Antiarrhythmic Drugs (antiarrhythmic + drug)

Distribution by Scientific Domains

Kinds of Antiarrhythmic Drugs

  • class iii antiarrhythmic drug
  • iii antiarrhythmic drug

  • Terms modified by Antiarrhythmic Drugs

  • antiarrhythmic drug therapy

  • Selected Abstracts

    The Mechanisms of Atrial Fibrillation

    In this article we have reviewed the mechanisms of atrial fibrillation (AF) with special emphasis on the thoracic veins. Based on a number of features, the thoracic veins are highly arrhythmogenic. The pulmonary vein (PV)-left atrial (LA) junction has discontinuous myocardial fibers separated by fibrotic tissues. The PV muscle sleeve is highly anisotropic. The vein of Marshall (VOM) in humans has multiple small muscle bundles separated by fibrosis and fat. Insulated muscle fibers can promote reentrant excitation, automaticity, and triggered activity. The PV muscle sleeves contain periodic acid-Schiff (PAS)-positive large pale cells that are morphologically reminiscent of Purkinje cells. These special cells could be the sources of focal discharge. Antiarrhythmic drugs have significant effects on PV muscle sleeves both at baseline and during AF. Both class I and III drugs have effects on wavefront traveling from PV to LA and from LA to PV. Separating the thoracic veins and the LA with ablation techniques also prevents PV-LA interaction. By reducing PV-LA interaction, pharmacological therapy and PV isolation reduce the activation rate in PV, intracellular calcium accumulation, and triggered activity. Therefore, thoracic vein isolation is an important technique in AF control. We conclude that thoracic veins are important in the generation and maintenance of AF. [source]

    Quadruple Pads Approach for External Cardioversion of Atrial Fibrillation

    MARROUCHE, N.F., et al.: Quadruple Pads Approach for External Cardioversion of Atrial Fibrillation. This study examined the alternative of transthoracic quadruple pads shock delivery of two simultaneous 360-J shocks to convert refractory AF in patients failing standard external cardioversion. Forty-six patients (mean age 58 ± 11 years, 23 men) with chronic AF (duration 14 ± 17 months, range 1,60 months) were included. The left atrial diameter was 47 ± 7 mm. The left ventricular ejection fraction was 59 ± 11%. Antiarrhythmic drugs had failed to convert 44 (96%) of these patients. All patients underwent conventional external transthoracic cardioversion with pads applied in the antero-apical position using energy settings of 200 and 360 J, consecutively. In all patients who failed conventional cardioversion, quadruple pads were applied. Quadruple pads consisted of four pads, two in the antero-posterior position and two in a second apex-posterior position. Standard cardioversion to sinus rhythm was successful in 19 (41%) patients after use of a single 200-J shock and an additional 8 (17%) after a single 360-J shock. The total success rate was 58% after conventional cardioversion. The quadruple pads were successful in 14 (74%) of the remaining 19 patients. Four of the five patients who failed the quadruple pads approach subsequently also failed internal cardioversion. Thus, the cardioversion success rate was increased from 48% using the conventional approach to 89% using the quadruple pads approach. Quadruple pads external cardioversion is highly effective in converting chronic AF refractory to standard shock protocols to sinus rhythm. Moreover, the failure of the quadruple pads approach seems to predict poor response to internal cardioversion. [source]

    Update on atrial fibrillation: Part II

    Irina Savelieva MD
    Abstract Antiarrhythmic drugs are an essential tool in the management of atrial fibrillation (AF). Although we are already on the threshold of a large expansion in the use of ablation therapies, these will not, however, be appropriate for all patients, and pharmacological therapies will continue to have an important place in the management of atrial fibrillation. The plethora of antiarrhythmic drugs currently available for the treatment of atrial fibrillation is a reflection that none is wholly satisfactory, each having limited efficacy combined with poor safety and tolerability. Improved class III antiarrhythmic drugs, such as dronedarone, new classes of antiarrhythmic agents, such as atrial repolarization delaying agents, and upstream therapies dealing with substrate, represent potential sources of new pharmacological therapies. Copyright © 2008 Wiley Periodicals, Inc. [source]

    Dronedarone: a new option in atrial fibrillation

    FUTURE PRESCRIBER, Issue 1 2009
    Professor A. John Camm MD
    Many antiarrhythmic agents exploiting new mechanisms of action (as well as modified analogues of traditional antiarrhythmic drugs, with different combinations of ion channel- and receptor-blocking effects and less complicated metabolic profiles) are currently being investigated. Dronedarone is an amiodarone derivative that is devoid of iodine atoms and is believed to have a better safety profile than amiodarone. It is the only antiarrhythmic drug for the treatment of atrial fibrillation (AF) that has been shown to improve survival in high-risk patients. This review provides a contemporary insight into the clinical development of dronedarone, its efficacy and safety in preventing recurrent AF, and its potential additional advantage of improving outcome in patients with AF. Copyright © 2009 John Wiley & Sons, Ltd. [source]

