Michela Casella

Pulmonary-Vein Isolation for Atrial Fibrillation in Patients with Heart Failure

BACKGROUND Pulmonary-vein isolation is increasingly being used to treat atrial fibrillation in patients with heart failure. METHODS In this prospective, multicenter clinical trial, we randomly assigned patients with symptomatic, drug-resistant atrial fibrillation, an ejection fraction of 40% or less, and New York Heart Association class II or III heart failure to undergo either pulmonary-vein isolation or atrioventricular-node ablation with biventricular pacing. All patients completed the Minnesota Living with Heart Failure questionnaire (scores range from 0 to 105, with a higher score indicating a worse quality of life) and underwent echocardiography and a 6-minute walk test (the composite primary end point). Over a 6-month period, patients were monitored for both symptomatic and asymptomatic episodes of atrial fibrillation. RESULTS In all, 41 patients underwent pulmonary-vein isolation, and 40 underwent atrioventricular-node ablation with biventricular pacing; none were lost to follow-up at 6 months. The composite primary end point favored the group that underwent pulmonary-vein isolation, with an improved questionnaire score at 6 months (60, vs. 82 in the group that underwent atrioventricular-node ablation with biventricular pacing; P<0.001), a longer 6-minute-walk distance (340 m vs. 297 m, P<0.001), and a higher ejection fraction (35% vs. 28%, P<0.001). In the group that underwent pulmonary-vein isolation, 88% of patients receiving antiarrhythmic drugs and 71% of those not receiving such drugs were free of atrial fibrillation at 6 months. In the group that underwent pulmonary-vein isolation, pulmonary-vein stenosis developed in two patients, pericardial effusion in one, and pulmonary edema in another; in the group that underwent atrioventricular-node ablation with biventricular pacing, lead dislodgment was found in one patient and pneumothorax in another. CONCLUSIONS Pulmonary-vein isolation was superior to atrioventricular-node ablation with biventricular pacing in patients with heart failure who had drug-refractory atrial fibrillation. (ClinicalTrials.gov number, NCT00599976.)

Left Atrial Appendage An Underrecognized Trigger Site of Atrial Fibrillation

Background— Together with pulmonary veins, many extrapulmonary vein areas may be the source of initiation and maintenance of atrial fibrillation. The left atrial appendage (LAA) is an underestimated site of initiation of atrial fibrillation. Here, we report the prevalence of triggers from the LAA and the best strategy for successful ablation. Methods and Results— Nine hundred eighty-seven consecutive patients (29% paroxysmal, 71% nonparoxysmal) undergoing redo catheter ablation for atrial fibrillation were enrolled. Two hundred sixty-six patients (27%) showed firing from the LAA and became the study population. In 86 of 987 patients (8.7%; 5 paroxysmal, 81 nonparoxysmal), the LAA was found to be the only source of arrhythmia with no pulmonary veins or other extrapulmonary vein site reconnection. Ablation was performed either with focal lesion (n=56; group 2) or to achieve LAA isolation by placement of the circular catheter at the ostium of the LAA guided by intracardiac echocardiography (167 patients; group 3). In the remaining patients, LAA firing was not ablated (n=43; group 1). At the 12±3-month follow-up, 32 patients (74%) in group 1 had recurrence compared with 38 (68%) in group 2 and 25 (15%) in group 3 (P<0.001). Conclusions— The LAA appears to be responsible for arrhythmias in 27% of patients presenting for repeat procedures. Isolation of the LAA could achieve freedom from atrial fibrillation in patients presenting for a repeat procedure when arrhythmias initiating from this structure are demonstrated.

Ablation for longstanding permanent atrial fibrillation: Results from a randomized study comparing three different strategies

