AF Pts Research Articles

Patient-tailored low-voltage-guided ablation of atrial fibrillation: initial experience using a novel ultra-low-temperature cryoablation system

Abstract Introduction The ideal ablation strategy for patients (pts) with persistent atrial fibrillation (PersAF) is still debated. In recent randomized studies, strategies of ablating electrically abnormal atrial regions in addition to pulmonary vein isolation (PVI) have shown promise, and a novel ultra-low-temperature cryoablation (ULTC) system might overcome the limitations of radiofrequency (RF) energy to create transmural lesions in diseased tissue. Purpose Aim of this study is to report procedural aspects, acute efficacy, and safety of our initial experience in treating AF pts with this novel ULTC system. Methods Patients scheduled for catheter ablation who had a high likelihood of having left atrial (LA) low voltage zones (LVZ) underwent ablation with the ULTC system. A detailed high-density LA 3D-electronatomical map was created in sinus rhythm using a multi-electrode catheter. Bipolar LVZs were defined as at least 1cm2 surface of bipolar voltage <0.5mV. The ablation strategy consisted of PVI and linear ablation of the LVZs, transecting (if narrow) or isolating (if broad) the areas of abnormal signals and anchoring these lines to electrically silent structures (PVs or mitral valve ring). Electrical isolation and block across linear ablations were tested as universally accepted. Continuous variables are expressed as median (and interquartile ranges). Results From April to September 2023, 25 pts (10 female) were included (see table for patients´ and procedural characteristics). Procedure duration was 210 (135-270) min, and diminished over time from initially (in the first 12 pts) 260 (203.75-302.50) min to 190 (135-235) min (p=0.047). PVI was achieved in 15/18 pts (83%) using the ULTC, in the remaining 3 pts RF energy touch-up was needed. Linear ablation and isolation of LVZs were always (41/41 in 22pts, 100%) successfully achieved with the ULTC (see figure for an example). Except for 1 right phrenic nerve palsy, no major acute complications were observed. Post-procedural chest pain was not reported by any patient, in 1 patient mild pericardial effusion was detected and treated conservatively. During the 48h post-procedural ECG-monitoring, no sustained atrial arrhythmias occurred. Conclusions This is the first report of patient-tailored low-voltage-guided AF-ablation using a novel ULTC system. Despite representing our initial clinical experience, acute efficacy was very good (95% of acute bidirectional block across lines). Procedure-duration decreased over time, indicating an initial learning curve. Acute safety was reassuring but particular attention should be paid for phrenic nerve function during ablation of the right PVs. The absence of post-procedural pain, pericardial effusion, or acute post-procedural arrhythmias indicates limited ablation-induced inflammation.Result of ULTC ablation in a diseased LA

Risk and benefits of baseline antiplatelet therapy in 58,598 patients with atrial fibrillation randomized to NOACs vs warfarin

Abstract Background The efficacy and safety of NOAC versus warfarin (W) may differ in AF pts receiving antiplatelet therapy (APT) at baseline. Moreover, prior individual trial-specific analyses examining the treatment effect of NOAC vs. W as a function of APT are underpowered for interaction testing. Purpose We evaluated outcomes by randomized anticoagulant stratified by baseline APT in a pooled individual pt-level meta-analysis of 4 pivotal RCTs of NOAC vs. W in AF: RE-LY, ROCKET-AF, ARISTOTLE, and ENGAGE AF-TIMI 48. Methods Pts were stratified by use of APT vs. no APT at baseline. Pts randomized to low-dose NOAC not globally approved (edoxaban 30/15 mg or dabigatran 110 mg) were excluded. The primary efficacy and safety outcomes were stroke/systemic embolic events (S/SEE) and major bleeding, respectively; ischemic stroke (IS), intracranial hemorrhage (ICH), major GI bleeding and all-cause mortality (ACM) were secondary outcomes. Each outcome was assessed by randomized treatment using a Cox model stratified by trial with adjustment for age, sex, weight, CrCl, smoking status, HTN, DM, CAD, prior MI, PAD, and prior stroke. Interaction testing was performed by APT at baseline. Results Of 58,598 pts, 19,774 (34%) were on APT at baseline (92% aspirin only, 5% P2Y12 only, 3% DAPT). Pts treated with APT had greater prevalence of CAD (41% vs. 24%), prior MI (22% vs. 11%), and PAD (6% vs. 4%) (p<0.001 for each). Reflective of these baseline differences, the annualized event rate for each outcome was higher in the APT vs. no APT group (Figure). The treatment effect (HR) of NOAC vs. W for all 6 clinical outcomes was consistent irrespective of baseline APT (p-interaction [aHR] for each = NS; Figure). However, the absolute risk reduction (ARR) for NOAC vs. W differed for ICH and major GI bleeding as a function of baseline APT (Figure). Specifically, for ICH, a greater absolute benefit was seen with NOAC vs. W in those on APT at baseline (ARR 0.6% vs. 0.3%; p-int = 0.007). Conversely, for major GI bleeding, NOAC vs. W was associated with greater absolute risk in those on APT (ARR -0.6% vs. -0.2%; p-int = 0.04). Conclusions The treatment effect of NOAC vs. W is consistent irrespective of APT at baseline for S/SEE, major bleeding, and ACM. Given higher rates of bleeding in AF pts treated with both APT and anticoagulation, concomitant APT should be avoided when possible. In pts requiring concomitant APT, NOAC instead of W should be considered owing to greater absolute safety benefit for ICH, which should be weighed against individual patient-specific risk factors for GI bleeding.

