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Introduction: Left atrial (LA) scar, identified by bipolar voltage mapping, is a frequent finding in patients with non-paroxysmal atrial fibrillation (NPAF). We evaluated the most common sites of scar formation in the LA in a series of NPAF patients. Methods: Consecutive NPAF patients undergoing their first catheter ablation at our center were included in this analysis. Voltage mapping was performed in sinus rhythm (SR) using a 3D electro-anatomic mapping system and a 10-pole circular mapping catheter. The LA was divided into following regions: septum, posterior wall, lateral wall, anterior wall and roof. The threshold for low voltage was Results: A total of 359 NPAF (224, 62.4% persistent AF) patients undergoing their first ablation procedure with voltage mapping performed in SR were included in this study. Mean number of points taken to map the scar was 281.2±96.3. Low voltage area was detected in 209/359 (58%) cases; 108 (48.62%) persistent AF, 101(74.8%) long-standing persistent AF, p Conclusion: In the NPAF population, LA scar was detected in significantly less number of persistent AF patients. Scars were mostly located in the posterior wall of left atrium followed by the antero-septum region. Characterization of the LA scars would be helpful in optimizing the ablation targets.

Introduction: Scar-related VT is common in post-MI patients. We evaluated the benefits of remapping with the multi-electrode catheter after acute success was achieved with the single-point ablation catheter in post-MI VT patients undergoing catheter ablation. Methods: Consecutive post-MI patients undergoing VT ablation were included. 3-D electroanatomic maps were obtained in sinus rhythm and/or during hemodynamically-stable VT with the multi-electrode PentaRay catheter. All underwent substrate mapping with standard scar settings (≤ 1.5 mV). Ablation was performed with the single-point ablation catheter and acute success was defined as non-inducibility of all VT at the end of the procedure. After acute success was achieved, some operators remapped with the PentaRay catheter to identify residual abnormal potentials. Results: A total of 121 patients (table) undergoing VT ablation were prospectively analyzed. Acute success was achieved in 117 (96.6%) cases. Remapping with the PentaRay catheter was performed in 102 (84.3%) cases. Few sites with delayed potentials were detected in 66/102 (61%) cases. These sites were targeted for further ablation. At 1 year follow-up, 76/102 (74.5%) of the remap population and 14/19 (73.6%) patients from the no-remap group remained arrhythmia-free off-AAD (p=NS). Conclusion: In our series, detection of few sites with late potentials by remapping with the multi-electrode catheter, after achieving acute success with single-point ablation did not improve the success rate at 1 year. Thus, the clinical benefits of remapping with multi-electrode catheters is not clear in VT patients undergoing substrate-based catheter ablation.

Introduction: Intramural PVCs are identified by equal but not remarkably early activation on at least two separate sites. The site of origin of these foci is typically determined by a deductive approach using extensive mapping in the surrounding areas. Ablation of the intramural VT is particularly challenging, since conventional ablation strategies often fail to obtain transmural lesion formation. We report the long-term success rate of ablation of the intramural PVCs at our center. Methods: Consecutive patients undergoing VT ablation at our center were screened and 73 patients with intramural PVCs identified by activation mapping and pace mapping were included in the analysis. Pace-mapping was performed at a pacing cycle length equal to the coupling interval of the spontaneous PVCs. If these PVCs could not be eliminated by conventional ablation, bipolar ablation or ablation from multiple sides or ablation using half-normal saline (HNS) was performed. Standardized RF power settings (up to 40W) were used during the procedure. Ablation was performed using 4-mm irrigated tip catheter guided by 3-D mapping system and intra-cardiac echocardiography. Patients were followed with remote monitoring as well as ICD interrogations and office visits every 3 months for 3 years. Results: A total of 73 patients were included in the analysis (mean age 56.2±8.6 years, 69.8% male, LVEF 54±12%). The intramural focus was effectively ablated by bipolar ablation or ablation from multiple sides in 51 (69.8%) and with the use of HNS in the remaining 22 patients. Median RF time was 11.14±8.7 minutes. Acute success (non-inducibility of the VT) was achieved in 71 (97.2%) patients. At 3 years follow-up, 66 (90.4%) remained arrhythmia-free. Conclusion: Intramural PVCs could be successfully ablated using bipolar or multiple-side ablations or utilizing half-normal saline with high long-term success rate.

Introduction: Loss-of-function (LOF) polymorphisms of the cytochrome P450 2C19 (CYP2C19) gene are associated with reduced hepatic bioactivation of clopidogrel. Hypothesis: To evaluate the prevalence of LOF polymorphisms of CYP2C19 and the incidence of device-related thrombosis (DRT) when clopidogrel is replaced with half dose novel oral anticoagulant (NOAC) in patients with reduced clopidogrel metabolism. Methods: Consecutive Watchman patients were genotyped for CYP2C19 polymorphisms. Patients with reduced clopidogrel metabolism received half dose NOAC plus aspirin during the “dual antiplatelet therapy (DAPT) phase” post-Watchman implantation (between 45 days and 6 months). The incidence of DRT among genotyped patients (Group I, n=401) and a control group without genotypization (Group II, n=357) which received standard DAPT is reported. Results: Overall, 758 Watchman patients were included (mean age: 75±8 yrs, 63% males, CHA 2 DS 2 -VASc: 4.6±1.5; HAS-BLED: 3.2±1.1). Of the 401 Group 1 patients, 25.69% (n=103) were reduced clopidogrel metabolizers. In 87.4% of them, clopidogrel was replaced with half-dose NOAC during the “DAPT phase” post-Watchman implantation whereas 12.6% received ASA plus full-dose NOAC due to the presence of a significant peri-device leak. During the “DAPT phase”, DRT was documented in 1 (0.2%) patient of Group I and 7 (1.96%) patients of Group II (p=0.029). On multivariate analysis, a genotype-tailored antithrombotic strategy was associated with a significant reduction in DRT (odds ratio: 0.11; 95% confidence interval: 0.01 - 0.98; p-value: 0.048). Conclusions: Approximately 25% of our Watchman patients had clopidogrel resistance. Substitution of clopidogrel with half dose NOAC in reduced clopidogrel metabolizers significantly reduced the incidence of DRT.

Background: A considerable proportion of elderly patients are known to have coexistent atrial fibrillation (AF) and amyloidosis. Both conditions increase stroke risk. Objective: We evaluated the best anticoagulation strategy in a series of AF patients with amyloidosis. Methods: Consecutive AF patients with coexistent amyloidosis undergoing catheter ablation at our center were included in the analysis. Based on the stroke-prophylaxis approach they were divided into 2 groups; group 1: left atrial appendage occlusion (LAAO) with Watchman and group 2: oral anticoagulation. Following LAAO, all patients remained on full dose non-vitamin K oral anticoagulants (NOAC) for 45 days. Transesophageal echocardiogram (TEE) was performed at 45 days to assess completeness of closure. If the occlusion was complete, patients were kept on aspirin, 81 mg/day for long-term. In case of leak or dense ‘smoke’ in the left atrium (LA) or enlarged LA, they were prescribed half-dose NOAC. NOACs included dabigatran, apixaban, endoxaban and rivaroxaban. Group 2 patients remained on full-dose NOAC during the whole study period (1 year). All patients were prospectively followed up for 1 year. Results: A total of 87 patients were included in the analysis; group 1: 56 and group 2: 31 . CHA 2 DS 2 -VASc score was comparable between the groups (gr. 1: 3.7±1.6 and gr. 2: 3.2±1.7, p=0.18). The most commonly used NOACs were apixaban (45, 51.7%) and rivaroxaban (34, 39%). After the 45-day TEE, 34 patients from group 1 remained on baby-aspirin and 22 on half-dose NOAC. Of the 22, 12 patients had leaks Conclusion: In our series of patients with coexistent AF and amyloidosis, half-dose NOAC following LAA occlusion procedure was observed to be the safest stroke-prophylaxis strategy.