BACKGROUND This prospective multicenter randomized study aimed to compare the efficacy of 3 common ablation methods used for longstanding permanent atrial fibrillation (AF). METHODS A total of 144 patients with longstanding permanent AF (median duration 28 months) were randomly assigned to circumferential pulmonary vein ablation (CPVA, group 1, n = 47), to pulmonary vein antrum isolation (PVAI, group 2, n = 48) or to a hybrid strategy combining ablation of complex fractionated or rapid atrial electrograms (CFAE) in both atria followed by a pulmonary vein antrum isolation (CFAE + PVAI, group 3, n = 49). RESULTS Scarring in the left atrium and structural heart disease/hypertension were present in most patients (65%). After a mean follow-up of 16 months, 11% of patients in group 1, 40% of patients in group 2 and 61% of patients in group 3 were in sinus rhythm after one procedure and with no antiarrhythmic drugs (P < .001). Sinus rhythm maintenance would increase respectively to 28% (group 1), 83% (group 2), and 94% (group 3) after 2 procedures and with antiarrhythmic drugs (AADs, P < .001). The AF terminated during ablation, either by conversion to sinus rhythm or organization into an atrial tachyarrhythmia, in 13% of patients (group 1), 44% (group 2), and 74% (group 3) respectively. CFAE alone, performed as the first step of the ablation in group 3, organized AF in only 1 patient. CONCLUSION In this study, the hybrid AF ablation strategy including antrum isolation and CFAE ablation had the highest likelihood of maintaining sinus rhythm in patients with longstanding permanent AF. Electrical isolation of the PVs, although inadequate if performed alone, is relevant to achieve long-term sinus rhythm maintenance after ablation. Bi-atrial CFAE ablation had a minimal impact on AF termination during ablation.

Periprocedural Stroke and Management of Major Bleeding Complications in Patients Undergoing Catheter Ablation of Atrial Fibrillation The Impact of Periprocedural Therapeutic International Normalized Ratio

Background— Catheter ablation of atrial fibrillation is associated with the potential risk of periprocedural stroke, which can range between 1% and 5%. We developed a prospective database to evaluate the prevalence of stroke over time and to assess whether the periprocedural anticoagulation strategy and use of open irrigation ablation catheter have resulted in a reduction of this complication. Methods and Results— We collected data from 9 centers performing the same ablation procedure with the same anticoagulation protocol. We divided the patients into 3 groups: ablation with an 8-mm catheter off warfarin (group 1), ablation with an open irrigated catheter off warfarin (group 2), and ablation with an open irrigated catheter on warfarin (group 3). Outcome data on stroke/transient ischemic attack and bleeding complications during and early after the procedures were collected. Of 6454 consecutive patients in the study, 2488 were in group 1, 1348 were in group 2, and 2618 were in group 3. Periprocedural stroke/transient ischemic attack occurred in 27 patients (1.1%) in group 1 and 12 patients (0.9%) in group 2. Despite a higher prevalence of nonparoxysmal atrial fibrillation and more patients with CHADS2 (congestive heart failure, hypertension, age >75 years, diabetes mellitus, and prior stroke or transient ischemic attack) score >2, no stroke/transient ischemic attack was reported in group 3. Complications among groups 1, 2, and 3, including major bleeding (10 [0.4%], 11 [0.8%], and 10 [0.4%], respectively; P>0.05) and pericardial effusion (11 [0.4%], 11 [0.8%], and 12 [0.5%]; P>0.05), were equally distributed. Conclusion— The combination of an open irrigation ablation catheter and periprocedural therapeutic anticoagulation with warfarin may reduce the risk of periprocedural stroke without increasing the risk of pericardial effusion or other bleeding complications.

Periprocedural Stroke and Bleeding Complications in Patients Undergoing Catheter Ablation of Atrial Fibrillation With Different Anticoagulation Management Results From the Role of Coumadin in Preventing Thromboembolism in Atrial Fibrillation (AF) Patients Undergoing Catheter Ablation (COMPARE) Randomized Trial

Background— Periprocedural thromboembolic and hemorrhagic events are worrisome complications of catheter ablation for atrial fibrillation (AF). The periprocedural anticoagulation management could play a role in the incidence of these complications. Although ablation procedures performed without warfarin discontinuation seem to be associated with lower thromboembolic risk, no randomized study exists. Methods and Results— This was a prospective, open-label, randomized, parallel-group, multicenter study assessing the role of continuous warfarin therapy in preventing periprocedural thromboembolic and hemorrhagic events after radiofrequency catheter ablation. Patients with CHADS2 score ≥1 were included. Patients were randomly assigned in a 1:1 ratio to the off-warfarin or on-warfarin arm. The incidence of thromboembolic events in the 48 hours after ablation was the primary end point of the study. The study enrolled 1584 patients: 790 assigned to discontinue warfarin (group 1) and 794 assigned to continuous warfarin (group 2). No statistical difference in baseline characteristics was observed. There were 39 thromboembolic events (3.7% strokes [n=29] and 1.3% transient ischemic attacks [n=10]) in group 1: two events (0.87%) in patients with paroxysmal AF, 4 (2.3%) in patients with persistent AF, and 33 (8.5%) in patients with long-standing persistent AF. Only 2 strokes (0.25%) in patients with long-standing persistent AF were observed in group 2 (P<0.001). Warfarin discontinuation emerged as a strong predictor of periprocedural thromboembolism (odds ratio, 13; 95% confidence interval, 3.1–55.6; P<0.001). Conclusion— This is the first randomized study showing that performing catheter ablation of AF without warfarin discontinuation reduces the occurrence of periprocedural stroke and minor bleeding complications compared with bridging with low-molecular-weight heparin. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01006876.

