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Background BrS is diagnosed in patients with ST-segment elevation with type1 morphology ≥2mm in one or more leads among the right precordial leads V1 and/or V2 positioned in the second, third or fourth intercostal space, occurring either spontaneously or after provocative drug test with intravenous administration of sodium channel blockers (ie. ajmaline, flecainide, procainamide or pilsicainide). The specific protocol for Ajmaline provocation testing for diagnosis of BrS has been debated between ICC services worldwide. Concerns regarding safety and false positive rates are perceived to be associated with a more rapid infusion protocol. This retrospective observational cohort study describes the safety and positivity rates for patients undergoing ajmaline provocation challenge by both protocols over nine years. Method Consecutive adults undergoing ajmaline challenge test from Mach 2011 to Feb 2020 were retrospectively collected. Data on patient demographics, indication for testing, genetic information, adverse events and positivity rates were compared by test protocol used. Slow protocol was defined as total dose of 1mg/kg ajmaline capped at 100mg given at rate of 10mg/min over 10 minutes. Rapid protocol was defined as 1mg/kg ajmaline capped at 100mg given over 5 minutes. Results A total of 350 ajmaline challenges were included (275 (73%) slow vs. 75 (27%) rapid protocol) [Mean age 40±15 years; 53% male]. Indication for conducting the test was a) Family history of Brugada syndrome 164 (43%) b) Family history of SADS/SUD 103 (28%), c) OOHCA 22 (6%) d) abnormal ECG 39 (11%) and e) syncope 22 (6%). Among the positive test group, average time for test positivity is 5.92 minutes and average dose was 55mgs (p Conclusion In NI ICC service to date, we have performed 350 Ajmaline test over the last nine years. Our positivity rate was 21% (75/350). We did not identify any significant evidence of ventricular dysrhythmia (0) or QRS broadening (2) that resulting in early termination of the protocol. Abnormal ECG with absence of symptoms yields low. Therefore we will continue fast protocol in our service for efficiency in our unit. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Belfast Health and Social Care TrustCormac Felowship

Background/Introduction Brugada syndrome (BrS) is a hereditary channelopathy with an increased risk of sudden cardiac death. Most BrS patients manifest non type 1 Brugada pattern electrocardiography (ECG). Sodium channel blockade is a well-established diagnostic tool for Brugada syndrome. However, intravenous sodium channel blockade is not readily available in all parts of the world. In addition, severe ventricular arrhythmias during drug challenge have an estimated prevalence of 1%. Determining the predictors of a positive test would improve our understanding and facilitate appropriate use of these tests. Purpose We aimed to identify ECG predictors of Brugada type response during flecainide challenge and provide an independent assessment of current published ECG criteria predictive of a positive flecainide challenge. Methods We analysed the clinical and electrocardiographic data of 526 consecutive individuals referred from a national pre-participation exercise screening program who underwent flecainide challenge for an ECG suspicious of Brugada pattern. ECG recordings included both conventional and high precordial leads (1 and 2 space up ECGs in V1 and V2 – 1V1, 1V2, 2V1, 2V2). Twelve-lead ECGs were evaluated for the width of the β angle, β score, baseline J wave elevation, width of QRS, absence of isoelectric segment in lead II, ST/ QT ratio, presence of S wave in Leads II, III and V5 as well as the presence of R wave in aVR. Results Flecainide challenge was positive in 121 (23%) of the 526 cases. Baseline QRS duration was greater in the conventional lead placement [V1 (102.4±20.0 ms vs 97.6±14.0 ms, p=0.003), V2 (111.1±33.5 ms vs 100.9±13.1 ms, p=0.001)] as well as 1 space up [1V1 (108.9±21.0 ms vs 100.6±18.2 ms, p Conclusion In this population, a wider QRS duration, shortened ST segment in lead II and ST/QT ratio were predictors of a positive response to flecainide challenge when BrS was suspected on a baseline ECG. Prior published ECG parameters such as β angle, β score, baseline J wave elevation, presence of S wave in Leads II, III and V5 as well as the presence of R wave in aVR did not perform as well in predicting for a positive response to flecainide challenge in our population. Funding Acknowledgement Type of funding sources: None. Baseline CharacteristicsECG Findings

