F E Marchlinski

Comparison of antiarrhythmic drug therapy and radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation: A randomized controlled trial

CONTEXT Antiarrhythmic drugs are commonly used for prevention of recurrent atrial fibrillation (AF) despite inconsistent efficacy and frequent adverse effects. Catheter ablation has been proposed as an alternative treatment for paroxysmal AF. OBJECTIVE To determine the efficacy of catheter ablation compared with antiarrhythmic drug therapy (ADT) in treating symptomatic paroxysmal AF. DESIGN, SETTING, AND PARTICIPANTS A prospective, multicenter, randomized (2:1), unblinded, Bayesian-designed study conducted at 19 hospitals of 167 patients who did not respond to at least 1 antiarrhythmic drug and who experienced at least 3 AF episodes within 6 months before randomization. Enrollment occurred between October 25, 2004, and October 11, 2007, with the last follow-up on January 19, 2009. INTERVENTION Catheter ablation (n = 106) or ADT (n = 61), with assessment for effectiveness in a comparable 9-month follow-up period. MAIN OUTCOME MEASURES Time to protocol-defined treatment failure. The proportion of patients who experienced major treatment-related adverse events within 30 days of catheter ablation or ADT was also reported. RESULTS At the end of the 9-month effectiveness evaluation period, 66% of patients in the catheter ablation group remained free from protocol-defined treatment failure compared with 16% of patients treated with ADT. The hazard ratio of catheter ablation to ADT was 0.30 (95% confidence interval, 0.19-0.47; P < .001). Major 30-day treatment-related adverse events occurred in 5 of 57 patients (8.8%) treated with ADT and 5 of 103 patients (4.9%) treated with catheter ablation. Mean quality of life scores improved significantly in patients treated by catheter ablation compared with ADT at 3 months; improvement was maintained during the course of the study. CONCLUSION Among patients with paroxysmal AF who had not responded to at least 1 antiarrhythmic drug, the use of catheter ablation compared with ADT resulted in a longer time to treatment failure during the 9-month follow-up period. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00116428.

Role of triple extrastimuli during electrophysiologic study of patients with documented sustained ventricular tachyarrhythmias.

Electrophysiologic studies were performed in 172 consecutive patients for evaluation of documented sustained ventricular tachyarrhythmias. One hundred thirteen patients presented with sustained ventricular tachycardia that was hemodynamically stable, and 59 patients presented with cardiac arrest. Seventy-one patients without previously documented or suspected ventricular arrhythmias were also studied to determine the specificity of our electrophysiologic study protocol. The stimulation protocol included single, double, and triple right ventricular extrastimuli and rapid ventricular pacing at multiple cycle lengths performed at one or more right ventricular sites. Stimulation was performed at one or more left ventricular sites in patients with documented spontaneous arrhythmias when right ventricular programmed stimulation failed to induce sustained ventricular tachycardia. Ventricular tachyarrhythmias were induced in 110 (97%) of the patients who presented with sustained ventricular tachycardia, in 48 (81%) of the patients who presented with cardiac arrest, and in 28 (40%) of the patients without documented spontaneous arrhythmias. Right ventricular triple extrastimuli induced tachycardia in 22% of patients who presented with sustained ventricular tachycardia vs 46% of those who presented with cardiac arrest (p less than .001). Left ventricular stimulation was required for tachycardia induction in 3% of patients with stable tachycardia vs 19% of those with cardiac arrest (p less than .01). Triple extrastimuli induced 57% of tachycardias in the 28 patients without spontaneous arrhythmias, and virtually all of these tachycardias were polymorphic and nonsustained. The cycle lengths of tachycardias induced in each group by double and triple extrastimuli were similar, but the tachycardias induced in patients with cardiac arrest were significantly faster than those induced in the ventricular tachycardia group (mean cycle length 218 vs 291 msec, p less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Endocardial catheter mapping in patients in sinus rhythm: relationship to underlying heart disease and ventricular arrhythmias.

Catheter mapping during sinus rhythm was performed in 132 patients with coronary artery disease and 26 patients with congestive noncoronary cardiomyopathy. Each of the patients had a clinical history of one of the following: no ventricular arrhythmia, nonsustained ventricular tachycardia, cardiac arrest, or sustained ventricular tachycardia. The characteristics of the endocardial electrogram and other measured indexes of slow endocardial conduction were compared between patients with different types of disease and in different arrhythmia groups to determine if differences existed. The cardiomyopathic group had a higher percent of normal endocardial electrograms than the coronary artery disease group, with no evidence of slow endocardial conduction. The sustained ventricular tachycardia group exhibited a greater percent of abnormal endocardial electrograms and more evidence of slow endocardial conduction, distinguishing this group from the three other arrhythmia groups. We conclude the following: The underlying electrophysiologic substrate varies in patients with different ventricular arrhythmias. It is therefore inappropriate to analyze all patients with ventricular arrhythmias as a single group. Patients with congestive noncoronary cardiomyopathy, regardless of the type of their arrhythmia, have a relatively normal endocardium. Those patients with serious ventricular arrhythmias should not be considered candidates for surgery directed at removing abnormal endocardium.