Introduction: General anesthesia is routinely used during the implantation of S-ICD which dramatically prolongs total procedure time, patient recovery time and adds unnecessary potential complications. The tumescent local anesthesia (TLA) technique provides anesthesia of large areas of skin and subcutaneous tissue by means of the direct infiltration of large volumes of a dilute local anesthetic solution into subcutaneous fat. Hypothesis: TLA during S-ICD implantation is feasible and associated with a reduction in total procedure time. Methods: A retrospective analysis was conducted in two medical centers during 2019. Five patients underwent S-ICD with TLA due to baseline conditions that represented relative contraindications to general anesthesia (e.g, muscular dystrophy). A large volume of a local anesthesia solution (i.e., 1 liter of normal saline, 30 cc of 1% lidocaine, 30 cc of bupivacaine, 1 mg of epinephrine, 12.5 mEq of sodium bicarbonate) was used in each patient and injected 10 minutes prior to incisions. Five other patients who underwent S-ICD under general anesthesia served as controls. The skin-to-skin time, total length of procedure and post-procedural pain levels were compared between groups. Results: A total of 10 patients were included (male: 60%; mean age: 62 ± 16). All devices were implanted for primary prevention of sudden cardiac death. TLA was considered the best anesthetic approach in five patients who had medical conditions that represented a high risk of complications if general anesthesia was employed. In the group of TLA, an average of 260 ± 45 cc was administered. The skin-to-skin times were 44.8 ± 13.9 minutes in patients who underwent general anesthesia vs. 46.2 ± 14.3 minutes in TLA (p = 0.3). The total procedural time was 148 ± 28 min vs 64.2 ± 13.4 min (p Conclusions: S-ICD implantation using TLA appears to be a feasible and safe option in patients with contraindications to general anesthesia. This technique significantly decreases total procedure time with better post-procedural pain control.

Introduction: The Transcatheter Leak Closure With Detachable Coils Following Incomplete Left Atrial Appendage Closure Procedures (TREASURE) is a prospective, nonrandomized, single-center study. This study was undertaken to investigate the efficacy of transcatheter leak closure with endovascular coils in patient with incomplete percutaneous/epicardial left atrial appendage (LAA) closure procedures and high thromboembolic (TE)- and bleeding-risk. Hypothesis: We report the efficacy of transcatheter leak closure with endovascular coils in patients with incomplete LAA closure. Methods: Sixty-five consecutive patients with a clinically relevant residual leak (mean age: 72±8 years; 73.8% males; CHA 2 DS 2 -VASc: 4.7±1.1; HAS-BLED: 3.7±0.7) underwent percutaneous closure of the LAA patency via embolization coils. Trans-esophageal echocardiography (TEE) was performed at 60±15 days post-procedure. Results: LAA closure had been previously attempted with a Watchman device in 62 patients, and a LARIAT in 3. Baseline TEE documented a moderate or severe leak in 14 (21.5%) and 51 (78.5%) patients, respectively. Procedure and fluoroscopy times were 69±37min and 22±15min, respectively; the mean volume of iodinated contrast medium used was 82±43mL. Coil deployment was successful in all cases [median n. of coils attempted: 3 (IQR:2-5); median n. of coils deployed: 3 (IQR: 2-4)]. The overall complication rate was 3.1% (1 pericardial tamponade, 1 pericardial effusion). Peri-procedural angiographic and TEE outcomes demonstrated complete obliteration or a negligible residual opacification with a trivial residual jet in 62 cases (95.4%), and a partial occlusion with moderate residual jet in 3 (6.4%). Follow-up TEE after 67±12 days revealed complete LAA sealing or a negligible residual leak in 63 cases (96.9%). Coil deployment led to an average reduction of 90.1% in leak size (p Conclusions: Transcatheter LAA leak occlusion via endovascular coils appears to be a safe, effective, and promising approach in high TE-risk patients with incomplete LAA closure.

Introduction: Radiofrequency catheter ablation (CA) is the preferred treatment for premature ventricular contractions (PVCs). Ionizing radiation has major side effects for both patients and personnel in the electrophysiology laboratory. Fluoroless procedures are routinely performed for atrial fibrillation and simple PVC cases. Nonetheless, left ventricular (LV) summit/intramural PVCs cases are more challenging and clinical outcomes and complications have been poorly studied in this category with the use of fluoroless ablation. Hypothesis: We aimed to compare acute, long-term success rate and complications between fluoroless procedures versus standard approach for left ventricular (LV) summit/intramural PVCs. Methods: We conducted a retrospective analysis of patients who underwent PVC ablation under fluoroscopy and non-fluoroscopy at two institutions. Results: A total of 41 cases were enrolled (male: 61%; mean age: 55 ). Twenty-five cases underwent ablation under fluoroscopy whereas 16 underwent non-fluoroscopy ablation. Acute success was seen in 88% of non-fluoroscopy cases compared to 87.5% in the fluoroscopy group ( p = 0.9). The PVC recurrence at 12 months was similar between both groups (non-fluoroscopy: 15% vs Fluoroscopy: 18%) ( p = 0.9). No complications occurred in any group. Conclusions: Fluoroless CA is an emerging technique in the treatment of LV summit/intramural PVCs that appears to have similar clinical outcomes and complications compared to conventional fluoroscopic procedures.

Introduction: Interventional therapies aiming at excluding the left atrial appendage (LAA) from systemic circulation have been established as a valid alternative to oral anticoagulation (OAC) in patients at high thromboembolic (TE) risk. However, their efficacy on stroke prophylaxis may be compromised owing to incomplete LAA closure. Additionally, the need for an alternative TE prevention may remain unmet in patients with contraindications to OAC whose appendage anatomy is unsuitable for some conventional devices commercially available. Hypothesis: We aimed at evaluating the feasibility of LAA closure with the novel Gore® Cardioform Septal Occluder (CSO) in patients with incomplete appendage ligation or anatomical features which do not meet the manufacturer’s requirements for Watchman deployment. Methods: Twenty-one consecutive patients (mean age: 72±6 years; 85.7% males; CHA 2 DS 2 -VASc: 4.5±1.4; HAS-BLED: 3.6±1.0) were included. Trans-esophageal echocardiography (TEE) was performed within 2 months to assess for residual LAA patency. Results: Fourteen patients had incomplete LAA closure following surgical (n=6) or Lariat ligation (n=8). In 7 patients with an appendage anatomy unsuitable for Watchman deployment, the mean maximal landing zone size and LAA depth were 14.4±1.3mm and 18.6±2.8mm. Successful CSO deployment was achieved in all patients. No peri-procedural complications were documented.Procedure and fluoroscopy times were 46±13min and 14±5min. Follow-up TEE after 58±9 days revealed complete LAA closure in all patients. Conclusions: Transcatheter LAA closure via a CSO device might be a valid alternative in patients with residual leaks following failed appendage ligation or whose LAA anatomy does not meet the minimal anatomical criteria to accommodate a Watchman device.

