Acute Atrial Fibrillation Termination Research Articles

153-02: Antazoline – new effective antiarrhythmic drug for acute termination of atrial fibrillation. Insights into drug-induced electrocardiographic and haemodynamic effects

153-02: Antazoline – new effective antiarrhythmic drug for acute termination of atrial fibrillation. Insights into drug-induced electrocardiographic and haemodynamic effects

Persistent Atrial Fibrillation FromtheOnset: A Specific Subgroup of Patients With Biatrial Substrate Involvement and Poorer Clinical Outcome.

This study sought to characterize the clinical characteristics, atrial substrate, and prognosis in a subgroup of patients with persistent atrial fibrillation (AF) from the onset (PsAFonset). Patients with AF frequently progress from trigger-driven paroxysmal arrhythmias to substrate-dependent persistent arrhythmias. Patients referred for persistent AF (PsAF) ablation were enrolled from 3 centers. Consecutive patients with PsAFonset (n= 129) were compared with patients with PsAF that progressed from paroxysmal AF (n= 231). In addition, 90 patients (30 patients with PsAFonset and 60 control subjects) were studied with noninvasive mapping to characterize the AF drivers. The degree of fractionation and endocardial voltages were assessed invasively. Patients with PsAFonset were younger (p= 0.047) and more obese (p< 0.001); there were more men (p=0.034), more patients with hypertension (p= 0.044), and these patients had larger left (p< 0.05) and right atria (p< 0.05). Baseline AF cycle length was shorter in the PsAFonset group (p< 0.01); the degree of fractionation was higher (p< 0.001 for both atria), and the endocardial voltage was lower (p< 0.05 for both atria). Patients with PsAFonsethad higher a number of re-entrant driver regions (p< 0.001) and extrapulmonary vein regions that had re-entrant drivers (p< 0.05), whereas control subjects displayed more focal driver regions (p= 0.029). The acute AF termination rate was lower in the PsAFonset group (42% vs. 81%; p< 0.001). During a mean follow-up of 17 ± 11 months fromthelast procedure, patients with PsAFonset had significantly higher AF, atrial tachycardia (AT), and AF/AT recurrence rates (p< 0.01). Patients with PsAFonset represent a distinct subgroup defined by specific demographics, underlying diffuse biatrial substrate disease, and worse clinical outcome. The findings highlight the importance of defining criteria for early detection of atrial substrate disease.

Efficacy and safety of novel epicardial circumferential left atrial ablation with pulmonary vein isolation in sustained atrial fibrillation.

The aim of this study was to examine the efficacy and safety of this novel epicardial circumferential left atrial ablation (CLAA) with pulmonary vein isolation (PVI) in sustained atrial fibrillation (AF). Thirty domestic pigs were divided equally into 3 groups: AF without ablation (AF group), AF with PVI (PVI group), and AF with CLAA and PVI (CLAA+PVI group). AF was induced by rapid atrial pacing. After AF was induced, CLAA and PVI were performed for pigs in CLAA+PVI group, and PVI was performed for pigs in PVI group. AF vulnerability, AF duration, and histology were performed in all groups. All pigs developed sustained AF after 6.27±0.69weeks of rapid atrial pacing. All pigs successfully underwent isolated PVI or CLAA with PVI on the beating heart in PVI group or CLAA+PVI group. Isolated PVI terminated AF in 3 of 20 pigs (15%), and CLAA with PVI terminated AF in 5 of 8 pigs (62.5%, P=0.022). Compared with AF group (10/10), the incidence of sustained AF by burst pacing was significantly decreased in PVI group (3/10, P=0.003) or CLAA+PVI group (0/10, P<0.001). There was no significant difference between PVI group and CLAA+PVI group (P=0.211). AF duration was significantly decreased in CLAA+PVI group (734.70±177.81s, 95% CI 607.51-861.89) compared with PVI group (1217.90±444.10s, 95% CI 900.21-1535.59, P=0.008). Also, AF duration was significantly decreased in PVI group (P=0.003) or CLAA+PVI group (P<0.001) in comparison with AF duration in AF group (average 1800s). Epicardial CLAA could ablate the left atrial roof and posterior wall together safely and reliably. Compared with PVI alone, CLAA with PVI may be able to improve the rate of acute termination of persistent AF. It may be useful in selecting the best ablation approaches for patients with persistent AF.

