S389Poster Session V

Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study with a prolonged QRS were at increased risk for hospitalization and death.Methods: All patients in the AFFIRM trial with a QRS duration measured at baseline were studied. Cox models were applied to the data, relating the hazard ratio (HR) of all-cause/cardiovascular mortality and hospitalizations. QRS duration was expressed in milliseconds (ms) and divided into three categories ≥130 ms, 100-129 ms, or < 100 ms with the latter as the reference category, both among patients with and without heart failure (HF) while controlling for multiple potential clinical confounders. HF was defined as history of congestive HF and/or ejection fraction ≤45%.Results: Among the 3,959 patients eligible patients, 633 died during follow-up ( 290 patients had HF). A cardiovascular cause of mortality was identified in 317 patients (179 had HF). QRS duration predicted cardiac hospitalization in all patients, with an increased HR of 1.16 (95% CI 1.03 to 1.32, p = 0.014) for QRS 100-129 and of 1.38 (CI 95% 1.15 to 1.65, p = 0.001) for QRS ≥130. Among patients without HF, there was no significant association of QRS duration with overall (p = 0.84) or cardiovascular mortality (p = 0.405). Among all patients with HF, a QRS duration between 100-129 elevated the HR of cardiovascular and all cause mortality by 1.52 (95% CI 1.06 to 2.17, p = 0.022) and 1.52 (95% CI 1.15 to 2, p = 0.0029) respectively. Similarly, a QRS duration ≥130 increased cardiovascular and all cause mortality by 1.61 (95% CI 1.06 to 2.46, p = 0.027) and 1.51 (95% CI 1.08 to 2.1, p = 0.016).Conclusions: A prolonged QRS was an independent predictor of increased cardiac hospitalizations in all patients with AF. However a prolonged QRS duration increases the risk of cardiovascular and all cause mortality only in patients with AF and HF.

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RECURRENT ATRIAL FIBRILLATION IS MORE COMMON THAN ATYPICAL ATRIAL FLUTTER AFTER SEGMENTAL VERSUS CIRCUMFERENTIAL PULMONARY VEIN ABLATION FOR PAROXYSMAL ATRIAL FIBRILLATION AND IS ASSOCIATED WITH A GREATER NUMBER OF PULMONARY VEIN RECONNECTIONSHiro Kawata, MD, Navinder Sawhney, MD, FHRS, Kishlay Anand, MD, Siva Mulpuru, MD, Huy Phan, MD, PhD and Gregory Feld, MD. University of California, San Diego, Sulpizio Cardiovascular Center, La Jolla, CAIntroduction: Atrial fibrillation (AF) or atypical atrial flutter (AFL) may recur after pulmonary vein (PV) isolation (PVI), but the mechanism is unclear. The aim of this study was to assess PV conduction in patients (pts) with recurrent atrial arrhythmias after initially successful PVI.Methods: Among 461 consecutive pts undergoing PVI by radiofrequency catheter ablation for paroxysmal AF (PAF), 80 had recurrent atrial arrhythmias and underwent repeat ablation. We analyzed PV conduction in 320 PVs at repeat ablation, 11.2±8.8 months after initial ablation.Results: Two hundred forty five of the previously isolated PVs (245/320 or 76.5%) showed electrical reconnection. Seventy-five of 80 pts (93.8%) had reconnection of at least one PV. In the 80 pts with arrhythmia recurrence, 49 originally underwent segmental PVI and 31 underwent circumferential PVI. The number of reconnected PVs was significantly higher in pts undergoing segmental PVI versus pts undergoing circumferential PVI (3.28 vs 2.84, p=0.01). Pts undergoing segmental PVI had a significantly greater chance of developing recurrent AF versus atypical AFL (p<0.0021). Pts with recurrent AF had a significantly greater number of PV reconnections than pts with recurrent

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ELECTROPHYSIOLOGIC PREFERENTIAL CONDUCTION PROPERTY AND ITS ARRHYTHMOGENISITY OF MARSHALL BUNDLE IN PATIENTS WITH ATRIAL FIBRILLATIONToshiya Kurotobi, MD, PhD, Yoshihisa Shimada, MD, PhD, Naoto Kino, MD, Daisuke Tonomura, MD, Kentaro Yano, MD, Keiichi Furubayashi, MD, PhD, Takashi Tsuchida, MD, PhD and Hitoshi Fukumoto, MD, PhD. Shiroyama Hospital, Habikino, JapanIntroduction: Left lateral ridge (LLR) and left pulmonary veins (LPVs) carina containing Marshall bundle (MB) could be crucial anatomical structure as the arrhythmogenisity of atrial fibrillation (AF). The continuous and/or partial MB conduction between CS musculature and LPVs mimicking accessory pathway might affect the increased arrhythmogenisty of LPVs. In this study, we examined the relation between the preferential conduction properties of MB and the arrhythmogenisity of LPVs.Methods: The study population included 40 consecutive AF patients undergoing catheter ablation (CA) (mean age; 63). Double 20-pole circular catheters were placed in the upper and lower LPVs. Radiofrequency energy (RF) along LLR was sequentially delivered in lower to upper manner (from the bottom of the inferior LPV, the anterior wall of inferior LPV, the LPVs carina, to the anterior wall of superior LPV) during postero-lateral CS pacing in the setting of isoproterenol infusion (0.5-2μg/min).Results: The earliest activated site of upper LPV during CS pacing was commonly observed at the carina lesion in 32 of 40 patients (80%), and that of lower PVs was in 34 of 40 (85%) at the bottom of lower LPV. The conduction time between the LPVs and the CS stimulus site was significantly prolonged during RF (before vs. after, upper; 91±26 ms vs. 127±38 ms, p<0.001, lower; 86±21ms vs. 103±22ms, p<0.001). The remarkable prolongation more than 30 ms was observed in 19of 40 patients (48%) (both LPVs; 6, only upper LPVs;12, only lower LPV; 1). The sites of the remarkable prolongation was observed at the carina between LPVs (4), the anterior site of upper LPV carina (10), at the anterior wall of lower LPV (3), and at the bottom of lower LPVs (2). Thirty-three arrhythmogenic foci (AFCs) of LPVs was observed in 23/ 40 patients (56%), and the earliest activated site of AFCs was found at the carina lesion in 14 of 23 (61%). The conduction time between the upper LPV and the CS after RF was significantly longer in patients with AFCs of upper LPV AFCs than in patients without those (107±36 ms vs. 146±40 ms, p<0.01).Conclusions: MB includes the preferential conduction property between CS and LPVs, and the observation of these findings during RF could provide us the information about the LPVs arrhythmogenisity.

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MORBIDITY AND MORTALITY AMONG PATIENTS WITH ATRIAL FIBRILLATION AND PROLONGED QRS: INSIGHT FROM THE AFFIRM STUDYMatthew Whitbeck, MD, Richard Charnigo, PhD, Brandon Fornwalt, PhD, Gustavo Morales, MD, Jignesh Shah, MD, Milagros M. Zegarra, MD, Joseph Thompson, MD, Tzy Shiuan Bruce. Kuo, MD, Nael Aboul Hosn, MD, Rong Bai, MD, Luigi Di Biase, MD, Andrea Natale, MD and Claude S. Elayi, MD. University of Kentucky, Lexington, KY, Texas Cardiac Arrhythmia Institute, Austin, TX, Texas Cardiac Arrhythmia Institute, Austin, KYIntroduction: Outcomes in patients with atrial fibrillation (AF) and prolonged QRS duration are not extensively described. We aimed to determine whether AF patients enrolled in the Atrial

S390 Heart Rhythm, Vol. 9, No. 5, May Supplement 2012

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SIGNIFICANCE OF ADENOSINE TRIPHOSPHATE-INDUCED ATRIAL FIBRILLATION FROM NON-PV FOCISusumu Tao, MD, Yasuteru Yamauchi, MD, Shingo Maeda, MD, Hiroyuki Okada, MD and Toru Obayashi, MD. Musashino red cross hospital, Tokyo, JapanIntroduction: We reported previously that adenosine triphosphate (ATP)-induced AF is strongly related to clinical atrial fibrillation (AF) and ATP injection is useful to identify arrhythmogenic pulmonary vein (PV). However, clinical significance of ATP-induced AF from non-PV foci remains unclear.Methods: We analyzed the consecutive 256 patients (188 with paroxysmal AF and 68 with persistent AF, age 61.8±10.9 years, 201 male), who underwent extensive PV isolation for AF. We injected ATP 20mg before and after PV isolation, and searched trigger sites of ATP-induced AF and PV dormant conduction. In all patients, we added radiofrequency application to eliminate PV dormant conduction.Results: 25 patients (9.8%) in whom AF was induced from non-PV foci by ATP were defined as Group A, and the others were defined as Group B. Trigger sites of non-PV AF were right atrium including sinus venosa, crista terminalis, and right atrial appendage (RAA), in 18 patients, and left atrium in 7 patients. The inducibility of AF from non-PV foci by ATP injection was significantly higher in patients with paroxysmal AF (22 of 188 patients ) than persistent AF (3 of 68 patients) (12% vs 5%; p<0.05). During a mean follow-up of 13±6 months, AF recurrent rate in patients with paroxysmal AF was significantly higher in Goup A (11 of 22 patients) than in Group B (32 of 166 patients) (50% vs 19%; p<0.05). Among 3 patients who underwent second session in Group A, PV reconnection was not observed in 2 patients, suggesting AF with non-PV origin. In each patient AF was induced repeatedly from RAA and sinus venosa by ATP injection and we performed radiofrequency application to RAA and sinus venosa respectively. After seccond session AF recurrence was not observed in two patients.Conclusions: ATP-induced AF from non-PV foci was related to higher clinical AF recurrent rate. ATP injection is useful to identify non-PV ectopies.

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60 MINUTES WAITING VERSUS SUPPLEMENTARY ADENOSINE ADMINISTRATION FOR PV CONDUCTION RECOVERYDipen C. Shah, MD, Chan-Il Park, MD, Haran Burri, MD, Henri Sunthorn, MD and Pascale Gentil-Baron, RN. Hopital Cantonal De Geneve, Division of Cardiology, Geneva, SwitzerlandIntroduction: Conduction recovery between the left atrium (LA) and pulmonary veins (PV) is very frequently seen in patients with atrial fibrillation (AF) recurrence after successful PV isolation (PVI). Reversible thermal effects on the electrical activity of ablated tissue are thought to be responsible. We compared prolonged surveillance post PVI alone versus supplementary Adenosine administration to unmask dormant LA - PV conduction.Methods: Two consecutive groups of patients with paroxysmal AF were studied. Circular mapping guided individual PVI was performed followed if necessary by additional substrate ablation. For the first group (Gr W) a ≥ 60 min waiting period (after all PVI) was enforced for conduction recovery (CR). For the second group, waiting for spontaneous PVCR was combined with IV adenosine administration to unmask dormant PV conduction (Gr W+A) within 60 minutes. For both groups, additional ablation was performed to eliminate spontaneous and adenosine

atypical AFL (3.39 vs 2.00, p<0.001). Using multivariate analysis, the only independent predictor of a higher rate of PV reconnection was recurrence of AF after the initial ablation.Conclusions: At least one LA-PV reconnection was found in the majority of patients with recurrent atrial arrhythmias after previously successful PV isolation. Pts undergoing segmental PVI tended to develop recurrent AF rather than atypical AFL, and had a higher number of PV reconnections.

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THE IMPACT OF IMPAIRED RENAL FUNCTION ON THE CARDIOVASCULAR MORTALITY AND THROMBOEMBOLIC EVENTS IN THE LOW RISK ATRIAL FIBRILLATION PATIENTSWen-Yu Lin, MD, Yenn-Jiang Lin, MD and Shih-Ann Chen, MD. Tri-Service General Hospital, Taipei, Taiwan, Taipei Veterans General Hospital, Taipei, TaiwanIntroduction: Atrial fibrillation (AF) patients with high CHA2DS2-VASC score are at increased risk for systemic thromboembolism. However, residual cardiovascular risk in the low risk patients (≤1 non-major risk factors) remain unclear. We proposed that renal dysfunction could have additive prognostic value in these patients.Methods: This study included 617 consecutive non-valvular AF patients (495 paroxysmal AF, and 122 non-paroxysmal AF) who received pharmacological rhythm control without ablation. The estimated glomerular filtration rate (eGFR) was calculated using the Cockcroft-Gault equation, and these patients were divided into groups by eGFR (≥60 and <60 ml/min/1.73m2) and CHA2DS2-VASC score (<2 and ≥2) at the baseline of follow-up. The end-point was occurrence of major cardiovascular (CV) events, including the CV death, ischemic stroke, transient ischemic attack (TIA), coronary artery disease, pulmonary embolism, and peripheral vascular embolism.Results: During a follow-up of 50.6±39.7 months, 85 patients (13.8%) experienced major CV events. In CHA2DS2-VASC score of 0-1 patients, there were 27 patients suffered from major CV events with annual events rate of 1.74% per year. Mutivariate Cox regression analysis demonstrated that renal function was the only predictor in these patients. Patients with decreased eGFR (<60 ml/min/1.73m2) were associated with higher major CV events rate compared to preserved eGFR (1.21% vs. 6.78% per year, respectively, with a hazard ratio of 5.051, P <0.001, Figure).Conclusions: Decreased eGFR (<60 ml/min/1.73m2) serves as an additive risk factor of cardiovascular mortality and thromboembolism in the low risk AF patients.

S391Poster Session V

Time from procedure to scan (months) 9.7 (±2.9) 7.3 (±3.9) ns

GCA score 0.91 (±0.53) 0.56 (±0.53) 0.16

Fazekas score 1.27 (±0.90) 0.89 (±0.92) 0.36

Conclusions: We found no evidence of increased white matter abnormality in patients ablated with the PVAC™ catheter compared to conventional irrigated RF LASSO guided point-point ablation in the medium term. No patients suffered a CVA or TIA during the trial or follow-up period.

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THROMBOEMBOLIC RISK IN 16,274 PATIENTS WITH ATRIAL FIBRILLATION UNDERGOING DIRECT CURRENT CARDIOVERSION WITH AND WITHOUT PRIOR ORAL ANTICOAGULANT THERAPY - A NATIONWIDE STUDYMorten L. Hansen, Sr., MD, PhD, Jonas Bjerring Olesen, MD, Martin Huth Ruwald, MD, Deniz Karasoy, MD, Lars Køber, MD, DMSc, Jim Hansen, MD, DMSc, Gunnar Gislason, MD, PhD and Christian Torp-Pedersen, MD, DMSc. Department of Cardiology, Gentofte University Hospital, Hellerup, Denmark, Department of Cardiology, The Heart Centre, Rigshospitalet-Copenhagen University Hospital, Copenhagen, DenmarkIntroduction: Direct current (DC) cardioversion in patients with estimated atrial fibrillation duration below 48 hours is often performed without prior anticoagulant coverage. We compared the thromboembolic risk in patients undergoing DC cardioversion for atrial fibrillation with and without prior oral anticoagulant coverage.Methods: A total of 16,274 patients discharged after a first-time DC cardioversion for atrial fibrillation between 2000 and 2008, were identified from the Danish National Patient Registry. Use of oral anticoagulant therapy within 90 days prior to DC cardioversion was obtained from the Danish Register of Medicinal Product Statistics. The risk of thromboembolism was estimated by calculating incidence rates and by multivariable adjusted Cox proportional-hazard models.Results: During the initial 30 days following discharge, the thromboembolic incidence rate was 11.70 per 100 patient-years for the no prior oral anticoagulant therapy group (n = 5,084 (31.2%)), as compared with 4.16 per 100 patient-years for the prior oral anticoagulant therapy group (n = 11,190 (68.8%)), (hazard ratio (HR) in the no prior oral anticoagulant therapy group, 2.43; 95% confidence interval [CI], 1.52 to 3.86). Thromboembolic risk stratification by the CHADS2 score did not change the results.Conclusions: Early DC cardioversion for atrial fibrillation without prior anticoagulation is associated with a high risk of thromboembolism. Notably, the risk is highest in the immediate period after cardioversion. Current strategies of early DC cardioversion without prior anticoagulation may warrant re-evaluation.

provoked PVCR.Results: 78 consecutive patients (55 M, 60 11 yrs) with paroxysmal AF were studied. In Gr W (39 patients, 29 M, 60±12 yrs,Contact force optimized PVI in 2), spontaneous PVCR was observed in 19/147 PVs during the waiting period and eliminated. In Gr W+A (39 patients, 26 M, 60 11yrs, Contact force optimized PVI in 23), spontaneous PVCR was observed in 19/156 PVs and dormant PV conduction unmasked by adenosine in 31/156 PVs. Spontaneous PVCR after Adenosine administration was observed in 5 PVs. Spontaneous PVCR and dormant PV conduction were successfully eliminated by additional RF. After a single procedure, 65% patients in Gr W (f-up 17 5 mnths) and 81% patients in Gr W+A (f-up 8 2 mnths) remained in stable sinus rhythm without anti-arrhythmic drugs (p=0.11).Conclusions: More frequent use of contact force optimization for PVI did not reduce spontaneous PVCR during 60 minutes surveillance. Eliminating adenosine induced dormant PV conduction and spontaneous PVCR by additional ablation during 60 min surveillance after initially successful PVI may improve maintenance of stable sinus rhythm without antiarrhythmic drug treatment during follow-up.

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MRI ASSESSED BRAIN ABNORMALITY IN PATIENTS WHO HAVE UNDERGONE PULMONARY VEIN ISOLATION: A RANDOMISED COMPARISON OF PHASED MULTI-ELECTRODE RADIOFREQUENCY ABLATION (PVAC™) OR CONVENTIONAL LASSO GUIDED IRRIGATED RADIOFREQUENCY ABLATION TECHNIQUESA. Neil Sulke, MD, Steven Podd, MBBS, David F. Sallomi, MBBS, Emma J. Owens, MBBS, Nick J. Barlow, MBBS and Stephen S. Furniss, MD. Eastbourne General Hospital, E. Sussex, United KingdomIntroduction: Pulmonary vein isolation (PVI) ablation is a standard treatment for atrial fibrillation (AF). A serious non-reversible adverse event is cerebro-vascular accident (CVA). Recent data has suggested that patients treated with the PVAC™ Phased multi-electrode radiofrequency (RF) ablation catheter may result in clinically silent micro-emboli post ablation. Using diffusion weighted MRI we evaluated the amount of white matter change and atrophy in patients who have undergone PVI ablation with PVAC™ and with conventional irrigated RF ablation with LASSO technology. Rates of clinical CVA between these two techniques have yet to be compared in randomised trials.Methods: 40 patients were randomised to PVI ablation with the PVAC™ catheter system or to conventional point-point irrigated RF ablation with LASSO. All patients underwent a DWI-MRI brain scan between 1 and 12 months post ablation. The images were reviewed and scored by 2 radiologists independently, who were blinded to ablation technique, using the Global Cerebral Atrophy score (GCA) and the Fazekas score. The results were meaned and compared to procedural technique, procedural times and INRs at time of ablation. All procedures were undertaken with the patients fully heparinarised with ACT ≥300s and all patients remained on warfarin before, during and after the ablation.Results:

PVAC™ LASSO P value

Number of patients 20 20Age 67.5 (±9.5) 63.78

(±12.53) nsHypertension 9 (45%) 8 (40%) nsDiabetes 1 (5%) 1 (5%) nsProcedural time (mins) 87.2

(±30.5) 124.3 (±34.6) <0.01Average INR at time of procedure 2.5 (±0.6) 2.2 (±0.6) ns

S392 Heart Rhythm, Vol. 9, No. 5, May Supplement 2012

Methods: We retrospectively reviewed medical records from patients receiving HeartMate II continuous flow LVAD from June 2009 to July 2010 at a single center. Data were obtained from inpatient and outpatient electronic medical records including ICD interrogations from one year prior to last date of chart review, death, or transplantation. Four patients had an ICD implanted prior to discharge from LVAD implantation; the remaining had a preexisting ICD. Paroxysmal atrial fibrillation was defined as > 30 seconds of recorded atrial fibrillation. Usual anticoagulation practice was aspirin 81mg daily and warfarin with goal INR 1.5-2.0 in those without atrial fibrillation and 2.0-2.5 in those with atrial fibrillation.Results: 37 consecutive patients had LVAD implantation from June 2009 to July 2010. Median age was 58 at time of implantation. 15 patients had LVAD as destination therapy. Median duration of follow-up was 277 days. A total of 23 patients had atrial arrhythmias before or after LVAD implantation (62% of overall group; 16 prior to LVAD, 7 after LVAD). Of the 16 patients with a history of atrial arrhythmia prior to LVAD, 11 had paroxysmal atrial fibrillation, 4 had persistent atrial fibrillation, 3 had atrial flutter). New onset atrial fibrillation or flutter occurred in 7 patients after LVAD implantation (30% of overall group). The number of inappropriate ICD therapies for atrial arrhythmias was 10 episodes in 3 patients, and the number of appropriate ICD therapies was 65 episodes in 11 patients. There was one stroke and two TIAs in patients with preexisting atrial fibrillation, and no neurologic events in patients without atrial fibrillation.Conclusions: LVAD implantation is associated with a high prevalence of atrial arrhythmias. This finding warrants further studies into the prediction of atrial arrhythmias after LVAD and optimal methods of thromboembolism prevention.

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A NOVEL CACNA1C MUTATION IN SHORT QT SYNDROMEYanfei Ruan, MD, Mirella Memmi, PhD, Raffaella Bloise, MD, Valeria Novelli, PhD, Stephan Heo, MD, Marina Cerrone, MD, Nian Liu, MD, Carlo Napolitano, MD, PhD and Silvia G. Priori, MD, PhD. Cardiovascular Genetics Program,The Leon H. Charney Division of Cardiology,NYU Langone Medical Cente, New York, NY, IRCCS Fondazione Salvatore Maugeri,Molecular Cardiology, Pavia, Italy, New york university school of medicine, New York, NY, Cardiovascular Genetics Program,The Leon H. Charney Division of Cardiology,NYU Langone Medical Center;IRCCS Fondazione Salvatore Maugeri,Molecular Cardiology;Cardiology, University of Pavia, New York, NYIntroduction: Short QT syndrome(SQTS) is a genetically determined ion-channel disorder, which is characterized by an abnormally short QT interval and increased risk of ventricular fibrillation and cardiac death. It has been reported that loss-of-function mutations in genes encoding the cardiac L-type calcium channel to be associated with a familial sudden cardiac death syndrome in which a Brugada syndrome phenotype is combined with shorter QT intervals. Here we report a novel CACNA1C mutation identified in a SQTS patient without Brugada syndrome phenotype.Methods: Gene Screening was performed in genomic DNA of proband. Membrane currents were measured using patch clamp procedures in HEK 293 cells.Results: Proband is a 12-year-old girl. She had 2 cardiac arrests when she was 4 months old; she had 2 episodes of ventricular fibrillation when she underwent cardiac catheterization. Then she was treated with beta blockers for 3 years. She never had new episodes. ECG showed QT of 220 msec without the elevation of right precordial ST-segment. Gene Screening identified CACNA1C R1906Q. WT and R1906Q CACNA1C were expressed in HEK 293 cells. Voltage clamp demonstrated that

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IMPACT OF DIFFERENT CATHETER ABLATION STRATEGIES ON PROCEDURE OUTCOME IN COEXISTENT ATRIAL FLUTTER AND FIBRILLATION: RESULTS FROM A SINGLE-BLINDED RANDOMIZED STUDY (APPROVAL)Sanghamitra Mohanty, MD, Prasant Mohanty, MBBS, Luigi Di Biase, MD, PHD, FHRS, Rong Bai, MD, Pasquale Santangeli, MD, Agnes Pump, MD, David Burkhardt, MD, Joseph Gallinghouse, MD, Rodney Horton, MD, Javier Sanchez, MD, Shane Bailey, MD, Jason Zagrodzky, MD and Andrea Natale, MD, FHRS. St. David’s Medical Center, Austin, TXIntroduction: This study aimed to compare the impact of different ablation strategies on AF recurrence and quality of life (QoL) in coexistent atrial fibrillation (AF) and flutter (AFL).Methods: Three-hundred sixty consecutively 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 months follow-up. QoL was assessed at baseline and 12-month follow-up using 4 questionnaires; Medical Outcome Study Short Form (SF-36), Hospital Anxiety and Depression Score (HAD), Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI).Results: Of the 182 patients in group 1, 58 (63±8 years, 78% male, 59±8 LVEF) had AF+AFL ablation and 124 (61±11 years, 72% male, 59±7 LVEF) had just AF ablation. In group 2 (62±9 years, 76% male, 58±10 LVEF) only flutter was ablated by achieving bidirectional isthmus conduction block. Baseline characteristics were not different across groups. At 16±4 months follow-up, 125 (69%) in group 1 and 34 (19%) in group 2 were arrhythmia-free (p <0.001). In group 1, scores on almost all QoL subscales showed significant improvement at follow-up, whereas group 2 patients derived relatively minor benefit (Table). STAI scores showed no significant association with ablation outcome.Conclusions: In patients with coexistent AF and AFL, lower AF recurrence and better QoL is associated with AF ± AFL ablation than with lone AFL ablation. This is the first study showing that in patients blinded to the procedure, QoL is not impacted by a placebo effect.

