Emile G. Daoud

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.

Catheter Ablation Versus Antiarrhythmic Drugs for Atrial Fibrillation The A4 Study

Background— The mainstay of treatment for atrial fibrillation (AF) remains pharmacological; however, catheter ablation has increasingly been used over the last decade. The relative merits of each strategy have not been extensively studied. Methods and Results— We conducted a randomized multicenter comparison of these 2 treatment strategies in patients with paroxysmal AF resistant to at least 1 antiarrhythmic drug. The primary end point was absence of recurrent AF between months 3 and 12, absence of recurrent AF after up to 3 ablation procedures, or changes in antiarrhythmic drugs during the first 3 months. Ablation consisted of pulmonary vein isolation in all cases, whereas additional extrapulmonary vein lesions were at the discretion of the physician. Crossover was permitted at 3 months in case of failure. Echocardiographic data, symptom score, exercise capacity, quality of life, and AF burden were evaluated at 3, 6, and 12 months by the supervising committee. Of 149 eligible patients, 112 (18 women [16%]; age, 51.1±11.1 years) were enrolled and randomized to ablation (n=53) or “new” antiarrhythmic drugs alone or in combination (n=59). Crossover from the antiarrhythmic drugs and ablation groups occurred in 37 (63%) and 5 patients (9%), respectively (P=0.0001). At the 1-year follow-up, 13 of 55 patients (23%) and 46 of 52 patients (89%) had no recurrence of AF in the antiarrhythmic drug and ablation groups, respectively (P<0.0001). Symptom score, exercise capacity, and quality of life were significantly higher in the ablation group. Conclusion— This randomized multicenter study demonstrates the superiority of catheter ablation over antiarrhythmic drugs in patients with AF with regard to maintenance of sinus rhythm and improvement in symptoms, exercise capacity, and quality of life.

Irrigated Radiofrequency Catheter Ablation Guided by Electroanatomic Mapping for Recurrent Ventricular Tachycardia After Myocardial Infarction The Multicenter Thermocool Ventricular Tachycardia Ablation Trial

Background— Recurrent ventricular tachycardia (VT) is an important cause of mortality and morbidity late after myocardial infarction. With frequent use of implantable cardioverter-defibrillators, these VTs are often poorly defined and not tolerated for mapping, factors previously viewed as relative contraindications to ablation. This observational multicenter study assessed the outcome of VT ablation with a saline-irrigated catheter combined with an electroanatomic mapping system. Methods and Results— Two hundred thirty-one patients (median LV ejection fraction, 0.25; heart failure in 62%) with recurrent episodes of monomorphic VT (median, 11 in the preceding 6 months) caused by prior myocardial infarction were enrolled. All inducible monomorphic VTs with a rate approximating or slower than any spontaneous VTs were targeted for ablation guided by electroanatomic mapping during sinus rhythm and/or VT. Patients were not excluded for multiple VTs (median, 3 per patient) or unmappable VT (present in 69% of patients). Ablation abolished all inducible VTs in 49% of patients. The primary end point of freedom from recurrent incessant VT or intermittent VT after 6 months of follow-up was achieved for 123 patients (53%). In 142 patients with implantable cardioverter-defibrillators before and after ablation for intermittent VT who survived 6 months, VT episodes were reduced from a median of 11.5 to 0 (P<0.0001). The 1-year mortality rate was 18%, with 72.5% of deaths attributed to ventricular arrhythmias or heart failure. The procedure mortality rate was 3%, with no strokes. Conclusions— Catheter ablation is a reasonable option to reduce episodes of recurrent VT in patients with prior myocardial infarction, even when multiple and/or unmappable VTs are present. This population remains at high risk for death, warranting surveillance and further study.

Preoperative Amiodarone as Prophylaxis against Atrial Fibrillation after Heart Surgery

Background Atrial fibrillation occurs commonly after open-heart surgery and may delay hospital discharge. The purpose of this study was to assess the use of preoperative amiodarone as prophylaxis against atrial fibrillation after cardiac surgery. Methods In this double-blind, randomized study, 124 patients were given either oral amiodarone (64 patients) or placebo (60 patients) for a minimum of seven days before elective cardiac surgery. Therapy consisted of 600 mg of amiodarone per day for seven days, then 200 mg per day until the day of discharge from the hospital. The mean (±SD) preoperative total dose of amiodarone was 4.8±0.96 g over a period of 13 ± 7 days. Results Postoperative atrial fibrillation occurred in 16 of the 64 patients in the amiodarone group (25 percent) and 32 of the 60 patients in the placebo group (53 percent) (P = 0.003). Patients in the amiodarone group were hospitalized for significantly fewer days than were patients in the placebo group (6.5 ± 2.6 vs. 7.9 ± 4.3 days, P = 0.04). ...

