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Background Thromboembolic stroke is a rare but devastating consequence of atrial fibrillation (AF) ablation. Transesopheageal echocardiography (TEE) is recommended to rule out left atrial appendage thrombus (LAA); however, its utilization is variable. Objective To assess whether TEE is mandatory in patients undergoing AF ablation on uninterrupted DOACs. Methods Data from our prospective, multicenter registry of AF patients undergoing radiofrequency catheter ablation on uninterrupted DOACs was analyzed. All included patients were on anticoagulation for at least four-weeks before ablation. All AF ablation procedures were performed under ICE guidance. Prior to transseptal puncture, heparin bolus was administered, followed by continuous infusion, with target activated clotting time over 300 seconds. Results A total of 6186 patients [3180 (51.4%): apixaban, 2528 (40.9%): rivaroxaban, 404 (6.5%): dabigatran, and 74 (1.2%): edoxaban] were analyzed. The mean age of the study population was 69.4 ± 10.3 years, of which 4194 (67.8%) patients were male and 5120 (82.8%) patients had persistent and long-standing persistent AF. The mean CHA2DS2-VASc score was 2.86 ± 1.58; the mean CHADS2 score was 1.65 ± 1.14. ICE ruled out LAA and LA thrombus in all patients and revealed ‘smoke’ in 1672 (27.03%) patients. Transient ischemic attack was noted in one patient with long-standing persistent AF, in the setting of a missed dose of rivaroxaban prior to ablation. Conclusion Our study showed that performance of AF ablation in patients on uninterrupted DOACs without TEE is safe and feasible in high stroke-risk patients. Elimination of routine pre-ablation TEE would have significant economic and clinical implications.

Background Atrial fibrillation (AF) triggers within the coronary sinus (CS)/great cardiac vein (GCV) and the left atrial appendage (LAA) have been recognized as nonpulmonary vein triggers of AF. Objective The aim of this study was to describe an electrical connection between the LAA and CS/GCV and its importance in achieving LAA electrical isolation (LAAEI). Methods A total of 488 consecutive patients undergoing catheter ablation for persistent or long-standing persistent AF who showed firing from the LAA and/or from the CS/GCV were enrolled in this multicenter prospective study. In all patients, potential defragmentation of the CS/GCV to achieve isolation and LAAEI was attempted with both endocardial and epicardial ablation. Results In 7% (n = 34) of these patients, after attempting endocardial LAAEI, the LAA was isolated during epicardial ablation in the GCV. In 8% (n = 39) of patients after attempting endocardial LAA isolation, the LAA was isolated during ablation along the endocardial aspect of the GCV. The presence of a venous branch connecting the GCV with the LAA was found in all these patients. In 23% (n = 112) of patients, the isolation of the LAA also isolated the GCV. In all these patients, LAA dissociated firing was present together with the CS/GCV recordings. Conclusion These findings suggest the presence of a distinct electrical connection between the GCV and the LAA. The clinical relevance of our results requires further investigation. Ablation in the CS/GCV can result in inadvertent isolation of the LAA. Ablation of the GCV is relevant to achieve LAAEI. Considering the potential long-term implications, ablation in the distal CS/GCV should prompt assessment of LAA conduction.

The optimal site of ablation of idiopathic left ventricular outflow tract (LVOT) ventricular arrhythmias (VAs) is challenging as activation mapping can reveal similar activation times in different anatomical sites, suggesting an intramural origin.We sought to assess whether in patients with intramural VAs and with multiple early activation sites (EASs), sequential ablation of all the early EASs could improve acute and long-term clinical outcomes.A total of 116 patients undergoing catheter ablation for symptomatic LVOT VAs were enrolled in this study. Thirty-nine patients (34%) were referred for a redo procedure, whereas the remaining presented for a first procedure. Mapping was performed manually in 86 cases (74%) and with a magnetic robotic system (Niobe, Stereotaxis, St. Louis, MO) in the remainder of the cases.Of the 116 patients, 15 (13%) were found to have multiple sites of equally early activation. In patients with multiple EASs, the mean pre-QRS activation time was significantly less than in patients with a single EASs (-26 ± 3 ms vs -38 ± 6 ms; P .005). Sequential ablation of all the EASs was possible in 14 patients (93%), resulting in complete arrhythmia suppression. After a mean follow-up of 21 ± 5 months, all patients with successful ablation of all multiple early EASs remained free from clinical VAs.Intramural LVOT VAs manifesting with multiple EASs require ablation at all sites to achieve acute and long-term success, particularly if none of the EASs is-30ms pre-QRS activation time.

We investigated the feasibility to proactively stimulate subsequent closure of a patent foramen ovale (PFO) by injuring (mechanical trauma or radiofrequency [RF] energy) the opposing surfaces of the septum primum (SP) and septum secundum (SS). 1. Mechanical Injury: The interatrial septum of patients who underwent multiple left atrial (LA) ablations over 6 years, where a PFO was used for LA access, were examined. Patients whose PFO was absent during a later procedure were identified. Eleven patients with LA accessed via a PFO also underwent subsequent LA procedures. 2. Ablation: Ten patients undergoing ablation for drug-resistant atrial fibrillation (AF), who also had a PFO, were studied. RF delivery was extended along the upper SP. Transthoracic echocardiogram (TTE) bubble study was repeated after 3 months. 1. Mechanical Injury: Seven were male with a mean age of 58.3 ± 9.99. LA size was 42.73 ± 3.52 mm. The mean left ventricular ejection fraction (EF) was 62 ± 7.4%. During the repeat procedure, in 4 patients, the PFO could not be visualized and the fossa ovalis (FO) was punctured. The fourth patient had three procedures. During the second procedure the PFO was accessed, but with difficulty. During the third procedure, it was no longer present. All four patients had subsequent TTE showing no PFO. 2. Ablation: Seven were male with a mean age of 61.1 ± 9.8 years. The mean EF and LA diameters were 55 ± 5% and 4.4 ± 0.8 cm respectively. The mean RF time was 5.4 ± 2.2 min. At 3 months, 9 patients out of 10 showed no interatrial communication. Injury of tunnel surfaces of the SP and SS by mechanical trauma or ablation can fuse the foramen ovale.

Background We compared the cognitive status and quality of life in patients with atrial fibrillation undergoing left atrial appendage occlusion (LAAO) or remaining on oral anticoagulation (OAC) after atrial fibrillation ablation. Methods and Results Cognition was assessed by the Montreal Cognitive Assessment (MoCA) survey at baseline and follow‐up. Consecutive patients receiving LAAO or OAC after atrial fibrillation ablation were screened, and patients with a score of ≤17 were excluded from the study. Quality of life was measured at baseline and 1 year using the Atrial Fibrillation Effect on Quality of Life survey. A total of 50 patients (CHA 2 DS 2 ‐VASc [congestive heart failure, hypertension, age≥75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65–74 years, sex category] score: 3.30±1.43) in the LAAO group and 48 (CHA 2 DS 2 ‐VASc score 2.73±1.25) in the OAC group were included in this prospective study. Mean baseline MoCA score was 26.18 and 26.08 in the LAAO and OAC groups, respectively ( P =0.846). At 1 year, scores were 26.94 and 23.38 in the respective groups. MoCA score decreased by an estimated −2.74 (95% CI, −3.61 to −1.87; P P =0.07). After adjusting for baseline clinical characteristics, remaining on OAC was an independent predictor of MoCA change at 1 year (regression coefficient, −3.38; 95% CI, −4.75 to −2.02; P Conclusions In this series, a significant difference in the postprocedure MoCA score was observed in postablation patients with atrial fibrillation receiving LAAO versus remaining on OAC with a substantial decline in the score in the OAC group. However, quality of life improved similarly across groups. Registration https://www.ClinicalTrials.gov . Unique identifier: NCT01816308