Introduction: Macro-reentrant arrhythmias involving the cavo-tricuspid isthmus (CTI) are common in patients with atrial fibrillation (AF). Bidirectional CTI block is the ablation strategy of choice, but it can be surprisingly difficult to obtain at times. Objective: Aim of this study was to systematically assess the characteristics of the CTI to determine its most common anatomical variants to be anticipated for ablation. Methods: This is a prospective observational study in which intracardiac echocardiography (ICE) was used to visualize the CTI of patients undergoing AF ablation. The presence of anatomical variants was recorded, and length was measured along the central CTI in atrial systole. CTI systolic shortening measured in sinus rhythm and defined as: [(diastolic length - systolic length)/(diastolic length)]x100. Results: 180 patients (65±9 years old, 31% female, 37% paroxysmal AF) are included in the study. Mean CTI length was 31±9 mm, with a systolic shortening of 25±13%. A prominent Eustachian ridge was present in 32%, a Chiari network in 11%, and at least one pouch-like recess in 35%, with a mean depth of 5.3±2.5 mm (Figure). A longer CTI was observed in patients with non-PAF compared with patients with PAF (33 vs. 27 mm, P Conclusion: Anatomical variants of the CTI are common and should be anticipated in case of a challenging CTI ablation. A long CTI is associated with OSA and might warrant further clinical screening to identify this common AF comorbidity. CTI systolic shortening correlates with the type of AF and could represent a measure of right atrial contractility.

Background: Transthyretin (TTR), a transport protein produced by liver, is closely associated with amyloidosis. Tetramers of TTR circulating in blood can dissociate to monomers that misassemble into amyloid fibrils. Although amyloidosis is a frequent finding in aged atrial fibrillation (AF) patients, the relevance of serum-TTR in AF is unknown. Objective: We evaluated if post-ablation change in serum-TTR level has any prognostic association with long-term ablation outcome in AF patients. Methods: One-hundred-forty-five patients (age: 62.8 ± 6.2years, male 69%, non-paroxysmal AF 41%, BMI : 30.8 ± 6.3) were included in this prospective study. Patients with chronic inflammatory conditions or taking anti-inflammatory drugs were excluded. All patients received pulmonary vein isolation plus isolation of left atrial posterior wall and superior vena cava. In non-paroxysmal AF, non-PV triggers identified by isoproterenol challenge were ablated. Fasting blood samples were collected at baseline and 24-hours post-ablation. Samples were tested for TTR using an automated quantitative test. Results: Mean TTR concentration was 27.94±6.5 mg/dL at baseline and 26.33±9.2 mg/dL at 24-hour post ablation (p Conclusion: Our findings demonstrated significant association of higher recurrence rate with decreased serum-TTR tetramer level at 24-hour post-ablation.

Background: Electrical isolation of the left atrial appendage (LAAEI) is considered in patients presenting with recurrence following effective PV isolation. Objective: We evaluated the prevalence of LAA reconnection following LAAEI in patients undergoing repeat procedure for AF recurrence. Methods: Consecutive AF patients undergoing repeat ablation for arrhythmia recurrence following LAAEI were included in this analysis. Transesophageal echocardiogram (TEE) was performed in all at baseline to evaluate LAA function. Isoproterenol infusion up to 30 μg/min for 10 to 15 min was administered to detect LAA triggers. Re-isolation of the LAA was performed if triggers were detected. Off-drug success rate was assessed in all. Results: A total of 594 post-LAAEI patients with recurrent AF were included in the analysis. At the redo, PVs were found to be electrically silent in all. LAA reconnection was detected in 214 (36%) patients. Baseline TEE revealed normal LAA contractility and flow-velocity in all. Re-isolation of the LAA was performed in these 214 patients. In patients with no LAA reconnection (n=380), non-PV triggers from other sites were targeted for ablation. There was no difference in the clinical characteristics of patients with vs. without LAA reconnection (Table). At 2 years after the repeat procedure, 201 (94%) patients with and 351 (92.3%) without LAA reconnection were arrhythmia-free off-drugs (p=0.47). Conclusion: In this series, LAA reconnection rate was 36% after single LAAEI procedure and re-isolation of the appendage led to high success rate. Additionally, normal LAA functions detected by TEE correctly predicted recovery of conduction in the LAA.

Background: Ablation strategy for long-standing persistent atrial fibrillation (LSPAF) is highly variable with diverse outcomes. Objective: We evaluated the change in left ventricular ejection fraction (LVEF) with different ablation approaches in LSPAF patients with heart failure (HF). Methods: Consecutive LSPAF patients with HF (LVEF group 1: received standard ablation (PV isolation+ isolation of left atrial posterior wall and superior vena cava) and group 2: standard ablation plus isolation of coronary sinus (CS) and left atrial appendage (LAA). High-dose isoproterenol challenge (20-30 μg for 10-15 min) was utilized to reveal LAA and CS triggers; electrical isolation was the procedural endpoint for LAA and CS ablation. If PVs were electrically silent due to presence of severe scar, LAA and CS were empirically isolated even in the absence of detectable triggers. LVEF was measured by transesophageal echocardiogram (TEE) performed at baseline and 6 months post-ablation. Patients were monitored for arrhythmia-recurrence off-antiarrhythmic drugs (AAD) as per our standard protocol. Results: Group 1 included 52 patients and group 2 had 106. Baseline characteristics were comparable across groups (age: 66.2 ± 7.3 and 64.4 ± 9.4; male: 41 (78.8%) and 87 (82.1%); BMI: 32.3 ± 6.8 and 30.4 ± 6.4 in group 1 and 2). Mean baseline LVEF (%) was 36.2±5.5 and 35.1±8.3 in group 1 and 2 respectively (p=NS). At the 6-month TEE, mean LVEF was significantly higher than the baseline value in group 2 (47.7±11 vs 35.1±8.3, p Conclusion: In our study population, ablation strategy including LAA and CS isolation along with the standard ablation resulted in significant improvement in the LVEF as well as higher rate of arrhythmia-free survival.