Left Ventricular-Based Cardiac Stimulation Post AV Nodal Ablation Evaluation (The PAVE Study)

Background: Chronic right ventricular pacing has been reported to promote cardiac dyssynchrony. The PAVE trial prospectively compared chronic biventricular pacing to right ventricular pacing in patients undergoing ablation of the AV node for management of atrial fibrillation with rapid ventricular rates.

The Relationship between Daily Atrial Tachyarrhythmia Burden from Implantable Device Diagnostics and Stroke Risk: The TRENDS Study

Background—It is unknown if brief episodes of device-detected atrial fibrillation (AF) increase thromboembolic event (TE) risk. Methods and Results—TRENDS was a prospective, observational study enrolling patients with ≥1 stroke risk factor (heart failure, hypertension, age ≥65 years, diabetes, or prior TE) receiving pacemakers or defibrillators that monitor atrial tachycardia (AT)/AF burden (defined as the longest total AT/AF duration on any given day during the prior 30-day period). This time-varying exposure was updated daily during follow-up and related to TE risk. Annualized TE rates were determined according to AT/AF burden subsets: zero, low (<5.5 hours [median duration of subsets with nonzero burden]), and high (≥5.5 hours). A multivariate Cox model provided hazard ratios including terms for stroke risk factors and time-varying AT/AF burden and antithrombotic therapy. Patients (n=2486) had at least 30 days of device data for analysis. During a mean follow-up of 1.4 years, annualized TE risk (including transient ischemic attacks) was 1.1% for zero, 1.1% for low, and 2.4% for high burden subsets of 30-day windows. Compared with zero burden, adjusted hazard ratios (95% CIs) in the low and high burden subsets were 0.98 (0.34 to 2.82, P=0.97) and 2.20 (0.96 to 5.05, P=0.06), respectively. Conclusions—The TE rate was low compared with patients with traditional AF with similar risk profiles. The data suggest that TE risk is a quantitative function of AT/AF burden. AT/AF burden ≥5.5 hours on any of 30 prior days appeared to double TE risk. Additional studies are needed to more precisely investigate the relationship between stroke risk and AT/AF burden.

Association of Atrial Tissue Fibrosis Identified by Delayed Enhancement MRI and Atrial Fibrillation Catheter Ablation: The DECAAF Study

IMPORTANCE Left atrial fibrosis is prominent in patients with atrial fibrillation (AF). Extensive atrial tissue fibrosis identified by delayed enhancement magnetic resonance imaging (MRI) has been associated with poor outcomes of AF catheter ablation. OBJECTIVE To characterize the feasibility of atrial tissue fibrosis estimation by delayed enhancement MRI and its association with subsequent AF ablation outcome. DESIGN, SETTING, AND PARTICIPANTS Multicenter, prospective, observational cohort study of patients diagnosed with paroxysmal and persistent AF (undergoing their first catheter ablation) conducted between August 2010 and August 2011 at 15 centers in the United States, Europe, and Australia. Delayed enhancement MRI images were obtained up to 30 days before ablation. MAIN OUTCOMES AND MEASURES Fibrosis quantification was performed at a core laboratory blinded to the participating center, ablation approach, and procedure outcome. Fibrosis blinded to the treating physicians was categorized as stage 1 (<10% of the atrial wall), 2 (≥10%-<20%), 3 (≥20%-<30%), and 4 (≥30%). Patients were followed up for recurrent arrhythmia per current guidelines using electrocardiography or ambulatory monitor recording and results were analyzed at a core laboratory. Cumulative incidence of recurrence was estimated by stage at days 325 and 475 after a 90-day blanking period (standard time allowed for arrhythmias related to ablation-induced inflammation to subside) and the risk of recurrence was estimated (adjusting for 10 demographic and clinical covariates). RESULTS Atrial tissue fibrosis estimation by delayed enhancement MRI was successfully quantified in 272 of 329 enrolled patients (57 patients [17%] were excluded due to poor MRI quality). There were 260 patients who were followed up after the blanking period (mean [SD] age of 59.1 [10.7] years, 31.5% female, 64.6% with paroxysmal AF). For recurrent arrhythmia, the unadjusted overall hazard ratio per 1% increase in left atrial fibrosis was 1.06 (95% CI, 1.03-1.08; P < .001). Estimated unadjusted cumulative incidence of recurrent arrhythmia by day 325 for stage 1 fibrosis was 15.3% (95% CI, 7.6%-29.6%); stage 2, 32.6% (95% CI, 24.3%-42.9%); stage 3, 45.9% (95% CI, 35.5%-57.5%); and stage 4, 51.1% (95% CI, 32.8%-72.2%) and by day 475 was 15.3% (95% CI, 7.6%-29.6%), 35.8% (95% CI, 26.2%-47.6%), 45.9% (95% CI, 35.6%-57.5%), and 69.4% (95% CI, 48.6%-87.7%), respectively. Similar results were obtained after covariate adjustment. The addition of fibrosis to a recurrence prediction model that includes traditional clinical covariates resulted in an improved predictive accuracy with the C statistic increasing from 0.65 to 0.69 (risk difference of 0.05; 95% CI, 0.01-0.09). CONCLUSIONS AND RELEVANCE Among patients with AF undergoing catheter ablation, atrial tissue fibrosis estimated by delayed enhancement MRI was independently associated with likelihood of recurrent arrhythmia. The clinical implications of this association warrant further investigation.

