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S291 Poster Session IV POSTER PO04: Poster Session IV Friday, May 10, 2013 9:30 a.m. - noon PO04-01 COMPRESSION BANDAGES DO NOT REDUCE GROIN HEMATOMAS AFTER AF ABLATION Cherie Jaynes, BSN, Judith Hildreth, BSN, Ken Hopper, MBA, Antonio Moyeda, CVT, Sanjiv M. Narayan, MD, PHD, FHRS, Marian Holland, MD and David E. Krummen, MD, FHRS. VA San Diego Healthcare System, San Diego, CA Introduction: Many strategies have been used to prevent groin bleeds after AF ablation, that is a potentially significant complication. We hypothesized that pressure dressings in the acute post-procedural period, that may cause discomfort and precipitate movement and bleeding upon removal, may not reduce the incidence of groin hematomas compared to manual compression alone. Methods: We performed a non-randomized open-label 2:1 comparison of no pressure dressing (group 2) vs pressure dressing (group 1) in 78 AF patients (age 62±10years), using a case-cohort design. All patients underwent AF ablation via femoral venous access, during uninterrupted warfarin, with intra-procedural heparin (target ACT 350-400 seconds), reversal of heparin with protamine and manual compression for 10-20 minutes. Results: A total of 19 cases of groin bleeds were documented in the first week post ablation, none of which required surgical repair nor transfusion. In Group I, 6/26 patients had bleeds, while in group II, 13/52 had bleeds (p=0.85). There was also no difference in the incidence of early bleeds (overnight, <8 hours) of 3/26 vs 8/52 (p=0.65). Notably, complaints of groin symptoms (pain or discomfort) was higher for patients in group I (compression bandage discomfort) than in group II (p<0.05). Groups did not differ in weight (104±23vs 104±21 kg, p=NS), height (1.8±0.09 vs 1.8±0.07 m, p=NS), or INR on the procedural day (2.5±0.5 vs 2.3±0.6, p=NS). Two patients were Jehovah’s witnesses. Conclusion: In this 2:1 open label case-cohort study after AF ablation, compression dressings often caused discomfort yet did not reduce the incidence of groin bleeds compared to manual pressure alone in patients with a wide range of heights and weights. These results may impact post-procedural management of AF ablation. PO04-02 NEGATIVE ATRIAL FIBRILLATION ABLATION REFERRAL BIAS IN AFRICAN-AMERICANS Allyson Prasad, MSN, CRNP, Erica Zado, PA, Gregory Supple, MD and Mathew D. Hutchinson, MD. University Of Pennsylvania, Philadelphia, PA Introduction: The prevalence of atrial fibrillation (AF) in African-Americans (A-A) is reported to be 40% lower than in Caucasian-Americans (C-A). Although A-A’s comprise 12% of the US population, little is known about their referral patterns or response to atrial fibrillation (AF) ablation. Methods: We examined 2482 patients referred to our institution for a first AF ablation between 11/2000-1/2012 with self-identified racial groups. We compared baseline demographics and procedural outcome in self-identified A-A vs. C-A patients. Results: From the original cohort, 2.5% identified as A-A and 95% identified as C-A. A-A patients more frequently had hypertension, diabetes, left ventricular cardiomyopathy, and clinical heart failure (Table). At a mean follow-up of 718 days, A-A achieved freedom from AF less frequently than C-A (52% vs. 66%, p=0.04). Conclusion: After accounting for US demography and reduced AF prevalence, A-A patients with AF are referred for ablation substantially less frequently than C-A patients (three times less frequently than anticipated). This referral bias is particularly remarkable in our cohort given that A-A’s comprise 43% of the population of our medical center’s county. The reduced procedural efficacy in the A-A patients may be due to a higher prevalence of comorbid medical conditions in patients referred for ablation. PO04-03 TELEMEDICINE WOUND CHECK BY EMAIL Staci M. Kaczor, MSN, NP, RN, Brynn E. Dechert, NP, Brian Armstrong, RN, Martin J. LaPage, MD, FHRS, Gerald A. Serwer, MD, FHRS and David J. Bradley, MD. C.S. Mott Children’s Hospital, Ann Arbor, MI Introduction: Surveillance for wound infections is an important part of follow-up after pacemaker and ICD implantations. It is a convention at many referral centers to arrange for a local physician to evaluate an implant wound 7-14 days post implant. This may result in inappropriate treatment or confusion on the part of a provider who has not been involved with the procedure. We recently instituted a two-week wound follow-up using an Emailed digital image in place of an in-person visit locally. Methods: We reviewed our early experience with the telemedicine wound check by Email. Patient photographs and other clinical data were reviewed. Results: Ten patients submitted images a mean 12 (range 1-22) days post device implant. There were 6 pacemakers and 4 ICDs. Based on the submitted images, 9 were considered reassuring, and 1 was asked to present for evaluation. The one seen in person underwent incision and drainage in 1, and S. aureus was recovered on culture. Eight patients required no intervention. One patient on anticoagulation therapy had an acceptable image but reported bloody drainage, and was advised to place a pressure dressing. Despite this process 2 patients were started empirically on antibiotics by local providers. Patients’ residences were a mean 81 (range 5-254) miles from the implanting center. Conclusion: Based on the very good quality of patient digital photos we consider telemedicine wound checks a viable means of device follow-up. We propose the use of this new method of photo follow-up for pacemaker and ICD implantation wound care. The images appear to be diagnostic and the process is a significant convenience to patients who reside a distance from the implanting center.
Transcript
Page 1: PO04‐01 to PO04‐136

S291Poster Session IV

POSTER PO04: Poster Session IVFriday, May 10, 20139:30 a.m. - noon

PO04-01

COMPRESSION BANDAGES DO NOT REDUCE GROIN HEMATOMAS AFTER AF ABLATIONCherie Jaynes, BSN, Judith Hildreth, BSN, Ken Hopper, MBA, Antonio Moyeda, CVT, Sanjiv M. Narayan, MD, PHD, FHRS, Marian Holland, MD and David E. Krummen, MD, FHRS. VA San Diego Healthcare System, San Diego, CAIntroduction: Many strategies have been used to prevent groin bleeds after AF ablation, that is a potentially significant complication. We hypothesized that pressure dressings in the acute post-procedural period, that may cause discomfort and precipitate movement and bleeding upon removal, may not reduce the incidence of groin hematomas compared to manual compression alone.Methods: We performed a non-randomized open-label 2:1 comparison of no pressure dressing (group 2) vs pressure dressing (group 1) in 78 AF patients (age 62±10years), using a case-cohort design. All patients underwent AF ablation via femoral venous access, during uninterrupted warfarin, with intra-procedural heparin (target ACT 350-400 seconds), reversal of heparin with protamine and manual compression for 10-20 minutes.Results: A total of 19 cases of groin bleeds were documented in the first week post ablation, none of which required surgical repair nor transfusion. In Group I, 6/26 patients had bleeds, while in group II, 13/52 had bleeds (p=0.85). There was also no difference in the incidence of early bleeds (overnight, <8 hours) of 3/26 vs 8/52 (p=0.65). Notably, complaints of groin symptoms (pain or discomfort) was higher for patients in group I (compression bandage discomfort) than in group II (p<0.05). Groups did not differ in weight (104±23vs 104±21 kg, p=NS), height (1.8±0.09 vs 1.8±0.07 m, p=NS), or INR on the procedural day (2.5±0.5 vs 2.3±0.6, p=NS). Two patients were Jehovah’s witnesses.Conclusion: In this 2:1 open label case-cohort study after AF ablation, compression dressings often caused discomfort yet did not reduce the incidence of groin bleeds compared to manual pressure alone in patients with a wide range of heights and weights. These results may impact post-procedural management of AF ablation.

PO04-02

NEGATIVE ATRIAL FIBRILLATION ABLATION REFERRAL BIAS IN AFRICAN-AMERICANSAllyson Prasad, MSN, CRNP, Erica Zado, PA, Gregory Supple, MD and Mathew D. Hutchinson, MD. University Of Pennsylvania, Philadelphia, PAIntroduction: The prevalence of atrial fibrillation (AF) in African-Americans (A-A) is reported to be 40% lower than in Caucasian-Americans (C-A). Although A-A’s comprise 12% of the US population, little is known about their referral patterns or response to atrial fibrillation (AF) ablation.Methods: We examined 2482 patients referred to our institution for a first AF ablation between 11/2000-1/2012 with self-identified racial groups. We compared baseline demographics and procedural outcome in self-identified A-A vs. C-A patients.Results: From the original cohort, 2.5% identified as A-A and 95% identified as C-A. A-A patients more frequently had hypertension, diabetes, left ventricular cardiomyopathy, and

clinical heart failure (Table). At a mean follow-up of 718 days, A-A achieved freedom from AF less frequently than C-A (52% vs. 66%, p=0.04).Conclusion: After accounting for US demography and reduced AF prevalence, A-A patients with AF are referred for ablation substantially less frequently than C-A patients (three times less frequently than anticipated). This referral bias is particularly remarkable in our cohort given that A-A’s comprise 43% of the population of our medical center’s county. The reduced procedural efficacy in the A-A patients may be due to a higher prevalence of comorbid medical conditions in patients referred for ablation.

PO04-03

TELEMEDICINE WOUND CHECK BY EMAILStaci M. Kaczor, MSN, NP, RN, Brynn E. Dechert, NP, Brian Armstrong, RN, Martin J. LaPage, MD, FHRS, Gerald A. Serwer, MD, FHRS and David J. Bradley, MD. C.S. Mott Children’s Hospital, Ann Arbor, MIIntroduction: Surveillance for wound infections is an important part of follow-up after pacemaker and ICD implantations. It is a convention at many referral centers to arrange for a local physician to evaluate an implant wound 7-14 days post implant. This may result in inappropriate treatment or confusion on the part of a provider who has not been involved with the procedure. We recently instituted a two-week wound follow-up using an Emailed digital image in place of an in-person visit locally.Methods: We reviewed our early experience with the telemedicine wound check by Email. Patient photographs and other clinical data were reviewed.Results: Ten patients submitted images a mean 12 (range 1-22) days post device implant. There were 6 pacemakers and 4 ICDs. Based on the submitted images, 9 were considered reassuring, and 1 was asked to present for evaluation. The one seen in person underwent incision and drainage in 1, and S. aureus was recovered on culture. Eight patients required no intervention. One patient on anticoagulation therapy had an acceptable image but reported bloody drainage, and was advised to place a pressure dressing. Despite this process 2 patients were started empirically on antibiotics by local providers. Patients’ residences were a mean 81 (range 5-254) miles from the implanting center.Conclusion: Based on the very good quality of patient digital photos we consider telemedicine wound checks a viable means of device follow-up. We propose the use of this new method of photo follow-up for pacemaker and ICD implantation wound care. The images appear to be diagnostic and the process is a significant convenience to patients who reside a distance from the implanting center.

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S292 Heart Rhythm, Vol. 10, No. 5, May Supplement 2013

PO04-05

EARLY RECURRENCE POST AF ABLATION DOES NOT APPEAR TO BE ASSOCIATED WITH LATE RECURRENCESJessiciah M. Windfelder, MSN, ACNP, Nazem Akoum, MD, Heather Margetts, MD, Chankevin Tek, BSc, Sara Hamele, MSN, CRNP, Alex Gouttsoul, PA and Nassir Marrouche, MD, FHRS. Comprehensive Arrhythmia Research And Management (CARMA) Center, Salt Lake City, UTIntroduction: Early recurrence post AF (ERAF) ablation is thought to be associated with low success rates. We studied the relationship between ERAF and late recurrence post AF ablation.Methods: A retrospective analysis of 113 patients who underwent AF ablation was performed. University of Utah post AF ablation surveillance protocol includes 60-day cardiac event monitoring with autotrigger device. It also includes 8-day holter monitoring at 3, 6 and 12 months post ablation. Recurrences were documented as early (first 90 days post ablation) or late (after 90 days) up to one year post ablation.Results: A total of 113 patients were included. Mean age 66 +/-12. 60% males. A total of 87 (77%) patients had documented ERAF on autotrigger event monitors during the first 60 days post AF ablation. A total of 21 (18.5%) patients had late AF recurrences. 41.6% patients were discharged on Antiarrhythmic drugs (AAD). 58.4% without AAD (p 0.7). 36.5% of recurrences required treatment with either medication change or DC cardioversion to maintain sinus rhythm. See figure.Conclusion: Our preliminary findings demonstrate that ERAF is highly prevalent post AF ablation. Even though ERAF does not predict long-term recurrences, it requires treatment in 1/3 of patients. Prophylactic treatment with AAD immediately follow ablation does not prevent ERAF.

PO04-06

RADIOLOGY UTILIZATION IN PATIENTS WITH AND WITHOUT PACEMAKERS, EVIDENCE OF A GAP IN CARECandace Gunnarsson, EdD, Micheal P. Ryan, MS, Mintu P. Turakhia, MD, Steven D. Wolff, MD, PhD, Andrea L. Swain, MBA, Sarah A. Mollenkopf, MPH and Matthew R. Reynolds, MD. S2 Statistical Solutions Inc., Cincinnati, OH, Stanford University School of Medicine, Palo Alto, CA, Carnegie Hill Radiology, New York, NY, Medtronic, Inc, Mounds View, MN, Harvard Clinical Research Institute, Boston, MAIntroduction:Up to 75% of pacemaker patients will need MRI scan over the lifetime of their device, but may receive other radiology tests due to pacemaker/MRI incompatibility. MRI is critical for certain diagnoses, including Stroke/TIA. We examined the differences in radiology use between patients with and without pacemakers, at time of stroke/TIA.

PO04-04

COMMON QTC FORMULAS OVERESTIMATE THE QT/RR IN ATRIAL FIBRILLATION: IMPLICATIONS FOR DOFETILIDE LOADINGKimberly D. Guise, NP, Leonard Gettes, MD, Irion Pursell, RN and Eugene H. Chung, MD, FHRS. UNC Heart and Vascular, Chapel Hill, NCIntroduction: In patients with atrial fibrillation (AF), assessing the QT interval is difficult due to the wide ranges of heart rates and RR intervals. Overestimation of the QTC can result in premature dose reduction and decreased efficacy of dofetilide. Commonly used QTC formulas were based on the linear relationship between QT and RR in sinus rhythm. We examined the QT/RR and the performance of the Bazett and Friderica formulas in a cohort of patients undergoing dofetilide loading for persistent AF.Methods: We studied 10 consecutive patients admitted for dofetilide loading. The last ECG while still in AF (but after at least one dose) was examined: 9 or 10 (if feasible) RR and corresponding QT intervals for each patient were recorded. The mean QT and RR intervals and the corresponding QTC’s by the Bazett and Friderica formulas were calculated. These were compared to the post CV QTC in sinus rhythm.Results: The (mean QT)/(mean RR) ratio was nonlinear, and no QT was over 500 msec (Fig A). Bazett’s corrected the QT for all 10 patients to an approximate QTC of 460 msec (Fig B) and overestimated 7 of the post CV QTCs and did not predict 3 post CV QTCs that were over 500 msec (Fig D). The trend with the Friderica correction (Fig C) most correlated with the post CV QTC trend but did not predict the 2 patients with prolonged post CV QTCs.Conclusion: The relationship between QT and RR is complex in AF and conventional correction formulas may not be appropriate in predicting the post CV QTC in patients receiving dofetilide. Our work will continue to focus on optimizing antiarrhythmic drug loading in patients with AF.

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S293Poster Session IV

study period. On necropsy, all devices were noted to be securely implanted in the RV apex without extrusion of helix beyond the RV wall. Besides mild endocardial fibrosis at the right ventricular apex surrounding the distal portion of the LCP, there were no other visible cardiac abnormalities.Conclusion: We demonstrate i) the feasibility of implantation, ii) efficacy and, iii) safety of a novel leadless cardiac pacemaker implanted in the RV apex.

PO04-08

RIGHT VENTRICULAR PACING AS BACKUP TO HIS BUNDLE PACING TO MINIMIZE BATTERY DRAINAGEClarence Khoo, MD, Matthew Bennett, MD, John Lemaitre, MD, Santabhanu Chakrabarti, MD, Marc Deyell, MD, Jason Andrade, MD, Andrew Krahn, MD and Stanley Tung, MD. University of British Columbia, Vancouver, BC, CanadaIntroduction: His-bundle pacing (HBP) is an alternative to right ventricular pacing (RVP) in patients with permanent atrial fibrillation (AF) and slow ventricular rate. RVP-associated ventricular dysfunction may be prevented, at the cost of more rapid battery drainage due to higher capture thresholds of HBP. We report a series of patients where HBP was performed with back-up RVP.Methods: Seven patients with permanent AF and complete heart block (mean 79 yrs, 6 Medtronic Adapta DR, 1 Medtornic Protecta DR) at our institution had successful implantation of a HBP lead (Medtronic 3830) connected to the atrial port. An RV lead was also implanted and connected to the ventricular port. The devices were programmed to DDDR, DDIR or Managed Ventricular Pacing® (MVP; AAIR - DDDR) mode with HBP output at <2x capture threshold. RVP output was kept at 2-3x capture threshold.Results: The HBP QRS complexes were identical to the intrinsic QRS in all patients (Figure 1A, B). Backup RVP could be demonstrated with loss of HBP capture during atrial channel (HBP) capture threshold testing (Figure 1B). This allowed for a mean HBP output of 3.4 ± 1.2 V at 0.47 ± 0.10 msec, representing a safety margin of 1.7 ± 0.7x capture threshold. Total backup RVP pacing was <1% at follow up in all patients. There was a trend towards improved left ventricular ejection fraction (LVEF) from 45 ± 19% to 52 ± 16% (p = 0.62) after a mean follow-up of 40 ± 28months.Conclusion: The use of MVP for HBP allows lower than conventional output for HBP while maintaining reliable back up RVP. This allows for safe and effective delivery of HBP while minimizing battery depletion.

Methods:Using administrative health claims data from the MarketScan® Commercial and Medicare databases from Truven Health Analytics, Inc., we identified patients with and without pacemakers who had continuous health plan enrollment in calendar year 2010. Pacemaker and non-pacemaker cohorts were defined by presence of a code for an implant before 1/1/2010 or absence of a code through 12/31/2010. These cohorts were then propensity matched in a 1:1 ratio on age, gender and comorbid conditions. We then compared the proportions of matched patients using various radiology imaging modalities and also evaluated a subgroup with stroke/TIA within 3 days of radiology testing.Results:27,580 pacemaker patients were matched to the same number of non-pacemaker patients. The number of radiology procedures per patient for those with radiology (approximately 80% of patients) was similar for the pacemaker and non-pacemaker cohorts (5.07 and 5.15, respectively). The most frequently occurring radiology procedure for both groups was ultrasound/echo/Doppler (>36%), followed by X-ray/fluoroscopy (29%, 28%), CT/CTA (27%, 23%), nuclear (7%, 6%), and MRI/MRA (0%, 6%). For the stroke/TIA subgroup (n=2204, 4%) a condition where MRI is the preferred diagnostic, 49% of non-pacemaker patients underwent MR imaging within ±3 days of the diagnosis (vs 0.3% of pacemaker patients). Non-pacemaker patients had 4.5 imaging procedures on average within ±3 days of their stroke/TIA diagnosis, compared with 3.5 for pacemaker patients (P<.0001).Conclusion:In our matched cohort of pacemaker and non-pacemaker patients, there was no difference in overall utilization of radiology tests. Patients with stroke/TIA who have pacemaker implants do not receive MRIs and also receive statistically significantly less imaging at the time of stroke/TIA diagnosis.

