Arrhythmia Recurrence In Patients Research Articles

Efficacy and safety of sustained-release propafenone (propafenone SR) for patients with atrial fibrillation

The objective of this randomized, double-blind, placebo-controlled clinical trial was to test the efficacy and safety of a new sustained-release preparation of the antiarrhythmic drug propafenone (propafenone SR) in reducing the frequency of symptomatic arrhythmia recurrences in patients with atrial fibrillation (AF). Patients with a history of symptomatic AF who were in sinus rhythm were randomly assigned to receive placebo or propafenone SR 425, 325, or 225 mg, all twice daily. Recurrent symptomatic arrhythmias were documented using transtelephone electrocardiographic monitoring. Electrocardiograms were reviewed by an event committee that was blinded to treatment assignment. In the primary efficacy analysis, propafenone SR significantly lengthened the time to first symptomatic atrial arrhythmia recurrence at all 3 doses compared with placebo as assessed by log-rank test: propafenone SR 425 mg twice daily versus placebo twice daily, p <0.001; 325 mg twice daily versus placebo twice daily, p <0.001; and 225 mg twice daily versus placebo twice daily, p = 0.014. The median time to recurrence was 41 days in the placebo twice daily group, >300 days in the propafenone SR 425-mg group, 291 days in the 325-mg group, and 112 days in the 225-mg group. Adverse effects leading to withdrawal were higher in the propafenone SR 425-mg twice daily group than in any other group. Thus, propafenone SR has important and statistically significant antiarrhythmic effects in patients with AF.

Azimilide for atrial fibrillation: clinical trial results and implications.

Azimilide dihydrochloride (or azimilide) is a class III antiarrhythmic drug currently under investigation that has been tested in atrial fibrillation in four randomized, placebo-controlled clinical trials to assess efficacy and dose range. These investigational trials showed that doses of azimilide 100 and 125 mg once daily prolonged the time to symptomatic arrhythmia recurrence in patients with a history of symptomatic atrial fibrillation, atrial flutter or both. Doses of 75 mg or less were not useful in this indication. Safety of azimilide has been examined in several different types of studies. In a large randomized clinical trial of post-infarct patients, azimilide neither increased nor decreased mortality risk. In patients with supraventricular arrhythmias, the most common adverse effects reported by patients on azimilide were approximately equal in frequency with those on placebo: headache, asthenia, infection, diarrhea and dizziness. Infrequent cases of torsade de pointes and severe neutropenia were reported in patients taking azimilide. Azimilide is an investigational antiarrhythmic drug that has shown efficacy in patients with atrial fibrillation.

Symptoms at the time of arrhythmia recurrence in patients receiving azimilide for control of atrial fibrillation or flutter: results from randomized trials

Background Azimilide is a new antiarrhythmic agent being developed for the management for atrial fibrillation and flutter (AF). Four randomized, placebo-controlled, double-blind trials have been performed that investigated the effect of azimilide on time to first recurrence of symptomatic AF. This paper examines the data collected during those studies regarding the symptoms reported by patients at the time of AF recurrence Methods At the time that patients reported their first documented symptomatic recurrence of arrhythmia, they were systematically asked whether or not they were experiencing any of the following 6 symptoms: palpitation, fatigue, chest pain, shortness of breath, dizziness, or sweating. Patients were required to answer yes or no. A symptom score was created varying from 0 to 6, in increasing order of number of symptoms reported. This was compared for patients receiving either of 2 doses of azimilide or placebo. The relationship between the number of symptoms, heart rate at time of arrhythmia recurrence and treatment was analyzed. Results In 2 separate studies, azimilide at a dose of 125 mg/day significantly reduced the number of symptoms at the time of arrhythmia recurrence compared to placebo. On the other hand, in 2 studies, the dose of 100 mg/day did not significantly reduce symptom burden. The individual symptoms significantly reduced by azimilide125 mg/day were fatigue, shortness of breath, chest pain and dizziness. Palpitations and sweating were not significantly reduced. Modeling of heart rate at the time of arrhythmia recurrence, symptoms and treatment indicated that a small reduction in heart rate with azimilide accounted for only a small part of the symptom reduction. There was another effect of azimilide: an average reduction of 0.38 symptoms ( P < .01) that was independent of heart rate. Conclusion Azimilide (125 mg/day) reduces the number of symptoms reported at the time of AF recurrence.