Background: Left atrial appendage electrical isolation (LAAEI) has been proposed for the treatment of nonparoxysmal atrial fibrillation (AF). The long-term clinical outcomes of this approach remain unclear. The objective of our study was to investigate the incremental benefit and safety of LAAEI in patients undergoing catheter ablation for nonparoxysmal AF. Methods: Propensity score-matched analysis was performed using a prospective registry database from 2010 to 2014. All patients in the LAAEI group were matched based on baseline characteristics, echocardiographic parameters, and procedural ablation techniques. Results: We identified 1842 patients who underwent catheter ablation for nonparoxysmal AF. Propensity score matching yielded 1092 patients, 546 patients with LAAEI, and 546 patients without LAAEI. At 5-year follow-up, overall freedom from all-atrial arrhythmia recurrence, off-antiarrhythmic drugs, in patients who underwent LAAEI was 68.9% versus 50.2% in those who underwent standard ablation alone ( P P =0.36). At 5-year follow-up, 382 (70%) patients in the LAAEI group remained on oral anticoagulation versus 217 (39.7%) in the non-LAAEI group. At 5-year follow-up, thromboembolic events occurred in 15/546 (2.75%) in the LAAEI group and 4/546 (0.73%) in the non-LAAEI group ( P =0.01). No thromboembolic events occurred in either group on-oral anticoagulation. In patients who were off-oral anticoagulation, at 5-year follow-up, thromboembolic events occurred in 15/164 (9.1%) in the LAAEI group and 4/329 (1.2%) in the non-LAAEI group ( P Conclusions: At 5-year follow-up, LAAEI was associated with significantly higher freedom from all-atrial arrhythmia recurrence in patients with persistent and long-standing persistent AF without increasing acute procedural complication rate. In patients off-oral anticoagulation, there appears to be a higher risk of thromboembolic events in the LAAEI group.

Background Substrate catheter ablation of scar-related ventricular tachycardia (VT) is a widely accepted therapeutic option for patients with ischemic cardiomyopathy (ICM). Objective The purpose of this study was to investigate whether concomitant amiodarone therapy affects procedural outcomes. Methods A total of 134 consecutive patients (89% male; age 66 ± 10 years) with ICM undergoing catheter ablation of VT were included in the study. Patients were sorted by amiodarone therapy before ablation. In all patients, a substrate-based catheter ablation (endocardial ± epicardial) in sinus rhythm abolishing all “abnormal” electrograms within the scar was performed. The endpoint of the procedure was VT noninducibility. After the ablation procedure, all antiarrhythmic medications were discontinued. All patients had an implantable cardioverter-defibrillator, and recurrences were analyzed through the device. Results In 84 patients (63%), the ablation was performed on amiodarone; the remaining 50 patients (37%) were off amiodarone. Patients had comparable baseline characteristics. Mean scar size area was 143.6 ± 44.9 cm2 on amiodarone vs 139.2 ± 36.8 cm2 off amiodarone (P = .56). More radiofrequency time was necessary to achieve noninducibility in the off-amiodarone group compared to the on-amiodarone group (68.1 ± 20.1 minutes vs 51.5 ± 19.7 minutes; P Conclusion Albeit, VT noninducibility after substrate catheter ablation for scar related VT was achieved faster, with less radiofrequency time and less need for epicardial ablation in patients taking amiodarone, these patients had significantly higher VT recurrence at long-term follow-up when this medication was discontinued.

Direct oral anticoagulants (DOACs) are contraindicated in patients with atrial fibrillation (AF) and mechanical cardiac valves. However, safety and efficacy are controversial in patients with biological cardiac valves. We report the safety and feasibility of periprocedural and long-term treatment with DOACs in patients with biological valves undergoing ablation for AF. A total of 127 patients with AF and biological cardiac valve undergoing CA on uninterrupted DOAC were matched by gender and age with 127 patients with AF and biological cardiac valves undergoing CA on uninterrupted warfarin. All patients were anticoagulated for at least 3–4 weeks prior to ablation with either rivaroxaban (70%) or apixaban (30%), which were continued for at least 3 months and subsequently based on CHA2DS2-VASc score. Mean age of the study population was 63.0 ± 10.9 with 66% being male. The majority of patients on NOACs had aortic valve replacement (59%), while mitral valve was replaced in 41% of patients, which did not differ from the matched cohort on coumadin (aortic valve 57% and mitral valve 43%, (p = 0.8) (p = 0.8), respectively). The CHADS2 score was ≥ 2 in 90 patients (71.0%) on DOAC and 86 patients in (68%) the control (p = 0.6) group. Patients underwent ablation predominantly with uninterrupted rivaroxaban [89 (70%)], while the remaining 38 patients (30%) underwent ablation while on apixaban. Two groin hematomas were observed periprocedurally in both groups. No stroke/transient ischemic attack (TIA) was observed both periprocedurally and at long-term follow-up in either group. Periprocedural and long-term administration of DOACs in patients with biological cardiac valves undergoing AF ablation appears as safe as warfarin therapy.

Background Pulmonary vein isolation (PVI) is the mainstay of catheter ablation (CA) for paroxysmal atrial fibrillation (AF). However, for persistent and long-standing persistent AF, there are no established strategies to improve the success rate of CA. Despite studies indicating that prophylactic cavotricuspid isthmus (CTI) ablation provides no or limited incremental benefit in patients with AF, it is still routinely performed worldwide. Objective We sought to examine whether CTI ablation for AF is associated with improvement in recurrence of all-atrial arrhythmias, compared with PVI alone in patients with and without typical atrial flutter (AFL). Methods A systematic review of PubMed, Cochrane, and Embase was performed for clinical studies including AF patients, reporting outcomes of CTI + PVI versus PVI alone. The primary efficacy endpoint was recurrence of all-atrial arrhythmias. Results Five studies comprising 1400 patients undergoing CTI + PVI versus PVI alone were included; 1110 patients had AF without AFL, and 290 patients had coexistent AF and AFL. After a mean follow-up of 14.4 ± 4.8 months, CTI + PVI was not associated with improvement in recurrence of all-atrial arrhythmias when compared with PVI alone (risk ratio [RR]: 1.29; 95% confidence interval [CI]: 0.93-1.79;p = .13). In the subgroup analysis, there were no differences between both groups in patients with AF without AFL (RR: 1.55; 95% CI: 0.96-2.48; p = .07), and in patients with AF and AFL (RR: 0.91; 95% CI: 0.6-1.39; p = .68). Conclusion In AF patients, irrespective of the presence of typical AFL, additional CTI ablation is not associated with improvement in recurrence of all-atrial arrhythmias, compared with PVI alone.

The CABANA trial reported that catheter ablation, when compared with drug therapy, did not significantly reduce the primary composite end point of death, disabling stroke, serious bleeding, or cardiac arrest in patients with atrial fibrillation. Despite multiple limitations in study design, the CABANA trial still confirmed that catheter ablation of atrial fibrillation led to clinically important and significant improvements in quality of life at 12 months without increasing the risk of complications.