PO04-07

FEASIBILITY AND EFFICACY OF PERCUTANEOUSLY DELIVERED LEADLESS CARDIAC PACING IN AN IN VIVO OVINE MODELJacob S. Koruth, MD, Alexander Khairkhahan, MSc, David A. Ligon, MEng, Frederick St Goar, MD, Randall Lee, MD, PhD, Leonardo Ribeiro, MD, Srinivas Dukkipati, MD, Petr Neuzil, MD, PhD and Vivek Y. Reddy, MD. Mt Sinai Medical Center, New York, NY, Nanostim, Inc., Sunnyvale, CA, Fogarty Institute for Innovation, Mt View, CA, UCSF School of Medicine, San Fransico, CA, Na Homolce, Prague, Czech RepublicIntroduction: A novel leadless pacemaker has been developed to deliver pacing current to the ventricle. In this study, we examined the feasibility and safety of this percutaneously-delivered leadless cardiac pacemaker (LCP) in an in vivo ovine model.Methods: 11 sheep underwent percutaneous venous access with an 18Fr sheath. The LCP was implanted in the RV apex using a deflectable sheath under fluoroscopic guidance. Non-invasive follow-up was serially conducted to assess thresholds and animals were euthanized at 90 days (one animal was euthanized at 22 days for an unrelated illness) and the hearts were examined at necropsy.Results: The LCP needed repositioning from its initial location in 3/10. Mean pacing (pulse width 0.4ms) and sensing thresholds at implant were-1.2±0.7V and 9.1±3.9mV, and at 90 days- 0.7±0.2V and 8.1±3.9mV respectively. There were no device dislodgements or embolizations. Based on a predictive model (using on-board cell charge meter, programmed settings, and event counters) the calculated longevity with 100% pacing at 60 bpm with an output of 2.5 V at 0.4 ms was 8.2 (7.4-8.5) yrs. All implanted LCPs demonstrated communication with the external programmer and there were no device failures throughout the

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S294 Heart Rhythm, Vol. 10, No. 5, May Supplement 2013

PO04-10

REMOTE MONITORING IS ASSOCIATED WITH REDUCTION IN MORTALITY IN PACEMAKER PATIENTSRanjan K. Thakur, MD, FHRS, Brett Faulknier, DO, Jeffery D. Snell, BA, Nirav Dalal, MS, MBA and Mark Richards, MD, PhD. Sparrow Thoracic Cardiovascular Institute, Lansing, MI, WVU Physicians of Charleston, Dept of Electrophysiology, Charleston, WV, St. Jude Medical, Sylmar, CA, Northwest Ohio Cardiology Consultants, Toledo, OHIntroduction: The impact of remote monitoring (RM) on clinical outcomes of pacemaker (PM) patients (pts) is not well understood. The purpose of this analysis is to compare outcomes of PM pts enrolled in the Merlin.net™ RM service (RMS) to pts undergoing only in-clinic follow-up.Methods: The BRADYCARE Registry is a multicenter registry of pts with a St Jude Medical PM followed every 6 months for ≥1 year post-implant. At enrollment, baseline pt characteristics and histories were collected. In this analysis, de novo PM pts were grouped into an RMS group, who had in-clinic and remote follow-ups, and a No RMS group that had only in-clinic follow-ups. RMS schedules were set at the discretion of the managing clinic. Hospitalizations and deaths were monitored. A Cox proportional hazards regression model was performed and all-cause mortality for the two groups compared.Results: There were 1,492 (59%) pts followed for 12.4±3.6 months in RMS and 1,018 pts in No RMS followed for 12.3±3.6 months (P >0.05). Baseline and outcome pt characteristics are shown in the Table, where NS denotes P >0.05 and S denotes P <0.05. All-cause mortality was lower for RMS vs. No RMS (37/K pt-yr vs. 80/K pt-yr, P<0.01). After adjusting for significant covariates, the hazard ratio for death was higher for No RMS at 1.9 (95% CI 1.35 - 2.69, P <0.01).Conclusion: In this contemporary pacemaker registry, remote monitoring was associated with a reduction in one-year mortality post-implant, even after adjusting for associated comorbiditites. The reasons for this marked reduction are the focus of further investigation.Baseline & Outcome Patient Characteristics

RMS No RMS P-valueN 1,492 1,018Age 75±10 76±11 NSGender-Male 834 (55.9%) 539 (52.9%) NSAV-Block 360 (24.1%) 260 (25.5%) NSSSS 983 (65.9%) 667 (65.5%) NSPts Hospitalized 224 (15.0%) 148 (14.5%) NSMean Days in Hosp. 0.82 (3.8) 0.83 (3.6) NSDeaths 58 (3.9%) 84 (8.3%) S

PO04-11

INCIDENCE OF DEFIBRILLATOR SHOCKS AFTER ELECTIVE GENERATOR EXCHANGE FOLLOWING UNEVENTFUL FIRST BATTERY LIFEFaisal M. Merchant, MD, Paul Jones, MS, Scott Wehrenberg, MS, Michael S. Lloyd, MD and Leslie A. Saxon, MD. Emory University School of Medicine, Atlanta, GA, Boston Scientific Corporation, St. Paul, MN, University of Southern California, Los Angeles, CAIntroduction: A significant number of ICD patients do not experience shocks after ICD implant. Elective generator exchange (GE) has been associated with increased risk of infection and ICD lead failure. There is a paucity of contemporary data reporting on shock incidence with replacement devices.Methods: The ALTITUDE study group was designed to analyze the LATITUDE® remote monitoring system (Boston Scientific)

PO04-09

CHADS2 AND CHA2DS2-VASC SCORES FOR PREDICTION OF NEW ONSET OF AF IN PACEMAKER PATIENTS: RESULTS FROM THE BRADYCARE TRIALMark Richards, MD, PhD, Brett Faulknier, DO, Yelena Nabutovsky, MS and Ranjan Thakur, MD, MPH, FHRS. NWOCC, Toledo, OH, WVU Physicians of Charleston Department of Electrophysiology, Charleston, WV, St. Jude Medical, Sunnyvale, CA, Thoracic Cardiovascular Healthcare Foundation, Lansing, MIIntroduction: CHADS2 and CHA2DS2-VASc scores are used to estimate stroke risk in patients (pts) with atrial fibrillation (AF). This study compared the efficacy of these scores to predict new AF in pacemaker pts without a prior history of documented AF.Methods: Data from all non-CRT pacemaker pts without a prior history of AF from BRADYCARE, a multicenter observational study of pacemaker pts, were included in this analysis. CHADS2 and CHA2DS2-VASc scores were determined based on information at enrollment. AF events were monitored and reported via scheduled and unscheduled follow-up (FU) visits, at hospitalizations, and through device-detected AF events (duration >6 hours, atrial rate >180 bpm). Non-parametric maximum likelihood estimation of the survival function, log-rank test, and Weibull proportional hazards models for interval-censored data were used to determine the effect of CHADS2 and CHA2DS2-VASc scores on event-free survival.Results: Data were available for 1157 pts (age 73.0 ±12.0 years, 56.4% male, CHADS2 score = 1.9 ± 1.2, CHA2DS2-VASc score = 3.6 ± 1.6). During a mean FU of 21.5 ± 4.7 months, 243 pts developed new AF. CHADS2 score ≥1 and CHA2DS2-VASc score ≥ 2 predicted the occurrence of new AF (p ≤ 0.05, Table) with similar efficacy.Conclusion: CHADS2 and CHA2DS2-VASc scores predict the occurence of new AF in pacemaker pts with comparable efficacy. Close monitoring of pts with higher risk scores may lead to early detection of AF, earlier use of anticoagulants, and increased stroke prevention.

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S295Poster Session IV

ICD patients was not associated with a reduction in risk for ICD therapies. Recovery of LV function should not obviate the need of an ICD at the time of pulse generator replacement.Table 1: Comparison of ICD therapies in patients with and without LVEF improvement

Improvement in LVEF ≥ 40%(N = 78)

No Improvement in LVEF(N = 179)

P value

Rate of Appropriate Therapies (per 100 patient-year) 13 ± 39 20 ± 71 0.63No. of Patients with Appropriate Therapies 12 (15.4%) 32 (17.9%) 0.72Rate of Inappropriate Therapies (per 100 patient-year) 26 ± 122 13 ± 44 0.90No. of Patients with Inappropriate Therapies 10 (12.8%) 22 (12.3%) 1.00

Mortality 9 (11.5%) 26 (14.5%) 0.13

PO04-13

EXERCISE TREADMILL TESTING IS A USEFUL TOOL FOR ELIMINATING T WAVE OVERSENSING IN PATIENTS WITH SUBCUTANEOUS CARDIOVERTER DEFIBRILLATORSMarshall W. Winner, III, MD, Troy Rhodes, MD, Charles Love, MD, German Kamalov, MD, Jose Torres, MD, Raul Weiss, MD and Ismail Hamam, MD. Wexner Medical Center at The Ohio State University, Columbus, OHIntroduction: Subcutaneous cardioverter defibrillators (S-ICDs) eliminate the need for intravascular leads; however, appropriate sensing without a transvenous lead has been called into question. Patient activity may result in morphological changes in the QRS and T-wave leading to oversensing by the S-ICD. Exercise Treadmill Testing (ETT) may be a useful tool to evaluate these changes.Methods: We performed a retrospective chart review of all pts who received an SICD at our institution between 4/10 and 4/11. We analyzed all patients that had detection or therapy for T-Wave oversensing (TWO) by the S-ICD.Results: Forty-one pts had an S-ICD implanted during the study period (47.4 +/- 14.9 years; 18 (44%) female). Six (15%) patients received inappropriate shocks for TWO. ETT was performed in 5 of 6 patients. Vector reprogramming was successful in 3 of 5 (60%) patients undergoing ETT. One patient’s S-ICD was removed for the lack of appropriate vector programmability and one patient had the S-ICD turn off due to terminal lung cancer. One patient’s sensing vector was reprogrammed without the aid of ETT. During a mean follow-up period of 24 months only 1 patient received a shock from T-wave oversensing after reprogramming guided by ETT.Conclusion: TWO is a common cause of inappropriate shocks in patients with an S-ICD. ETT is a helpful tool in the selection of the appropriate sensing vector and elimination of TWO. In a single patient ETT lead to S-ICD extraction.

to evaluate patient outcomes across the United States. Patients undergoing elective GE (n=35954) who transmit data remotely were analyzed to determine the incidence of ICD shocks after GE. Kaplan-Meier analysis was used to assess time-dependent risk of ICD shocks.Results: A total of 23735 patients (66%) did not experience a shock with the first ICD (Group A) and 12219 (34%) received at least one shock (Group B). Group A patients were older and more often female (71 versus 68 years, 71% versus 78% male, p<. 001) Over an average follow up of 1.9 ± 1.2 years after GE, the proportion of patients with shocks and risk of ICD shocks was lower in Group A (11% vs. 30%, RR 0.37, 95% CI 0.35-0.39, p < 0.001, Figure). The time to first shock after GE was greater for Group A compared to Group B (435 versus 319 days, p<0.001). Shocks for heart rates >200 bpm were observed in 10% of Group A patients at 3 years and 18% at 5 years after GE.Conclusion: In this large cohort of ICD patients implanted across the U.S., two thirds do not receive ICD shock therapy prior to GE, yet the cumulative risk of shock after GE is 35.9% at five years. For those that experience shocks with the initial device, risk of further shocks after GE is even higher. These data support GE in patients after ICD implant.

PO04-12

THE RATE OF APPROPRIATE IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR THERAPY REMAINS HIGH DESPITE LEFT VENTRICULAR FUNCTION RECOVERYClarence Khoo, MD, John A. Yeung-Lai-Wah, MBChB and Matthew Bennett, MD. University of British Columbia, Vancouver, BC, CanadaIntroduction: Reduced left ventricular ejection fraction (LVEF) remains the predominant indication for insertion of an implantable cardioverter-defibrillator (ICD) for the primary prevention of ventricular arrhythmias. It is unclear if LVEF improvement with heart failure therapy lowers the risk of ventricular tachyarrhythmia. Our study seeks to determine the usefulness of ICD in patients with an improvement in LVEF.Methods: 257 consecutive primary prevention subjects who underwent ICD implantation between 1998 and 2008 with an initial LVEF < 35% and follow-up of ≥ 12 months were included. Recovery of LV function was defined as an LVEF increase to ≥ 40%Results: LVEF improved in 78 patients from 29 ± 7% to 48 ± 9% after a mean of 360 ± 471 days. Mean age was 60 ± 12 years, 73% male, and 53% with an ischemic cardiomyopathy. The 179 patients without LVEF recovery were more likely male (89%) and had a lower initial LVEF (25 ± 6%). Table 1 compares patients with and without improvement in LVEF. The rate of ICD therapies (both appropriate and inappropriate) was unchanged despite improvement of LVEF. Multivariate analysis demonstrated that predictors of appropriate ICD therapies included ischemic cardiomyopathy (OR 3.49), atrial fibrillation (OR 3.75) and beta blocker use (OR 0.35); LVEF improvement was not a predictor.Conclusion: Improvement of LVEF ≥ 40% in primary prevention

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PREDICTORS OF DEATH WITHOUT PRIOR APPROPRIATE ICD INTERVENTION: INSIGHTS FROM THE MADIT-CRT TRIALPasquale Santangeli, MD, Anne-Christine Ruwald, MD, Paul J. Wang, MD, Scott McNitt, PhD, Amin Al-Ahmad, MD, Wojciech Zareba, MD, PHD, FHRS and Arthur J. Moss, MD. Stanford University School of Medicine, Stanford, CA, University of Rochester Medical Center, Rochester, NYIntroduction: The occurrence of death without prior appropriate ICD intervention has not been previously investigated.Methods: Using multivariate Cox analysis and best subset regression we identified predictors of death without any prior appropriate ICD intervention in the MADIT-CRT trial. A risk score to identify these patients was created from the rounded hazard ratios (HR).Results: Death without prior appropriate ICD therapy occurred in 132 out of 1820 patients (7%), and was predicted by 6 factors: creatinine ≥ 1.4 mg/dl (HR=2.91 [2.03-4.17], p<0.001), NYHA class III within 3 month (HR=2.15 [1.36-3.39], p=0.001), ejection fraction ≤ 25 % (HR=2.13 [1.39-3.28], p<0.001), diabetes (HR=1.60 [1.12-2.28], p=0.010), age ≥ 65 years (HR=1.90 [1.27-2.84], p=0.002), and CRT-D therapy in the absence of left bundle brand block (LBBB) (HR=1.78 [1.16-2.74], p=0.009). When applying the risk score derived from the HRs of the predictors (Figure), the cumulative risk of death without prior appropriate ICD therapy at 4 years was 2%, 6% and 16%, respectively for increasing risk score tertile. For each risk score tertile the risk of death in patients without prior appropriate ICD therapy increased by a factor 2.6 (HR=2.56 [1.97-3.32], p<0.001).Conclusion: High-risk comorbidities and more advanced heart failure increase the risk of death without prior appropriate ICD intervention. A simple risk score comprising 6 clinical factors can be used to identify these patients.

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CLINICAL EVALUATION OF REMOTE MONITORING WITH DIRECT ALERTS TO REDUCE TIME FROM EVENT TO CLINICAL DECISION: THE REACT STUDY RESULTSJanet M. McComb, MD, Wilfried Mullens, PhD, Maurizio Landolina, MD, Ignacio Fernandez-Lozano, PhD, Giancarlo Speca, MD, Ralph Bosch, MD, Burkert Pieske, PhD, Dominique Blommaert, PhD, Peter Mortensen, MD, Antonio Marco Willem Alings, PhD and Kai Nyman, MD. Freeman Hospital, Newcastle-upon-Tyne, United Kingdom, Ziekenhuis Oost Limburg, Genk, Belgium, Policlinico S. Matteo, Pavia, Italy, Hospital Universitario Puerta de hierro, Madrid, Spain, Ospedale G. Mazzini di Teramo, Teramo, Italy, Praxis fuer Kardiologie - Partnergesellschaft, Ludwigsburg, Germany, University Klinikum Abteilung für Kardiologie, Graz, Austria, CHU Mont Godinne,

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FINAL RHYTHM OF DECEASED ICD PATIENTS: CAN WE RETRIEVE INFORMATION REGARDING MODE OF DEATH FROM POST MORTEM ICD INTERROGATION?Nils Gosau, MD, Stephan Willems, MD, Daniel Steven, MD, Boris Hoffmann, MD, Arian Sultan, MD, Helge Servatius, MD, Iris Wilke, MD and Klaus Püschel, MD. Department of Cardiology/Electrophysiology, Hamburg, Germany, University of Hamburg, Department of Forensic Pathology, Hamburg, GermanyIntroduction: Due to their extensive capabilities of arrhythmia diagnostics ICDs might give clues towards the clinical state of a dying patient even long after his death. Furthermore it is the task of an ICD to prevent a sudden and otherwise virtually unpreventable death. This makes the question why the patient actually died all the more interesting.Methods: From January of 2009 until November of 2012 an autopsy was performed on 34 deceased ICD patients (m:f 26:8, 76%:24%, mean age 68 y.) at our institution by forensic or clinical pathologists. The ICDs were explanted and interrogated.Results: Inadequate therapies (e.g. due to Atrial Fibrillation) at time of death were not noticed. Concluding from clinical data and autopsy 3 pts. (9%) died from noncardiac death, 5 from acute coronary syndrome (ACS, 15%), of which 2 (6 or 40% resp.) presented shockable ventricular arrhythmia (VT/VF) at time of death. 10 pts. (29%) died from heart failure without ACS or VT/VF. 12 pts. (35%) showed VT/VF at time of death, all were treated with ATP and/or DC shock. Primary arrhythmia was VT or VF in equal shares (6 pts. or 18% each). 2 pts. (6%) developed pulseless electrical activity (PEA) while ACLS was performed after successful DC shocks. An adequate arrhythmia did not lead to sufficient ICD therapy in 4 pts. (12%): in one pt. each, ineffective therapy due to lead defect and insufficient detection due to undersensing occurred, a suggestive therapy was held back by the respective software algorithm in 2 pts.Conclusion: Post mortem ICD interrogation gives us further insight towards the actual mode of death of a patient. Since possibly erroneous ICD performance was observed in this scenario, post mortem ICD interrogation should be performed more often to gain more experience concerning this subject.