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ATRIAL ARRHYTHMIAS AND STROKE IN PATIENTS RECEIVING CONTINUOUS FLOW LEFT VENTRICULAR ASSIST DEVICEPeter M. Jessel, MD, Christopher V. Chien, MD, Ajay Tripuraneni, MD, Jack Kron, MD, Karl Stajduhar, MD, Charles A. Henrikson, MD and Eric C. Stecker, MD, MPH. Oregon Health & Science University, Portland, ORIntroduction: The burden of ventricular arrhythmias after left ventricular assist device (LVAD) implantation has been well described, but the prevalence of atrial arrhythmias and their impact on the risk of stroke after LVAD is unknown.

S393Poster Session V

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THE KCNQ1 VARIANT R231H CONFERS A HIGH RISK FOR EARLY ONSET ATRIAL FIBRILLATIONDaniel C. Bartos, BS, Jeffrey B. Anderson, MD, MPH, Don E. Burgess, PhD, Jonathan N. Johnson, MD, David J. Tester, BS, Rachel Bastiaenen, MRCP, Elijah R. Behr, MD, Michael J. Ackerman, MD, PhD, Pascale Guicheney, PhD and Brian P. Delisle, PhD. University of Kentucky, Lexington, KY, The Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, Mayo Clinic, Rochester, MN, St. George’s University of London, London, United Kingdom, INSERM, Paris, France, University of Kentucky, Lexington, KYIntroduction: Long QT syndrome type 1 (LQT1) is caused by mutations in KCNQ1, which encodes the voltage-gated K+ channel α-subunit Kv7.1. Kv7.1 combines with the K+ channel β-subunit KCNE1 to generate the slowly activating delayed rectifier K+ current (IKs) in the heart. Several LQT1 mutations are linked to atrial fibrillation at < 50 years of age (early onset AF). This study determines whether these KCNQ1 mutations have functional phenotypes that predispose patients to AF.Methods: The KCNQ1 mutations R231H or T322A were identified in two index patients diagnosed with LQT1 & early onset AF. We evaluated additional genotype positive patients for R231H or T322A KCNQ1; studied the functional phenotypes of R231H & T322A in vitro; & simulated these effects in a modified Courtemanche-Ramirez-Nattel (CRN) human atrial action potential (AP) model.Results: Including the index patients, eleven R231H patients & thirteen T322A patients were evaluated. Eight R231H patients have early onset AF & only one has a long resting QTc interval. In contrast, only one T322A patient presented with early-onset AF (which was alleviated after pulmonary vein isolation) & ten have long resting QTc intervals. We expressed wild type KCNQ1 (WT), R231H, or T322A in HEK293 cells. All expression studies included KCNE1. Cells expressing WT generated current similar to IKs (n = 18); cells expressing R231H generated a time- & voltage-independent current (n = 10); & cells expressing T322A generated no current (n = 7). We co-expressed WT with R231H or T322A to mimic the patients’ heterozygous genotypes. Cells co-expressing WT & R231H had similar current amplitudes as cells expressing WT, but they activated at negative potentials with a time- & voltage-independent component (n=12). In contrast, cells co-expressing WT & T322A have decreased current amplitudes by 67% (n = 10). Simulating these effects using the modified CRN model predicted that R231H shortens atrial AP duration by > 50% & T322A prolongs it by < 11%.

current density significantly decreased in R1906Q compared with WT at test potential between -20 mV to +50 mV. At +10 mV, R1906Q current density decreased to 51% of WT (4.72±0.94 pA/pF, n=21 vs 9.24±1.02 pA/pF, n=25, p<0.001). There was no difference of steady-state activation and inactivation between WT and mutant channel.Conclusions: We report a novel CACNA1C mutation with loss of function in a SQTS patient without Brugada syndrome phenotype, suggesting that CACNA1C screening is warranted in SQTS.

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FLECAINIDE CHALLENGE IN KCHIP2 KNOCKOUT MICE AS A NOVEL MODEL OF BRUGADA SYNDROMEAlbert Y. Sun, MD and Geoffrey S. Pitt, MD, PhD. Duke University Medical Center, Durham, NCIntroduction: The Brugada Syndrome is characterized by ST elevation in the right-sided precordial ECG leads, a feature that can be unmasked via the administration of a sodium channel blocker. This characteristic ECG pattern is thought to be a result of a transmural voltage gradient involving the right ventricle and outflow tract. The transient outward potassium current (Ito) is heavily responsible for the electrical heterogeneity in this region. We propose that knockout mice of the Ito auxiliary subunit KChIP2 can recapitulate the characteristic Brugada pattern on ECG with flecainide administration.Methods: 21 mice (11 KChIP2 knockout (KO) and 10 wildtype (WT)) were anesthetized and had ECG recordings performed in a lead II and an anterior precordial position at baseline and after IP administration of flecainide (20mg/kg). To account for variable QRS morphology among mice, the ratio of R wave maximum height to the ST segment maximum height was used to quantify changes in ST segment elevation.(Figure 1)Results: There was no significant difference in R max/ST max ratio between WT and KO’s when measured in the lead II or anterior precordial configuration at baseline. With administration of flecainide, the R max/ST max ratio also did not differ in lead II however there was a significant difference between WT and KO mice (3.96 vs 0.76 p=0.001) (Figure 2) in the anterior precordial configuration indicating a marked ST elevation in KO mice.Conclusions: Administration of flecainide to KChIP2 knockout mice recapitulates the clinical findings seen in human Brugada Syndrome drug challenges. The pleotropic effects of KChIP2 make this a prime model in the study of the Brugada Syndrome.

S394 Heart Rhythm, Vol. 9, No. 5, May Supplement 2012

3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine).Methods: Electrophysiology assays to test for block of hNaV1.5 late and peak INa and other major human cardiac ion channels were performed at room temperature with automated whole-cell patch clamp (Gohm seal) using HEK293 or CHO cell lines for channel expression. The effect of GS-458967 on 162 ion channels, ion transporters, receptors, and enzymes was tested in cell-free and cell-based binding assays. The effect of GS-458967 on 442 kinases was tested using the KinomeScan assay.Results: In HEK293 cells expressing hNaV1.5, GS-458967 selectively blocked late INa generated by 10 nM ATX-II (IC50=0.06±0.01 μM, n=5-13) (mean at end of 250 ms step to -20 mV from HP -120 mV, 0.1 Hz) and caused significantly less block of peak INa (IC50=8.46±0.36 μM, n=5-13) (peak during 20 ms step to -20 mV from HP -120 mV, 0.1 Hz). Block by GS-458967 of 11 other major cardiac ion channel currents was significantly less than block of late INa. In competition binding studies on 162 targets, GS-458967 (10 μM) displaced 70% of ligand bound to the Na+ channel. Displacement of ligand bound to all other targets was less than 50%. Note that the concentration tested was more than 200-fold higher than the IC50 for block of late INa. The effects of GS-458967 (3 μM) on 442 kinases were not significant.Conclusions: Our results demonstrate that GS-458967 is a highly selective blocker of late INa. The magnitude of the selectivity of GS-458967 makes this compound useful in studies designed to determine the role of late INa under pathological conditions. In addition, it should help elucidate the physiological role of the much smaller late INa observed in cardiomyocytes under normal conditions.

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REMODELING OF MECHANICAL JUNCTIONS AND OF MICROTUBULE−ASSOCIATED PROTEINS ACCOMPANY CARDIAC CONNEXIN43 LATERALIZATIONHalina Chkourko, MS, Guadalupe Guerrero-Serna, PhD, Xianming Ling, PhD, Nedal Darwish, No Degree, Keith E. Cook, PhD, Jeffrey R. Martens, PhD, Eli Rothenberg, PhD, Hassan Musa, PhD and Mario Delmar, MD, PhD. New York University, New York, NY, University of Michigan, Ann Arbor, MIIntroduction: Desmosomes and adherens junctions provide mechanical continuity between cardiac cells, whereas gap junctions allow for cell-cell coupling. These structures reside at the intercalated disc (ID). Also at the ID is the voltage-gated sodium channel (VGSC) complex. Functional interactions between desmosomes, gap junctions, and VGSC have been demonstrated. Separate studies show, under various conditions, reduced presence of gap junctions at the ID, and redistribution of connexin43 (Cx43) to plaques oriented parallel to fiber direction (gap junction “lateralization”); the mechanisms of Cx43 lateralization, and the fate of desmosomal and sodium channel molecules in the setting of Cx43 remodeling, remain understudied.Methods: Adult sheep were subjected to right ventricular pressure overload (pulmonary hypertension; PH). Heart tissue/cells were assessed by microscopy/patch clamp.Results: Lateralization of Cx43 was accompanied by redistribution of mechanical junction molecules. Desmosomes and gap junction plaques were demonstrable by electron microscopy. Quantitative analysis revealed high Pearson’s correlation coefficients (PCC) for the co-localization of Cx43 with desmosomal molecules both at the ID (ranged between 0.4 and 0.5) and at the lateral membranes (ranged between 0.22 and 0.33). In contrast, Nav1.5 (VGSC α subunit) failed to re-organize in plaques (PCC: 0.155 at ID and 0.036 +/- 0.012 with lateralized Cx43). Cx43/desmosomal remodeling was accompanied by

Conclusions: The functional phenotype of R231H confers a high penetrance for early onset AF (73%) by decreasing atrial refractoriness; whereas, T322A does not. Additional factors likely contribute to the long QTc in the R231H patient and early-onset AF in the T322A patient.

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DOES SCN10A GENE PRODUCT PLAY A ROLE IN CANINE PURKINJE CELL ELECTROPHYSIOLOGY?Wen Dun, PhD and Penelope Boyden, PhD. Columbia Univ, Pharmacology, New York, NYIntroduction: Several GWAS studies have recently linked SCN10A to prolonged PR intervals in patients. One study reported the expression of Nav1.8 channel in the murine His-Purkinje system using RT-PCR analysis, and went on to show that a selective Nav1.8 channel blocker, A-803467, prolonged QRS duration in the ECG of mice (Nature Genetics, 2010). The aim of our study was to examine whether the neuronal Nav1.8 channel (SCN10A) protein was present in canine Purkinje cells and it did functionally contribute to the Purkinje cell sodium currents (INa).Methods: Whole cell voltage clamp and immunohistochemical techniques were used to identify the role of the Nav1.8 channel in canine Purkinje cells. Anti- Nav1.8 rabbit polyclonal antibody (Sigma, 1:100) was used to detect Nav1.8 protein in the immunohistochemical study of frozen sections.Results: Electrophysiological studies showed that the selective Nav1.8 channel blocker, A-803467 (100 nM), did not affect INa and its gating functions. INa (pA/pF) was 8.9±3.5 in control compared with 9.4±3.9 in presence of A-803467 (n=5, P>0.05). The half-maximal voltage (V0.5) of the availability curve was -88.8±1.5 in control versus -89.5±1.4 in presence of A-803467 (n=5, P>0.05). The time constants (τ1 and τ2 ms) of recovery from INa inactivation (Vh=-100 mV) were 39.8±3.1 and 554.1±58.2 in control versus 43.8±5.0 and 436.0±47.9 in A-803467 (n=5, P>0.05). Immunohistochemical confocal studies revealed that intense Nav1.8 staining coursed between Purkinje cell bundles. Intense Nav1.8 immunostaining was also seen around small capillaries in the Purkinje tissue sections. However, there were no immuno-signals depicting Nav1.8 staining in the Purkinje cells. Furthermore, co-immunostaining with antibody to neuronal nuclei (Anti-NeuN, Millipore) showed that the intense Nav1.8 staining was distributed with the neuronal cells between the Purkinje cell bundles.Conclusions: Our results suggest that Nav1.8 channel is not present in canine Purkinje cells. Therefore, SCN10A gene product Nav1.8 does not directly play a role in the cardiac conduction system. However, detected Nav1.8 immuno-signals in Purkinje tissue sections appear to be associated with neurons which could have an effect on cardiac electrophysiology.

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DISCOVERY OF GS-458967: A NOVEL AND HIGHLY-SELECTIVE INHIBITOR OF CARDIAC SODIUM CHANNEL LATE CURRENTCatherine J. Smith-Maxwell, PhD, Cheng Xie, PhD, Kim Chan, PhD, Dmitry Koltun, PhD, Jeff Zablocki, PhD, John Shryock, PhD and Luiz Belardinelli, MD. Gilead Sciences, Palo Alto, CA, Gilead Sciences, Foster City, CAIntroduction: Previous studies have shown that a pathological increase in late sodium current (INa) in the heart is associated with increased mechanical and electrical dysfunction. Study of the role of late INa in cardiac disease has been hampered by the lack of selective blockers. We have identified a novel selective inhibitor of late INa, GS-458967 (6-(4-(trifluoromethoxy)phenyl)-

S395Poster Session V

Pfeiffer, BS, Fabio Dezi, MS and Charles Antzelevitch, PHD, FHRS. Masonic Medical Research Laboratory, Utica, NY, Gilead Sciences, Palo Alto, CA, Gilead Sciences, Palo Alto, NYIntroduction: Recent studies have shown that SCN10A, encoding the TTX-resistant neuronal sodium channel Nav1.8, is expressed in the human heart. Several genome-wide association studies (GWAS) report single nucleotide polymorphisms (SNPs) in SCN10A to be associated with cardiac conduction disease and arrhythmogenesis. Our understanding of the association between these clinical manifestation and the SCN10A variants remains poorly understood. In this study, we tested the hypothesis that Nav1.8 modulates the expression of Nav1.5, the principal cardiac sodium channel.Methods: SCN10A was screened by direct sequencing of all exons and intron borders in probands with Brugada syndrome (BrS), right bundle branch block (RBBB) and cardiac conduction disease (CCD). Wild type (WT) and mutant SCN10A channels were co-expressed with SCN5A and SCN3B in HEK293 cells, and studied using co-immunoprecipitation (Co-IP) and whole-cell patch-clamp technique.Results: Mutations in SCN10A were identified in 3 probands with BrS, RBBB and CCD. Proband 1 was an asymptomatic 19 y/o male with typical BrS Type-1 ST segment elevation in V1 and V2, and inducible VF during procainamide challenge. Proband 2 presented with RBBB and family history of sudden cardiac death (SCD) in a 1.5 month old cousin. Both carried a novel N-terminal SCN10A mutation, R14L, in exon 1, which was absent in 223 controls. Proband 3, a 24 y/o female, showed 1st degree AV block (PR interval=270 ms) and incomplete RBBB. A R1268Q-SCN10A mutation located in exon 21 at DIII-S4/S5 was identified in this case and was not found in 224 controls. Proband 3’s sister experienced SCD at age 16. Residues R14 and R1268 are highly conserved among species. Co-IP indicated structural association between Nav1.5 and Nav1.8 when Navβ3 was co-expressed. Co-expression of SCN5A/WT+SCN3B/WT with SCN10A/R14L or SCN10A/R1268Q resulted in 75.5% and 84.4% reduction of peak sodium channel current (INa) compared to co-expression with SCN10A/WT (n=8-9, p<0.05 for each group respectively).Conclusions: Our findings suggest that both R14L and R1268Q missense mutations in SCN10A contribute to the development of BrS, CCD and SCD by causing loss of function in INa secondary to reduced functional expression of the Nav1.5 and Nav1.8 protein complex.

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FREQUENCIES OF MITOCHONDRIAL DNA 4977BP DELETION MUTATION AND SINGLE NUCLEOTIDE POLYMORPHISM ON 4Q25 GENE IN PATIENTS WITH ATRIAL FIBRILLATION ACCORDING TO AGINGJaemin Shim, MD, Sook Kyoung Kim, PhD, Kyoung-Jin Shin, PhD, Myung Jin Park, MS, Jung Min Kim, MSc, Jae Hyung Park, PhD, Boyoung Joung, MD, PhD, Moon-Hyoung Lee, MD, PhD and Hui-Nam Pak, MD, PHD, FHRS. Yonsei University Health System, Seoul, Korea, Republic ofIntroduction: It has been reported that somatic mutations in the mitochondrial DNA 4977bp deletion (mtDNA4977-mut) are related to oxidative stress and cardiovascular disease. Nuclear DNA polymorphism in chromosome 4q25 (rs2200733) has been known to be prevalent among patients with atrial fibrillation (AF). We hypothesized that mtDNA4977-mut and rs2200733 work differently depending on the age of patients with AF.Methods: We observed for the mtDNA4977-mut and rs2200733 polymorphism in 212 patients with non-valvular AF (51 ± 13 years old, male 83.5%, 153 paroxysmal AF, 59 persistent AF) who underwent catheter ablation and 219 age-matched control.

lateralization of two microtubule-associated proteins: EB1 and kinesin (Kif5b). Patch clamp studies demonstrated reduced amplitude and kinetics of sodium current and small reduction in electrical coupling.Conclusions: Cx43 lateralization is part of a complex remodeling that includes mechanical and gap junctions, but exclude components of the VGSC. Lateralization likely results from redirectionality of microtubule-mediated forward trafficking. Remodeling of junctions may preserve electrical synchrony if ID integrity is disrupted.

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COMMON GENETIC POLYMORPHISM AT 4Q25 PREDICTS ATRIAL FIBRILLATION RECURRENCE AFTER SUCCESSFUL CARDIOVERSIONBabar Parvez, MD, Raafia Muhammad, MD, Jc. Estrada, MD, Rachael Richardson, RN, Benjamin Shoemaker, MD, Lan Jiang, MS, Marcia Blair, MS, Dan Roden, MD and Dawood Darbar, MD. Vanderbilt University, Nashville, TNIntroduction: Genome-wide association (GWA) studies have identified 3 loci at 4q25 (near PITX2), 16q22 (in ZFHX3), and 1q21 (in KCNN3) that associate with atrial fibrillation (AF). The aim of this study was to prospectively evaluate if AF recurrence after successful cardioversion is modulated by common AF susceptibility alleles at these loci.Methods: 208 patients (age 65±11 years, 77% men) with persistent AF were enrolled into the Vanderbilt AF direct current cardioversion (DCCV) Registry. Following successful restoration of sinus rhythm, patients were prospectively evaluated at 3, 6 and 12 months for AF recurrence, documented by 12-lead ECG or Holter monitors. Seven single nucleotide polymorphisms (SNPs): rs2200733 and rs10033464 at 4q25; rs7193343 in ZFHX3; rs13376333 in KCNN3 and rs1800469, rs1800470 and rs1800471 in transforming growth factor (TGF)-β1 at 19q13.2; 19q31.1 which causes selective atrial fibrosis and AF propensity were genotyped.Results: The final study cohort consisted of 196 patients (2 patients withdrew consents, 2 had pacemakers and 8 had atrial thrombi identified prior to DCCV). In 172 (88%) patients sinus rhythm was successfully restored with DCCV, of which 108 (63%) had AF recurrence at a median of 59 [27 - 176] days. Multiple clinical and echocardiographic variables failed to predict AF recurrence. However, presence of any common SNP (rs2200733 or rs10033464) at the 4q25 locus was an independent predictor of AF recurrence, (hazard ratio [HR]: 2.1, 95% confidence interval [CI]: 1.2-3.6, P=0.006). Furthermore, rs2200733 alone was an independent predictor of AF recurrence (additive model HR: 2.4, (1.4-4.1), P=0.001) and exhibited a graded allelic dose response for early AF recurrence (homozygous variants: 7 [4-97] days, heterozygous: 68 [32-327] days and wild type: 148 [36-442] days, P=0.008).Conclusions: This is the first study to prospectively evaluate genetic predictors of AF recurrence in patients undergoing elective DCCV. A common polymorphism on chromosome 4q25 is an independent predictor of AF recurrence after successful restoration of sinus rhythm. These findings implicate an altered atrial substrate in AF patients carrying 4q25 genetic variants and point to a potential role of stratification by genotype.

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GENETIC VARIANTS IN SCN10A ASSOCIATED WITH BRUGADA SYNDROME, RIGHT BUNDLE BRANCH BLOCK AND ATRIOVENTRICULAR BLOCKDan Hu, MD, PhD, Hector Barajas-Martinez, PhD, Kris Kahlig, PhD, Sridharan Rajamani, PhD, Luiz Belardinelli, MD, Ryan

S396 Heart Rhythm, Vol. 9, No. 5, May Supplement 2012

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CHROMOSOME 4Q25 ATRIAL FIBRILLATION SUSCEPTIBILITY ALLELES DO NOT CORRELATE WITH PULMONARY VEIN OR LEFT ATRIAL SIZEMoore B. Shoemaker, MD, Farhaan Ahmad, MD, Raafia Muhammad, MD, Babar Parvez, MD, Yanna Song, MS, Gayle Kucera, RN, Tanya Stubblefield, RN, Marcia Blair, MS, S. Patrick Whalen, MD, Christopher Ellis, MD, Pablo Saavedra, MD, William Bradham, MD, PhD, Mark Lawson, MD, Dan Roden, MD and Dawood Darbar, MD, PhD. Vanderbilt University, Nashville, TNIntroduction: Common single nucleotide polymorphisms (SNPs) on chromosome 4q25 have consistently been associated with either typical or lone AF. The closest gene, PITX2, participates in formation of the pulmonary vein (PV) myocardium and in Pitx2 knock-out mice results in increased inducibility of AF. Here, we sought to determine whether 4q25 AF susceptibility alleles correlated with PV size and structural remodeling seen on cardiac MRI.Methods: Three hundred fifty three patients (median age 59 years, 70% male) enrolled in the Vanderbilt AF Registry underwent pulmonary vein isolation (PVI) between 2004 and 2011. DNA samples were genotyped at two 4q25 SNPs, rs2200733 and rs10033464. A cardiac MRI was performed prior to initial PVI. Cumulative PV diameter was the sum of all PVs including common or accessory PVs. Analyses were adjusted for age, gender, height, BMI, time since AF diagnosis, LVEF, lone AF, non-paroxysmal AF, HTN, CAD, CHF and history of CABG.Results: Two hundred sixty three patients underwent MRI. The study cohort consisted of 219 patients (30 failed genotyping, 14 were excluded due to prior PVI/valve surgery). There was no difference in cumulative or individual PV diameters, or LA size between wild-type and variant allele carriers for either 4q25 SNP (Table 1). Age, CAD, LVEF, and BMI were predictors of cumulative PV size. Age, BMI, non-paroxysmal AF, and LVEF were predictors of LA diameter.Conclusions: Although carriers of 4q25 variant alleles are at increased risk for development of AF and demonstrate a lower response rate to PVI and antiarrhythmic drug therapy, this effect does not appear to be modulated through an effect by 4q25 loci on PV and/or LA structural changes.