Endo-epicardial homogenization of the scar versus limited substrate ablation for the treatment of electrical storms in patients with ischemic cardiomyopathy.

OBJECTIVES This study investigated the impact on recurrences of 2 different substrate approaches for the treatment of these arrhythmias. BACKGROUND Catheter ablation of electrical storms (ES) for ventricular arrhythmias (VAs) has shown moderate long-term efficacy in patients with ischemic cardiomyopathy. METHODS Ninety-two consecutive patients (81% male, age 62 ± 13 years) with ischemic cardiomyopathy and ES underwent catheter ablation. Patients were treated either by confining the radiofrequency lesions to the endocardial surface with limited substrate ablation (Group 1, n = 49) or underwent endocardial and epicardial ablation of abnormal potentials within the scar (homogenization of the scar, Group 2, n = 43). Epicardial access was obtained in all Group 2 patients, whereas epicardial ablation was performed in 33% (14) of these patients. RESULTS Mean ejection fraction was 27 ± 5. During a mean follow-up of 25 ± 10 months, the VAs recurrence rate of any ventricular tachycardia (VTs) was 47% (23 of 49 patients) in Group 1 and 19% (8 of 43 patients) in Group 2 (log-rank p = 0.006). One patient in Group 1 and 1 patient in Group 2 died at follow-up for noncardiac reasons. CONCLUSIONS Our study demonstrates that ablation using endo-epicardial homogenization of the scar significantly increases freedom from VAs in ischemic cardiomyopathy patients.

Periprocedural Stroke and Bleeding Complications in Patients undergoing Catheter Ablation of Atrial Fibrillation with Different Anticoagulation Management: Results from the "COMPARE" Randomized Trial

Background— Periprocedural thromboembolic and hemorrhagic events are worrisome complications of catheter ablation for atrial fibrillation (AF). The periprocedural anticoagulation management could play a role in the incidence of these complications. Although ablation procedures performed without warfarin discontinuation seem to be associated with lower thromboembolic risk, no randomized study exists. Methods and Results— This was a prospective, open-label, randomized, parallel-group, multicenter study assessing the role of continuous warfarin therapy in preventing periprocedural thromboembolic and hemorrhagic events after radiofrequency catheter ablation. Patients with CHADS2 score ≥1 were included. Patients were randomly assigned in a 1:1 ratio to the off-warfarin or on-warfarin arm. The incidence of thromboembolic events in the 48 hours after ablation was the primary end point of the study. The study enrolled 1584 patients: 790 assigned to discontinue warfarin (group 1) and 794 assigned to continuous warfarin (group 2). No statistical difference in baseline characteristics was observed. There were 39 thromboembolic events (3.7% strokes [n=29] and 1.3% transient ischemic attacks [n=10]) in group 1: two events (0.87%) in patients with paroxysmal AF, 4 (2.3%) in patients with persistent AF, and 33 (8.5%) in patients with long-standing persistent AF. Only 2 strokes (0.25%) in patients with long-standing persistent AF were observed in group 2 (P<0.001). Warfarin discontinuation emerged as a strong predictor of periprocedural thromboembolism (odds ratio, 13; 95% confidence interval, 3.1–55.6; P<0.001). Conclusion— This is the first randomized study showing that performing catheter ablation of AF without warfarin discontinuation reduces the occurrence of periprocedural stroke and minor bleeding complications compared with bridging with low-molecular-weight heparin. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01006876.