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Results: Fifty-eight patients (52 male, 90%) with a mean age of 46±12 years were included. Circumstances of diagnosis were aborted SD (n=4; 7 %), syncope (n=25; 43%) and systematic ECG or familial screening (n=29; 50%). Thirty-seven patients had a cardioverter-defibrillator (ICD) implantation. Reasons for ICD implantation were prior cardiac arrest (n=4), syncope (n=17) including vagal syncope (n=2), sustained VA induced during EPS (n=14) or family history of SD (n=2). All patients with inducible ventricular fibrillation (n=17) or ventricular tachycardia (n=2) during EPS had received an ICD. During a mean FU of 61±47 months, VA occurred in 7 patients (ICD shocks n=5, anti-tachycardia pacing n=2). All of them were previously symptomatic (syncope n=6, aborted SD n=1). Five of these patients had spontaneous type 1 ECG and 2 had drug-induced type 1 ECG. The only predictor of VA was the presence of previous symptoms (p=0.004). None of the asymptomatic BS patients experienced appropriate shock, syncope or SD during FU. Fifteen patients (41%) experienced 24 ICD-related complications. The most frequent complication was lead dysfunction (n=12).Conclusion: In BS patients from two tertiary centers in Quebec, appropriate ICD therapy occurred in symptomatic patients. None of the asymptomatic patients had an arrhythmic event after a mean FU of 61 months.

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COMBINED IDENTIFICATION OF SEPTAL FLASH AND MYOCARDIAL SCAR BY CARDIAC MAGNETIC RESONANCE IMPROVES PREDICTION OF CRT RESPONSEManav Sohal, MBBS, Sana Amraoui, MBBS, Zhong Chen, MBBS, Eva Sammut, MBBS, Jaswinder Gill, MD, MBBS, Michael Cooklin, MD, MBBS, Mark O.Neill, DPhil, MD, FHRS, Matt Wright, MBBS, PhD, Reza Razavi, MD, MBBS, Gerry Carr-White, MBBS, PhD and Christopher A. Rinaldi, MD, MBBS. King’s College London, London, United Kingdom, Hôpital Cardiologique du Haut-Lévèque, Bordeaux, France, Guy’s and St. Thomas’ NHS Foundation Trust, London, United KingdomIntroduction:Septal flash (SF) describes early inward motion of the ventricular septum in patients with (LBBB) and correction corresponds to increased response to cardiac resynchronization therapy (CRT). SF has traditionally been assessed by echocardiography. We sought to determine if cardiac magnetic resonance (CMR) imaging could identify SF and if the additional assessment of scar would improve the ability of CMR to predict CRT response.Methods:Fifty-two patients with LBBB and heart failure underwent prospective CMR scanning prior to CRT implant. Short-axis and 4-chamber long axis steady-state free precession (SSFP) cine images with temporal resolution of 30ms were analyzed for the presence of SF by visual inspection and with the use of endocardial contour tracking software (TomTec; Munich). The presence and extent of myocardial scar was assessed using delayed-enhancement gadolinium imaging during CMR. The association between SF, scar and reverse remodeling (RR) at 6 months was explored.Results:RR to CRT at 6 months was 52%. CMR-derived SF was identified in 24 (46%) patients. The prevalence of SF when assessed using echocardiography was 50%.RR was significantly more likely in the group with SF (88% vs 21%; P150ms and absence of scar as predictors of RR, SF was the only independent predictor.Conclusion:SF can be assessed by CMR and predicts increased response to CRT. The additional value of CMR is the assessment of scar. The presence of SF with no scar is a highly specific predictor of CRT response.

Montgodinne, Belgium, Aarhus University Hospital Skejby, Aarhus, Denmark, Amphia Ziekenhuis, Breda, Netherlands, Keski-Suomo Hospital, Jyväskylä, FinlandIntroduction: Modern implantable cardiac devices offer a range of monitoring functions designed to detect clinically relevant events occurring outside the hospital. Remote monitoring offers an opportunity to reduce the time between the occurrence of clinically significant events and the time to intervene.Methods: The REACT study was a prospective, randomized, parallel, open trial that enrolled patients (pts) with St. Jude Medical ICDs or CRT-Ds. Pts were randomized to remote monitoring with Direct Alerts ON or standard in-clinic visits (OFF). The primary endpoint was the time between detection of a clinical event by the device (the time when the device triggered an alert) and the subsequent clinical decision by a physician in response to the alert; this was evaluated on an intention-to-treat analysis. If a pt incurred multiple events in advance of a clinical decision, only the first event was tallied.Results: Enrollment included 220 pts between March 2010 and February 2011 in 28 centers (11 countries) that were followed for 12 months. Clinical events occurred in 66 patients, (42 ON and 24 OFF). Log rank test showed that time to clinical decision in the ON group was significantly shorter than that in the OFF group (p=0.008, Figure). The time between an event and a clinical decision was 8.0±18.1 days (ON) vs 18.6±33.2 (OFF).Conclusion: The time between the occurrence of a clinical event and a clinical decision in response to the event was significantly shorter when using the Direct Alerts notification via remote monitoring compared to standard in-clinic visits.

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BRUGADA SYNDROME: THE QUEBEC EXPERIENCEAntoine Roux, MD, Isabelle Nault, MD, Jean Champagne, MD, Mario Talajic, MD, Paul Khairy, MD, PhD, Denis Roy, MD, Laurent Macle, MD, Marc Dubuc, MD, Peter Guerra, MD, Bernard Thibault, MD and Lena Rivard, MD. University Hospital G. Montpied, Clermont-Ferrand, France, Quebec Heart and Lung Institute-Laval Hospital, Quebec, QC, Canada, Montreal Heart Institute, Montreal, QC, CanadaIntroduction: Risk stratification in patients with Brugada syndrome (BS) is still controversial. Most commonly accepted predictors of adverse outcome are clinical symptoms and spontaneous type 1 ECG, whereas induction at electrophysiological study (EPS) and family history of sudden death (SD) are controversial. The aim of this study was to assess the incidence and risk factors of ventricular arrhythmic (VA) events in patients with BS in Quebec, Canada.Methods: Consecutive patients with BS type 1 ECG (spontaneous or induced) were recruited at two tertiary centers (Montreal Heart Institute and Quebec Heart and Lung Institute) between 2002 and 2011. Their files were retrospectively reviewed and follow-up (FU) was conducted prospectively.

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PERFORMANCE OF EVOKED RESPONSE DETERMINATION OF CAPTURE DETECTION BY A HYBRID LEFT VENTRICULAR AUTOTHRESHOLD ALGORITHMDeepa Mahajan, PhD, Michael Giudici, MD, Christopher Schulze, DO, Gautham Kalahasty, MD, Shibaji Shome, PhD, Amy Brisben, PhD, Phillip Schrumpf, RN, Aaron McCabe, PhD and Kenneth A. Ellenbogen, MD. Boston Scientific, St Paul, MN, University of Iowa Hospitals, Iowa City, IA, Cardiology Consultants of Philadelphia, Yardley, PA, Virginia Commonwealth University School of Medicine, Richmond, VA, Minnetronix, St Paul, MNIntroduction: Accurate automatic threshold (AT) testing with pacing threshold trending and output adjustment may simplify device follow-up and improve device longevity. A new hybrid Left Ventricular Autothreshold (LVAT) technology consists of an independent pace/sense (IPS) method, in which the evoked response (ER) is sensed from one electrode when the other is used for pacing in bipolar LV leads (for unipolar vectors), and a shared cathode sensing method (SCS), in which the same cathode is used for pacing as well as sensing ER (for bipolar vectors). This study’s objective was to evaluate the capture detection performance of the LVAT algorithm for CRT devices based on the LV ER in bipolar LV leads.Methods: This analysis was performed by pooling data from phase 2 and 3 of the ELEVATE study. In both phases, the data were collected during LV step-down pacing tests from patients with CRT-D devices (BSC, MN, USA). In phase 2, ER from 4 unipolar pacing vectors were collected using IPS method, and in phase 3, ER from the 2 true bipolar pacing vectors were collected using SCS method. Each paced beat in the AT tests was classified as capture (C), non-capture (NC), or fusion (F) by visual examination of the surface ECG (Gold Standard (GS)). Accuracy was determined by comparing the GS to offline AT algorithm beat classification.Results: Data from 144 patients (95 with IPS and 39 with SCS) were analyzed. Bipolar LV leads from 3 manufacturers were used. In the 1012 AT tests conducted, 64502 C and 2092 NC beats were collected and the accuracy for detecting C and NC were 99.0% and 96.3% respectively. Also, 645 (1%) C beats were detected as F and 63 NC (3%) beats were classified as F by the algorithm due to a transient signal drift.Conclusion: The present hybrid LVAT capture detection method classified C and NC with an accuracy of over 98%. Moreover, the fusion misclassifications are not likely to result in a threshold lower than the true threshold since LVAT does not decrease the pacing voltage on fusion classification. This result further supports the utilization of LV evoked response signals from bipolar LV leads for capture detection in CRT patients.

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LEFT VENTRICULAR ENDOCARDIAL PACING THROUGH THE INTERVENTRICULAR SEPTUM: A NOVEL APPROACH FOR CRTTimothy R. Betts, MD, FRCP, James Gamble, MBChB, Kelvin C. Wong, MD, Kim Rajappan, MD and Yaver Bashir, MD, FRCP. Oxford University Hospitals NHS Trust, Oxford, United KingdomIntroduction: Left ventricular pacing through the CS and LV veins is the standard approach for CRT. When this route is unavailable, surgical implantation has associated morbidity and LV endocardial pacing through an atrial transseptal route is complex, exposes the lead to the systemic circulation and may interfere with mitral valve function. LV endocardial pacing through the interventriuclar septum may offer a simpler

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DEVELOPMENT OF A FRAGMENTED QRS COMPLEX ON 12-LEAD EKG AFTER IMPLANTATION OF A CONTINUOUS-FLOW LVAD IS NOT ASSOCIATED WITH INCREASED RISK OF VENTRICULAR ARRHYTHMIAIsac C. Thomas, MD, David P. Cork, MD, Hemal Nayak, MD, John F. Beshai, MD, Martin C. Burke, DO and Joshua D. Moss, MD. University of Chicago, Chicago, ILIntroduction:Ventricular arrhythmias (VA) in the months following continuous-flow LVAD implantation are associated with a significant risk of mortality. It has been postulated that some VA may be precipitated by the placement of the LVAD itself. We sought to study the association between the development of a fragmented QRS complex (fQRS) post-LVAD implant and the risk of VA.Methods:The records of 105 consecutive adult patients receiving a continuous-flow LVAD between 2008 and 2010 at the University of Chicago were reviewed. Pre- and post-implant EKG’s were analyzed for the presence of fQRS, which can include various RSR’ patterns without a typical bundle-branch block, using standard criteria. Review of ICD device interrogations was used to determine the incidence of VA. The association between development of a fQRS and the incidence of VA was analyzed.Results:99 patients with available pre- and post-LVAD EKG’s were included. 43 patients had fQRS following LVAD implantation, compared to 26 patients prior to LVAD (p<.001). The incidence of QRS fragmentation in the anterior territory (precordial leads V1 through V5) increased 4-fold after LVAD (p<0.001), and accounted for 84% of all new fragmented QRS territories that developed after LVAD implant. 38 patients had available ICD interrogation data, 12 of whom (32%) had fQRS in the anterior territory following LVAD implant. The incidence of VA did not differ significantly between those patients with fQRS and those without (p=0.93). The use of antiarrhythmic drugs during hospitalization following LVAD also did not differ significantly between groups (p=0.67).Conclusion:Incidence of fQRS increases significantly following continuous flow LVAD implantation, predominantly in the anterior territory. While the presence fQRS has been shown to be an independent predictor of VA in patients with heart disease, it was not associated with a significantly increased risk of VA in this population.

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AV interval was 14±7% and the mean variation with best and worst VV interval was 13±6%. Regardless of best VV interval, the AHR when pacing from the proximal LV vector before the distal resulted in greater AHR than if the direction was reversed.Conclusion:There is significant variation in AHR between and within individuals when AV and VV intervals are adjusted during MSP. Pacing the more proximal vector of the Quartet® lead first seems to confer greater benefit than distal to proximal pacing of the LV.

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LONG-TERM RESULTS AFTER CARDIAC RESYNCHRONIZATION THERAPY WITH OR WITHOUT SURGICAL REVASCULARIZATION IN PATIENTS WITH ISCHEMIC HEART FAILURE AND LEFT VENTRICLE DYSSYNCHRONY.Alexander Romanov, MD, PhD, Evgeny Pokushalov, MD, PhD, Sergey Artyomenko, MD, Natalya Shirokova, MD, PhD, Alexander Karaskov, MD, PhD, Suneet Mittal, MD and Jonathan S. Steinberg, MD. Research Institute of Circulation Pathology, Novosibirsk, Russian Federation, The Valley Health System and Columbia University College of Physicians & Surgeons, New York, NYIntroduction: Patients with ischemic cardiomyopathy (ICM), heart failure and prolonged QRS may be eligible for surgical revascularization and cardiac resynchronization therapy (CRT) device implantation. We tested the hypothesis that epicardial CRT concomitantly with surgical revascularization is superior to CRT and medical therapy in these high risk patients.Methods: Ninety seven consecutive ICM patients with severe heart failure (III-IV NYHA FC, EF < 35%) were randomly assigned to endocardial CRT implantation plus medical therapy (n=48) or epicardial CRT implantation plus CABG (n=49). Patients with left main stenosis more than 50% were not included. The primary end point was reduction in left ventricle systolic volume (LVESV) by 15% measured by echocardiography after 12 months of the follow up. The major secondary endpoint was all-cause death. The patients were followed for a minimum of 36 months.Results: At 36 months, the mean LVESV was significantly lower in epicardial CRT plus CABG group compared with CRT plus medical therapy group (112.4±20.7 ml vs. 139.8±20.5 ml, P=0.002). The proportion of patients with LVESV reduction by ≥15% was 86% in epicardial CRT plus CABG group and 68% in CRT plus medical therapy group (p=0.034).In epicardial CRT plus CABG group, 7 patients (14.3%) died at 3-year follow compared with 14 (29.2%) in CRT plus medical therapy group (Log-Rank test, p=0.01).Conclusion: In patients with ischemic heart failure and LV

alternative route. This pilot study was performed to assess feasibility and refine the puncture technique. Methods: Patients with previous failed CS lead implant and no contraindications to oral anticoagulation were selected. Patients were started on warfarin with the procedure performed with an INR of 2-3. Left ventriculography and coronary angiography were performed to identify LV borders and septal vessels. Subclavian vein access was used for a superior approach ventricular transseptal puncture with a steerable sheath and dilator and a standard BRK needle (pt 1), Baylis NRG RF needle (pts 2 and 3), RF energy delivered via a diathermy pen to a 0.032 guidewire (pts 4 and 6) and a Baylis Nykanen RF energy guidewire (pt 5) under fluoroscopic guidance. The sheath was exchanged for a slitable CS sheath to deliver a standard 65cm bipolar active fixation pacing lead to the lateral left ventricular endocardial wall. Threshold, impedance, sensing and diaphragmatic stimulation were assessed. Patients were reviewed at 3 months to assess lead parameters and response to CRT. Results: All 6 patients (5 male, age 67±11, 4 ischemic, 2 non-ischemic cardiomyopathy) enrolled had successful attempts. LV lead implant procedure time was 66 ± 19 mins. Procedure time shortened with experience and procedures using guidewires rather than needles were quickest. Mean threshold and R wave at implant was 0.7 ± 0.3 V at 0.4 s pulse width and 11.6 ± 5.5 mV. There were no procedure-related complications. At 3 month FU mean threshold and R wave was 1.5 ± 0.7 V at 0.4 s pulse width and 11.2 ± 4.6 mV. 5/6 patients were classed as responders.Conclusion: LV endocardial pacing through a ventricular septal puncture is feasible, particularly when using a RF energy guidewire. Further studies are underway to assess long-term feasibility, safety and magnitude of response to CRT.

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THE ACUTE HAEMODYNAMIC EFFECTS OF AV AND VV OPTIMIZATION DURING MULTI-SITE PACING USING A QUADRIPOLAR LV PACING LEADManav Sohal, MBBS, Steven Niederer, PhD, Anoop Shetty, MBChB, Zhong Chen, MBBS, Julian Bostock, MSc, Jaswinder Gill, MD, MBBS, Michael Cooklin, MD, MBBS, Mark O’Neill, DPhil, MD, FHRS, Matthew Wright, MBBS, PhD, Reza Razavi, MD, MBBS and Christopher A. Rinaldi, MD, MBBS. King’s College London, London, United Kingdom, Guy’s and St. Thomas’ NHS Foundation Trust, London, United KingdomIntroduction:Multi-site pacing (MSP) has shown promise as an effective means of delivering CRT. The Quartet® quadripolar LV pacing lead allows the option of pacing via 10 vectors. We sought to assess the variation of acute hemodynamic response (AHR) to MSP via the Quartet® lead with adjustment of AV and VV intervals.Methods:Six patients with implanted Quartet® leads were studied using investigational MSP software. A RADI pressure wire was deployed into the LV to measure LV dP/dtmax. MSP was performed using the distal electrode-RV coil as vector 1 (LV1) and the proximal electrode-RV coil as vector 2 (LV2). AV intervals were adjusted from 200ms in decrements of 20ms down to 80ms with simultaneous VV timings. VV optimization was then performed at the optimal AV interval. VV timings assessed were: simultaneous; LV1-LV2-RV with a delay of 20ms between each V pacing site; LV2-LV1-RV with a delay of 20ms; LV1-LV2-RV with a delay of 40ms; LV2-LV1-RV with a delay of 40ms.Results:Five patients were in sinus rhythm. There was marked variation in the optimal AV interval within and between patients (figure 1). The same was found when assessing VV intervals (figure 1). The mean variation in AHR between best and worst

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VENTRICULAR ARRHYTHMIA, ICD THERAPY AND SUDDEN CARDIAC DEATH AMONG PATIENTS WITH CRT FROM CUBIC REGISTRYYoji Okamoto, MD, Satoki Fujii, MD, Hiroshi Tasaka, MD, Satoshi Shizuta, MD, Koichi Inoue, MD, Takeshi Arita, MD, Kenji Ando, MD, Kazushige Kadota, MD, Takeshi Kimura, MD, Takaaki Isshiki, MD, Kazuaki Mitsudo, MD, Masakiyo Nobuyoshi, MD, CUBIC (CRT Utilization By Interventional Cardiologists) registry. Kurashiki Central Hospital, Kurashiki, Japan, Kyoto University Hospital, Kyoto, Japan, Sakurabasi Watanabe Hospital, Osaka, Japan, Kokura memorial hospital, Kokura, Japan, Teikyo University Hospital, Tokyo, JapanIntroduction: Cardiac resynchronization therapy (CRT) has been known to be effective for drug resistant heart failure with cardiac dyssynchrony. However, ventricular arrhythmic events are not well examined among the Japanese population with CRT. In this study we examined VF, VT, ICD therapy and sudden cardiac death (VAE: ventricular arrhythmia event) during the observational period from the CUBIC (CRT Utilization By Interventional Cardiologists) registry.Methods: We investigated 945 patients from CUBIC registry (age 69±11, male 70%, NYHA class 2.9±0.6, ischemic heart disease 30%, pre-EF 28.1±9.4%, CRT-D 67.7%). The patients were divided into two groups. Group 1 consisted patients with one of the following: history of VF, sustain VT or cardiac arrest while undergoing CRT. Group 2 consisted of patients with no previous aforementioned cardiac events.Results: Event free survival rate from VAE was significantly higher in group 2 compared to group 1 (44.2% vs. 30.3% at 4-year, p<0.0001) (figure).Furthermore, a multivariate study was performed on group 2 using Cox regression with analysis based on clinical characteristic. When analyzing the data, Males were shown to have a significantly higher incidence of VAE (HR=1.442: 95%CI 1.128-1.843, p=0.003). It was also shown that patients with NYHA IV had a stronger predictive values of VAE when comparing to patients with NYHA II(HR=1.889: 95% CI 1.337-2.667, p=0.0001).Conclusion: Males and NYHA IV have been shown to be important predictive factors for VAE. Defibrillator function for secondary prevention was shown to be reasonable among Japanese CRT population.

dyssynchrony, who can be treated with surgical revascularization or medical therapy, epicardial implantation of a CRT system concomitantly with CABG was superior to CRT plus medical therapy resulting in more reverse ventricular remodeling and lower mortality in long-term follow up.