Clinical predictors and time course of arrhythmia recurrence in patients with early reinitiation of atrial fibrillation after successful internal cardioversion.

Early reinitiation of atrial fibrillation (ERAF) was commonly observed after successful electrical cardioversion, however, the effect of ERAF on the subsequent time course of arrhythmia recurrence remains unclear. The aim of this study was to evaluate the clinical predictors and time course of AF recurrence with respect to the occurrence of ERAF after successful cardioversion. The clinical predictors and time course of AF recurrence were prospectively evaluated in 124 patients (94 men, 30 women; mean age 65 +/- 9 years) with persistent AF (mean AF duration 36 +/- 40 months), who underwent internal cardioversion. After cardioversion, all patients received treatment with sotalol and were monitored for AF recurrence. Successful restoration of sinus rhythm was achieved in 104 (84%) of 124 patients. ERAF was observed in 28 (27%) of 104 patients in whom 26 of them were successfully treated acutely with intravenous sotalol and repeated cardioversion. After a mean follow-up of 26 months, 29 (28%) of 104 patients remained in sinus rhythm. Kaplan-Meier analysis revealed a significantly poorer outcome with regard to the recurrence of AF in patients with ERAF (hazard ratio 1.7,P = 0.03) and in those with AF for more than 3 years (hazard ratio 1.6,P = 0.03). Despite treatment with sotalol, patients with ERAF had a significantly higher AF recurrence rate within the first day (13/26 [50%] vs 12/76 [16%],P < 0.01), but not during long-term follow-up (21/26 [81%] vs 52/76 [68%],P = 0.3). In contrast, patients with AF for more than 3 years had a similar AF recurrence rate within the first day (7/29 [24%] vs 18/73 [25%],P = 1.0), but a significantly higher recurrence rate during long-term follow-up (27/29 [93%] vs 46/73 [37%],P < 0.01). In conclusion, the occurrence of ERAF and long AF duration were independent predictors for AF recurrence after successful internal cardioversion. The difference in the time course of AF recurrence in patients with ERAF from those with long AF duration suggests distinct arrhythmogenic mechanisms.

Atrial fibrillatory frequency predicts atrial defibrillation threshold and early arrhythmia recurrence in patients undergoing internal cardioversion of persistent atrial fibrillation.

This study was conducted to analyze the meaning of AF frequency obtained from the surface ECG for prediction of energy requirements and early arrhythmia relapse in patients undergoing internal cardioversion of persistent AF. Nineteen consecutive patients (mean age 58 +/- 11 years; 11 men, 8 women) with persistent AF (> 7 days) underwent internal cardioversion. A biphasic shock synchronized to the R wave was delivered between two catheters positioned in the high right atrium (HRA) and the coronary sinus (CS). AFfrequency was estimated prior to cardioversion from surface ECG lead V1. After filtering, QRST complexes were subtracted using a template matching and averaging algorithm. The resulting fibrillatory baseline signal was subjected to Fourier transformation, displayed as a frequency power spectrum and the peak frequency was determined in the 3-12 Hzfrequencyband. Atrial defibrillation threshold (ADFT) was determined using a step-up protocol. All patients were cardioverted successfully with a mean ADFT of 7.6 +/- 6.5 J(range 0.5-25). There was a strong positive correlation between fibrillatory frequency and ADFT (R = 0.71, P = 0.001). AF recurrence within 30 days after successful cardioversion occurred in 11 (58%) patients. Receiver operating characteristic (ROC) analysis revealed a fibrillatory frequency > or = 7 Hz to be 64% sensitive and 88% specific to predict AF recurrence. It was observed in 4 (36%) of 11 cases with a fibrillatory frequency < 7 Hz, as opposed to 7 (88%) of 8 cases with a fibrillatory frequency > or = 7 Hz (P = 0.02). Fibrillatory frequency obtained from the surface ECG predicts ADFT and early AF recurrence in patients with persistent AF undergoing internal cardioversion.