Summary Background MABp1, an antibody that targets interleukin 1α, has been associated with antitumour activity and relief of debilitating symptoms in patients with advanced colorectal cancer. We sought to establish the effect of MABp1 with a new primary endpoint in patients with advanced colorectal cancer. Methods Eligible patients for the double-blind phase of this ongoing, placebo-controlled, randomised, phase 3 trial, had metastatic or unresectable disease, Eastern Cooperative Oncology Group performance status score 1 or 2, systemic inflammation, weight loss, and other disease-related morbidities associated with poor prognosis, and were refractory to oxaliplatin and irinotecan. Patients were randomly assigned 2:1 to receive either MABp1 or placebo. Randomisation codes were obtained from a centrally held list via an interactive web response system. Patients received an intravenous infusion of 7·5 mg/kg MABp1 or placebo given every 2 weeks for 8 weeks. The primary endpoint was assessed in patients who received at least one dose of MABp1 or placebo (modified intention-to-treat population), and was a composite of stable or increased lean body mass and stability or improvement in two of three symptoms (pain, fatigue, or anorexia) at week 8 compared with baseline measurements. This study is registered with ClinicalTrials.gov, number NCT02138422. Findings Patients were enrolled between May 20, 2014, and Sept 2, 2015. The double-blind phase of the study was completed on Nov 3, 2015. Of 333 patients randomly assigned treatment, 207 received at least one dose of MABp1 and 102 at least one dose of placebo. 68 (33%) and 19 (19%) patients, respectively, achieved the primary endpoint (relative risk 1·76, 95% CI 1·12–2·77, p=0·0045). The most common grade 3–4 adverse events in the MABp1 group compared with in the placebo group were anaemia (eight [4%] of 207 vs five [5%] of 102 patients), increased concentration of alkaline phosphatase (nine [4%] vs two [2%]), fatigue (six [3%] vs seven [7%]), and increased concentration of aspartate aminotransferase (six [3%] vs two [2%]). After 8 weeks, 17 (8%) patients in the MABp1 group and 11 (11%) in the placebo group had died, but no death was judged to be related to treatment. The incidence of serious adverse events was not significantly different in the MABp1 group and placebo groups (47 [23%] vs 33 [32%], p=0·07). Interpretation The primary endpoint was a useful means of measuring clinical performance in patients. MABp1 might represent a new standard in the management of advanced colorectal cancer. Funding XBiotech.

Bermekimab is a true human monoclonal antibody that targets interleukin-1alpa (IL-1α), an inflammation-mediating alarmin. IL-1 receptor antagonist (IL-1Ra) is a natural molecule that blocks IL-1α activity by occupying the IL-1 receptor. The effect of endogenous IL-1Ra levels on the effectiveness of bermekimab is unknown. We investigated whether pre-treatment levels of circulating IL-1Ra, assessed by an enzyme-linked immunoassay, correlated with achievement of the primary outcome endpoint (effect on lean body mass and symptoms at week 8) in a Phase III study (2:1 randomization) of bermekimab versus placebo (each with best supportive care) in advanced colorectal cancer. Patients who responded to bermekimab in terms of achieving the primary endpoint had lower levels of IL-1Ra than non-responders (N = 204 patients; median = 843 vs. 1035 pg/ml, p=0.0092); no such relationship was observed in the placebo arm (N = 100 patients; 901 vs. 984 pg/ml, p = 0.55). Multivariate analysis corroborated that, in the bermekimab group, patients with lower baseline IL-1Ra levels were more likely to achieve the primary endpoint (odds ratio (OR) 1.7 (95% confidence interval (CI), 1.1 to 2.6), p = 0.017); in contrast, in the placebo arm, pre-treatment plasma IL-1Ra levels were not associated with outcome (OR 1.2 (95% CI 0.6 to 2.5), p = 0.57). The current findings demonstrate that, in a randomized phase III trial, patients with advanced colorectal cancer and lower levels of circulating IL-1Ra are more responsive to treatment with the IL-1α-targeting antibody bermekimab and these observations define a potential biomarker for anti-IL-1α therapy.

Aims Left atrial (LA) scarring, a consequence of cardiac fibrosis is a powerful predictor of procedure-outcome in atrial fibrillation (AF) patients undergoing catheter ablation. We sought to compare the long-term outcome in patients with paroxysmal AF (PAF) and severe LA scarring identified by 3D mapping, undergoing pulmonary vein isolation (PVAI) only or PVAI and the entire scar areas (scar homogenization) or PVAI+ ablation of the non-PV triggers. Methods and results Totally, 177 consecutive patients with PAF and severe LA scarring were included. Patients underwent PVAI only ( n = 45, Group 1), PVAI+ scar homogenization ( n = 66, Group 2) or PVAI+ ablation of non-PV triggers ( n = 66, Group 3) based on operator’s choice. Baseline characteristics were similar across the groups. After first procedure, all patients were followed-up for a minimum of 2 years. The success rate at the end of the follow-up was 18% (8 pts), 21% (14 pts), and 61% (40 pts) in Groups 1, 2, and 3, respectively. Cumulative probability of AF-free survival was significantly higher in Group 3 (overall log-rank P

Background: Longstanding persistent (LSP) atrial fibrillation (AF) is the most challenging type of AF. In addition to pulmonary vein isolation, substrate modification and triggers ablation ...

Gender-Specific Link of Exercise Intensity With AFBackground Despite widespread interest and extensive research, the association between different levels of physical activity (PA) and risk of atrial fibrillation (AF) is still not clearly defined. Therefore, we systematically evaluated and summarized the evidences regarding association of different intensity of PA with the risk of AF in this meta-analysis. Methods and Results An extensive literature search was performed on databases for studies showing association of exercise with AF risk. Twenty-two studies were identified that included 656,750 subjects. Meta-analytic estimates were derived using random-effects models and pooled odds ratio estimates were obtained. Potential sources of heterogeneity were examined in sensitivity analyses, and publication biases were estimated. Pooled analysis of 7 studies with 93,995 participants reported high risk of incident AF with sedentary lifestyle (pooled OR 2.47 [95% CI 1.25–3.7], P = 0.005). In 3 trials, 149,048 women involved in moderate PA were 8.6% less likely to develop AF compared to women with sedentary life (OR 0.91 [95% CI 0.78–0.97], P = 0.002). Women performing intense exercise were found to have 28% lower risk of AF (OR 0.72 [95% CI 0.57–0.88], P < 0.001). The overall pooled estimate indicated a protective impact of moderate PA in men (pooled OR 0.8133 [95% CI 0.26–1.004], P = 0.06) whereas vigorous PA was associated with a significantly increased AF risk (pooled OR 3.30 [1.97–4.63], P = 0.0002). Conclusion Sedentary lifestyle significantly increases and moderate amount of physical activity reduces the risk of AF in both men and women. However, intense exercise has a gender-specific association with AF risk.

BACKGROUND Nonrandomized studies have reported focal impulse and rotor modulation (FIRM)-guided ablation to be superior to pulmonary vein antrum isolation (PVAI) for persistent atrial fibrillation and long-standing persistent atrial fibrillation. OBJECTIVES This study sought to compare efficacy of FIRM ablation with or without PVAI versus PVAI plus non-PV trigger ablation in randomized persistent atrial fibrillation and long-standing persistent atrial fibrillation patients. METHODS Nonparoxysmal atrial fibrillation (AF) patients undergoing first ablation were randomized to FIRM only (group 1), FIRM + PVAI (group 2) or PVAI + posterior wall + non-PV trigger ablation (group 3). Primary endpoint was freedom from atrial tachycardia/AF. The secondary endpoint was acute procedural success, defined as AF termination, ≥10% slowing, or organization into atrial tachycardia. RESULTS A total of 113 patients were enrolled at 3 centers; 29 in group 1 and 42 each in groups 2 and 3. Group 1 enrollment was terminated early for futility. Focal drivers or rotors were detected in all group 1 and 2 patients. Procedure time was significantly shorter in group 3 versus groups 1 and 2 (p < 0.001). In groups 1 and 2, acute success after rotor-only ablation was achieved in 12 patients (41%) and 11 (26%), respectively. After 12 ± 7 months' follow-up, 4 patients (14%), 22 (52.4%), and 32 (76%) in groups 1, 2, and 3, respectively, were AF/atrial tachycardia-free while off antiarrhythmic drugs (log-rank p