Selective Complex Fractionated Atrial Electrograms Targeting for Atrial Fibrillation Study (SELECT AF)

Background— This study compared generalized complex fractionated atrial electrograms (CFAE) ablation versus a selective CFAE ablation strategy targeting areas of continuous electric activity. Methods and Results— Subjects with symptomatic, persistent/high-burden paroxysmal atrial fibrillation (AF) were enrolled at 6 centers (n=86) and randomized to 1 of 2 arms. For group I, all CFAE regions with an interval confidence level &gt;7 were ablated followed by pulmonary vein isolation (PVI). For group II, only CFAE sites with continuous electric activity were ablated followed by PVI. For PVI, all 4 PV antra were isolated with confirmed entrance block. Subjects were followed for 1 year with a visit, ECG, and 48-hour Holter every 3 months. Symptoms were confirmed by loop recording. The primary end point was freedom from arrhythmia &gt;30 seconds at 1 year. For both group I and II, CFAE ablation prolonged AF cycle length (25±33 versus 23±33 ms; P =0.78) and resulted in similar rates of AF termination (37% versus 28%; P =0.42). Radiofrequency duration during CFAE ablation was significantly less in group II (23±20 versus 38±20 minutes; P =0.002). At 1-year follow-up, freedom from AF/atrial flutter/atrial tachycardia recurrence was significantly higher in group I versus group II after 1 procedure (50% versus 28%; P =0.03). There were also significantly fewer repeat procedures in group I (13% versus 36%; P =0.021). Conclusions— Continuous electric activity ablation+PVI result in a similar incidence of acute AF termination with significantly less radiofrequency time. However, incidence of repeat procedures and long-term recurrence of AF/atrial flutter/atrial tachycardia are significantly lower using generalized CFAE ablation+PVI. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00926783

Acute Termination of Human Atrial Fibrillation by Identification and Catheter Ablation of Localized Rotors and Sources: First Multicenter Experience of Focal Impulse and Rotor Modulation (FIRM) Ablation

Catheter ablation of atrial fibrillation (AF) currently relies on eliminating triggers, and no reliable method exists to map the arrhythmia itself to identify ablation targets. The aim of this multicenter study was to define the use of Focal Impulse and Rotor Modulation (FIRM) for identifying ablation targets. We prospectively enrolled the first (n = 14, 11 males) consecutive patients undergoing FIRM-guided ablation for persistent (n = 11) and paroxysmal AF at 5 centers. A 64-pole basket catheter was used for panoramic right and left atrial mapping during AF. AF electrograms were analyzed using a novel system to identify sustained rotors (spiral waves), or focal beats (centrifugal activation to surrounding atrium). Ablation was performed first at identified sources. The primary endpoints were acute AF termination or organization (>10% cycle length prolongation). Conventional ablation was performed only after FIRM-guided ablation. Twelve out of 14 cases were mapped. AF sources were demonstrated in all patients (average of 1.9 ± 0.8 per patient). Sources were left atrial in 18 cases, and right atrial in 5 cases, and 21/23 were rotors. FIRM-guided ablation achieved the acute endpoint in all patients, consisting of AF termination in n = 8 (4.9 ± 3.9 minutes at the primary source), and organization in n = 4. Total FIRM time for all patients was 12.3 ± 8.6 minutes. FIRM-guided ablation revealed localized AF rotors/focal sources in patients with paroxysmal, persistent and longstanding persistent AF. Brief targeted FIRM-guided ablation at a priori identified sites terminated or substantially organized AF in all cases prior to any other ablation.