    Fetal arrhythmia: Prenatal diagnosis and perinatal management

    Yasuki Maeno
    Abstract The importance of managing fetal arrhythmia has increased over the past three decades. Although most fetal arrhythmias are benign, some types cause fetal hydrops and can lead to fetal death. With the aim of improving the outcome in such cases, various studies for prenatal diagnosis and perinatal management have been published. Detailed analysis of the type of arrhythmia in utero is possible using M-mode and Doppler echocardiography. In particular, a simultaneous record of Doppler waveform at the superior venous cava and the ascending aorta has become an important and useful method of assessing the interval between atrial and ventricular contractions. Common causes of fetal tachycardia (ventricular heart rate faster than 180 bpm), are paroxysmal supraventricular tachycardia (SVT) with 1:1 atrioventricular (AV) relation and atrial flutter with 2:1 AV relation. Of fetal SVT, short ventriculo-atrial (VA) interval tachycardia due to atrioventricular reentrant tachycardia is more common than long VA interval. Most fetuses with tachycardia are successfully treated in utero by transplacental administration of antiarrhythmic drugs. Digoxin is widely accepted as a first-line antiarrhythmic drug. Sotalol, flecainide and amiodarone are used as second-line drugs when digoxin fails to achieve conversion to sinus rhythm. Fetal bradycardia is diagnosed when the fetal ventricular heart rate is slower than 100 bpm, mainly due to AV block. Approximately half of all cases are caused by associated congenital heart disease, and the remaining cases that have normal cardiac structure are often caused by maternal SS-A antibody. The efficacy of prenatal treatment for fetal AV block is limited compared with treatment for fetal tachycardia. Beta stimulants and steroids have been reported as effective transplacental treatments for fetal AV block. Perinatal management based on prospective clinical study protocol rather than individual experience is crucial for further improvement of outcome in fetuses with tachycardia and bradycardia. [source]

    Intravenous Administration of Class I Antiarrhythmic Drug Induced T Wave Alternans in an Asymptomatic Brugada Syndrome Patient

    A 53-year-old man with an abnormal ECG was referred to the Nihon University School of Medicine. The 12-lead ECG showed right bundle branch block and saddleback-type ST elevation in leads V1,V3 (Brugada-type ECG). Signal-averaged ECG showed positive late potentials. Double ventricular extrastimuli (S1: 500 ms, S2: 250 ms, S3: 210 ms) induced VF. Amiodarone (200 mg/day) was administered for 6 months and programmed ventricular stimulation was repeated. VF was induced again by double ventricular stimuli (S1: 600 ms, S2: 240 ms, S3: 170 ms). Intravenous administration of class Ic antiarrhythmic drug, pilsicainide (1 mg/kg), augmented ST-T elevation in leads V1,V3, and visible ST-T alternans that was enhanced by atrial pacing was observed in leads V2 and V3. Visible ST-T wave alternans disappeared in 15 minutes. However, microvolt T wave alternans was present during atrial pacing at a rate of 70/min without visible ST-T alternans. (PACE 2003; 26:1900,1903) [source]

    Steady-State versus Non-Steady-State QT-RR Relationships in 24-hour Holter Recordings

    The aim of the present study was to investigate the QT-RR interval relationship in ambulatory ECG recordings with special emphasis on the physiological circumstances under which the QT-RR intervals follow a linear relation. Continuous ECG recordings make it possible to automatically measure QT duration in individual subjects under various physiological circumstances. However, identification of QT prolongation in Holter recordings is hampered by the rate dependence of QT duration. Comparison of QT duration and QT interval rate dependence between different individuals implies that the nature of the QT-RR relationship is defined in ambulatory ECG. Holter recordings were performed in healthy volunteers at baseline and after administration of dofetilide, a Class III antiarrhythmic drug. After dofetilide, beat-to-beat automated QT measurements on Holter tapes were compared with manually measured QT intervals on standard ECGs matched by time. The QT-RR relationship was analyzed at baseline in individual and group data during three different periods: 24-hour, daytime, and nighttime. Data were collected under steady-state or non-steady-state conditions of cycle length and fitted with various correction formulae. Our study demonstrated an excellent agreement between manually and automated measurements. The classic Bazett correction formula did not fit the QT-RR data points in individual or group data. When heart beats were selected for a steady rhythm during the preceding minute, QT-RR intervals fit a linear relationship during the day and night periods, but not during the 24-hour period in both individual and group data. In contrast, in the absence of beat selection, data fit a more complex curvilinear relationship irrespective of the period. Our study provides the basis for comparison of QT interval durations and QT-RR relationships between individuals and between groups of subjects. [source]

    The Novel Antiarrhythmic Drug Dronedarone: Comparison with Amiodarone

    Sven Kathofer
    ABSTRACT Dronedarone is a noniodinated benzofuran derivative that has been developed to overcome the limiting iodine-associated adverse effects of the commonly used antiarrhythmic drug, amiodarone. It displays a wide cellular electrophysiological spectrum largely similar to amiodarone, inhibiting the potassium currents Ikr, IKs, IKI, IKACh, and Isus, as well as sodium currents and L-type calcium currents in isolated cardiomyocytes. In addition, dronedarone exhibits antiadrenergic properties. In vivo, dronedarone has been shown to be more effective than amiodarone in several arrhythmia models, particularly in preventing ischemia- and reperfusion-induced ventricular fibrillation and in reducing mortality. However, an increased incidence of torsades de pointes with dronedarone in dogs shows that possible proarrhythmic effects of dronedarone require further evaluation. The clinical trails DAFNE, EURIDIS, and ADONIS indicated safety, antiarrhythmic efficacy and low proarrhythmic potential of the drug in low-risk patients. In contrast, the increased incidence of death in the dronedarone group of the discontinued ANDROMEDA trial raises safety concerns for patients with congestive heart failure and moderate to severe left ventricular dysfunction. Dronedarone appears to be effective in preventing relapses of atrial fibrillation and atrial flutter. Torsades de pointes, the most severe adverse effect associated with amiodarone, has not yet been reported in humans with dronedarone. Unlike amiodarone, dronedarone had little effect on thyroid function and hormone levels in animal models and had no significant effects on human thyroid function in clinical trials. In conclusion, dronedarone could be a useful drug for prevention of atrial fibrillation and atrial flutter relapses in low-risk patients. However, further experimental studies and long-term clinical trials are required to provide additional evidence of efficacy and safety of dronedarone. [source]

    Procainamide and Survival in Ventricular Fibrillation Out-of-hospital Cardiac Arrest