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THE ROLE OF ELECTRICAL DELAY (QLV) TO PREDICT REDUCTION IN MITRAL REGURGITATION FOLLOWING CARDIAC RESYNCHRONIZATION THERAPY: FINDINGS FROM THE SMART-AV TRIALJagmeet P. Singh, MD, Kenneth A. Ellenbogen, MD, Kenneth M. Stein, MD, Alan Waggoner, BA, Yinghong Yu, MS, Timothy E. Meyer, PhD, Nicholas Wold, MS and Michael R. Gold, MD, PhD. Massachusetts General Hospital, Boston, MA, Virginia Commonwealth University Medical Center, Richmond, VA, Boston Scientific Corp, St. Paul, MN, Washington University School of Medicine, St. Louis, MO, Medical University of South Carolina, Charleston, SCIntroduction: Mitral regurgitation (MR) in patients (pts) with LV dysfunction is a risk factor for poor clinical outcome. Markers of electrical dyssynchrony (i.e. QLV) are predictive of LV volume response with cardiac resynchronization therapy (CRT). We sought to test the hypothesis that pacing at a site with long QLV is more effective in reducing MR area as well.Methods: A total of 426 patients enrolled in SMART-AV (66% male, mean age 66 ± 11 years, left ventricular ejection fraction (LVEF): 28% ± 9%, QRS width 149 ± 25 msec, LVESV 128 ± 62 ml ) were analyzed. QLV was defined as the time from first surface ECG deflection to LV electrogram peak during sinus rhythm at implant. Patients were grouped by QLV quartiles reported previously. Changes in MR area from implant to 6 months were classified as decreased (<-15%), unchanged and increased (>15%) for each QLV quartile. A Cochran-Mantel-Haenszel correlation test was utilized to compare the response rates across the QLV groups.Results: The cutoffs of QLV quartiles were 70 ms, 95 ms, and 120 ms. The change in MR area with CRT for the 4 groups are shown (Figure). The best outcomes were observed with the longest QLV quartile.Conclusion: Baseline electrical dyssynchrony as assessed by QLV in the SMART-AV sub-study was strongly associated with the change in MR area following CRT. The longer the electrical delay, the better the improvement in MR area.

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may have unique cardiac tissue properties that may interfere with long term lead performance. We sought to characterize the performance of implanted leads among a cohort of patients with CS and ICDs.Methods: We performed a nested case-control study on the cohort of patients at the University of Colorado Hospital with CS and an ICD compared to controls who had other indications for an ICD. We compared the measured lead parameters at the time of routine interrogation to assess the differences between groups over time.Results: 46 CS patients with ICDs were compared to 117 controls. The mean duration of follow-up was 36 months. The measured electrograms (EGM) at implant were not different between groups (R-waves: CS: 11.7 +/- 5.0 mV, control: 11.0 +/- 5.0 mV; P-waves: CS: 3.3 +/- 1.7 mV, control: 2.9 +/- 1.5 mV). Patients with CS have a high incidence of significant (greater than 50%) reduction in measured P- and R-wave EGMs (10 vs. 3 patients, HR 9.10 [95% CI, 2.50-33.05], Figure 1).Conclusion: Compared to patients with other forms of cardiomyopathy, local characteristics at the lead/tissue interface in sarcoidosis can adversely affect EGM potentials over time. Further investigation is needed to characterize whether inflammation and local granuloma formation at the lead insertion site is causal. CS patients with ICDs should be followed to monitor for reduction in R- and P-wave sensed EGMs, which can necessitate DFT testing or lead revision.

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INCIDENCE, MANAGEMENT AND OUTCOMES OF ARTERIO-VENOUS FISTULA COMPLICATING TRANSVENOUS LASER LEAD EXTRACTIONEdmond M. Cronin, MBChB, Michael P. Brunner, MD, John Rickard, MD, David O. Martin, MD, MPH, Oussama M. Wazni, MD, Bruce L. Wilkoff, MD and Bryan J. Baranowski, MD. Cleveland Clinic, Cleveland, OHIntroduction: Arterio-venous (AV) fistula is an infrequently reported complication of transvenous laser lead extraction (TLE), but may be under-recognized. We describe the incidence, management, and outcomes in our experience.Methods: All TLE procedures from January 2002 to December 2012 were reviewed. Extraction was defined as removal of a lead implanted for more than one year, or with the use of specialized extraction tools. AV fistula was diagnosed on the basis of clinical suspicion, either at the time of the procedure or subsequently, supported by radiographic or autopsy evidence.Results: Of 2368 TLE procedures, AV fistula occurred in 8 procedures (0.3%, 6 pacemakers and 2 ICDs), and presented 0-586 (median 3) days post procedure. Intra-procedural signs included pulsatile backflow from the laser sheath and hypotension in an ipsilateral arterial pressure line. A continuous

PO04-27

IMPACT OF ACTIVE VERSUS PASSIVE FIXATION LEADS ON PACEMAKER LONGEVITYNaeem Al-Shoaibi, MBBS, Nitin Kansal, MD, andrew H. Ha, MD, Horacio J. Quiroga, MD, Syamkumar Divakara. Menon, MD, Jeff Healey, S, MD, Carlos S. Ribas, MD, Carlos Morillo, MD and Stuart Connolly, MD. McMASTER UNIVERSITY, Hamilton, ON, CanadaIntroduction: The choice between active vs passive fixation leads at the time of pacemaker implantation is primarily based on operators experience. However, there is a paucity of data on the clinical benefits such as device longevity and complication rate of using either type of lead fixation system.Methods: Consecutive patients who received a pacemaker at our academic center over a 6 month period were retrospectively analyzed. Either a passive or active ventricular lead chosen based on operators preference. Pacing threshold and impedance were collected 3 weeks post implant and used to calculated device longevity based on pacing at 60 beats per minute with pulse width of 0.4ms in a single chamber St. Jude Accent device. Longevity calculation included safety margin at twice and three times pacing threshold, and pacing at 50% and 100%. Lead dislodgment rate was also collected.Results: Overall, 362 patients underwent pacemaker implantation (197 passive). At 3 weeks, 311 patients (167 passive) had complete follow up. Patient characteristics in both groups were similar in terms of age, gender and pacemaker indication. Both mean pacing threshold and impedance were significantly lower in the passive lead group compared to active lead group. Depending on percentage of pacing and safety margin parameters, Passive fixation lead could potentially save up to 2 years in battery life compared to active fixation lead (P< 0.001) (Table 1). Lead dislodgment rate was not significantly different among groups (2.5% vs 4.2% ).Conclusion: Passive ventricular leads have significantly lower pacing thresholds and may potentially prolong estimated battery life by 2 years. Passive ventricular leads did not have an increased risk of dislodgment.Table 1 (result)

Variable Passive Fixation lead (n=167)

Active fixation lead (n=144) P value

Mean threshold at 3 weeks (SD) 0.6mV ± 0.2 1.0mV ± 0.4 < 0.001Mean impedance at 3 weeks (SD) 564Ω ± 11 640Ω ±103 < 0.001Estimated longevity (yr±SD) at 50 % pacing, safety margin x2 pacing threshold 17.8 0.6 16.7 ± 0.7 < 0.001

Estimated longevity (yr±SD) at 100 % pacing, safety margin x2 pacing threshold 17.2 ± 0.9 15.3 ± 1.2 < 0.001

Estimated longevity (yr±SD) at 50 % pacing, safety margin x3 pacing threshold 12.8 ± 2.9 11.2 ± 3.5 < 0.001

Estimated longevity (yr±SD) at 100 % pacing, safety margin x3 pacing threshold 10.3 ± 3.9 8.7 ± 4.5 = 0.001

PO04-28

PATIENTS WITH CARDIAC SARCOIDOSIS AND ICDS HAVE A HIGH INCIDENCE OF LATE REDUCTION OF MEASURED ELECTROGRAMSMatthew M. Zipse, MD, Paul D. Varosy, MD, Joseph L. Schuller, MD, David A. Steckman, MD, David F. Katz, MD, Jaime E. Gonzalez, MD, Raphael K. Sung, MD, Wendy S. Tzou, MD, Duy T. Nguyen, MD, Ryan G. Aleong, MD and William H. Sauer, MD. University of Colorado, Aurora, CO, VA Eastern Colorado Health Care System, Denver, COIntroduction: An ICD is indicated for some patients with cardiac sarcoidosis (CS) for prevention of sudden death. These patients

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leads. These novel leads may permit CRT implanters the ability to position LV leads in sites which were previously unattainable.

PO04-31

COMPARISON OF TRANSESOPHAGEAL AND INTRACARDIAC ECHOCARDIOGRAPHY IN PATIENTS UNDERGOING LEAD EXTRACTION FOR INFECTIONFaiz A. Subzposh, MD, Aswin Matthew, MD, Joshua Grant, DO, Eric Miller, BS, Brian Cooper, MD, Heath Saltzman, MD, Andrew Kohut, MD and Steven Kutalek, MD. Drexel College of Medicine, philadelphia, PAIntroduction: The sensitivity of transesophageal echocardiography (TEE) has been reported to be between 94-96%, making it to date the best available modality to visualize and confirm the presence of infective vegetations (IV) indicative of endocarditis. Intracardiac echocardiography (ICE) has shown utility in detection of IV but its efficacy is unknown.Methods: Single center extraction records were reviewed from 2009-2012 of patients who underwent both TEE and ICE prior to lead extraction. We reviewed demographics, comorbidities, pre-extraction TEE, and intraoperative ICE reports. Comparisons were made using Cohen’s Kappa coefficient.Results: 43 patients were found to have both pre-procedure TEE and perioperative ICE (Table 1). Cohens Kappa coefficient was calculated to 0.733 showing strong agreement between IV identification capabilities of TEE and ICE. Assuming TEE as the gold standard for identification of IV, the sensitivity of ICE is 93.3%, with a specificity of 80%. Two patients had IV seen by ICE but not seen by TEE, both of the cases were bacteremic patients, making it more likely to be true vegetations.Conclusion: Our data supports the utility of ICE in assessing IV, and suggests that ICE may be useful in detecting IV missed by TEE. With a sensitivity very close to TEE, ICE has proven to be a valuable tool, for confirming the diagnosis of endocarditis, and for observing the stability of the IV through the extraction procedure.Comparison of ICE and TEE

Intracardiac EchoVegetation Seen No Vegetation Seen

Transesophageal Echo Vegetation Seen 31 2No Vegetation Seen 2 8

PO04-32

LEAD RETRIEVAL ANALYSIS: INSULATION DEGRADATION HINDERS LONG TERM PERFORMANCEMariya Tohfafarosh, BS, Alex Sevit, Jasmine Patel, PhD, Arnold Greenspon, MD, Jordan M. Prutkin, MD and Steven Kurtz, PhD. Drexel University, Philadelphia, PA, Exponent Inc., Philadelphia, PA, Thomas Jefferson University Hospital, Philadelphia, PA, University of Washington, Seattle, WAIntroduction: Lead insulation polymers such as polyurethanes (PU) or polydimethylsiloxane (PDMS) degrade over time: PU via metal ion oxidation and PDMS via surface hydrolysis. Both are susceptible to environmental stress cracking. Such changes could give rise to lead failure. We systematically analyzed retrieved pacing and ICD leads for biodegradation since little in vivo data is available.Methods: Sections of leads implanted >4 yrs were analyzed under Fourier transform infrared spectroscopy (FTIR) for chemical degradation and scanning electron microscopy (SEM) for physical degradation. Oxidation of PUs was quantified by ether index (EI): the ratio of 1111 cm-1peak (C-O-C stretching) to 1413 cm-1 peak (C-C stretching), while hydrolysis of PDMS was characterized by presence of hydroxyl group (3200-3600 cm-1 peak).

murmur was present in all patients. Catheter angiography was most sensitive for locating the site. Fistulae occurred between the brachiocephalic artery and left brachiocephalic vein (3); left internal mammary artery and left subclavian vein (3); left subclavian artery and left subclavian vein (1); and aortic arch and left subclavian vein (1). One fistula closed spontaneously, others were closed with covered stents (4), or glue (1). One attempt at closure failed and one was diagnosed post-mortem. Compared to patients who did not develop AV fistula, cases were more likely to have required a powered sheath (7/7 (100%) vs 1315/2360 (55.7%), p=0.009), however there were no differences in age, gender, indication for extraction, number or age of leads, or ICD vs pacemaker leads, and prior open heart surgery was not protective (4/8 (50%) vs 893/2360 (37.8%), p=0.357). Three of eight (37.5%) patients with AV fistula died, all with delayed diagnosis.Conclusion: AV fistula is an infrequent, though likely under-recognized, complication of TLE. Arterial backflow during or a continuous murmur post device extraction should prompt further investigation for the presence of AV fistula, which requires a high index of suspicion to diagnose, may present late, and is associated with significant morbidity and mortality.

PO04-30

A NOVEL ACTIVE FIXATION LEFT VENTRICULAR LEAD: EXTRACTION EXPERIENCE IN AN ANIMAL MODELstuart W. adler, II, MD, Amy Thompson, BS, John Sommer, BS, Douglas Hine, MS, Nicole Kirchhof, DVM and Laurie Foerster, BS. Health East Heart Care, St Paul, MN, Medtronic INC, Minneapolis, MNIntroduction: Left Ventricular (LV) lead stability within the coronary sinus (CS) remains an important and largely unmet need for Cardiac Resynchronization Therapy (CRT). A novel active fixation side helix (AFSH) mechanism may permit implanters the ability to securely fix the lead in a desired location, regardless of CS anatomy. Extraction of chronic leads can be challenging, as a result the helix is designed to release from the CS vein wall. The purpose of this study was to evaluate the extractability of this novel active fixation LV lead in a chronic animal model.Methods: Nine sheep were implanted via jugular approach with one LV lead and one Right Ventricular (RV) lead (Model 4076, Medtronic). Six sheep were implanted with an AFSH-LV lead, (3 bipole (Model 20066) and 3 quadpole (Model 20096)), and three sheep were implanted with a control LV lead (Model 4193, Medtronic). Electrical performance was measured. At 1 year, all leads were extracted using a locking stylet and a force gauge to measure the removal force applied. Sheep were monitored for 90 minutes for occurrence of complications before sacrifice. Gross pathologic examination of the hearts as well as histopathology of the tissues along the course of the lead was performed.Results: All sheep were successfully implanted and electrical performance was stable throughout the duration of the study. At 1 year, all AFSH-LV and RV leads were successfully extracted. The peak removal force was 1.03 ± 0.09 lbs. for the Model 20066, 0.82 ± 0.30 lbs. for the Model 20096, and 0.63 ± 0.13 lbs. for the Model 4193. The entire lead was removed in 100% of cases. Gross pathology revealed no hemopericardium, venous perforation/tear, or intimal abrasions for any of the LV leads. Histopathology yielded no evidence of collateral damage adjacent to the AFSH fixation mechanism. The degree of perilead fibrosis was similar for all three LV lead models.Conclusion: This study demonstrated feasibility and safety of implanting novel AFSH-LV leads. At 1 year these leads were all successfully extracted at forces similar to passive fixation LV

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S303Poster Session IV

appreciable differences in pacing thresholds among the 10 vectors, and PNS was more frequent using conventional (bipolar lead-based) vectors (27% with LVtip-LVdistal ring and 32% with LVtip-RVcoil) than using other non-conventional vectors (respectively 12%, 13%, 13%, and 14%). At 3 months, PNS was observed in 4.9% of pts, lead dislodgement in 4.0% of pts, pacing threshold increasing to >3V in 2.0% of pts and loss of capture in 1.0 % of pts. Vector reprogramming resolved all of the cases of PNS and threshold increases. Among the 72 pts completing 6 months follow-up, one pt (1.4%) exhibited PNS, which was resolved by vector reprogramming; overall, the pacing and PNS thresholds did not change.Conclusion: The SJM QuartetTM LV lead has optimal pacing parameters and low dislodgement rates through 6 months of follow-up. The additional and unique pacing vectors of this quadripolar lead allow for highly effective noninvasive management of PNS and pacing thresholds in CRT patients.

PO04-34

VARIATION IN EPICARDIAL CONDUCTION DURING PACING FROM A MULTI-POLAR LEFT VENTRICULAR CATHETERBrett D. Atwater, MD, Nathan A. Grentz, BSc, Eric E. Johnson, MD, W. Ben. Johnson, MD, Robert H. Hoyt, MD and John F. Beshai, MD. Duke Univ Medical Center; Durham VA Medical Center, Durham, NC, Medtronic Inc, MoundsView, MN, Stern Cardiovascular Center, Germantown, TN, Iowa Heart Center, Des Moines, IA, University of Chicago, Chicago, ILIntroduction: Quadripolar left ventricular (LV) leads allow pacing and sensing at multiple sites, and may be used for multisite pacing. Variation in LV paced conduction along the lead path, however, is not well described. We investigated how LV conduction propagates along a simulated quadripolar lead path and how conduction varies with changes in LV pacing site.Methods: Prior to LV lead implant, a decapolar catheter with 2-5-2 mm spacing was placed in a lateral position via a coronary vein and confirmed by fluoroscopy in 11 patients. The conduction time between LV bipoles was measured with pacing from the most distal bipole (LV 1-2) and from the most proximal bipole (LV 9-10) to determine if the time required to depolarize the tissue along the catheter varied with pacing site. Data were summarized as mean ± standard deviation.Results: There was no significant difference in conduction time to the opposite end of the catheter with pacing from LV 1-2 vs. LV 9-10 (68 ± 19 vs. 66 ± 20 ms, p=.41). Conduction time increased with distance from the pacing site, and varied between patients (Figure) with no clear difference between ischemic (n=5) and non-ischemic patients. The conduction time to LV 9-10 during pacing at LV 1-2 varied widely between patients, ranging from 42 to 94 ms.Conclusion: LV conduction time along the catheter was similar when pacing the most distal and proximal sites and intra-LV conduction time during LV pacing displayed marked variability between patients. These findings may have implications for selection of single or multiple LV pacing sites in patients with quadripolar LV leads.