Effect of Atrial Fibrillation on Atrial Refractoriness in Humans

BACKGROUND The acute effect of atrial fibrillation (AF) on the atrial effective refractory period (ERP) in humans is unknown. METHODS AND RESULTS In 20 patients without structural heart disease, the atrial ERP was measured before and after pacing-induced AF at drive cycle lengths of 350 and 500 ms. Immediately after spontaneous AF conversion, the post-AF ERP was measured. The pre-AF ERPs at 350 and 500 ms were 206 +/- 23 and 216 +/- 17 ms, respectively. The time to spontaneous conversion of AF was 7.3 +/- 1.9 minutes. The first post-AF ERPs at drive cycle lengths of 350 and 500 ms were 175 +/- 30 ms (P < .0001 versus pre-AF) and 191 +/- 30 ms (P < .0001 versus pre-AF), respectively. The post-AF ERP returned to the pre-AF ERP value after a mean of 8.4 +/- 0.3 minutes. In 15 patients, during the determination of the post-AF ERP, secondary episodes of AF lasting 1 +/- 1.5 minutes were reinduced 6 +/- 3 times per patient. There was a significant inverse logarithmic relationship between the time to reinduction of AF and the duration of secondary episodes of AF (P < .0001, r = 5). CONCLUSIONS In humans, several minutes of induced AF is sufficient to shorten the ERP for up to approximately 8 minutes. The temporal recovery of the ERP is reflected in progressively shorter episodes of reinduced AF. These data imply that AF transiently shortens the atrial wavelength and suggest a mechanism by which AF may perpetuate itself.

Effect of an irregular ventricular rhythm on cardiac output

Impairment of cardiac function in atrial fibrillation has been attributed to loss of atrial contraction and to a rapid ventricular rate. The results of this study suggest that irregularity of the ventricular rhythm, independent of the ventricular rate, may also contribute to impairment of cardiac function during atrial fibrillation.

Radiofrequency Catheter Modification of Atrioventricular Conduction to Control the Ventricular Rate during Atrial Fibrillation

BACKGROUND In some patients with atrial fibrillation, the ventricular rate may be difficult to control with medications. We evaluated a radiofrequency catheter technique to modify atrioventricular conduction in atrial fibrillation in order to control the ventricular rate without creating pathologic atrioventricular block. METHODS We studied 19 consecutive patients with atrial fibrillation and uncontrolled ventricular rates refractory to drug therapy. They had had atrial fibrillation for a mean (+/- SD) of 5.5 +/- 4.9 years, had had 4.9 +/- 0.9 unsuccessful drug trials, and were 62 +/- 15 years old. Before the procedure, the maximal ventricular rate during exercise was 180 +/- 39 beats per minute. A total of 11 +/- 5 radiofrequency-energy applications were delivered to the posterior septal or midseptal right atrium, near the ostium of the coronary sinus. RESULTS Successful control of the ventricular rate without pathologic atrioventricular block was achieved in 14 of the 19 patients (74 percent). Persistent third-degree atrioventricular block requiring a permanent pacemaker occurred inadvertently in four patients (21 percent). Atrioventricular conduction was intentionally ablated in one patient. The 14 patients who had successful modification of conduction had persistent reductions in maximal ventricular rate during exercise (rate at three months, 126 +/- 24 beats per minute; P < 0.01). These patients had resolution of symptoms related to rapid rates during 8 +/- 2 months of follow-up. One patient had a recurrence of a rapid ventricular rate but was again asymptomatic after a second modification procedure. One patient with dilated cardiomyopathy died suddenly, five months after a successful procedure. CONCLUSIONS A catheter technique to modify atrioventricular conduction without creating pathologic atrioventricular block is feasible in the majority of patients with symptomatic atrial fibrillation and a rapid ventricular rate refractory to drug therapy.