    David T. Markel
    Abstract Objectives:, Procainamide is an antiarrhythmic drug of unproven efficacy in cardiac arrest. The association between procainamide and survival from out-of-hospital cardiac arrest was investigated to better determine the drug's potential role in resuscitation. Methods:, The authors conducted a 10-year study of all witnessed, out-of-hospital, ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) cardiac arrests treated by emergency medical services (EMS) in King County, Washington. Patients were considered eligible for procainamide if they received more than three defibrillation shocks and intravenous (IV) bolus lidocaine. Four logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CI) describing the relationship between procainamide and survival. Results:, Of the 665 eligible patients, 176 received procainamide, and 489 did not. On average, procainamide recipients received more shocks and pharmacologic interventions and had lengthier resuscitations. Adjusted for their clinical and resuscitation characteristics, procainamide recipients had a lower likelihood of survival to hospital discharge (OR = 0.52; 95% CI = 0.36 to 0.75). Further adjustment for receipt of other cardiac medications during resuscitation negated this apparent adverse association (OR = 1.02; 95% CI = 0.66 to 1.57). Conclusions:, In this observational study of out-of-hospital VF and pulseless VT arrest, procainamide as second-line antiarrhythmic treatment was not associated with survival in models attempting to best account for confounding. The results suggest that procainamide, as administered in this investigation, does not have a large impact on outcome, but cannot eliminate the possibility of a smaller, clinically relevant effect on survival. ACADEMIC EMERGENCY MEDICINE 2010; 17:617,623 © 2010 by the Society for Academic Emergency Medicine [source]

    Effects of intravenous dofetilide in patients with frequent premature ventricular contractions: A clinical trial

    Peter E. Pool M.D.
    Abstract Background: Although suppression of premature ventricular contractions (PVCs) is not a predictor of mortality over the long term, the extent of PVC suppression is an important characteristic of any antiarrhythmic drug. Hypothesis: This study was undertaken to determine whether intravenous (IV) dofetilide has the ability to suppress PVCs in patients who have frequent occurrences. Methods: Subjects were men and women, aged 18 to 75 years, with > 30 PVCs/h on two consecutive 24-h Holter recordings while drug free, and > 50 PVCs/h during a 2-hour telemetric electrocardiogram. The study was randomized, double-blind, and placebo controlled. Subjects received a single-blind, IV infusion of placebo and were randomized (3:1) to receive a double-blind second infusion of placebo or an infusion of dofetilide (a 15-min loading infusion of 4 g/kg followed by a 60-min maintenance infusion of 3.5 g/kg, for a total dose of 7.5 g/kg). Results: Dofetilide produced an 82.6% and placebo a 2.9% median reduction in PVCs. Drug responder rate, defined as 80% reduction in PVCs, was 50% in the dofetilide group and 0% in the placebo group. Conclusion: Intravenous dofetilide significantly reduced PVCs in patients who had > 30 PVCs/h at baseline, and it produced , 80% reduction in PVCs in 50% of all subjects. [source]

    Dronedarone: a new option in atrial fibrillation

    FUTURE PRESCRIBER, Issue 1 2009
    Professor A. John Camm MD
    Many antiarrhythmic agents exploiting new mechanisms of action (as well as modified analogues of traditional antiarrhythmic drugs, with different combinations of ion channel- and receptor-blocking effects and less complicated metabolic profiles) are currently being investigated. Dronedarone is an amiodarone derivative that is devoid of iodine atoms and is believed to have a better safety profile than amiodarone. It is the only antiarrhythmic drug for the treatment of atrial fibrillation (AF) that has been shown to improve survival in high-risk patients. This review provides a contemporary insight into the clinical development of dronedarone, its efficacy and safety in preventing recurrent AF, and its potential additional advantage of improving outcome in patients with AF. Copyright © 2009 John Wiley & Sons, Ltd. [source]

    Triggering Pulmonary Veins: A Paradoxical Predictor for Atrial Fibrillation Recurrence After PV Isolation

    Triggering Pulmonary Veins and Recurrence After Ablation.,Purpose: To identify procedural parameters predicting recurrence of atrial fibrillation (AF) after a first circumferential pulmonary vein isolation (CPVI). Methods: One hundred seventy-one patients undergoing CARTO-guided CPVI for recurrent AF with a left atrial (LA) diameter <45 mm were studied. Follow-up (symptoms and 7-day Holter) was performed at 1 and 3 months and every 3 months thereafter. Clinical and procedural characteristics between successful patients and patients undergoing repeat ablation were compared. In addition, procedural parameters of the first procedure were compared with parameters during repeat ablation. Results: After first CPVI, 80% of patients were free of AF without antiarrhythmic drugs after a follow-up (FU) of 28 ± 11 months (N = 136). Thirty-five patients (20%) had recurrence of AF of which 25 underwent repeat ablation (N = 25). Clinical characteristics did not differ between the successful and repeat group. A triggering vein during the index procedure was significantly more observed in the repeat group (56% vs 11%, P < 0.001). At repeat ablation, 2.6 ± 1.2 veins per patient were reconnected. Whereas there was no preferential reconnecting PV, all PVs triggering at index were reconnected (100%). Conclusions: (1) In patients with symptomatic recurrent AF, the presence of a triggering pulmonary vein during ablation is a paradoxical predictor for AF recurrence after PV isolation. (2) The consistent finding of reconnection of the triggering PV at repeat ablation, suggests that, in these patients, the triggering PV is the culprit vein and that reconnection invariably results in clinical AF recurrence. (3) The present study advocates a strategy of even more stringent PV isolation in case of a triggering PV. (J Cardiovasc Electrophysiol, Vol. 21, pp. 381,388, April 2010) [source]

    Hybrid Therapy of Radiofrequency Catheter Ablation and Percutaneous Transvenous Mitral Commissurotomy in Patients With Atrial Fibrillation and Mitral Stenosis