Predicting factors for atrial fibrillation acute termination during catheter ablation procedures: Implications for catheter ablation strategy and long-term outcome

Termination of atrial fibrillation (AF) can be achieved by catheter ablation. It has been used as one of the procedural endpoints for AF ablation. The purpose of this study was to investigate the factors that predict AF termination and the association with long-term outcomes. Eighty-five consecutive AF patients (33 paroxysmal, 52 nonparoxysmal) underwent three-dimensional mapping and catheter ablation. A stepwise ablation approach included circumferential pulmonary vein (PV) isolation and left atrial (LA) linear ablation, followed by LA and right atrial (RA) electrogram-based (complex fractionated atrial electrogram) ablation. Clinical and electrophysiologic characteristics were assessed to evaluate the predictors of acute AF termination. In univariate analysis, a diagnosis of paroxysmal AF, shorter AF history, absence of history of heart failure, smaller LA diameter, longer postablation coronary sinus cycle length, lower LA and RA mean dominant frequencies, lower RA max dominant frequency, and higher LA voltage were related to acute termination of AF during ablation. Multivariate analysis showed that smaller LA diameter and lower preablation mean RA dominant frequency were independent predictors of AF termination. Multivariate analysis also showed that larger LA diameter and the presence of RA non-PV ectopy during the index procedure could predict late recurrence during long-term (13 +/- 8 months) follow-up. LA size and RA non-PV drivers are important for acute termination of AF and for long-term success. Careful selection of patients, extensive RA mapping, and LA ablation may enhance long-term ablation efficacy.

Acute Effects and Long-Term Outcome of Pulmonary Vein Isolation in Combination With Electrogram-Guided Substrate Ablation for Persistent Atrial Fibrillation

Complex fractionated atrial electrographic (CFAE) catheter ablation is a new approach for the treatment of atrial fibrillation (AF). It is unclear if acute results of this approach correspond to long-term outcome. The purpose of this study was to prospectively assess acute and long-term successes of an ablation approach combining pulmonary vein isolation (PVI) and ablation of CFAE areas for treatment of persistent AF. PVI and ablation of CFAE areas were performed in 35 patients with persistent AF (30 men, 57+/-9 years of age). At the end of the ablation procedure AF had terminated in 23 of 35 patients (66%) by conversion to sinus rhythm (8 of 23 patients, 35%) or organization to atrial tachycardia (15 of 23 patients, 65%). AF persisted in 12 of 35 patients (34%). At the end of the follow-up period (19+/-12 months), sinus rhythm was present in 26 of 35 patients (74%), including 9 patients with a repeat procedure. This group of 26 patients consisted of 7 of 8 patients (88%) with acute sinus rhythm after the first ablation, 11 of 15 patients (73%) with organization, and 8 of 12 patients (66%) with ongoing AF (p=0.32). In conclusion, a combined approach of PVI and CFAE ablation in persistent AF leads to acute AF termination in 66% and long-term maintenance of sinus rhythm in 74% of cases. However, long-term outcome was not predictable by acute results of the ablation procedure.

Abstract 2441: A Controlled Randomized Trial of Biatrial Ablation for Curing Long-lasting Permanent Atrial Fibrillation (The Decomplex Trial)

Background: patients with long-lasting permanent atrial fibrillation (AF) are often destined to remain in AF life-long. In this cohort outcomes of ablation techniques are disappointing, with 20 –74% success rate and 30 –50% repeat procedure. The adjunctive clinical benefit of targeting multiple right and left atrial (LA) sites beyond the pulmonary vein (PV)-LA junction with the aim of achieving acute AF termination has not been prospectively evaluated in a randomized study. Methods and results: 60 patients with permanent atrial fibrillation of more than 1 year duration, with early recurrence after electrical cardioversion and medical therapy with one or more antiarrhythmic agents were enrolled (mean age 59±10, mean AF duration 60 months, mean LA dimension 44±7 mm, left ventricular EF &gt;40% in all) and randomized to standard circumferential PV ablation (CPVA, control group, N=30) or an extended CPVA schema targeting also inferior LA, atrial septum, LA appendage, coronary sinus and right atrium (test group, N=30). In the test group the procedural endpoint was sinus rhythm (SR) restoration by radiofrequency energy; at each step average cycle length was measured and ablation was stopped if patient gained SR. In the control group the standard CPVA technique was applied. All patient transmitted daily transtelephonic ECG strips whereas at 3, 6 and 12 months an echocardiogram and a 48 hour Holter was obtained. Antiarrhythmic drug therapy was continued for 3 months after ablation in both group (blanking period in which patients were allowed to undergo electrical cardioversion). AF terminated in 5% and 55% of control and test subjects; mean procedure duration was 66 and 88 minutes in the 2 groups; No significant complications occurred in both groups. After a mean follow-up of 4 months, 67% of control patients were sinus as compared with 83% in the test group (p&lt;0.05). 2 and 2 patient undergoing a repeat procedure for recurrent AF for AF (N=2) and AT (N=2). Acute AF termination was the strongest endpoint of SR maitainance (p&lt;0.01) Conclusion: Preliminary data show that a modified CPVA ablation strategy in patients with permanent AF is associated with acute AF termination in 55% of patients and achieves medium term restoration and maintenance of sinus rhythm in 83% of patients.