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

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. 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 < or = 0.015) and not taking (17/22 patients; P < or = 0.017) antiarrhythmic drugs. Median time between atrial arrhythmia detections for all 65 patients was 10.8 minutes. 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.

Azimilide reduces symptom burden at the time of arrhythmia recurrence in patients with atrial fibrillation

Azimilide reduces symptom burden at the time of arrhythmia recurrence in patients with atrial fibrillation

Atrial fibrillatory frequency predicts atrial defibrillation threshold and early arrhythmia recurrence in patients undergoing internal cardioversion of persistent AF Andreas Bollmann, Maika Mende, Annerose Neugebauer, Dietrich Pfeiffer. University Hospital, Department of Cardiology, Leipzig, Germany, University Hospital, Department of Cardiology, Magdeburg, Germany

Atrial fibrillatory frequency predicts atrial defibrillation threshold and early arrhythmia recurrence in patients undergoing internal cardioversion of persistent AF Andreas Bollmann, Maika Mende, Annerose Neugebauer, Dietrich Pfeiffer. University Hospital, Department of Cardiology, Leipzig, Germany, University Hospital, Department of Cardiology, Magdeburg, Germany

Antiarrhythmic effects of azimilide in atrial fibrillation: efficacy and dose-response

OBJECTIVESThe purpose of this study was to assess the effectiveness of azimilide, a class III antiarrhythmic drug, in reducing the frequency of symptomatic arrhythmia recurrences in patients with atrial fibrillation, atrial flutter or both.BACKGROUNDAtrial fibrillation is an increasingly common disorder of the heart rhythm, and most patients with this problem are identified because they have symptoms associated with their arrhythmia. New antiarrhythmic therapies are needed to treat patients with this problem.METHODSA total of 384 patients with a history of atrial fibrillation, atrial flutter or both were randomly assigned to receive once daily doses of placebo or azimilide; recurrent symptomatic arrhythmias were documented using transtelephonic electrocardiogram (ECG) recording. Azimilide 50 mg, 100 mg or 125 mg was tested; the primary efficacy analysis compared the time to first symptomatic recurrence in the combined azimilide 100 mg and 125 mg dose groups with that in the placebo group using the log-rank test.RESULTSIn the primary efficacy analysis, the time to first symptomatic arrhythmia recurrence was significantly prolonged in the combined azimilide 100 mg and 125 mg daily dose group compared with the placebo group (chi-square 7.96, p = 0.005); the hazard ratio (placebo:azimilide) for this comparison was 1.58 (95% confidence interval [CI] = 1.15, 2.16). In comparisons between individual doses and placebo, the hazard ratio for the 50 mg daily dose was 1.17 (95% CI = 0.83, 1.66; p = 0.37); for the 100 mg group, dose was 1.38 (95% CI = 0.96, 1.98; p = 0.08), and for the 125 mg group, dose was 1.83 (95% CI = 1.24, 2.70; p = 0.002).CONCLUSIONSAzimilide significantly lengthened the symptomatic arrhythmia-free interval in patients with a history of atrial fibrillation, atrial flutter or both.

Arrhythmia recurrence in patients with a healed myocardial infarction who received an implantable defibrillator: analysis according to the clinical presentation

OBJECTIVESThe purpose of this study was to analyze the type of arrhythmia recurrence, based on stored electrograms, in patients with a healed myocardial infarction (MI) who received an implantable defibrillator.BACKGROUNDPrevious studies suggest that patients presenting with cardiac arrest (CA) tend to recur as ventricular fibrillation (VF), whereas those suffering sustained monomorphic ventricular tachycardia (SMVT) tend to recur as SMVT. However, these data have not been confirmed in a homogeneous population of patients with MI.METHODSA total of 88 patients was divided into three groups according to their clinical presentation: SMVT (n = 57), CA (n = 16) or syncope (n = 15).RESULTSThere were no significant differences in clinical characteristics among groups. In the electrophysiologic study SMVT was induced in 93%, 94% and 80% of patients, respectively (p = NS). During the follow-up period, 52% of patients presented a total of 671 episodes of ventricular arrhythmia treated by the defibrillator. All recurrences were as SMVT except for one VF. There were 610 episodes of SMVT treated with antitachycardia pacing, with an effectiveness of 96%. A total of 61 episodes was treated initially with cardioversion. No differences in the probability of recurrence were observed among groups, although the statistical power was low (50%).CONCLUSIONSIn patients with an old infarction and malignant ventricular arrhythmias, the majority of recurrences are due to SMVT independently of the clinical presentation (SMVT, CA or syncope) or the induced arrhythmia at the electrophysiologic study. The programming of an antitachycardia zone seems to be appropriate also for patients who present with CA or syncope.