    AF Ablation and PTMC.,Background: The rhythm control of atrial fibrillation (AF) associated with mitral stenosis (MS) is often difficult using antiarrhythmic drugs (AADs), even after a percutaneous transvenous mitral commissurotomy (PTMC). Few studies have examined the efficacy and safety of simultaneously performing radiofrequency catheter ablation (RFCA) and a PTMC in patients with MS and AF. Methods: Twenty consecutive patients with drug-resistant AF and rheumatic MS underwent RFCA combined with a PTMC (n = 10; persistent AF-8, long-lasting [>1 year] persistent AF-2; RFCA group) or transthoracic direct cardioversion (DC) following a PTMC (n = 10; persistent AF-7, long-lasting persistent AF-3; DC group). In all patients, the mitral valve morphology was amenable to a PTMC, and more than 2 AADs had been ineffective in maintaining sinus rhythm (SR). In the RFCA group, a segmental pulmonary vein isolation (PVI) was performed in the initial 5 patients, and an extensive PVI was performed in the remaining 5. Results: During a mean follow-up period of 4.0 ± 2.7 years, 8 patients (80%) in the RFCA group were maintained in SR, as compared to 1 (10%) in the DC group (hazard ratio, 0.16; 95% confidence interval, 0.03 to 0.75; P = 0.008 by the log-rank test). The prevalence of the concomitant use of class I and/or class III AADs was comparable between the 2 groups (P = 0.70). No complications occurred during the procedure or follow-up period in either group. Conclusions: The hybrid therapy using RFCA and a PTMC was safe and feasible, and significantly improved the AF free survival rate compared to DC following a PTMC. (J Cardiovasc Electrophysiol, Vol. 21, pp. 284,289, March 2010) [source]

    Sotalol and a Broken Heart

    Sotalol and a Broken Heart., An 82-year-old woman with persistent atrial fibrillation underwent successful electrical cardioversion and was begun on sotalol. After 3 days of in-hospital observation she had only mild lengthening of the QT interval. Two weeks later in clinic, the day after her husband's unexpected death, she was noted to have profound QT interval prolongation. Although she was asymptomatic and echocardiography did not disclose regional wall motion abnormalities consistent with takotsubo cardiomyopathy, she probably had a forme fruste of stress cardiomyopathy. Following emotional trauma, a period of heightened vigilance for ventricular proarrhythmia is probably warranted in women treated with antiarrhythmic drugs that lengthen repolarization. (J Cardiovasc Electrophysiol, Vol. 21, pp. 207-210, February 2010) [source]

    Age-Related Increase in Atrial Fibrillation Induced by Transvenous Catheter-Based Atrial Burst Pacing: An In Vivo Rat Model of Inducible Atrial Fibrillation

    AF Rat Model Induced by Transvenous Catheter Pacing.,Introduction: Large animal models of atrial fibrillation (AF) are well established, but limited experimental reports exist on small animal models. We sought to develop an in vivo rat model of AF using a transvenous catheter and to evaluate the model's underlying characteristics. Methods and Results: Echocardiogram, surface electrocardiogram (ECG), and atrial effective refractory period (AERP) were recorded at baseline in young (3 months) and middle-aged (9 months) Wistar rats. AF inducibility and duration were measured through transvenous electrode catheter in young (n = 11) and middle-aged rats (n = 11) and middle-aged rats treated with either pilsicainide (1 mg/kg iv, n = 7) or amiodarone (10 mg/kg iv, n = 9). Degrees of interstitial fibrosis and cellular hypertrophy in the atria were assessed histologically. The P-wave duration and AERP were significantly longer and echocardiographic left atrial dimension significantly larger in middle-aged versus young rats. AF was inducible in >90% of all procedures in both untreated rat groups, whereas AF inducibility was reduced by the antiarrhythmic drugs. The AF duration was significantly longer in middle-aged than in young rats and was significantly shortened by treatment with either pilsicainide or amiodarone. Histologic analysis revealed significant increases in atrial interstitial fibrosis and cellular diameter in middle-aged versus young rats. Conclusions: Transvenous catheter-based AF is significantly longer in middle-aged than in young rats and is markedly reduced by treatment with antiarrhythmic drugs. This rat model of AF is simple, reproducible, and reliable for examining pharmacologic effects on AF and studying the process of atrial remodeling.(J Cardiovasc Electrophysiol, Vol. 21, pp. 88,93, January 2010) [source]

    Cryoballoon Pulmonary Vein Isolation Guided by Transesophageal Echocardiography: Novel Aspects on an Emerging Ablation Technique

    Background: Pulmonary vein (PV) isolation using a balloon-mounted cryoablation system is a new technology for the percutaneous treatment of atrial fibrillation (AF). Transesophageal echocardiography (TEE) allows real-time visualization of cryoballoon positioning and successful vein occlusion via color Doppler. We hypothesized that PV mechanical occlusion monitored with TEE could predict effective electrical isolation. Methods: We studied 124 PVs in 30 patients. Under continuous TEE assessment, a cryoballoon was placed in the antrum of each PV aiming for complete PV occlusion as documented by color Doppler. At the end of the procedure, PV electrical isolation was evaluated using a circumferential mapping catheter. Results: Of the 124 PVs studied, 123 (99.2%) could be visualized by TEE: the antrum was completely visualized in 80 of them (64.5%), partially in 36 (29.0%), and only disappearance of proximal flow could be observed in the remaining 7 PVs (5.7%). Vein occlusion could be achieved in 111 of the 123 (90.2%) visualized PVs. Postinterventional mapping demonstrated electrical isolation in 109 of 111 occluded PVs (positive predictive value 98.2%) and only in 1 of 12 nonoccluded PVs (negative predictive value 91.7%, P < 0.001). After a mean follow-up of 7.4 ± 3.7 months, 73.3% of patients remained in sinus rhythm without antiarrhythmic drugs. Conclusion: Color Doppler documented PV occlusion during cryoballoon ablation can predict effective electrical isolation. [source]