Ablation of Ventricular Arrhythmias in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy: Arrhythmia-Free Survival after Endo-Epicardial Substrate Based Mapping and Ablation

Background— In patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy, freedom from ventricular arrhythmias (VAs) after endocardial ablation is limited. We compared the long-term freedom from recurrent VAs by using endocardial-alone ablation versus endo-epicardial substrate-based ablation. Methods and Results— Forty-nine patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy undergoing ablation of ventricular tachycardia (VT) were divided into 2 groups: endocardial-alone ablation (group 1, n=23) and endo-epicardial ablation (group 2, n=26). All patients had an implantable cardioverter-defibrillator (ICD). Conventional and 3D mappings were used to determine the mechanism of induced VTs and to identify area of “scar” or “abnormal” myocardium. All critical sites responsible for VTs and points with “abnormal” potential were targeted for ablation from endocardium (group 1) or from both endocardium and epicardium (group 2). The procedural end point was noninducibility of sustained, monomorphic VT with isoproterenol. The presence of frequent premature ventricular contractions at the end of ablation was recorded. Patients were followed up by ECG, Holter, and ICD interrogation. After a follow-up of at least 3 years, freedom from VAs or ICD therapy was 52.2% (12/23) in group 1 and 84.6% (22/26) in group 2 (P=0.029), with 21.7% (5/23) and 69.2% (18/26) patients off antiarrhythmic drugs (P<0.001), respectively. Compared with patients with no premature ventricular contractions after ablation, patients with frequent premature ventricular contractions after ablation were more likely to have VA recurrence/ICD therapy [3/33 (9%) versus 12/16 (75%); log-rank P<0.001]. Conclusions— An endo-epicardial–based ablation strategy achieves higher long-term freedom from recurrent VAs off antiarrhythmic therapy in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy when compared with endocardial-alone ablation. The presence of ≥10 premature ventricular contractions per minute after ablation is associated with more VA recurrence.Background— In patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy, freedom from ventricular arrhythmias (VAs) after endocardial ablation is limited. We compared the long-term freedom from recurrent VAs by using endocardial-alone ablation versus endo-epicardial substrate-based ablation. Methods and Results— Forty-nine patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy undergoing ablation of ventricular tachycardia (VT) were divided into 2 groups: endocardial-alone ablation (group 1, n=23) and endo-epicardial ablation (group 2, n=26). All patients had an implantable cardioverter-defibrillator (ICD). Conventional and 3D mappings were used to determine the mechanism of induced VTs and to identify area of “scar” or “abnormal” myocardium. All critical sites responsible for VTs and points with “abnormal” potential were targeted for ablation from endocardium (group 1) or from both endocardium and epicardium (group 2). The procedural end point was noninducibility of sustained, monomorphic VT with isoproterenol. The presence of frequent premature ventricular contractions at the end of ablation was recorded. Patients were followed up by ECG, Holter, and ICD interrogation. After a follow-up of at least 3 years, freedom from VAs or ICD therapy was 52.2% (12/23) in group 1 and 84.6% (22/26) in group 2 ( P =0.029), with 21.7% (5/23) and 69.2% (18/26) patients off antiarrhythmic drugs ( P <0.001), respectively. Compared with patients with no premature ventricular contractions after ablation, patients with frequent premature ventricular contractions after ablation were more likely to have VA recurrence/ICD therapy [3/33 (9%) versus 12/16 (75%); log-rank P <0.001]. Conclusions— An endo-epicardial–based ablation strategy achieves higher long-term freedom from recurrent VAs off antiarrhythmic therapy in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy when compared with endocardial-alone ablation. The presence of ≥10 premature ventricular contractions per minute after ablation is associated with more VA recurrence.

Atrial Fibrillation Ablation Strategies for Paroxysmal Patients: randomized comparison between different techniques.

