Improved suppression of recurrent atrial fibrillation with dual-site right atrial pacing and antiarrhythmic drug therapy

OBJECTIVES: We compared the safety, tolerance and effectiveness of overdrive high right atrial (RA), dual-site RA and support (DDI or VDI) pacing (SP) in patients with symptomatic atrial fibrillation (AF) and bradycardias. BACKGROUND: Optimal pacing methods for AF prevention remain unclear. METHODS: Patients (n = 118) were randomized to each of three pacing modes in a crossover trial. RESULTS: Mode adherence was superior for dual-site RA (5.8 months) compared with SP (3.3 months; p < 0.001) and high RA pacing (4.7 months; p = 0.006). Adverse event-free survival improved with dual-site RA (p = 0.007 vs. SP) and was comparable to high RA (p = 0. 75). AF-free survival trended to improve with dual-site RA (hazard ratio [HR] 0.715, p = 0.07 vs. SP) but not high RA (HR = 0.71, p = 0.19) or when dual-site RA was compared with high RA (HR = 0.835, p = 0.175). Time-to-recurrence was longer in dual-site RA (1.77 months) compared with high RA (0.62 months, p < 0.09) or SP (0.44 months, p < 0.05). In antiarrhythmic drug-treated patients, dual-site RA reduced recurrence risk compared with SP (HR = 0.638, p = 0.011) and high RA (HR = 0.669, p = 0.06). In patients with < or =1 AF event/week, dual-site RA improved AF suppression (HR = 0.464, p = 0.004 vs. SP; HR = 0.623, p = 0.006 vs. high RA). Dual-site RA improved AF-free and mode survival (p < 0.03 vs. high RA, p < 0.001 vs. SP) and reduced asymptomatic AF (p < 0.01 vs. high RA). CONCLUSION: Dual-site RA is safe and better tolerated than high RA and SP. In patients on antiarrhythmics, dual-site RA prolonged and high RA trended to prolong time-to-recurrent AF compared with SP. Dual-site RA provides superior symptomatic and asymptomatic AF prevention compared with high RA in patients with symptomatic AF frequency of < or =1/week.     

Syncope in patients with atrial flutter during treatment with class Ic antiarrhythmic drugs

We describe 2 atrial flutter (AFL) patients with syncope during treatment with class Ic antiarrhythmic drugs. During the syncope, 1:1 atrioventricular (AV) conduction during AFL preceded a wide QRS tachycardia. The class Ic drugs, flecainide and pilsicainide, slowed the atrial rate, resulting in AFL with 1:1 AV conduction, and the width of the QRS complexes became wider during the tachycardia. Syncope was abolished after successful radiofrequency catheter ablation of the AFL. These potential proarrhythmic effects of the class Ic drugs should be taken into account in AFL patients, and concomitant use of beta-blocking agents would be critical to prevent proarrhythmias.     

Acute effects of a class IA antiarrhythmic drug on the ventricular evoked response amplitude in patients with cardiac pacemakers

Some newer cardiac pacemakers are able to control the efficacy of the ventricular pacing pulse beat by beat and to adjust the ventricular output to the actual pacing threshold. This capture verification is based on the detection of the ventricular evoked response amplitude, which has to be detected immediately after the pacing pulse. The sensitivity of the pacemaker to detect the evoked response amplitude must be adjusted individually to avoid the simultaneous detection of lead polarization. The aim of the present study was to evaluate the acute effects of a class IA antiarrhythmic drug on the evoked response amplitude and polarization in 13 pacemaker patients. The implanted pacemaker was the VVIR pacemaker Regency (St. Jude Medical), which provides the automatic capture verification algorithm Autocapture. The patients received 50 mg of ajmaline intravenously within 1 min. The evoked response amplitude and polarization were measured before and 2, 4, 6 and 8 min after ajmaline injection. The evoked response amplitude significantly decreased from 8.0 +/- 4.0 mV to a minimum value of 6.4 +/- 3.1 mV 2 min after drug administration. The decrease remained significant from the end of the application up to 6 min. The recommended sensitivity setting for the evoked response significantly (p < 0.05) decreased from 4.0 +/- 2.3 mV before to 3.1 +/- 1.3 mV 2 min after administration. No significant changes were observed for polarization. After the ajmaline application in 2 patients, the pacemaker recommended the deactivation of Autocapture for 9 min in 1 patient and 12 min in the other. The reasons were a decrease in the evoked response amplitude from 3.1 to 1.9 mV and from 9.0 to 5.7 mV, respectively, with a polarization ranging to about 3.0 mV. In conclusion, the ajmaline injection decreased the evoked response amplitude for some minutes. These findings indicate that antiarrhythmic drugs can alter the automatic capture verification function.     