Background Bradyarrhythmia is a known complication to direct current cardioversion (DC-cardioversion) in patients with atrial fibrillation (AF). However, whether concomitant treatment with anti-arrhythmic drugs (AADs) is associated with an increased risk of bradyarrhythmia in relation to the procedure is unknown. Purpose To investigate the short-term risk of bradyarrhythmia associated with AAD treatment in AF patients undergoing DC-cardioversion. Methods Using Danish nationwide registers, all AF patients treated with either an AAD (amiodarone, sotalol, dronedarone, flecainide, or propafenone) or rate-lowering drugs (beta-blocker, non- dihydropyridine calcium-antagonist, or digoxin) were identified at their first DC-cardioversion between 2001 and 2016. Patients were excluded if they were under 18 or above 100 years of age or had a pacemaker or implantable cardioverter defibrillator. The event of interest was a composite outcome of either a diagnosis of bradyarrhythmia (sinoatrial arrest, atrioventricular block, or unspecified bradycardia) or a procedure of pacemaker implantation. Patients were followed from the date of DC-cardioversion until event of interest, 90 days after the procedure, or at study end. Absolute risks of bradyarrhythmic events were estimated using the Aalen-Johansen estimator taking the competing risk of death into account. Hazard ratios (HR) with 95% confidence intervals (95% CI) of bradyarrhythmic events were computed using multivariable Cox models adjusted for age, sex, calendar year, as well as relevant comorbidity and concomitant medication. Results A total of 22,344 patients were included in the study with 3,224 (14%) individuals treated with an AAD. The median age was 67 years (interquartile range [IQR] 59–73) and most were males (69%). Patients treated with AADs were younger and had more ischemic heart disease, heart failure, and valvular disease. During follow-up we identified 601 cases of bradyarrhythmia. We found an absolute risk of bradyarrhythmic events at 90 days after cardioversion of 3.7% (95% CI 3.1–4.4) for patients treated with an AAD and 2.5% (95% CI 2.3–2.7) for patients treated with rate-lowering drugs (P Conclusion Using a large nationwide study population of patients with AF undergoing DC-cardioversion, concomitant treatment with AADs was associated with an increased risk of bradyarrhythmic events. Moreover, the absolute risks of bradyarrhythmic events after DC-cardioversion were higher than what has previously been reported. These data provide valuable insights aiding physicians in clinical decision making as well as informing patients prior to the procedure. Figure 1. Absolute risk and adjusted hazard ratio (HR) of bradyarrythmia. AAD: Anti-arrhythmic drugs. CI: Confidence Interval. Funding Acknowledgement Type of funding source: None

Background/Introduction The negative inotropic effect of certain antiarrhythmic drugs limits their use for acute cardioversion of new-onset paroxysmal atrial fibrillation (AF). Purpose In an intact porcine model of AF, we examined the effects of pulmonary and intravenous (IV) administration of flecainide on left ventricular (LV) contractility, i.e., LV dP/dt max, at doses that are effective in converting AF to sinus rhythm. The magnitude of the decrease in LV dP/dt max and time that it remained below baseline, measured by the area under the curve (AUC), is referred to as negative inotropic burden. Methods Flecainide was delivered via intratracheal administration at 1.5 mg/kg bolus and compared to IV infusion at 1.0 mg/kg over 2 min (lower-dose, rapid) and 2.0 mg/kg over 10 min (ESC guideline) in 11 closed-chest, anesthetized Yorkshire pigs. These doses of flecainide have been shown effective in converting AF to sinus rhythm. Catheters were fluoroscopically positioned in the right atrium for pacing at 140 beats/min and in the LV to measure QRS complex duration and contractility (LV dP/dt). Intratracheal flecainide was delivered via a catheter positioned at the bifurcation of the main bronchi. Results The peak plasma levels (Cmax values) were similar but the AUC of plasma concentrations over time was greater for the higher-dose, slow IV infusion of flecainide than for either intratracheal instillation (by 32%) or lower-dose, rapid IV infusion (by 88%). Based on AUCs of LV dP/dt max (figure, left panel), the negative inotropic burden is 3.1- to 3.8-fold greater for the higher IV (1006% • min) than for the lower IV (323%·min) or the intratracheal doses (263% • min). There was a corresponding inverse increase in the AUC of QRS complex prolongation. The decrease in LV dP/dt max (Δ%) was correlated with the prolongation of the QRS complex (Δms) (y = −1.4337x + 3.6613, r2=0.69, p Conclusion Rapid delivery of pulmonary or IV flecainide reduces the dose of drug required to achieve Cmax levels associated with conversion of AF. The attendant decrease across time in exposure of the ventricles to flecainide reduces QRS complex prolongation and the accompanying negative inotropic burden. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): InCarda Therapeutics, Inc.