Results: Analysis of 15/55 leads retrieved from 31 patients demonstrated chemical degradation in 5/5 PU and 6/10 PDMS leads (implantation time: 8.5 ± 3.3 yrs). EI decayed over time in PU leads such that ether content decreased by 46% at 8.4 yrs post implantation. Fidelis leads (n=2) showed EI reduction of 50-72% at 5-6 yrs. FTIR on PDMS outer surface confirmed presence of hydroxyl groups. Two leads removed for electrical failure exhibited both chemical and physical degradation. Environmental stress cracking was observed under SEM (Fig.) in both types of leads, which correlated with the spectral analysis.Conclusion: Systematic analysis of retrieved leads yields important information regarding lead performance and biodegradation. PDMS and PU both degrade in unique ways, potentially causing lead malfunction. Continued analysis of retrieved leads is warranted.

PO04-33

EFFICACY OF A QUADRIPOLAR LEFT VENTRICULAR PACING LEAD: IMPLANT AND 6 MONTH FOLLOW-UP RESULTS FROM A 143-PATIENT MULTICENTER ITALIAN PROSPECTIVE REGISTRYMaria Grazia Bongiorni, MD, Gabriele Giannola, MD, PhD, Giovanni B. Forleo, MD, PhD, Quintino Parisi, MD, Leonardo Calò, MD, Ennio Pisanò, MD, Marcello Piacenti, MD, Carlo D’Agostino, MD, Gerardo Ansalone, MD and Valeria Calvi, MD. Cardiology Department - University Hospital of Pisa, Pisa, Italy, Electrophysiology and Cardiostimulation Unit - Fondazione Istituto San Raffaele - G. Giglio di Cefalù, Cefalù (PA), Italy, Department of Internal Medicine, Division of Cardiology - University of Rome “Tor Vergata”, Roma, Italy, Fondazione di Ricerca e Cura “Giovanni Paolo II”, Campobasso, Italy, Division of Cardiology, Policlinico Casilino, Roma, Italy, Cardiology Department - Vito Fazzi Hospital, Lecce, Italy, CNR, Institute of Clinical Physiology, Fondazione G. Monasterio, Pisa, Italy, Cardiology Department - Di Venere Hospital, Bari, Italy, Cardiology Unit - Madre G. Vannini Hospital, Roma, Italy, Electrophysiology Unit, Cardiology Department - Ferrarotto Hospital - University of Catania, Catania, ItalyIntroduction: The QuartetTM left ventricular (LV) lead (1458Q St. Jude Medical) is a quadripolar lead (tip and three ring electrodes) designed to allow 10 different pacing configurations. Recent single centre reports suggest that quadripolar technology increases the ability to obtain acceptable pacing thresholds and to avoid phrenic nerve stimulation (PNS).Methods:This multicenter Italian prospective registry was designed to evaluate the QuartetTM lead at implant and at 3 and 6 months follow-up. At implant, pacing parameters and PNS thresholds in all 10 configurations were obtained along with fluoroscopy and procedure times. Electrical measurements, including pacing and PNS thresholds, were once again recorded for all 10 pacing configurations at 3 and 6 months follow-up.Results: 143 patients (pts) in 29 Italian centers were implanted with the QuartetTM lead. Pts were 70.6±10.3 years, 78% male, 53% ischemic, LVEF 27.6±6.4%, QRS duration 149.5±24.2 ms. LV lead implant time was 23.5±22.1 min, and total procedure fluoroscopy time was 23.9±19.3 min. At implant, there were

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PO04-36

A NOVEL APPROACH TO SCREENING FOR SLEEP APNEA UTILIZING DATA FROM IMPLANTABLE CARDIOVERTER DEFIBRILLATORSSanjaya K. Gupta, MD. St. Luke’s East Hospital, Lee’s Summit, MOIntroduction: Obstructive sleep apnea (OSA) is common among patients with congestive heart failure, with estimates of prevalence ranging from 40% - 70%. Many patients are often undiagnosed due to the similarity between the symptoms of congestive heart failure and OSA such as fatigue, daytime somnolence and frequent nocturnal arousals. Consequently, OSA is often under treated, which may lead to worsened clinical outcomes. The purpose of this project is to investigate whether data obtained from remote downloads of ICDs could be used to predict the presence or absence of OSA among patients with congestive heart failure.Methods: Remote monitor transmissions were reviewed from 370 consecutive patients with implantable cardioverter defibrillators (ICDs) or cardiac resynchronization therapy defibrillators (CRT-Ds) in a device clinic over a 6 month period. The reviewer was blinded to the results of any sleep studies. The reviewer recorded the presence of nocturnal arrhythmias and type of device (ICD or CRT-D). Nocturnal arrhythmias were defined as either NSVT or atrial fibrillation that lasted for greater than 3 seconds and occurred between 2200 and 0700. Only a single remote transmission was reviewed and previous remote transmissions from the same patient were excluded from analysis. Age and body mass index at the time of remote download was recorded from the electronic medical record. A composite risk score for OSA was determined for each patient with points assigned as follows: nocturnal atrial fibrillation (+1), nocturnal NSVT (+1), BMI >30 (+1), BMI >40 (+2), BMI<30 (-1), Age <70 years (+1), Age >70 years (-1).Results: A composite risk score of 2-5 had a sensitivity of 55.26% for the presence of OSA and score of 0 or 1 had a specificity of 67.35% for the absence of OSA. A risk score of 2-5 had a positive predictive value of 56.76% for the presence of OSA while a risk score of 0 or 1 had a negative predictive value of 66.00% for the absence of OSAConclusion: A risk score utilizing only the age, BMI and the presence or absence of nocturnal arrhythmias as recorded on a remote monitoring transmission provided a reasonable approximation of the presence or absence of sleep apnea. However, additional clinical and/or device data would need to be incorporated to improve the predictive accuracy of this risk score.

PO04-37

DEVICE DIAGNOSTICS IN THE PREDICTION OF CLINICAL RESPONSE: DO WE STILL NEED THE SIX-MINUTE WALK TEST IN LONGITUDINAL CRT CLINICS?Eszter M. Vegh, MD, Jagdesh Kandala, MD, MPH, Mary Orencole, NP, Chelsea Smith, Amanda M. Anderson, Alexandra L. Miller, BSc, Theofanie Mela, MD, Gaurav A. Upadhyay, MD and Jagmeet P. Singh, MD, PhD. Massachusetts General Hospital, Boston, MAIntroduction: Our aim was to investigate the relative predictive value of device-based physical activity data as compared to six-minute walk test (6MWT) in predicting clinical response to CRT.Methods: We retrospectively reviewed consecutive CRT patients followed in a multidisciplinary clinic 1-, 3- and 6-months after implant. Physical activity data recorded on devices was converted to minutes/day and grouped into tertiles for analysis. 6MWT was also performed at each clinic visit. Functional

PO04-35

SIGNS OF CARDIAC MEMORY DURING BIVENTRICULAR AND LEFT VENTRICULAR PACINGLaura Perrotta, MD, Martina Nesti, MD, Giulia Pontecorboli, MD, Paolo Pieragnoli, MD, Giuseppe Ricciardi, MD, Alenja Bertini, MD, Simone Bartolini, MD and Luigi Padeletti, MD. University of Florence, Florence, ItalyIntroduction: “Cardiac memory’’ (CM) refers to a change in repolarization induced by an altered pathway of activation. It has been described after resumption of spontaneous ventricular activation (SVA) in patients undergoing right ventricular or biventricular pacing (BIV) during cardiac resynchronization therapy (CRT). The effects of left ventricular (LV) pacing on CM induction have not been investigated. To investigate the development of CM during CRT in patients undergoing BIV and LV pacing through vectorcardiography (VCG).Methods: We enrolled 21 patients with symptomatic HF (III-IV NHYA) on optimal medical therapy who underwent CRT according to last guidelines for cardiac pacing. All patients were in sinus rhythm with left bundle branch block (LBBB). Fourteen patients underwent BIV stimulation, 7 underwent LV stimulation only. VCG was acquired during SVA at baseline and during AAI and DDD pacing immediately after and 7 and 90 days after the implant.Results: At baseline, in both groups, the QRS and T vectors angles were those specific of LBBB pattern. During DDD pacing, in BIV patients QRS vector angle changed to the right superior quadrant in the frontal plane (p<0.005) otherwise in LV patients no significant difference was observed in QRS vector direction (p=N.S.). After 7 days, during AAI pacing, T vector angle changed significantly only in BIV patients, following the direction of the paced QRS to the right superior quadrant in the frontal plane (p=0.026) and amplitude significantly increased (7 days: 1.77±1.27 mV vs baseline 1.13±0.69 mV; p=0.026) with a further significant increase at 90 days (2.21±1.50 mV; p=0.01 vs baseline and p= 0.04 vs 7days). In LV patients, no significant T angle changes were observed during SVA, as a consequence of no significant modifications of the paced QRS vector compared to baseline. However T amplitude significantly increasedat 7 days (1.82±1.11 mV vs 1.18±08; p= 0.02) and at 90 days (2.19±1.26 mV; p=0.018 vs baseline).Conclusion: In patients with LBBB, BIV stimulation induces cardiac memory development as a significant change in T vector magnitude and angle, while LV stimulation doesn’t induce significant modifications in QRS and T vector angles and CM is manifested only as a significant T vector amplitude change.

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be achieved given the high patient compliance with the device monitoring period.

PO04-39

HISTOPATHOLOGY OF NON-RESPONSE TO CARDIAC RESYNCHRONIZATION THERAPY (CRT)Gaurav A. Upadhyay, MD, Jagdesh Kandala, MD, MPH, James R. Stone, MD, PhD, Kimberly A. Parks, DO and Jagmeet P. Singh, MD, DPHIL, FHRS. Massachusetts General Hospital, Boston, MAIntroduction: Although a significant minority of patients do not demonstrate clinical benefit after CRT, the etiology of ‘non-response’ remains debated. We sought to characterize the histopathologic features associated with non-response.Methods: Explanted hearts of CRT patients undergoing cardiac transplantation were examined. Hematoxylin and eosin (HE) specimen were performed per protocol and presence of hypersensitivity myocarditis was identified. Electron micrography (EM) was performed as needed. Left ventricular (LV) lead position was evaluated and leads positioned either on scar, in the apical region, or along the true anterior or posterior walls were considered suboptimal.Results: 30 hearts were analyzed: 15 from patients with ischemic (ICM) and 15 with nonischemic cardiomyopathy (NICM). HE findings associated with non-response included presence of hypersensitivity myocarditis (4), Chagas’ myocarditis (2), sarcoidosis (1), myofibrillar disarray (1) and familial NICM (1). EM findings associated with non-response included presence of lysosomal inclusions (2), glycogen storage disease (1), and giant mitochondria (1). Suboptimal LV lead position was more frequent in NICM than ICM patients (60% vs. 27%, p=0.07). Overall, plausible explanation for non-response was found in 90% of patients. Despite a greater incidence of suboptimal LV lead position along with HE and EM abnormalities, patients with NICM demonstrated improved overall survival relative to ICM patients (Figure) after transplant.Conclusion: Pathologic inspection of explanted hearts provided insight into etiopathology of non-response to CRT in a majority of patients.

response to CRT was defined as ≥1 improvement of NYHA class at 6-months. The primary end-point was a composite of time to first heart failure hospitalization, transplant, LVAD, or all-cause death at 3 years.Results: 175 patients were studied: mean age of patients was 67±13 years, mean LVEF was 25±7%, 77% were male, and 68% with NYHA class III. At baseline, 6MWT and mean activity level was 1032±335 m and 153±89 min/day respectively. Functional improvement was noted in 98 (56%) patients and the composite outcome was reached in 34 (19.4%) patients. Physical activity and 6MWT data at 1-, 3- and 6-month visits were correlated (R=0.391, 0.363, 0.413, p>0.001 respectively). Lower device-measured physical activity and walk test groups at 1 and 3 month demonstrated higher incidence of composite clinical events (Graph).Conclusion: Automatically acquired device measures of physical activity correlate with 6MWT and can meaningfully contribute to the prediction of long-term clinical events after CRT.

PO04-38

WEARABLE WIRELESS ARRHYTHMIA DETECTION PATCHES: DIAGNOSTIC ARRHYTHMIA YIELD, TIME TO FIRST ARRHYTHMIA, AND PATIENT COMPLIANCEJerold S. Shinbane, MD, FHRS, Matt Merkert, BS, Richard Fogoros, MD, Vipin Mehta, BS, Michael Cao, MD and Leslie A. Saxon, MD. USC Keck School of Medicine, Division of Cardiovascular Medicine, Los Angeles, CA, Corventis, Inc., San Jose, CAIntroduction: Wireless arrhythmia detection systems allow monitoring for extended time periods. We sought to identify the diagnostic yield of a wearable, wireless arrhythmia detection patch for clinically relevant arrhythmias (CRA) and patient compliance.Methods: Electrograms from the United States NUVANT MCT database were analyzed for CRA, including auto-triggered (AT) and patient- triggered (PT) events. CRA were defined as any PT event and AT events with the exception of: AT sinus tachycardia, AT atrial ectopy < 5 sec, AT ventricular single beats or couplets. AT 2nd degree AV Block Type I was CRA only if outside of the 1am to 5am time period. AT bradycardia was CRA only if it was <=40 and outside of the 1am to 5 am time period. AT pauses were > 3 sec, and PT pauses were > 2 sec. Diagnostic yield was defined as the percent of patients with a CRA. The time to first CRA was identified. Compliance was defined as continuous days of recording/prescription time period.Results: Of 277,000 electrograms recorded in 732 patients, 64% of patients had CRA (Table).The time to first CRA was 5.8 + 6.1 days. Compliance for the subset of patients (n=714) with the most common prescription time periods of 7, 14, 21 and 30 days was 90% of days prescribed.Conclusion: Wearable wireless arrhythmia detection patches provide a high diagnostic yield for CRA. The time to first CRA supports technologies providing longer monitoring than that provided by standard 1 to 2 day ambulatory monitors, which can

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PO04-41

DEVICE-DEPENDENT INCREASED RISK OF DEATH AMONG PATIENTS WITH CARDIOVASCULAR IMPLANTABLE ELECTRONIC DEVICE INFECTIONS PERSISTS AFTER TREATMENTMuhammad R. Sohail, MD, Charles A. Henrikson, MD, Mary Jo Braid-Forbes, MPH, Kevin F. Forbes, PhD and Daniel J. Lerner, MD. Mayo Clinic College of Medicine, Rochester, MN, Oregon Health & Science University, Portland, OR, Braid-Forbes Health Research, Silver Spring, MD, Catholic University of America, Washington, DC, TYRX Inc, Monmouth Junction, NJIntroduction: Patients with Cardiovascular implantable electronic device (CIED) infections are at increased risk of death, both during and following treatment of the infection. The purpose of this analysis was to determine the device-specifi c magnitude and durability of the increased risk of death associated with device infection, in the 3 years following treatment.Methods: Our study population consisted of a retrospective cohort of 200,219 Medicare fee-for-service patients admitted for CIED generator implantation, replacement, or revision between January 1, 2007 and December 31, 2007. We calculated device-specifi c relative risk (RR) of death during the fi rst, second, and third years following discharge. We compared mortality rate of patients with CIED infection to those without it. Risk adjustments were made for age, ethnicity, sex, and 28 comorbidities.Results: Following 131,342 pacemaker procedures, 3-year mortality was 53.8% with device infection vs. 33.0% without (P<0.001). Moreover, device infection was associated with an increased relative risk (RR) of death in each of the fi rst 3 years, compared to patients without infection (RR: 1y 2.10 [95%CI 1.97-2.23], 2y 1.24 [1.12-1.38], 3y 1.24 [1.10-1.39]). Similarly, following 37,642 implantable cardioverter-defi brillator (ICD) procedures, 3-year mortality was 47.7% with infection vs. 31.6% without (P<0.001). Device infection was associated with an increased RR of death in each of the fi rst 2 years (RR: 1y 1.62 [1.44-1.84], 2y 1.46 [1.23-1.74], 3y 1.04 [0.84-1.29]). Following 27,261 cardiac resynchronization device with defi brillator (CRT-D) procedures, 3-year mortality was 50.8% with infection vs. 36.5% without (P<0.001). Device infection was associated with an increased RR of death during the fi rst year (RR: 1y 1.59 [1.37-1.84], 2y 1.15 [0.91-1.43], 3y 1.05 [0.82-1.34]).Conclusion: CIED infection is associated with persistent and signifi cantly higher risk of death for at least 1-3 years, depending on the device type, following treatment. The etiology for this increased risk of death is not known and warrants further evaluation.

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ANGIOTENSIN CONVERTING ENZYME INHIBITOR/RECEPTOR BLOCKER UTILIZATION IS ASSOCIATED WITH BETTER SURVIVAL IN PATIENTS UNDERGOING CARDIAC RESYNCHRONIZATION THERAPYAttila Roka, MD, PhD and Mark H. Schoenfeld, MD, FHRS. Yale New Haven Hospital, New Haven, CTIntroduction: The newest ACC/AHA/HRS guidelines indicate the importance of cardiac resynchronization therapy (CRT) in those patients with depressed ejection fraction and intraventricular conduction delay who have ongoing symptoms despite optimal medical therapy. The long-term effects of heart failure or antilipid medication utilizaton in patients being referred for CRT-defi brillators (CRT-D) is less known.Methods: We analyzed the survival of 228 consecutive CRT-D patients, implanted between 2007 and 2012 (75% male, 51% ischemic etiology, 17% upgrade of a prior pacemaker). Usage

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FOLLOW-UP OF PATIENTS WITH NEW CARDIOVASCULAR IMPLANTABLE ELECTRONIC DEVICES: DOES ADHERENCE TO THE EXPERTS’ RECOMMENDATIONS IMPROVE OUTCOMES?Paul L. Hess, MD, Xiaojuan Mi, PhD, Lesley H. Curtis, PhD, Bruce L. Wilkoff, MD, Donald Hegland, MD and Sana M. Al-Khatib, MD. Duke Clinical Research Institute, Durham, NC, Cleveland Clinic, Cleveland, OH, Duke University Medical Center, Durham, NCIntroduction: Many patients do not attend an in-person follow-up visit between 2 and 12 weeks after cardiovascular implantable electronic device (CIED) placement as recommended by the Heart Rhythm Society/ European Heart Rhythm Association (HRS/EHRA). Whether adherence to the HRS/EHRA recommendations is associated with better patient outcomes is unknown.Methods: Using clinical data from the National Cardiovascular Data Registry’s ICD Registry linked to Medicare claims data, we studied the impact of follow-up within 2-12 weeks after CIED placement between January 1, 2005, and September 30, 2008, on all-cause mortality and readmission rates within 1 year with unadjusted and adjusted Cox proportional hazards modeling.Results: Compared with patients who did not receive the recommended follow-up (n=43,060), those who did (n=30,256) were more likely to be older, white, and had a lower burden of comorbid illnesses such as diabetes mellitus and chronic lung disease. Compared with patients who did not receive the recommended follow-up, patients who did had signifi cantly lower adjusted all-cause mortality and higher adjusted cardiovascular readmissions (see Table).

Conclusion: Our analysis is the fi rst to show an association between the experts’ recommendations on adequate follow-up of CIEDs and lower mortality. Quality improvement initiatives should focus on improving adherence of CIED follow-up to experts’ recommendations.