PO-01-187 FEASIBILITY OF FLUOROLESS PULMONARY VEIN ISOLATION USING A SINGLE-SHOT CONFORMABLE PULSED FIELD ABLATION CATHETER

Fluoroless pulmonary vein isolation (PVI) using point-by-point ablation catheters guided by electroanatomical mapping (EAM) systems is standard practice in many operators’ practice. While “single-shot” PVI tools have a streamlined procedural workflow, and with a safety profile enhanced by the emergence of pulsed field ablation (PFA) technology, these catheters have not been able to support a completely fluoroless workflow. A novel 8-Fr single-shot large lattice catheter with integrated magnetically-tracked EAM and PFA capabilities has been developed. To report for the first time the feasibility of performing single-shot PVI using a completely fluoroless approach. This 8 Fr PFA catheter (SpherePVI; Affera-Medtronic Inc) has a conformable large lattice framework that is expandable to 34 mm in diameter to permit “customization” to varying pulmonary vein anatomies (see Figure). It was delivered using an 8.5 Fr deflectable sheath (Agilis, Abbott Inc), and used with a custom EAM system (Prism-1; Affera-Medtronic Inc.) to render PV and left atrial anatomy. The PFA generator (HexaPULSE; Affera-Medtronic Inc) delivered biphasic waveforms (5 sec per application; 1.3-2.0 kV[±]); goal of 1-3 lesions per PV) from six elements situated circumferentially around the equatorial plane of the lattice. These cases conducted at a single center as part of a first-in-human study (NCT05115214): under general anesthesia, ICE was used to guide transeptal puncture and catheter positioning; fluoroscopy was initially used, followed by completely fluoroless ablation (using only ICE and EAM). The fluoroless cohort (n = 4 AF pts) was well matched with the control cohort (n = 5 AF pts) with similar baseline characteristics except for having more male patients (see Table). PVI was 100% successful in both groups. For PVI, both the number of PFA lesions delivered (16.3±0.5 vs 16.6±0.9 in the fluoroless and control groups, respectively) and the PVI ablation times (time only during lesion application; 1.6±0.0 min vs 1.6±0.1 min), and transpired time (defined as time transpiring between first to last lesion application; 8.3±1.1 min vs 9.6±2.2 min) were comparable. The total fluoroscopy time in the control group was 5.5±2.7 min. There were no serious adverse events in either group. This case series provides the proof-of-principle that fluoroless single-short PVI is feasible, safe and effective using a conformable large lattice PFA catheter.

AB-452675-2 PULMONARY VEIN ISOLATION USING A NOVEL MAP-AND-ABLATE SPHERICAL ARRAY PULSED FIELD ABLATION CATHETER: THE PULSE-EU PAROXYSMAL AF COHORT

Despite the promise of pulsed field ablation (PFA), there is much about the biophysics of this novel energy technology that remains to be understood. Preclinical studies have shown that close electrode-tissue proximity increases the likelihood of achieving transmural PFA lesions by maximizing the electric field penetration into the target tissue. The current single-shot PFA catheters are capable of performing pulmonary vein isolation (PVI), but cannot reliably confirm tissue contact. To report the clinical outcomes using a novel Map-and-Ablate spherical array multielectrode catheter that is able to verify tissue contact and deliver single-shot PFA. In the first-in-human PULSE-EU study, paroxysmal AF pts underwent PVI using the spherical array PFA catheter (Globe; Kardium Inc., Canada) using a 16Fr deflectable sheath under general anesthesia and ICE-guidance. Using a custom mapping system integrated with the PFA catheter (GPS; Kardium Inc.) the array catheter rendered contact and voltage anatomic maps. The spherical array was positioned at each PV ostia and PF applications (1.7 kV/lesion, ungated, micro-second scale pulses) were delivered after verifying tissue contact (Figure). Follow-up included post-procedure EGD and plans for protocol-mandated invasive remapping at 2-3 mo after the index procedure. A total of 24 pts (age 59.9±10.8 years; gender women-37.5%; LA 42.5±3.7 mm; LVEF 62.6±8.0%%) underwent PVI with a total procedure duration of 71.5±22.9 min. All PVs (96 of 96 PVs) were acutely isolated, typically with a single application. There were no acute reconnections. The total pulse delivery time and LA catheter dwell time were 42.2±7.6 sec and 36.8±13.7 min, respectively. There were no serious procedure or device related adverse events including no stroke/TIA, pericardial effusion, phrenic nerve injury, or esophageal complications. One patient had pericarditis which was treated medically. Post-procedure EGD revealed no thermal injury in 21 of 21 pts. PV remapping has thus far been performed in 6 pts, and revealed durable PVI in all 24 of 24 (100%) PVs. [Remapping data on the remaining cohort will be available by May 2023.] In this first-in-human PULSE-EU clinical study, the spherical array PFA catheter was able to render atrial anatomy, isolate PVs (with initial data indicating 100% durability), and perform pre-/post- electrical mapping.