Background— Whether different ablation strategies affect paroxysmal atrial fibrillation (AF) long-term freedom from AF/atrial tachyarrhythmia is unclear. We sought to compare the effect of 3 different ablation approaches on the long-term success in patients with paroxysmal AF. Methods and Results— One hundred three consecutive patients with paroxysmal AF scheduled for ablation and presenting in the electrophysiology laboratory in AF were selected for this study. Patients were randomized to pulmonary vein antrum isolation (PVAI; n=35) versus biatrial ablation of the complex fractionated atrial electrograms (CFAEs; n=34) versus PVAI followed by CFAEs (n=34). Patients were given event recorders and followed up at 3, 6, 9, 12, and 15 months postablation. There was no statistical significant difference between the groups in term of sex, age, AF duration, left atrial size, and ejection fraction. At 1 year follow-up, freedom from AF/atrial tachyarrhythmia was documented in 89% of patients in the PVAI group, 91% in the PVAI plus CFAEs group, and 23% in the CFAEs group ( P <0.001) after a single procedure and with antiarrhythmic drugs. Conclusion— No difference in terms of success rate was seen between PVAI alone and PVAI associated with defragmentation. CFAEs ablation alone had the smallest impact on AF recurrences at 1-year follow-up. These results suggest that antral isolation is sufficient to treat most patients with paroxysmal AF. Received March 19, 2008; accepted February 11, 2009. # CLINICAL PERSPECTIVE {#article-title-2}Background—Whether different ablation strategies affect paroxysmal atrial fibrillation (AF) long-term freedom from AF/atrial tachyarrhythmia is unclear. We sought to compare the effect of 3 different ablation approaches on the long-term success in patients with paroxysmal AF. Methods and Results—One hundred three consecutive patients with paroxysmal AF scheduled for ablation and presenting in the electrophysiology laboratory in AF were selected for this study. Patients were randomized to pulmonary vein antrum isolation (PVAI; n=35) versus biatrial ablation of the complex fractionated atrial electrograms (CFAEs; n=34) versus PVAI followed by CFAEs (n=34). Patients were given event recorders and followed up at 3, 6, 9, 12, and 15 months postablation. There was no statistical significant difference between the groups in term of sex, age, AF duration, left atrial size, and ejection fraction. At 1 year follow-up, freedom from AF/atrial tachyarrhythmia was documented in 89% of patients in the PVAI group, 91% in the PVAI plus CFAEs group, and 23% in the CFAEs group (P<0.001) after a single procedure and with antiarrhythmic drugs. Conclusion—No difference in terms of success rate was seen between PVAI alone and PVAI associated with defragmentation. CFAEs ablation alone had the smallest impact on AF recurrences at 1-year follow-up. These results suggest that antral isolation is sufficient to treat most patients with paroxysmal AF.

Ablation Versus Amiodarone for Treatment of Persistent Atrial Fibrillation in Patients With Congestive Heart Failure and an Implanted Device: Results From the AATAC Multicenter Randomized Trial

Background— Whether catheter ablation (CA) is superior to amiodarone (AMIO) for the treatment of persistent atrial fibrillation (AF) in patients with heart failure is unknown. Methods and Results— This was an open-label, randomized, parallel-group, multicenter study. Patients with persistent AF, dual-chamber implantable cardioverter defibrillator or cardiac resynchronization therapy defibrillator, New York Heart Association II to III, and left ventricular ejection fraction <40% within the past 6 months were randomly assigned (1:1 ratio) to undergo CA for AF (group 1, n=102) or receive AMIO (group 2, n=101). Recurrence of AF was the primary end point. All-cause mortality and unplanned hospitalization were the secondary end points. Patients were followed up for a minimum of 24 months. At the end of follow-up, 71 (70%; 95% confidence interval, 60%–78%) patients in group 1 were recurrence free after an average of 1.4±0.6 procedures in comparison with 34 (34%; 95% confidence interval, 25%–44%) in group 2 (log-rank P<0.001). The success rate of CA in the different centers after a single procedure ranged from 29% to 61%. After adjusting for covariates in the multivariable model, AMIO therapy was found to be significantly more likely to fail (hazard ratio, 2.5; 95% confidence interval, 1.5–4.3; P<0.001) than CA. Over the 2-year follow-up, the unplanned hospitalization rate was (32 [31%] in group 1 and 58 [57%] in group 2; P<0.001), showing 45% relative risk reduction (relative risk, 0.55; 95% confidence interval, 0.39–0.76). A significantly lower mortality was observed in CA (8 [8%] versus AMIO (18 [18%]; P=0.037). Conclusions— This multicenter randomized study shows that CA of AF is superior to AMIO in achieving freedom from AF at long-term follow-up and reducing unplanned hospitalization and mortality in patients with heart failure and persistent AF. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00729911.