Influence of beta-blockers on the frequency of arrhythmia recurrences in patients with implantable cardioverter-defibrillator: an intraindividual comparison

We studied retrospectively 60 consecutive recipients of an implantable cardioverter-defibrillator and identified 16 patients who were temporarily on and off beta-blockers (further medication unchanged). An intraindividual analysis revealed that 56% of the patients experienced more arrhythmic episodes during follow-up off beta-blockers compared to 44% while being on beta-blockers. Also, the mean episode frequency during follow-up time on and off beta-blockers was comparable (0.4±0.6 vs. 0.5±0.5, ns).

Predictors of Arrhythmic Death and Cardiac Arrest in the ESVEM Trial

The purpose of this study was to determine if the presenting ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation/cardiac arrest) predicted the type of arrhythmia recurrence in patients treated with antiarrhythmic drugs. In the previously reported Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) trial, there were 486 patients who were randomized to antiarrhythmic drug testing guided by electrophysiological study or by ambulatory ECG monitoring. Use of a defibrillator (implantable cardioverter-defibrillator, ICD) without stored electrograms among 81 patients precluded determination of the type of arrhythmia recurrence; thus these patients were censored at the time of ICD implantation. Of the 486 patients, 381 presented with ventricular tachycardia and 105 with cardiac arrest. Over a 6-year follow-up period, 285 of the 486 patients had an arrhythmia recurrence; of these, 97 had an arrhythmic death or cardiac arrest as a first recurrence. In the current analysis, all 129 arrhythmic deaths/cardiac arrests that occurred any time during follow-up were evaluated as end points. Although univariate analysis suggested that there was an association between the presenting arrhythmia and outcome, multivariate analysis failed to substantiate the predictive value of the presenting arrhythmia. Left ventricular ejection fraction was the single most important predictor of arrhythmic death or cardiac arrest. This information may be an important factor in deciding whether to advise ICD therapy.

Fractal dimension predicts arrhythmia recurrence in patients being treated for life-threatening ventricular arrhythmias

Ambulatory electrocardiographic (Holter) recordings are widely used for arrhythmia detection, risk stratification, and to guide therapy of various arrhythmias. The most common information obtained is the frequency of single ventricular premature complexes (VPCs), couplets, and runs of ventricular tachycardia (VT). Recently, additional useful information has been acquired from Holter recordings: parameters of heart rate variability and fractal dimension (fractal D). ',2 The latter is derived from the application of signal-processing methods that use nonlinear dynamics to assess the time distribution of VPC occurrence.

Inability of the Signal‐Averaged Electrocardiogram to Determine Risk of Arrhythmia Recurrence in Patients with Implantable Cardioverter Defibrillators