Transesophageal atrial pacing: a first-choice technique in atrial flutter therapy

Here we report on a study of 181 episodes of spontaneous atrial flutter (AF) (mean atrial cycle length 250 +/- 32 msec) treated by transesophageal atrial pacing (TAP) in 138 patients (92 men and 46 women; mean age 59.5 +/- 12.6 years). TAP was effective in 163 episodes (90%); sinus rhythm resumption was immediate in 36 (19.9%) and followed a short period of atrial fibrillation in 64 (35.3%); in 63 episodes (34.8%) a stable atrial fibrillation was obtained. TAP was unsuccessful in 18 cases (10%). All the patients tolerated the procedure well. A statistical elaboration with the Fisher exact test did not evidence a correlation between efficacy and age, sex, atrial cycle length, or underlying heart disease but showed a significant correlation between efficacy and AF duration of less than 1 day (p less than 0.05) and absence of antiarrhythmic pharmacologic pretreatment (p less than 0.01). These data strongly support the immediate first-choice use of TAP in AF therapy.     

Excitable gap composition in the presence of antiarrhythmic drugs in common human atrial flutter

BACKGROUND AND OBJECTIVE: Recurrence of atrial flutter (AFl) on antiarrhythmic drugs is frequently observed. To determine the reasons for drug inefficacy, the electrophysiological parameters of AFl were studied in eight patients without drug, six patients on sotalol (Sot), eight patients on amiodarone (Amio) and four patients on propafenone (PPF) who presented to the electrophysiology laboratory for conversion of AFl by rapid atrial pacing. METHODS: A quadripolar electrode catheter was positioned in the right atrium in the pathway of the AFl circuit. The duration and composition of the excitable gap (EG) were determined by premature stimuli during AFl. RESULTS: The EG in AFl recurring on Sot (80 +/- 25 ms), Amio (78 +/- 13 ms) and PPF (83 +/- 26 ms) was not significantly different from that without drug (88 +/- 14 ms). Furthermore, a fully excitable portion of the EG was present whether with or without drug. CONCLUSIONS: AFl recurrence on Amio, PPF or Sot is associated with the continued presence of an EG and fully excitable portion. These findings explain the persistent viability of the AFl circuit despite drug therapy in these patients.     

Demonstration of macroreentry and feasibility of operative therapy in the common type of atrial flutter

Two patients are described who had recurrent and long-standing atrial flutter of the common type and were referred for electrophysiologic testing and surgical management. In both patients, atrial flutter could be initiated and terminated by programmed stimulation. Atrial endocardial mapping showed earliest activation during flutter at the orifice of the coronary sinus, with activity proceeding to the low atrial septum, high lateral right atrium and low right atrium, respectively. Programmed atrial extrasystoles from the high right atrium at a time when the atrial septal region was refractory advanced atrial flutter in proportion to prematurity of the extrastimulus, while maintaining the low to high activation sequence. Intraoperatively, epicardial atrial mapping revealed a large right atrial reentrant circuit beginning in the posteroseptal region and proceeding superiorly and laterally through the right atrial free wall before returning to its starting point. The narrowest part of the circuit and that showing relatively slow conduction during atrial flutter was observed in the low right atrial tissue between the tricuspid valve ring and the orifices of the inferior vena cava and proximal coronary sinus, respectively. Cryosurgical ablation around the orifice of the coronary sinus and surrounding atrial wall has prevented recurrent atrial flutter over short term follow-up in both patients, although 1 of the patients has required antiarrhythmic therapy for postoperative atrial fibrillation.     