Abstract 14123: AF Ablation Using a Novel “Single-Shot” Map-and-Ablate Spherical Array Pulsed Field Ablation Catheter: Impact of Application Repetition on PV Isolation Durability in the PULSE-EU Study

Introduction: Preclinical studies have revealed that pulse field ablation (PFA) lesion dimension increases with consecutive applications at a similar electric field. Whether durability of pulmonary vein isolation (PVI) is predicated on repetitive PFA applications is unknown. In the first-in-human PULSE-EU clinical trial (NCT05164107), the ability of this map-and-ablate PFA catheter to achieve durable PVI was assessed, both with single vs repetitive PFA applications. Methods: Under general anesthesia, paroxysmal AF pts underwent PVI using the spherical array PFA catheter (Globe; Kardium Inc, Canada) delivered with a deflectable 19Fr transeptal sheath and ICE-guidance. Using a custom mapping system, the PFA catheter rendered contact and voltage anatomic maps ( Figure ). The spherical array is positioned at the PV ostium and PFA is performed (1.6-2 kV/lesion, ungated 3s pulses). Follow-up was post-procedure EGD and brain MRI within 1 day, and invasive remapping at ⁓2 months. Results: A total of 21 pts (age 63±11 years; M/F 33%/67%) underwent PVI in 2 groups: Gp1-single PF application/PV, and Gp2-3 PF applications/PV. In Gp1 (n=11 pts) and Gp2 (n=10 pts), PVI was acutely successful in 100% of PVs in both groups. Pulse delivery times and total procedure times were 75.2±7.4 sec/pt vs 24.5±5.5 sec/pt and 73.2±13.7 mins​ vs 93.7±18.5 mins​ in Gp2 vs Gp1. There was no stroke/TIA, pericardial effusion, phrenic nerve injury, or esophageal complications. EGD was normal in all 9/9 pts. Brain MRI showed silent cerebral lesions (DWI+/FLAIR-) in 3/16 (18.8%) pts. PV remapping revealed durable PVI in 25/40 (62.5%) PVs in 10 pts in Gp1, compared with all 34/34 (100%) PVs in 9 pts in Gp2; this translates to all PVs being durably isolated in 27% vs 100% (p<0.05) of pts in Gp1 and Gp2. Conclusion: The “single-shot” map-and-ablate spherical array PFA catheter can safely isolate PVs. Repetitive PFA applications is key for lesion consolidation to improve PVI durability.

Preventive counseling with subsequent remote support does not further improve the quality of life after catheter ablation of atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: None. Background Atrial fibrillation (AF) is associated with substantially reduced quality of life (QoL). Both catheter ablation (CA) and education have a potential to improve QoL in AF patients (pts). Purpose To assess the impact of preventive counseling with long-term support on QoL in pts after CA performed for paroxysmal AF. Methods A prospective randomized controlled study with 2 parallel groups of pts with paroxysmal AF after CA (radiofrequency or cryoablation). Pts were randomized (1:1) into 2 groups. Before discharge, both groups received 1 preventive counseling session with focus on their individual risk factors profile. After discharge pts from intervention group received biweekly preventive counseling via email for 3 months (6 sessions). Control group received usual care. QoL was assessed at baseline and at 12 months using SF-36 questionnaire. Results A total of 90 pts aged 35 to 80 years were enrolled (mean age, 57.4 ± 9.9 years, men, 52.2%). Both groups had a poor QoL at baseline, and both groups experienced improvement in the physical health component at 1 year, but the degree of this improvement in the intervention group was similar to the control (table). Conclusions Preventive counseling with remote support via email does not further improve QoL in AF pts after CA. Intervention group Control group P Integral component of physical health Baseline (points) mean ± SD 44.1 ± 7.9 40.2 ± 8.7 0.028 Mе (25%; 75%) 44.5 (38.7; 50.1) 38.6 (34.4; 47.1) At 12 months (points) mean ± SD 49.4 ± 6.0* 45.7 ± 7.7* 0.010 Ме (25%; 75%) 51.0 (45.2; 53.9) 46.3 (42.4; 50.6) Δ% after 12 months, Ме (25%; 75%) 11.8 (1.4; 32.7) 18.7 (-0.3; 30.4) n/s Integral component of mental health Baseline (points) mean ± SD 46.1 ± 9.0 45.0 ± 8.4 n/s Mе (25%; 75%) 47.8 (39.1; 53.9) 48.0 (37.2; 52.0) At 12 months (points) mean ± SD 48.2 ± 8.1 46.8 ± 8.7 n/s Ме (25%; 75%) 50.1 (46.1; 53.6) 48.0 (41.0; 54.3) Δ% after 12 months, Ме (25%; 75%) 3.6 (-10.8; 32.6) 8.9 (-15.6; 30.8) n/s * p <0.001 vs baseline

Abstract 12991: Growth Differentiation Factor-15 is a New Predictor of Cardiovascular Events in Atrial Fibrillation Patients After Elective Percutaneous Coronary Intervention