Background: Autoimmune disorders (AuID) are pro-inflammatory conditions and inflammation is known to promote atrial fibrillation (AF). We evaluated the arrhythmia profile in female AF patients with vs without AuID. Methods: Consecutive female patients undergoing their first catheter ablation at our center were included in the analysis and divided into two groups; group 1: with AuID (n=192) and group 2: no AuID (n=2324). All received PV isolation + isolation of left atrial posterior wall and superior vena cava. Additionally, non-PV triggers identified by isoproterenol-challenge were ablated in all.Patients were included in group 1 if they had an established diagnosis of Type 1 Diabetes (DM), rheumatoid arthritis (RA), Lupus, inflammatory bowel disease (IBD), Psoriasis, Sjogren syndrome, Grave’s disease or Celiac disease. Results: Baseline characteristics of the study groups are provided in table 1. Most prevalent AuID were DM (56, 29%), RA (52, 27%), Lupus (35, 18.2%) and IBD (40, 20.8%). Patients with AuID were significantly younger and more had non-paroxysmal AF. They also had larger LA diameter and lower LVEF compared to the group with no AuID. Significantly higher number of non-PV triggers were detected in group 1 patients (149 (77.6%) vs 883 (38%), p Conclusion: Women with autoimmune diseases experienced AF at an earlier age with significantly more non-paroxysmal AF compared to those without. However, similar ablation success was observed in both groups that could be attributed to the ablation strategy including all detectable non-PV triggers. Table

Background: Left atrial (LA) scar can be identified with bipolar voltage mapping during sinus rhythm (SR). It is not clear whether the same voltage criteria can be applied during atrial fibrillation (AF). Objective: Aim of this study was to compare voltage maps performed in the same patient both in AF and SR. Methods: Voltage mapping was performed using a 10-pole circular mapping catheter in patients with non-paroxysmal AF undergoing first time RF ablation. For descriptive purposes, the LA was divided in 6 regions: septum, posterior wall (PW), inferior wall (IW), lateral wall, anterior wall, and roof. The threshold for low voltage was 35%. Results: 16 patients (62% persistent AF, 38% longstanding persistent AF) were included in the study. The map density was comparable during AF and SR (mean points per map 551 vs 547, paired t test P = NS). 2 patients displayed normal voltage during both AF and SR. 14 patients showed areas of low voltage during AF, which were still present during SR in 8. All patients with mild “scarring” during AF (n = 4), showed normal voltage during SR. Of the 7 patients with moderate “scarring”, 2 patients showed normal voltage during SR, while in the remaining 5 “scarring” was only mild during SR. 3 patients showed extensive “scarring” during AF, which was only moderate during SR. During AF, areas of low voltage were more commonly observed in the PW (12/14) followed by the IW (6/14) and antero-septum (4/14); while in SR, in the antero-septum (4/8), PW (3/8) and IW (3/8). Interestingly, in all patients both the PW/IW and (less dramatically) the antero-septum showed more “scarring” during AF as compared to SR. Conclusion: Areas of low voltage are more severe and diffuse during AF when compared to SR. When areas of low voltage are detected during AF, they are more commonly seen in the PW, IW and antero-septal areas.

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.

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 …

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 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.

Background: Prolongation of the PR interval in the electrocardiogram (ECG) is known to be associated with increased risk of atrial fibrillation (AF). We examined the association of selected single nucleotide polymorphisms (SNPs) with PR interval in AF patients. Methods: Four hundred AF patients undergoing catheter ablation were prospectively enrolled at our center. DNA extraction and genotyping for 16 AF-related SNPS from blood samples were performed using Qiagen QiaAMP kit and TaqMan assay respectively. A total of 371 DNA samples were available for genotyping. Multivariate linear regression analyses (after adjusting for age, gender, BMI, AF type) were applied to test allelic association (for minor allelic frequency) with baseline PR interval. PR interval duration in millisecond (ms) was derived from 12-lead ECGs recorded at the time of patient enrollment. Results: Three hundred seventy-one AF patients (67% male, 62±12 year, left atrial size 45.3±7 mm, 64% non-paroxysmal) undergoing catheter ablation were included in the analysis. Two SNPs, rs3807989 and rs7193343 were identified to have significant association with baseline PR interval. For rs3807989 (7q31), median [interquartile range] of PR interval durations were 174 (149-202), 169 (145-194), 162 (137-184) ms for AA, AG, GG (risk allele: A) respectively. The regression analysis for rs3807989 in a dominant model, showed significant allelic association (regression coefficient (beta) 9.8 [95% CI 1.58 to 18.02], p=0.019) with prolonged PR interval. For rs7193343, median [interquartile range] of PR interval durations were 169 (144-194), 162 (142-184), 154 (128-186) ms for CC, CT, TT (risk allele: T) respectively. When considering the effect of rs7193343 fitted with an additive model, significant inverse association with PR interval was observed (beta -7.4 [95% CI -14.23 to -2.63], p=0.032). Conclusion: We identified two novel genetic markers located near developmental genes CAV1 and ZFHX3 to be associated with PR interval; rs3807989 correlated directly with prolonged PR duration while rs7193343 demonstrated inverse correlation with the phenotype. Defining the etiology of this differential association will provide important insight into underlying AF mechanisms.

Introduction: Bipolar voltage mapping detects areas of scar and guides ablation of VT. The role of endocardial unipolar voltage mapping is not well defined. We examined the endo-epicardial substrate in a mixed cohort of patients with structural heard disease (SHD) to determine whether an endocardial unipolar low voltage area predicts the presence and location of an epicardial scar. Results: Data from 24 consecutive patients with SHD (11 ICM, 6 NICM, 3 HCM, 2 ARVC, 1 myocarditis, 1 Brugada) with a detailed (mean points per map 200) combined endocardial-epicardial substrate mapping were retrospectively reviewed. Maps were obtained using a 3D mapping system (CARTO 3) and normal thresholds used were ≤1.5 mV for bipolar voltage, and ≤5.5 (RV) or ≤8.3 mV (LV) for unipolar voltage. Mapping was performed in the LV in 17 patients, in the RV in 6 patients, in both in 1 patient. An endocardial unipolar low voltage area was found in 21/25 maps. In 12/21 maps there was no corresponding epicardial scar, while in 3/4 cases an epicardial scar was detected despite a negative unipolar map (PPV=43%, NPV=25%, P=NS; Fig. 1). In the 9 cases with both positive endocardial unipolar and epicardial bipolar maps, the epicardial scar was found in the corresponding ventricular region of the endocardial low-voltage area, although unipolar area had a tendency to overestimate the area of the scar (115 vs 95 cm 2 ). Conclusion: In this series of patients with SHD, analysis of unipolar voltage maps could not reliably predict the epicardial arrhythmogenic substrate. There is a modest correlation between areas of endocardial unipolar low voltage and epicardial scars (57% of patients with an abnormal unipolar map had a normal epicardial substrate). Moreover, an epicardial substrate cannot be safely excluded based on a normal unipolar endocardial map. Fig. 1 Abnormal bipolar epicardial map (left) with corresponding normal unipolar endocardial map (right) in a patient with ARVC. Pink dots represent area of defragmentation.