Treatment of atrial flutter and rapid atrial tachycardia with transesophageal atrial pacing

Eight patients with atrial flutter (AF) and rapid atrial tachycardia (AT) (5 common AF, 1 uncommon AF and 2 AT) were treated with transesophageal atrial pacing (TEAP). In 5 patients no antiarrhythmic agent was used during this study, and in 3 patients procainamide was administrated intravenously. Conversion to sinus rhythm was successfully achieved in 7 patients (5 common AF and 2 AT). Two patients were converted to sinus rhythm immediately after pacing, and transient atrial fibrillation was induced before conversion to sinus rhythm in 5 patients. TEAP failed to terminate the arrhythmia in 1 patient with uncommon AF. Administration of procainamide reduced the atrial rate in 2 common AF and 1 AT, which were successfully converted to sinus rhythm by TEAP, but induced a rapid ventricular response in 2 patients, one of whom also developed hypotension before conversion. No significant complication due to TEAP was observed in this study. In conclusion, TEAP is a noninvasive method with fewer complications and has nearly the same high efficacy for converting AF and rapid AT to sinus rhythm as DC cardioversion or transvenous atrial pacing.     

Predictors of atrial flutter with 1:1 conduction in patients treated with class I antiarrhythmic drugs for atrial tachyarrhythmias

OBJECTIVES: The purpose of the study was to look for the predictor factors of atrial proarrhythmic effects of class I antiarrhythmic drugs. BACKGROUND: Class I antiarrhythmic drugs may induce or exacerbate cardiac arrhythmias. The predictors of ventricular proarrhythmia are known. The predictors of atrial flutter with 1:1 conduction are unknown. METHODS: Clinical history, EGG, signal-averaged EGG (SAECG) and electrophysiologic study were analysed in 24 cases of 1:1 atrial flutter with class I AA drugs and in 100 control patients without history of 1:1 atrial flutter with class I AA drugs. RESULTS: The ages of patients varied from 46 to 78 years. Underlying heart disease was present in nine patients. The surface EGG revealed the presence of a short PR interval (PR<0.13 ms), visible in leads V5, V6 in eight (35%) patients with normal P wave duration; in other patients with prolonged P wave duration, PR seemed normaL On SAECG recording, there was a pseudofusion between P wave and QRS complex. The electrophysiologic study revealed some signs indicating a rapid AV nodal conduction (short AH interval or rate of 2nd degree AV block at atrial pacing >200 beats/mm) in 19 of the 23 studied patients. All patients, except one, had at least one sign indicating a rapid AV nodal conduction (short PR and/or P wave-QRS complex continuity on SAECG). In the control group, seven patients (7%) had a short PR interval (P<0.01) and 11 (11%) had a pseudofusion between P wave and QRS complex on SAECG (P<0.001). The P wave-QRS complex pseudofusion on SAECG had a sensitivity of 100% and a specificity of 89% for the prediction of an atrial proarrhythmic effect with class I antiarrhythmic drug. CONCLUSION: We recommend avoiding class I AA drugs in patients with a short PR interval on surface EGG and to record SAECG in those with apparently normal PR interval to detect a continuity between P wave and QRS complex, which could indicate a rapid AV nodal conduction, predisposing to 1:1 atrial flutter with the drug.     