It is unclear whether isolation of the left atrial posterior wall (LAPW) offers additional benefits over pulmonary vein antrum isolation (PVAI) alone in patients with persistent atrial fibrillation (AF).We sought to determine the impact of PVAI and LAPW isolation (PVAI+LAPW) versus PVAI alone on the outcome of ablation of persistent AF.During the first procedure, PVAI was performed in 20 patients (group 1), whereas in 32 patients (group 2), PVAI was extended to the left atrial (LA) septum and coronary sinus (CS), and isolation of the LAPW was targeted (ePVAI+LAPW). Isolation of the superior vena cava was achieved in both groups. All patients, regardless of arrhythmia recurrence, underwent a second procedure 3 months after the first procedure. In patients with reconnection of pulmonary veins or LAPW, reisolation was performed, and a third procedure was performed 3 months later to verify isolation. Patients entered follow-up only after PVAI (group 1) or PVAI+LAPW (group 2) isolation was proven.At the 1-, 2-, and 3-year follow-up examinations, the rates of freedom from atrial tachyarrhythmia without use of an antiarrhythmic drug were 20%, 15%, and 10% in group 1 and 65%, 50%, and 40% in group 2, respectively (log-rank P.001). The median recurrence-free survival time was 8.5 months (interquartile range 6.5-11.0) in group 1 and 28.0 months (interquartile range 8.5-32.0) in group 2.Proven isolation of the LAPW provides additional benefits over PVAI alone in the treatment of persistent AF and improves procedural outcome at follow-up. However, the ablation strategy of ePVAI+LAPW is still associated with a significant high incidence of very late recurrence of atrial tachyarrhythmia."Outcome of Atrial Fibrillation Ablation After Permanent Pulmonary Vein Antrum Isolation With or Without Proven Left Atrial Posterior Wall Isolation" (LIBERATION). ClinicalTrials.gov Identifier: NCT01660100.

INTRODUCTION Outcome data after catheter ablation (CA) for longstanding persistent atrial fibrillation (LSPAF) lasting less than 2 years are limited and highly variable with different ablation approaches. We aimed to assess the long-term outcomes in patients with LSPAF lasting less than 2 years undergoing extended pulmonary vein antrum isolation (PVAI) versus those with additional non-pulmonary vein (PV) trigger ablation. METHODS AND RESULTS In this prospective analysis, 381 consecutive patients with LSPAF lasting less than 2 years (age: 64 ± 9 years, 76% male, atrial fibrillation duration: 19 ± 5 months) undergoing their first CA were classified into two groups: Group 1 (n = 104) received PVAI extended to PW plus isolation of superior vena cava (SVC) and Group 2 ( n = 277) received PVAI + PW + SVC + non-PV-trigger ablation. All patients were followed-up for at least 2 years. In case of recurrence, repeat procedure was offered and non-PV triggers were targeted for ablation in all. After a single procedure, 26 (25%) patients in Group 1 and 172 (62.1%) in Group 2 remained arrhythmia-free (P

Background: This meta-analysis systematically evaluated the outcome of pulmonary vein isolation (PVI) with and without focal impulse and rotor modulation (FIRM) ablation in patients with atrial fibrillation. Methods and Results: Extensive literature search was performed for studies reporting outcomes of PVI alone and PVI+FIRM procedures. For PVI alone, only randomized trials conducted in the past 3 years reporting single-procedure off-antiarrhythmic drugs success rate at ≥12-month follow-up were included. In PVI+FIRM group, all published studies reporting single-procedure off-antiarrhythmic drugs success rate with at least 1-year follow-up were identified. Meta-analytic estimates were derived using DerSimonian and Laird random-effects models, and pooled estimates of success rate (95% confidence interval) were computed. Statistical heterogeneity was assessed using Cochran Q test and I 2 . Study quality was assessed using Newcastle–Ottawa Scale. Fifteen trials were included, 10 with PVI+FIRM (n=511, nonrandomized prospective design), and 5 with PVI-only trials (n=295, randomized trials). All patients in PVI-only trials had 100% nonparoxysmal atrial fibrillation, except 1 study, and no prior ablations. About 24% of PVI+FIRM population had paroxysmal atrial fibrillation. After 15.9±5.5 (median 12) months follow-up, the off-antiarrhythmic drugs pooled success rate was 50% in FIRM+PVI (95% confidence interval, 28%–72%) and 58% in PVI (95% confidence interval, 46%–71%). Difference in effect size between groups was not statistically significant ( P =0.21). No significant heterogeneity (total or within group) was observed in this meta-analysis (negative I 2 values considered equal to zero). Conclusions: The overall pooled estimate did not show any therapeutic benefit of PVI+FIRM approach over PVI alone, which suggests the need to reevaluate the clinical use of FIRM ablation in atrial fibrillation.

Background Catheter ablation reduces ventricular tachycardia (VT) recurrence and implantable cardioverter defibrillator shocks in patients with VT and ischemic cardiomyopathy. The most effective catheter ablation technique is unknown. Objectives This study determined rates of VT recurrence in patients undergoing ablation limited to clinical VT along with mappable VTs (“clinical ablation”) versus substrate-based ablation. Methods Subjects with ischemic cardiomyopathy and hemodynamically tolerated VT were randomized to clinical ablation (n = 60) versus substrate-based ablation that targeted all “abnormal” electrograms in the scar (n = 58). Primary endpoint was recurrence of VT. Secondary endpoints included periprocedural complications, 12-month mortality, and rehospitalizations. Results At 12-month follow-up, 9 (15.5%) and 29 (48.3%) patients had VT recurrence in substrate-based and clinical VT ablation groups, respectively (log-rank p Conclusions An extensive substrate-based ablation approach is superior to ablation targeting only clinical and stable VTs in patients with ischemic cardiomyopathy presenting with tolerated VT. (Ablation of Clinical Ventricular Tachycardia Versus Addition of Substrate Ablation on the Long Term Success Rate of VT Ablation (VISTA); NCT01045668 )

Angiotensin-converting enzyme inhibitors (ACEIs) reduce the incidence of atrial fibrillation (AF).The purpose of this study was to assess the impact of upstream ACEI therapy on postablation AF recurrence and hospitalization in patients with low left ventricular ejection fraction (LVEF).Three hundred forty-five consecutive patients undergoing first AF ablation with low LVEF (≤45%) were classified into group 1 (ACEI+, n = 187 [54%], of whom 44 patients [23.5%] had paroxysmal AF [PAF]) or group 2 (ACEI-, n = 158 [46%]; 31 of these 158 patients [19.6%] had PAF). Additionally, 703 consecutive patients with LVEF45% undergoing first AF ablation were included for a secondary analysis to evaluate the effect of ACEI treatment in normal ejection fraction. In group 1, ACEI therapy started ≥3 months before ablation and continued through follow-up.Baseline characteristics were similar except for hypertension, which was significantly more prevalent in ACEI+ (71% vs 51%, P.001). At 24 ± 7 months of follow-up, 109 nonparoxysmal AF patients in group 1 (76%) and 81 (64%) in group 2 (P = .015) were recurrence free. In multivariate analysis, ACEI therapy was an independent predictor of recurrence (hazard ratio for ACEI-, 1.7, 95% confidence interval 1.1-2.7; P = .026]. However, among PAF patients, ACEI use was not associated with ablation success (80% vs 77% in ACEI+ and ACEI-, respectively; P = .82). In the normal-EF population, the success rates between ACEI+ and ACEI- cohorts were similar (71% vs 74%, P = .31). After the index procedure, 17 patients (9.1%) in the ACEI+ group and 28 (17.7%) in the ACEI- cohort (P= .02) required rehospitalization, for a 49% relative risk reduction (relative risk 0.51, 95% confidence interval 0.29-0.90).Preablation use of an ACEI is associated with improvement in ablation outcome in patients with nonparoxysmal AF with low LVEF.