Introduction: Patients (pts) with AF, undergoing elective PCI, receiving multicomponent antithrombotic therapy (MAT) have high risk of stroke/systemic embolism and coronary events. There is no biochemical markers associated with negative prognosis in AF pts after elective PCI. Growth differentiation factor-15 (GDF-15) has demonstrated strong relationship with adverse prognosis in pts with cardiovascular disease. Purpose: To investigate the prognostic value of GDF-15 level in AF pts after elective PCI. Methods: 150 pts (104 males), aged 70.8±8.5 years, with AF after elective PCI were enrolled in the prospective study. All pts received DOACs and double (89.3%) or single (10.7%) antiplatelet therapy. Median duration of follow up period was 11.5 months [IQR 8.0; 12.0]. Efficacy endpoint of the study was the sum of cardiovascular events (CVE): ACS, ischemic stroke (IS), VTE, cardiovascular death and need for unplanned PCI. Plasma samples for GDF-15 were analyzed using ELISA. Results: AF pts receiving MAT demonstrated high thrombotic risk (CHA 2 DS 2 -VASc, Med 5 [IQR 4; 6]), high rate of comorbidity (index Charlson, Med 7 [IQR 5; 9]). Frequency of CVE during follow up period was 16% (ACS 2; fatal IS 2; VTE 2, include 1 fatal pulmonary embolism; cardiovascular death 2; pts needed an unplanned PCI 16). Median GDF-15 level was 1270 pg/ml [IQR 953; 1778]. According to multiple regression analysis GDF-15 level was associated with the D-dimer (t=3.20; p=0.0018), diabetes mellitus (t=3.97; p=0.0001) and clinical and angiographic Syntax II score (t=4.77; p<0.0001). In pts with only coronary artery disease, the level of GDF-15 was significantly lower than in pts with atherosclerotic lesion of 3 vascular pools (p=0,0119). According to ROC analysis GDF-15 level > 1191 pg / ml (sensitivity 83.0, specifity 50.0) increase the probability of the development of CVE (AUC=0.647, p=0.0076, 95% CI 0.565–0.723). Kaplan-Meier curves demonstrated significant difference in CVE free survival between the patients with GDF-15 level > and ≤ 1191 pg/ml (75.9% and 94.0% respectively, log-rank test p = 0.0032, [HR 4.36, CI 1.50-7.48]). Conclusions: GDF-15 is a possible marker of CVE determining prognosis in AF pts after elective PCI. The results could be used to individualize the duration of MAT.

Assessment of correlation between silent brain damages and clinical characteristics in patients with persistent atrial fibrillation and concomitant arterial hypertension

Abstract Introduction Silent cerebral microembolic lesions (SML) are known to occur with higher prevalence in persistent AF and could be potential reason of cognitive decline. It seems reasonable to investigate which factors may be related with the SML occurrence in AF pts to implicate it in the future prophylaxis. Purpose To estimate association between brain MRI findings (incidence of silent cerebral microembolism and microbleedings) in patients with persistent atrial fibrillation and their clinical characteristics including concomitant arterial hypertension (AH) and CHA2DS2-VASc score. Methods Pts with persistent AF (n=69) were included in the study. All subjects underwent clinical assessment, thromboembolic and hemorrhagic risk calculation using CHA2DS2-VASc and HAS-BLED score with subsequent cranial MRI examination. The incidence of SML (registered on MRI like small focal hyperintense areas in the brain matter) and microbleedings were assessed. The pts were divided into groups: Gr1 (n=49) – pts with revealed SML, Gr2 (n=20) – without silent brain damages. Clinical characteristics of pts were compared regarding to presence of SML and microbleedings using Mann-Whitney U test. Spearman analysis and ROC- analysis were used for correlation assessment. Results The total incidence of SML was 71% (n=49). Isolated microbleedings were found in 13% (n=9) pts., 59.4% (n=41) pts were anticoagulant naïve. The most part of investigated pts (82.6%, n=57) had well controlled AH: 42 pts (85.7%) in Gr1 and 15 (75%) in Gr2, p=0.1. Persons with SML were significantly older compared to the pts without SML – 59.6±7.1 years vs 52.1±8.9 (p=0.005), had lower EF – 54.4±9.4% vs 58.5±6.8% (p=0,04), higher CHA2DS2-VASc score – 2 [1; 3] vs 1 [0; 1.5] and higher HAS-BLED score – 0 [0; 3] vs 1 [0; 2] (p=0.02). Notably, higher fasting plasma glucose level was registered in Gr1 in comparison with Gr2 – 6.34±2.4 mmol/l vs 5.4±0.5 mmol/l (p=0.008). Significant correlations were calculated between SML and CHA2DS2-VASc score (AUC – 0.875, CI: 0.773–0.977, p=0.006), SML and degree of AH (AUC – 0.658, CI: 0.512–0.803, p=0.039), SML and age (AUC – 0.757, CI: 0.62–0.895, p=0.001). The age cut-off value for revealing SML on brain MRI in pts with persistent AF was determined: 45.5 years (AUC – 0.757, Sensitivity – 97.9%, Specificity – 71.4%, p=0.001). Individuals with microbleedings had only significantly higher CHA2DS2-VASc score – 3 [1; 4] vs 1 [0; 4] (p=0.002) with weak positive correlation (r=0.32, n=69, p=0.009). Conclusion The correlation between brain SML and CHA2DS2-VASc score confirms the ability of that score to predict not only clinically apparent thromboembolic events but also silent microembolism in persistent AF. Brain SML in pts with persistent AF are associated with higher CHA2DS2-VASc score, higher fasting plasma glucose, degree of arterial hypertension. Notably that pts revealing SML on brain MRI were younger compared to the age using in CHA2DS2-VASc score. Funding Acknowledgement Type of funding source: None

P441Targeted ablation of residual luminal pulmonary vein potentials through high density mapping: preliminary results from the CHARISMA registry