Introduction: Remote magnetic navigation (RMN) and ablation with the magnetic irrigated tip catheter has been reported as a feasible and safe technique for the treatment of ventricular arrhythmias (VA). We compared the procedural benefit and the outcomes of patients with ischemic cardiomyopathy (IC) undergoing VAs ablation with the RMN versus the manual approach. Methods: Consecutive pts with IC undergoing VAs ablation both with RMN and with manual ablation at different Institutions were enrolled. Substrate mapping and ablation technique with scar homogenization were utilized for ablation with the end point of elimination of all abnormal electrograms within and or around the scar area. Procedural data and outcomes were analyzed. Post-ablation pacing maneuvers and isoproterenol were used to verify Vas inducibility. Results: A total of 218 consecutive pts (85.3% male, 69.2±7.7 years, LVEF 30.6±8.2) with IC were included with 80 pts undergoing manual ablation while 138 pts underwent RMN ablation. Patients with a scar size < 60 cm2 at the 3D voltage mapping system were excluded. The mean scar size was 140 ± 61 cm2. VT was inducible in 83% pts with a cycle length of 352.1±70.7 msec. The density of the substrate map was higher in the RMN group when compared to the manual ablation group (553±118 vs 347±97, p At 15.4±6.8 months follow-up the success rate in the RMN group was 81.2% (112) while in the manual ablation group 55 (69%) pts were recurrence free (p=0.037). There was one pericardial tamponade which required pericardiocentesis in the manual ablation group. Conclusion: This study shows that VAs ablation using RMN in pts with IC and a scar size greater than 60 cm2 increases success rate at follow up when compared to manual ablation. The better outcome might be due to the higher amount of time dedicated to RF applications to achieve scar homogenization rather than mapping

Introduction: Atrial fibrillation (AF) is common after coronary artery bypass grafting (CABG). Ranolazine is a novel drug used in the treatment of angina, which also has antiarrhythmic properties. Recent studies demonstrated the benefit of ranolazine in preventing post-operative AF (POAF) in patients undergoing CABG. Hypothesis: To assess the role of ranolazine in preventing POAF in patients undergoing CABG surgery. Methods: We performed comprehensive search of PubMed, MEDLINE, and Cochrane library database on the study assessing the effectiveness of ranolazine in preventing POAF by comparing it with standard therapy. Meta-analysis was performed by fixed effect model by entering POAF events and the total population from each study. Data are expressed as Odds ratio (OR) with 95% confidence interval (CI). Results: A total of three studies with 628 patients (259 pts in ranolazine group, 369 pts in standard therapy group) were included in the meta-analysis. In pooled analysis, ranolazine was associated with 54% reduction in post-operative AF events compared to standard therapy [odds ratio = 0.46 (0.31, 0.70), P Conclusions: Ranolazine may prove beneficial in the prevention of POAF following CABG. However, because of small number of studies further research with large randomized clinical trial is warranted to determine specific dose and duration of ranolazine therapy.

Background: Atrial fibrosis or scar is considered a substrate change related to atrial fibrillation (AF); by slowing conduction and increasing heterogeneity it could provide a substrate for AF. However, it is still not known whether AF causes the profibrotic changes in the left atrial wall or simply facilitates the manifestation of an existing aging-related structural remodeling in older patients. We examined scar prevalence and severity in patients aged ≥ 75 years with and without AF to address this question. Method: Five hundred seventy one patients undergoing radio-frequency catheter ablation for AF or supraventricular tachycardia (SVT) were included in this prospective analysis and classified into 2 groups; group 1: patients with AF (n=308, 62% male, median 77.8 (75 to 91) years, 46% paroxysmal and 64% persistent AF) and group 2: patients with diagnosis of SVT (n=263, 56% male, median 80 (75 to 88) years). Left atrial (LA) scarring was determined by three-Dimensional (3D) voltage mapping. Scar was defined as an area with a bipolar voltage amplitude ≤ 0.05 mV, indistinguishable from noise. The degree of scar was described as a percentage of the LA area (mild 60%) involved. Results: Age and gender distribution was similar in both groups. Left atrial scar was detected in 172 (56%) patients in group 1 and 134 (51%) in group 2 (p=0.24). After adjusting for age and gender in multivariable logistic model, diagnosis of AF or SVT did not show to have any association with the incidence of scar (p=0.22). Based on the 3D mapping, 52(30%) patients were classified as having mild LA scarring, 88(51%) moderate scar and 32(19%) with severe scar in group 1. Distribution of scar severity in group 2 was: mild 50(37%), moderate 67(50%), and severe in 17(13%), which was similar to that of AF patients (p=0.248). Conclusion: Similar prevalence and distribution of severity of the left atrial scarring in elderly patients with and without atrial fibrillation suggest age-dependent substrate remodeling to be the major contributor of scar formation. Our results indicate that scar could facilitate atrial fibrillation in predisposed subjects only.

Introduction: The objective of this retrospective multicenter study is to report the initial long-term performance results after percutaneous exclusion of the LAA with the endo-epicardial Lariat device to prevent AF-related thromboembolic events. Methods and results: Patients with successful LAA ligation and at least 1-year follow-up were analyzed (N=355). At 1 year, TEE follow-up was present in 172 patients. A leak was defined as presence of flow into the LAA as assessed by TEE. At 6 months, 19 (11%) patients had a leak; 2 strokes occurred: 1 in a patient without a leak and 1 associated with mesenteric ischemia in a patient without a known acute leak, who died before repeat TEE could be performed. At 12 months, 34 (20%) patients had a leak; 6 patients developed a neurological event (5 strokes and 1 TIA), 4 in patients with a leak, 2 in patients without a leak. 3% were followed-up for more than one 1 year (with a mean of 21±9 months). 1 additional thromboembolic event (TIA) occurred 14 months post-implant in a patient without anticoagulation and with a partially excluded LAA (stump), although no leak or thrombus were detected on standard TEE. Among patients with a leak (36% of those with long-term follow-up), 75% were on long-term anticoagulation and no additional TE events were detected. Out of 355 patients, 9 (2.5%) patients had a neurological event: 4 with a leak, 4 without a leak and 1 in a patient where TEE was not repeated. Considering those with known LAA status, thromboembolic events were more common in patients with a leak (4/34 vs 4/136; RR 4, 95% CI 1.1-15.4). Conclusion: In this multicenter experience with the Lariat device, the rate of leaks was high (20% of those with TEE follow-up at 1 year). Thromboembolic events were not rare (overall, 2.5%), and occurred more frequently in patients with a leak (RR 4).

Background: Radiofrequency catheter ablation is widely-used to target frequent premature ventricular complexes (PVCs) in patients with and without structural heart disease, with reported ablation-success rate being in the 80% range. However the risk-factors that correlate with ablation-failure have not been defined yet. We aimed to assess the prevalence of recurrent PVCs in the immediate post-ablation period and their relevance in relation to the clinical outcome of catheter ablation of PVCs. Methods: A consecutive series of 104 patients (age: 58±15 years, male 57%, LVEF 54±10.8) with frequent PVCs and without structural heart disease referred for catheter ablation at our center, were included in this prospective analysis. Successful ablation was defined as the absence of spontaneous or induced clinical PVC, both with or without isoproterenol at the end of the procedure. Arrhythmia burden was assessed at baseline and follow-up using 24-hour Holter recording. Telemetry was performed for at least 12 hours in the immediate post-ablation period. Ablation success was defined as ≥ 90% reduction of the initial PVC burden at 3-month follow-up. Results: At baseline, the mean number of PVC morphologies was 1.4± 2.2 and the predominant PVCs commonly originated from right ventricular outflow tract [34 (32.6%)], coronary cusps [28 (27%)], interventricular septum [16 (15.3%)] and left ventricular outflow tract [13 (12.5%)]. Elimination of predominant PVCs was achieved in all patients. In the 12-hour post-ablation period, recurrence of PVCs was observed in 16 (15%) patients, which were transitory and never documented at follow-up monitoring. The most common sites of origin of these early PVCs were anterior cardiac veins, papillary muscles and mitral valve annulus. At follow-up, recurrence was reported in 5 of the 104 patients (4.8%) of which only one had early PVCs during the 12-hour post-ablation period. Conclusions: Recurrence of PVCs in the immediate post-ablation period is transient and not indicative of the failure of the index procedure. Furthermore, pre-discharge PVCs do not demonstrate any definite correlation with the risk of late recurrence. This is most likely the result of myocardial irritation secondary to the trauma of the ablation procedure.