The mtDNA4977-mut was detected in the peripheral blood with fragment analyses following PCR amplifications with two fluorescent primer sets.Results: 1.The overall frequency of the mtDNA4977-mut in patients with AF was not significantly different from that of control (24.5% vs. 19.6%, p=0.111), but AF patients with the mtDNA4977-mut were older than those without the mtDNA4977-mut (58 ± 12 vs. 49 ± 12 years old, p<0.0001). 2. Although the frequency of the rs2200733 variant (%) was significantly higher in patients with AF than control (90.5% vs. 72.9%, p<0.0001), there was no difference in age between the patients with and without the rs2200733 variant (p=0.153). 3. In the group of age ≥65 years, the mtDNA4977-mut was more common in patients with AF (n=38; 47.4%) than control (n=30; 20%, p=0.019). But the mtDNA4977-mut frequencies were not different between AF and control <65 years old (p=0.952). 4. In contrast, there was no difference in the frequencies of the rs2200733 variants between AF and control in those ≥65 years old (p=0.129). But the rs2200733 frequencies were significantly higher in AF patients <65 years old (n=151; 93.4%) than their age-matched control (n=185; 74.6%, p<0.0001).Conclusions: Both the mtDNA4977-mut and 4q25 polymorphism were associated with AF. The mtDNA4977-mut, an age-related somatic mutation, is associated with the older AF patients. The rs2200733, a chromosome 4q25 nuclear polymorphism, is closely related to the AF patients younger than 65 years old.

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AN ECG ENDOPHENOTYPE FOR A COMMON GENETIC VARIANT ASSOCIATED WITH ATRIAL FIBRILLATIONBabar Parvez, MD, Raafia Muhammad, MD, Benjamin Shoemaker, MD, Marcia Blair, MSc, Tanya Stubblefield, RN, Gayle Kucera, RN, Joshua Denny, MD, Dan Roden, MD and Dawood Darbar, MD. Vanderbilt University, Nashville, TNIntroduction: Common single nucleotide polymorphisms (SNPs) on chromosome 4q25 (near PITX2) have been consistently associated with atrial fibrillation (AF). The aim of this study was to assess whether a common tag SNP for this region (rs2200733) correlates with ECG parameters in patients with lone and typical AF.Methods: We examined the effect of rs2200733 genotype on the PR interval in Caucasians measured from the ECG in the absence of AV nodal blocking agents among lone AF probands (n=169), typical AF probands (n=274) and a healthy population with normal ECGs and no AF, drawn from the Vanderbilt Genome-Electronic Records (VGER) dataset (n=1403). For subjects with typical AF, ECG parameters were evaluated before the onset of AF (3.8±1.5 years).Results: The T allele rs2200733 had higher frequency in lone AF probands (22%) vs. typical AF (13%) and VGER (12%). There were no significant differences in the baseline characteristics of carriers of the variant allele (CT and TT) vs. wild type (CC) in lone AF (age 54±13 years, 72% men), typical AF (age 67±10 years, 77% men) and VGER (age 50±15, 43% men) subjects. In all 3 study cohorts, we observed a graded variant allelic dose response for PR interval prolongation and under a multivariable dominant model, carriers of the variant allele had prolonged PR interval compared to wild type group (Table).Conclusions: In this study, we showed that a common 4q25 AF susceptibility allele (rs2200733) is associated with PR interval prolongation in patients with lone and typical AF. This common genetic variant may serve as an ECG endophenotype for individuals carrying this 4q25 variant, and implicates slow atrial conduction as a modulator of 4q25-mediated AF.

S397Poster Session V

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NUCLEOSIDE DIPHOSPHATE KINASE B IS A NOVEL RECEPTOR-INDEPENDENT ACTIVATOR OF G-PROTEIN SIGNALING IN CLINICAL AND EXPERIMENTAL ATRIAL FIBRILATIONIssam Abu-Taha, BSc, Niels Voigt, MD, Stanely Nattel, MD, Thomas Wieland, PhD and Dobromir Dobrev, MD. Experimental Cardiology, University of Heidelberg, Mannheim, Germany, Montreal Heart Institute Research Center, Montreal, QC, Canada, Institute of Experiemental Pharmacology and Toxicology, Mannheim, GermanyIntroduction: Chronic atrial fibrillation (cAF) is associated with abnormal atrial Ca2+ and protein-kinase signaling, with G-protein related, cyclic AMP (cAMP)-mediated protein kinase A hyperphosphorylation playing a significant pathophysiological role. In the ventricle, nucleoside diphosphate kinase B (NDPK-B) increases cAMP levels through receptor-independent Gs-protein activation involving direct Gs-protein β-subunit interactionb/phosphorylation. Here, we assessed NDPK-B expression and Gs-protein signaling in atria from sinus rhythm (SR) versus cAF patients, and in dogs with atrial tachycardia remodeling (ATR).Methods: NDPK-B and G-protein expression was assessed in atria from 22 SR and 23 cAF patients and in atria from 7 control and 7 ATR (1-wk at 400 bpm) dogs by immunoblotting (GAPDH-controlled). cAMP levels were measured by immunoassay.Results: NDPK-B was robustly expressed in atria from both dogs and patients. In cAF patients, the protein levels of NDPK-B were increased by 96%* (fold-GAPDH: cAF, 1.960 ± 0.2291 n=7 vs SR, 1.02±0.132 n=6; *P<0.05) and this was accompanied by 80%* increases in both Gas and Gβ1 proteins. Protein levels of Gαi2, Gαi3 and Gβ2 were unchanged. Similarly, protein abundances of NDPK-B (increased by 161%*), Gαs (by 45%*) and Gβ1 (by 120%*) were higher in ATR than in control dogs, whereas Gαi2 and Gαi3 were unaltered. In cAF patients, immunoprecipitation of Gβ1 resulted in enhanced co-immunoprecipitation of NDPK-B and immunoprecipitation of NDPK-B yielded in increased co-immunoprecipitation of Gβ1, pointing to augmented complex formation between NDPK-B and Gβ1 in cAF patients. Basal cAMP content, measured in the presence of the b-adrenoceptor antagonist propranolol (100 µM) and phosphodiessterase inhibitor IBMX (1 mM), was higher in cAF than in Ctl patients (cAF, 20.21±1.75*, n=16 vs Ctl, 13.1±0.9, n=16 pmol/mg), indicating an increase in receptor-independent Gs activation and thus cAMP formation in cAF patients.

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CAMKII INHIBITION PREVENTS LATE INA-INDUCED ATRIAL FIBRILLATION AND CONTRACTURE IN THE ISOLATED RAT RIGHT ATRIAFaquan Liang, PhD, Peidong Fan, PhD, Jessie Jia, MS, Suya Yang, MS, Zhan Jiang, BS, Luiz Belardinelli, MD and Lina Yao, PhD. Gilead Sciences, Inc, Palo Alto, CA, CAIntroduction: Increase in late INa (INaL) has been implicated in cardiac arrhythmia and diastolic heart failure. Augmented INaL can lead to a rise in intracellular Na+ and Ca2+ and subsequent activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII). However, it remains unclear whether activation of CaMKII contributes to INaL-mediated atrial fibrillation and diastolic dysfunction.Methods: Right atrium isolated from rat was suspended in a DMT myograph chamber. The spontaneous beating and force of atria were recorded on a PowerLab data acquisition system. The atrium was preincubated for 30 min with a CaMKII inhibitor KN93 or a negative control, KN92, and then treated with Anemone toxin II (ATX-II) to increase late INaL.Results: The isolated rat right atria were beating spontaneously with an average of 291±9 bpm. ATX-II (50 nM) induced a rapid increase in atrial diastolic tension (contracture) and fibrillation (Fig A and C). KN93 concentration-dependently attenuated ATX-II-induced increase in maximal diastolic tension (Fig A), and delayed the time to onset of ATX-II-induced atrial contracture (Fig B). KN93 also reduced ATX-II-induced atrial fibrillation (Fig C), and abnormal atrial beating (Fig D). A 30min incubation of the right atria with 50 nM ATX-II resulted in a 2.5-fold increase in phosphorylation of CaMKII.Conclusions: Inhibition of CaMKII prevented ATX-II-induced atrial fibrillation and contracture in the isolated rat right atria. Activation of CaMKII contributes to INaL-mediated atrial fibrillation and diastolic dysfunction.

S398 Heart Rhythm, Vol. 9, No. 5, May Supplement 2012

PhD, Francis G. Spinale, MD and Michael R. Gold, MD. Yale University School of Medicine, New Haven, CT, Medical University of South Carolina, Charleston, SC, Medical University of South Carolina, New Haven, SC, Medical University of South Carolina, Charleston, CTIntroduction: Structural remodeling plays in important role in the pathogenesis and recurrence of atrial fibrillation (AF). While electrical cardioversion (EC) is highly successful for the acute restoration of sinus rhythm among patients with persistent AF, recurrence rates are high. The present study tested the hypothesis that alterations in the underlying structural / molecular processes, such as matrix metalloproteinases (MMPs) and tissue inhibitors of the MMPs (TIMPs) are predictive of AF recurrence following EC.Methods: Pre-EC plasma samples were obtained from patients with persistent AF (n=82, 76% male, 66±9 yrs mean±S.D). Left ventricular ejection fraction (LVEF) was 64±12% and left atrial (LA) volume was 44±15 mL/m2. Plasma MMP (8 MMP types), TIMP (all 4 TIMP types), NT-proBNP and hsCRP levels were measured using a high-sensitivity multiplex assay or ELISA. .Results: EC was successful in restoring sinus rhythm in all patients, but 35 (43%) reverted to AF within 3 months. The AF recurrence group had a similar LVEF and LA volume compared to those who maintained sinus rhythm (65±11 vs. 63±12%, p=NS, and 46±17 vs. 43±13 mL/m2, p=NS). Pre-EC plasma MMP-9 levels were higher (52333±45651 vs. 21906±45114 pg/mL, p<0.05) and TIMP-4 levels lower (2624±1271 vs. 3655±2425 pg/mL, p<0.05) in the AF recurrence group. Univariate receiver operator characteristics analysis revealed that the area under the curve (AUC) for MMP-9 (0.77, p=0.046), MMP-3 (0.66, p=0.024), TIMP-4, (0.64, p=0.047), but not NT-proBNP (0.59, p=0.12) or hsCRP (0.56, p=0.19) were predictive for AF recurrence. In multivariate AUC analysis, combination of MMP-9, MMP-3, and TIMP-4 provided stepwise increments in the ability to predict AF recurrence (AUC: 0.82, p=0.012).Conclusions: These findings indicate that circulating levels of MMPs and TIMPs may be independent predictors of AF recurrence. Thus, plasma levels of MMPs and TIMPs may be used to develop a novel biomarker “signature” to guide AF therapy.

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ANGIOTENSIN II AND NADPH OXIDASE ARE UPSTREAM TRANSCRIPTIONAL REGULATOR OF NEURONAL NITRIC OXIDE SYNTHASE IN LEFT VENTRICULAR MYOCARDIUMEue-Keun Choi, MD, PhD, Ji Hyun Jang, BS, Chun Zi Jin, BS, Sung Joon Kim, MD, PhD, Seil Oh, MD, PhD and Yin Hua Zhang, PhD. Seoul National University College of Medicine, Seoul, Korea, Republic ofIntroduction: Nitric oxide (NO) deficiency is well established to be responsible for increased oxidative stress and myocardial pathogenesis. Recently, neuronal nitric oxide synthase (nNOS) protein expression and activity are shown to be increased in hypertrophic and failing myocardium and nNOS-derived NO is responsible for the “maintenance” of myocardial NO and suppresses the sources of cardiac oxidative stress. So far, mechanism mediating nNOS up-regulation in the heart under stress remains unidentified. Here, we hypothesized that increased intracellular ROS by angiotensin II (Ang II) is responsible for the transcriptional modification of nNOS.Methods: nNOS mRNA expression (Quantitative real time RT-PCR) was compared between control and Ang II-incubated LV myocytes (1 μM, 3hrs). nNOS protein level (Immunoblotting) was detected with specific nNOS antibody in LV homogenates from rats and from canine of sinus rhythm or rapid pacing-induced atrial fibrillation (AF). Intracellular ROS was detected by using

Conclusions: NDPK-B is expressed in human and canine atria, is upregulated in both clinical and experimental AF, and enhances Gs and cAMP signaling. NDPK-B may constitute a novel pathway for abnormal atrial G-protein/cAMP signaling, with potentially important implications for AF pathophysiology.

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INHIBITION OF C-SRC TYROSINE KINASE PREVENTS THE EFFECT OF MITOCHONDRIAL OXIDATIVE STRESS ON GAP JUNCTION REMODELING, REDUCTION OF CARDIAC SODIUM CURRENT AND VENTRICULAR TACHYCARDIAAli A. Sovari, MD, Cody A. Rutledge, BS, Divya Arasu, BS, Euy-Myong Jeong, PhD, Man Liu, PhD, Elena Dolmatova, MD, Hong Liu, MD, PhD, Alex Tan, MD, Nooshin Vahdani, BS, Lianzhi Gu, MD, PhD, Marcelo G. Bonini, PhD, Heather S. Duffy, PhD and Samuel C. Dudley, MD, PhD. UIC, Chicago, IL, BIDMC-Harvard University, Boston, MAIntroduction: Mitochondria are major sources of cardiac ROS. Slower conduction between myocytes is a known mechanism of genesis of arrhythmia. Nevertheless, the impact of ROS on conduction and mechanisms of prevention are not well identified. In a mouse model of Manganese SOD (MnSOD) knockout, we investigated the effect of increased mitochondrial ROS on gap junctions, sodium current and myocardial fibrosis which are main substrates for slow conduction. We also tested the effect of c-Src tyrosine kinase inhibition on connexin43 (Cx43) remodeling, decreased cardiac sodium current and ventricular tachycardia (VT).Methods: Wild type and MnSOD+/- mice (4-6 weeks old) with and without treatment with the c-Src inhibitor PP1 (1.5mg/kg IP three times/week x 2 weeks) were studied. Western blotting, immunohistochemistry staining, Masson’s Trichrome staining, electron microscopy study, mitoSOX experiment for mitochondrial ROS measurement, patch clamping, fluorescent dye diffusion (functional assesment of gap junctions), and in-vivo epicardial mapping were performed.Results: MnSOD+/- myocytes showed 66% increase in the level of mitochondrial ROS, decrease in Cx43 level to 27%, decrease in INa to 60%, and 2.1 fold increase in phospho (Tyr416) Src protein level compared to the control (all P<0.05). Electron microscopy showed evidence of mitochondrial damage and early degeneration in MnSOD+/- myocytes. Dye diffusion showed decreased in longitudinal spread to approximately 65% of the control (P<0.05). There was no difference in collagen content between MnSOD+/- and control mice (3±1% vs. 4.5±1%, P=NS) at the age they were studied. Sustained VT was induced in 85% of MnSOD+/- mice (83% monomorphic) compared to none in the control group (P<0.05). Treatment with PP1 effectively increased Cx43 at the gap junctions to the 73% of the control (all P<0.05). PP1 treatment normalized the INa and the gap junction dye spread, and decreased VT inducibility to 20% in MnSOD+/- mice (all P<0.05).Conclusions: Cx43 remodeling and INa reduction are major substrates for VT in mitochondrial oxidative stress. Inhibition of c-Src prevents the effect of mitochondrial oxidative stress on Cx43, INa and VT inducibility. Thus c-Src inhibition may be an effective antiarrhythmic therapy.

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PRE-CARDIOVERSION PLASMA LEVELS OF MATRIX METALLOPROTEINASES AND TISSUE INHIBITORS OF THE METALLOPROTEINASES PREDICT RECURRENCE OF ATRIAL FIBRILLATION FOLLOWING CARDIOVERSIONJoseph G. Akar, MD, PhD, Rupak Mukherjee, PhD, Deborah K. Adams, PhD, Heather B. Ketchabaw, PhD, Catherine D. McClure, PhD, Robert E. Stroud, PhD, Allison D. Rice,

S399Poster Session V

PO05-90

ADRENERGIC STIMULATION AND THE VULNERABILITY TO DEVELOP ATRIAL FIBRILLATION IN A COMPUTER MODEL OF ATRIAL MYOCYTESTalal Moukabary, MD, David Haines, MD, FHRS and Mario Gonzalez, MD, FHRS. Penn State University, Hershey, PA, William Beaumont Hospital, Royal Oak, MIIntroduction: In atrial fibers, adrenergic stimulation shortens action potential duration (APD). The present study analyzes whether adrenergic stimulation in addition to shortening the APD, can induce oscillations in APD (alternans) that may induce atrial fibrillation.Methods: The Courtemanche human atrial computer model was used. Pacing was performed at a cycle length of 1000 ms, followed by progressively shorter S1-S2 coupling intervals. APD restitution curves were constructed by plotting cycle lengths vs action potential durations at 90% repolarization. APD alternans was evaluated by suddenly changing the pacing CL from 1000 to shorter CLs. To study the adrenergic effects (AE), the channel conductance for the L-type calcium current and the slowly activating potassium current were reduced and increased to simulate adrenergic blockade and stimulation, respectively.Results: A 3-D representation of the relationship between CL, AE, and APD alternans is shown (Figure). APD alternans is represented as ± 1 standard deviation. Maximum APD alternans increased from 20 to 38 ms with AE of 200% (arrow). Maximum APD restitution curve slope increased from 0.928 to 1.69 with enhancement of AE to 200% (adrenergic stimulation) and decreased to 0.348 with a AE at 50% (adrenergic blockade). There was a strong correlation between the curve slope and AE (r= 0.9753).Conclusions: Adrenergic stimulation by increasing calcium and potassium currents increases APD restitution curve slope and alternans in modeled human atrial myocytes. These oscillations in APD in single cells underlie the arrhythmogenic action of adrenergic stimulation in atrial myocytes

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2’ 7’-dichlorodihydro fluorescein diacetate (H2DCF-DA, 5-10 μM, 15 min, 37oC) in LV myocytes with and without Ang II and NADPH oxidase activity was assessed by measuring superoxide using lucigenin-enhanced chemiluminescence (lucigenin, 5 μM, 37oC).Results: Ang II increased mRNA and protein expression of nNOS in rat LV myocyte homogenates (P=0.0002, n=10 for nNOS mRNA and P=0.03 for nNOS protein, n=9). Similar increase in nNOS protein level was observed in canine LV myocardium (but not in left atrium or in right ventricule) from AF compare to those from sinus rhythm. Ang II stimulates NADPH oxidase and increases intracellular ROS. Inhibition of NADPH oxidase or scavenging superoxide abolished Ang II increase in nNOS mRNA and protein expression, suggesting that NADPH oxidase-ROS axis is an upstream mediator of nNOS transcription by Ang II. Ang II-stimulated nNOS, in turn, inactivated NADPH oxidase activity and reduced intracellular ROS and superoxide, since inhibition of nNOS significantly elevated ROS and O2-.Conclusions: Ang II promotes nNOS transcription and protein expression via NADPH oxidase production of intracellular ROS in cardiac myocytes. nNOS, in turn, attenuates oxidative stress by inhibiting NADPH oxidase activity.

PO05-89

MECHANO-ELECTRICAL COUPLING IN THE ASYNCHRONOUS HEART: CONSEQUENCES FOR RESYNCHRONIZATION THERAPYNico Kuijpers, PhD, Evelien Hermeling, PhD, Tammo Delhaas, PhD and Frits Prinzen, PhD. Maastricht University, Maastricht, NetherlandsIntroduction: Cardiac Resynchronization Therapy (CRT) aims at improving cardiac function in heart failure patients with left bundle branch block (LBBB). The hypothesis was assessed that both deterioration of cardiac function in the asynchronous LBBB-heart and gradual improvement of function during the first weeks of pacing therapy can be explained by mechano-electrical coupling (MEC).Methods: A multi-scale computational model of cardiovascular dynamics was used incorporating mechanical interaction between the left and right ventricular free wall and the ventricular septum. Hemodynamics was modeled by linking both ventricles to the pulmonary and systemic circulations. Each ventricular wall was described by a fiber composed of mechanically and electrically coupled segments. Ionic membrane currents and calcium handling were described for each segment. Contractile force was related to intracellular calcium concentration and sarcomere length. MEC was incorporated by adaptation of L-type Ca2+ current to local mechanical load.Results: Both during LBBB and during CRT, MEC reduced dispersion of repolarization and leveled shortening through changes in calcium handling (Figure). With LBBB, ejection fraction (EF) decreased from 62.5% to 52.5% due to MEC, indicating deterioration of pump function. During CRT, EF increased from 52.3% to 56.1%, indicating improvement of function.Conclusions: Progressive deterioration of cardiac function in the chronically asynchronous heart can be explained by MEC. Analogously, MEC may explain the gradual improvement of cardiac function after onset of pacing therapy.

S400 Heart Rhythm, Vol. 9, No. 5, May Supplement 2012

distribution of ganglion rich fibrofatty tissue.Methods: HF was induced in 6 dogs by ventricular tachypacing (240 beats/min, 3 weeks). AF-EGMs were recorded (121 EGMs/site) in the posterior left atrium (PLA) and left atrial appendage(LAA) pre and post double autonomic blockade (DB)(propranolol+atropine). EGMs were assessed for dominant frequency (DF), organizational index, fractionation intervals (FI) and Shannon’s entropy (ShEn). After mapping, tissue was Masson-Trichrome stained to assess for nerve trunks and % fibrofatty tissue. Correlation between the change(Δ) in EGMs and tissue content was assessed.Results: %fat was greater in the PLA vs LAA (38±19 vs. 18±7% (p<0.001)). Nerve trunks were found in the PLA (43±9), but not LAA (p<0.01). In the PLA, DB decreased DF, increased FI (Fig 1A) and decreased % CFAEs (34±15 to 21±13%, p=0.01). ΔShEn with DB correlated with % fat (Fig 1B). Fig 1C shows that DB effect on EGMs was more pronounced over nerve-rich fat.Conclusions: Autonomic blockade in the HF PLA causes EGM changes that correlate with the distribution of nerve-rich fibrofatty tissue in PLA. Thus, assessing AF EGM content in presence of autonomic blockade may help better target autonomic ganglia during ablation.