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Variable Hazard Ratio

Lower 95% CI

Upper 95% CI

P Value

Age 1.049 1.046 1.059 <0.001Female sex 0.758 0.716 0.802 <0.001Hip fracture 1.622 1.431 1.839 <0.001Heart failure 3.283 3.057 3.526 <0.001Hypertension 1.556 1.461 1.657 <0.001Ischemic heart disease 1.515 1.420 1.616 <0.001Diabetes mellitus 1.163 1.088 1.244 <0.001

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THE IMPACT OF CORONARY ARTERY DISEASE INTERVENTION ON THE INCIDENCE AND PROGNOSIS OF ATRIAL FIBRILLATION AFTER ACUTE MYOCARDIAL INFARCTION: A SYSTEMATIC REVIEWMuayad Alasady, MBBS, Walter P. Abhayaratna, MBBS, PhD, Rajeev K. Pathak, MBBS, Nicholas. Chia, David Barlow, Rajiv Mahajan, MD, Han Lim, MBBS and Prashanthan Sanders, MBBS, PhD. University of Adelaide/ Royal Adelaide Hospital, Adelaide, Australia, Clinical trail Unit/ Australian National University, Canberra, AustraliaIntroduction: Atrial fibrillation (AF) commonly complicates acute myocardial infarction (AMI) and is usually associated with increased in-hospital and long-term mortality rates. Although the prognosis of AMI in the modern interventional era (1990-2000s) is much improved compared to the pre-interventional era (1980s), it is unclear whether the advances in the management of AMI have had any impact on AF incidence and prognosis after AMI.Objective: The aim of this systematic review was to compare the incidence and prognosis of AF after AMI during the pre-thrombolytic (1980s), thrombolytic (1990s) and percutaneous coronary intervention (PCI) era.Method: Using the keywords of AF, AMI and prognosis; PubMed and Medline were searched for prospective cohort and case-control studies that were conducted between 1980 and December 2010.Results: Of the 1250 studies retrieved, 53 met the inclusion criteria including 9, 25 and 15 studies that represented each progressive decade of the analysis. The pooled incidence of AF post AMI over the entire period was 10% (range7.8-18%). There was a declining incidence of AF over the 3 decades (p<0.001, 95% CI (0.086-0.10). The presence of AF post AMI remains a significant risk factor of all cause and cardiovascular mortality (pooled RR 2.5, 95% CI 2.04-2.89), but the strength of association has not changed over time (P=0.5). AF patients were older compared to non-AF patients throughout the three eras (p=0.005).Conclusion: Intervention to treat the primary coronary insult has resulted in a decreasing incidence of AF. However, the consequent negative impact of AF on prognosis post MI remains unchanged.

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PREVENTION OF SUDDEN CARDIAC DEATH (SCD) IN ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA/CARDIOMYOPATHY (ARVD/C): 92 CASES DIAGNOSED POST-MORTEMRicha Gupta, BS, Cynthia James, PhD, Crystal Tichnell, MS, Aditya Bhonsale, MBBS, Brittney Murray, MS, Harikrishna Tandri, MBBS, Daniel P. Judge, MD and Hugh Calkins, MD, FHRS. The Johns Hopkins University School of Medicine, Baltimore, MDIntroduction: Sudden cardiac death (SCD) may be the first symptom in ARVD/C.Methods: We reviewed autopsy reports, medical history,

and compliance with guidelines (use of a medication in the absence of contraindications) for beta-blockers, angiotensin converting enzyme inhibitors/receptor blockers (ACEI/ARB), statins and aldosterone antagonists were determined for each patient. Differences in long-term survival were compared with Kaplan-Meier/Mantel-Cox log rank statistics.Results: Mortality was 19.3% over a follow-up of 1088±553 days. Underutilization of medications at the time of CRT-D implantation was common: 12.3% for beta-blockers, 21.1% for ACEI/ARB, 12.3% for statins and 70.2% for aldosterone antagonists. Use of an ACEI/ARB had a significant effect on survival after CRT-D implant (Figure).Conclusion: ACEI/ARB utilization was associated with better survival in patients who underwent CRT-D implantation. As medical therapy may have a synergistic effect in CRT-D patients, its optimal use should be emphasized in this fragile population.

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FRACTURE HISTORY IS AN INDEPENDENT PREDICTOR OF INCIDENT ATRIAL FIBRILLATIONChristopher X. Wong, MBBS, Thomas Sullivan, BSc, Siang Wei Gan, Sarah W. Lee, Michelle T. Sun, Kurt C. Roberts-Thomson, MBBS, PhD and Prashanthan Sanders, MBBS, PhD. Centre for Heart Rhythm Disorders, University of Adelaide and Royal Adelaide Hospital, Adelaide, AustraliaIntroduction: Emerging evidence suggests a link between cardiovascular disease, osteoporosis and increased fracture risk. Significant relationships have been previously reported between fractures and diverse cardiovascular conditions such as myocardial infarction, heart failure and stroke. Given the emerging epidemic of atrial fibrillation (AF), a condition sharing common etiologic mechanisms with other cardiovascular diseases, we used a population-based cohort to examine whether fracture history is also associated with an increased risk of incident AF.Methods: Consecutive patients presenting to a single University Hospital between 2001 and 2011 were identified. Diagnoses of hip fracture and AF were identified from coding databases. A multivariate Cox proportional hazards model was employed to model time to AF occurrence. Age and gender were fitted as time-invariant covariates, while hip fracture and other AF risk factors were fitted as time-varying covariates.Results: A total of 73,094 individuals without a history of AF were included in the analysis. Of these, 4,992 (6.6%) developed AF during follow-up. Table 1 shows the results of the multivariate model. The presence of hip fracture, either at baseline or during follow-up, increased the risk of subsequent incident AF by 62%.Conclusion: In this population-based cohort study, we found that a history of hip fracture conferred a significant excess risk of incident AF. This association provides further evidence supporting common relationships between osteoporosis and cardiovascular disease.

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hospitalized on the index ED visit. Adverse events occurred in 163 (36.7%) patients including 40 (9%) with an event within 5 days, 94 (21.3%) with events between 6 - 30 days, and 29 (6.6%) who had adverse events both in 0 - 5 days and 6 - 30 days. The Table provides a detailed listing of the adverse events.Conclusion: Despite high hospitalization rates, 36% of ED patients with symptomatic AF/AFL experience an adverse event within 30 days including nearly 10% of patients with events within 5 days.5-Day and 30-Day Adverse Events Subsequent to Index ED Visit/Hospital DischargeOutcome 0-5 Days from

Index ED Visit6-30 Days from Index ED Visit

Return ED visit 21 (4.8%) 84 (19%)Unscheduled Hospitalization 16 (3.7%) 76 (17.2%)Unscheduled Hospitalization > 48 hours 12 (2.7%) 50 (11.3%)Acute Atrial Arrhythmia Requiring Treatment 24 (5.4%) 46 (10.4%)Acute Ischemic Cerebrovascular Accident 3 (0.9%) 7 (1.8%)Acute Hemorrhagic Cerebrovascular Accident 1 (0.2%) 1 (0.2%)Acute Decompensated Heart Failure 4 (0.9%) 10 (2.3%)Cardiac Arrest 3 (0.7%) 8 (1.8%)Death 5 (1.1%) 24 (5.4%)

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INCIDENCE AND PREDICTORS OF “LATE PHASE” VERSUS “EARLY PHASE” POST-OPERATIVE ATRIAL FIBRILLATIONElham Bidar, MD, Bart Maesen, MD, Fred Nieman, PhD, Ulrich Schotten, MD, PhD and Jos G. Maessen, MD, PhD. Maastricht University Medical Centre, Maastricht, NetherlandsIntroduction: Although post-operative atrial fibrillation (POAF) is considered a transient arrhythmia in the first week after surgery, it is potentially a recurrent phenomenon. Specific risk factors for “late-POAF”, occurring between 5 and 30 days after the operation, have not yet been established. We aimed to determine the 30-day incidence and predictors of POAF.Methods: Patients (n=148) without a history of AF undergoing aortic valve replacement (AVR) or coronary artery bypass grafting (CABG) were randomized into a pacing group (n=75) and a control group (n=73). Continuous postoperative rhythm monitoring using telemetry and a trans-telephonic event recorder (Vitaphone ™) detected AF episodes for 30 days. All patients received a class II/III anti-arrhythmic drug (Sotalol) as a standardized treatment for 30 days post-operatively.Results: AF was defined as episodes lasting longer than 10 seconds. Baseline characteristics were comparable in both groups. POAF occurred in 73 patients (49.3%) of whom 60 patients (40.5%) showed POAF during post-operative days (POD) 0-5 and 37 patients (25%) during POD 6-30. Prolonged aortic cross clamp time (ACCT) was an important univariate predictor of total 30 day and of late phase POAF (POD 6-30) (p=0.017 and p= 0.03 respectively). Cox regression analysis using 15 predetermined risk factors for POAF and pacing showed different positive interactive effects for early (i.e. baseline CRP, MI, low BMI) and late POAF (i.e. high BMI, DM, baseline CRP, early POAF, creatinin, type of operation, smoking and male gender). The average AF duration per event for early POAF was significantly longer (average 32.51 mins, 0 - 451) compared to late POAF (average 10.6 mins, 0 - 450, p<0.001). Patients developing late POAF in addition to early POAF (n=36) had longer early POAF events (63.34 mins) compared to those who only developed early POAF (35.06 mins, p= 0.013).Conclusion: POAF is not a transient arrhythmia in the first

and family history of 117 consecutive cases of SCD between 1986-2010 diagnosed with ARVD/C post-mortem. Cases were excluded if 1- the autopsy report was incomplete - missing histology, gross description, or both (7), 2- histologic review by a cardiac pathologist suggested another diagnosis (7), 3- evaluation of family members resulted in an alternate diagnosis (3), or 4- the autopsy report was inconclusive (8). This resulted in 92 SCD cases, which we compared to 128 gene-positive ARVD/C cases that presented while living.Results: Average age of SCD was 34.9 years (8-79, SD 14.8) with men (45/92) dying younger than women (47/92), (31.7 vs. 38.0 yrs, p=0.04). SCD occurred most often during daily activity 33/92 (36%), 21/92 (23%) during exercise, 13/92 (14%) during sleep, and 25/92 (27%) unknown. Men were more likely than women to have SCD during exercise (45% vs. 18%, p=0.01). Nearly half (46%) had cardiac symptoms prior to death, syncope being the most common. On autopsy 66/92 hearts had RV fibrosis and fat, 24 had fat only, and 2 only fibrosis. Nearly half (47%) of cases had LV involvement (7 fat only, 18 fat and fibrosis, 18 fibrosis only). There was no association between sex and LV or RV pattern of involvement. Only 8/82 (10%) presenting with SCD had a known family history prior to SCD. Following death, 175 first-degree family members were screened resulting in 42 diagnoses. As compared to patients diagnosed while living, average age of symptom onset in SCD cases was similar (33.1 vs. 29.4 yrs, p=0.13), as was age of SCD compared to age of first life-threatening ventricular arrhythmia (VF, resuscitated SCD, sustained VT) among the living cases (34.9 vs. 32.1 yrs, p=0.16).Conclusion: Half of SCD ARVD/C cases have prior cardiac symptoms, providing opportunity for prevention. Consistent with findings from living ARVD/C cohorts, men experience SCD at a younger age than women. Dedicated screening of family members following SCD results in a relatively high rate of detection of additional cases.

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INCIDENCE OF 5 AND 30 DAY ADVERSE EVENTS IN EMERGENCY DEPARTMENT PATIENTS WITH SYMPTOMATIC ATRIAL FIBRILLATION AND ATRIAL FLUTTERTyler W. Barrett, MD, Robert L. Abraham, MD, Cathy A. Jenkins, MS, Alan B. Storrow, MD, Frank E. Harrell Jr., PhD, Karen F. Miller, RN, MN, Kelly M. Moser, BS, Stephan Russ, MD, MPH, Dan Roden, MD and Dawood Darbar, MD. Vanderbilt University Medical Center, Nashville, TNIntroduction: More than 65% of ED visits for atrial fibrillation (AF) and atrial flutter (AFL) in the United States result in admission contributing to healthcare costs of up to $26 billion. As a first step in developing an AF/AFL disposition decision aid, we measured the incidence of 5 and 30 day adverse events in patients who visited the ED for symptomatic AF/AFL.Methods: We performed a prospective, observational cohort study and enrolled ED patients at a single urban, tertiary care hospital who had a new or established ED diagnosis of AF or AFL, confirmed on ECG, as well as signs or symptoms believed related to AF or AFL. Patients were excluded if they sought ED treatment for a complaint not related to AF or AFL. Our composite primary outcome was determined by phone follow-up at 5 and 30 days after the ED visit and included the outcomes listed in the Table.Results: We enrolled 459 ED patients between 6/8/2010 and 8/31/2012. Of these, 9 (2%) patients were withdrawn following consent and 8 (1.7%) were lost to follow-up. The median age is 68 (IQR: 59, 78) years, 157 (35.5%) are women, 43 (9.7%) are African-American, and 395 (89.4%) are Caucasian. AF was newly diagnosed in 123 (27.8%), 285 (64.5%) patients had symptom duration < 48 hours, and 361 (81.7%) patients were

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arrhythmias (IVA) have been previously reported. The aim of this study was to determine the incidence, clinical and electrophysiologic (EP) characteristics of spontaneous AVNRT in patients with IVA.Methods: Study population consisted of 365 consecutive patients (217 F/148 M, 44±14 y/o) with IVA between April 2005 and November 2012. All patients underwent transthoracic echocardiography and 24-hour Holter monitoring for determination of premature ventricular contraction (PVC) burden and for the type of IVA (PVC and/or VT). Coronary angiography and cardiac MRI were performed in selected patients. Spontaneous AVNRT was documented either on 12-lead ECG and/or 24-hour Holter monitoring in each patient. The definitive diagnosis and type of AVNRT was based on EP study.Results: Spontaneous AVNRT was present in 32 (8.8%) patients (12M/20F, 16 to 69 y/o). 4 out of 32 (12%) patients had monomorphic, frequent PVCs and/or VT during AVNRT (Double Tachycardia). Clinical characteristics including age, gender, type of IVA, 12-lead ECG characteristics of PVCs and presence of PVC-induced cardiomyopathy were not different in patients with or without spontaneous AVNRT. Patients with spontaneous AVNRT were more symptomatic (97% vs 49%, p=<0.0001), had lower PVC load (6.1±7% [median=1.9] vs 12±12% [median=9], p=0.001) and had greater left ventricular ejection fraction (LVEF) (64±4% [median=66] vs 59±10% [median=64], p=0.014) in comparison to patients without spontaneous AVNRT. All patients with spontaneous AVNRT underwent successful slow pathway ablation. 31 patients had slow/fast and 1 patient had fast/slow type AVNRT. 7 out of 32 (22%) patients had PVC burden of 12%. 5 of these patients underwent PVC ablation and antiarrhythmic therapy was used in 2 patients.Conclusion: Spontaneous AVNRT among patients with IVAs was relatively common in our study population. Greater LVEF in patients with spontaneous AVNRT can be explained by earlier recognition of IVAs due to presence of symptoms and/or lower PVC burden.

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WHAT RISK FACTORS CAUSE BOTH INCIDENT AF AND STROKE? AN ANALYSIS OF 1.8M AT-RISK U.S. PATIENTSMatthew R. Reynolds, MD, Tina D. Hunter, PhD, Sarah A. Mollenkopf, MPH and Mintu P. Turakhia, MD. Harvard Clinical Research Institute, Boston, MA, S2 Statistical Solutions, Inc., Cincinnati, OH, Medtronic, Inc., Mounds View, MN, Stanford University School of Medicine, Palo Alto, CAIntroduction:The aim of this study is to quantify the incident AF and stroke among patients at high risk of AF and stroke based on combinations of seven common baseline risk factors.Methods:Using claims data from the Truven Health MarketScan® Commercial and Medicare Supplemental Databases, we identified patients with continuous medical and pharmacy enrollment for calendar year 2007 with at least one of the following baseline risk factors that are known to be associated with either AF and/or stroke: 1) heart failure (HF), 2) hypertension (HTN), 3) diabetes, 4) age ≥65-74, 5) age ≥75, 6) coronary artery disease (CAD), and 7) chronic kidney disease. Based on epidemiological data, we defined patients as high risk of AF or stroke if they had two or more of the first five risk factors or three or more of any seven risk factors. The incidence of stroke and AF diagnosis were tracked for each calendar year from 2008-2010 overall and as a function of risk factors. Multivariable survival models were developed for the times to stroke event and AF diagnosis among the high risk patients and an age-matched cohort with lower risk.Results:Of the 1,851,653 high risk patients identified, 7.26% had a stroke event, 6.65% had an AF diagnosis and 1.29% had both

week after cardiac surgery. Late POAF has different predictors compared to early POAF suggesting a different underlying mechanism.

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ATRIAL ARRHYTHMIAS ARE COMMON AND ARISE FROM DIVERSE MECHANISMS IN PATIENTS WITH CARDIAC SARCOIDOSISMatthew M. Zipse, MD, Joseph L. Schuller, MD, David F. Katz, MD, David A. Steckman, MD, Jaime E. Gonzalez, MD, Raphael K. Sung, MD, Wendy S. Tzou, MD, Duy T. Nguyen, MD, Ryan G. Aleong, MD, Paul D. Varosy, MD and William H. Sauer, MD. University of Colorado, Aurora, CO, VA Eastern Colorado Health Care System, Denver, COIntroduction: Atrial arrhythmias have been described as a rare manifestation of cardiac sarcoidosis (CS). We sought to characterize these arrhythmias with electrophysiologic (EP) testing in symptomatic CS patients.Methods: 65 consecutive patients with biopsy-proven sarcoidosis and evidence of cardiac involvement comprised the cohort. The subjects who underwent electrophysiologic testing for evaluation of symptomatic atrial arrhythmias associated with CS were evaluated for arrhythmia mechanism using response to arrhythmia resetting and pharmacologic challenge. Electroanatomical (EAM) mapping with atrial voltage and arrhythmia activation data were further analyzed for characterization of sarcoidosis-related atrial arrhythmias.Results: Of the 65 subjects with CS, 15 patients (23%) had 27 atrial arrhythmias (9 Atrial Fibrillation; 3 Atrial Flutter; 16 Atrial Tachycardia). Of these, 6 non-AF atrial arrhythmias were targeted for ablation (3 Atrial Flutter; 3 Focal Atrial Tachycardia). The mechanism of the non-AF atrial arrhythmias were determined to be from triggered activity in 2, abnormal automaticity in 9, and reentrant in 8. All non-AF arrhythmias were related to atrial scar identified on electroanatomical maps. In addition to the 6 atrial arrhythmias targeted for ablation, AV node ablation was required for adequate control of multiple atrial arrhythmias including AF in two cases, while the initiation or uptitration of immunosuppression alone was sufficient for management of all arrhythmias in 3 cases. Immunosuppression alone reduced arrhythmia burden in the 9 patients with AF. Of note, there were 2 patients who received inappropriate ICD shocks within 1 year after ICD implantation from the atrial arrhythmias eventually studied.Conclusion: Atrial arrhythmias are common in patients with cardiac sarcoidosis and may cause inappropriate ICD shocks. The mechanisms for the organized atrial arrhythmias are diverse and always related to atrial scar. While immunosuppression appears to reduce AF burden in patients with sarcoidosis, Catheter ablation of focal and reentrant atrial tachycardia is effective in this population.