    Patients with Scar-Related Right Ventricular Tachycardia: Determinants of Long-Term Outcome

    Introduction: Patients with established arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) based on task force (TF) criteria and ventricular tachycardia (VT) are at risk of VT recurrence and sudden death. Data on patients with VT due to right ventricular (RV) scar not fulfilling TF criteria are lacking. The purpose of this study was to assess the long-term arrhythmia recurrence rate and outcome in patients with scar-related right VT with and without a diagnosis of ARVC/D. Methods: Sixty-four patients (age 43.5 ± 15 years, 49 males) presenting with nonischemic scar-related VT of RV origin were studied. Scar was identified by electroanatomical mapping, contrast echocardiography, and/or magnetic resonance imaging (MRI). Patients were evaluated and treated according to a standard institute protocol. Results: Twenty-nine (45%) patients were diagnosed with ARVC/D according to TF criteria (TF+) and 35 (55%) with RV scar of undetermined origin (TF,) at the end of follow-up (64 ± 42 months). Patients were treated with antiarrhythmic drugs, radiofrequency catheter ablation, and/or implantable cardioverter-defibrillator (ICD) implantation. VT recurrence-free survival for TF+ and TF, was 76% versus 74% at 1 year and 45% versus 50% at 4 years (P = ns). Patients with fast index VT (cycle length [CL], 250 ms, n = 31) were more likely to experience a fast VT during follow-up than patients with a slow index VT (CL > 250 ms, n = 33) (61% vs 3%, P < 0.001). Conclusions: Scar-related RV VTs have a high recurrence rate in TF+ and TF, patients. Patients presenting with a fast index VT are at high risk for fast VT recurrence and may benefit most from ICD therapy. [source]

    Mode of Induction of Ventricular Tachycardia and Prognosis in Patients with Coronary Disease: The Multicenter UnSustained Tachycardia Trial (MUSTT)

    Introduction: Programmed stimulation is an important prognostic tool in the evaluation of patients with an ejection fraction ,40% after myocardial infarction. Many believe that ventricular tachycardia (VT) requiring 3 ventricular extrastimuli (VES) for induction is less likely to occur spontaneously and has less predictive value. However, it is unknown whether the mode of VT induction is associated with long-term prognosis. Methods and Results: We analyzed a cohort of 371 patients enrolled in MUSTT who had inducible monomorphic VT and who were not treated with antiarrhythmic drugs or an implantable cardioverter defibrillator during the trial. Patients in whom sustained VT was induced with 1 or 2 VES or burst pacing (single VES n = 15, double VES n = 127, burst n = 7, total n = 149) were compared with those in whom VT was induced with 3 VES (n = 222). Compared with the others, patients requiring 3 VES were closer to their most recent myocardial infarction (17 vs 51 months, P = 0.035) and showed a trend toward a lower ejection fraction (26% vs 30%, P = 0.057). VT requiring 3 VES had a shorter cycle length (240 vs 260 ms, P < 0.001). Despite these findings, there was no difference in the incidence of arrhythmic death or cardiac arrest (HR 1.02; 95% CI 0.69-1.51) or all-cause mortality (HR 1.03; 95% CI 0.76-1.39) according to the mode of induction in adjusted analyses. Conclusions: The prognostic significance of VT induced by 3 VES is similar to that of VT induced by 1 or 2 VES, or burst pacing, in patients with coronary disease and abnormal LV function. [source]

    Effect of Radiofrequency Ablation of Atrial Flutter on the Natural History of Subsequent Atrial Arrhythmias

    Introduction: Patients with atrial flutter (AFL) treated medically are at high risk for subsequent development of atrial fibrillation (AF). Whether curative radiofrequency ablation of AFL can modify the natural history of arrhythmia progression is not clear. We aimed to determine whether ablation of AFL decreases the subsequent development of AF in patients without previous AF. Methods and Results: Patients with AFL as the sole atrial arrhythmia were selected from patients who underwent successful AFL ablation at Mayo Clinic between 1997 and 2003 (N = 137). The cohort was divided by presence (n = 50) or absence (n = 87) of structural heart disease. A control group comprised 59 patients with AFL and no history of paroxysmal AF, who received only medical therapy. Occurrence of AF after AFL ablation was compared among study groups and controls. Symptomatic AF occurred in 49 patients during 5 years of follow-up after AFL ablation, with similar frequency in both study groups. The cumulative probability of paroxysmal and chronic AF was similar in controls and each study group. By multivariate analysis, the AFL ablation procedure carries significant risk of AF occurrence during follow-up. Fifty patients discontinued antiarrhythmic drugs after AFL ablation, and the rate of cardioversions decreased. Conclusion: Successful ablation of AFL does not improve the natural history of atrial arrhythmia progression; postablation AF is frequent. This suggests that AFL may be initiated by bursts of AF and that in the absence of AFL substrate the AF continues to progress. [source]

    Pathophysiology and Disease Progression of Atrial Fibrillation: Importance of Achieving and Maintaining Sinus Rhythm

    Atrial fibrillation (AF) is a progressive disease in which arrhythmia-induced remodeling facilitates evolution from paroxysmal AF to persistent and permanent AF. Changes in electrical, structural, and contractile properties of cardiac tissue that are thought to underlie AF maintenance and progression are reviewed. Also examined is the negative impact of AF on clinical outcomes, as well as the potential benefits of restoration and maintenance of sinus rhythm. Because of the limited efficacy and adverse effects of current antiarrhythmics, new antiarrhythmic drugs need to be developed that provide safer and more effective rhythm control in AF. [source]

    Rationale and Design of ATHENA: A Placebo-Controlled, Double-Blind, Parallel Arm Trial to Assess the Efficacy of Dronedarone 400 mg Bid for the Prevention of Cardiovascular Hospitalization or Death from Any Cause in PatiENts with Atrial Fibrillation/Atrial Flutter