The goal of this study was to evaluate the impact of hypertension on the outcome of atrial fibrillation (AF) ablation.Hypertension is a well-known independent risk factor for incident AF.A total of 531 consecutive patients undergoing AF ablation were enrolled in this study and divided into 3 groups: patients with uncontrolled hypertension despite medical treatment (group I, n = 160), patients with controlled hypertension (group II, n = 192), and patients without hypertension (group III, n = 179). Pulmonary vein (PV) antrum and posterior wall isolation was always performed, and non-PV triggers were identified during isoproterenol infusion. All patients underwent extensive follow-up.Three groups differed in terms of left atrial (LA) size, non-PV triggers, and moderate/severe LA scar. Non-PV triggers were present in 94 (58.8%), 64 (33.3%), and 50 (27.9%) patients in groups I, II, and III, respectively (p 0.001). After 19 ± 7.7 months of follow-up, 65 (40.6%), 54 (28.1%), and 46 (25.7%) patients in groups I, II, and III had recurrences (log-rank test, p = 0.003). Among patients in group I who underwent additional non-PV trigger ablation, freedom from AF/atrial tachycardia was 69.8%, which was similar to groups II and III procedural success (log-rank p = 0.7). After adjusting for confounders, uncontrolled hypertension (group I) (hazard ratio [HR]: 1.52, p = 0.045), non-PV triggers (HR: 1.85, p 0.001), and nonparoxysmal AF (HR: 1.64, p = 0.002) demonstrated significant association with arrhythmia recurrence.Controlled hypertension does not affect the AF ablation outcome when compared with patients without hypertension. By contrast, uncontrolled hypertension confers higher AF recurrence risk and requires more extensive ablation.

Benefits of PVI in Patients with Atrial Flutter Background This study examined incidence of AF following cavotricuspid isthmus (CTI) ablation alone or CTI plus prophylactic pulmonary vein isolation (PVI) in patients presenting with isolated atrial flutter (AFL) with no history of AF. Methods and Results We enrolled 216 patients with isolated typical atrial flutter and randomized them to CTI alone (group 1, n = 108, 61.2 ± 9.7 year, 75% male) or CTI+PVI ablation (group 2, n = 108, 62.4 ± 9.3 year, 73% male). Insertible loop recorder (ILR) was implanted in 21 and 19 patients from groups 1 and 2, respectively. Remaining patients were monitored with event recorders, ECG, 7-day Holter. Follow-up period was for 18 ± 6 months. Compared to group 1, group 2 had significantly longer procedural duration (75.9 ± 33 min vs. 161 ± 48 min [P < 0.001]) and fluoroscopy time (15.9 ± 12.3 min vs. 56.4+21 min [P < 0.001]). At the end of follow-up, 65 (60.2%) in group 1 and 77 (71.3%) in group 2 were arrhythmia free off-AAD (log-rank P = 0.044). A subgroup analysis was performed with 55 year age cut-off. In the

Background Advanced non-small cell lung cancer (NSCLC) patients were treated as part of a Phase I dose escalation and expansion study evaluating a true human monoclonal antibody targeting IL-1α (Xilonix), which is intended to modulate the malignant phenotype—inhibiting tumor growth, spread and offering relief of symptoms. Methods Sixteen NSCLC patients were included. Patients failed a median of 4 chemotherapy regimens, including 10/16 failing anti-EGFR therapy. Disease progression was evaluated using a multi-modal approach: tumor response, patient reported outcomes (EORTC-QLQC30), and lean body mass (LBM). Patients received infusions every 2 or 3 weeks until progression, and were followed 24 months to assess survival. Results There were no infusion reactions, dose-limiting toxicities, or deaths due to therapy. Albeit not statistically significant, there was a trend in IL-6 (−2.6 ± 18.5 (0.1 [−2.8–2.4]), platelet counts (−11 ± 54 (−4[−36.0–1.0]), CRP (−3.3 ± 30.2 (0.4 [−10.7–1.8]) and LBM (1.0 ± 2.5 (0.4 [−0.5–2.6]). Self-reported outcomes revealed reductions in pain, fatigue and improvement in appetite. Median survival was 7.6 (IQR 4.4–11.5) months, stratification based on prior anti-EGFR therapy revealed a median survival of 9.4 months (IQR 7.6–12.5) for those pretreated (N = 10) versus a survival of 4.8 months (IQR 4.3–5.7) for those without (N = 6, logrank p = 0.187). Conclusion Xilonix was well tolerated, with gains in LBM and improvement in symptoms suggesting a clinically important response. Although not statistically significant, the survival outcomes observed for patients with and without prior anti-EGFR therapy raises intriguing questions about the potential synergy of IL-1α blockade and anti-EGFR therapy. Further study for this agent in NSCLC is warranted.

INTRODUCTION Monomorphic ventricular tachycardia (VT) is an important cause of morbidity and mortality. Use and outcome data of catheter ablation for VT in nonischemic cardiomyopathy (NICM) are limited. METHODS AND RESULTS We obtained data from the 2003-2014 National Inpatient Sample databases. We used propensity score matching to compare patients undergoing catheter ablation versus medical therapy of VT related to NICM, and described the temporal trends in utilization and in-hospital outcomes of catheter ablation of VT in patients with NICM in the United States. From 2003 to 2014, of 133,529 patients hospitalized with the principal diagnosis of VT in NICM, 14,651 (11.0%) underwent catheter ablation. In this period, there was an increasing trend in utilization of catheter ablation (9.3% in 2003-2004 to 12.1% in 2003-2014, adjusted OR [per year], 1.12; 95% CI, 1.08-1.16; Ptrend

AIMS This study investigated the impact of weight loss in longstanding persistent (LSPAF) patients undergoing catheter ablation (CA). METHODS Ninety consecutive obese LSPAF patients were approached; 58 volunteered to try weight loss interventions for up to 1 year (group 1), while 32 patients declined weight loss interventions and were included as a control (group 2). Both groups remained on antiarrhythmic drugs. If they continued to experience AF, CA was performed. Body weight was measured at 6-month intervals and arrhythmia status was assessed by event recorder, electrocardiogram (ECG), and Holter monitoring. Symptom severity and quality of life (QoL) were evaluated by AFSS and SF-36 survey, respectively. A scoring algorithm with two summary measures, physical component score (PCS) and mental component score (MCS), was prepared for QoL analysis. RESULTS Significant reduction in body weight (median -24.9 (IQR -19.1 to -56.7) kg, P

Aims To compare the long-term outcomes of standard ablation of stable ventricular tachycardia (VT) vs. substrate modification, and of complete vs. incomplete substrate modification in patients with structural heart disease (SHD) presenting with VT. Methods and results An electronic search was performed using major databases. The main outcomes were a composite of long-term ventricular arrhythmia (VA) recurrence and all-cause mortality of standard ablation of stable VT vs. substrate modification, and long-term VA recurrence in complete vs. incomplete substrate modification. Six studies were included for the comparison of standard ablation of stable VT vs. substrate modification, with a total of 396 patients (mean age 63 ± 10 years, 87% males), and seven studies were included to assess the impact of extensive substrate modification, with a total of 391 patients (mean age 64 ± years, 90% males). More than 70% of all the patients included had ischaemic cardiomyopathy. Substrate modification was associated with decreased composite VA recurrence/all-cause mortality compared to standard ablation of stable VTs [risk ratio (RR) 0.57, 95% confidence interval (CI) 0.40-0.81]. Complete substrate modification was associated with decreased VA recurrence as compared to incomplete substrate modification (RR 0.39, 95% CI 0.27-0.58). Conclusion In patients with SHD who had VT related mainly to ischaemic substrates, there was a significantly lower risk of the composite primary outcome of long-term VA recurrence and all-cause mortality among those undergoing substrate modification compared to standard ablation. Long-term success is improved when performing complete substrate modification.