Introduction: Focal impulse and rotor modulation (FIRM)-guided ablation targets localized sources that are thought to sustain AF. In previous reports, it has been shown that FIRM is effective in terminating or organizing AF. We sought to evaluate the acute success of FIRM in patients with persistent and LSP AF undergoing ablation in our centers. Methods: This was a multicenter prospective observational study. FIRM was performed alone or before conventional ablation. Rotors were ablated as confirmed by their absence during remapping and acute success was defined as AF termination, organization or slowing 10%. Results: 57 patients were enrolled (mean age 63 ± 10; 7% LSP). Rotors-only ablation was performed in 56% of patients, and preceded conventional ablation in 44%. There were no major periprocedural adverse events. No focal impulses were found, while rotors were present in all patients (3.9 ± 1.2 per patient; 66% in the LA). In the RA, the majority of rotors were in the lateral wall (53%) and in the septum (30%). In the LA, most of the rotors were in proximity of the pulmonary veins (48%), with the second most common locations being around the mitral annulus or in the septum (17% and 13% respectively). Mean procedural time for FIRM only procedures was 226 ± 52 minutes vs a median of 210 (168-240) minutes for FIRM + conventional ablation procedures (p = NS). Overall acute success was achieved in 35% of patients (3% AF termination, 16% AF organization, 16% AF slowing) with a mean RF time to complete FIRM ablation of 30 ± 15 minutes; no difference in acute success was found when comparing persistent to LSP patients (28% vs 50%; p = NS). Conventional ablation following FIRM did not significantly increase the rate of acute success (1 additional patient converted to sinus rhythm during pulmonary vein isolation). Conclusion: Rotors were present in all patients undergoing ablation for non-paroxysmal AF, most commonly the right atrial lateral wall, septum or around the pulmonary veins. Their ablation was not effective in obtaining AF organization/termination during the procedure.

Background: 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 and severe LA scarring/fibrosis identified by 3D mapping undergoing ablation of the pulmonary veins (PVAI) only or PVAI and the entire scar areas (scar homogenization) or PVAI plus ablation of the non-PV triggers. Methods: One-hundred seventy seven consecutive patients with paroxysmal atrial fibrillation and severe left atrial scarring were included in this study. LA scarring was diagnosed by 3D voltage mapping. The degree of scar was described as severe when >60% of the LA area was involved. Non-PV triggers were defined as ectopic triggers originating from sites other than pulmonary veins such as interatrial septum, superior vena cava, left atrial appendage, ligament of Marshall, crista terminalis and coronary sinus. Patients underwent ablation of the pulmonary vein antrum (PVAI) only (n=45, group 1), PVAI extended to the entire scar areas (scar homogenization [n=66, group 2]) or PVAI plus ablation of non-PV triggers (n=66, group 3). Choice of ablation strategy was determined by the operator. Patients were followed up for arrhythmia recurrence with event recorders, ECG and Holter monitoring. Results: Baseline characteristics were not different between the groups (age 63±9 vs 58±10 vs. 60±11 years, p=0.23; male 71%, vs. 72% vs. 73% p= 0.91). After a single procedure, all patients were followed-up for a minimum of two years. The long-term success rate at the end of the follow up was 19% (12 pts) in group 1, 21% (14 pts) in group 2, and 61% (40 pts) in group 3. Kaplan-Meier log-rank test indicated that the cumulative probability of AF-free survival was significantly higher in group 3 (overall log-rank p Conclusions: In patients with paroxysmal atrial fibrillation and severe left atrial scarring, PVAI plus ablation of non-PV triggers is associated with significantly better long-term outcome than PVAI alone or when PVAI is combined with scar homogenization.

Introduction: Post-operative atrial fibrillation (AF) is reported in up to 5-40% of patients following coronary artery bypass graft (CABG) surgery. Age-related atrial dilatation and fibrosis, electrical remodeling, autonomic imbalance and post-operative inflammation are few of the many pathophysiological factors that play an important role in the genesis and persistence of post-CABG AF. Recent data on fibroblast-myocyte interaction indicates the central role of cardiac fibrosis in the origin of non-pulmonary vein (non-PV) drivers that serve as a source for maintenance of AF. Therefore, we sought to examine the prevalence of non-PV triggers and their impact on ablation outcome in post-CABG AF patients. Methods: Two-hundred sixty seven patients with history of CABG undergoing catheter ablation for atrial fibrillation were included in this analysis (61±11 years, 69% male, LVEF 50±10%, LA size 41.0±6.8mm, non-PAF 72%). All patients underwent pulmonary vein antrum (PVAI) and posterior wall isolation. Non-PV triggers were defined as ectopic triggers originating from sites other than pulmonary veins such as interatrial septum, superior vena cava, left atrial appendage, coronary sinus, ligament of Marshall, crista terminalis. Those were identified by isoproterenol challenge and were ablated based on operator choice. Results: During ablation, non-PV triggers were detected in 243 (91%) patients. The triggers were most commonly mapped to CS (62%) and LAA (70%). Additional sites of non-PV triggers were LA septum, superior vena cave, crista terminalis and mitral valve annulus. Based on operator choice, non-PV triggers were ablated in 118 of the 243 patients and not targeted in 125 patients. At the end of 32±7 month follow-up after a single procedure, overall success rate was 130 (53.5%). Of the 118 patients undergoing non-PV trigger ablation, 81(68.6%) patients remained arrhythmia-free off anti-arrhythmic drugs compared to 49 of 125 (39.2%) where non-PV ablation was not performed (log rank p Conclusion: Our results for the first time demonstrate that non-PV foci are highly prevalent in post-CABG AF patients and ablation of those triggers results in significantly better long-term outcome.

Introduction: We sought to investigate the characteristics and outcomes of patients who underwent RF ablation of PM ventricular arrhythmias (VA) in our center. Results: 26 patients were included, median age was 66 years (16 to 85), 46% female, all with normal LVEF. PM VAs were PVCs in 68% patients, and PVC + VT in 32%. Site of origin was the LV infero-septal PM in 73%, LV antero-lateral PM in 15% and right ventricular RV septal PM in 12%. 46% of patients showed other VAs in addition to the one originating from the PMs; in 33% of these patients, additional VAs were 2 or more. These VAs were mostly PVCs (92%), localized in the LVOT (64% - 56 % in the basal LV and 44% in the aortic cusps) and the septal RVOT (36%). The only additional VT was fascicular. All the PMs and mappable additional VAs were ablated with RF energy through an irrigated catheter and the aid of ICE; a remote magnetic navigation system (RMS) was used in half of the procedures. In one case, PVC suppression required additional epicardial ablation. Major complications occurred in 2 patients (8%): 1 pericardial effusion (the patient underwent ablation of a crista terminalis premature atrial complex in the same procedure) and 1 pseudoaneurysm. Acute success (PM VA suppression/non-inducibility) was achieved in 96% of patients (the patient with pericardial effusion could be anticoagulated further and the procedure was stopped). After a median follow-up period of 8 (4-14) months, long-term success (no PM VT recurrence or PVC burden reduced by 80% off antiarrhythmic drugs) was 92% after a single procedure, 96% after repeat procedures. When considering additional VAs, the only recurrence was a parahisian RVOT PVC. No difference in acute or overall long-term success was observed when comparing RMS-guided vs standard procedures (respectively 92% vs 100 % and 100% vs 92%; P = NS). Conclusion: PM VAs are most commonly PVCs originating from the LV infero-septal PM and are frequently (48%) associated with an additional ventricular focus (LVOT > RVOT >> fascicular VT). RF ablation is safe and effective in eliminating or significantly reduce the burden of PM VAs, as well the extra-PM foci that are commonly encountered in this population. RMS guided ablation is not inferior to standard ablation in this subset of patients.