    Background: Atrial fibrillation (AF) is the most commonly encountered clinical arrhythmia, predominantly affecting elderly patients. There is a continued need for new antiarrhythmic drugs to treat the ever-increasing number of patients with this arrhythmia. Dronedarone is a new antiarrhythmic compound currently being developed for treatment of AF. Methods: The ATHENA trial (A placebo-controlled, double-blind, parallel arm Trial to assess the efficacy of dronedarone 400 mg bid for the prevention of cardiovascular Hospitalization or death from any cause in patiENts with Atrial fibrillation/atrial flutter) is the largest single antiarrhythmic drug trial ever conducted. More than 4,600 patients with a history of AF or atrial flutter (AFL) have been randomized to receive dronedarone 400 mg bid or matching placebo. The primary study endpoint is time to first cardiovascular hospitalization or death from any cause. The study has completed patient enrollment in December 2006 and is expected to end follow-up 1 year later. Conclusion: ATHENA will be the largest efficacy and safety trial of dronedarone, a multichannel blocker compound with properties from class I, II, III, and IV antiarrhythmic drugs developed to treat patients with AF. [source]

    Transthoracic Tissue Doppler Imaging of the Atria: A Novel Method to Determine the Atrial Fibrillation Cycle Length

    Background: The atrial fibrillation cycle length (AFCL) is a critical parameter for the perpetuation and termination of AF. In the present study, we evaluated a new method to measure the AFCL based on transthoracic tissue Doppler imaging (TDI) of the right atrium (RA) and left atrium (LA). Methods: Twenty patients with AF (6 acute AF, 14 persistent or permanent AF) were studied. A quadripolar catheter was positioned at RA or LA to measure AFCL (AFCLEGM, gold standard). Transthoracic echocardiography (apical 4-chamber view) was used to perform pulsed wave TDI at the free wall of RA or LA. AFCLTDI was defined as the time interval between two consecutive positive to negative crossings of the baseline of the atrial time velocity curves. AFCLEGM and AFCLTDI were measured at baseline and during a 10-minute infusion of flecainide (1.5 mg/kg). Results: Measurement of AFCLTDI was feasible in all but one patient. At baseline, AFCLEGM was 170 ± 22 ms, AFCLTDI 172 ± 22 ms (difference 2 ± 5 ms). AFCLTDI correlated significantly with AFCLEGM (R = 0.91, P < 0.0001). Bland-Altman analysis showed a bias of ,2 ms with a 95% limit of agreement between ,26 ms and +22 ms. During flecainide, the AFCLTDI method yielded an AFCL prolongation from 176 ± 23 ms at baseline to 279 ± 68 ms (P < 0.01) after 10 minutes of infusion (57 ± 26%). Conclusions: (1) Tissue Doppler imaging of the atria during transthoracic echocardiography can be used to reliably determine the AFCL during both acute and persistent or permanent AF. (2) Continuous measurement of AFCL with TDI can be used to monitor the effect of antiarrhythmic drugs on atrial rate during AF. (3) This novel method is attractive because of the ease of acquiring the data and its noninvasive character. [source]

    Comparison of Cool Tip Versus 8-mm Tip Catheter in Achieving Electrical Isolation of Pulmonary Veins for Long-Term Control of Atrial Fibrillation: A Prospective Randomized Pilot Study

    Objective: To compare safety and efficacy of 8-mm versus cooled tip catheter in achieving electrical isolation (EI) of pulmonary veins (PV) for long-term control of atrial fibrillation (AF). Background: There is paucity of studies comparing safety/efficacy of 8-mm and cooled tip catheters in patients undergoing AF ablation. Methods and Results: This was a randomized and patient-blinded study. Subjects were followed by clinic visits (at 6 weeks and 6 months) and transtelephonic monitoring (3-week duration) done around each visit. Primary endpoints were: (1) long-term AF control (complete freedom and/or >90% reduction in AF burden on or off antiarrhythmic drugs at 6 months after a single ablation), and (2) occurrence of serious adverse events (cardiac tamponade, stroke, LA-esophageal fistula, and/or death). Eighty-two patients (age 56 ± 9 years, 60 males, paroxysmal AF = 59) were randomized (42 patients to 8-mm tip and 40 patients to cooled tip). EI of PVs was achieved in shorter time by the 8-mm tip as compared with cooled tip catheter (40 ± 23 minutes vs 50 ± 30 minutes; P < 0.05) but long-term AF control was not different between the two (32 patients [78%] vs 28 patients [70%], respectively; P = NS). One serious adverse event occurred in each group (LA-esophageal fistula and stroke, respectively) and no significant PV stenosis was observed in either. Conclusion: EI of PVs using either 8-mm or cooled tip catheter results in long-term AF control in the majority after a single ablation procedure, with comparable efficacy and safety. [source]

    Effect of Chronic Amiodarone Therapy on Excitable Gap During Typical Human Atrial Flutter