Abstract Background A high incidence of pulmonary vein (PV) reconnection has been reported in patients (pts) with clinical recurrences of AF. Low-voltage activity beyond PVs (e.g. antral activity) may contribute to ablation failures in the long term. Detailed characterization of PV antra through high density mapping (HDM) and automated algorithm is still lacking. Purpose to characterize PV gaps and the low-voltage activity in tissue such as the PV antra during and after ablation of PVs in AF pts. Methods Consecutive pts undergoing AF ablation from the CHARISMA registry with complete characterization of residual PV antral activity were included. A complete map of the left atrium and PVs was performed prior and after ablation through the Rhythmia HDM system. A novel map analysis tool (Lumipoint - LM -) that automatically identifies split potentials and continuous activation was used sequentially on each PV component, in order to assess the presence of gaps (PVG) and residual potential within the antral scar (RAP, defined as any low voltage high frequency fractionated signal propagating within the antral scar without conduction into the vein) and characterize electrical propagation. After ablation we reassessed with repeat voltage and propagation maps that electrical quiescence was achieved. Ablation endpoint was PV isolation. Results Thirty-six cases of AF ablation were analyzed (11 de novo, 25 redo). A total of 36 PVG in 13 (36%) patients were detected after remap (1 case of de novo) or initial map of redo patients (12 cases). A total of 34 RAP in 20 cases (56%) were found: 4 (36%) cases of de novo (all after ablation and remap) and 16 (64%) cases of redo (all after initial map). In 7 (19%) cases we found at least one RAP in pts with complete absence of PV conduction. 100% of PVG (n = 36) and 89% of RAP (n = 29) were fully detected though a first pass automated annotation. In 5 RAPs (11%) an additional temporal consistency of low-voltage signal relative to neighboring activation was needed due to the very low voltage EGM (≤0.1 mV). PVGs were more common at right PV sites (n = 26, 72%) and anterior PV sites (n = 20, 55.6%) whereas RAPs were detected more frequently at left PV sites (n = 20, 59%) and anterior PV sites (n = 21, 62%). RAP showed a lower median voltage compared with PVG (0.22[0.2-0.3]mV for RAP vs 0.97[0.6-1.3]mV for PVG, p < 0.0001) whereas the median number of EGM peaks were higher (6.5[5-8] for RAP vs 3[2-4] for PVG, p < 0.0001). No complications during the procedures were reported. The acute procedural success was 100%, with all PVs successfully isolated and RAPs completely abolished in all study pts. Conclusion In our preliminary experience, local vulnerabilities in antral lesion sets were commonly discernible using HDM system both in de novo or redo patients when no PV conduction was present. The applied workflow seemed to be useful to quickly pinpoint and accelerate the search of local PV activity or concealed low-voltage activity.

EFFICACY AND SAFETY OF EDOXABAN IN PATIENTS WITH ATRIAL FIBRILLATION AND ACTIVE MALIGNANCY: AN ANALYSIS OF ENGAGE AF – TIMI 48 RANDOMIZED CLINICAL TRIAL

Background: Anticoagulation in cancer pts with AF is a challenge due to the prothrombotic state and potential for bleeding associated with malignancy. Data on NOACs in cancer are sparse. Our aim is to evaluate the efficacy and safety of edoxaban in AF pts with active malignancy. Methods: ENGAGE AF

Bruton's Tyrosine Kinase Inhibition Is Associated with Manageable Cardiac Toxicity

Introduction: Ibrutinib (Ibr) is a small molecule that effectively targets B cell malignancies by inhibiting Bruton's tyrosine kinase activity (BTK). Clinical studies have shown a consistent increase in OS, PFS and response rate for relapsed-refractory CLL and mantle cell lymphoma (MCL) with variable cardiac toxicity (CT) (Table 1).Methods: Retrospective analysis of pts treated at The Abramson Cancer Center at the University of Pennsylvania to identify the incidence and characteristics of Ibr related CT.Results: We identified 32 pts treated with Ibr (87.6% CLL, 6.2 MCL, 6.2% other). The median age was 65 yrs (47-83). 53% of patients had a prior history of cardiovascular (CV) comorbidities: 16% hypertension (HTN), 3 % arrhythmia, 9% CAD, 0% with heart failure. During the course of therapy, we identified 11 pts (mean age 69.6 yrs; range 51-83) with presumed Ibr-induced CT: 5 with AF (16%), 4 patients with aggravation of pre-existing HTN (13%), 1 with sinus bradycardia (3%), and 1 with unexplained syncope (3%). 88% were male and all had at least one cardiac co-morbidity. The median time to onset of AF was 197 days (63-358) and acceleration of HTN 42 days (27-57). All of the HTN patients had pre-existing HTN and of the 5 pts with AF, 2 had a history of HTN, 2 PAF, and 3 CAD. All patients were co-managed by the treating oncologist and cardiologist. Successful management of CT did not require Ibr discontinuation in all pts. We observed no arrhythmia or treatment related embolic/bleeding events; AF pts were all anticoagulated (3% warfarin, 87% novel antithrombotic drug). In 2/5 AF pts, Ibr dose was reduced. BTK inhibition may induce unique CT by affecting the regulation of off target kinases with BTK selectivity (Table 2). Table 3 provides recommendations for management of Ibr related CT for the practicing oncologist.Conclusions: We identified a 34% incidence of Ibr related CT. These results are unique in that we provide long-term follow up of such events and demonstrate that in practice, Ibr related CT can successfully be managed by the medical oncologist / cardio-oncology team. No pts discontinued Ibr in this series due to CT events. Pre-existing CV disease is a major risk factor for Ibr-related AF and HTN. The absence of cardiac co-morbidity may have negative predictive value. In conclusion, there is a potential for CT in elderly patients with pre-existing cardiac disease and HTN treated with Ibr. This suggests the need for proactive co-management of these patients with cardiologists trained in cardio-oncology.Table 1Reported CT among CLL/ mantle cell lymphoma ptsCardiac EventCLL (Byrd, 2013)MCL (Wang, 2014)RESONATE (Byrd, 2014)Follow-up analysis (Byrd, 2015)AF3 (4%)5 (4.5%)6 (3%)8 (6%)Peripheral edema18 (21%)3 (2.7%)22 (11%)NAHypertension5 (11%)NANA27 (20%)DyspneaNA30 (27%)23 (12%)NASupraventricular tachycardia1 (1%)NANANATable 2Possible mechanisms of Ibr-related CTProteinRelation to BCR signalingProposed mechanismClinical CTPhosphatidylinositol 3-kinase (PI3K)Upstream activator and downstream substrate of BTKAlter gene expression in ventricular tissue;Compromised regulation of autonomic calcium oscillations in cardiac cells to alter automaticityAF, Hemodynamic compromise, BradycardiaHeat shock protein 70Decreased HSP 70 levels in response to attenuated PI3K activityCompromised role in cardiac remodeling under pressure overload or stressAF, hypertensionPhospholipase C gamma 2 (PLCγ-2)Downstream protein activated by BTK in BCR signalingAttenuated activation of PLCγ-2 compromises calcium signalingAF, cardiac arrhythmiaTable 3Penn recommendations for management of Ibr treated patients with CTAFExclude hyperthyroidismConsider Ibr dose reductionRate control beta or calcium channel blocker. Start at low dose, uptitrate to HR < 100. If limited by hypotension, consider digoxinCVA Prevention with anticoagulation based on CHA2DS2-VASC scoreHTNACE inhibitors and/or calcium channel blockers as first lineBradycardiaDifferentiate whether pt is symptomaticIf asymptomatic and HR increases appropriately with exertion, no further evaluation or treatment necessary Avoid negative chronotropic medications DisclosuresSchuster:Novartis: Research Funding; Gilead: Research Funding; Janssen: Research Funding; Hoffman-LaRoche: Research Funding; Celgene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Genentech: Consultancy; Nordic Nanovector: Membership on an entity's Board of Directors or advisory committees. Svoboda:Seattle Genetics: Research Funding; Celgene: Research Funding; Immunomedics: Research Funding; Celldex: Research Funding. Rago:Gilead Sciences: Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees. Mato:Genentech: Consultancy; Gilead: Consultancy, Research Funding; Celgene Corporation: Consultancy, Research Funding; TG Therapeutics: Research Funding; Pronai Pharmaceuticals: Research Funding; Pharmacyclics: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding.