PO05-93

SYNCHRONISATION OF WAVEFRONTS PRECEDES SELF TERMINATING VENTRICULAR FIBRILLATION IN THE HUMAN HEARTRichard H. Clayton, PhD, Martyn P. Nash, PhD, Chris P. Bradley, PhD, Martin Hayward, FRCS, David J. Paterson, ScD and Peter Taggart, MD, ScD. Univ of Sheffield, Sheffield, United Kingdom, Auckland Bioengineering Institute and Engineering Science, Auckland, New Zealand, Auckland Bioengineering Institute, Auckland, New Zealand, The Heart Hospital, London, United Kingdom, University of Oxford, Oxford, United KingdomIntroduction: Self terminating ventricular fibrillation (STVF) has been reported in the literature, but has not been studied in detail in the human heart.Methods: We recorded epicardial activation patterns during 5 episodes of STVF and 5 episodes of sustained VF in 9 patients aged between 59 and 80 having cardiac surgery with cardiopulmonary bypass for either coronary artery disease or aortic valve replacement. VF was induced by burst pacing. Epicardial activity was sampled at 1 kHz from a sock with 256 unipolar contact electrodes placed over the ventricular epicardium. Episodes of VF lasted up to 3.5 minutes, with global cardiac ischemia after 30 s of VF. Electrograms were processed (Nash et al., Circulation 2006) to extract dominant frequency (DF), numbers of epicardial phase singularities (nPS), and activation times.Results: Five episodes of STVF occurred in 4 patients (mean

PO05-91

DIGITAL 3D RECONSTRUCTIONS OF THE CORONARY ARTERIES AND CARDIAC VEINS OF PERFUSION-FIXED HUMAN HEARTS USING CONTRAST-COMPUTED TOMOGRAPHYJulianne H. Eggum, BS, Matthew R. Venegoni, BA and Paul A. Iaizzo, PhD. University of Minnesota, Minneapolis, MNIntroduction: A more thorough understanding of the anatomical relationship between the coronary arteries and cardiac veins is of great importance for the development of cardiac devices. These models are of particular interest for the design of minimally invasive coronary sinus (CS) occluders and CS delivered mitral valve annuloplasty devices. More specifically, it is important that the deployment of such devices does not damage the nearby coronary artery system.Methods: First, we obtained computed tomography (CT) scans of 8 perfusion fixed human hearts while injecting contrast into the cardiac veins via the CS ostium. Next, we obtained additional CT scans while injecting contrast in the coronary arteries. We used Mimics Software (Materialise, Leuven, Belgium) to create and then combine 3D digital reconstructions of the vessel systems.Results: The figure displays three coronary systems of varying diseased states. We found that the circumflex artery lies between the CS and posterior mitral valve annulus in 4 of the models (50%). It should also be noted that we were not able to access this parameter in 2 of the models (25%) due to incomplete contrast filling of the circumflex.Conclusions: Using these models, device developers and clinicians can take various anatomical measurements such as the distance between a given artery and vein to optimize device design. We will continue to develop this novel database of human cardiac vascular systems.

PO05-92

USING AUTONOMIC BLOCKADE-INDUCED CHANGES IN AF ELECTROGRAMS TO PREDICT THE LOCATION OF GANGLIONATED PLEXI IN THE HEART FAILURE ATRIUMHemantha K. Koduri, MD, Jason Ng, PhD, Ivan Cokic, MD, Gary Aistrup, PhD, David Gordon, MD, PhD, Aaron Kunamalla, BS, Andrew Wasserstrom, PhD, Bradley Knight, MD, Jeffrey Goldberger, MD and Rishi Arora, MD. Feinberg Cardiovascular Research Institute, Chicago, ILIntroduction: Incorporating Ganglionated Plexi (GP) ablation into standard AF ablation strategies is thought to increase ablation success. However, current techniques for predicting GP location during ablation lack precision. We hypothesized that in HF, the regional responsiveness of AF electrograms (EGMs) to autonomic blockade would correlate with the location and

S401Poster Session V

2.7- 7.9%). In contrast, in the animals where the VAQRS_HW was reached with simultaneous BiV pacing, sequential pacing did not lead to hemodynamic improvement (0%; -5.1- 0%).Conclusions: In this canine LBBB model, vectorcardiography was useful to detect optimal resynchronization and direct further optimization of AV- and VV-interval, if needed. A similar approach would be easy to achieve in patients.

PO05-95

ELECTROPHYSIOLOGICAL CONSEQUENCES OF CONNEXIN43 EXPRESSION IN INTRACARDIAC SKELETAL MUSCLE GRAFTSPo-Cheng Chang, MD, Hans Reinecke, PhD, Mark H. Soonpaa, PhD, Young Soo Lee, MD, PhD, Loren J. Field, PhD, Charles E. Murry, MD, PhD, Peng-Sheng Chen, MD, Shien-Fong Lin, PhD and Michael Rubart, MD. Indiana University School of Medicine, Indianapolis, IN, University of Washington Medicine at South Lake Union, Seattle, WA, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, INIntroduction: Intracardiac skeletal muscle (SM) grafts are electrically insulated from the host myocardium due to lack of gap junctional coupling between skeletal and cardiac myocytes, limiting their suitability for cardiac repair. Here, we investigated if expression of connexin (Cx)43 in SM enables electrical donor-host coupling.Methods: N/AResults: Enhanced green fluorescent protein (EGFP)-expressing C2C12 myoblasts [EGFP/(-)] or EGFP-expressing C2C12 myoblasts carrying a transgene encoding the muscle creatine kinase promoter and Cx43 [EGFP/Cx43] were transplanted into mouse hearts. Two to 3 weeks later, hearts were isolated, Langendorff perfused, stained with di-4-ANEPPS, and voltage mapped at 1-ms temporal and 70-µm spatial resolution. Blebbistatin (10 μM) was used to suppress contraction. Optical maps revealed conduction slowing at engraftment sites of both EGFP/(-) SM (38±9 cm/s vs. 49±11cm/s in host myocardium; CL=120 ms; n=5; P<0.01) and EGFP/Cx43 SM (41±6 cm/s vs. 54±7 cm/s; n=6; P<0.001). EGFP/Cx43 SM graft sites exhibited fast and slow signal components (left panel in Fig.), representing compound contributions from two different groups of simultaneously and

duration 34 s, range 12-78 s). Mean(±SD) DF was similar in the first 30 s of STVF compared to the first 30 s of sustained VF recorded from 5 comparable patients (5.4 ± 0.6 Hz vs 5.6 ± 0.6 Hz, NS), but nPS during the first 30 s of STVF was lower than in sustained VF (6.3 ± 2.3 vs 8.5 ± 3.8, p=0.0062). In the STVF recordings average activation interval increased in the 1-2 s interval prior to termination (see figure), consistent with synchronisation of activation.Conclusions: Epicardial activation patterns during STVF have similar activation frequency to sustained VF, but have fewer nPS, indicating that STVF may be more organised than sustained VF. Immediately prior to termination in STVF, epicardial activation slows and becomes synchronised.

PO05-94

OPTIMIZATION OF AV- AND VV-INTERVALS DURING BIVENTRICULAR PACING USING VECTORCARDIOGRAPHY IN CANINE LBBB HEARTSCaroline J.M. van Deursen, MD, Marc Strik, MD, Leonard M. Rademakers, MD, PhD, Arne van Hunnik, BSc, Marion Kuiper, BSc, Wecke Liliane, MD, PhD, Crijns J.G.M. Harry, MD, PhD, Kevin Vernooy, MD, PhD and Prinzen W. Frits, PhD. Maastricht University Medical Center, Maastricht, NetherlandsIntroduction: In cardiac resynchronization therapy (CRT), fusion between right and left ventricular (LV) activation wavefronts is warranted for optimal pump function. The QRS vector amplitude (VAQRS) reflects electrical interventricular dyssynchrony and its value halfway between that during left bundle branch block (LBBB) and LV-pacing (VAQRS_HW) reflects optimal resynchronization. We investigated whether optimal resynchronization is achieved with simultaneous biventricular (BiV) pacing using VAQRS and if VAQRS_HW can be used to optimize atrioventricular (AV)- and interventricular (VV)-intervals.Methods: In 24 canine hearts with LBBB (12 acute, 6 with heart failure and 6 with myocardial infarction), BiV and LV pacing was applied at 7 sites per dog. In 6 animals additional sequential BiV pacing was performed. Surface ECGs were recorded from the limb leads and the VAQRS was calculated in the frontal plane vectorcardiogram. Systolic function was assessed as LV dP/dtmax.Results: In 50.4% of 119 tested cases simultaneous BiV pacing was not able to converse VAQRS to at least the halfway value (see figure). In these animals the VAQRS_HW was achieved using sequential BiV pacing and this was accompanied with improvement in LV dP/dtmax (median 5.3%; interquartile range

S402 Heart Rhythm, Vol. 9, No. 5, May Supplement 2012

PO05-97

REPOLARIZATION GRADIENTS CORRELATE TO DOMINANT FREQUENCY GRADIENTS AND INCREASED VULNERABILITY TO ARRHYTHMIAS IN A CANINE MODEL OF HEART FAILUREThomas H. Everett, IV, PhD, George Hulley, MD, Roger Chang, BS, Emily E. Wilson, BS and Jeffrey E. Olgin, MD. University of California San Francisco, Medicine, Division of Cardiology, San Francisco, CAIntroduction: The effect of substrate on the dominant frequencies (DF) during ventricular fibrillation (VF) and how they correlate to the action potential duration (APD) is not known. Using optical mapping the epicardial (epi), endocardial (endo) and transmural (trans) surfaces of the LV were mapped during pacing and VF.Methods: Seventeen dogs were divided into 2 groups: structurally normal hearts (Control, n = 11), and congestive heart failure (CHF) induced with ventricular tachypacing for 3 weeks at 220 BPM (n=6). At follow up, the hearts were excised, perfused, and optical action potentials were recorded from a 2 x 2 cm area of a LV wedge preparation at the epi surface, endo surface which included a papillary muscle, and a trans cross section using a 16 x 16 photodiode array. Pacing was performed on each surface at a cycle lengths of 600ms - 250ms in 50ms steps. At all cycle lengths, APD at 80% repolarization (APD80) was determined for each recorded optical signal, and APD80 maps were constructed. VF was initiated with either an S1/S2 or burst pacing. Several 4 sec VF episodes were recorded at each site. The optical electrograms were digitized at 2 kHz and a fast Fourier-transform (FFT) was calculated. The dominant frequency (DF) was determined as the largest peak of the FFT.Results: Every mapped surface in the CHF group showed an APD80 gradient which included islands of higher APD80s on the trans surface (M-cells). Only 2 mapped control surfaces showed a gradient.Conclusions: In the CHF model, APD gradients correlated with an increased vulnerability to VF. In addition, high DFs correlated to lower APDs and vice versa, indicating that the CHF substrate creates unique APD and DF characteristics.

EPI APD Endo APD Trans APDTop 10% DFs 105±35 96±17 111±30Bottom 10% DFs 126±37 117±15 139±41p-value 0.07 0.002 0.07Control VF vulnerabilityfrom S1/S2 pacing 23% 29% 31%

CHF VF vulnerabilityfrom S1/S2 pacing 65% 69% 75%

p-value 0.0008 0.01 0.03

PO05-98

INTERCELLULAR UNCOUPLING UNMASKS ANISOTROPIC CONDUCTION DEPENDENCE ON THE SODIUM CURRENTRengasayee Veeraraghavan, PhD, Joyce Lin, PhD, James P. Keener, PhD and Steven Poelzing, PhD. University of Utah, Salt Lake City, UTIntroduction: It has been proposed that ephaptic coupling may play a role in cardiac conduction. However, this hypothesis has yet to be experimentally demonstrated. We hypothesized that ephaptic coupling could be unmasked by uncoupling tissue and inhibiting the inward sodium current (INa).Methods: Conduction velocity (CV) and anisotropy (AR) were quantified by optical mapping in Langendorff-perfused guinea pig ventricles (n=3 for all groups). Mannitol (26.1g/l) was perfused to increase VIS; carbenoxolone (Cbx, 25 µM) was perfused to

sequentially activated myocytes. Because slow deflections were not observed at EGFP/(-) SM graft sites, they likely reflected abnormal impulse propagation across EGFP/Cx43 grafts.Conclusions: Thus, Cx43 expression in SM grafts enables donor-host electrical coupling, but propagation across grafts is impaired.

PO05-96

MECHANISM OF LOW ENERGY MULTI-STAGE ELECTROTHERAPY FOR CARDIOVERSION OF AF REVEALED BY OPTICAL MAPPINGAjit H. Janardhan, MD, PhD, Wenwen Li, PhD, Di Lang, MS, Sarah R. Gutbrod, BS, Richard B. Schuessler, PhD and Igor R. Efimov, PhD. Washington University, Saint Louis, MOIntroduction: We previously demonstrated Multi-Stage Electrotherapy (MSE) significantly reduces the atrial defibrillation threshold (ADFT) compared to a single shock in canine models of AF in vivo. Here we describe the mechanism of MSE using optical mapping in a canine model.Methods: Persistent AF (lasting more than 30 minutes) was induced by 6±2 weeks of atrial tachypacing. Animals (n=4) were anesthetized and hearts excised. Isolated atria were perfused through the right and left coronary arteries. Optical mapping was performed. AF was induced by burst pacing alone. Defibrillation by a single biphasic shock or MSE was recorded. MSE consists of 3 sequential stages. Stage 1: 2 biphasic shocks delivered within 1 AF cycle length (CL); Stage 2: 6 monophasic shocks delivered at 88% of the AF CL at twice the atrial capture voltage; Stage 3: 8 pacing stimuli at 88% of the AF CL delivered from the RA. All shocks were applied from two parallel mesh electrodes placed on either side of the atria. Sequential activation maps were constructed to characterize activation during application of MSE.Results: Sustained AF was induced in 3 of 4 preparations. Average AF CL was 126±17 ms. Activation maps showed AF was maintained by 2-5 ectopic foci/micro-reentrant circuits (EF/MR) adjacent to the pulmonary veins. Crowded isochrones were seen around pulmonary veins. MSE Stage 1 shocks caused uniform, simultaneous atrial activation. Post-shock, re-emergent EF/MR were gradually eliminated by the train of Stage 2 shocks, resulting in a more homogeneous activation pattern. The activation pattern was consistent with each paced beat in Stage 3, after which sinus rhythm was restored. The mean ADFT of MSE was 38.8 ± 9.9 V (1.2 ± 0.2 J) versus 94.0 ± 13.4 V/cm (3.4 ± 0.4 J) for a single BP shock (p<0.05). During in vivo testing the mean ADFT of MSE was 18.5 ± 14.9 V (0.10 ± 0.14 J) versus 154.1±22.9 V (1.02 ± 0.44 J) for a single BP shock (p<0.001).Conclusions: Low energy MSE terminates persistent AF by eliminating EF/MR over several stages. Stage 1 biphasic shocks uniformly excite the atria, Stage 2 entrainment shocks gradually suppress re-emergent EF/MR and Stage 3 pacing maintains a consistent atrial activation pattern until sinus rhythm is restored.

S403Poster Session V

PO05-100

STREPTOZOTOCIN-INDUCED TYPE I DIABETES DOES NOT ALTER ATRIAL CONDUCTIONMelissa Neo, BSc, David Morris, BSc, Do-Yeon Kim, BSc, Prashanthan Sanders, MBBS, PhD and David Saint, PhD. University of Adelaide, Adelaide, AustraliaIntroduction: The relationship between diabetes mellitus (DM) and development of atrial fibrillation (AF) is not completely understood and likely multi-factorial. Population-based studies have identified DM as an independent risk factor of AF, however the underlying mechanisms of atrial electrophysiological changes in DM are unknown. Specifically, models of type I diabetes investigating atrial conduction changes are lacking.Methods: 60mg/kg of Streptozotocin (STZ) was administered to 4 Zucker lean rats (3 months old) to induce type I diabetes and the right atria removed following a 7 day waiting period. The right atria of age-matched Zucker lean (control, n=4) and obese (n=4) rats were also isolated and each atria was placed with the epicardial surface in contact with a 9x10 multi-electrode array. Atrial orientation and pacing sites remained consistent for each experiment.Results: Obese rats presented with heavier body mass compared to treated and control lean rats (p<0.05). The STZ treated rats had significantly higher glucose levels compared to age-matched controls (p<0.05). Similarly this was also observed for obese rats compared to the age-matched lean controls (p<0.05). In obese rats, only left ventricular mass was significantly heavier than lean controls (p<0.05); this was not observed between obese and STZ treatment groups. Atrial conduction velocity and heterogeneity index were not significantly different between all groups. However at a pacing cycle length of 300ms, the effective refractory period was significantly shorter in STZ treated rats compared to control (p<0.01) and obese rats (p<0.01).Conclusions: In this model of acute induction of type I diabetes, lean rats did not demonstrate significant cardiac hypertrophy but presented with similar conduction parameters. Additionally, reduced refractoriness was observed in these rats compared to obese rats. Further studies investigating the progressive nature of type I diabetes-induced atrial remodelling are required.

PO05-101

CARBENOXOLONE LIMITS INCREASE IN CONNEXIN43 EXPRESSION IN ISCHAEMIC RAT VENTRICULAR TISSUEEugene TY. Chang, MSc, Fu Siong Ng, MBBS, PhD, Rasheda A. Chowdhury, PhD, Linda Inuabasi, BSc, Emmanuel Dupont, PhD and Nicholas S. Peters, MD. Imperial College London, London, United Kingdom, University of Surrey, Guildford, United KingdomIntroduction: Carbenoxolone (CBX) is a gap junction uncoupler known to slow myocardial conduction velocity. However the molecular mechanisms by which CBX uncouples cardiomyocytes is unclear, and may involve altering the phosphorylation state of the gap junctional protein Connexin43 (Cx43) or affecting the quantity of Cx43. Using Western blotting, we studied the effects of CBX on the quantity of Cx43 in (1) cultured HL-1 atrial myocytes and (2) Langendorff rat hearts subjected to regional ischaemia.Methods: (1) Cultured HL-1 mouse atrial myocytes were incubated with 0-400 μM CBX for up to 2 hours and 1 hour washout (n=3). (2) For whole heart Langendorff studies, four groups of experiments were carried out: 30 mins Langendorff perfusion (control), 30 mins 30μMCBX perfusion, 30 mins LAD ischaemia, 30 mins LAD ischaemia + CBX (n=3 in each group).

uncouple gap junctions (Gj). INa was inhibited by flecainide (0.5 µM). All differences are reported with a p<0.05.Results: During control, longitudinal CV (CV-L) and transverse CV (CV-T) were 52±1cm/s and 21±1cm/s respectively; ARθ was 2.5±0.1. Flecainide uniformly decreased longitudinal CV (CV-L) and transverse CV (CV-T) relative to control without changing anisotropy. Mannitol (edema) preferentially decreased CV-T and increased AR to 3.0±0.1 relative to control. Importantly, flecainide + mannitol also preferentially decreased CV-T and further increased AR to 3.3±0.2 relative to mannitol alone. With Gj uncoupling, Cbx preferentially decreased CV-T and increased AR to 2.9±0.1 relative to control. Importantly, flecainide + cbx further decreased CV-T preferentially and raised AR to 3.3±0.2 relative to Cbx alone. Interestingly, only a computer model including ephaptic coupling and co-localization of sodium channels with Gj could recapitulate the above mentioned experimental findings.Conclusions: INa blockade isotropically affects CV, but preferentially alters CV-T during edema or Gj uncoupling. These data suggest that the cellular localization of INa with Gj is important for modulating anisotropic cardiac conduction when the distance between myocytes increases or gap junctions are uncoupled as occurs in a variety of cardiac pathologies linked to sudden death.

PO05-99

ANTIFIBRILLATORY EFFECTS OF VAGUS NERVE STIMULATION IN THE VENTRICLE VIA NITRIC OXIDE INVOLVE CGMP-DEPENDENT MECHANISMSKieran E. Brack, PhD, Ayushman Gupta, No Degree and G. André Ng, MBChB, PhD. University of Leicester, Leicester, United KingdomIntroduction: We have previously shown that vagus nerve stimulation (VNS) increases effective refractory period (ERP) and ventricular fibrillation threshold (VFT), via a nitric oxide (NO) dependent mechanism. NO can activate soluble guanylyl cyclase [sGC] to produce cyclic guanylyl monophosphate (cGMP) and modulate cardiac function. The aim of this study was to investigate if the effects of VNS-NO pathway on ERP and VFT were mediated via cGMP mechanisms.Methods: Adult NZW rabbit (n=7, 2.5-4kg) hearts were perfused in constant flow Langendorff mode. ERP were measured using single extrastimulus protocol (300ms cycle length). VFT was the minimum current needed to induce sustained VF with burst pacing (30x30ms). These were measured at baseline [BL] and with: 1) NO donor (Sodium Nitroprusside [SNP], 100μM), 2) sGC inhibition (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one [ODQ], 10μM), 3) vagus nerve stimulation [VNS, 10H9V] and (4) VNS or SNP in the presence of ODQ. Data are mean±SEM, Students T-Test, P<0.05 compared with BL.Results: (Table): SNP and VNS both increased ERP and VFT. The effects of SNP were preserved during sGC inhibition, whilst the effects from VNS were inhibited.Conclusions: Cyclic GMP is involved in the protective effects of VNS-NO pathway against VF but concurrent cGMP independent mechanisms could also be at work.Table: NO and VNS modulation of ERP and VFT

BL SNP BL ODQ BL SNP&ODQERP 124.0±2.9 139.0±4.0* 136.4±1.8 131.4±4.2 130.0±5.0 148.2±9.3*VFT 4.6±1.0 11.6±2.4 * 3.9±0.8 3.1±0.9 2.7±1.4 7.2±1.9*

BL VNS VNS&ODQERP 135.0±2.0 153.8±5.5* 141.3±13.4VFT 3.3±0.9 6.8±1.7* 3.4±1.4

S404 Heart Rhythm, Vol. 9, No. 5, May Supplement 2012

PO05-103

ACTIVATED C-JUN N-TERMINAL KINASE CONTRIBUTES TO SIGNIFICANTLY INCREASED PACING-INDUCED ATRIAL FIBRILLATION IN AGED RABBITS IN VIVOQiang Zhang, MD, Jiajie Yan, BS, Gregory Walcott, MD and Xun Ai, MD. University of Alabama at Birmingham, Birmingham, ALIntroduction: The c-Jun N-terminal kinase (JNK), is invoked in response to stress stimuli, which are enhanced in the natural aging process. JNK has been found to be important in the development of cardiovascular diseases (e.g. heart failure, hypertrophy). However, the contribution of JNK in atrial fibrillation (AF), a serious health problem in the elderly, has yet to be understood. We have previously shown that enhanced activation of JNK is associated with reduced connexin 43 (Cx43) and slowed conduction in aged rabbit left atria (LA). The goal of this study was to further determine the role of JNK activation in AF development. Atrial arrhythmia was induced in vivo using an open chest atrial burst pacing protocol in 6 aged (~54 mo) and 5 young (~6 mo) New Zealand male rabbits as well as 4 young rabbits treated with anisomycin (15mg/kg I.V. for 4 doses; based on its specific effects on JNK activation and Cx43 reduction in atrial myocytes). The pacing-induced arrhythmias were defined as a fast irregular (standard deviation > 10% of mean cycle length; AF) or regular (tachycardia) atrial rhythm (>10Hz, lasted >1s). After the pacing procedure, LA tissue was collected for immunoblotting to assess Cx43 and activated JNK (phosphorylated JNK) protein expression. Aged rabbits showed a significantly increased inducibility for pacing-induced atrial arrhythmias (5 out of 6 vs 0 out of 5 in young), and average duration of the arrhythmia was 29.8±11.5s. Young rabbits treated with anisomycin also had an increased inducibility of atrial arrhythmias (4 out of 4; duration = 27.1±17.3s). Atrial effective refractory periods were unchanged among the three groups. With immunoblotting assay, Cx43 protein expression reduced significantly in LA from both aged and anisomycin-treated young rabbits (40% & 24% vs. young controls; p<0.05 & 0.01, respectively; n=4, 3, 3), while levels of Cx40 and sodium channel SCN5A remained unaltered. Activated JNK was markedly increased in both aged and JNK-activated young rabbits (45% & 70% vs young controls; p<0.01 & 0.001, respectively).Methods: N/AResults:N/AConclusions: Thus, our results suggest that JNK activation may contribute to Cx43 reduction and AF development. Modulation of JNK signaling may be a potential therapeutic approach to prevent and treat AF in the elderly.