    Introduction: Class I antiarrhythmic drugs increase duration of the excitable gap (EG) during typical atrial flutter whereas intravenous class III drugs decrease the EG. The effect of chronic oral amiodarone therapy on the EG is unknown. Methods and Results: EG was prospectively determined by introducing a premature stimulus and analyzing the response pattern during typical atrial flutter in 30 patients without antiarrhythmic drugs and in 20 patients under chronic oral amiodarone therapy. EG was calculated by the difference between the longest coupling interval leading to resetting and the effective atrial refractory period (EARP). A fully EG was defined by the portion of EG where the response curve of the return cycles was flat. A partially EG was defined by the portion of EG where the return cycle increases while coupling interval decreases. A resetting response curve was constructed by plotting the duration of the return cycle against the value of the coupling interval. Cycle length (CL; 222 ± 17 vs 267 ± 20 msec, P < 0.0001), EARP (128 ± 16 vs 152 ± 18 msec, P < 0.0001), and EG (54 ± 19 vs 70 ± 21 msec, P = 0.01) were significantly longer in patients taking amiodarone than in controls. Compared to CL, the relative part of the EARP (57 ± 7 vs 57 ± 6%, P = 0.96) and EG (24 ± 7 vs 26 ± 8%, P = 0.41) were comparable in both groups. The fully EG was larger in patients under chronic amiodarone therapy than in controls (39 ± 21 vs 26 ± 20 msec, P = 0.03). Neither duration of the partially EG (28 ± 15 vs 31 ± 15 msec, P = 0.42) nor slope of the ascending portion of the resetting response curve (1.15 ± 0.5 vs 1.13 ± 0.4 msec/msec, P = 0.71) differed between the two groups. Conclusion: EG in patients under chronic amiodarone therapy is significantly larger than in controls, mainly because of a longer fully EG. This observation may be explained by opposite effects on conduction velocity and refractoriness. [source]

    Total Atrioventricular Nodal Ablation Increases Atrial Fibrillation Burden in Patients with Paroxysmal Atrial Fibrillation Despite Continuation of Antiarrhythmic Drug Therapy

    Introduction: Total atrioventricular nodal (TAVN) ablation and pacing is an accepted and safe treatment for patients with drug-refractory paroxysmal atrial fibrillation (AF). Many patients develop permanent AF within the first 6 months after TAVN ablation. This usually is ascribed to the cessation of antiarrhythmic drug therapy. We hypothesized that TAVN ablation itself creates an atrial substrate prone to AF. Methods and Results: Patients participating in the Atrial Pacing Periablation for Paroxysmal Atrial Fibrillation (PA3) study who remained on stable antiarrhythmic drug therapy throughout follow-up were included in this analysis. AF burden and the development of persistent AF in the preablation period were compared to two consecutive postablation periods. Echocardiographic changes also were evaluated. Twenty-two patients remained on stable drug therapy (9 men and 13 women, age 59 ± 3 years). One patient developed persistent AF preablation compared to 10 postablation (P < 0.05). AF burden preablation was 3.0 ± 1.2 hours/day and increased to 10.4 ± 2.2 hours/day and 11.8 ± 2.3 hours/day in the two postablation follow-up periods (P < 0.05). In patients with fractional shortening (FS) >30% prior to ablation, FS decreased significantly from 39.4%± 1.3% to 36.4%± 1.7% (P < 0.05). In contrast, in patients with a FS ,30% prior to ablation, FS increased from 27%± 0.8% to 33.6 ± 1.7% (P < 0.05). Conclusion: TAVN ablation increases AF burden and facilitates the development of persistent AF in patients with paroxysmal AF despite the continuation of antiarrhythmic drugs. Loss of AV and/or interventricular synchrony may lead to altered cardiac hemodynamics resulting in atrial stretch and increasing AF burden. (J Cardiovasc Electrophysiol, Vol. 14, pp. 1296-1301, December 2003) [source]

    Usefulness of a New Radiofrequency Thermal Balloon Catheter for Pulmonary Vein Isolation:

    A New Device for Treatment of Atrial Fibrillation
    Introduction: A rapidly firing or triggered ectopic focus located within a pulmonary vein (PV) or close to the PV ostium could induce atrial fibrillation (AF). The aim of this study was to evaluate the efficacy and safety of a radiofrequency thermal balloon catheter for isolation of the PV from the left atrium (LA). Methods and Results: Twenty patients with drug-resistant paroxysmal AF were treated by isolating the superior PVs using an RF thermal balloon catheter. Using a transseptal approach, the balloon, which had an inflated diameter 5 to 10 mm larger than that of the PV ostium, was wedged at the LA-PV junction. It was heated by a very-high-frequency current (13.56 MHZ) applied to the coil electrode inside the balloon for 2 to 3 minutes, and the procedure was repeated up to four times. The balloon center temperature was maintained at 60° to 75°C by regulating generator output. Successful PV isolation was achieved in 19 of the 20 left superior PVs and in all 20 of the right superior PVs and was associated with a decrease in amplitude of the ostial potentials. Total procedure time was1.8 ± 0.5hours, which included22 ± 7minutes of fluoroscopy time. After a follow-up period of8.1 ± 0.8months, 17 patients were free from AF, with 10 not taking any antiarrhythmic drugs and 7 taking the same antiarrhythmic agent as before ablation. Electron beam computed tomography revealed no complications, such as PV stenosis at ablation sites. Conclusion: The PV and its ostial region can be safely and quickly isolated from the LA by circumferential ablation around the PV ostia using a radiofrequency thermal balloon catheter for treatment of AF. (J Cardiovasc Electrophysiol, Vol. 14, pp. 609-615, June 2003) [source]

    Irrigated-Tip Catheter Ablation of Pulmonary Veins for Treatment of Atrial Fibrillation

    Irrigated-Tip Catheter Ablation of PVs.Introduction: Catheter ablation of pulmonary veins (PV) for treatment of atrial fibrillation (AF) is limited by the disparate requirements of sufficient energy delivery to achieve PV isolation while avoiding PV stenosis. The aim of the present study was to evaluate the safety and efficacy of using an irrigated-tip catheter for systematic isolation of PV. Methods and Results: The study population consisted of 136 consecutive patients (109 men, mean age 52 ± 10 years) with symptomatic, drug-refractory paroxysmal (122) or persistent (14) AF. Cavotricuspid isthmus ablation and systematic radiofrequency isolation of all four PVs (guided by a circumferential mapping catheter) was performed in all patients with a protocol using an irrigated-tip catheter. PV diameter was assessed by selective angiography. The electrophysiologic endpoint of PV isolation was achieved in 100% of patients. Bidirectional cavotricuspid isthmus block was achieved in 99% of patients. Moderate PV stenosis (50% narrowing) was observed in one patient (0.7%) without clinical consequence. No other complications were observed. Reablation procedures were required in 67 patients (49%). After a mean follow-up of 8.8 ± 5.3 months, 81% of patients were free of AF clinical recurrence, including 66% not taking any antiarrhythmic drugs. Conclusion: Systematic radiofrequency ablation of PV using an irrigated-tip catheter in patients with atrial fibrillation allows complete isolation of all four PVs with a very low incidence of stenosis. [source]