New advances in class III antiarrhythmic drug therapy

In the past 2 years, significant advances have been made in class III antiarrhythmic drug therapy. In patients with ventricular arrhythmias and implantable cardioverter defibrillators (ICDs), antiarrhythmic agents are increasingly being used as adjunct therapy to decrease the frequency of ICD discharges. Sotalol was recently shown to be effective in reducing tachyarrhythmias in patients with ICDs. Intravenous amiodarone is being used for the acute treatment of unstable ventricular arrhythmia and is being investigated for the treatment of acute out-of-hospital cardiac arrest. Class III agents are increasingly being used for prophylaxis in patients who have atrial fibrillation or atrial flutter, and data point to an important role for these agents in reducing supraventricular tachyarrhythmias after cardiac surgery. Future studies will need to directly compare these agents with pure anti-adrenergic maneuvers in postoperative patients. In addition to terminating atrial fibrillation and atrial flutter, ibutilide significantly reduces human atrial defibrillation thresholds and increases the percentage of patients who can be cardioverted from atrial fibrillation to sinus rhythm. The US Food and Drug Administration is expected to approve dofetilide for clinical use soon, and it is currently reviewing azimilide (which seems to be devoid of frequency-dependent effects on repolarization) for prophylaxis against atrial fibrillation and atrial flutter. Dronedarone, tedisamal, and trecetilide are now under active study intended to determine their usefulness in patients with cardiac arrhythmias. Experimental studies are ongoing to identify pharmacologic agents that will selectively prolong repolarization in the atria without exerting electrophysiologic effects in the ventricles.     

Failure of rapid atrial pacing in the conversion of atrial flutter

Rapid atrial pacing, at rates of 150 to 600/min with stimulus strength up to 15 ma, was attempted in 15 patients with atrial flutter. In 13 of the patients, atrial capture was achieved with changes in both atrial and ventricular rates. In 7 of these, flutter resumed upon cessation of pacing. In the other 6, rapid atrial pacing produced atrial fibrillation which persisted until cardioversion. In 2 patients, atrial capture could not be obtained because of increased atrial refractoriness secondary to flutter. Thus, rapid atrial pacing was ineffective in converting atrial flutter to normal sinus rhythm in all 15 patients. This was in contrast to direct-current cardioversion which was successful in 12 of the patients, in all of whom stable sinus rhythm developed. The 3 patients who did not undergo cardioversion subsequently experienced spontaneous conversion to sinus rhythm. These results suggest that rapid atrial pacing has little place in the management of atrial flutter.     

Prospective randomized comparison of antiarrhythmic therapy versus first-line radiofrequency ablation in patients with atrial flutter

BACKGROUND

Despite the high success rate of radiofrequency (RF) ablation, pharmacologic therapy is still considered the standard initial therapeutic approach for atrial flutter.

OBJECTIVE

We prospectively compared the outcome at follow-up of patients with atrial flutter randomly assigned to drug therapy or RF ablation.

METHODS

Patients with at least two episodes of symptomatic atrial flutter in the last four months were randomized to regimens of either antiarrhythmic drug therapy or first-line RF ablation. After institution of therapy, end points included recurrence of atrial flutter, rehospitalization and quality of life.

RESULTS

A total of 61 patients entered the study, 30 of whom were randomized to drug therapy and 31 to RF ablation. After a mean follow-up of 21 ± 11 months, 11 of 30 (36%) patients receiving drugs were in sinus rhythm, versus 25 of 31 (80%) patients who underwent RF ablation (p < 0.01). Of the patients receiving drugs, 63% required one or more rehospitalizations, whereas post-RF ablation, only 22% of patients were rehospitalized (p < 0.01). Following RF ablation, 29% of patients developed atrial fibrillation which was seen in 53% of patients receiving medications (p < 0.05). Sense of well being (pre-RF 2.0 ± 0.3 vs. post-RF 3.8 ± 0.5, p < 0.01) and function in daily life (pre-RF 2.3 ± 0.4 vs. post-RF 3.6 ± 0.6, p < 0.01) improved after ablation, but did not change significantly in patients treated with drugs.

CONCLUSION

In a selected group of patients with atrial flutter, RF ablation could be considered a first-line therapy due to the better success rate and impact on quality of life, the lower occurrence of atrial fibrillation and the lower need for rehospitalization at follow-up.     