Background/Introduction Atrial fibrillation (AF) is the most common cardiac arrhythmia with a considerable impact on patients' quality of life (QoL). Flecainide acetate, is a class Ic antiarrhythmic agent, recommended as first line treatment in AF patients without underlying structural heart disease. Purpose This prospective, multicenter, nationwide, observational study aimed to evaluate the effect of oral treatment with controlled-release (CR) flecainide administered once daily on AF patients' QoL and treatment compliance during a 12-week period. Methods A total of 70 cardiologists participated in the study enrolling consecutive adult patients with paroxysmal or persistent AF, treated with flecainide CR in the context of a rhythm control strategy. The effect on QoL was assessed by the Canadian Cardiovascular Society Severity of Atrial Fibrillation scale (CCS-SAF) measured at baseline and at 12 weeks of treatment. Results In total, 679 patients (53.2% females, mean age 65.9±11.7 years, 86.9% paroxysmal AF) were included in the analysis. At least one prior antiarrhythmic treatment was documented in 43.8% of patients. The initial daily dose of flecainide CR was 100mg in 71.7% of the patients, with a titration to 200mg by the end of study achieved in 67%. In 93.6% of patients an excellent compliance score (100%) to treatment was recorded at the end of the study period. Treatment with flecainide CR resulted in a significant improvement in QoL as presented in the table. Table 1 CCS-SAF score Baseline (Week 0) End of study visit (Week 12) N=679 N=634 Class 1 (minimal effect on QoL) 343 (50.5) 464 (73.2) Class 2 (minor effect on QoL) 253 (37.2) 140 (22.1) Class 3 (moderate effect on QoL) 73 (10.8) 28 (4.4) Class 4 (severely impairs QoL) 10 (1.5) 2 (0.3) CCS-SAF continuous score Mean ± SD 1.64±0.73 1.32±0.57 Change from baseline‡ Mean (95% CI) −0.325 (−0.379, −0.271) p-value Conclusions This prospective, multicenter, observational study demonstrated that treatment of AF patients with flecainide CR, was associated with a significant improvement of QoL and excellent compliance to treatment. Acknowledgement/Funding Sponsored by WinMedica S.A.

Aims Published reports regarding inferolateral early repolarization (ER) syndrome (ERS) before 2013 possibly included patients with Brugada-pattern electrocardiogram (BrP-ECG) recorded only in the high intercostal spaces (HICS). We investigated the significance of HICS ECG recording in ERS patients. Methods and results Fifty-six patients showing inferolateral ER in the standard ECG and spontaneous ventricular fibrillation (VF) not linked to structural heart disease underwent drug provocation tests by sodium channel blockade with right precordial ECG (V1–V3) recording in the 2nd–4th intercostal spaces. The prevalence and long-term outcome of ERS patients with and without BrP-ECG in HICS were investigated. After 18 patients showing type 1 BrP-ECG in the standard ECG were excluded, 38 patients (34 males, mean age; 40.4 ± 13.6 years) were classified into four groups [group A ( n = 6;16%):patients with ER and type 1 BrP-ECG only in HICS, group B ( n = 5;13%):ERS with non-type 1 BrP-ECG only in HICS, group C ( n = 8;21%):ERS with non-type 1 BrP-ECG in the standard ECG, and group D ( n = 19;50%):ERS only, spontaneously or after drug provocation test]. During follow-up of 110.0 ± 55.4 months, the rate of VF recurrence including electrical storm was significantly higher in groups A (4/6:67%), B (4/5:80%), and C (4/8:50%) compared with D (2/19:11%) (A, B, and C vs. D, P < 0.05). Conclusions Approximately 30% of the patients with ERS who had been diagnosed with the previous criteria showed BrP-ECG only in HICS. Ventricular fibrillation mostly recurred in patients showing BrP-ECG in any precordial lead including HICS; these comprised 50% of the ERS cohort.