Abstract 17169: The Impact of Renal Function on Outcomes With Edoxaban in the ENGAGE AF-TIMI 48 Trial

Background: Edoxaban (edox), an oral factor Xa inhibitor with 50% renal clearance, was non-inferior to warfarin for prevention of thromboembolic events and significantly reduced bleeding in pts with AF. However, a detailed analysis of the impact of creatinine clearance (CrCl) on clinical outcomes with edox has not been described. Purpose: We evaluated the safety, efficacy and net clinical outcome of edox vs warfarin (warf) across the range of baseline CrCl in the ENGAGE AF-TIMI 48 trial. Methods: 14,071 AF pts at moderate-to-high risk of stroke were randomized to edox 60mg QD or warf. Severe renal dysfunction (CrCl&lt;30ml/min) was exclusionary and a CrCl 30-50 resulted in a 50% dose reduction of edox (30mg QD). Endpoints of stroke or systemic embolism (SSE), ISTH major bleeding (MB) and the primary net clinical outcome of SSE/MB and all-cause mortality (ACM) were evaluated by intention-to-treat analysis by the pre-specified singular CrCl cutpoint of 50ml/min and additional exploratory cutpoints. Results: The relative risk of SSE with edox vs warf in the pre-specified analysis in those with CrCl≤50 (HR 0.87, 0.65-1.18) was similar to those with CrCl&gt;50 (HR 0.87, 0.72-1.04; p-int=0.94). Evaluation by more granular, exploratory cutpoints demonstrated higher rates of SSE (Fig 1a; p-int&lt;0.001) and ischemic stroke (p-int=0.05) with edox vs warf in the upper range of CrCl, but lower rates of bleeding were observed at all levels of CrCl with edox (Fig 1a; p-int=0.39). For the net clinical outcome (SSE/MB/ACM), there was no significant difference between edox and warf at higher levels of renal function due to the preserved effect on bleeding and mortality (Fig 1b; p-int 0.17). An on-treatment analysis with plasma drug levels will be shown. Conclusion: While there is a trend towards decreasing efficacy with increasing CrCl for edox compared to well-managed warfarin, the overall safety and net clinical benefit of edox compared to warfarin is consistent across renal function groups.

0131: Strategy of anticoagulation in pacemaker and ICD replacement procedure in real life. The French Electra survey

to evaluate routine French implanters strategy in device replacement in patients under anticoagulation for atrial Fibrillation (AF pts). A questionnaire was e-mailed to 140 French implanters. 102 aswers were obtained. In AF patients, admission is on day of procedure D0 (10%) or D-1(80%) whether pts are on vitamine K antagonist(VKA) or New Oral AntiCoagulant (NOAC). In AF pts under VKA, only 4%bridge to Low Weight Heparine (LWH) or Unfractionated Heparine (UH) while treatment is interrupted without substitution (wos) by 61% and continued without interruption by 32%. In AF pts under NOAC, only 5%bridge to UH or LWH while treatment is interrupted on D-3 (13%), D-2(25%), D-1(44%). When interrupted, NOAC are resumed at D0 (23%), D+1(54%), D+2(10%), D+3(3%). Most of implanters hospitalize AF pts at D-1 of replacement procedure. Short discontinuation (VKA, NOAC) or uninterruption (VKA) is prefered to bridging strategy.