Endocardial activation of left bundle branch block.

Endocardial catheter mapping was performed in 18 patients with left bundle branch block (LBBB). Four patients had no organic heart disease (group I), six had cardiomyopathy (group II), and eight had coronary artery disease and previous infarction (group III). Twelve patients had one septal site of left ventricular endocardial breakthrough, while six had two left ventricular endocardial breakthrough sites, with one site always being septal. There was no significant difference among the groups with respect to time of left ventricular breakthrough (group I, 44 msec after the onset of the QRS complex; group II, 58 msec; and group III, 51 msec). Total left ventricular endocardial activation time was significantly longer in group III (119 msec) than group I (81 msec; p less than .05) and group II (61 msec; p less than .001). Duration of total right ventricular endocardial activation was 36 msec (seven patients). The final site of right ventricular activation was at 44 msec after the onset of the QRS complex. We conclude that (1) right ventricular activation occurs before initiation of left ventricular activation in patients with LBBB, (2) left ventricular endocardial activation in patients with LBBB most likely occurs as a result of right-to-left transseptal activation, (3) left ventricular endocardial activation sequence in patients with LBBB is heterogeneous, and (4) patients with coronary artery disease and LBBB have significantly longer total left ventricular endocardial activation times than patients with no organic heart disease or those with cardiomyopathies.

The value of catheter mapping during sinus rhythm to localize site of origin of ventricular tachycardia.

We assessed the value of endocardial catheter mapping in 52 patients in sinus rhythm and with 102 morphologically distinct ventricular tachycardias. The local bipolar electrograms from various regions of the left ventricle were assessed and quantitatively classified with respect to the characteristics of amplitude and duration. With the use of this assessment we found that electrograms from the site of origin were of significantly lower amplitude and longer duration; however, because such an overlap occurred with electrograms that were not from sites of origin, this does not serve as a useful clinical marker. Various types of electrograms, including normal, abnormal, fractionated, abnormal late, fractionated late, and longest, were evaluated with respect to sensitivity, specificity, and positive predictive value. None of these types possessed the ability to reliably localize the site of origin of ventricular tachycardia. We therefore conclude that endocardial catheter mapping during sinus rhythm is not useful as a guide in localized surgical therapy of ventricular tachycardia. Surgery guided only by the results of mapping during sinus rhythm would result in a more extensive excision than that directed by maps obtained during ventricular tachycardia and in some cases would result in the exclusion of the area considered to be the site of origin of the tachycardia.

Sustained ventricular tachycardia in patients with idiopathic dilated cardiomyopathy: electrophysiologic testing and lack of response to antiarrhythmic drug therapy.

Eleven consecutive patients with idiopathic dilated cardiomyopathy and spontaneous, sustained ventricular tachycardia (VT) of uniform morphology underwent programmed ventricular stimulation and serial antiarrhythmic drug testing. The mean ejection fraction was 30 +/- 6.4%. Sustained VT was induced by programmed electrical stimulation in all 11 patients. A mean of 3.7 +/- 2.4 antiarrhythmic drugs were evaluated by programmed stimulation, including at least one experimental agent in eight patients. In nine of 11 patients VT remained inducible on all drug therapy. During a mean follow-up period of 21 +/- 14 months there were four sudden deaths and two patients with recurrences of VT. In all six patients with sudden death or recurrence of VT, the arrhythmia remained inducible on drug therapy. Three patients who died suddenly had a hemodynamically stable, induced tachycardia on antiarrhythmic therapy. Of eight patients treated with amiodarone, only two were successfully treated. We conclude that in patients with sustained VT and idiopathic dilated cardiomyopathy, VT can be induced by programmed electrical stimulation. VT will usually remain inducible on antiarrhythmic therapy, and sudden death can occur despite slowing and improved tolerance of the induced arrhythmia. Amiodarone may have limited efficacy, and more aggressive therapy, such as surgery or implantation of an automatic internal defibrillator, should be considered in this patient population.

Nonsustained ventricular tachycardia in patients with coronary artery disease: role of electrophysiologic study.

Sixty-two consecutive patients with chronic coronary artery disease referred for evaluation of nonsustained ventricular tachycardia (VT) underwent electrophysiologic studies. Sustained VT was induced by one to three ventricular extrastimuli in 28 patients (45%). Therapy was guided by the results of electrophysiologic testing in 44 patients: 19 patients without inducible sustained VT received no antiarrhythmic therapy, and 25 patients with inducible sustained or symptomatic nonsustained VT received therapy guided by the results of electrophysiologic studies. The results of electrophysiologic studies were ignored by physicians for a second group of 18 patients: four had inducible sustained VT but received no antiarrhythmic therapy, and 14 had inducible sustained or nonsustained VT and received antiarrhythmic therapy not guided by results of electrophysiologic testing. After a mean follow-up period of 28 months, 11 patients had died suddenly. Seven of the 11 patients who died suddenly had inducible sustained VT. Three of 44 patients in the group receiving therapy guided by electrophysiologic studies died suddenly versus eight of 18 in the group receiving therapy not guided by electrophysiologic studies (p = .001). Only one of 19 patients without inducible sustained VT who were not treated experienced sudden death. Two of four patients with inducible sustained VT who did not receive antiarrhythmic therapy died suddenly. Multivariate analysis of the relationship of induced arrhythmias, left ventricular ejection fraction, site of myocardial infarction, history of syncope, or type of antiarrhythmic therapy to outcome revealed a greater than twofold increased risk for sudden cardiac death in patients whose therapy was not guided by results of electrophysiologic study.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormal signal-averaged electrocardiograms in patients with nonischemic congestive cardiomyopathy: relationship to sustained ventricular tachyarrhythmias.