Aims This study compared the efficacy and safety of intravenous flecainide and ibutilide for immediate cardioversion of atrial fibrillation (AF). Methods and results We conducted a prospective, randomised trial, including 207 patients with AF of recent onset (⩽48 h). Flecainide was given over 20 min at a dose of 2 mg/kg body weight (maximum 200 mg), ibutilide was infused at a dose of 1 mg (or 0.01 mg/kg if less than 60 kg) over 10 min, followed by a 10 min observation period and an identical second dose if AF did not convert to sinus rhythm (SR). Treatment was considered successful if SR occurred within 90 min of starting medication. The conversion rates were 56.4% in patients given flecainide and 50.0% in patients given ibutilide \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((P=0.34)\) \end{document}. Multivariate analysis revealed that a lower age for women independently increased the probability of conversion. None of the other variables, including left atrial size, left ventricular systolic function, presence of left ventricular hypertrophy, plasma levels of potassium or magnesium at baseline, or concomitant use of digoxin, beta-blocker, diltiazem or verapamil were predictors of conversion. The frequency of adverse events was comparable in the two treatment groups. Conclusions There was no significant difference in the cardioversion efficacy or in the risk of adverse events between flecainide and ibutilide in patients with AF of recent onset. In patients without contraindications to both medications, the physician's choice has to be governed by other factors.

Aims To evaluate the impact, on atrial fibrillation (AF) recurrences, of verapamil addition to a class IC or III antiarrhythmic drug in patients, with persistent AF, who underwent an electrical cardioversion (EC). Methods and results Three hundred sixty-three patients were randomized to receive four different pre-treatment protocols: oral amiodarone (group A), oral flecainide (group F), oral amiodarone plus oral verapamil (group A+V), oral flecainide plus oral verapamil (group F+V). Patients who showed an AF recurrence within 3 months were assigned to the alternative group and underwent a second EC after 48h. During 3 months of follow-up, 89 patients (27.5%) had an AF recurrence. By univariate analysis, verapamil reduced AF recurrences if added to amiodarone or flecainide (from 35% to 20%, P =0.004). Applying Cox proportional hazards regression model, only the younger age, the shorter duration of AF, and the use of verapamil were predictor of maintenance of sinus rhythm after cardioversion. In patients with primary AF recurrence, verapamil addition to group A and F patients, significantly decreased secondary AF recurrence rate as compared to group A+V and F+V patients who stopped the verapamil therapy (68% vs 88%, P =0.03). Conclusions The addition of verapamil to class IC or III antiarrhythmic drug significantly reduced the AF recurrences, that were more frequent in older patients and in patients with longer lasting AF; moreover, verapamil was effective in reducing the secondary AF recurrences, too.

AIMS Catheter ablation of the inferior vena cava-tricuspid annulus isthmus and continuation of antiarrhythmic drug therapy have been shown to be an effective hybrid therapy for atrial flutter which results from antiarrhythmic drug treatment of atrial fibrillation. The aim of this study was to determine the risk factors for recurrence of atrial fibrillation in patients undergoing hybrid therapy for antiarrhythmic drug-induced atrial flutter. METHODS AND RESULTS 90 patients with paroxysmal (n=46) or persistent atrial fibrillation (n=44) developed atrial flutter due to the administration of amiodarone (n=48), flecainide (n=22), propafenone (n=14) or sotalol (n=6). Recurrence of atrial fibrillation after ablation was assessed during follow-up on continued antiarrhythmic drug therapy and during long-term follow-up, irrespective of the initial antiarrhythmic medication. During the follow-up on continued antiarrhythmic drug therapy (16+/-13 months), recurrence of atrial fibrillation was documented in 24 of 90 patients (27%). The presence of accompanying pre-ablation episodes of atrial fibrillation on antiarrhythmic treatment (Odds ratio 7.1, 95% confidence interval 2.3 to 25, p=0.001) and decreased left ventricular ejection fraction (Odds ratio 3.7, 95% confidence interval 1.01 to 12.5, p=0.048) were significant and independent predictors of post-ablation atrial fibrillation. Antiarrhythmic medication was discontinued during long-term follow-up due to adverse drug effects (amiodarone, n=12; flecainide, n=1) in 13 patients (14%). During the long-term follow-up, irrespective of the initial antiarrhythmic medication (21+/-15 months), stable sinus rhythm was maintained in 60 of 90 patients (67%). CONCLUSION Hybrid therapy can be considered as the first line therapy for patients with antiarrhythmic drug-induced atrial flutter but patients should be carefully evaluated for accompanying pre-ablation episodes of atrial fibrillation and possible adverse drug effects before initiation of hybrid therapy.