Abstract 13259: Electrophysiologic Mapping Identifies Stable Organized Tachyarrhythmias ("Rotors") in Both Atria during Spontaneous Atrial Fibrillation with Systolic Heart Failure

Introduction: Stable organized atrial tachyarrhythmias (ATs) /"rotors" that maintain AF have been identified in patients (pts) with paroxysmal atrial fibrillation (PAF) &amp; persistent AF (PRAF) with no or minimal heart disease. Hypothesis: Biatrial ATs occur in AF pts with systolic heart failure (HF). Methods: We performed simultaneous contact catheter mapping of the RA &amp; LA using 3 D non-contact mapping ) in 83 refractory AF pts during spontaneous AF episodes.Spontaneous atrial premature beats (APBs) &amp; triggered ATs were analyzed. We also compared regional distribution of ATs &amp; activation patterns in pts with &amp; without HF. Results: 24 HF pts, mean age of 62±9 years, 75% male with mean left ventricular ejection fraction (LVEF) 45.5±9% and mean left atrial (LA) size 4.35±0.8 cm were mapped. They had 42 APBs that triggered 26 distinct organized stable ATs/"rotors". Each pt had 1 to 4 RA or LA regions showing triggering APBs (mean 1.75/pt) initiating AT. APBs arose predominantly from the RA or LA septum (45%) &amp; superior LA/PV (24%) regions (Fig 1a). A biatrial distribution of the stable ATs/"rotors" occcurred in HF pts (Fig 1b) with few focal ATs. Compared to pts without HF (n=59), HF pts (n=24) trended to have more PRAF (83% vs 66%, p=0.18). 78 organized stable ATs/"rotors" were compared for regional distribution in PRAF pts with HF (n=16) &amp; without HF (n=32). Stable ATs with focal LA/PV origin were uncommon in both groups (7% vs. 15%). LA ATs/"rotors" were similar (26% vs. 17%; p=0.58) as were typical RA flutter and atypical RA ATs/"rotors" in both groups (Fig 1c). Conclusions: 1. A majority of APBs initiating AF in HF pts originated from the septal and superior LA/PV regions. 2. While triggers are still frequently present with the LA/PV origin in HF pts, stable ATs/"rotors" had biatrial distribution &amp; a lesser frequency of focal LA/PV ATs. 3. This spectrum of ATs/"rotors" was similar to PRAF pts without HF, potentially supporting similar ablative interventions in both pt groups.

Can We Predict the Occurrence of Atrial Fibrillation Following Typical Right Atrial Flutter Ablation?

s S233 days before the procedure for both apixabanand warfarintreated pts. A second bridging anticoagulant was used in 1335 procedures (11.7%) and was most commonly low molecular weight heparin (86.1%). CONCLUSION: Invasive procedures are common in AF pts. The majority of procedures are non-major and non-emergent, and anticoagulation therapy was likely to be stopped peri-procedure. Overall and among emergent procedures, the rates of clinical events in the first 30 days post-procedure were low and comparable between pts receiving warfarin and apixaban. 353 EARLY RETURN ED VISITS FOR ATRIAL FIBRILLATION ARE COMMON: CAN THEY BE PREDICTED? V Dragan, Z Mariano, P Angaran, CJ Gilbert, I Mangat, P Dorian

Apixaban versus warfarin in patients with atrial fibrillation and valvular heart disease: findings from the ARISTOTLE study

Purpose: Apixaban is indicated for the prevention of stroke and systemic embolism (SE) in pts with non-valvular AF. In this context, valvular refers only to clinically significant mitral stenosis (MS) and not other valvular heart disease (VHD). Little is known about the efficacy and safety of apixaban in pts with AF and VHD. Methods: We used data from 18,197 pts with AF and ≥1 risk factor for stroke in ARISTOTLE with available information on VHD. Pts with clinically significant MS and mechanical heart valves were not eligible. Of these, 4808 (26.4%) had VHD defined by any history of at least moderate mitral regurgitation (3526), MS (131), aortic regurgitation (887), aortic stenosis (384), tricuspid regurgitation (2124), or valve surgery (251). We compared the effect of apixaban vs. warfarin on rates of stroke or SE and major bleeding in pts with and without VHD using Cox proportional hazards modeling. Results: Pts with VHD were older, had more prior MI and prior bleeding, had a higher mean CHADS2 score, and had less hypertension and diabetes than pts without VHD. Pts with VHD had higher rates of stroke or SE and bleeding than pts without VHD. The benefits of apixaban compared with warfarin in reducing stroke and SE (interaction p=0.38), causing less major bleeding (interaction p=0.23), and decreasing death (interaction p=0.10) were consistent irrespective of the presence of VHD (Fig). ![Figure][1] Conclusions: Pts with AF and VHD are at high risk for thromboembolic events and bleeding. Apixaban was similarly efficacious and safe in AF pts with and without VHD. Additional research is needed on the efficacy and safety of apixaban in pts with AF and VHD, particularly those with clinically significant MS and mechanical prosthetic valves. [1]: pending:yes

Watchman Left Atrial Appendage Closure in Atrial Fibrillation Patients with Contraindication to Oral Anticoagulation: The SA Plavix Registry (ASAP)

AF patients at the highest risk for embolic stroke also experience the greatest risk of hemorrhagic complications of anticoagulant use. The PROTECT AF trial revealed that LAA closure using the Watchman device was non-inferior to Warfarin for preventing stroke in AF pts with CHADS2 ≥ 1. However, these pts were treated with Warfarin post-implant until a TEE demonstrated LAA closure at 6 wks. Due to the pressing need for strategies that can prevent stroke in pts with contraindications to Warfarin, we performed a prospective study of Watchman implantation in Warfarin-contraindicated pts.