    Effect of Action Potential Duration and Conduction Velocity Restitution and Their Spatial Dispersion on Alternans and the Stability of Arrhythmias

    Restitution and Spatial Heterogeneities vs Arrhythmias.Introduction: The slope of the action potential duration (APD) restitution curve has been used to explain wavebreaks during arrhythmia initiation and maintenance. This hypothesis remains incomplete to fully describe the experimental data. Other factors contributing to wavebreaks must be studied to further understand arrhythmia dynamics. Methods and Results: Control APDs were measured from isolated rabbit hearts using a monophasic action potential probe. APD and conduction velocity (CV) restitution were quantified over the heart surface for two drugs, diacetyl monoxime (DAM) and cytochalasin D (CytoD), using a dual camera video imaging system. For all pacing intervals: (1) control APDs were shorter than for CytoD but longer than for DAM; and (2) CV was greater for CytoD compared with DAM. APD dispersion increased as pacing interval decreased for both drugs. For DAM, increased dispersion was due to a difference in APD restitution between the right and left ventricle. For CytoD, increased dispersion was due to discordant alternans, with no significant spatial variation in restitution. Fibrillation was sustained only in the control hearts; with DAM, stable reentry was sustained with shorter APD and cycle length compared with CytoD for which only nonsustained unstable reentry occurred. Conclusion: Alternans and arrhythmia dynamics are affected by the spatial dispersion of APD restitution as well as CV restitution, not simply the slope of APD restitution. Therefore, a direct link of the APD restitution slope to alternans and arrhythmia dynamics in rabbit heart does not exist. Designing antiarrhythmic drugs to alter only the restitution slope may not be appropriate. [source]

    Temporal Patterns of Atrial Arrhythmia Recurrences in Patients with Implantable Defibrillators: Implications for Assessing Antiarrhythmic Therapies

    Temporal Patterns of Atrial Arrhythmias.Introduction: The statistical measures commonly used to assess therapies for recurrent atrial arrhythmias (such as time to first recurrence) often assume a uniformly random pattern of arrhythmic events over time. However, the true temporal pattern of atrial arrhythmia recurrences is unknown. The aim of this study was to use linear and nonlinear analyses to characterize the temporal pattern of atrial arrhythmia recurrences in patients with implantable cardioverter defibrillators. Methods and Results: The time and date of atrial tachyarrhythmias recorded in 65 patients with combined atrial and ventricular defibrillators were used to construct a probability density function (PDF) and a model of a Poisson distribution of arrhythmic events for each patient. Average patient age was 66 ± 10 years and follow-up was 7.8 ± 4.8 months. A total of 10,759 episodes of atrial tachyarrhythmias were analyzed (range 43 to 618 episodes per patient). The PDF fit a power law distribution for all 65 patients, with an average r2= 0.89 ± 0.08. The PDF distribution differed significantly from the model Poisson distribution in 47 of 65 patients (P = 0.0002). Differences from the Poisson distribution were noted for patients both taking (30/43 patients; P < 0.015) and not taking (17/22 patients; P < 0.017) antiarrhythmic drugs. Median time between atrial arrhythmia detections for all 65 patients was 10.8 minutes. Conclusion: In implantable cardioverter defibrillator patients, the temporal pattern of frequent recurrences of atrial tachyarrhythmias usually is characterized by a power law distribution. The unique statistical properties of this type of distribution should be considered in designing outcome measures for treatment of atrial tachyarrhythmias. [source]

    Catheter Ablation of Chronic Atrial Fibrillation Targeting the Reinitiating Triggers

    Trigger Ablation in Chronic AF. Introduction: We assessed the mode of reinitiation of atrial fibrillation (AF) after cardioversion and the efficacy of ablating these foci of reinitiation in patients with chronic AF. Methods and Results: Fifteen patients, 7 with structural heart disease, underwent mapping and catheter ablation of drug-resistant AF documented to he persistent for 5 ± 4 months. In all patients, cardioversion was followed by documentation of P on T atrial ectopy and early recurrence, which allowed mapping of the reinitiating trigger or the source of ectopy. Radiofrequency (RF) ablation was performed at pulmonary vein (PV) ostia using a target temperature of 50°C and a power limit of 30 to 40 W, with the endpoint being interruption of all local muscle conduction. A total of 32 arrhythmogenic PVs and 2 atrial foci (left septum and left appendage) were identified: 1, 2, and 3 or 4 PVs in 5, 3, and 6 patients. RF applications at the ostial perimeter resulted in progressively increasing delay, followed by abolition of PV potentials in 8, but potentials persisted in 6. A single ablation session was performed in 7 patients and 8 underwent two or three sessions because of recurrence of AF; ablation was directed at the same source due to recovery of local PV potential or at a different PV. No PV stenosis was noted either acutely or at repeated follow-up angiograms. Nine patients (60%) were in stable sinus rhythm without antiarrhythmic drugs at follow-up of 11 ± 8 months. Anticoagulants were interrupted in 7 patients. Conclusion: PVs are the dominant triggers reinitiating chronic AF in this patient population. Elimination of PV potentials by ostial RF applications results in stable sinus rhythm in 60%. A larger group and longer follow-up are needed to investigate further the role of trigger ablation in curative therapy for chronic AF. [source]