Signal-averaged electrocardiography has been used to identify patients at risk for arrhythmic death after myocardial infarction. Since patients with implantable cardioverter defibrillators (ICDs) are at high risk for arrhythmic events, they should also be expected to have a high incidence of abnormal signal-averaged electrocardiograms (SAECGs). However, whether the SAECG can discriminate patients who will have arrhythmia recurrence and receive appropriate ICD shocks from those who will have no recurrence and no shocks is unknown. This study examines the usefulness of the SAECG to separate appropriate users from non-users of the ICD. Fifty patients with ICDs participated in this study. Those who received a shock preceded by symptoms, a shock without preceding symptoms but with electrocardiographic documentation of ventricular fibrillation or ventricular tachycardia, or a shock while asleep were classified as ICD users. All other patients were classified as nonusers. The SAECG was classified as normal if the QRS duration on the standard electrocardiogram was less than or equal to 110 msec and if the total filtered QRS duration was less than 120 msec, the root-mean square voltage of the terminal 40 msec was greater than 25 muV, and the terminal low amplitude signal duration measured less than 38 msec. The SAECG was classified as abnormal if the QRS duration on the standard electrocardiogram was less than or equal to 110 msec and any one of these three criteria were outside the "normal range." The SAECG was classified as indeterminate if the QRS duration on the standard 12-lead electrocardiogram was greater than 110 msec. For the entire group of 50 patients, 8 (16%), 12 (24%), and 30 (60%) had normal, abnormal, and indeterminate SAECGs, respectively. Of the 22 ICD users, 1 (5%), 5 (23%), and 16 (73%) patients had normal, abnormal, and indeterminate SAECGs, respectively. Of the 28 ICD nonusers, 7 (25%), 7 (25%), and 14 (50%) patients had normal, abnormal, and indeterminate SAECGs, respectively. ICD users had lower left ventricular ejection fractions (P = 0.0002), a higher incidence of ventricular tachycardia (P = 0.04), prior exposure to a greater number of antiarrhythmic drugs (P = 0.04), and a lower likelihood for survival (P = 0.02) compared to the ICD nonusers. There was no statistically significant difference between the ICD users and nonusers as stratified by SAECG classification regardless of whether or not the interminate studies were included or excluded from the analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Predictors of efficacy of amiodarone and characteristics of recurrence of arrhythmia in patients with sustained ventricular tachycardia and coronary artery disease.

The value of serial electropharmacologic testing during long-term oral amiodarone therapy for prediction of long-term drug efficacy as well as characteristics of arrhythmia recurrence is controversial. One-hundred four consecutive patients with coronary artery disease and sustained ventricular tachyarrhythmias (VT) underwent initial electrophysiologic (EP) evaluation in the drug-free state and again after an amiodarone loading period of 25 +/- 14 days (mean +/- SD). Twenty-six patients (25%) had no inducible ventricular tachyarrhythmia during therapy with amiodarone (VT control group), whereas arrhythmia inducibility persisted in the remaining 78 patients (VT noncontrol group). During 17.4 +/- 13.7 months of follow-up, two patients in the VT control group either had VT recurrence or died suddenly compared with 21 VT recurrences and eight sudden cardiac deaths in the VT noncontrol group (actuarial event rates at 36 months of 0.11 and 0.56, respectively, p = .0065). The cycle lengths of recurrent VT in these 21 patients in the VT noncontrol group were compared with those observed at final EP testing. A significant linear correlation was demonstrated (r = .76, p = .0001). Subgroup analysis of patients in the VT noncontrol group showed no EP predictors of outcome, including cycle length of induced VT. However, patients dying suddenly during the follow-up period had a higher prevalence of new or worsening congestive heart failure (75%) compared with patients with VT recurrence (19%) or those with no arrhythmic event (29%) (p less than .02).2off

Effectiveness of pacemaker treatment in the bradycardia-tachycardia syndrome

Thirty-one patients with the bradycardia-tachycardia syndrome treated with permanent ventricular pacemakers were studied. All were symptomatic before pacemaker insertion, and their symptoms were not controlled with drug therapy alone. Bradycardia and tachycardia associated with multiple arrhythmias were present in all cases; heart rate was less than 40 beats/min in 58 percent of patients and more than 140 beats/min in 71 percent. Conduction abnormalities were present in 61 percent. After insertion of a demand pacemaker, 27 patients (87 percent) were symptom-free for 1 month to 5 years. Although four patients with a normally functioning pacemaker continued to have recurrent arrhythmia, the presence of a pacemaker facilitated further pharmacologic treatment of the disturbance. Pacemaker insertion has been found to be a satisfactory method of treating the symptoms and preventing the recurrence of arrhythmias in patients with the bradycardia-tachycardia syndrome by allowing the use of digitalis and other antiarrhythmic agents.