Introduction: The best treatment option for the management of patients (pts) with heart failure (HF) and persistent AF is unknown. The AATAC trial showed that catheter ablation (CA) is superior to Amiodarone in achieving freedom from AF at follow up. In this analysis we present the outcome sorted by type of AF procedure. Methods: AATAC was a randomized multicenter study. Pts with persistent AF, dual chamber ICD or CRTD, NYHA II-III and LV EF Results: PVI was performed in 22 patients undergoing ablation, while PVI+PW+NPV ablation was performed in 80 patients. Baseline characteristics were not different between the groups. At 26±8 months follow-up, the success rates in PVI, PVI+PW+NPV, and AMIO groups were 8 [36.4%] and 63 [78.8%] and 34 (34.0%) respectively, p Conclusion: This randomized study shows that PVI alone has a low success rate similar to Amiodarone when compared to PVI plus posterior wall plus non pv trigger in patients with heart failure and persistent AF.

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 P P P 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.

Introduction: Earlier studies have demonstrated that some AF patients develop spontaneous atrial scarring that leads to genesis and perpetuation of the arrhythmia. However, it is still unclear why it happens in some and not in others. Therefore, we hypothesized that the atrial scar phenotype is associated with certain specific genetic variants and examined the relationship between AF-related single-nucleotide polymorphisms (SNP) and left atrial scar. Methods: Four hundred AF patients (67% male, 62±12 year, left atrial size 45.3±7 mm, 64% non-paroxysmal) undergoing catheter ablation were prospectively enrolled at our center. DNA extraction and genotyping for 16 AF-associated SNPS identified by GWAS study were performed from the collected blood samples using Qiagen QiaAMP 96 well blood kit and TaqMan assay respectively. Three hundred seventy-two DNA samples were available for genotyping. The Hardy-Weinberg equilibrium was assessed using Chi-square analyses. Multivariable logistic model was utilized to identify predictors of LA scar after adjusting for age, gender, LA size, hypertension and diabetes mellitus and odds ratio (OR) and 95% confidence intervals were computed. Results: Of all 16 SNPs, rs3807989 showed a strong inverse association with LA scar at univariate analysis (0.54 [0.348-0.89] p= 0.014) in the overall population. After adjustment for covariates, the association became highly significant indicating a 50% reduction in scar risk (OR 0.50 (0.30-0.83) p=0.007). When stratified by type of AF, rs3807989 genotype predicted a substantially stronger 69% risk-reduction in the non-PAF population (OR 0.31 (0.15-0.62) p=0.0009). Conclusion: The SNP, rs3807989 on chromosome 7p31, was demonstrated to be associated with reduced risk of left atrial scar formation in AF patients. This genetic variant is located in close proximity to the caveolin-1 gene which is known to have an anti-fibrotic role by inhibiting transforming growth factor-β1, a key mediator in the fibrosis process. Therefore, it can be postulated that by some unknown mechanism the candidate chromosomal variant potentially upregulates caveolin-1 function resulting in attenuation of fibrosis and scar formation.

Introduction: Periprocedural anticoagulation management is key to minimize bleeding and thromboembolic complications during and after radiofrequency catheter ablation. Uninterrupted strategies with warfarin in high risk patients have shown superiority over interrupted strategies. We sought to assess the safety and feasibility uninterrupted rivaroxaban during atrial fibrillation (AF) ablation in patients with long standing persistent atrial fibrillation. Methods: One hundred and ninety six (196) consecutive patients undergoing AF ablation with uninterrupted rivaroxaban (last dose taken with food the night before the procedure and the following dose taken the night of the procedure) were matched by age and sex with an equal number of patients undergoing AF ablation with uninterrupted warfarin on a “therapeutic range”. All patients underwent pulmonary vein antrum isolation and ablation of non pulmonary vein triggers as disclosed by isoproterenol challenge test. Results: Baseline characteristics and procedural variables were similar between groups. Mean INR in warfarin group was 2.2 ± 0.5. CHADS2 Score was ≥ 2 in 141 (72%) in the rivaroxaban group and 130 (66%) in the warfarin patients (p=0.20). One pericardial tamponade and one groin hematoma occurred in rivaroxaban group while 2 patients in warfarin group developed groin hematoma. One TIA with positive MRI was present in the rivaroxaban group. Conclusions: Uninterrupted rivaroxaban therapy appears to be as safe and efficacious as uninterrupted warfarin strategy in preventing bleeding and thromboembolic events in patients undergoing long standing persistent AF ablation.

Introduction: Earlier evidences support the origin of ectopic beats from non-pulmonary vein (non-PV) areas that initiate and maintain AF and elimination of these triggers is known to provide better arrhythmia-free survival. Of the different types, non-paroxysmal AF (NPAF) are more prevalently associated with non-PV drivers. Although emerging data on myocytes-fibroblast interactions provide some insight into the pathophysiology of non-PV triggers, the exact mechanism of origin of these ectopic foci is still unknown. Therefore, we examined the association of several AF-specific genetic variants with prevalence of non-PV triggers in NPAF patients undergoing catheter ablation. Methods: Four hundred AF patients (67% male, 62±12 year, left atrial size 45.3±7 mm, 64% non-paroxysmal) undergoing catheter ablation were prospectively enrolled at our center. DNA extraction and genotyping for 16 AF-associated SNPS from collected blood samples were performed using Qiagen QiaAMP 96 well blood kit and TaqMan assay respectively. Three hundred seventy-two DNA samples were available for genotyping. Multivariate logistic regression analysis (adjusted covariates: age, gender, LA size, hypertension and diabetes) was used for assessing predictive role of individual SNP; and logistic kernel-machine approach was applied to test the cumulative effect of multiple SNPs as a group with non-PV triggers. Result: In the non-paroxysmal AF population, significant allelic association was detected between non-PV triggers and rs6599230 (OR 0.57 [95% CI 0.31-0.88], p=0.042) and rs1448817 (OR 1.82 [95%CI 1.12-3.40], p=0.034). Interestingly, rs6599230 suggested a protective effect with 43% risk reduction while rs1448817 was an independent predictor of higher risk of developing non-PV triggers. Conclusion: Our results identified predictive association of two genetic variants, rs6599230 and rs1448817, with non-PV triggers in non-paroxysmal AF patients. Interestingly, the association was distinctive. The SNP, rs6599230 located in close proximity to SCN5A gene, was found to have a protective effect against development of arrhythmogenic triggers in the extra-PV sites whereas rs1448817 on chromosome 4q25 increased the risks of having non-PV triggers.