Ablation Outcome in Silent Longstanding Persistent AFBackground Impact of catheter ablation on exercise performance, quality of life (QoL) and symptom perception in asymptomatic longstanding persistent AF (LSP-AF) patients has not been reported yet. Methods and Results Sixty-one consecutive patients (mean age 62 ±13 years, 71% males) with asymptomatic LSP-AF undergoing first catheter ablation were enrolled. Extended pulmonary vein antrum isolation plus ablation of complex fractionated atrial electrograms and nonpulmonary vein triggers was performed in all. QoL survey was taken at baseline and 12-months postablation, using Short Form-36 (SF-36). Information on arrhythmia perception was obtained using a standard questionnaire and corroborating symptoms with documented evidence of arrhythmia. Exercise tests were performed on 38 patients at baseline and 5 months after procedure. Recurrence was assessed using event recorder, cardiology evaluation, electrocardiogram, and 7-day holter monitoring. After 20 ± 5 months follow-up, 36 (57%) patients remained recurrence-free off-AAD. Of the 25 patients experiencing recurrence, 21 (84%) were symptomatic. Compared to baseline, follow-up SF-36 scores improved significantly in many measures. For patients with successful ablation, physical component summary (PCS) and mental component summary (MCS) demonstrated substantial improvement (MCS: 64.2 ± 22.3 to 70.1 ± 18.6 [P = 0.041]; PCS: 62.6 ± 18.4 to 70.0 ± 14.4 [P = 0.032]). Postablation exercise study in recurrence-free patients showed significant reduction in resting and peak heart rate (75 ± 11 vs. 90 ± 17 and 132 ± 20 vs. 154.5 ± 36, respectively, P < 0.001), increase in peak oxygen pulse (13.4 ± 3 vs. 18.9 ± 16 mL/beat, Δ5.5 ± 15, P = 0.001), peak VO2/kg (19.7 ± 5 to 23.4 ± 13 mL/kg/min [Δ 3.7 ± 10, P = 0.043]), and corresponding MET (5.6 ± 1 to 6.7 ± 4 [Δ1.1 ± 3, P = 0.03]). No improvement was observed in patients with failed procedures. Conclusion Successful ablation improves exercise performance and QoL in asymptomatic LSP-AF patients.

Ablation Outcome in AF with Concurrent MS and OSA Introduction Metabolic syndrome (MS) and obstructive sleep apnea (OSA) are well-known independent risk factors for atrial fibrillation (AF) recurrence. This study evaluated ablation outcome in AF patients with coexistent MS and OSA and influence of lifestyle modifications (LSM) on arrhythmia recurrence. Methods and Results We included 1,257 AF patients undergoing first catheter ablation (30% paroxysmal AF). Patients having MS + OSA were classified into Group 1 (n = 126; 64 ± 8 years; 76% male). Group 2 (n = 1,131; 62 ± 11 years; 72% male) included those with either MS (n = 431) or OSA (n = 112; no CPAP users) or neither of these comorbidities (n = 588). Patients experiencing recurrence after first procedure were divided into 2 subgroups; those having sporadic events (frequency < 2 months) remained on previously ineffective antiarrhythmic drugs (AAD) and aggressive LSM, while those with persistent arrhythmia (incessant or ≥2 months) underwent repeat ablation. After 34 ± 8 months of first procedure, 66 (52%) in Group 1 and 386 (34%) in Group 2 had recurrence (P < 0.001). Recurrence rate in only-MS, only-OSA, and without MS/OSA groups were 40%, 38%, and 29%, respectively. Patients with MS + OSA experienced substantially higher recurrence compared to those with lone MS or OSA (52% vs. 40% vs. 38%; P = 0.036). Of the 452 patients having recurrence, 250 underwent redo-ablation and 194 remained on AAD and LSM. At 20 ± 6 months, 76% of the redo group remained arrhythmia-free off AAD whereas 74% of the LSM group were free from recurrence (P = 0.71), 33% of which were off AAD. Conclusions MS and OSA have additive negative effect on arrhythmia recurrence following single procedure. Repeat ablation or compliant LSM increase freedom from recurrent AF.

Long-Term Outcome of AF Ablation in MMV PatientsIntroduction It is unclear whether extended pulmonary vein antrum isolation (PVAI) plus nonpulmonary vein (non-PV) trigger elimination prevents more arrhythmia recurrence than PVAI alone in patients with mechanical mitral valve (MMV) undergoing AF ablation. This study compared the efficacy and long-term outcome of 2 ablation strategies—PVAI alone versus extended PVAI plus non-PV trigger elimination—for the treatment of AF in patients with MMV. Methods and Results One hundred and nine consecutive AF patients with MMV were divided into 2 groups: standard PVAI was performed in group 1 (N = 45); in group 2 (N = 64) PVAI was extended to the LA posterior wall, LA septum, and CS; and all non-PV triggers were eliminated. Patients were followed up for 3 years. At the 12th month, 7 (15.6%) patients in group 1, and 39 (60.9%) patients in group 2 were arrhythmia free (log-rank P < 0.001). Four patients (8.9%; 3 cases of AT and 1 case of AF) from group 1, and 12 patients (18.8%; 9 cases of AT, and 3 cases of AFL) from group 2 experienced very late recurrence. At 36 ± 7 months follow-up, the cumulative recurrence after a single procedure was 42/45 (93.3%) in group 1, and 37/64 (57.8%) in group 2 (log-rank P < 0.001). Conclusion Compared with the standard PVAI alone, a strategy including extended PVAI and non-PV trigger elimination is associated with a higher 12-month and long-term arrhythmia-free survival in patients with MMV undergoing AF ablation. Very late recurrence may occur years after the initial procedure with focal AT as the most common type of recurrent arrhythmia.

Summary Background Inflammation is an important feature of the malignant phenotype and promotes angiogenesis, tumour invasiveness, metastases, and cachexia. We used a first-in-class, monoclonal antibody (MABp1) cloned from a human being to target interleukin-1α, a mediator of chronic inflammation. We aimed to assess the safety and tolerability of MABp1 for interleukin-1α blockade in a refractory cancer population. Methods We did an open-label, dose-escalation, and phase 1 study of MABp1 in adults with metastatic cancer at the MD Anderson Clinical Center for Targeted Therapy (Houston, TX, USA). We used a standard 3+3 design to identify the maximum tolerated dose. Patients received MABp1 intravenously once every 3 weeks through four dose levels: 0·25 mg/kg, 0·75 mg/kg, 1·25 mg/kg, and 3·75 mg/kg. After the dose-escalation phase, a second dosing arm was started with dosing every 2 weeks at the maximum tolerated dose. The primary objectives were safety, tolerability, characterisation of the pharmacokinetic profile, and identification of the recommended phase 2 dose. Secondary endpoints included pharmacodynamic effects and antitumour activity. All patients who received at least one dose of MABp1 were included in the safety analyses. This trial is registered with ClinicalTrials.gov, NCT01021072. Findings Between March 15, 2010, and July 30, 2012, 52 patients with metastatic cancer (18 tumour types) received anti-interleukin-1α monotherapy in dose-escalation and expansion groups. MABp1 was well tolerated, with no dose-limiting toxicities or immunogenicity. Thus, the recommended phase 2 dose was concluded to be 3·75 mg/kg every 2 weeks. Pharmacokinetic data were consistent at all dose levels and showed no evidence of accumulation or increased clearance of MABp1 at increasing doses. For 42 assessable patients, median plasma interleukin-6 concentrations had decreased from baseline to week 8 by a median of 2·7 pg/mL (IQR −12·6 to 3·0; p=0·08). Of the 34 patients restaged, one patient had a partial response and ten had stable disease. 30 patients were assessable for change in lean body mass, which increased by a mean of 1·02 kg (SD 2·24; p=0·02) between baseline and week 8. The most common adverse events possibly related to the study drug were proteinuria (n=11; 21%), nausea (7; 13%), and fatigue (7; 13%). The most frequent grade 3–4 adverse events (regardless of relation to treatment) were fatigue (3; 6%), dyspnoea (2; 4%), and headache (2; 4%). Two patients (4%) had grade 5 events (death due to disease progression), which were unrelated to treatment. Interpretation MABp1 was well tolerated, no dose-limiting toxicities were experienced in this study, and disease control was observed. Further study of MABp1 anti-interleukin-1α antibody therapy for advanced stage cancer is warranted. Funding XBiotech.