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SPONTANEOUS ATRIOVENTRICULAR NODAL REENTRANT TACHYCARDIA IN PATIENTS WITH IDIOPATHIC VENTRICULAR ARRHYTHMIAS: THE INCIDENCE, CLINICAL AND ELECTROPHYSIOLOGIC CHARACTERISTICSCan Hasdemir, MD, Alpay Alp, Evrim Simsek, MD, Nuri Kose, MD and Serdar Payzin, MD. Ege University School of Medicine, Bornova, Izmir, Turkey, St. Jude Medical, Izmir, Turkey, Yucelen Hospital, Mugla, TurkeyIntroduction: Coexistence of spontaneous atrioventricular nodal reentrant tachycardia (AVNRT) and idiopathic ventricular

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surface highest dominant frequency (HDF) represents reentry drivers.Methods: Body surface potentials (n=67) were obtained in 13 patients during AF with a left-right frequency gradient. Stability of rotors on the body surface was evaluated on phase maps before and after band-pass filtering at the HDF. Relationship between epicardial and body surface patterns was also analyzed in a computer model of spherical atria inside in a passive torso. A stable rotor on the left hemisphere driving irregular activity elsewhere was simulated and electrical potentials calculated everywhere. Filaments connecting the reentrant activity on the epicardial and torso surfaces were identified.Results: In patients, unfiltered surface maps showed unstable singularity points (SPs) of reentries, whereas HDF band-pass filtered maps presented stable SPs (Panels A-D). Maps at HDF presented stable reentry patterns in 67.7±13.9 % of the time across all patients. Simulations clarified the origins of the surface reentrant patterns: i) All torso filaments were continuous and thus all surface SPs originate at epicardial SPs. ii) Without filtering, the filaments are deflected by the irregular propagation on the right hemisphere (Panel E). Filtering cancelled that distortion allowing a stable projection of the stable driving rotor on the surface (Panel F).Conclusion: Surface AF activation patterns at the HDF are suggested to represent reentrant drivers in the majority of the AF patients we studied.

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WOMEN HAVE A TWO-FOLD HIGHER RISK FOR DEVELOPING CARDIAC TAMPONADE DURING AF ABLATION PROCEDURES: RESULTS FROM A MULTICENTER INTERNATIONAL SURVEY IN 27,249 CASES.Yoav Michowitz, MD, Michael Rahkovich, MD, Erica S. Zado, PA, Silke John, MD, Luigi Di Biase, MD, PhD, Roger Winkle, MD, Evgeny Mikhaylov, MD, Yan Yao, MD, PhD, Hildegard Tanner, MD, Emanuele Bertaglia, MD, Jean Champagne, MD, Koichiro Kumagai, MD, David Luria, MD, Dmitry Lebedev, MD, Paolo Della Bella, MD, Mark E. Josephson, MD, John M. Miller, MD, Jeremy N. Ruskin, MD, Andrea Natale, MD, Christopher Piorkowski, MD, Francis E. Marchlinski, MD and Bernard Belhassen, MD. Tel-Aviv Medical Center, Tel-Aviv, Israel, Hospital of the University of Pennsylvania, Philadelphia, PA, Leipzig Heart Center, Leipzig, Germany, Texas Cardiac Arrhythmia Institute, St. David’s Medical Center, Austin, TX, Silicon Valley Cardiology, Palo Alto, CA, Almazov Federal Heart,

AF and stroke in a subsequent year. In contrast, the rates for the age-matched lower risk group were 2.70%, 3.02%, and 0.38%, respectively for the same time period. The risk combination with the highest incidence of stroke and AF was hypertension and age ≥75. This cohort consisted of 298,560 patients with 28,968 stroke events and 32,268 diagnoses of AF through 2010. The hazard ratios for stroke and AF were 9.64 and 14.83, respectively, compared to a patient with lower risk factors (p<.0001).Conclusion:In an insured U.S. population at high risk for stroke and AF, patients with hypertension and age ≥75 had the most stroke and AF events in subsequent years. Therefore, increased prevention and detection efforts within this cohort may have the highest impact on outcomes.

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USE OF ACTIVE CONTACT IMPEDANCE MAPPING TO DIFFERENTIATE FOCAL FIRING FROM MICRO-REENTRYAllan Greenspan, MD and Sumeet Mainigi, MD. Albert Einstein Medical Center, Philadelphia, PAIntroduction: Recently a new 3D electroanatomic mapping technique, utilizing tissue impedance(Z) measurements during SVT was found useful in differentiating focal firing from macro-reentry by demonstrating the presence of a contiguous low impedance area (CLIA) in focal AT but not in macroreentrant flutters. However some arrhythmias result from micro-reentrant circuits that often mimic focal AT. To determine if impedance mapping could help establish a micro-reentrant arrhythmia mechanism based on the absence of a CLIA we studied 12 patients with documented AVNRT.Methods: We performed standard local activation time(LAT) electroanatomic mapping and Z mapping during SVT in 12 consecutive patients with AVNRT documented by standard pacing maneuvers. We employed the Carto 3 mapping system and a 4 mm tip RF ablation catheter accumulating 50-150 points throughout the RA. Z maps were generated by passing a 10 microvolt 50 Hz current through the mapping catheter, measuring the resultant voltage and calculating the tissue Z. Low Z was operationally defined as the minimum Z plus 10% of the Z range and normal Z as greater than the minuimum Z plus 20% of the range. The Z maps were examined for the presence of a contiguous low Z area(CLIA) with a surface area of 1.3-5.5 cm2.Results: In all 12 patients LAT mapping demonstrated a typical centripetal activation pattern with earliest activation at the infero-apical RA septal region,-30 to -85 msec prior to the reference with negative unipolar electrograms. None of the Z maps demonstrated a CLIA in the region of earliest activation or anywhere else.Conclusion: Despite an LAT map consistent with focal firing in AVNRT, the Z map ruled out focal firing by showing the absence of a CLIA. Z mapping appears to be an effective technique to identify micro-reentry as an arrhythmia mechanism.

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NONINVASIVE IDENTIFICATION OF REENTRANT DRIVERS OF ATRIAL FIBRILLATIONOmer Berenfeld, PhD, Miguel Rodrigo Bort, PhD, Andreu M. Climent, PhD, Alejandro Liberos Mascarell, MD, Jorge Pedron Torrecilla, MD, José Millet Roig, PhD, Angel Arenal, MD, Francisco Fernández-Avilés, MD, Felipe Atienza, MD, PhD and Maria S. Guillem, PhD. University of Michigan, Ann Arbor, MI, Universitat Politecnica de Valencia, Valencia, Spain, Hospital Universitario Gregorio Maranon, Madrid, SpainIntroduction: Noninvasive identification of atrial fibrillation (AF) mechanisms could improve treatment. We hypothesize that body

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or termination of MAT. We reviewed 16 consecutive cases of drug-refractory MAT received ablation targeting at the channels with continuous activation.Methods: Sixteen patients (10 male, 49 ± 12 years) received CARTO-guided ablation during Aug 2009 to Nov 2012. Mitral isthmus-dependent MAT was excluded. The reentrant circuits were marked according to activation maps (Figure 1a). Continuous activation was defined as visually verified low-voltage, three or more consecutive deflections (Figure 1b). All continuous activations were tagged, but only those located on the reentrant circuits were targeted for ablation.Results: Continuous activation was found in all patients (mean length 57 ± 53 mm). MAT was terminated during ablation in 14 of 16 patients (88%). The length of channel with continuous activation was significantly shorter in the successful group (n=14) than the failure group (n=2) (40 ± 29 vs. 176 ± 20 mm, p=0.02). There were no differences of MAT cycle length (282 ± 66 vs. 342 ± 93 ms, p = 0.27), longest duration of continuous activation (110 ± 41 vs. 80 ± 12 ms, p = 0.32), minimal BiVolt (0.14 ± 0.11 vs. 0.09 ± 0.04 mV, p = 0.5) and maximal BiVolt (0.69 ± 0.68 vs. 0.88 ± 0.31 mV, p = 0.72) of targeted channels between two groups.Conclusion: Ablation of MAT targeting at channels with continuous activation yields high success rate. A shorter length of the channels predicts a higher success rate of ablation.

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IBUTILIDE INCREASES THE VARIABILITY AND COMPLEXITY OF ATRIAL FIBRILLATION ELECTROGRAMS: INSIGHTS INTO ANTIARRHYTHMIC MECHANISMS USING NOVEL SIGNAL ANALYSESAngelo B. Biviano, MD, MPH, Edward Ciaccio, PhD, William Whang, MD and Hasan Garan, MD. New York Presbyterian Hospital and Columbia Univ Medical Center, New York, NYIntroduction: We used novel electrogram (EGM) analysis techniques to characterize how ibutilide administration changes the frequency, morphology, and repeatability of AF EGM signals, thereby providing insight into ibutilide’s antiarrhythmic mechanism of action.Methods: AF recordings were collected from 21 patients with AF both before and after ibutilide administration. The effects of ibutilide on the following AF EGM parameters were assessed: 1) dominant frequency, 2) variations in EGM amplitude and overall morphology, 3) repetition of electrogram patterns, and 4) complexity of the AF frequency spectra.Results: When comparing pre- vs. post-ibutilide administration EGMs, DF decreased from 5.45 to 4.02 Hz (p<0.0001). There was an increase both in the variability of AF EGM amplitudes (p=0.003) and variability of overall AF EGM morphologies (p=0.003). AF EGM pattern repetitiveness decreased (p=0.01),

Blood and Endocrinology Centre, Saint-Petersburg, Russian Federation, Clinical EP Laboratory and Arrhythmia Service Center of Fuwai Heart Hospital, Beijing, China, Department of Cardiology, Inselspital, University Hospital, Bern, Switzerland, Cardiology Clinic, Department of Cardiological, Thoracic and Vascular Sciences, University of Padua, Padua, Italy, Institut Universitaire de Cardiologie et Pneumologie de Québec, Quebec City, QC, Canada, Department of Cardiology, Fukuoka University, Fukuoka, Japan, Sheba Medical Center, Ramat Gan, Israel, Arrhythmia Department, Centro Cardiologico Monzino, Institute of Cardiology, Milan, Italy, Beth Israel Deaconess Medical Center, Boston, MA, Krannert Institute of Cardiology, Indianapolis, IN, Massachusetts General Hospital, Boston, MAIntroduction: Cardiac tamponade is the most dramatic complication observed during AF ablation and the leading cause of procedure-related mortality. Female gender is a known risk factor for complications during AF ablation; however, it is unknown whether women have a higher risk of tamponade. This multicenter survey was designed to assess the risk of cardiac tamponade during AF ablation procedures according to patient gender in a large cohort of patients.Methods: A systematic Medline review was conducted for all English language papers published between 2000-2012 dealing with AF ablation in patients ≥19 years old. All authors reporting tamponade as a procedure complication in their publications were contacted for providing more detailed information on: a) total number of procedures performed in each patient gender; b) total number of acute tamponade in regard to patient gender; c) age and management of patients experiencing tamponade. In a second step, authors were invited to update their results to include all AF ablation procedures performed in their laboratory.Results: Twenty seven EP centers provided detailed information on 27,249 ablation procedures (Table). Overall 260 (1%) cases of tamponade were reported (males 0.75%, females 1.5%, P<0.0001). The incidence of tamponade in the participating centers varied from 0.2 to 3.7% in men and from 0.2 % to 6.9 % in women. There was no gender difference in the mode of management.Conclusion: Tamponade during AF ablation procedures is relatively rare. Women have a twofold higher risk for developing this complication. This gender difference should be taken in account when obtaining informed patient consent before the procedure.

Male Female P valueTotal procedures (n). 19,554 (71.7%) 7695 (28.3%)Tamponade (n) 147 (0.75%) 113 (1.5%) <0.0001ManagementPericardiocentesis 83% 84% NSSurgery 17% 16% NSAge of patients with tamponade (years) 61±9 62±9 NS

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ABLATION OF MACROREENTRANT ATRIAL TACHYCARDIA TARGETING AT CHANNELS WITH CONTINUOUS ACTIVATIONHung-Ta Wo, MD, Chung-Chuan Chou, MD, Ming-Shien Wen, MD, Chun-Chieh Wang, MD, San-Jou Yeh, MD and Delon Wu, MD. Chang Gung Memorial Hospital, Linko, Taoyuan county, TaiwanIntroduction: Macroreentrant atrial tachycardia (MAT) in diseased atria is challenging for ablation. At present, the best results were achieved by entrainment combined with electroanatomical mapping. But entrainment studies in diseased atria have several pitfalls, such as failure of capture, acceleration

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NON-INFLUENCE OF LIPID LOWERING THERAPY IN ATRIAL FIBRILLATION RECURRENCEPeeyush Grover, MD, Neeraj Shah, MD, Nileshkumar J. Patel, MD, Kathan Mehta, MD, Vikas Singh, MD, George R. Marzouka, MD, Ankit Rathod, MD, Abhishek Deshmukh, MD, Hakan Paydak, MD, Ghanshyam Savani, MD, Ankit Chothani, MD, Apurva O. Badheka, MD and Raul D. Mitrani, MD. University of Miami Miller School of Medicine, Miami, FL, Staten Island University Hospital, New York, NY, Drexel University School of Public Health, Philadelphia, PA, Cedar Sinai Medical Center, Los Angeles, CA, University of Arkansas, Little Rock, AR, Washington Hospital Center, Washington, DCIntroduction: Lipid lowering therapy (LLT) has been shown to have anti-arrhythmic properties. We sought to determine whether it has a role in preventing atrial fibrillation (AF) recurrence.Methods: We performed a post hoc analysis of patients enrolled in Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial, including only patients in sinus rhythm at baseline (n=2,095). AF recurrence was determined on the basis of electrocardiograms done during each follow-up visit. The end point was the time to first AF recurrence (in months). Cox proportional hazards analysis was performed, after controlling for confounding factors.Results: 493 (23.5%) participants were on LLT at the time of randomization. AF recurred in 1,479 (70.6%) of patients with a mean follow-up of 18.5 months and maximum follow-up of 68.5 months. LLT was not associated with AF recurrence both in a univariate (hazard ratio (HR) 0.98, 95 % Confidence Interval (CI) 0.87-1.1, p=0.78) and multivariate model (HR 0.99, 95 % CI 0.87-1.1, p=0.96). Similar results were observed in rate control (n=1055) with HR 1.01 (95 % CI 0.84-1.2, p=0.92) & rhythm control (n=1040) arms with HR 0.99 (95 % CI 0.81-1.2, p=0.90). Upon addition of echocardiographic parameters to the model, LLT continued to have no statistically significant association with AF recurrence in the overall population (n=1434) (HR 1.05, 95% CI 0.90-1.2, p=0.52) as well as rate (n=722) (HR 1.06, 95% CI 0.85-1.3, p=0.59) and rhythm (n=712) (HR 1.02, 95% CI 080-1.3, p=0.86) control arms.Conclusion: LLT does not seem to have any effect in preventing AF recurrence in the AFFIRM patient population nor did LLT influence AF recurrence in either the rate or rhythm control arms.

and the AF frequency spectral profile manifested greater complexity (p=0.02). There were no significant differences in the studied parameters between patients whose baseline rhythm was AF vs. sinus rhythm.Conclusion: Novel electrogram signal analysis techniques reveal that ibutilide administration causes increased complexity in the atrial electrical activation pattern while decreasing rate. These findings may be explained by the progressive unmasking of lower frequency, less homogeneous, and increasingly disparate drivers of AF over the course of ibutilide administration, until AF maintenance becomes more difficult and either transforms to atrial tachycardia or terminates to sinus rhythm.

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PLATELET ACTIVATION AND ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH ATRIAL FIBRILLATION: IMPORTANCE OF CO-MORBID CONDITIONSHan S. Lim, MBBS, PhD, Scott R. Willoughby, PhD, Carlee Schultz, BSc, Muayad Alasady, MBChB, Dennis H. Lau, MBBS, PhD, Rajiv Mahajan, MD, Anand N. Ganesan, MBBS, PhD, Anthony G. Brooks, PhD, Kurt C. Roberts-Thomson, MBBS, PhD, Glenn D. Young, MBBS, Matthew I. Worthley, MBBS, PhD and Prashanthan Sanders, MBBS, PhD. Centre for Heart Rhythm Disorders, University of Adelaide and Royal Adelaide Hospital, Adelaide, AustraliaIntroduction: While atrial fibrillation (AF) is associated with increased left atrial (LA) thromboembolic risk it is still unclear whether this increased risk is due to AF per se or the accompanying comorbidities.Methods: Sixty patients undergoing catheter ablation for AF (30 lone AF, 30 AF with comorbidities) and 16 patients with left-sided accessory pathways (controls) were prospectively recruited. Blood samples were obtained from the LA, right atrium (RA) and femoral vein (FV) after transeptal puncture. Platelet activation (platelet P-selectin) was measured by flow cytometry and asymmetric dimethylarginine (ADMA) was measured using ELISA.Results: In patients with lone AF and AF with comorbidities, platelet activation was significantly elevated in the LA compared to the FV (Lone AF: LogP-selectin 2.7±0.1% LA vs. 2.5±0.1 FV, p<0.05; AF and comorbidities: LogP-selectin 2.9%±0.1 LA vs. 2.7±0.1 FV; p<0.05). There was no significant difference between sites in controls (p=0.1). For ADMA, there was no significant site difference in the lone AF, AF with comorbidities and control groups. However, between groups, there was a significant stepwise increase in ADMA from controls to lone AF and then patients with AF and comorbidities (p<0.001 between groups, see Figure).Conclusion: Left atrial platelet activation is significantly elevated compared to the peripheral circulation in patients with lone non-valvular AF. A stepwise increase was observed for ADMA in controls, patients with lone AF and patients with AF and comorbidities, suggesting AF per se and its associated comorbidities both contribute to endothelial dysfunction and prothrombotic risk.

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CHARACTERISTICS OF STIFF LEFT ATRIAL PHYSIOLOGY IN PATIENTS WITH ATRIAL FIBRILLATION: CLINICAL, ELECTROANATOMICAL CHARACTERISTICS, AND ABLATION OUTCOMEJunbeom Park, Sr., MD, Hee Sun Mun, MD, Jin Wi, MD, Jaemin Shim, MD, Jae-Sun Uhm, MD, Boyoung Joung, MD, PhD, Moon Hyoung Lee, MD, PhD and Hui-Nam Pak, MD, PhD. Yonsei university, Seoul, Republic of KoreaIntroduction: Stiff LA physiology (SLP) after cardiac surgery or radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) has been reported to be associated with poor hemodynamic or electrophysiologic outcomes. We explored the characteristics of SLP in pre-RFCA patients with AF, and compared their clinical outcome.Methods: We measured left arial pressure (LAP)during sinus rhythmin 440 non-valvular AF patients (76.7% male, 71.8% paroximal AF, 57.5±11.3years) who underwent RFCA. Based on median value of LA v-wave (LAPpeak) 19mmHg, we compared low LAP (L-LAP, n=211), high LAP with E/Em<8 (SLP, n=64), and high LAP with E/Em≥8 (elevated LV filling pressure; H-LVFP, n=165) in terms of clinical, imaging parameters, LA voltage (NavX, n=207), and clinical recurrence rates.Results: 1. SLP group was younger (52.7±10.7 vs. 57.4±11.8 years old, p<0.005) and more likely to be male (89.1% vs. 76.3%, p=0.01) than L-LAP or H-LVFP groups. 2. SLP group had lower mean LA voltage than L-LAP group (1.1±0.6mV vs. 1.4±0.7mV, p=0.031), and smaller LA volume index than H-LVFP group (31.2±10.8mL/m2vs. 37.1±12.5 mL/m2, p=0.002). 3. During 13.4±5.9 months follow-up, clinical AF recurrence rates were 12.3% (L-LAP), 21.9% (SLP), and 23.5% (H-LVFP), respectively (p=0.013).Conclusion: SLP was commonly found in relatively young male AF patients with small LA and low LA voltage. Clinical recurrence rate was higher in SLP and H-LVFP groups than in L-LAP group.