Introduction: Radiofrequency catheter ablation of atrial fibrillation is performed under fluoroscopic guidance and therefore carries radiation risk exposure for the both the patient and the operator. Three-dimensional mapping systems and newer technologies to allow non-fluoroscopic catheter visualization together with intracardiac echo have reduced but not abolished the fluoroscopy exposure. We aim to demonstrate the feasibility, the safety and the efficacy of catheter ablation for atrial fibrillation without the use of fluoroscopy. Methods: A totally fluoro-less approach was developed for AF ablation at our Institution. 94 consecutive AF patients underwent zero fluoroscopy catheter ablation for atrial fibrillation. In the zero fluoroscopy cases, the fluoroscopy arm was kept far away from the patient table. Access including double trans-septal, mapping with the Carto 3 system and ablation were all performed without fluoroscopy with the use of ICE and the Carto 3 system. These 94 patients were compared with 94 control patients matched for age, sex and type of AF who underwent AF ablation by the same operator with the use of fluoroscopy. Results: Baseline characteristics were similar between fluoroless (N=94, Age=64.5 ± 10.1, 75.5% male, 48% paroxysmal) and control (N=94, Age=65.1 ± 9.9, 72.3% male, 50% paroxysmal) group. Non-PV triggers were detected and ablated in 51 (54.3%) and 56 (59.6%) patients in fluoroless and control group respectively (p=0.5). Average fluoro time in control group was 10.1 ± 4.7 minutes. Procedure duration was comparable (120.4 ± 25.8 vs. 122.2 ± 28.7, p =0.6). After the short term median follow-up of 4.5 (4 – 6.5) months, 10 (10.6 %) patients in flourless and 9 (9.6%) patients in control group experienced recurrences (p=0.8).One pericardial effusion requiring pericardiocenteis occurred in the fluoroless group. Conclusions: Our series show that zero fluoroscopy ablation of atrial fibrillation with the use of newer technologies is feasible, safe and efficacious at the short term follow up. Importantly in our series the double transeptal was performed without fluoroscopy and the ablation was not limited to the pulmonary veins only but included ablation of the posterior wall, the coronary sinus and the left atrial appendage.

Introduction: Catheter ablation of atrial fibrillation (AF) is the most valid therapeutic option to achieve rhythm control. Pulmonary veins (PV) are the most known trigger of AF, although recently we have become more aware of the importance of non-PV triggers. Expression of microRNA (miRNA) has been shown to be regulated in many cardiovascular disease. We sought to study expression patterns of miRNA in patients (pts) with AF undergoing ablation to facilitate their application as both diagnostic and prognostic markers. Methods: As part of the standard procedure for AF ablation a double transseptal sample of myocardial tissue is obtained via a transseptal needle. The small piece of atrial septal tissue can be retrieved from the needle as a result of piercing the atrial septum. MiRNA was hybridized to microarrays to determine relative levels of miRNAs in the samples. For a subset of the miRNAs we validated expression through quantitative real time PCR. All pts underwent PV-antrum and non-PV trigger ablation guided by isoproterenol challenge test. Results: Atrial tissue of 11 pts undergoing AF ablation has been utilized for MiRNA assessment. Mean age was 61.27 ± 10.5 years and 8 (72.7%) pts were male. Six (54.5 %) pts had paroxysmal AF. During the ablation non-PV triggers were detected in 8 (72.7 %) pts. Recurrence of AF occurred in 3(27.3 %) pts. Expression of miR-21, miR-26a and miR-29a was higher in pts with non-PV triggers, while miR-30c had lower expression in pts who had recurrence of atrial tachyarrhythmias. Spearman’s nonparametric correlation coefficient was calculated and miR-21, miR-26a, miR-29a were positively correlated with non-PV triggers (r = 0.58, p=0.06 for all three miRNAs), while miR-30c level had inverse correlation (r = (-) 0.78 %, p=0.005) with recurrence (Figure). Conclusions: Expression of miR-21, miR-26a, miR-29a correlates with the presence of non-PV triggers. This information could be clinically relevant in planning patient specific procedures.

Introduction: Catheter ablation of cavo-tricuspid isthmus (CTI) is considered to be the most effective therapy for eliminating target arrhythmia in lone atrial flutter (AFL). However, many patients subsequently develop AF after CTI ablation. Therefore, prophylactic pulmonary vein antrum isolation (PVAI) along with CTI ablation could be considered as an alternate option in these patients. We aimed to compare long-term incidence of post-ablation atrial fibrillation following CTI alone or CTI plus PVAI in patients presenting with isolated AFL and no history of atrial fibrillation. Methods: This multi-center prospective randomized study enrolled 216 patients undergoing catheter ablation for isolated typical atrial flutter. Patients were randomized to CTI alone (group 1, n=108, 61.2±9.7 year, 75% male, LVEF 59±10%) or combined ablation CTI+PVAI (group 2, n=108, 62.4±9.3 year, 73% male, LVEF 57±11%). Insertible Loop Recorder (ILR) was implanted in 21 and 19 patients from group 1 and 2 respectively, on the day of the ablation procedure. Remaining patients were monitored for recurrence with event recorders, ECG, 7-day Holter and cardiology evaluation. All patients were followed up for 18±6 months for recurrence. Results: Compared to group 1, group 2 had significantly longer average procedural duration (75.9±33 min vs. 161±48 min [p Conclusion: Prophylactic PVAI in lone atrial flutter caused marked reduction in new-onset AF in patients ≥ 55 years whereas younger patients (

Introduction: Catheter ablation of persistent atrial fibrillation (AF) has a lower success rate when compared to paroxysmal AF patients. Whether in persistent AF patients ablation of the pulmonary vein antrum and posterior wall is sufficient to achieve long term freedom from AF is debated in the literature. We investigated if the ablation on non pv triggers from first procedure in addition to PV and posterior wall(PW) isolation could improve the procedural success rate. Methods: 622 consecutive pts with persistent AF undergoing the first AF ablation were analysed and divided into 2 groups according to their ablation strategy. In group 1, pulmonary vein plus posterior wall ablation was performed (n=203) while in group 2 pulmonary veins plus posterior wall plus sustained and non sustained non pv triggers as disclosed by isoproterenol challenge were ablated. (n=419). All patients were followed up with intensive holter and event monitoring. Results: Clinical baseline characteristics were not statistically different between groups. After 17.8 ± 8.8 months follow-up, 118(58.1%) Group I and 283 (67.5%) Group II patients were free from any atrial tachyarrhythmias (log-rank p= 0.027). After adjusting for age, gender and clinically relevant variables, PVI and PW ablation alone was associated with significantly high recurrence. (Hazard ratio: 1.4, 95% Confidence Interval = 1.1– 1.8, p=0.02). Further, Group I patients undergoing redo procedure after a failed ablation had more NPV trigger Group II (80% vs 60%, p = 0.002, respectively, figure), while the number of patients with PV reconnection were similar between groups (65% vs. 64%, p=1.0). Conclusions: The results of our study shows that after a single procedure the ablation of non PV triggers, improves the long-term success rate in patients with persistent AF.

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 CHADS 2 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 P 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.