In this meta-analysis we systemically evaluated the evidences regarding the association of subclinical events of rapid atrial rate episodes (AHRE) detected by implanted devices, with risk of stroke. Pubmed, Medline and other databases were searched for trials that reported relation between

Administration of Isuprel/Adenosine After PulmonaryVein Antrum IsolationBackground Pulmonary vein antrum isolation (PVAI) remains associated with atrial fibrillation (AF) recurrence. We administered adenosine and isoproterenol (ISP) after PVAI to uncover non-PV atrial triggers and PV reconnection, potentially increasing ablation success rate. Methods One hundred and ninety-two consecutive patients with symptomatic AF presenting for PVAI were prospectively studied (group 1). Following PVAI, adenosine (18–24 mg) and ISP (20–30 mcg/min) were administered intravenously. Supplemental ablation was performed in patients with non-PV triggers that induced AF (group 1A). Other subgroups included patients with (group 1B) or without (group 1C) consistent non-PV atrial foci that did not induce AF. A cohort of 196 matched control patients undergoing PVAI without drug challenge was used for comparison (group 2). Results A total of 132 atrial non-PV foci were revealed (31 inducing AF). The majority of atrial foci were observed with ISP (113/132, 86%). Less than 5% of patients had persistent PV recovery during the drug challenge. During a mean follow-up of 22 ± 8 months, PVAI was successful in 110/192 (57%, group 1) versus 100/196 (52%, group 2), P = 0.038. Furthermore, the success rate was statistically different between group 1A (25/32, 78%), group 1B (28/83, 34%), and group 1C (57/74, 74%), P < 0.001. Conclusion After PVAI, ablation guided by the administration of adenosine and ISP to target non-PV triggers inducing AF increased AF ablation outcomes. Patients with non-PV foci that did not induce AF had no further ablation, with the lowest ablation success rate. This group may likely benefit from further ablation after PVAI.

AF Ablation in Patients with Large LA Introduction The effect of catheter ablation on severe left atrial enlargement especially in nonparoxysmal atrial fibrillation (NPAF) patients is not well understood. Whether reverse remodelling may occur after ablation has not been evaluated in this setting. Methods and results Fifty consecutive patients with left atrial diameter (LAD) ≥50 mm, and LA volume >200 cc undergoing catheter ablation for drug-refractory NPAF were included in this study. Transthoracic echocardiographic measurements were performed at baseline and at 12-months postprocedure. Left ventricular end-diastolic and end-systolic dimensions were indexed by body surface area (LVEDDI, LVESDI). Electroanatomic mapping system (Carto or NavX system) and computed tomography (CT) were used for 3-dimensional reconstruction of the LA. All patients underwent posterior wall isolation and pulmonary vein (PV) antrum and extra PV trigger ablations. Long-term follow-up was monitored by event recordings, 7-day Holter monitors and office visits. The mean age was 65 ± 10 years, 78% male, persistent AF 22 (44%), longstanding AF 28 (56%), LAD diameter 56.9 ± 7.8 mm, left ventricular ejection fraction (LVEF) 53 ± 14 and median AF duration 72 (49–96) months. At 12-month follow-up, 27 patients (54%) remained arrhythmia-free off antiarrhythmic drugs. Significant reduction in LAD at follow-up (≥10% reduction) was observed in 52% (26/50) of the total population and among the 63% (17/27) of recurrence-free patients. Magnitude of LA reduction was identically distributed among the persistent and longstanding persistent AF cohorts (16 ± 12% vs 14 ± 16%, respectively, P = 0.15). A significant 20% improvement in LVEF (from 53 ± 14 to 58 ± 9, P = 0.03) was found in the overall population. Improvement was noted in recurrence-free patients. No significant change in LVEDDI and LVESDI was noted. After adjusting for baseline risk factors in a multivariable model, a reduction in LAD was identified as a strong predictor of long-term success (beta = –11.1, P = 0.013). Preexisting LA scarring was associated with increased LAD (beta = 2.7, P = 0.023). No periprocedural or long-term complications were reported. Conclusion Our results show that atrial fibrillation ablation is effective in NPAF patients with severe LA enlargement and is associated with LA reverse remodeling and improvement in LVEF.

Background— This study examined the impact of different ablation strategies on atrial fibrillation (AF) recurrence and quality of life in coexistent AF and atrial flutter (AFL). Methods and Results— Three-hundred sixty enrolled patients with documented AF and AFL were blinded and randomized to group 1, AF±AFL ablation (n=182), or group 2, AFL ablation only (n=178). AF recurrence was evaluated with event recording and 7-day Holter at 3, 6, 9, and 12-month follow-ups. Quality of life was assessed at baseline and at the 12-month follow-up with 4 questionnaires: the Medical Outcome Study Short Form, the Hospital Anxiety and Depression Score, the Beck Depression Inventory, and the State-Trait Anxiety Inventory. Of the 182 patients in group 1, 58 (age, 63±8 years; 78% male; left ventricular ejection fraction, 59±8%) had AF+AFL ablation and 124 (age, 61±11 years; 72% male; left ventricular ejection fraction, 59±7%) had AF ablation only. In group 2 (age, 62±9 years; 76% male; left ventricular ejection fraction, 58±10%), only AFL was ablated by achieving bidirectional isthmus conduction block. Baseline characteristics were not different across groups. At 21±9 months of follow-up, 117 in group 1 (64%) and 34 in group 2 (19%) were arrhythmia free ( P Conclusions— In coexistent AF and AFL, lower recurrence rate and better quality of life are associated with AF ablation only or AF+AFL ablation than with lone AFL ablation. Furthermore, quality of life directly correlates with freedom from arrhythmia, as shown in this study for the first time in patients blinded to the procedure. Clinical Trial Registration— URL: http://www.clinicaltrial.gov/ . Unique identifier: NCT01439386.