Samples were separated into membrane-bound (docked) and non-membranal (undocked) parts for Western blot analysis of Cx43.Results: Carbenoxolone did not significantly alter Cx43 expression in HL-1 atrial myocytes (Baseline 0.76±0.24, 400μM CBX 0.61±0.07 for docked Cx43 after one hour). In rat ventricular tissue, regional ischaemia significantly increased Cx43 expression in the ischaemia tissue, compared to control (from 0.55±0.04 to 1.30±0.12 for docked Cx43, p=0.046 vs control). 30μM CBX had no significant effect on Cx43 quantity (0.76±0.24). However, when CBX was administered in the context of ischaemia, this attenuated the increase in Cx43 (1.11±0.13) which was not significantly different to control. These concentrations of CBX have previously been shown to significantly decrease conduction velocity in both models.Conclusions: In both atrial HL-1 cultured cells and in rat ventricular myocardium, short-term CBX administration of up to 2 hours did not significantly affect Cx43 levels, suggesting that its short-term effect of conduction slowing is mediated by another mechanism. However, CBX did appear to attenuate the increase in Cx43 seen in ischaemic tissue, suggesting that, when given in the context of ischaemia, the mechanism of action may involve regulation of Cx43 levels.

PO05-102

CARDIAC CONTRACTILITY MODULATION INCREASES VENTRICULAR FIBRILLATION SUSCEPTIBILITYJames Winter, PhD, Kieran E. Brack, PhD and G. André Ng, PhD, FRCP. University of Leicester, Leicester, United KingdomIntroduction: Cardiac contractility modulation (CCM) is a new treatment being developed for heart failure (HF) with the application of electrical current during absolute refractory period. We have previously shown that CCM increases ventricular force through β1-adrenoceptor activation, a potential pro-arrhythmic mechanism. This study assesses the effect of CCM on ventricular fibrillation threshold (VFT).Methods: Adult male NZW rabbit (2-3kg,n=10) hearts were perfused in constant flow Langendorff mode. VFT was defined as the minimum current required to induce sustained VF with rapid pacing (30x30ms). The effects of CCM (20mA, 20ms) on left ventricular (LV) basal (B) and apical monophasic action potential duration (MAPD) were assessed during constant pacing (200bpm). The spatial effects of CCM on LV APD were assessed using optical mapping with di-4-ANNEPS (20uL bolus 1mg/ml). The effects of metoprolol (MET,1.8µM) on CCM effects on MAPD and VFT were assessed.Results: CCM significantly shortened MAPD close to stimulation site (B: 105±4 vs 127±13ms, P<0.01). VFT was reduced with CCM (4.6±2 vs 5.6±0.4mA, P<0.05) which was correlated (r2=0.29, P<0.05) with increased MAPD dispersion (18±4 vs 4±1ms, P<0.05). Optical mapping revealed a greater range of CCM induced shortening with basal stimulation than with apical stimulation (Fig. 1). MET abolished the CCM-mediated change in MAPD, MAPD dispersion and VFT.Conclusions: CCM increases susceptibility to ventricular fibrillation via a β1-adrenoceptor mechanism that is related to an increase in MAPD dispersion. The use of CCM in HF should be approached with caution.

S405Poster Session V

hemodynamic assessment, and imaging (MRI and DEXA). Electrophysiological evaluation included: ERP (6 sites), conduction velocity (CV), voltage mapping and inducibility of AF.Results: Stable obese sheep (110±9 kg) reduced weight to 79±7 kg (p<0.001); but, not to the control level (60±7 kg). Total body fat reduced from 35±6 kg to 17±6 kg. Weight reduction was associated with reductions in atrial size (p<0.001) and pressures (=0.01), and marked improvement in conduction abnormalities (See table). However, there was no change in the occurrence of spontaneous or induced AF episodes (p=0.76).Conclusions: Though weight loss results in revere electro-structural and hemodynamic remodeling of the atria, the vulnerability for AF did not diminish over the study timeline.Study results comparing obese sheep before and after weight reductionParameter Obese Weight Reduction p valueLA volume(ml) 86±15.0 66.4±8.8 <0.001LVEF (%) 70.4±5.9 69.8±5.3 nsLA mean (mmHg) 8.1±2.8 5.8±2.7 0.01Fractionated signals (%) 44.6±15.4 36.0±12.0 0.02Conduction Velocity (m/s) 1.02±0.13 1.34±0.15 <0.001Voltage (mV) 4.3 4.3 nsERP mean (ms) CL 300ms 180 187 nsTotal AF episodes (No.) 5.5±4.6 4.4±3.1 nsSpontaneous AF episodes (No.) 2.6±2.2 1.3±1.2 ns

PO05-106

EXTRACELLULAR MATRIX REMODELING IN CANINE ATRIA WITH RIGHT VENTRICULAR PACINGJih-Min Lin, MD, PhD and Jiunn-Lee Lin, MD, PhD. Keelung General Hospital, Keelung, Taiwan, National Taiwan University Hospital, Taipei, TaiwanIntroduction: The risk of atrial fibrillation is proportional to cumulative ventricular pacing burden. However, the extracellular matrix remodeling in atria after right ventricular (RV) pacing remained unclear.Methods: We performed dual-chamber pacemaker implantation in 6 dogs and another 4 dogs were sham-operated. The pacemakers were programmed to VDD mode after AV nodal ablation achieved in the 6 dogs. After 3 months of atrial-sensed obligatory RV pacing, we analyzed the activity of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) by zymography and in situ gelatinase activity (MMP-2 and MMP-9) in right atrium (RA) and left atrium (LA). The expression of tissue inhibitor of matrix metalloproteinase-1 and -3 (TIMP-1, 3) were also measured by western blotting. The extracellular matrix component was quantitated by Masson trichrome stain in LA.Results: The activity of MMP-2 in LA showed no difference between pacing and sham group. The activity of MMP-9 in LA and MMP-2 in RA showed a trend of increase in pacing group and MMP-9 in RA showed 1.68 folds of increase in pacing group. The result of in situ zymography demonstrated both increased gelatinase activity in RA and LA with significance. The expression of TIMP-1 and 3 in were both increased in RA, but remained no changes in LA. However, the fibrosis component of LA is increased in pacing group (9.1% in pacing group vs 6.2% in sham group, p,0.05).Conclusions: RV apical pacing elicits differential extracellular matrix regulated-proteins expression changes in RA and LA. The fibrosis content is also increased in left atria after RV pacing. These changes facilitated atrial fibrillation development and our findings help understanding the structural remodel in atria after RV pacing.

PO05-104

EPICARDIAL GANGLIONATED PLEXUS STIMULATION PREVENTS VENTRICULAR ARRHYTHMIAS AND ATTENUATES CARDIAC REMODELING DURING MYOCARDIAL ISCHEMIA/REPERFUSIONLilei Yu, MD, PhD, Bing Huang, MD, Wenbo He, MD, Xiaoya Zhou, MD, Zhibing Lu, MD, PhD, Xiaorong Hu, MD, PhD, Bo Cui, MD, PhD, Liu Wu, MD and Hong Jiang, MD. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan City, ChinaIntroduction: Vagal nerve stimulation has been shown to ameliorate myocardial ischemia/reperfusion (I/R) injury by releasing parasympathetic neurotransmitter acetylcholine. Since atrial epicardial ganglionated plexuses are known to contain a large amount of parasympathetic elements, we hypothesized that atrial epicardial ganglionated plexus stimulation (GP-S) may prevent complications induced by myocardial I/RMethods: We assessed the effects of 1hour GP-S(n=12) or control (n=15) on spontaneous ventricular arrhythmias, infarct size and acute inflammatory reactions during the first 2 hours of reperfusion in dogs subjected to 45 minutes of ischemia induced by occlusion of the left anterior descending coronary artery (LAD). A bipolar plaque electrode was sutured overlying the fad pad containing the superior left ganglionated plexus (SLGP), located at the junction of left pulmonary artery and left superior pulmonary vein. GP-S was performed by applying high frequency electrical stimulation (HFS: 20Hz, 0.1msec duration, square waves) to the SLGP. The lowest voltage level of GP-S that induced approximately 10% sinus rhythm slowing was chosen as the voltage for GP-S.Results: Our results show that the incidence of ventricular arrhythmias significantly decreased in GP-S group (2 of 12) compared with control group (12 of 15) (p < 0.05).Infarct size, expressed as a percentage of the left ventricle, was reduced significantly from 18.2 +/- 2.5 in controls to 8.3 +/- 2.0 (p < 0.05) in GP-S group. The GP-S group showed significantly reduced matrix metalloproteinase-8 and-9 and tumor necrosis factor-alpha and decreased myocardial infiltration of neutrophils compared with the control groupConclusions: GP-S protects against ventricular arrhythmias and cardiac remodeling resulting from brief myocardial I/R. GP-S may serve as a non-pharmacological clinical approach to improve acute myocardial I/R such as during coronary bypass or cardiac valve surgery.

PO05-105

WEIGHT REDUCTION IS ASSOCIATED WITH A REVERSE-REMODELING OF THE ATRIA BUT NOT THE VULNERABILITY FOR AF: A CHRONIC OVINE STUDYRajiv Mahajan, MD, Anthony Brooks, MBBS, PhD, Nicholas Shipp, PhD, Shivshankar Thanigaimani, MS, Hany Abed, MBBS, Muayad Alasady, MD, Han Lim, MBBS, Sachin Nayyar, MD, Anand Ganesan, MBBS, PhD, Kurt C. Roberts-Thomson, MBBS, PhD and Prashanthan Sanders, MBBS, PhD. CHRD, University of Adelaide and Royal Adelaide Hospital, Adelaide, AustraliaIntroduction: is recognized as a novel risk factor for atrial fibrillation (AF). Here, we evaluate the effect of weight reduction on the atrial substrate and vulnerability for AF.Methods: 10 sheep had induced obesity by ad-libitum calorie dense diet over a 9 month period. Animals were then subject to an 8 month weight reduction study by restricted feeding to good quality cereal hay. In the obese state and after 8 months of weight reduction animals underwent: bi-atrial endocardial electroanatomic (EA) and electrophysiological mapping,

S406 Heart Rhythm, Vol. 9, No. 5, May Supplement 2012

mA increments until 2 mA was reached, or when dogs failed to tolerate the VNS.Results: There was no change of heart rate at 0.25 mA in 3 of 4 dogs studied. However, when VNS output reached 0.5 mA - 1.25 mA (threshold), we observed initial bradycardia followed by elevated SGNA and tachycardia (Figure). There was no difference of the integrated SGNA between “on times” (53.8 ± 21.8 mv-s) and “off times” (53.9 ± 21.8 mv-s) during 0.25 mA VNS in any dog studied, with average difference (delta) of 0.1 ± 0.33 mv-s. However, when VNS was suprathreshold (strong enough to induce initial bradycardia), the delta SGNA between “on” and “off times” increased progressively to 5.4 ± 2.38 mv-s at 1.0 mA (p=0.017, n=4) and 14.2 ± 8.86 mv-s at 1.5 mA (p=0.049, n=4). The difference of heart rate (bpm) between “on” and “off times” were 3.7 ± 3.68 at 1.0 mA (p=0.267, n=3) and 0.6 ± 0.62 at 1.5 mA (p=0.951, n=3).Conclusions: Suprathreshold VNS results in initial bradycardia followed by large increase of SGNA in spite of continued VNS. Averaged heart rate is a poor indicator of overall autonomic nerve activity patterns.

PO05-109

INNOVATIVE TWELVE-HOLE OPEN IRRIGATION GOLD ELECTRODE ALLOWS FOR REDUCED IRRIGATION FLOW RATE WITHOUT COMPROMISING ABLATION SAFETY AND EFFECTIVENESSTamas Szili-Torok, MD, PhD, Endre Zima, MD, PhD, Eszter Vegh, PhD, Gabor Szeplaki, MD, Martha Hubay, MD, PhD, Luc Jordaens, MD, PhD and Bela Merkely, MD, PhD. Erasmus MC, Rotterdam, Netherlands, Semmelweis University, Heart Center, Budapest, HungaryIntroduction: Novel electrode materials and configurations of irrigation holes are applied for more efficient cooling of RF ablation electrodes, aiming at safe creation of large lesions at low irrigation flow rate. We tested the hypothesis that a novel gold RF ablation electrode with innovative configuration of 12 irrigation holes allows for safe and effective lesion creation at reduced irrigation flow rate using a canine thigh muscle model.Methods: In 5 dogs, the skin over the thigh muscle was incised and skin edges raised to form a cradle which was flushed with blood (37 °C, 250 ml/min). Settings: electrode orientation: parallel and perpendicular to the muscle surface; irrigation flow rate (F): 8 and 15 ml/min; contact force: 10 g; RF power: 30 W, applied for 60 s. Electrode temperatures (Te), coagulum formation and steam pops were recorded and lesion volumes (V) determined by microscopy. A novel gold electrode design (12H Au: AlCath Flux eXtra Gold, 12 holes) was compared to a standard platinum-iridium electrode (6H PtIr: AlCath Flux FullCircle, 6 holes) (both 7F, 3.5 mm, Biotronik, Berlin, Germany).Results: Coagulum was not observed on muscle surface and on electrode. Steam pop occurrence was not significantly influenced

PO05-107

DYNAMIC REGULATION OF ATRIAL CORONARY BLOOD FLOWKelly A. van Bragt, MSc, Arne van Hunnik, BSc, Hussein Nasrallah, MSc, Marion Kuiper, BSc, Ulrich Schotten, MD, PhD and Sander Verheule, PhD. Maastricht University, Maastricht, NetherlandsIntroduction: During normal sinus rhythm, the atria receive approximately 5% of the total coronary flow. Surprisingly little is known about the regulation of atrial blood flow and under which circumstances, e.g. atrial fibrillation (AF), atrial demand exceeds supply. Here, we present a first characterization of atrial coronary anatomy and atrial coronary blood flow regulation in pigs.Methods: Six normal Dutch Landrace pigs (45-80 kg) were instrumented with Doppler flow probes on a left atrial (LA) and left ventricular (LV) branch of the circumflex(LCx) artery, echo crystals to determine the LA work index, LV volume catheter and pressure catheters (aorta, LA, RA and LV). All parameters were monitored during sinus rhythm, adenosine-infusion and atrial pacing. In two additional pigs, corrosion casts of the coronary circulation were produced to visualize the atrial vasculature.Results: Both the RA and LA possess extensive capillary networks, supplied by 2 to 4 arteries branching from the right coronary and LCx arteries, respectively. In some cases, only one larger branch from the LCx was found, that continued as a ‘left atrial circumflex’, with a number of branches to the LA. Atrial coronary flow reserve, measured by intracoronary adenosine administration, was lower for the LA than for the LV (3.06±0.68 vs 4.14±0.95). During the cardiac cycle, atrial coronary flow decreased during atrial contraction and was out of phase with the flow pattern in the LV branch. Acute AF (5 minutes) decreased vascular resistance of the LV and LA branch to 71±13 and 65±19% of baseline, respectively. During atrial pacing, both LA flow and work increased with increasing pacing frequency. LA flow was significantly increased at 120 bpm (130±26% increase and 47±10% of maximal atrial flow) and 150 bpm (201±96% increase and 67±43% of maximal atrial flow) compared to sinus rhythm (30±11% of maximal flow). Mean atrial flow was positively correlated with atrial work.Conclusions: The atrial coronary flow reserve is lower than the ventricular flow reserve. Atrial coronary flow was regulated independently from ventricular flow and already approached its flow reserve during atrial pacing. Resistance was decreased during acute AF in both the LV and LA branch.

PO05-108

EFFECTS OF SUPRATHRESHOLD VAGAL STIMULATION ON STELLATE GANGLION NERVE ACTIVITY IN AMBULATORY DOGSKyoung-suk Rhee, MD, PhD, Chia-Hsiang Hsueh, PhD, Hyung Wook Park, MD, PhD, Young Soo Lee, MD, PhD, Jason Garlie, MD, Lan S. Chen, MD, Shien-Fong Lin, PhD and Peng-Sheng Chen, MD. Krannert Institute of Cardiology, Indianapolis, IN, Department of Neurology, Indiana Universigy School of Medicine, Indianapolis, INIntroduction: Vagus nerve stimulation (VNS) is thought to antagonize sympathetic nerve activity. However, whether or not VNS suppresses stellate ganglion nerve activity (SGNA) in ambulatory dogs remains unknown.Methods: We performed left cervical VNS (30 s on, 30 s off; 30 Hz) for 24-hr in 4 ambulatory dogs using a Cyberonics vagal stimulator while simultaneously recording left SGNA, left thoracic vagal nerve activity (VNA) and subcutaneous ECG. The amplitude of VNS was titrated upwards every 24 hours in 0.25

S407Poster Session V

PO05-111

THREE DISTINCT ACTIVATION PATTERNS IN LONG-DURATION VENTRICULAR FIBRILLATION IN CANINE HEARTS INITIATE FROM THE ENDOCARDIUMLi Li, PhD, Derek J. Dosdall, PhD, Jian Huang, MD, PhD and Raymond E. Ideker, MD, PhD. University of Alabama at Birmingham, Birmingham, AL, University of Utah, Salt Lake City, UTIntroduction: During long-duration ventricular fibrillation (VF) three types of activation patterns exist on canine LV endocardium. Typically during the first 2 minutes and sometimes thereafter is a chaotic pattern, consistent with wandering wavelets. Another is highly synchronized, with the whole endocardium activating almost simultaneously and long, irregular gaps between activations, consistent with triggered activity. The third has regular cycle lengths, with global endocardial reentry sometimes observed, consistent with a mother rotor. We tested the hypothesis that all patterns initiate from the endocardium and drive the transmural LV.Methods: In 6 anesthetized dogs, a 64 electrode basket catheter recorded from the LV endocardium, and 54 6-electrode (2 mm spacing) plunge needles were inserted transmurally to record from most of the LV freewall. Electrically induced VF was recorded for 7 minutes.Results: After 2 minutes of VF, the basket always had the highest activation rates (ARs) for all three patterns (Fig). AR in the plunge needles decreased from the endocardium to the epicardium. As VF progressed, the incidence of intramural conduction block increased. For the regular and the chaotic patterns, a transmural regularity gradient was observed with the endocardium most regular. For the synchronized pattern, a transmural synchronicity gradient was observed with the endocardium most synchronized.Conclusions: After 2 minutes of VF, for all VF patterns, activations initiate from the endocardium and propagate toward the epicardium, blocking en route, forming a transmural AR gradient.

PO05-112

SHORT-TERM EFFECT OF CARDIAC SYMPATHETIC NERVE ACTIVITIES ON FREQUENCY DOMAIN HEART RATE VARIABILITYEue-Keun Choi, MD, PhD, Seung-Min Lee, BS, Il-Young Oh, MD and Seil Oh, MD, PhD. Seoul National University College of Medicine, Seoul, Korea, Republic ofIntroduction: Heart rate variability (HRV) is well known index reflecting cardiac autonomic balance. However, there is little study comparing HRV with directly measured autonomic nerve activity (ANA). We sought to directly record the ANA and to test the hypothesis that the change of ANA has impact on short-term frequency domain HRV indices.

by irrigation flow rate. At reduced flow rate 12H Au resulted in larger or similar lesions compared to 6H PtIr at normal flow rate.Conclusions: The 12H Au electrode allows for reduction of irrigation flow rate without compromising safety and effectiveness of ablation. This feature is particularly important with respect to ablation in heart failure patients.* p < 0.05 (8 ml/min vs 15 ml/min))

12H Au Parallel

12H Au Perpendicular

6H PtIr Parallel

6H PtIr Perpendicular

F [ml/min] 8 15 8 15 8 15 8 15

N 14 14 12 11 15 14 12 11

V [mm3] 861* 624 908 949 504 769 629 805

Te [°C] 39.4 37.3 42.1 36.7 53.8 50.2 46.7 41.0

PO05-110

FOCAL MECHANISM UNDERLYING SPONTANEOUS AND NOREPINEPHRINE-INDUCED VENTRICULAR TACHYCARDIA IN A NEW ARRHYTHMOGENIC CANINE MODEL OF NONISCHEMIC HEART FAILUREChenguang Liu, PhD and Steven M. Pogwizd, MD. University of Alabama at Birmingham, Birmingham, ALIntroduction: Heart failure (HF) is associated with high mortality from sudden arrhythmic death. Future developments in device-based and pharmacologic therapies require large animal models that resemble human HF (in contractile dysfunction, arrhythmogenicity), that are large enough for device implantation, and that are irreversible (for long-term studies). The goal of our studies was to characterize arrhythmogenesis in our newly developed canine HF model.Methods: HF was induced by combined aortic insufficiency and aortic constriction. Holter monitoring showed spontaneous ventricular tachycardia (VT). Three HF dogs underwent 3-D cardiac mapping (using plunge needle electrodes, up to 240 intramural sites) during spontaneous rhythm and infusion of norepinephrine (NE, 1.6-3.2 μg/kg/min). A total of 151 beats (42 spontaneous and 109 with NE infusion) were analyzed.Results: HF dogs had decreased systolic function (LV fractional shortening 34±3% vs 41±3% at baseline, p<0.05). Mapping of HF dogs revealed that sinus rhythm activated with a total activation time (TA) of 40±2 ms. Spontaneously-occurring VT (N=6) initiated primarily in the LV subendocardium at a coupling interval (CI) of 358±23 ms. In all cases spontaneous VT initiated by a focal (nonreentrant) mechanism, based on the absence of intervening electrical activity for 324±22 ms, and propagated with a TA of 88±3 ms. Norepinephrine-induced VT was longer than spontaneous VT (8.8±2.0 vs 3.7±0.3 beats long; p<0.05; N=10, 6) and was more rapid (CI of 228±9 vs 299±13 ms; p<0.0001; N=57, 22). All NE-induced VT beats likewise initiated by a focal mechanism, and the activation sequences were often similar to spontaneous VT. However, there was no difference in the TA of the preceding sinus beats or of VT beats.Conclusions: In this new large-animal model of nonischemic HF, spontaneous VT initiated primarily in the subendocardium by a focal (nonreentrant) mechanism, similar to what we have demonstrated in the failing human heart. NE-induced VT was longer and faster, but arose by a similar mechanism and with a comparable activation time as spontaneous VT. This novel irreversible and arrhythmogenic HF model will assist in understanding the complex mechanisms in nonischemic HF and in development of new therapies.

S408 Heart Rhythm, Vol. 9, No. 5, May Supplement 2012

no significant difference (P=0.74). However, in exercise group, DSPR2834H had increased P wave amplitude and decreased R wave amplitude (P = 0.02 and P =0.001 respectively) compared to NTG mice.RV dimensions were measured in NTG (N=8) and DSPR2834H (N=15) in the short axis view with a mean days of exercise of 22 ± 5 days and 21 ± 5 days respectively (P =0.74). In the exercise group, RV dimension adjusted for days of exercise, age and gender was significantly higher (P =0.004) in DSPR2834H mutant as compared to NTG mice . No statistical significant difference in RV dimensions was seen among sedentary mice in these two groups (P =0.07).Conclusions: We report significant early changes due to exercise in some of the quantitative ECG parameters in mutant DSPR2834H Tg mice compared to NTG mice. Early appearance of significant echocardiographic changes of RV enlargement due to exercise was also observed in the DSPR2834H Tg mice.