Aims Permanent atrial fibrillation develops in many patients after ablation and pacing therapy. We compared a strategy that initially allowed patients to remain in atrial fibrillation with a strategy that initially attempted to restore and maintain sinus rhythm. Methods and Results In this multicentre randomized controlled trial, 68 patients affected by severely symptomatic paroxysmal atrial fibrillation were assigned, after successful atrioventricular junction ablation and pacing treatment, to antiarrhythmic drug therapy with amiodarone, propafenone, flecainide or sotalol and were compared with 69 patients assigned, after successful AV junction ablation and pacing treatment, to no antiarrhythmic drug therapy. The patients were followed-up for 12 to 24 months (mean 16±4). The drug arm patients had a 57% reduction in the risk of developing permanent atrial fibrillation (21% vs 37%, P =0·02). Evaluation after 12 months revealed similar quality of life scores and echocardiographic parameters in the two groups, but the drug arm patients had more episodes of heart failure and hospitalizations ( P =0·05). The outcome was similar between the 40 patients who developed permanent atrial fibrillation and the 97 who did not. Conclusion Conventional antiarrhythmic therapy reduces the risk of development of permanent atrial fibrillation after ablation and pacing therapy. The present data do not support the concept that the development of permanent atrial fibrillation is related to an adverse outcome when a perfect control of heart rate is obtained by ablation and pacing. Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved

The incidence and severity of tachyarrhythmias, both supraventricular tachycardia and ventricular tachycardia may increase during pregnancy. Although the reasons for this observation are unclear, some explanations have been proposed: increased awareness, haemodynamic, hormonal, autonomic, and emotional changes related to pregnancy, which may include: increases in plasma catecholamine concentrations and adrenergic receptor sensitivity, atrial stretch and increased end-diastolic volumes due to intravascular volume expansion. Treatment of tachyarrhythmias during pregnancy and lactation is complicated by concerns regarding safety and tolerability for the fetus or infant. All commonly used antiarrhythmic drugs cross the placenta and are excreted in breast milk. Their plasma concentration in the fetus and infant are partly determined by differences in pH between their serum and that of the mother (most antiarrhythmic drugs are alkalic compounds and accumulate in acidic environments). Teratogenic risk is greatest during the period of organogenesis, i.e. during the first 8 weeks. However, other adverse effects may still occur during the latter periods of pregnancy, e.g. uterine perfusion and contractility may be affected by antiarrhythmic drugs, influencing fetal growth and labour. However, quinidine, procainamide, lidocaine, flecainide, propranolol, amiodarone, verapamil, and digoxin do not reduce human placental blood flow (but adenosine does). Physiological changes in the mother may alter the effective plasma concentration of antiarrhythmic drugs. The increased intravascular

Background Endocardial mapping of atrial fibrillation in humans is limited by its low resolution and by complexities in the arrhythmia and atrial anatomy. Methods and Results A catheter mounted non-contact multielectrode was deployed in the right atrium of 11 patients with atrial fibrillation and used to reconstruct 3360 electrograms, superimposed onto a computer-simulated model of the endocardium, using inverse solution mathematics. This allows construction of isopotential maps of the right atrium. Patients had either sustained atrial fibrillation (n=3) for >6 months or developed atrial fibrillation during the study (n=8). Spontaneous initiation of atrial fibrillation was recorded in one patient and was demonstrated by the non-contact system to arise from two successive atrial ectopic beats from the site of a roving contact catheter. Reconstruction of electrograms recorded during atrial fibrillation was validated by comparison with contact electrograms with cross-correlation. During established atrial fibrillation, four patients predominantly had a single right atrial wave front, two had two wave fronts and five patients had three to five wave fronts for most of the time. Periods of electrical silence were seen in the right atrium in eight patients, after which, activity emerged from consistent septal sites alone, suggesting a left atrial origin. During intravenous administration of flecainide, atrial fibrillation in two patients terminated spontaneously or following pacing manoeuvres, while in the remaining patient sinus rhythm was restored via atrial tachycardia. Conclusion Non-contact mapping of the right atrium has demonstrated modes of initiation and termination of atrial fibrillation, characterized different patterns of right atrial activation in atrial fibrillation and suggests that the left atrium may sustain atrial fibrillation in some patients. Simultaneous mapping of the right and left atrium is required to further elucidate the mechanisms of human atrial fibrillation.

