereas verapamil did not change it significantly. Both verapamil and bepridil administration prolonged AV nodal conduction (39% and 44%, respectively), lengthened AV nodal effective refractory period (18% and 17% respectively) and increased the Wenckebach cycle length of the AV node (24% and 25%, respectively) to a significant degree (p <0.05). Bepridil also lengthened atrial and ventricular effective refractory periods (p <0.01) and QT interval (p <0.0001) in the group as a whole; in those receiving ajmaline and bepridil only atrial refractoriness was significantly altered (p <0.05). After treatment for 3 to 5 days with oral bepridil, 19 patients underwent repeat study. There was further slowing in sinus rate and prolongation in both atrial effective refractory period and QT interval; the AV Wenckebach cycle length had returned toward the control level, but was still significantly increased (p <0.01). In the 17 cases in whom reinducibility of AV reentry tachycardla was tested, 7 had no inducible arrhythmia, 6 had non-sustained AV reentrant tachycardia and 4 had sustained but slower tachycardia. Thus, bepridil has both AV nodal and myocardial electrophysiologic actions which suggest a useful role in the treatment and prophylaxis of supraventricular arrhythmias.