The use of atrial pacing to induce atrial fibrillation and flutter

We studied the clinical and electrophysiological significance of induction of atrial fibrillation or atrial flutter by atrial electrical stimulation. Our atrial fibrillation/flutter induction protocol included incremental atrial pacing up to a rate of 200 beats/min, ramp up to 250 and 300 beats/min, and bursts up to 600 beats/min. The end point was sustained atrial fibrillation/flutter induction (30 sec). We performed a provocative study on 72 subjects previously divided into three groups: the first was the control group; the second comprised patients with spontaneous paroxysmal atrial fibrillation/flutter; the third comprised patients without spontaneous atrial fibrillation/flutter, but with pathologies assumed to put them at risk for atrial fibrillation/flutter. We were unable to induce sustained atrial fibrillation/flutter in the control group, but were able to induce these arrhythmias in 95% of the subjects with spontaneous atrial fibrillation/flutter. Thus the methods have a sensitivity of 95% and a specificity of 100%. We were also able to induce atrial fibrillation/flutter in 57% of patients at risk for atrial fibrillation/flutter, that is a lower incidence than patients with spontaneous episodes. When sustained atrial fibrillation/flutter could be induced, it was well tolerated and stopped spontaneously in less than 24 hours without treatment. The technique thus involves no risk and demonstrates that antiarrhythmic therapy is usually superfluous in interrupting induced atrial fibrillation/flutter.     

Role of combination drug therapy with a class IC antiarrhythmic agent and mexiletine for ventricular tachycardia

The combination of mexiletine and a class IC antiarrhythmic agent (encainide, propafenone or flecainide) was evaluated by electrophysiologic testing in 14 patients with a history of sustained ventricular tachycardia whose tachycardia remained inducible during therapy with the class IC drug alone. During the control drug-free state, all patients had inducible ventricular tachycardia, with a mean cycle length of 260 ms (range 190 to 400). During monotherapy with the IC agent the tachycardia remained inducible in each patient, but there was a significant increase in the cycle length to 340 ms (240 to 500) (p less than 0.001). The effective refractory period of the ventricle was not altered. Treatment with mexiletine (oral in 13 and intravenous in 1) was begun and electrophysiologic testing was repeated. Ventricular tachycardia in one patient was rendered noninducible and one patient had arrhythmia aggravation. The tachycardia in the remaining 12 patients remained inducible but its average cycle length increased further to 392 ms (340 to 460) (p = NS). Nine patients had rate slowing and the average cycle length of the ventricular tachycardia in this group was significantly increased (302 to 388 ms, p less than 0.05). The average effective refractory period was significantly increased during combination therapy (267 ms) compared with no drug therapy (235 ms) and therapy with the class IC drug alone (247 ms) (p less than 0.05). After a mean follow-up interval of 22 months, seven patients continue on the combined treatment and have no ventricular tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Radiofrequency ablation of atrial flutter due to administration of class IC antiarrhythmic drugs for atrial fibrillation

In selected patients, atrial fibrillation (AF) converts to atrial flutter (AFI) due to treatment with class IC antiarrhythmic drugs. In this study, we prospectively investigated the effects of AFI ablation and continuation of drug therapy in patients with AF who developed AFI due to long-term administration of class IC antiarrhythmic drugs. The study population consisted of 187 patients from an AF registry with paroxysmal AF who were orally treated with flecainide (n = 96) or propafenone (n = 91). Twenty-four patients (12.8%) developed AFI during the course of treatment. In 20 of these patients (10.7%), electrophysiologic study revealed typical AFI. These patients underwent radiofrequency ablation of AFI. Ablation failed in 1 patient. All patients continued preexisting drug treatment. Recurrence of AF was assessed by ambulatory Holter monitoring and serial questionnaires. During a mean follow-up of 11 +/- 4 months, the incidence of AF episodes was significantly lower in patients with a combined therapy (2.7 +/- 3.6 per year) than in control subjects with a sole drug treatment (7.8 +/- 9.2 per year, p <0.05) and than before therapy (10.2 +/- 5.4 per year, p <0.001). Subgroup analysis revealed that 7 patients (36.8%) remained symptom free with no evidence of atrial tachyarrhythmia. Eight additional patients (42.1%) had ongoing paroxysmal AF, however, with a significantly lower incidence of AF episodes than before therapy (2.3 +/- 1.6 per year vs 11.5 +/- 5.0 per year, p <0.001). In the remaining 4 patients (14.7%), no beneficial effect of AFI ablation was found. It is concluded that in patients with AF who develop typical AFI due to administration of class IC antiarrhythmic agents, a combined therapy with catheter ablation of AFI and continuation of drug treatment is highly effective in reducing occurrence and duration of atrial tachyarrhythmias.     