This statistical viewpoint refers to ‘Increased mortality among patients taking digoxin—analysis from the AFFIRM study’[†][1], by M.G. Whitbeck et al. , on page 1481; and ‘Lack of evidence of increased mortality among patients with atrial fibrillation taking digoxin: findings from post hoc propensity-matched analysis of the AFFIRM trial’[‡][1], by M. Gheorghiade et al., on page 1489 Two reports relating to the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Trial1 explore the association of digoxin use with mortality among patients with atrial fibrillation (AF). The AFFIRM trial randomized 4060 patients with AF and a high risk of stroke or death to rate control vs. rhythm control. In the rate control arm, different therapies were allowed to achieve adequate heart rate control, including digoxin, beta-blockers, calcium channel blockers (verapamil and diltiazem), and combinations of these drugs. In the rhythm control arm, antiarrhythmic drugs included amiodarone, disopyramide, flecainide, moricizine, procainamide, propafenone, quinidine, sotalol, and combinations of these drugs. While the strategy of rate control vs. rhythm control was randomized, the choice of specific agents used was left to the discretion of the treating physician in both arms. During a mean follow-up of 3.5 years, there were 356 deaths (23.8%) in the rhythm control group and 310 deaths (21.3%) among the rate control group, a directionally but not significantly lower mortality with rate control ( P = 0.08). In the article by Whitbeck et al. , digoxin use was assessed at randomization and during follow-up.2 The association of digoxin use with mortality was evaluated treating digoxin as a time-dependent covariate in a Cox proportional hazard model.3 By using digoxin as a time-dependent covariate, patients changed from being in the ‘on-digoxin’ group to the ‘not on-digoxin’ group if their medication use changed over time in the study, and … [1]: #fn-2

Atrial fibrillation is a very common arrhythmia in patients with structural heart disease, but it also occurs in patients without underlying heart disease. Acute therapy for paroxysmal atrial fibrillation is very dependent on the clinical condition of the patient. Direct current cardioversion is usually the first choice whenever the arrhythmia precipitates heart failure or severe angina, while more stable patients are normally treated with drugs. Most episodes of atrial fibrillation eventually convert to sinus rhythm even in the absence of treatment. Antiarrhythmic drugs can be used to control the ventricular response or to restore sinus rhythm, and several have been tested to assess their ability to convert recent onset atrial fibrillation. The success rate has varied, but generally flecainide and propafenone appear the most effective. Digitalis and calcium channel blockers do not increase the likelihood of reversion but they reduce ventricular rate. Amiodarone has been tested as a possible alternative to flecainide and propafenone. The pros and the cons of these and other drugs in the setting of paroxysmal atrial fibrillation will be discussed. In particular, special emphasis will be given to the differences in the design and in patient selection of the trials that tested antiarrhythmic drugs in paroxysmal atrial fibrillation.

This editorial refers to “Flecainide versus ibutilide for immediate cardioversion of atrial fibrillation of recent onset”1 by J. Reisinger et al. on page 1318 Atrial fibrillation is the most common, clinically relevant arrhythmia with a prevalence of about 2% in the general population. The symptoms in atrial fibrillation are primarily caused by fast ventricular rates, which can be controlled by using the atrio-ventricular node blocking drugs or, even more effectively, by converting atrial fibrillation to sinus rhythm. Although the traditional treatment options available to treat atrial fibrillation are rhythm control versus ventricular rate control, the best method to control ventricular rate, however, is by conversion to sinus rhythm. Even though the reported rate of spontaneous conversion is up to 50%, in the first 24 h after the onset of atrial fibrillation, the earlier restoration of sinus rhythm by cardioversion will result in an early alleviation of the patient's symptoms, will eliminate the need for the use of atrio-ventricular node blocking drugs for rate control, will decrease the chances of thromboembolism, will prevent tachycardia-related cardiomyopathy, and will lessen atrial mechanical dysfunction and electrophysiological remodelling. Atrial electrophysiological remodelling, which begins to take place within a few hours of the initiation of atrial fibrillation, results in a decreased atrial refractoriness that may facilitate atrial fibrillation and decrease the chances of successful cardioversion. Moreover, the post-conversion atrial stunning, a phenomenon clearly responsible for post-conversion thromboembolism, is also related to the duration of atrial fibrillation, which makes the case even stronger for an early conversion to sinus rhythm.1 Therefore, if it is decided to restore sinus rhythm, why not attempt it as soon as possible? The most efficient and immediate method of atrial fibrillation cardioversion is by direct electric current, which is successful in 80–90% of cases. The potential drawbacks of direct current … *Correspondence to: Ijaz A. Khan, Division of Cardiology, University of Maryland School of Medicine, 22 South Greene Street, S3B06, Baltimore, MD 21201, USA. Tel.: +1-410-328-2251; fax: +1-410-328-2255 E-mail address: ikhan{at}medicine.umaryland.edu