PO05-114

GERMAN ABLATION REGISTRY: CRYOBALLOON COMPARED TO RF IN AF ABLATIONMartin Schmidt, MD, Uwe Dorwarth, MD, Dietrich Andresen, MD, Johannes Brachmann, MD, Karlheinz Kuck, MD, Malte Kuniss, MD, Thorsten Lewalter, MD, Stephan Spitzer, MD, Stephan Willems, MD, Jochen Senges, MD and Ellen Hoffmann, MD. Klinikum Bogenhausen, München, Germany, Vivantes Klinik Berlin, Berlin, Germany, Klinikum Coburg, Coburg, Germany, Asklepios Klinik Hamburg, Hamburg, Germany, Kerckhoff Klinikum Bad Nauheim, Bad Nauheim, Germany, Isar Klinik München, München, Germany, Praxisklinik Herz und Gefäße, Dresden, Germany, Universitäres Herzzentrum Hamburg, Hamburg, Germany, IHF Ludwigshafen, Ludwigshafen, GermanyIntroduction: Catheter ablation is extensively used with curative intention in atrial fibrillation (AF). Radiofrequency ablation has long been standard of care, cryoballoon technology has emerged a feasible approach with promising results. The purpose of this prospective registry was to assess efficacy and complication rates in PV ablation with different energy sources for paroxysmal AF.Methods: Between March 2007 and September 2011 a total of 4002 consecutive patients with symptomatic px AF were enrolled in their respective centers. The cohort was devided into two groups: cryoballoon ablation (group 1, n=973 [24.3%], median age 63 years, 64.1% men) and RF ablation (group 2, n=3029 [75,7%], median age 63 years, 62.8% men).Results: Procedural results are given in the Table. Acute success rates were similar in both groups (97.4% in cryo vs. 97.5% in RF; p=0.92). AF recurrence rate at 12 months follow-up was not significantly different between both groups (45.2% after cryoablation and 45.0% after RF ablation; p=0.90). Within the follow-up period a redo AF ablation procedure was performed in 18.8% after cryo- but in 23.0% after RF ablation (p<0.05). Major complication rate was significantly higher in RF vs. cryoablation (4.4% in RF vs. 2.2% in cryo; p<0.01). Also minor bleedings (3.3% in RF vs. 2.0% in cryo; p<0.05) were more common in RF ablation. Phrenic nerve palsy was more often in cryo vs. RF ablation (p<0.05).Conclusions: A similar AF recurrency but lower major complication rate was found in cryoballoon compared to RF ablation. Phrenic nerve palsy was more frequent in cryoballoon ablation. Procedural and fluoroscopy times were higher in cryoballoon compared of RF ablation.

Methods: Stellate ganglion nerve activity (SGNA), vagal nerve activity (VNA) and superior left ganglionated plexi nerve activity (SLGPNA) were recorded in 5 ambulatory dogs by radiotransmitter. Integrated nerve activity (Int-NA) was calculated by custom-designed software, whereas various frequency domain indices of HRV were calculated every 30 seconds accordingly. We analyzed 50 episodes with SGNA (more than 2 times compared to baseline) but without VNA and SLGPNA.Results: SGNA discharges (291%) were associated with heart rate acceleration (109%, p=0.004). After SGNA discharges, low-frequency (LF) and LF/HF (high-frequency) ratio were increased significantly (330%, 476%, respectively, p<0.001 for all vs. baseline), whereas HF was decreased (60%, p<0.001 vs. baseline). After SGNA withdrawal, LF and LF/HF ratio were decreased (76%, 78%, respectively, p<0.001 for all vs. baseline), whereas HF was increased (191%, p<0.001 for vs. baseline).Conclusions: Cardiac sympathetic activation and withdrawal has impact on both LF and HF indices despite no parasympathetic and intrinsic ANA. These findings suggest that cardiac ANA can directly change the short-term frequency domain HRV indices in ambulatory dogs, and that short-term HRV response could be used as surrogate marker of ANA changes.

PO05-113

ELECTROCARDIOGRAPHIC AND ECHOCARDIOGRAPHIC FEATURES IN TRANSGENIC ARVC MICE SUBJECTED TO ENDURANCE EXERCISERahul Jain, MD, MPH, Ken Takagi, MD, Ruben Martherus, PhD, Kristen Kramer, BSc, Enkhsaikhan Purevjav, MD, PhD and Jeffrey A. Towbin, MD. Cincinnati Children’s Hospital, Cincinnati, OHIntroduction: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disorder that causes sudden death and right ventricular heart failure in the young. Clinically, it has been suggested that competitive sports may provoke ARVC in susceptible persons. The goal of this study was to investigate the cause and effect of exercise stress in the development of ARVC using transgenic (Tg) mouse with cardiac-restricted overexpression of mutant R2834H desmoplakin (DSP).Methods: Mutant DSPR2834H Tg and control non-transgenic (NTG) mice were divided into groups, sedentary and exercise. Mice in the exercise group were subjected to graded increase in intensity of exercise on a treadmill from the age of 4 weeks. Every 4 weeks, echocardiograms and ECGs (single lead) were recorded.Results: Initial data analysis showed that after mean days of exercise of 16 ± 15 days and 17 ± 14 days there was no significant difference in RR interval (P =0.68) between NTG (N=6) and DSPR2834H (N=8) , respectively. Overall, after inclusion of sedentary mice (N=23), P value was 0.33. Even after adjusting for age, gender and days of exercise, there was

S409Poster Session V

and without the use of additional mapping systems. In contrast to the point-by-point application, the novel technology allowes circular lesions about all 10 electrodes under energy oscillation.Methods: 517 consecutive PVIs were analysed, 100 patients (P) with the NavX™-system and 417 with the PVAC ® catheter. The clinical data of both groups are summarised in table 1.Results: Table 2 shows procedure data of both groups; procedure duration and fluoroscopy time were significant shorter in the PVAC-group. Table 3 shows rhythm results of both patient collectives. Conclusions: PVI by using the PVAC®-catheter gives equivalent long-term results with shorter procedure and fluoroscopy times, compared to the point-by-point PVI with electroanatomical mapping guidance.

PO05-117

COMPARISON WITH VARIOUS TIME- AND FREQUENCY- DOMAIN ALGORITHMS DEMONSTRATES POOR POINT-BY-POINT CORRELATIONS OF COMPLEX FRACTIONATED ATRIAL ELECTROGRAMSDennis H. Lau, MBBS, PhD, Bart Maesen, MD, Stef Zeemering, MSc, Pawel Kuklik, PhD, Sander Verheule, PhD, Jan Nijs, MD, Prashanthan Sanders, MBBS, PhD and Ulrich Schotten, MD, PhD. Maastricht University, Maastricht, Netherlands, University of Adelaide and Royal Adelaide Hospital, Adelaide, Australia, University Hospital of Maastricht, Maastricht, NetherlandsIntroduction: Several time- and frequency-domain algorithms are currently utilized to guide catheter ablation of complex fractionated atrial electrograms (CFAE) in patients with atrial fibrillation (AF). However, detailed comparisons of these algorithms have not been made previously.Methods: High density (16x16 electrodes, 1.5mm pitch) direct contact mapping of left atrial AF was performed in 8 persistent AF patients during cardiac surgery. Unipolar AF electrograms (10s) were converted to bipolar signals before application of the following semi-automated algorithms: complex fractionated electrogram-mean (CFE-m); interval confidence level (ICL); continuous electrical activity (CEA). Fourier transformation was used to derive dominant frequency (DF) while points with regularity index <0.2 were excluded from analysis.Results: As shown in the Figure, point-by-point correlations were

TableRF ablation Cryoballoon p-value

Procedure duration (minutes) 165 [120-210] 160 [130-200] 0.24Ablation time (seconds) 1978 [1227-3000] 2722 [2400-3520] <0.001Fluoroscopy time (minutes) 24 [16-38] 34 [26-46] <0.001Dose area product (cGy*cm2) 2840 [1470-5638] 4971 [2583-9200] <0.001

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INCIDENCE AND PREDICTORS OF ATRIAL FIBRILLATION AND ITS IMPACT ON LONG-TERM SURVIVAL IN PATIENTS WITH SUPRAVENTRICULAR ARRHYTHMIASCevher Ozcan, MD, Jordan Strom, MD, John Newell, BA, Moussa Mansour, MD and Jeremy Ruskin, MD. SUNY at Buffalo School of Medicine, Buffalo, NY, Massachusetts General Hospital, Boston, MAIntroduction: The incidence of atrial fibrillation (AF) in patients with other forms of supraventricular arrhythmias (SVA) including atrial flutter (AFL), atrial tachycardia (AT), atrioventricular reentry (AVRT) and AV nodal reentry (AVNRT) is not well documented. We evaluated the incidence and predictors of AF and its impact on long-term survival among patients with SVA. Methods: All patients who underwent electrophysiologic study and catheter ablation for SVA from 2000 to 2010 were included in this study. The patients were identified retrospectively and vital status determined prospectively. AF was determined at the time of the procedure and during the follow up. Observed survival in the study cohort was compared with the survival rates in the age- and sex-matched general population. The predictors of the development of AF were assessed. Results: A total of 1573 patients (mean age 50.5+/-18 years old, 47% female) were studied. The study group included patients with AVNRT (38.5%), AFL (29.6%), AVRT (22.6%) and AT (9.3%). During follow-up (mean 35; median 23 months), AF was documented in 424 patients (27%). The highest incidence of AF occurred in patients with AFL (57.5%). AF was also common in patients with AT (27.4%), AVRT (13.5%) and AVNRT (9.7%). Older age, prolonged PR interval, dilated left atrium, low left ventricular ejection fraction and presence of AFL were independent predictors for the development of AF. The highest incidence of death occurred in the subset of patients with AFL and AF. Long-term survival in patients with SVA was better in patients without AF compared to those with AF.Conclusions: The incidence of AF is high in patients with other SVA including AFL, AT, AVRT and AVNRT. The most common association is between AFL and AF. Long-term survival in patients with SVA is decreased in those who have concomitant AF.

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PULMONARY VEIN ISOLATION WITH A MULTIPOLAR ABLATION CATHETER (PVAC)COMPARED TO A NAVXTM-GUIDED APPROACHStefan Georg Spitzer, MD, PhD, Laszlo Karolyi, MD, Thomas Weinmann, MD, Carola Rämmler, MA, Tobias Otto, MA and Clemens Themba Kadalie, MD. Praxisklinik Herz und Gefaesse, Dresden, GermanyIntroduction: Pulmonary vein isolation (PVI) via point-by-point ablation is an effective approach, but time-consuming with the usage of 3-dimensional navigation systems, as for example the NavX ™ system (St. Jude Medical, MN, USA). With a circular ablation catheter (Pulmonary Vein Ablation Catheter ™ [PVAC®], Medtronic - Ablation Frontiers, Inc, Carlsbad, CA, USA), all pulmonary veins can be isolated with few RF energy applications

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Table showing demographics and LAEF of patients with and without post-operative AFAll patients (n=27)

No post-operative AF (n=18)

Post-operative AF (n=9) P-value

Age (years) 58±11 62±8 0.300Male/Female 22/5 16/2 6/3 0.250Hypertension (%) 63.6% 41.7% 87.5% 0.174Hyperlipidemia (%) 86.4% 75% 100% 0.130Diabetes (%) 54.5% 66.7% 37.5% 0.190Ischemic heart disease (%) 72.7% 83.3% 62.5% 0.254

LVEF (%) 61±6 62±6 58±6 0.173LA ejection force (kdynes) 8.9±4.5 10.1±5.1 6.8±1.9 0.030

Conclusions: Depressed pre-operative LAEF is strongly associated with post-operative AF in patients undergoing cardiac surgery.

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ACCURACY OF INTEGRATION OF THREE-DIMENSIONAL LEFT ATRIAL CARTO SOUND IMAGE WITH LEFT ATRIAL CT IMAGE: USEFULNESS OF REGISTRATION OF THE LEFT ATRIAL ROOF AND POSTERIOR WALL CONTOURSMasaomi Kimura, MD, PhD, Shingo Sasaki, MD, PhD, Shingen Owada, MD, PhD, Daisuke Horiuchi, MD, PhD, Kenichi Sasaki, MD, Taihei Itoh, MD, Yuji Ishida, MD, Takahiko Kinjo, MD and Ken Okumura, MD, PhD. Hirosaki University, Hirosaki, JapanIntroduction: CARTO SOUND (CS) system enables us to perform catheter ablation under real-time visualization. The system seems to be useful in integrating left atrial (LA) CS image with LA CT. The method of integration, however, is not established yet. Using the electroanatomical (EA) map of the LA roof (LAR) and posterior wall (LAPW), we previously reported the accuracy of integration of CARTO image with CT. By registering LAR and LAPW contours of CS image, we examined the accuracy of integration of LA CS image with CT.Methods: The consecutive 17 patients with paroxysmal AF (14 men; mean age, 60 years) undergoing circumferential pulmonary vein ablation (CPVA) were prospectively studied. Before the transseptal approach to the LA, three-dimensional (3D) CS image of LAR and LAPW was created by registering a mean of 10 contour lines, ranging from 7 to 13, between the right and left pulmonary vein antra at the end-expiratory phase (CS method). After transseptally inserting a mapping catheter into the LA, EA image of LAR and LAPW was obtained by mapping at a mean of 40 points, ranging from 38 to 43 (EA method). After visual alignment of LA CS or EA image and LA CT image using one anatomically defined position, the two images were integrated with the installed surface registration program. By measuring the distance between the two images using the installed software, the accuracy of integration of two methods was compared.Results: The mean distance between EA and CT images was 1.48 ±0.97 mm, with the mean minimum and maximum values of 0.06 and 3.81 mm, respectively. That between CS and CT images was 1.53±1.06 mm (P=NS versus EA method), with the mean minimum and maximum values of 0.03 and 4.03 mm, respectively. The time required for creating of EA image was 8.6±3.3 minutes, while that for CS image 5.2±2.5 minutes (p<0.05).Conclusions: Integration of 3D CS image of LAR and LAPW with LA CT using surface registration software is as accurate as that of 3D EA image with CT. Since 3D LA CS image can be obtained from the right atrium before transseptal LA approach and can be obtained in a shorter time than LA EA image, CS imaging and integration is useful in the catheter manipulation in the LA and accomplishment of CPVA in AF patients.

only modest amongst the time-domain algorithms (A: CFE-m & ICL, r= 0.356; B: CEA & ICL, r= -0.468; C: CFE-m & CEA, r= -0.836; all p<0.001). Specifically, higher ICL values paradoxically correlated with lower fractionation according to CFE-m and CEA. Furthermore, all the time-domain algorithms demonstrated only weak correlations with activation frequency (DF & CFE-m, r= 0.126; DF & CEA, r= -0.257; DF & ICL, r= 0.442; all p<0.001).Conclusions: The poor point-by-point correlation of CFAE as assessed by different algorithms demonstrates very limited reliability of current analysis techniques. Given this surprisingly low reliability together with our very limited understanding of the pathophysiology of CFAE, the strategy of CFAE ablation urgently requires re-evaluation.

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PRE-OPERATIVE DEPRESSED LEFT ATRIAL EJECTION FORCE IS ASSOCIATED WITH THE OCCURRENCE OF POST-OPERATIVE ATRIAL FIBRILLATION FOLLOWING ELECTIVE CARDIAC SURGERYShipei Law, MD, Zhong Liang, PhD, Eric Lim, MBBS, Nesan Shanmugam, MBBS, Boon Hean Ong, MBBS, Siang Hui Lai, MBBS, Khairunnisa Binte Katwadi, No Degree, Daniel Chong, MBBS, Boon Yew Tan, MBChB, Chi Keong Ching, MBBS, Wee Siong Teo, MBBS, Zee Pin Ding, MBBS, Yeow Leng Chua, MBBS and Reginald Liew, MBBS, PhD. DUKE NUS Graduate Medical School, Singapore, Singapore, National Heart Center Singapore, Singapore, Singapore, Singapore General Hospital, Singapore, SingaporeIntroduction: Post-operative atrial fibrillation (AF) is a cause of morbidity and mortality, occurring in up to 40% of patients after cardiac surgery. Left atrial (LA) enlargement is observed to be associated with post-operative AF, but the relationship between LA mechanical function and post-operative AF is unknown. We recently developed a method for LA mechanical function assessment in terms of LA ejection force (LAEF) using 2D and pulsed-Doppler echocardiography. It represents the capacity of LA to develop force and kinetic energy to eject blood into the LV. We hypothesize that depressed pre-operative LAEF is associated with post-operative AF after cardiac surgery.Methods: 27 patients undergoing elective cardiac surgery, with sinus rhythm and no history of AF, were prospectively recruited from Singapore General Hospital. All patients underwent pre-operative echocardiography and were monitored for post-operative AF during inpatient stay. The LAEF was calculated as 1/3 x mitral annulus area x blood density x peak velocity of A wave, according to Newton’s law of motion and hydrodynamics; where A is the peak Doppler-derived blood velocity with the sample volume placed at the mitral annulus level at atrial systole.Results: Post-operative AF occurred in 33% of subjects. LAEF was significantly lower in patients with post-operative AF than those without (6.80±1.90 vs 10.1±5.1 kdynes, p=0.03). On ROC analysis, LAEF with cutoff value of <8.65 kdynes was able to predict post-operative AF (sensitivity=0.78, specificity=0.46, AUC=0.71).

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HOW DO ANATOMICAL FACTORS AFFECT CONTACT FORCE DURING PV ABLATION?Dipen C. Shah, MD, Andre D’Avila, MD, Andrea Natale, MD, Petr Neuzil, MD, Jean-Paul Albenque, MD, Karl-Heinz Kuck, MD, PhD, Moussa Mansour, MD, Aude Yulzari, No Degree, Amin Ben Chikh, No Degree and Vivek Reddy, MD. Hopital Cantonal De Geneve, Division of Cardiology, Geneva, Switzerland, Mount Sinai School of Medicine, New York, NY, Texas Cardiac Arrhythmia Institute, Austin, TX, Na Homolce Hospital, Prague, Czech Republic, Clinique Pasteur, Toulouse, France, Asklepios Klinik St. Georg, Hamburg, Germany, Massachusets General Hospital, Boston, MA, Endosense SA, Meyrin-Geneva, SwitzerlandIntroduction: Various anatomical considerations contribute to difficulty in achieving stable catheter placement during RF ablation for pulmonary vein (PV) isolation (e.g. left atrial size and irregularity, PV diameter). Previous studies suggest that durable isolation of PVs depends on the operator’s ability to limit ablations with low contact force (CF) within all antral segments (Seg).Methods: TOCCASTAR is a prospective, randomized, multicenter study comparing a CF sensing catheter (TactiCath®, Endosense) with a control. Data was obtained from 3604 ablations in 66 pts treated for PAF with the study device. Data per pt and per Seg were collected on average CF, number and duration of ablations; total Force Time Integral (FTI) and power were also recorded (Table)Results: The ridge between the left PVs and the appendage is difficult to ablate as indicated by the highest number of ablations in left ant (p < 0.01) and the lowest CF (p < 0.01) relative to all Seg. Higher CF and FTI was achieved on the right PVs than the left (p < 0.01 and p = 0.02 respectively) possibly due to the location of the fulcrum of the septal crossing. The longer duration and higher FTI on the right PVs reflect propensity for dragging ablations. Fewer ablations were performed in inf Seg that may reflect sparsity of connections or effects of ablation in adjoining Seg.Conclusions: CF may have important diagnostic value for operators when they need to adapt to anatomic and technical limitations to improve the quality of catheter-tissue contact. In particular, ablations at the anterior aspect of left PVs require a specific approach to ensure good CF and optimal FTI to result in better lesion quality.

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PREDICTORS OF MRI ENHANCEMENT OF THE ESOPHAGUS FOLLOWING ATRIAL FIBRILLATION ABLATION: A CASE CONTROL STUDYAlexies Ramirez, MD, Nathan S. Burgon, BSc, Nazem Akoum, MD, Christopher J. McGann, MD, Brent Wilson, MD, Alexis Harrison, MD, Jessiciah Windfelder, MSN, ACNP and Nassir F. Marrouche, MD. Comprehensive Arrhythmia and Research Management (CARMA) Center, University of Utah, Salt Lake City, UTIntroduction: Late gadolinium enhancement magnetic resonance imaging (LGE-MRI) is able to identify thermal injury

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IDENTIFYING HIERARCHICAL ORGANIZATION IN COMPLEX FRACTIONATED ATRIAL ELECTROGRAMS USING WAVEFORM SIMILARITY MAPPING: A NOVEL APPROACH TO LOCALIZING POTENTIAL DRIVERS IN ATRIAL FIBRILLATIONBehnaz Ghoraani, PhD, Rupin Dalvi, MSc, Andrew Ha, MD, Andrew J. Wald, No Degree, Eric Moult, No Degree, Manoj Hemnani, No Degree, Sridhar Krishnan, PhD and Vijay S. Chauhan, MD. University Health Network, Toronto, ON, Canada, Queen’s University, Kingston, ON, Canada, Ryerson University, Toronto, ON, CanadaIntroduction: Complex fractionated bipolar atrial electrograms (CFAEs) provide targets for AF ablation, but many CFAEs are not relevant to AF perpetuation. The bipolar EGM is dependent on wavefront directionality and similar EGM morphology can indicate consistent, repetative activation. We evaluated bipolar CFAE waveform similarity in the left atrium (LA) as a measure of AF organization.Methods: In 16 patients (13 males, 57±8 y) with AF (5 paroxysmal, 11 persistent), bipolar recordings (2.5 sec) were made in the entire LA during AF using a roving 20-pole circular catheter before AF ablation. CFAEs were identified if bipolar recordings contained fractionated EGMs with multiple deflections (>7) and short cycle length (<120 ms). At recording sites with CFAEs, bipolar EGM morphologies were compared to one another using a template matching algorithm in order to derive a similarity index (SI) from 0 to 1.Results: For each patient, 376±58 bipolar recordings were made in the LA, of which 55±1% were excluded due to poor catheter contact. CFAEs were present in 23±13% of bipolar recordings. There was a consistent spatial gradient of SI at CFAE sites (Fig A) with the highest SI in the LIPV (median 0.55) and lowest SI in the posterior LA (median 0.33). The number of localized LA sites with high SI (>0.8) was 4.7±2.5. Among CFAE sites, only 3.6±3.2% exhibited high SI (>0.8). Figures B and C show a patient with 2 CFAE sites, one with low SI and the other with high SI.Conclusions: CFAE sites in the LA exhibit spatial gradients of waveform similarity and a few discrete regions have high waveform similarity. The latter represent CFAEs with more organized atrial activity which may potentially arise from focal sources.

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We defined “grade 1” as spatial shift between Lasso and PV < half of PV diameter; “grade2 shift”: entire Lasso shifting out of the PV.Results: Minor shifting (grade1) occurred in 23/90 (25.5%) of NavX vs. 6/90 (6.7%) of CARTO3 procedures (p=0.001). Grade1 shifting with NavX was managed through manual/automatic correction and allowed continuation of 3D-guided PVI. Grade2 shifting occurred in 5/90 (5.6%) with NavX and necessitated either repeat LA mapping or fluroscopic-guided ablation.No grade2 shifting was observed with CARTO3. In 3/90(3.3%) CARTO3 procedures system failure occurred and ablation was continued under fluoroscopy. There was no difference between the 2 EAS with regard to grade2 shifting or system failure: 5/90 (5.6%) vs. 3/90 (3.3%) (p=0.28). Total mapping and fluoro duration were longer with NavX (8,4+/-3,6min vs. 4,8+/-3,2min and 31,8+/-13,4min vs. 25,9+/-10,7min, p<0.001). Procedure duration did not differ between both groups (162+/-40min vs. 158+/-41min, p=0,47).Conclusions: When using general anaesthesia for ablation of AF, more minor map shifting was observed with NavX than with CARTO3 EAS. Major shifting or system failure may occur in both systems and imply need of further efforts in development of more precise and stable navigation systems in order to improve safety and outcome of PVI.