Thyroid hormone (TH) is known to enhance arrhythmogenicity, and high-normal thyroid function is related with an increased recurrence of atrial fibrillation (AF) after catheter ablation. However, the impact of thyroid hormone replacement (THR) on AF ablation is not well known. This study evaluated 1163 consecutive paroxysmal AF patients [160 (14%) on THR and 1003 (86%) without THR] undergoing their first catheter ablation. A total of 146 patients on THR and 146 controls were generated by propensity matching, based on calculated risk factor scores, using a logistic model (age, sex, body mass index, and left atrium size). The presence of non-pulmonary vein (PV) triggers was disclosed by a high-dose isoproterenol challenge (up to 30 μg/min) after PV isolation. Clinical characteristics were not different between the groups. When compared to the control, non-PV triggers were significantly greater in the THR patients [112 (77%) vs. 47 (32%), P

We read with interest the letters by Kosiuk et al, Skolnik, Turco, Liu and Yang, and Willey and Biviano. We thank these authors for their interest in our study. We agree with Kosiuk et al that the restoration of sinus rhythm in patients with heart failure and persistent atrial fibrillation (AF) is key to improving ejection fraction and 6-minute walk distance, and we agree with the authors’ data showing a reduction of inappropriate shocks attributable to atrial arrhythmias in patients undergoing ablation.1 Unfortunately, in our trial,2 we did not prospectively collect implantable cardioverter defibrillator inappropriate shocks, and we will not be able to provide solid data. We respectfully disagree with the idea of Dr Skolnik. As mentioned in the discussion and in the clinical perspective of the article, we are not proposing AF ablation in all patients with heart failure, but we are suggesting that this underused therapeutic approach is considered more and more in patients with heart failure.2 The PABA CHF (Comparison of Pulmonary Vein Isolation Versus AV Nodal Ablation With Biventricular Pacing for Patients With Atrial Fibrillation With Congestive Heart Failure) trial,3 although small, showed little improvement with the atrioventricular node ablation and cardiac resynchronization therapy (CRT) device implantation in comparison with ablation. In …

Whether ablation of non-pulmonary vein (PV) triggers after pulmonary vein antrum isolation (PVAI) improves the long-term procedure outcome in patients with paroxysmal atrial fibrillation (PAF) and left ventricular systolic dysfunction is unknown.We sought to evaluate whether a more extensive ablation procedure improves outcomes at follow-up.Consecutive patients with PAF refractory to antiarrhythmic drugs presenting for PVAI were prospectively studied. Patients were categorized into 2 groups: patients with left ventricular ejection fraction (LVEF) ≤35% (group I; n = 175) and patients with LVEF ≥50% (group II; n = 545). Patients in group I were further divided according to whether additional ablation of non-PV triggers was performed (group IA; n = 88) or not (group IB; n = 87). Long-term ablation success off antiarrhythmic drugs after a single procedure was analyzed.Patients in group I had more non-PV triggers than did patients in group II (69.1% vs 26.6%; P.001). During a follow-up of 15.8 ± 4.7 months, fewer patients in group I remained free from recurrences than those in group II (53.7% vs 81.7%; P.001). Long-term ablation success was higher in group IA than in group IB (75.0% vs 32.2%; P.001) and similar to that in group II (75.0% vs 81.7%; P = .44). In multivariate analysis, LVEF ≤35% (hazard ratio 1.68; P = .003) and non-PV triggers (hazard ratio 3.12; P.001) were independent predictors of recurrences.In patients with PAF and left ventricular systolic dysfunction, ablation of non-PV triggers in addition to PVAI significantly improves their long-term procedure outcome.

Background Transesophageal echocardiography (TEE) is recommended in patients undergoing atrial fibrillation (AF) ablation, but use of this strategy is variable. Objective To evaluate whether TEE is necessary before AF ablation in patients treated with novel oral anticoagulants (NOACs). Methods We performed a prospective multicenter registry of AF patients undergoing radiofrequency catheter ablation on uninterrupted NOACs (apixaban and rivaroxaban). All patients were on NOACs for at least 4 weeks before ablation. Heparin bolus was administered to all patients before transseptal catheterization to maintain a target activated clotting time above 300 seconds. A subset of 86 patients underwent brain diffuse magnetic resonance imaging (dMRI) to detect silent cerebral ischemia (SCI). Results A total of 970 patients (514 [53%] apixaban patients and 456 [47%] rivaroxaban patients) were enrolled for this study. The mean age was 69.5 ± 9.0 years, with 824 patients (85%) having nonparoxysmal AF, and 636 patients (65.6%) were male. The average CHA 2 DS 2 -VASc score was 3.01 ± 1.3 and CHADS 2 score was ≥2 in 609 patients (62.8%). Intracardiac echocardiogram ruled out left atrial appendage thrombus in all patients whose left atrial appendage was visualized (692, 71%), and detected "smoke" in 407 patients (42%). SCI at postprocedure dMRI was detected in 2.3% (2/86). One thromboembolic event (transient ischemic attack) (0.10%) with positive dMRI occurred in a patient on uninterrupted rivaroxaban with longstanding persistent AF. Conclusion Our study illustrates that performing AF ablation while on uninterrupted apixaban and rivaroxaban without TEE is feasible and safe. This finding has important clinical and economic relevance.

Variant rs2200733 on Chromosome 4q25 Confers Increased Risk. Introduction: Several genome-wide association studies have identified rs2200733, a single-nucleotide polymorphism (SNP) at 4q25 to be the most common chromosomal variant present in patients with atrial fibrillation (AF). We aimed to explore the association of rs2200733 with AF through a systematic review and meta-analysis. Method: An extensive literature search was performed on PubMed, and other databases using the key words “genetics” and “AF.” Seven case-control studies evaluating the association via multivariate analysis were identified including a total of 83,335 subjects (10,546 with AF, 72,789 referent individuals without AF). Meta-analytic estimates were derived using random effects models. Potential sources of heterogeneity were examined in sensitivity analyses, and publication biases were estimated. Result: At pooled analysis, there was a strong independent association between the variant rs2200733 and the risk of AF (OR 1.89 [95% CI 1.62–2.16], P < 0.001). Minor allelic frequencies for SNP rs22000733 were significantly more prevalent in AF population than non-AF. Metaregression results revealed that country of descent (logOR 0.38, P = 0.45) or site of study (logOR: −0.16, P = 0.41) did not moderate the overall effect size. Conclusion: Variant rs2200733 on chromosome 4q25 independently confers increased risk of AF. This finding will aid in improving our understanding of AF pathophysiology, risk prediction, and stratification of treatment strategy. (J Cardiovasc Electrophysiol, Vol. 24, pp. 155-161, February 2013)

Objectives This study investigated the left atrial appendage (LAA) by computed tomography (CT) and magnetic resonance imaging (MRI) to categorize different LAA morphologies and to correlate the morphology with the history of stroke/transient ischemic attack (TIA). Background LAA represents one of the major sources of cardiac thrombus formation responsible for TIA/stroke in patients with atrial fibrillation (AF). Methods We studied 932 patients with drug-refractory AF who were planning to undergo catheter ablation. All patients underwent cardiac CT or MRI of the LAA and were screened for history of TIA/stroke. Four different morphologies were used to categorize LAA: Cactus, Chicken Wing, Windsock, and Cauliflower. Results CT scans of 499 patients and MRI scans of 433 patients were analyzed (age 59 ± 10 years, 79% were male, and 14% had CHADS2 [Congestive heart failure, Hypertension, Age >75, Diabetes mellitus, and prior Stroke or transient ischemic attack] score ≥2). The distribution of different LAA morphologies was Cactus (278 [30%]), Chicken Wing (451 [48%]), Windsock (179 [19%]), and Cauliflower (24 [3%]). Of the 932 patients, 78 (8%) had a history of ischemic stroke or TIA. The prevalence of pre-procedure stroke/TIA in Cactus, Chicken Wing, Windsock, and Cauliflower morphologies was 12%, 4%, 10%, and 18%, respectively (p = 0.003). After controlling for CHADS2 score, gender, and AF types in a multivariable logistic model, Chicken Wing morphology was found to be 79% less likely to have a stroke/TIA history (odd ratio: 0.21, 95% confidence interval: 0.05 to 0.91, p = 0.036). In a separate multivariate model, we entered Chicken Wing as the reference group and assessed the likelihood of stroke in other groups in relation to reference. Compared with Chicken Wing, Cactus was 4.08 times (p = 0.046), Windsock was 4.5 times (p = 0.038), and Cauliflower was 8.0 times (p = 0.056) more likely to have had a stroke/TIA. Conclusions Patients with Chicken Wing LAA morphology are less likely to have an embolic event even after controlling for comorbidities and CHADS2 score. If confirmed, these results could have a relevant impact on the anticoagulation management of patients with a low-intermediate risk for stroke/TIA.

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.