In order to compare the long-term safety of flecainide and propafenone, an open label, randomized, parallel group study was performed in 335 patients with paroxysmal atrial fibrillation (n = 200) or paroxysmal supraventricular tachycardia (n = 135), and no history of heart disease. Patients were treated with an initial daily dose of flecainide 100 mg (n = 72) or propafenone 450 mg (n = 63) for paroxysmal supraventricular tachycardia and flecainide 200 mg (n = 97) or propafenone 450 mg (n = 103) for paroxysmal atrial fibrillation. Dose escalations were permitted after > or = 2 attacks, up to a maximum of flecainide 300 mg or propafenone 900 mg.day-1.Follow-up duration was 12 months, or when patients stopped the treatment as a result of inadequate efficacy or adverse experiences. Twelve patients on flecainide reported 16 cardiac adverse experiences, of whom six discontinued the treatment. Seven propafenone patients had eight cardiac adverse experiences, of whom five discontinued the treatment. Serious proarrhythmic events were infrequent: one case of ventricular tachycardia on propafenone: two cases of atrial fibrillation with rapid ventricular response on flecainide, associated in one patient with pulmonary oedema. An intention-to-treat analysis showed that the probability of 12 months' safe and effective treatment of paroxysmal supraventricular tachycardia was 93% for flecainide and 86% for propafenone (P = 0.24), whereas in paroxysmal atrial fibrillation it was 77% for flecainide and 75% for propafenone (P = 0.72). In conclusion, flecainide and propafenone were safe in the long-term treatment of patients with paroxysmal supraventricular tachyarrhythmias and without evidence of clinically significant heart disease.

We studied the effects of intravenous fiecainide (2 mg.kg−1) on atrial and ventricular refractoriness and conduction during sinus rhythm, induced atrial fibrillation and atrial pacing at rates of 100, 120 and 150 ppm, in 14 patients with normal left ventricle. Flecainide caused a significant increase in QRS duration during sinus rhythm (mean ± SD: 87.2 ± 8.4 ms vs 102.8 ± 9.1 ms, P

In atrial flutter, chemical conversion with class I drugs is often unsuccessful, whereas class III drugs seem more promising. The different electrophysiological effects of these drugs may explain this discrepancy. To date, only experimental data show the differential effects of these drugs on conversion rate and atrial flutter cycle length. This study evaluates the effects of the class IC antiarrhythmic drug flecainide, and of dofetilide, a new class III drug, on conversion rate and flutter cycle length in patients with atrial flutter. Flecainide (11 patients) was given as an intravenous bolus of 2 mg.kg-1 in 10 min and dofetilide (10 patients) as a maximum intravenous bolus of 8 micrograms.kg-1 in 15 min. Baseline characteristics were comparable between both groups. Only one patient treated with flecainide converted to sinus rhythm. This patient showed the largest flutter cycle length increase (280 to 420 ms). By contrast, seven of the 10 patients treated with dofetilide converted to sinus rhythm. Patients treated with flecainide showed a significantly larger increase in atrial flutter cycle length at the end of the infusion compared to the dofetilide-treated patients (from 226 +/- 28 to 317 +/- 52 ms vs from 221 +/- 26 to 239 +/- 39 ms, respectively). In conclusion, dofetilide is more effective than flecainide in the conversion of atrial flutter to sinus rhythm, despite the fact that flecainide produced a more prolonged flutter cycle length. Thus, action potential prolongation in the absence of conduction slowing seems more effective in terminating human atrial flutter than depression of the excitability.

In atrial flutter, chemical conversion with class I drugs is often unsuccessful, whereas class III drugs seem more promising. The different electrophysiological effects of these drugs may explain this discrepancy. To date, only experimental data show the differential effects of these drugs on conversion rate and atrial flutter cycle length. This study evaluates the effects of the class IC antiarrhythmic drug flecainide, and of dofetilide, a new class III drug, on conversion rate and flutter cycle length in patients with atrial flutter. Flecainide (11 patients) was given as an intravenous bolus of 2 mg . kg-1 in 10 min and dofetilide (10 patients) as a maximum intravenous bolus of 8 mug . kg-1 in 15 min. Baseline characteristics were comparable between both groups. Only one patient treated with flecainide converted to sinus rhythm. This patient showed the largest flutter cycle length increase (280 to 420 ms). By contrast, seven of the 10 patients treated with dofetilide converted to sinus rhythm. Patients treated with flecainide showed a significantly larger increase in atrial flutter cycle length at the end of the infusion compared to the dofetilide-treated patients (from 226 +/- 28 to 317 +/- 52 ms vs from 221 +/- 26 to 239 +/- 39 ms, respectively). In conclusion, dofetilide is more effective than flecainide in the conversion of atrial flutter to sinus rhythm, despite the fact that flecainide produced a more prolonged flutter cycle length. Thus, action potential prolongation in the absence of conduction slowing seems more effective in terminating human atrial flutter than depression of the excitability.