Abstract 2445: Comparison of Atrial Fibrillation Ablation Strategies for Paroxysmal patients presenting to the Electrophysiology Laboratory In atrial fibrillation

BACKGROUND : Whether different ablation strategies affect paroxysmal atrial fibrillation (AF) termination mode and long term cure is unclear. We compared the effect of different ablation strategies on the AF termination and long term success in patients with parox-AF presenting to the electrophysiology laboratory in AF. METHODS : One hundred and three (103) consecutive patients with parox-AF scheduled for AF ablation presenting in the lab in AF were selected for this study. The patients were randomized to PVAI only (35 pts) versus bi-atrial ablation of the complex fractionated atrial electrograms (CFAE defragmentation) including the coronary sinus (34 pts) versus CFAE followed by PVAI (34 pts) Modes of AF termination were: conversion to SR, organization into AT or persistence of AF requiring cardioversion following ablation. RESULTS are summarized below: There was no significant difference between the groups in term of sex, age, AF duration, LA size and EF. Follow up after a single procedure with AAD is summarized below CONCLUSION : Defragmentation alone had the smallest impact on both acute AF termination and one year follow-up cure rate. No difference in terms of acute and chronic success was seen between PVAI alone and PVAI asoociated with defragmentation. This suggests that PV isolation is critical to cure AF in paroxysmal AF and that adjunctive strategies have minimal impact on cure rate and should not be considered in all patients.

Catheter Ablation of Long‐Lasting Persistent Atrial Fibrillation: Clinical Outcome and Mechanisms of Subsequent Arrhythmias

Catheter ablation of atrial fibrillation (AF) is challenging in patients with long-standing persistent AF. The clinical outcome and subsequent arrhythmia recurrence after using an ablation method targeting multiple left atrial sites with the aim of achieving acute AF termination has not been characterized. Sixty patients (mean age: 53 +/- 9 years) with persistent AF (mean duration: 17 +/- 27 months) were prospectively followed after catheter ablation. Catheter ablation targeting the following sites was performed in a random sequence: (i) electrical isolation of all pulmonary veins (PV); (ii) disconnection of other thoracic veins; (iii) atrial ablation at sites possessing complex electrical activity, activation gradients, or short cycle lengths. Finally, linear ablation of the LA roof and mitral isthmus was performed if sinus rhythm was not restored following energy delivery to the above sites. At 1, 3, 6, and 12 months after ablation, patients underwent clinical review and 24-hour ambulatory ECG monitoring to identify asymptomatic arrhythmia. Repeat mapping and catheter ablation was performed in any patient experiencing recurrent atrial tachycardia (AT). Clinical success was defined as the absence of any sustained atrial arrhythmia. AF terminated during ablation in 52 patients (87%). The fluoroscopy and procedural durations were 84 +/- 30 minutes and 264 +/- 77 minutes, respectively. Three months after ablation, sustained ATs were documented in 24 patients (associated with AF in 2). Mapping in 23 patients showed a single AT in 7 while multiple ATs were observed in 16. Macroreentry was confirmed to be due to gaps in the ablation lines, while focal ATs originated from discrete sites or isthmuses near the left atrial appendage, coronary sinus, pulmonary veins, or fossa ovalis; these sites were similar to those at which the greatest impact was observed on the fibrillatory process during the initial ablation procedure. After repeat ablation, at 11 +/- 6 months of follow-up, 57 patients (95%) were in sinus rhythm and 3 developed recurrent AF or AT. All patients in sinus rhythm demonstrated improved exercise capacity and all but 2 had evidence of atrial transport as assessed by Doppler echocardiography (mitral A wave velocity 34 +/- 17 cm/sec) by 6 months. Catheter ablation of long-lasting persistent AF associated with acute AF termination achieves medium to long-term restoration and maintenance of sinus rhythm in 95% of patients. Arrhythmia recurrence in the majority of patients is AT.