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REAL-TIME NADH FLUORESCENCE IMAGING OF RADIOFREQUENCY ABLATION LESIONS AND GAPSMatthew Kay, ScD, Luther Swift, MSc, Huda Asfour, PhD, Marco Mercader, MD and Narine Sarvazyan, PhD. The George Washington University, Washington, DCIntroduction: During arrhythmia ablation therapy, radio frequency (RF) energy is used to create lesions that block the spread of electrical activity from sites of abnormal automaticity, such as the pulmonary veins. The main cause of AF recurrence after ablation therapy is gaps between RF lesions and failure of complete conduction block. There is a critical need to monitor the size and degree of tissue injury during RF ablation; however, the technology available to so do is very limited. We hypothesized that the fluorescence of endogenous NADH could be used as a marker of cardiac muscle injury during ablation procedures.Methods: Studies were conducted in blood-free and blood-perfused hearts from healthy adult Sprague-Dawley rats and New Zealand rabbits. RF ablation lesions were created on the

to the esophagus from atrial fibrillation (AF) catheter ablation (CA). We studied patient characteristics and ablation techniques to determine risk factors for esophageal injury caused by radiofrequency CA.Methods: Patients who underwent CA of AF had LGE-MRI immediately following their procedures. CA techniques included pulmonary vein isolation (PVI) and left atrial (LA) debulking in selected patients. A retrospective case control study was performed comparing patients with LGE-MRI enhancement of the esophagus after AF ablation with age and gender matched controls. The course of the esophagus relative to the PV antra in axial MRI sequences was categorized (Figure).Results: Thirty-three patients with esophageal enhancement were compared to 32 patients without enhancement. The measured distance between the posterior left atrial wall and both the anterior esophageal adventita and the mucosa was inversely related to the likelihood of esophageal injury (odds ratio 0.58, 95% confidence interval 0.36-0.96, p = 0.03). More patients in the enhancement group had the esophagus in location 4 compared to those without (52% vs 19%), Chi square, p = 0.03. There was no significant difference between PVI alone compared to PVI and left atrial debulking (p = 0.11).Conclusions: LGE-MRI immediately following ablation of AF is capable of identifying patients who may have sustained subclinical thermal injury to the esophagus. Proximity of the esophagus to the left pulmonary veins and the posterior LA wall are associated with increased risk while the ablation technique is not.

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SPATIAL ACCURACY OF 3D ELECTRO-ANATOMICAL SYSTEMS DURING PULMONARY VEIN ISOLATIONHeiko Lehrmann, MD, Patrick Hoermann, MD, Reinhold Weber, MD, Jochen Schiebeling-Roemer, MD, Juergen Allgeier, MD, Claudia Herrera-Siklody, MD, Amir S. Jadidi, MD and Thomas Arentz, MD. Heartcenter Bad Krozingen, Bad Krozingen, GermanyIntroduction: 3D electro-anatomical systems (EAS) are widely used for pulmonary vein isolation (PVI). We compared the stabitily of 2 current EAS.Methods: Since Oct 2010, 180 pts with AF underwent circumferential PVI under general anaesthesia. Pts were randomly assigned to either CARTO3 or NavX Velocity LA mapping. System accuracy was evaluated during and after PVI.

S413Poster Session V

and ventricular components (95% CI ± 6.6%, ICC=0.989). Inter- observer 95% limits of agreement were within ±10.7% (ICC=0.979), 7.4% (ICC=0.991) and 7.2% (ICC=0.991) for atrial, ventricular and total PAT, respectively.Conclusions: This study, for the first time, validates the use of a standard (clinical) CMR sequence for accurate and reproducible assessment of atrial PAT.

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IMPACT OF IRRIGATION FLOW RATE ON TISSUE TEMPERATURE PROFILE AND LESION GGEOMETRY IN AN OVINE THIGH MUSCLE RADIO-FREQUENCY ABLATION MODELSachin Nayyar, MD, Lorraine Mackenzie, PhD, Dennis H. Lau, MBBS, PhD, Douglas Kelly, PhD, Anthony G. Brooks, PhD, Kurt C. Roberts-Thomson, MBBS, PhD and Prashanthan Sanders, MBBS, PhD. Centre for Heart Rhythm Disorders, Royal Adelaide Hospital, Adelaide, AustraliaIntroduction: Optimal irrigation rates for standard irrigated radiofrequency (RF) ablation are unknown.Methods: RF was done on thigh muscle in 16 sheep using 3.5 mm tip irrigated ablation catheter (Thermocool®, Biosense Webster Inc) lowered at 90°angle & 10g force for 30s at each site. 353 lesions were produced at various power & IR rate combinations.Tissue temperature (TT) was recorded at surface, 3, 7 & 10 mm depth. Lesions were analyzed for depth, surface diameter (SD), maximum diameter (MD), depth at maximum diameter (DMD) & volume. Data was grouped into low vs high IR [<30: 2,10,20 ml/min (n=153); ≥30: 30,40,50,60 ml/min (n=200)] and low vs high power [≤30:10,20,30 W (n=133); >30: 35,40,45,50 W (n=220)].Results: Average power achieved was maximum at 30ml/min (35 ± 11 W), however it didn’t differ significantly among flow rates (p=0.6). Both catheter tip temperature & TT (surface & depth) increased with increasing power and decreased with increase in IR (p<0.05). Specifically, increase in IR reduced 3mm TT (p < 0.005) but not at 7 & 10 mm. TT at 7mm (42 ± 5 °C) was significantly higher than at 3mm (39 ± 6 °C) and 10mm (38 ± 6 °C) (p< 0.005) however change in IR didn’t alter TT arrangement at different depths (Depth*Flow p=0.07). Lesion volume (p=0.05) & depth (p=0.04) decreased with high IR at all powers (Figure), however MD, DMD & SD didn’tchange with IR. Steam pops were observed in 27/353 lesions (7.6%) & were more frequent at power ≥ 40 W (23/27,89%), & flow ≤ 30 ml/min (21/27,77%).Conclusions: Increase in IR flow potentially wastes RF energy by cooling superficial tissue & decreases lesion depth & volume. Increase in IR does not affect TT achieved in deep tissue however reduces steam pop formation.

epicardial surface of each heart using a 4mm standard blazer ablation catheter. The fluorescence of NADH (fNADH) was imaged to monitor the redox state of epicardial tissue. To image fNADH, light from a mercury lamp was filtered (350±25nm) and used to illuminate the epicardium. Emitted light was filtered (460±20nm) and imaged using a CCD camera. Hearts were then paced while imaging the fluorescence of a voltage sensitive dye to map conduction pathways.Results: RF lesions exhibited very low or non-detectable fNADH compared to the surrounding un-ablated myocardium. Lesion size and shape, as revealed by fNADH, closely matched with areas that stained negative for TTC (indication of nonviable tissue). Viable gaps between lesions smaller than 1mm were clearly indicated in fNADH images. Conduction through these gaps resulted in post-ablation reentries. RF lesions in blood-perfused hearts were clearly visible when the blood was displaced from the epicardial surface.Conclusions: In both blood-free and blood-perfused preparations, imaging of endogenous fNADH is useful for measuring RF lesion size and for identifying viable gaps. Results show that fNADH imaging could be incorporated into catheter-based devices to aid the treatment of atrial fibrillation and other types of cardiac arrhythmias.

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VALIDATION OF CARDIAC MAGNETIC RESONANCE ASSESSMENT OF ATRIAL PERICARDIAL ADIPOSE TISSUERajiv Mahajan, MD, Pawel Kuklik, PhD, Suchi Grover, MBBS, Nor Hanim Mohd. Amin, MD, Anthony Brooks, PhD, Prashanthan Sanders, MBBS, PhD and Joseph B. Selvanayagam, MBBS, PhD. CHRD, University of Adelaide and Royal Adelaide Hospital, Adelaide, Australia, Department of Cardiovascular Medicine, Flinders Medical Centre, Adelaide, AustraliaIntroduction: Total pericardial adipose tissue (PAT) and separately, atrial adipose tissue has both been shown to be independent predictors of AF. The quantification of atrial PAT, however, has not yet been validated. We sought to validate atrial PAT assessment by standard CMR measures in an ovine model.Methods: 10 merino cross sheep underwent CMR using a 1.5 Tesla system (Siemens, Sonata, Erlangen, Germany). The animals were mechanically ventilated which allowed breath-hold sequences. Both atrial and ventricular short axis (SA) images were acquired using ECG-gated steady state free precession sequences (TR/TE 52.05 ms/1.74 ms, flip angle 70°, matrix 256 × 150, FOV 380 mm with slice thickness 6 mm with no inter-slice gap).The consecutive end-diastolic phase from both atrial and ventricle images were used to determine the volume of atrial and ventricular PAT respectively. A 3D model was constructed offline using an in-house developed semi-automated software. Regions of adipose tissue were marked in each slice followed by linear interpolation of pixel intensities in spaces between consecutive image slices. Total volume of adipose tissue was calculated as a total volume of 3D model. This was multiplied with a factor of 0.9 to get mass. The sheep were euthanized and the PAT was removed and weighed for comparison to the corresponding CMR measurements.Results: MRI over-estimated total cardiac necropsy fat mass by 26 gms, with 95% CI of ± 23.0 gms. Corresponding ventricular and atrial components were overestimated by a mean of 19gms (95% limits of agreement ± 19.5gms) and 7.7gms (95% limits of agreement ±11.6gms), respectively. All MR fat estimates significantly correlated with autopsy measurements (ICC>0.80; p<0.03). Intra- observer reliability in MR measures was high, with 95 % levels of agreement within 5.5% (ICC= 0.995) for total fat mass and its individual atrial (95% CI ±8.3%, ICC=0.993)

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depolarization to ECG chest leads AF waves during pers-AF.Methods: Catheters (CAT) were introduced in 10 consecutive patients (60±5 y, AF duration 22±14 m) prior to ablation: 1) a quadripolar CAT in the RAA, 2) a decapolar CAT in the coronary sinus (CS) and 3) a duodecapolar CAT in the LA appendage (LAA). Local activation times were extracted from bipolar recordings using sliding windows. Chest lead V6 was placed in the back (V6b). Mean AF cycle length (AFCL) of leads V1 to V6b were computed as the inverse of the dominant frequency of ECG spectra after QRST cancellation, and compared to intracardiac RAA, LAA and CS AFCL using Pearson’s correlation coefficient.Results: The figure shows that the correlation between RAA and chest leads AFCL was maximal for V1 and progressively dropped till V5, with a moderate rise for V6b. LAA AFCL showed the opposite pattern with the highest correlation in V6B and the lowest one in V2. The correlation of CS AFCL was similar to the LAA one, but of lower magnitude.Conclusions: Our preliminary results suggest that the respective contribution of RAA and LAA activities can be estimated using a modified surface ECG. Whether this technique has the potential to guide ablation of LA and RA drivers in pers-AF needs further validation.

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INFLAMMATION AND SPONTANEOUS ATRIAL SCARRING IN LONG STANDING PERSISTENT ATRIAL FIBRILLATION: IMPLICATIONS IN PATIENTS UNDERGOING RADIOFREQUENCY ABLATIONAyman A. Hussein, MD, Rasha Al Bawardy, MD, Mohammed Chamsi-Pasha, MD, David O. Martin, MD, Thomas Dresing, MD, Mandeep Bhargava, MD, Thomas Callahan, MD, Mohamed Kanj, MD, Patrick Tchou, MD, Bruce D. Lindsay, MD, Andrea Natale, MD, Walid I. Saliba, MD and Oussama Wazni, MD. University of Maryland Medical Center, Baltimore, MD, Cleveland Clinic Foundation, Cleveland, OHIntroduction: The association between inflammation and atrial fibrillation is not well understood. We aimed to study the relationship between inflammation and spontaneous atrial scarring in patients with long standing persistent atrial fibrillation (LPAF) undergoing ablation.Methods: C-reactive protein (CRP) levels were measured in 580 consecutive patients with lone LPAF (continuous arrhythmia duration>6 months) on the day of AF ablation. Left atrial scarring (LASc) was defined as complete absence of atrial bipolar electrograms (recorded and filtered at 30 to 400 Hz) seen in all 10 poles of the Lasso catheter in at least three positions in the

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VENTRICULAR RATE REDUCTION BY MYOCARDIAL STIMULATION IN STABLE ATRIAL FIBRILLATION DOGSYong-Fu Xiao, MD, PhD, Jon F. Urban, PhD, John L. Sommer, No Degree and Scott Brabec, MS. Medtronic, Inc., Mounds View, MN, Medtronic, Inc., Minneapolis, MNIntroduction: Patients with atrial fibrillation (AF) often have rapid ventricular rates (VR) which can cause other cardiovascular complications. Rhythm and rate control is often used for AF treatment. As atrial impulses have to propagate through the atrial-ventricular node (AVN) to induce ventricular excitation, electrical stimulation of the AVN at a key time-point in the cardiac cycle may block some AF impulses to the ventricles and decrease VR. This approach is referred to here as Cardiac Electrical Window Therapy (CEWT). This study investigated if CEWT could slow VR in dogs with AF.Methods: Stable AF was induced in four dogs by on and off repetitive high frequency atrial burst stimulation. CEWT was delivered to the AVN and timed to R-wave sensed in the RV apex. Stimuli for CEWT were either single pulse or a train of 5 pulses with 20 ms interval between pulses. The latencies of stimuli timed to R-wave were varied for measurement of the size of CEWT time window.Results: CEWT stimulation of the AVN area reduced VR in three of four dogs, one using a fixed lead and two using a mapping catheter. The VR was reduced from 195 ± 15 bpm to 109 ± 22 bpm (mean ± SE, n = 3). The left panel shows an example where VR was immediately reduced from 210 bpm to 72 bpm when CEWT was turned on. Fast VR reoccurred immediately when CEWT was turned off (right panel). The latencies after sensing R-wave for single pulse stimuli to effectively slow VR (measured in the one dog using the fixed lead) ranged from 60 ms to 110 ms.Conclusions: Our data demonstrate that myocardial stimulation within a specific time window in the cardiac cycle slowed VR in AF dogs. However, more experiments are needed to replicate and understand CEWT in AF treatment.

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CONTRIBUTION OF LEFT AND RIGHT ATRIAL APPENDAGE ACTIVITIES TO ECG FIBRILLATION WAVESAndrea Buttu, MSc, Andrei Forclaz, MD, Patrizio Pascale, MD, Sanjiv M. Narayan, MD, PhD, Etienne Pruvot, MD and Jean-Marc Vesin, PhD. Federal Institute of Technology, Lausanne, Switzerland, University Hospital Center Vaudois, Lausanne, Switzerland, University Of California, San Diego, CAIntroduction: It was recently shown that atrial fibrillation (AF) waves on chest lead V1 adequately reflect right atrial appendage (RAA) activity during long standing persistent AF (pers-AF). The contribution of the left atrial (LA) activity to chest leads AF waves, however, remains unknown. Our study is aimed at evaluating the respective contribution of the RA and LA

S415Poster Session V

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IMPACT OF BASELINE ATRIAL FIBRILLATION CYCLE LENGTH ON ACUTE AND LONG-TERM OUTCOME OF PERSISTENT ATRIAL FIBRILLATION ABLATION USING A STEPWISE APPROACHSonia Ammar, MD, Maria Paulik, No Degree, Tilko Reents, MD, Stephanie Fichtner, MD, Patrik Schön, MD, Jinjin Wu, MD, Herribert Pavaci, MD, Clemens Jilek, MD, Suzanne Kathan, No Degree, Christof Kolb, MD, Gabriele Hessling, MD and Isabel Deisenhofer, MD. Deutsches Herzzentrum München, Munich, GermanyIntroduction: Results of catheter ablation of persistent atrial fibrillation (AF) are still unsatisfying. Acute and long term outcome depends on clinical, electrophysiological and procedural factors. We investigated the impact of the baseline AF cycle length (CL) on acute and long term results of persistent AF ablation using a stepwise ablation approach.Methods: We included 191 consecutive patients (male 76%, mean age 57±12 years) undergoing catheter ablation of persistent AF between January 2008 and February 2011. All patients received a pulmonary vein isolation (PVI). In the absence of sinus rhythm (SR), a stepwise approach with ablation of complex fractionated atrial electrograms (CFAE) and eventually ablation of subsequent atrial tachycardias (AT) (focal ablation of localized reentries and/or linear lesions for macroreentries) was performed. AF CL was measured in the left atrial appendage at baseline and following each ablation step during the procedure. Endpoint was freedom from AF after a single ablation off antiarrhythmic drugs (AAD) during a follow-up of 10±6 months.Results: A shorter AF CL at baseline was associated with a longer AF duration (r=-0.19, p=0.01) and a longer time since the last cardioversion (r=-0.20, p=0.02). Using our approach, AF termination was achieved in 57% of patients (32% into SR and 25% into an AT). There was no difference in baseline CL between patients with or without AF termination (167 ± 23 vs. 161 ± 26 ms, p=0.13). There was also no difference in baseline CL between patients undergoing a cardioversion of AF at end of the procedure and patients cardioverted for AT (164 ± 27 vs. 162 ± 25 ms, p=0.5). A longer baseline CL was correlated to a shorter procedure duration (r=-0,18, p=0.012). During follow-up, freedom from AF after a single procedure was achieved in 58% (sinus rhythm in 32 %, recurrent AT in 26%). Patients with shorter baseline CL (<150ms) had a similar outcome as patients with longer CL (Freedom from AF at 9 months: 52% vs. 55%, log Rank p=0.42)Conclusions: In this series of patients with persistent AF,

LA. All patients had isolation of the pulmonary veins and extra PV triggers when identified. All success rates were determined off antiarrhythmics.Results: Patients with higher burden of inflammation (with increasing CRP quartiles) were more likely to have hypertension (p=0.0004), diabetes (p=0.009) and larger atria (p=0.003). There was a significant increase in LASc with increasing CRP quartiles (p=0.0003). LASc was more frequently seen in patients with longer standing AF (22.3 vs. 3.5% in upper duration quartile vs. lower quartile, respectively, p<0.0001). Over a 24 months follow-up, 232 patients had arrhythmia recurrence. In Cox analyses, levels of CRP (HR per log increase 1.41, 95% CI 1.24-1.62, p<0.0001), LASc (HR 1.74, 95% CI 1.21-2.45, p=0.004) and longer duration of AF prior to ablation (HR per year increase 1.02, 95%CI 1.00-1.03, p=0.03) were found to predict arrhythmia recurrence. In covariate adjusted analyses, CRP was found to be an independent predictor of arrhythmia recurrence (HR per log increase 1.37, 95% CI 1.20-1.57, p<0.0001). The HRs for recurrent arrhythmia in increasing CRP quartiles compared to the first quartile were 1.15, 1.59 and 1.91 (ptrend=0.002).Conclusions: Inflammation is associated with left atrial scarring in LPAF. Both inflammation and LASc increase the risk of arrhythmia recurrence after ablation. In longer lasting AF, inflammation and scarring are the hallmarks of progressive atrial remodeling, therefore contributing to arrhythmia recurrences.

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OPTIMAL OBSERVATION TIME FOR WHETHER PULMONARY VEIN ISOLATION IS SUCCESSFULLY COMPLETED TO PREDICT PULMONARY VEIN RECONNECTION AFTER CIRCUMFERENTIAL PULMONARY VEIN ISOLATIONKohki Nakamura, MD, Shigeto Naito, MD, Nobusada Funabashi, MD, Akihisa Kataoka, MD, Hiroyuki Takaoka, MD, Kenichi Kaseno, MD, Koji Kumagai, MD, Yoshio Kobayashi, MD and Shigeru Oshima, MD. Gunma Prefectural Cardiovascular Center, Division of Cardiology, Maebashi, Japan, Chiba University Graduate School of Medicine, Department of Cardiovascular Science and Medicine, Chiba, JapanIntroduction: Recurrence of atrial fibrillation (AF) after pulmonary vein(PV) isolation (PVI) is often associated with PV reconnection (PVR). We aimed to identify factors that predict PV reconnection after circumferential PVI (CPVI) for AF.Methods: A total of 362 PVs from 91 consecutive AF patients (72 males; mean 60 ± 11 years; 49 paroxysmal/42 persistent) who underwent a 2nd ablation procedure for recurrent AF (mean 188 ± 143 days) were retrospectively analyzed. Results: PVR was observed in a total of 250 PVs among 87 patients. PV diameter (mm) was significantly greater and observation time (min) for whether PVI was successfully completed during the 1st PVI was significantly smaller in PVs with reconnection than in those without (all P<0.001). In a receiver operating characteristic analysis, the area under the curve of observation time during the 1st PVI was 0.673. At an optimal cutoff of 20 minutes for observation time, sensitivity and specificity for the prediction of PVR were 55.7% and 70.6%, respectively. PVs were divided into 2 groups on the basis of optimal cutoff values (observation time ≤20 minutes and ≥21 minutes). By a Kaplan-Meier analysis and log rank test, PVR was more frequent in PVs with observation time ≤20 minutes than in those with observation time ≥21 minutes (P=0.029).Conclusions: More than 20 minutes of observation time for whether PVI is successfully completed during the 1st PVI may be needed to prevent PVR and subsequent AF recurrence after CPVI.

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present study was to compare immediate results and short-term efficacy of a new circular ablation catheter (PVAC) compared with conventional point-by-point ablation and cryoballoon ablation.Methods: This prospective study enrolled 177 consecutive patients (pts) with symptomatic paroxysmal AF refractory to antiarrhythmic drugs: 108 pts underwent conventional ablation using 3.5-mm irrigated tip RF catheter guided by a 3D mapping system (3D-group), 35 pts using the duty-cycled bipolar and unipolar radiofrequency decapolar circular catheter (PVAC-group) and 34 pts using the Cryoballoon (CRYO-group)Results: The mean age was 54 ± 11 years, and 80% were male. Baseline characteristics were similar between groups. Acute complete PV isolation was achieved in 99% of PVs in the 3D-group and CRYO-group, and 98 % in the PVAC-group (p=NS). Fluoroscopy times were shorter in the 3D-group than the PVAC and CRYO-groups: 29 ± 10 min vs. 35 ± 12 min vs. 38 ± 11 min respectively (p < 0.01). Total procedure times were shorter in the PVAC-group than the 3D- and CRYO-groups: 171 ± 35 min vs. 205 ± 42 min vs. 222 ± 47 min (p < 0.01). Mean ablation time was shorter in the PVAC-group than the CRYO and 3D-groups: 1921 ± 493 sec vs. 2972 ± 559 sec vs. 3671 ± 911 sec respectively (p < 0.001). During a mean follow-up of 12.5 ± 2.2 months, 79% in the CRYO-group vs 62% in the PVAC and 70% in the 3D-groups were free of AF-recurrence without antiarrhythmic drugs (p=NS) after one procedure, No procedure-related major complication was observed.Conclusions: AF ablation using PVAC and Cryoballoon represent a safe alternative for PV isolation. PVAC reduces procedural time. The short-term efficacy is comparable between PVAC, Cryoballoon and a conventional point-by-point antral ablation technique.

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FOLLOW-UP OF PATIENTS WITH REPEATED PULMONARY VEIN ISOLATION AFTER A FIRST CRYOBALLOON ABLATIONRohit Bhagwandien, MD, Petter Janse, NP, Bruno Schwagten, MD, Dominic Theuns, PhD, Yves Van Belle, MD, PhD, Natasja de Groot, MD, PhD, Tamas Szili-Torok, MD, PhD and Luc Jordaens, MD, PhD. Erasmus MC, Rotterdam, NetherlandsIntroduction: Cryoballoon ablation (CBA) is an established method for pulmonary vein isolation (PVI) in patients with paroxysmal atrial fibrillation (AF) with success rates similar compared to radiofrequency (RF) ablation. The major cause of recurrence is re-conduction in the pulmonary veins. We studied the efficacy of repeated ablation after CBA.Methods: We included all consecutive patients, from November 2006 to December 2010, scheduled for CBA-PVI with a complete 1-year clinical follow-up after inclusion. The AF and AT free survival was calculated, including all recurrences >30 seconds, with a blanking period of 3 months after the first ablation procedure.Results: In total, 241 AF patients underwent CBA-PVI (age 56±10 years; Males 169). The mean follow-up was 1179±451 days. A total number of 96 (39%) patients had recurrence over this follow-up period. The AF free proportion was 171/241 patients (71%) at one year and became 150/241 (62%) at 24 months. A repeated CBA procedure was offered to 43 (18%), RF was used in 23 (10%) patients. The proportion of event free redo patients with CBA were 21/43 (49%) and 15/23 (65%) with RF. This was not statistical significant. The AF free proportion with one redo procedure became 80,4% at 24 months. We observed 3 patients with left sided atrial tachycardia, all after a previous redo procedure with RF.Conclusions: Repeated ablation after a first CBA is useful; it

baseline AF CL alone does not seem to be a predictor for acute and long-term outcome of catheter ablation using a stepwise approach. However, a shorter baseline AF CL predicts longer procedure times.

