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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.

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: 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— We examined the influence of catheter ablation and periprocedural anticoagulation regimen on trajectory of migraine in atrial fibrillation patients with or without migraine history. Methods and Results— Forty patients with (group 1: 64±8 years; men 78%) and 85 (group 2: 61±10 years; men 73%) without migraine history undergoing atrial fibrillation-ablation were enrolled. Migraine status and quality of life were evaluated using standardized questionnaires. Diffusion magnetic resonance imaging of brain was performed for all at pre and 24 hours post procedure. Catheter ablation was performed with (88, 70%) or without (37, 30%) continuous warfarin treatment. Fifty-four patients (11 and 43 from groups 1 and 2, respectively) had subtherapeutic international normalized ratio on procedure day. At 17±5 months follow-up, from group 1, 25 (63%) reported no migraine, 10 (25%) had P P Conclusions— In most patients, migraine symptoms improved substantially after catheter ablation. Interestingly, the only cases of new migraine and aggravation of pre-existent headache had subtherapeutic international normalized ratio during the procedure and new cerebral infarcts.

Background— Obstructive sleep apnea (OSA) may be associated with pulmonary vein antrum isolation (PVAI) failure. The aim of the present study was to investigate if treatment with continuous positive airway pressure (CPAP) improved PVAI success rates. Methods and Results— From January 2004 to December 2007, 3000 consecutive patients underwent PVAI. Patients were screened for OSA and CPAP use. Six hundred forty (21.3%) patients had OSA. Patients with OSA had more procedural failures ( P =0.024) and hematomas ( P P P =0.001). At the end of the follow-up period (32±14 months), 79% of the non-CPAP and 68% of the CPAP group were free of atrial fibrillation ( P =0.003). Not using CPAP in addition to having non-PV triggers strongly predicted procedural failure (hazard ratio, 8.81; P Conclusions— OSA was an independent predictor for PVAI failure. Treatment with CPAP improved PVAI success rates. Patients not treated with CPAP in addition to having higher prevalence of non-PV triggers were 8 times more likely to fail the procedure.

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: 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.

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: 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: 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.