Effect of electrode position on the outcome of cardioversion.

Acute termination of atrial fibrillation is the starting point of any therapy aimed at preventing atrial fibrillation and improves cardiac output in patients with hemodynamic compromise due to the arrhythmia. External electrical cardioversion is a simple procedure to terminate persistent atrial fibrillation in the majority of cases. Initially, Lown et al. used an anterior-lateral position of electrodes to apply a cardioversion shock. Recent pathophysiological studies have shown that atrial fibrillation is maintained by functional re-entry circuits anchored in the left atrium. As the left atrium is located posteriorly in the thorax, an anterior-posterior electrode position may be more efficient for external cardioversion of atrial fibrillation than the commonly used anterior-lateral electrode position. Several recent studies have confirmed that an anterior-posterior electrode position is superior to an anterior-lateral electrode position for external cardioversion of atrial fibrillation. There are no indications that an anterior-posterior electrode position is less safe than an anterior-lateral electrode position. We therefore suggest that an anterior-posterior electrode position should initially be used for external cardioversion of atrial fibrillation.

Clinical and electrophysiologic effects of calcium channel blockers in patients receiving ibutilide

Background Ibutilide is indicated for the acute termination of atrial fibrillation and atrial flutter. Recent work concludes that ibutilide activates a late inward sodium current that is blocked by nifedipine. Because calcium channel blockers are commonly used in patients with atrial fibrillation, it is important to exclude an antagonistic effect on ibutilide in the clinical setting. Methods We performed a retrospective electrocardiographic (ECG) review of patients enrolled in 3 clinical trials of ibutilide (2 atrial fibrillation conversion protocols and 1 ventricular tachycardia suppression protocol) to determine clinical efficacy and ECG effects of ibutilide in patients receiving and not receiving calcium channel blockers. Calcium channel blockers were administered as clinically indicated. A meta-analysis of the effects of calcium channel blockers on the conversion efficacy of atrial fibrillation and atrial flutter by ibutilide was also performed for studies in the literature. Results One hundred thirty patients were included in the ECG analysis (106 from atrial fibrillation protocols and 24 from the ventricular tachycardia protocol). Sixty-eight of the 130 patients were taking calcium channel blockers at the time of ibutilide administration. There were no differences in the QT or QTc intervals, conversion rate for atrial fibrillation or atrial flutter, or suppression of ventricular tachycardia between patients taking and not taking calcium channel blockers. In the meta-analysis of 4 studies, there was no difference in the conversion rates between patients taking (52%, n = 221) and not taking (45%, n = 402) calcium channel blockers (P =.09). Conclusions In the clinical setting, the concomitant use of calcium channel blockers does not alter the ECG effects or efficacy of ibutilide for the treatment of atrial or ventricular arrhythmias. (Am Heart J 2002;143:176-80.)

Transvenous atrial defibrillation--techniques and clinical applications.

Atrial fibrillation (AF) is the most common arrhythmia requiring treatment. The most desirable therapy may be restoration and maintenance of sinus rhythm. Limitations of the current methods for cardioversion of AF have prompted the development of transvenous atrial defibrillation (TADF) as an alternative and more effective technique for converting AF. Recent advances in the technique of TADF, particularly in the design and configuration of the electrodes, and the use of an optimal biphasic shock waveform have dramatically improved the efficacy of TADF for the termination of all types of AF. The reduction in voltage and energy requirements for cardioversion by TADF may allow the procedure to be performed with little or no sedation and the risk of general anesthesia may be avoided. Both experimental and clinical studies have demonstrated the feasibility, safety, and efficacy of using TADF as a new temporary or "permanent" mode of electrical therapy for AF. It has several potential applications, from acute termination of AF in the electrophysiology laboratory and in patients who have failed to respond to external cardioversion, to its use as an implantable device for treating recurrent AF. This article reviews the current technique and clinical applications of TADF for treatment of AF.