Abstract 19638: Watchman Left Atrial Appendage Closure in Atrial Fibrillation Patients with Contraindication to Oral Anticoagulation: The ‰ASA Plavix Registry” (ASAP)

Background: AF patients at the highest risk for embolic stroke also experience the greatest risk of hemorrhagic complications of anticoagulant use. The PROTECT AF trial revealed that LAA closure using the Watchman device was non-inferior to Warfarin for preventing stroke in AF pts with CHADS 2 ≥ 1. However, these pts were treated with Warfarin post-implant until a TEE demonstrated LAA closure at 6 wks. Due to the pressing need for strategies that can prevent stroke in pts with contraindications to Warfarin, we performed a prospective study of Watchman implantation in Warfarin-contraindicated pts. Methods: Prospective registry of pts with non-valvular AF, a CHADS 2 score ≥1, and a contraindication to Warfarin use. The Watchman device was implanted in standard fashion. Post-implant, patients were discharged on 6 mo of clopidogrel and life-long aspirin. Follow-up TEE was performed at 3/12 months. Results: At 4 centers, 150 pts were enrolled. The mean age was 72.5 ± 7.4 yrs. The prevalence of stroke risk factors was: CHF in 29%, HTN in 95%, Age ≥ 75 in 43%, DM in 32%, and stroke/TIA in 41%. The mean CHADS 2 score was 2.8 ± 1.2. The reason for Warfarin contraindication was: hemorrhagic tendencies (26%), blood dyscrasias (7%), bleeding tendencies (67%), unsupervised pts with senility/high fall risk (4%), and other (5%). Watchman implantation was successful in 95% (142/150). At 14.2 ± 8.7 mo of follow-up, there were 4 strokes (3 ischemic) and 6 instances of device-related thrombus by TEE. The observed rate of ischemic stroke 1.7% represents 77% fewer events from that expected in pts with a similar CHADS2 score treated with aspirin alone (7.3%; Figure). Data from additional follow-up (to a total of &gt;250 pt-yrs) will be available. Conclusion: Watchman implantation without a Warfarin transition is safe and effective in AF pts with contraindications to even short-term oral anticoagulation

TCT-83 Watchman Left Atrial Appendage Closure in Atrial Fibrillation Patients with Contraindication to Oral Anticoagulation: the “Aspirin Plavix Registry” (ASAP)

Background: AF patients at the highest risk for embolic stroke also experience the greatest risk of hemorrhagic complications of anticoagulant use. The PROTECT AF trial revealed that LAA closure using the Watchman device was non-inferior to Warfarin for preventing stroke in AF pts with CHADS2 ≥ 1. However, these pts were treated with Warfarin post-implant until a TEE demonstrated LAA closure at 6 wks. Due to the pressing need for strategies that can prevent stroke in pts with contraindications to Warfarin, we performed a prospective study of Watchman implantation in Warfarin-contraindicated pts. Methods: Prospective registry of pts with non-valvular AF, a CHADS2 score ≥1, and a contraindication to Warfarin use. The Watchman device was implanted in standard fashion. Post-implant, patients were discharged on 6 mo of clopidogrel and life-long aspirin. Follow-up TEE was performed at 3/12 months. Results: At 4 centers, 150 pts were enrolled. The mean age was 72.5 ± 7.4 yrs. The prevalence of stroke risk factor...

C0143 A retrospective study of thrombophilia testing requests in a large teaching hospital

data-bases relative to Apulia region's population from 1.1.02 to 31.12.10 combining the Apulia Patients’ Registry (info on residency, age, sex, alive status), the Territorial Pharmaceutical Prescriptions (information on anticoagulant therapies), the Disease Related Form (info on disease/hospitalizations, clinical risk profile, CHADS2 score, ischemic/hemorrhagic events and for calculation of costs). Results: In the time window 2002–2012, 99293 pts overall received at least one prescription for anticoagulants. A first prescription of warfarin showed a progressive increase of novel anticoagulated pts from 5227/y in 2003 to 9198/y in 2010, with a total number of 52640 anticoagulated pts alive on December 2010, with a population of Apulia of 4,264,117 inhabitants. Among them, the age distribution was b50 y.o. 2757 (0.1% of total population), 50–64 y.o. 8378 (1.1%), 65–74 y.o. 15014 (3.9%), 75–84 y.o. 20785 (7.7%), ≥85 y.o. 5706 (6.3%). During the same year an average of 8.5 (±5.3, SD, median 8, range from 1 to 61) packages of OA per patient was prescribed. 95% of pts received more than one and 87,6% of pts more than two packages. Comment: The regional population of patients with AF exposed to anticoagulants is increasing, with a progressive increase in age. With regard to the introduction of NOA, a great effort of all the physicians involved in treating these pts is necessary to monitor complication and obtain the greatest adherence /persistence in anticoagulant therapy. Therefore, the prospective registry to assess adherence, outcome and safety for the NAO in AF pts needs to take into consideration the above findings.