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THE EXTENT OF ABLATION LESIONS: DISPARITIES BETWEEN DIFFERENT PULMONARY VEIN ISOLATION STRATEGIESClaudia Herrera Siklody, MD, Serge Boveda, MD, Mélèze Hocini, MD, Jochen Schiebeling-Römer, MD, Dorothea Werner, MD, Amir S. Jadidi, MD, Arnaud Chaumeil, MD, Shinsuke Miyazaki, MD, Jeff Schweitzer, PhD and Thomas Arentz, MD. Herz Zentrum Bad Krozingen, Bad Krozingen, Germany, Clinique Pasteur, Toulouse, France, Hôpital Cardiologique du Haut-Lèveque, Pessac - Bordeaux, France, St. Jude Medical Germany, Eschborn, Germany, St Jude Medical, St Paul, MNIntroduction: Pulmonary vein isolation (PVI) is the base of atrial fibrillation (AF) catheter ablation. The extent of lesions deployed to achieve PVI plays an important role in its efficacy, especially in persistent AF patients (pts). We aimed to compare the size of the lesions created by 4 different currently used PVI strategies.Methods: We included pts with symptomatic AF referred for PVI to 3 high-volume centers. Ablation was conducted using either one of the following Methods. 1) segmental PVI with exclusive fluoroscopic guidance (Segm RF), 2) circumferential PVI using a 3-D mapping system (Circ RF), 3) the cryoballoon (Cryo) or 4) the multi-electrode duty-cycled RF ablation catheter (PVAC). Segm PVI and Circ PVI were performed with a conventional irrigated RF catheter. Each technique was only done in centers with sufficient expertise (>100 cases). A voltage map of the left atrium (LA) was collected both before and after ablation in all patients. Total LA surface was measured including the first 2 cm of all pulmonary veins and excluding the mitral valve opening and the left atrial appendage. Areas with an electrogram amplitude under 0.3 mV were considered as scar. The extent of ablation lesions was calculated by substracting preablation low-voltage areas under 0.3 mV from postablation scar areas.Results: 58 pts were included in the study (58±9 years-old, 38 with paroxysmal AF): 12 in the Segm RF group, 18 in the Circ RF group, 12 in the Cryo group and 16 in the PVAC group. There were no differences between groups concerning AF type and LA size. Total LA surface on the maps was also comparable among groups. However, Circ RF and Cryo led to 34.8% and 29.1% scarring of the LA surface respectively, against 16.8% and 19.1% using PVAC and Segm RF (p<0.001).Conclusions: Circ RF and Cryo resulted in comparably large ablation lesions, significantly bigger than Segm RF and PVAC, and encompassing a greater part of the antrum of the pulmonary veins.

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PROSPECTIVE STUDY COMPARING DUTY-CYCLED BIPOLAR AND UNIPOLAR RADIOFREQUENCY TO PULMONARY VEIN ISOLATION BY POINT-BY-POINT ABLATION AND CRYOBALLOON ABLATIONBilel Omar Mokrani, MD, Jean-François Sarrazin, MD, Jean Champagne, MD, Isabelle Nault, MD, Noura Zannad, MD, Olivier Barthez, MD, François Philippon, MD, Louis Blier, MD, Franck Molin, MD and Gilles O’hara, MD. IUCPQ, Quebec, QC, CanadaIntroduction: Pulmonary vein (PV) isolation is a therapeutic option for symptomatic atrial fibrillation (AF). New technologies may reduce procedure time and complexity. The aim of the

S417Poster Session V

Center, Baltimore, MDIntroduction: Elevated plasma B-type natriuretic peptide (BNP) levels have been reported in patients with atrial fibrillation (AF). Little is known about BNP in patients with long standing persistent AF (LPAF, continuous AF >6 months). We aimed to study the relationship between BNP levels and outcomes of LPAF ablation.Methods: Plasma BNP levels were measured in 580 consecutive patients with LPAF but otherwise no structural heart disease (lone AF) undergoing first time AF ablation. All measurements were performed on the day of ablation using the point-of-care TriageMeter assay (Biosite Diagnostics, San Diego, CA). All patients had isolation of all four pulmonary veins. Arrhythmia recurrences were identified by symptoms with documentation, event monitoring, Holters and ECGs. All success rates were determined off antiarrhythmics.Results: At baseline, factors associated with higher levels of BNP in LPAF patients were older age (p<0.0001), female gender (p<0.0001), systemic hypertension (p=0.007) and larger atrial size (p<0.0001). Patients with higher levels of BNP were more likely to have atrial scarring on voltage maps (13.9 vs. 8.7%, p=0.04). Over a 24 months follow-up, 232 patients had arrhythmia recurrence. Plasma BNP levels were found to be associated with arrhythmia recurrence in univariate Cox proportional hazards analysis (HR for +1 log increase 1.23, 95% CI 1.06-1.43, p=0.006). In covariate adjusted analyses, only duration of AF (HR for +1year increase 1.02, 95% CI 1.01-1.04, p=0.02) and BNP levels (HR for +1 log increase 1.22, 95% CI 1.04-1.43, p=0.01) were found to predict arrhythmia recurrences.Conclusions: Elevated plasma BNP levels are associated with arrhythmia recurrence after ablation of LPAF. Higher levels of BNP may reflect increased cardiac chamber wall stress and/or intrinsic atrial disease in these patients, thus increasing the risk of arrhythmia recurrence.

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IMPACT OF A NEW CONTACT FORCE SENSING CATHETER ON PROCEDURAL PARAMETERS IN RADIOFREQUENCY ABLATION OF ATRIAL FIBRILLATIONMartin Martinek, MD, PhD, Christine Lemes, MD, Elisabeth Sigmund, MD, Michael Derndorfer, MD, Hans-Joachim Nesser, MD, PhD and Helmut Puererfellner, MD, PHD, FHRS. Elisabethinen Linz GmbH, University Teaching Hospital, Linz, AustriaIntroduction: Left atrial radiofrequency ablation has been established for the treatment of atrial fibrillation. New catheter material with the unique opportunity to directly visualize catheter contact force and direction as well as integration of this information into a 3D electro-anatomic System (CARTO 3) have recently been released. The aim of this study was to assess the impact of this new technique on procedural parameters.Methods: A total of 29 consecutive patients (65% male, 59.6±10.5 years) undergoing catheter ablation for paroxysmal atrial fibrillation were included in the study. Pulmonary vein antrum isolation with documented entry and exit block was performed using either the standard NaviStar® ThermoCool® catheter (n=17) or the new ThermoCool® SmartTouch™ (n=12) contact force sensing catheter (both Biosense Webster). Both catheters are mounted with equal 3.5mm open-irrigated tips. A maximum of 25W was delivered at the left atrial posterior wall, 30W were used in other positions with an irrigation flow rate of 2ml/min at baseline and 20ml/min during radiofrequency application.Results: Procedural data showed a remarkable decline in ablation time (radiofrequency time needed to isolate all pulmonary veins) from 56.2±16.1 to 40.9±9.5 minutes (p=0.007)

can be successfully performed with both CBA and RF. One redo procedure increases the AF free proportion to 80,4%. We did not observe left sided atrial tachycardia after CBA alone.

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LONG TERM RESULTS OF CATHETER ABLATION FOR PAROXYSMAL ATRIAL FIBRILLATION IN PATIENTS WITH HEMODIALYSISMasateru Takigawa, MD, Taishi Kuwahara, MD, Kazuya Yamao, MD, Emiko Nakashima, MD, Yuji Watari, MD, Kenji Okubo, MD, Katsumasa Takagi, MD, Yoshihide Takahashi, MD, Atsushi Takahashi, MD, Shunsuke Kuroda, MD, Naohiko Kawaguchi, MD, Yuki Osaka, MD, Daiki Akiyama, MD, Tomoyo Sugiyama, MD, Tetsuo Kamiishi, MD, Shigeki Kimura, MD, Hiroyuki Hikita, MD and Mitsuaki Isobe, MD. Yokosuka Kyosai Hospital, Yokosuka, Japan, Tokyo Medical and Dental University, Tokyo, JapanIntroductions: Because of increasing patients with atrial fibrillation (AF), extensive pulmonary veins isolation (EPVI) recently becomes a standard treatment. However, the effectiveness of EPVI for patients with hemodialysis remains unknown.Methods: We studied 38 consecutive patients with chronic hemodialysis (mean age 62 ± 7 yrs, 65.8 % males) undergoing EPVI for paroxysmal AF (PAF). All patients were followed up at the outpatient clinic without any antiarrhythmics.Results: Acute success of EPVI was achieved in all patients. Sinus rhythm (SR) was maintained in 12 patients (31.6 %) after the 1st session during a mean follow-up of 19.4 ± 26.6 months. The 2nd session was performed in 18 out of 26 patients with recurrent AF, and 8 patients maintained SR. No patients underwent more than the 3rd or more sessions. Finally SR was present in 20 patients (55.6%) after the last procedure during a mean follow-up of 27.1 ± 27.7 months. Longer duration of AF was a significant predictor of AF recurrence (HR 1.31/1yr, 95%CI 1.08 - 1.61, P = 0.006).Conclusions: Although the indication of EPVI for AF patients with hemodialysis was carefully determined, the procedure was acceptable for the patients with clinically uncontrolled AF in these patients.

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PLASMA LEVELS OF B-TYPE NATRIURETIC PEPTIDE AND ARRHYTHMIA RECURRENCE AFTER ABLATION OF LONE LONG STANDING PERSISTENT ATRIAL FIBRILLATIONRasha Al-Bawardy, MD, Ayman Hussein, MD, Mohammed Chamsi-Pasha, MD, David O. Martin, MD, Thomas Dresing, MD, Mandeep Bhargava, MD, Thomas Callahan, MD, Mohamed Kanj, MD, Patrick Tchou, MD, Bruce D. Lindsay, MD, Walid Saliba, MD and Oussama Wazni, MD. Cleveland Clinic Foundation, Cleveland, OH, University of Maryland Medical

S418 Heart Rhythm, Vol. 9, No. 5, May Supplement 2012

University Of Virginia Med Ctr, Charlottsville, VA, Erasmus MC, Afdeling Cardiologie, Rotterdam, Netherlands, Endosense, Geneva, Switzerland, Mount Sinai School of Medicine, Cardiology, New York, NYIntroduction: Previous studies (Toccata, Efficas) have shown that RF ablations delivered with stable catheter position as described by optimal contact force (CF) are more likely to achieve transmural and durable lesions. Respiratory excursion during ablation may adversely influence catheter stability and energy delivery by reducing the CF needed to achieve optimal lesions. It was hypothesized that by minimizing respiratory motion, jet ventilation would improve lesion delivery as defined by procedural efficiencies and stability of CF.Methods: 51 subjects at 9 centers that received general anesthesia (GA) and who were enrolled in the TOCCASTAR Study for the treatment of PAF were evaluated. All pts were treated with a CF sensing catheter (TactiCath, Endosense). 24 pts received GA using high frequency jet mode of ventilation (GA-Jet), 27 received conventional GA. Avg CF, total Force Time Integral (FTI), avg ablation duration and CF stability were compared for the 2 groups.Results: Use of GA-Jet resulted in significantly greater avg CF but with less variation due to catheter instability as reflected by significantly lower SD of normalized CF. This group also received significantly higher total FTI and longer avg ablation duration suggesting that a stable catheter position permits the operator to perform longer lesions with proportionately more total energy delivered.Conclusions: Jet ventilation maximizes the stability of CF during respiration. Patients may experience less intermittent catheter contact and a correspondingly lower rate of chronic reconnection.

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ELECTROPHYSIOLOGICAL EFFECTS OF AN ANTEROSEPTAL LINE AS AN ALTERNATIVE TO MITRAL ISTHMUS ABLATION DURING PULMONARY VEIN ISOLATION AND LEFT ATRIAL SUBSTRATE MODIFICATIONMichele Brunelli, MD, PhD, Anett Große, MD, Santi Raffa, MD, PhD, Ulrike Wagner, No Degree, Mark Sammut, MD, Markus Roos, MD, Stefan Richter, MD, Susanne Gorki, MD, Elke Illhardt, MD and J. Christoph Geller, MD. Zentral Klinik Bad Berka, Bad Berka, GermanyIntroduction: Left atrial (LA) linear lesions (at the roof and the mitral isthmus) increase the efficacy of pulmonary vein isolation (PVI) in patients (pts) with long lasting or persistent episodes of atrial fibrillation (AF). Therefore, an anteroseptal line (ASL) has been proposed as an alternative. Aim of this study was to assess the success rates of MIL and ASL and compare the effects on bi-atrial and LA activation times.Methods: Consecutive pts with long lasting paroxysmal or persistent AF undergoing substrate modification in addition to PVI were randomized in a 1:1 to either MIL or ASL. The acute success rate was analyzed, and LA sinus rhythm activation maps (EnSite NavX, SJM) were compared after achievement of PVI and linear ablation.Results: 30 pts were enrolled (59±10 years old, CHA2DS2VASc

with a reduction in overall procedure time of 25.5±11.8 minutes (p=0.003). In parallel the total energy delivered could be significantly reduced from 78,051±18,239 to 63,421±13,511 Ws (p=0.026).Conclusions: The use of novel contact force sensing technology was able to significantly reduce ablation and procedure times in atrial fibrillation ablation in this small pilot study. Energy delivery was substantially reduced by avoiding radiofrequency ablation in positions with insufficient surface contact.

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LEFT ATRIAL LINEAR CRYOABLATION FOR ATRIAL FIBRILLATION USING AN 8MM TIP CATHETERTimothy R. Betts, MD, FRCP, Michael Jones, MD, Kelvin CK. Wong, MD, Norman Qureshi, MD, Kim Rajappan, MD and Yaver Bashir, MD. Oxford University Hospitals NHS Trust, Oxford, United KingdomIntroduction: Patients undergoing ablation for AFib or macroreentrant LA flutter may require roof and mitral isthmus (MI) linear lesions. RF linear ablation is often challenging and may be associated with complications. This study examined the feasibility and safety of LA linear ablation using an 8mm-tip cryoablation catheter.Methods: Patients undergoing initial or re-do ablation for paroxysmal or persistent atrial fibrillation with no previous roof or MI ablation were enrolled. An 8mm-tip cryoablation catheter was used with a 10F steerable sheath. After isolation of all 4 pulmonary veins, linear lesions were delivered in a point-by-point fashion (180s per lesion on roof and 240s per lesion on MI and distal CS to -80oC. Roof and MI block were confirmed using activation mapping, double potentials and differential pacing. Acute success rates and ablation times were compared to a group of 35 consecutive patients who had linear ablation with a 3.5mm-tip irrigated RF catheter through a steerable sheath (30W roof and distal CS, 40-50W MI).Results: 21 patients (age 53±11, 14 paroxysmal, LA diameter 39±5mm). In 2/21 MI block was unsuccessful and a roof line was not attempted. In the remaining MI block was achieved after a mean of 1845±733s, in 10/19 without the need for distal CS ablation. Roof line block was achieved in 17/18 patients after a mean of 954±378s ablation. There were no complications. When compared with RF energy ablation success rates were similar but cryoablation took significantly longer (table).Conclusions: LA linear cryoablation is safe and feasible. It is more time-consuming that RF energy although it has the potential to be less painful and better tolerated.

Cryo RF p valueMI acute success 19/21 (20%) 34/35 (97%) nsMI endo abl (min) 27.8±10 10.9±4.3 <0.05CS ablation 8/19 24/34 <0.05MI CS abl time (min) 6.6±3 5.4±2.6 nsMI total abl time (min) 30.8±12 9.7±8.2 <0.05Roof line acute success 17/18 (94%) 36/38 (95%) nsRoof line abl time (min) 15.9±6.3 6.6±2.9 <0.05

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JET VENTILATION STABILIZES CONTACT FORCE DURING RF ABLATION FOR PVIMoussa Mansour, MD, Dipen Shah, MD, E. Kevin Heist, MD, PHD, FHRS, Michael Mangrum, MD, Luc Jordaens, MD, PhD, Jeremy N. Ruskin, MD, David Harari, BS, Hendrik Lambert, PhD and Vivek Reddy, MD. Massachusetts General Hospital, Boston, MA, Hopital Universitaire de Genève, Department of Cardiology, Geneva, Switzerland, Cardiovascular Disease,

S419Poster Session V

use of a larger cryoballoon to avoid ablation deep in the vein, and more systematic phrenic nerve monitoring.

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SUCCESSFUL CATHETER ABLATION AND MAINTENANCE OF SINUS RHYTHM DECREASES PLATELET ACTIVATION AND IMPROVES ENDOTHELIAL FUNCTION IN PATIENTS WITH ATRIAL FIBRILLATIONHan S. Lim, MBBS, Scott R. Willoughby, PhD, Carlee Schultz, BSc, Adhiraj Chakrabarty, MBBS, Muayad Alasady, MBChB, Dennis H. Lau, MBBS, PhD, Rajiv Mahajan, MD, FRCS, Anand Ganesan, MBBS, PhD, Anthony G. Brooks, PhD, Hany S. Abed, MBBS, Sachin Nayyar, MD, Kurt C. Roberts-Thomson, MBBS, PhD, Glenn D. Young, MBBS, Matthew I. Worthley, PhD and Prashanthan Sanders, MBBS, PhD. Centre for Heart Rhythm Disorders, University of Adelaide and Royal Adelaide Hospital, Adelaide, AustraliaIntroduction: Platelet activation and endothelial dysfunction contribute to thrombotic risk in atrial fibrillation (AF) by virtue of Virchow’s Triad. The long term effects of catheter ablation (CA) for AF on these hemostatic mechanisms are unknown.Methods: Fifty seven patients undergoing CA for AF were prospectively studied. Blood samples were obtained at baseline prior to the procedure and at 6 months follow-up post ablation. Platelet activation was assessed by measuring CD62P (platelet P-selectin) and PAC-1 (glycoprotein IIb/IIIa) expression using whole blood flow cytometry. Endothelial function was assessed by measuring asymmetric dimethylarginine (ADMA) levels utilizing ELISA. Physician follow-up was performed at 6 weeks, 3 and 6 months post single procedure. Recurrence of AF was noted by ECG and 7 day Holter monitoring at each review.Results: Of the 57 patients who underwent CA for AF (27 paroxysmal, 22 persistent, and 8 long-standing persistent), 37 patients remained in sinus rhythm (SR group) at 6 months and 20 sustained recurrence of AF (AF recurrence group). Patients with AF recurrence were older, had a higher proportion of hypertension and long-standing persistent AF. There were no significant differences in CD62P (p=0.3), PAC-1 (p=0.1) and ADMA (p=0.8) levels at baseline between the two groups. In the SR group, markers of platelet activation decreased significantly at 6 month follow-up compared to baseline; log CD62P % 0.79±0.28 vs. 1.03±0.27 (p<0.05) and log PAC-1 % 0.22±0.58 vs. 0.89±0.31 (p<0.01). This was not significant in the AF recurrence group; log CD62P % 0.84±0.19 vs. 0.91±0.32 (p=0.8); log PAC-1 % 0.32±0.66 vs. 0.65±0.47 (p=0.1). For endothelial function, ADMA levels decreased significantly at 6 months compared to baseline in the SR group (log ADMA microM/L -0.40±0.07 vs. -0.34±0.11; p<0.05), but did not alter significantly in the group with AF recurrence (log ADMA microM/L -0.37±0.09 vs. -0.35±0.08; p=0.4).Conclusions: Catheter ablation and successful maintenance of SR leads to a decrease in platelet activation and improvement in endothelial function in patients with AF. These findings suggest that the prothrombotic state in patients with AF can be reduced following successful catheter ablation and maintenance of SR.

1.9±1.8, LA volume 132±+31ml, 22 pts persistent AF). After a procedural time of 364±57min, bidirectional block was achieved in 100% of the MILs (58±33min, RF 30±21min), requiring lesions inside the coronary sinus in most (13/15), 100% of the tricuspid isthmus ablations (18±10min, RF 9±6min), 93% (28/30) of the linear ablation at the LA roof (40±26, RF 25±13min) and 67% (10/15) of the ASL (50±34min, RF 33±20min). Anatomically, the ASL (58±9mm) was significantly longer than the MIL (39±7mm; P<.001). Successful MIL ablation did not prolong LA (97±13 vs. 97±13msec) and bi-atrial activation time (126±15 vs. 132±15msec after the P wave [PW]). In contrast, achievement of bidirectional block at the ASL prolonged both LA (100±24 vs 179±31msec; P<.001) and biatrial activation time (130±28 vs 209±35msec after the PW; P<.01). Interruption of the Bachmann’s bundle resulted in a typical delay of the LA anterior wall, the last activated area, and increased the PW duration (141±16 vs 174±24ms; P<.01). 4/5 pts without complete block showed a corridor of narrowly split double potentials, whereas at the LA breakthrough, in the area of the Bachmann’s bundle, continuous activity was recorded.Conclusions: Extensive ablation at the MIL achieves better results than ASL. Successful ASL ablation prolongs LA/biatrial activation time, results in delayed activation of the anterior LA and lengthens the PW duration. A wide Bachmann’s bundle insertion might explain difficulties in achieving bidirectional block when an ASL is attempted.

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COMPLICATION RATES UTILIZING CRYOBALLOON ABLATION FOR PAROXYSMAL ATRIAL FIBRILLATION: COMPARISON OF STOP-AF AND THE CONTINUED ACCESS PROTOCOLMoussa Mansour, MD, E. Kevin Heist, MD, PHD, FHRS, Robert Kowal, MD, PhD, Douglas Packer, MD, FHRS and Jeremy Ruskin, MD. Massachusetts General Hospital, Boston, MA, HeartPlace, The Baylor Univ Medical Center, Dallas, TX, Mayo Clinic - St. Marys Hospital, Rochester, MNIntroduction: The STOP-AF trial demonstrated greater effectiveness of cryoballoon ablation for paroxysmal atrial fibrillation (PAF) compared to patients randomized to drug therapy. The Continued Access Protocol (CAP) enrolled additional non-randomized patients for cryoballoon ablation of PAF after STOP-AF completed enrollment. We sought to determine whether complication rates differed between STOP-AF and CAP.Methods: In STOP-AF, 228 patients underwent 259 ablation procedures using the Medtronic Arctic Front ablation catheter; in CAP, 76 patients underwent 82 procedures using this technology. Complications, including phrenic nerve palsy, pulmonary vein stenosis, access site complications, cardiac perforation, peri-procedural stroke, death and arrhythmia were analyzed.Results: The incidence of phrenic nerve palsy was significantly lower in CAP vs. STOP-AF (3.7% vs. 11.2%, p=0.049). There was a trend towards lower PV stenosis in the CAP registry compared to STOP AF, but this did not reach statistical significance. The incidence of other complications was similar between CAP and STOP-AF (table). The smaller 23 mm balloon was used in 65.4% of procedures in STOP-AF vs. 54.8% of procedures in CAP. Phrenic nerve monitoring was inconsistent and not well documented in STOP-AF; however in CAP, phrenic nerve monitoring was confirmed during all right-sided pulmonary vein cryoablations.Conclusions: Phrenic nerve palsy complicated a significantly smaller percentage of cryoballoon ablation procedures in CAP vs. STOP-AF. This may be related to operator experience, the