We assessed whether signal-averaged electrocardiography could identify patients with sustained ventricular arrhythmias in 41 patients with non-ischemic cardiomyopathy. Twelve of these patients presented with sustained ventricular arrhythmia and 29 patients had no history of sustained ventricular arrhythmias. The mean ejection fractions in the groups were 30 +/- 9% and 24 +/- 9%, respectively. Results were compared with signal-averaged electrocardiograms in 55 normal individuals. The filtered QRS duration was longest in patients with sustained ventricular arrhythmias (130.2 +/- 19.5 vs 105.0 +/- 13.1 msec in the group without sustained ventricular arrhythmia, p less than .001 and 95.9 +/- 9.1 in the normal group, p less than .001). The voltage in the last 40 msec of the filtered QRS was lower in the sustained ventricular arrhythmia group (11.3 +/- 9.3 microV) than the group without sustained ventricular arrhythmia (53.5 +/- 28.3 microV; p less than .001) or the normal group (53.7 +/- 25.2 microV; p less than .001). Eighty-three percent of patients in the sustained ventricular arrhythmia group had an abnormal signal-averaged electrocardiogram characterized by both a long filtered QRS duration and a late potential of low voltage level; only 2% of normal subjects and 14% of patients without sustained ventricular arrhythmias had an abnormal signal-averaged electrocardiogram. The signal-averaged electrocardiogram can identify patients with nonischemic congestive cardiomyopathy and sustained ventricular arrhythmias.

Resetting response patterns during sustained ventricular tachycardia: relationship to the excitable gap.

We analyzed the resetting response (a noncompensatory pause after electrical stimulation) during 37 hemodynamically tolerated ventricular tachycardias (VTs) induced by programmed electrical stimulation in 32 patients with chronic coronary artery disease. The mean cycle length of VT was 369 +/- 59 msec. Single extrastimuli were delivered at the right ventricular apex during all 37 VTs, and double extrastimuli were delivered at the same site during 23 VTs. The resetting response pattern was considered increasing, decreasing, or flat if the return cycle increased, decreased, or remained constant in response to progressively shorter coupling intervals of the extrastimuli. Ten VTs had an increasing pattern and nine a flat pattern. In 11 VTs the pattern was mixed (flat at longer coupling intervals and increasing at shorter ones), and in the remaining seven the pattern could not be defined. No VT had a decreasing pattern. The mean duration of the resetting interval (range of coupling intervals resulting in resetting) was 66 +/- 45 msec, or 17% of the cycle length of VT. VT with a mixed pattern had longer resetting intervals than VT with an increasing pattern (102 +/- 34 vs 64 +/- 40 msec; p less than .035); however, cycle lengths of VT were similar (370 +/- 58 vs 386 +/- 86, p = NS). An excellent correlation was observed between the shortest return cycles in response to single and double extrastimuli (r = .99), with a mean difference of 5 msec. The cycle length of VT exceeded the return cycle (measured to the QRS onset) during 15 VTs (41%).(ABSTRACT TRUNCATED AT 250 WORDS)

Electrocardiographic changes after cardioversion of ventricular arrhythmias.

To evaluate rhythm and QRS-T changes after cardioversion of induced ventricular arrhythmias, 56 patients underwent continuous three-lead and serial 12-lead electrocardiographic monitoring for 15 min after 77 cardioversions. Fifty patients were cardioverted externally and nine internally with an implanted automatic cardioverter/defibrillator. Initial energy for external cardioversion was 200 Wsec in 57 of 64 arrhythmia episodes. Two hundred watt-seconds of energy effectively terminated 41 of 44 episodes of ventricular tachycardia and six of 13 episodes of ventricular fibrillation (p less than .001). Early bradycardia (mean cycle length greater than or equal to 1200 msec during the first 5 sec) occurred after 17 of 64 external and two of 13 internal cardioversions (p = NS) in a total of 16 patients. Bradycardia persisted at 10 sec after cardioversion in nine patients. Early bradycardia was associated with the need for multiple cardioversions to terminate the arrhythmia (six of 10 multiple cardioversions vs 13 of 67 single cardioversions, p less than .05) and the presence of inferior myocardial infarction (eight of 16 patients with vs eight of 40 patients without inferior infarction, p less than .05). Supraventricular tachycardia (cycle length less than or equal to 500 msec) occurred after 19 of 64 external and six of 13 internal cardioversions (p = NS). Nonsustained ventricular tachycardia (4 to 40 beats) was observed after seven external cardioversions, with three episodes lasting 3 sec or more.(ABSTRACT TRUNCATED AT 250 WORDS)