Current status of class III antiarrhythmic drug therapy

Studies in animal models, as well as clinical experience with amiodarone and sotalol, suggest that action potential prolongation may be a useful antiarrhythmic mode of action. A number of agents that produce this class III effect are currently under development. The single greatest liability for further development of this group of drugs is the occasional, and apparently unpredictable, development of exaggerated QT prolongation and polymorphic ventricular tachycardia (torsades de pointes). Available data suggest that QT interval prolongation is not a good indicator of whether or not a class III antarrhythmic will suppress a target arrhythmia; however, exaggerated QT prolongation is a predictor of torsades de pointes. Further studies to delineate the mechanism underlying the development of torsades de pointes might lead to safer and more effective antiarrhythmic drugs.     

Pronounced effect of procainamide on clockwise right atrial isthmus conduction compared with counterclockwise conduction: possible mechanism of the greater incidence of common atrial flutter during antiarrhythmic therapy

INTRODUCTION: It has been shown that the induction rates of common and reversed common atrial flutter are comparable during baseline control study, whereas the rate is significantly greater for common flutter than reversed common flutter during administration of antiarrhythmic agents. The mechanism of this discrepancy is not known. METHODS AND RESULTS: The study consisted of 15 patients (group 1) with clinically documented common atrial flutter either with (n = 10) or without (n = 5) Class I antiarrhythmic therapy, and 15 patients with paroxysmal supraventricular tachycardia (group 2). Bidirectional conduction velocity and minimal pacing cycle length of 1:1 conduction during incremental pacing from both the low lateral right atrium and coronary sinus were assessed. The response of these variables to procainamide was analyzed in correlation with the induction rate of each type of flutter during the pacing protocol. Conduction velocity in the clockwise (CW) direction was significantly slower for all pacing cycle lengths than conduction velocity in the counterclockwise (CCW) direction in group 1 but was similar in group 2. Minimal pacing cycle length of 1:1 conduction did not differ between CW and CCW conduction in either group. However, in group 1, minimal pacing cycle length of 1:1 conduction of CW conduction was prolonged to a greater degree after procainamide than that of CCW conduction. There also was a significant increase in the induction rate of common flutter. This preferential effect of procainamide on CW conduction was not observed in group 2. CONCLUSION: CW conduction over the isthmus is preferentially influenced by procainamide compared with CCW conduction, which may explain the greater incidence and induction probability of common flutter during antiarrhythmic therapy.     

对比普通与灌注冷却射频消融电极在Ⅰ型心房扑动消融中的作用

目的　对比普遍与灌注冷却射频消融电极在Ⅰ型心房扑动（CAFL）消融中的作用。方法　60例CAFL患者随机分为两组普通射频消融电极治疗组（CRF）和灌注冷却射频消融电极治疗组（IRF）,分别比较两组取得下腔静脉与三尖瓣环峡部双向阻滞的手术时间、X线照射时间、射频消融放电次数及放电时间、并观察消融时电能、阻抗以及温度的改变。结果　IRF组的手术时间、X线照射时间、射频消融时间均较CRF组短（P<0.01）,放电次数也少（P<0.05）,IRF组消融过程中阻抗变化小、电能稳定,温度差异不明显,而CRF组则相反,且有19例出现碳化现象,两组痛感差异无显著性,均无心包填塞、栓塞等并发症。结论　灌注冷却射频消融电极在CAFL消融中优越于普通射频消融电极。