Efficacy and safety of intravenously administered dofetilide in acute termination of atrial fibrillation and flutter: A multicenter, randomized, double-blind, placebo-controlled trial

Background This study was designed to assess the efficacy and safety of intravenous dofetilide in acute termination of atrial fibrillation (AF) and flutter (AFL). Dofetilide, an investigational class III antiarrhythmic agent, selectively inhibits the rapid component of the delayed rectifier potassium current, thus prolonging the effective refractory period and duration of the action potential. Dofetilide can be administered intravenously and has a rapid onset of electrophysiologic action. Methods and Results Ninety-six patients with AF (n = 79) or AFL (n = 17) with a median arrhythmia duration of 62 days (range 1 to 180) were randomized to placebo (n = 30) or 8 μg/kg IV dofetilide (n = 66) over 30 minutes. Conversion was defined as termination of the atrial arrhythmia within 3 hours from the start of infusion. The conversion rate was 30.3% after dofetilide and 3.3% after placebo ( P < .006). Conversion rate was higher in AFL than in AF: 64% versus 24% ( P = .012). In nonconverters, there was no statistically significant difference between the change in heart rate among the dofetilide-treated compared with the placebo-treated patients ( P = .42). Torsade de pointes ventricular tachycardia developed in 2 patients (3%). In both patients, drug infusion was discontinued before the event because of prolongation of the QT interval. Conclusions Intravenous dofetilide is effective in acute termination of AF and AFL of medium duration, with a particularly high efficacy rate in AFL. A small but serious risk of proarrhythmia must be anticipated. (Am Heart J 1999;137:1062-9.)

Conversion efficacy and safety of repeated doses of ibutilide in patients with atrial flutter and atrial fibrillation

Background A study was conducted to determine the efficacy and safety of ibutilide fumarate versus placebo in the acute termination of atrial flutter and fibrillation. Methods and Results Two hundred sixty-two patients aged 28 to 88 years with atrial flutter or fibrillation duration of 3 hours to 90 days were randomly assigned in a 5:1 ratio (ibutilide:placebo) to receive two 10-minute infusions, 10 minutes apart, of ibutilide (1 mg) or placebo. Patients were hospitalized and monitored by telemetry for 24 hours, with follow-up 72 hours later. Seventy-three (34.9%) of 209 evaluable ibutilide recipients had termination of atrial flutter or fibrillation within 1.5 hours compared with 0 (0%) of 41 placebo recipients. Those with atrial flutter had a higher success rate. At hour 24, 86.3% remained in normal or alternative sinus rhythm. Of the patients who received ibutilide, 2.3% experienced drug-related sustained polymorphic or monomorphic ventricular tachycardia and recovered after intervention. Additionally, 7.3% experienced nonsustained polymorphic or monomorphic ventricular tachycardia. Other frequent medical events in ibutilide recipients were generally also noted in the placebo group. Conclusions Ibutilide is effective and safe for acute termination of atrial fibrillation or atrial flutter. (Am Heart J 1998;136:632-42.)

Efficacy and safety of dofetilide, a new class III antiarrhythmic agent, in acute termination of atrial fibrillation or flutter after coronary artery bypass surgery

Ninety-eight patients, who developed atrial fibrillation/flutter after coronary artery bypass grafting within 1–6 days after surgery, were included into a double-blind, placebo-controlled, randomized trial to assess the efficacy and safety of dofetilide. Patients were randomly allocated to dofetilide 4 μg/kg i.v. ( n=33), dofetilide 8 μg/kg i.v. ( n=32) or placebo ( n=33) given intravenously over 15 min at a constant infusion rate. Responders were defined as patients who converted to sinus rhythm at any time during the initial 3 h after the start of the infusion. The conversion rates were 24% (8/33) on placebo, 36% (12/33) on dofetilide 4 μg/kg, and 44% (14/32) on dofetilide 8 μg/kg. The P-values (two-tailed) were 0.27 for dofetilide 4 μg/kg vs. placebo, 0.11 for dofetilide 8 μg/kg vs. placebo, and 0.10 for dose-response relationship. Short episodes of aberrant ventricular conduction and ventricular tachycardia were seen separately in three subjects after dofetilide 8 μg/kg. No episodes of torsades de pointes were noted. No negative inotropic effect was noted. In conclusion, dofetilide was well tolerated, but the effects on atrial fibrillation/flutter did not attain statistical significance, possibly due to the high placebo conversion rate.