Rapid atrial pacing is effective in terminating atrial flutter, but often results in transient or permanent atrial fibrillation rather than sinus rhythm. Class Ia antiarrhythmic drugs have earlier been shown to facilitate the direct conversion of atrial flutter to sinus rhythm. The present study was performed to test the hypothesis that flecainide, a group 1c antiarrhythmic drug, increases the direct conversion to sinus rhythm. In a series of 30 consecutive clinical episodes of atrial flutter treated with rapid atrial pacing, 12 episodes were in patients on flecainide treatment (group A), while in 13 episodes no patients were on group 1 antiarrhythmic drugs (group B). Direct conversion to sinus rhythm was achieved more often in group A (75%) than in group B (31%) P = 0.034. Both the flutter rates and the pacing rates used were lower in group A, 240 vs 280 beat. Min−1 and 375 vs 430 b. min−1, respectively. Patients with atrial flutter in whom rapid atrial pacing is to be performed should be considered for pretreatment with flecainide.

The effects of mexiletine, propafenone and flecainide on the parameters of signal-averaged electrocardiogram in 40 subjects with symptomatic and repetitive ventricular arrhythmias were studied. Mexiletine (n = 16) suppressed ventricular arrhythmias in 10 patients and did not produce any significant changes in filtered QRS duration (fQRS), root mean square voltage of the final 40 ms of filtered QRS (RMS40) or low amplitude terminal component duration (LAS40). Acute (n = 8, 450 mg) and chronic (n = 16, 600-1200 mg.day-1) administration of propafenone determined a significant increase in fQRS (from 123 +/- 2.2 to 139 +/- 3 ms) and a reduction in RMS40 (from 54 +/- 8.8 to 34 +/- 6.7 microV); as a consequence the incidence of ventricular late potentials rose from 43 to 62%. The observed effects were independent of anti-arrhythmic efficacy, which was 86% for this drug. Acute (n = 8, 200 mg) and chronic (n = 13, 200-300 mg.day-1) administration of flecainide was associated with a marked prolongation in fQRS (from 123 +/- 2.8 to 138 +/- 4.1 ms) and a reduction in RMS40 (from 69 +/- 11.5 to 47 +/- 11 microV); thus determining an increase in the incidence of ventricular late potentials from 29 to 48%. Changes in signal-averaged electrocardiogram were not related to drug efficacy, which was 81%. These data indicate that 1c anti-arrhythmic drugs consistently modified the parameters of signal-averaged electrocardiogram; the observed changes might reflect an inhomogeneous slowing of intramyocardial impulse propagation.

A 45-year-old patient with the Wolff-Parkinson-White syndrome suffering from recurrent intractable reciprocating atrioventricular tachycardia (RAVT) is reported. He used amiodarone, sotalol, quinidine, propafenone and flecainide unsuccessfully. An electrophysiological study (EPS) performed with four catheters localized the site of the anomalous pathway in the ostium of the coronary sinus. In this region we could also record a Kent potential. In the ostium of the coronary sinus, radiofrequencv energy was repeatedly applied until the conduction over the accessory pathway was abolished both in the anterograde and the retrograde direction. The Kent deflection detectable before ablation, could not be detected after it. During follow-up (1 month) the patient remained asymptomatic and the control EPS showed no evidence of pre-excitation, either anterogradely or retrogradely.

Fascicular tachycardia in young patients without overt heart disease constitutes a rare but electrophysiologically distinct arrhythmia entity. Microreentry within the left posterior fascicle has been proposed as its mechanism, but evidence for this is inconclusive. This report details a patient with incessant fascicular tachycardia. The electrophysiological features, in particular the pattern of resetting response, provided strong evidence for reentry as the tachycardia mechanism. Satisfactory long-term arrhythmia control was achieved with flecainide.