Electrophysiology and Pharmacology of Ibutilide

Ibutilide fumarate is a new class III intravenous antiarrhythmic agent indicated for the acute termination of atrial fibrillation and flutter. Ibutilide prolongs repolarization in the atria and ventricle by enhancing the inward depolarizing, slow sodium current, a unique mechanism of action for a class III agent. Atrial refractoriness is prolonged with no evidence of reverse use dependence. Ibutilide may also block the delayed rectifier current, but this does not appear to be clinically relevant. In vitro and at high doses, ibutilide may shorten action potential duration, although this effect has not been noted clinically. Ibutilide can cause torsades de pointes in a rabbit model of proarrhythmia dependent on the formation of early afterdepolarizations. However, it causes less proarrhythmia than sotalol, dofetilide, or sematilide in this model. The pharmacokinetics of ibutilide are linear, its extravascular distribution is rapid and extensive, while its systemic clearance is high (elimination half-life 3–6 hours). Eight metabolites are formed by the liver, only one of which is slightly active. QT prolongation is dose dependent, is maximal at the end of the infusion, and returns to baseline within 2–4 hours following infusion. The pharmacokinetics and electrophysiologic characteristics of ibutilide are complementary in that any risk of proarrhythmia is made manageable by a short half-life. Almost all reported cases of drug-induced torsades de pointes ventricular tachycardia associated with ibutilide have occurred within 40 minutes of starting the infusion. Nevertheless, clinicians using ibutilide can further reduce the chance of torsades de pointes by being very familiar with the criteria for patient selection, and by being prepared to treat it should it occur. When used with full knowledge of its potential risks, ibutilide is a very effective intravenous agent for the acute termination of atrial fibrillation and flutter and is likely to become a significant treatment option for these arrhythmias. (Am J Cardiol 1996;78 (suppl 8A):12–16)

Intravenous flecainide acetate for supraventricular tachycardias

Flecainide acetate, 2 mg/kg body weight, given intravenously at 10 mg/min was administered to 128 (74 male and 54 female) patients whose ages ranged from 11 to 86 years (mean 44). All patients had supraventricular tachycardias (SVT) that developed spontaneously or were induced during electrophysiologic study. There were 26 patients with atrial flutter, 34 with atrial fibrillation, 7 with ectopic atrial tachycardia, 41 with atrioventricular (AV) reentrant tachycardia and 40 with AV nodal reentrant tachycardia. Twenty patients had more than 1 variety of SVT. Flecainide was administered during SVT to 9 patients with atrial flutter, 11 with atrial fibrillation, 7 with atrial tachycardia, 38 with AV reentrant tachycardia and 34 with AV nodal reentrant tachycardia. In the remaining 31 patients with inducible SVT at electrophysiologic study, flecainide was administered during sinus rhythm. Reinitiation of SVT was attempted in these patients after completion of flecainide administration. Flecainide successfully terminated atrial flutter in 2 patients (22%), atrial fibrillation in 9 (82%), atrial tachycardia in 5 (71%), AV reentrant tachycardia in 32 (84%) and AV nodal reentrant tachycardia in 30 (88%). Reinitiation of SVT was possible in 10 of 26 patients with atrial flutter (38%), 5 of 34 with atrial fibrillation (15%), 3 of 7 with atrial tachycardia (43%), 14 of 41 with AV reentrant tachycardia (34%) and 11 of 40 with AV nodal reentrant tachycardia (27%). In patients with AV reentrant tachycardia and AV nodal reentrant tachycardia, reinitiation occurred when retrograde anomalous pathway refractoriness was not significantly prolonged by intravenous flecainide. Intravenous flecainide is successful in the acute termination of atrial fibrillation, atrial tachycardia, AV reentrant tachycardia and AV nodal reentrant tachycardia but appears to be of limited value for atrial flutter. Reinitiation of SVT may occur despite successful termination.