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P-WAVE CHARACTERISTICS AND HISTOLOGICAL ATRIAL ABNORMALITYYan Huo, MD, Petter Holmberg, MD, Lubov Mitrofanova, MD, Victoria Orshanskaya, MD, Fredrik Holmqvist, MD, PhD and Pyotr G. Platonov, MD, PHD, FHRS. 1, Department of Cardiology, Lund University Hospital, Lund University, Lund, Sweden; 2, Department of Electrophysiology, Leipzig Heart Center-University of Leipzig, Leipzig, Germany;, 1 - Lund, 2 - Leipzig, Germany, 1, Department of Cardiology, Lund University Hospital, Lund University, Lund, Sweden, 1 - Lund, Sweden, 3,

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DIGOXIN REMAINS A VALID RATE CONTROL OF CHOICE IN THE MANAGEMENT OF ATRIAL FIBRILLATION; ITS DELETERIOUS EFFECT ARE BALANCED BY THE ADDITION OF BETA-BLOCKERS AND CALCIUM CHANNEL BLOCKERS. AN ACAP-RACE REGISTRY ANALYSISChaithanya K. Pamidimukala, MBBS, Urvi Pai, MBBS, Alexandre M. Benjo, MD, PhD, Balaji Pratap, MD, Joseph Bastawrose, MBChB, Rishad Usmani, MD, Matthew Pierce, MD, Ramya Bharathi, BS, Ammy Malinay, RN, Ian M. Lizardo, BS, Joshua Aziz, BSc, Eyal Herzog, MD and Emad F. Aziz, DO. St. Luke s and Roosevelt Hospitals, Columbia University College of Physicians and Surgeons, New York, NY, St. Luke s and Roosevelt Hospitals, Columbia University, New York, NYIntroduction: Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice, and is a significant risk factor for ischemic stroke and death. Digitalis has been used for more than 200 years to treat heart conditions including AF.Methods: ACAP-RACE is a prospective longitudinal registry that has been established at our institution for the management of patients with AF. We evaluated patients admitted with AF, looking at the effect of different medical therapies on long-term outcome. The primary endpoint was a composite of atrial fibrillation readmission, stroke and death.Results: The cohort included 1662 subjects, 862 (52%) men, mean age of 71 ± 15 years. 76% had hypertension, 26% were diabetics, 21% had CAD, and 33% had heart failure. Rate and rhythm control therapies included 68% beta blockers (BB), 49% calcium channel blockers (CCB), 17% anti-arrhythmic drugs and 20% digoxin. 95% of the patients received anticoagulation. The use of digoxin was associated with the most efficacious rate control on our cohort but as demonstrated by KM curve, patients on digoxin alone had the worst outcome when compared to patients not receiving the drug; P<0.001. This detrimental effect seems to be evaded by adding BB or CCB to digoxin.Conclusion: Digoxin is an efficacious drug for rate controlling patients on AF but in our cohort it is associated with an increased incidence the composite of readmission, stroke and death. These deleterious effects seem to subside with the addition of BB or CCB. Based on our experience the use of digoxin should be reserved as second line treatment in combination with BB or CCB.

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after PVI it was always < 0.4 mV except for LSPV. On average, the peak-to-peak voltage for all PVs was significantly lower after PVI (0.97 ± 0.20 vs. 0.35 ± 0.21 mV, p < 0.01). Similarly, maximal slope before PVI was consistently > 0.1 mV/ms, whereas, after PVI it was always < 0.08mV/ms except for LSPV. On average, for all PVs it was significantly lower after PVI (0.18 ± 0.03 vs. 0.07 ± 0.03 mV/ms, p < 0.01).Conclusion: We created a database of B-EGM characteristics at the PV ostia. The value of this library as an aid to algorithmically interpret PVP can now be studied.

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4-YEAR FOLLOW-UP AFTER ABLATION OF PAROXYSMAL ATRIAL FIBRILLATION: CRYOBALLOON VERSUS RADIOFREQUENCY CATHETER ABLATIONMichael S. Kühne, MD, Sven Knecht, PhD, Beat Schaer, MD, Stefan Osswald, MD and Christian Sticherling, MD. Cardiology/Electrophysiology, University Hospital Basel, Basel, SwitzerlandIntroduction: Cryoballoon pulmonary vein (PV) isolation (Cryo-PVI) has emerged as a alternative technology for ablation of atrial fibrillation (AF). Information on long-term follow-up after Cryo-PVI compared to PVI using radiofrequency energy (RF-PVI) is not available.Methods: Cryo-PVI was performed in 25 patients using a 28-mm cryoballoon ablation catheter (Arctic Front, Medtronic). Each PV was treated with a minimum of 2 applications. Twenty-five patients undergoing RF-PVI using an open-irrigation RF ablation catheter and a 3D-electroanatomic mapping system served as a control group. The procedural endpoint was PVI confirmed by a circumferential mapping catheter. Follow-up was performed 3, 6 and 12 months after the procedure, and then at least every 12 months.Results: Fifty patients (age 59±9 years, ejection fraction 0.59±0.06, left atrial size 41±5 mm) with paroxysmal AF were included. After a single procedure and a follow-up of four years, 13 of 25 patients (52%) were free from arrhythmia without antiarrhythmic drugs, both in the Cryo-PVI group and the RF-PVI group. When including repeat procedures with a mean of 1.5±0.7 procedures per patient, 21 of 25 patients (84%) in the Cryo-PVI group and 20 of 25 patients (80%) in the RF-PVI group (1.4±0.6 procedures per patient) remained in stable sinus rhythm, respectively (p>0.99). One patient in the RF-PVI group experienced left atrial flutter. This was also counted as a recurrence.Conclusion: Single-procedure efficacy of PVI is approximately 50% after a follow-up of 4 years and this is independent of the energy source used. When including repeat procedures in 36% of patients, the success rate is increased to approximately 80%.

Almazov Federal Center for Heart Blood and Endocrinology, St. Petersburg, Russia., St. Petersburg, Russian Federation, 1, Department of Cardiology, Lund University Hospital, Lund University, Lund, Sweden, Lund, SwedenIntroduction:Fibro-fatty transformation of atrial walls is believed to be the leading cause of deteriorated atrial conduction, however any direct assessment of fibrosis extent in the major atrial conduction routes in relation to P-wave characteristics is lacking. We aimed at assessing P-wave morphology and duration in relation to histology of atrial myocardium.Methods: Atrial specimens from 11 patients died from cardiovascular causes (7 men; median age 73 years, range 54-82) were collected. Tissue samples were taken at the level of superior and inferior pulmonary veins, center of posterior left atrial wall, terminal crest (CT) and Bachmann’s bundle (BB) and stained with Masson’s trichrome for assessment of fibrosis and fatty tissue extent at all locations. Standard 12-lead ECGs in sinus rhythm recorded during hospital stay were retrieved from medical records, scanned for manual assessment of PWD and P-wave morphology. Partial interatrial block (pIAB) was defined as prolonged (≥120 ms) and bimodal P-wave in II, III and aVF.Results: The median PWD was 160 (range 120-200) ms. Fibrosis extent in CT highly correlated to PWD (r=0.914, p<0.001). The combination of fibrosis extent and fatty tissue in BB (16%, range 1-41%), CT (18%, range 3-47%) or SPV (15%, range 6-24%) correlated to PWD (r=0.627, p=0.039; r=0.795, p=0.003; and r=0.668, p=0.025, respectively). pIAB pattern was observed in 6 patients, however it was not associated with increased fibrosis or fatty tissue content at any sampling location.Conclusion: Our findings provide direct evidence of strong association between PWD and the extent of structural abnormalities in the atrial myocardium and the major atrial conduction routes, but do not support presumed association between fibrosis and ECG pattern of pIAB.

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ALGORITHMIC EGM ANALYSIS: A FIRST STEP TOWARDS AN AUTOMATED ASSESSMENT OF PULMONARY VEIN ISOLATIONMilad El Haddad, MS, Benjamin Berte, MD, Marta Acena, MD, Yves Vandekerckhove, MD, Roland Stroobandt, MD, PHD, FHRS, Rene Tavernier, MD, PhD and Mattias Duytschaever, MD, PhD. University of Ghent, Ghent, Belgium, AZ Sint-Jan Hospital, Bruges, Belgium, University Hospital of Ghent, Ghent, BelgiumIntroduction: Far-field potentials (FFP) and PV potentials (PVP) coexist in the bipolar electrogram (B-EGM) recorded at the PV ostium. The objective of this study was to characterize algorithmically -by morphology, amplitude and slope- the B-EGM before (FFP+PVP) and after proven isolation (FFP only).Methods: B-EGMs were recorded (3 sec) at the PV ostium by a decapolar circular catheter, before and after pulmonary vein isolation (PVI). Ninety seven PV (LSPV n=20, LIPV n=12, RSPV n=40 and RIPV n=25) exhibiting PV automaticity following PVI (unambiguous proof of entry block) were analyzed. A custom-made algorithm determined the morphology (flat, monophasic, biphasic, triphasic, multi-component, or double potential), peak-to-peak amplitude, and maximal slope. Each PV was divided into an anterior and posterior hemisphere.Results: In total, 1611 (765 before and 846 after PVI) B-EGM were analyzed. After PVI, except for LSPV, B-EGM morphology was characterized by a predominance (>85%) of flat, monophasic and biphasic potentials, whereas before PVI all types of morphology were equally distributed (fig1). Peak-to-peak voltage was consistently > 0.6 mV before PVI, whereas,

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with CHA2DS2-VASc risk score ≥ 2 who discontinued OAT after successful AF ablation.Results: 98 of 250 (37.7%) patients had a CHA2DS2-VASc risk score ≥ 2. 18 (18.4%) patients had a prior history of stroke. 55 (56%) patients were free from any recurrence and . OAT was discontinued in 29 (29.6%) patients (25 men, mean age 60+/-9.7 years, 8 (27.6%) paroxysmal AF, 8 (27.6%) persistent AF and 13 (44.8%) long-standing persistent AF, 2+/-0.8 procedures per patients). Follow-up without OAT was 6.3+/-3.2 years (median 6.4 years). OAT was switch to platelet aggregation inhibiting drugs in 13/29 patients (44.8%). The average CHA2DS2-VASc score was 2.7+/-0.9 (median 2). During follow-up, 4/29 (13.8%) patients who had discontinued OAT experienced an ischemic stroke (incidence rate 2.2%/year vs 0.6%/year in patients who have not stopped OAT, p=0.2). Stroke events occurred between 11 days and 9.3 years after OAT discontinuation (median 4.1 years).Conclusion: OAT was discontinued in one-third of patients at high risk for stroke. After long-term follow-up (median 6.4 years), the incidence of stroke was higher but did not reach statistical significance.

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CLINICAL AND PROCEDURAL FEATURES ASSOCIATED WITH HIGH RISK OF MULTIPLE PROCEDURES TO ACHIEVE PAROXYSMAL ATRIAL FIBRILLATION ABLATIONSana Amraoui, Sr., MD, Nicolas Derval, MD, Frederic Sacher, MD, PhD, Arnaud Denis, MD, Adlane Zemmoura, MD, Philippe Ritter, MD, PhD, Pierre Bordachar, MD, PhD, Michel Haissaguerre, MD, PhD and Pierre Jais, MD, PhD. Hopital Haut Leveque, Pessac, FranceIntroduction: Catheter ablation of paroxysmal AF has proven efficacy and safety. However, more than 20% of patients require more than one procedure to achieve clinical success. We aimed to identify groups of patients associated with higher risk of AF recurrence after PAF ablation.Methods: All patients referred for catheter ablation of PAF (<7 days) in our institution were included in the study. All patients had lasso-guided PVI, additional LA substrate ablation (complex fractionated electrogram (CFE), linear ablation) was performed if spontaneous or induced AF was sustained after PVI. Follow-up visit were performed at 3, 6 and 12 months with clinical evaluation, TTE, 24 hours holter monitoring. Recurrence was defined by more than 30 sec of documented AF or typical symptoms of palpitation. We used uni- and multivariable models to identify predictors of AF recurrence over 12 months follow-up.Results: A total of 338 Pts (55 ± 11,2 yrs, 25,2% females) underwent a first ablation for PAF between 2004 and 2010. Median longest reported AF episode was 12 hours, range 1 to 168H. After 12 ± 4,5 mo., 77,2% of pts were free of AF after a mean of 1.5 ± 0.8 procedures. After single procedure, criteria associated with more recurrence were: female gender (p=0,03), hypertension (p=0,01), longest episode > 24H (p=0,10) (univariable model). Patients with longest episode ≤ 24h had more chance to achieve success after 1 procedure (0R= 1,9; CI [1,02-3,78]).Conclusion: In PAF ablation longest episode of AF > 24h, hypertension and female gender are associated with higher risk of AF recurrence.

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ABLATION THERAPY VERSUS MEDICAL THERAPY IN ELDERLY ATRIAL FIBRILLATION -A PROPENSITY SCORE MATCHED COMPARATIVE STUDYXin Du, MD, Man Ning, MD, Jian-Zeng Dong, MD, Rong-Hui Yu, MD, De-Yong Long, MD, Ri-Bo Tang, MD, Jia-Hui Wu, MD, Song-Nan Li, MD, Xiao-Hui Liu, MD and Chang-Sheng Ma, MD. Department of Cardiology,Beijing Anzhen Hospital, Beijing, ChinaIntroduction: Catheter ablation for atrial fibrillation (AF)is efficientin maintaining sinus rhythm. Whether this therapy can reduce the risk of death and embolic events is unclear, especially in elderly patients.Methods: This case cohortstudy enrolledelderly AF patients (≥65 years) from 2 tertiary hospitalsand 2 level 2 hospitalsin Beijing.Pulmonary vein isolation (PVI) was performed in paroxysmal AF, while additional linear ablation at the roof, mitral isthmus and cavotricuspid isthmus was undertaken in persistent AF.Medical therapy was at the discretion of the treating physician. Each patient was followed up every 6 months by telephone.Propensity scores for receiving catheter ablation were calculated for each of the enrolled patients based on a multivariable logistic regression model which includedeighteen baseline characteristics variables. Ablated and medical therapy patients were matched on a 1:1 basis with a combination of nearest neighbor algorithm. Unadjusted comparisons of event rates for the primary outcomes including timeto first composite primary endpoint (death, stroke and peripherial embolism(PE))forthe 2 groupsweremadeusingtheKaplan-Meiermethodandlog-rank test was used to comparebetweenthe groups.Chi-square testwas used to comparethe rate of composite primary endpoints.Results: The study included 611 catheterablationpatientsand 1432 medically treated patients from November 2008 to December 2011.Thepropensity-matchingalgorithmproduced424pairsofpatients. Aftermatching,thepatientcharacteristics were wellbalanced (P>0.05)betweengroups except the payer type (P<0.001).In catheter ablation patients, 69.8%were in sinus rhythm during follow-up. In the ablation group, 16.7% patients were on warfarincompared to 26.3% in medical therapy group.Overallrateof the composite primary endpoint was1.6%/yearintheablation patients versus 7.3%/yearinthenon-ablation patients (HR 0.217(0.109-0.431).Conclusion: Inthepropensity-matchedsample, risk of death, stroke and PE were significantly lower intheablationgroupcomparedtomedical therapy group.

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LONG TERM FOLLOW-UP OF PATIENTS WITH AN INDICATION FOR ANTICOAGULATION (CHA2DS2-VASC SCORE ≥2) AFTER SUCCESSFUL ATRIAL FIBRILLATION ABLATIONArnaud Denis, MD, Nicolas Derval, MD, Zohra Kechida, MD, Daniel Scherr, MD, Khaled Ramoul, MD, Matthew Daly, MD, Yuki Komatsu, MD, Stephan Zellerhoff, MD, Laurence Jesel, MD, Ashok Shah, MD, Frederic Sacher, MD, Meleze Hocini, MD, Pierre Jais, MD and Michel Haissaguerre, MD. CHU Bordeaux, Bordeaux, FranceIntroduction: The aim of this study was to evaluate the long-term safety of oral anticoagulant therapy (OAT) discontinuation after successful atrial fibrillation (AF) ablation in CHA2DS2-VASc score ≥2 patients.Methods: We retrospectively studied 250 patients who underwent AF ablation between 2001 and 2008. Pulmonary vein isolation was done for all patients and additional stepwise approach was used for persistent AF. We included all patients

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FINDINGS IN PATIENTS UNDERGOING REPEATED PULMONARY VEIN ISOLATION PROCEDURES: EVIDENCE TO SUPPORT WHITTLING AWAYDavid Lin, MD, Sanjay Dixit, MD, Erica Zado, PA, Mathew Hutchinson, MD, David S. Frankel, MD, Joshua M. Cooper, MD, Michael Riley, MD, PhD, Rupa Bala, MD, Fermin C. Garcia, MD, Gregory Supple, MD, David Callans, MD and Francis E. Marchlinski, MD. Hospital of Univ of Pennsylvania, Cardiology, Philadelphia, PAIntroduction: At least 30% of patients (pts) undergoing atrial fibrillation (AF) ablation will require repeat procedures despite prior successful pulmonary vein isolation (PVI). PV reconnection is the typical finding at the 1st repeat procedure. However, PV status, arrhythmia sources and outcomes in pts requiring additional procedures have not been characterized.Methods: Pts included all who underwent PVI at our institution between November 2000 and January 2012. All pts with >3 procedures were included. Prior ablation consisted of antral PVI plus targeting of non-PV triggers of AF that could be provoked with isoproterenol +/or cardioversion. All pts with reconnected PVs underwent antral PVI and ablation of non-PV triggers when present without any additional empiric ablation. We report outcome in pts with >12 month followup from the last procedure.Results: Of 2886 pts who underwent their first PVI, 181 (6%) pts had 2 or more repeat procedure (3 procedures in 146 pts and >/= 4 procedures in 35 pts). In 12 pts, the recurrent clinical arrhythmia was other than AF and successfully eliminated and PVs not rechecked. Of the remaining 169 pts, 69 (41%) had 4 reconnected PVs, 27 (16%) had 3, 31 (18%) had 2, 29 (17%) had 1 reconnected PV. Only 13 (8%) had all PVs found to be isolated. Provocative techniques performed in 127 pts initiated PV triggers in 92 pts including AF or PV atrial tach in 51% and frequent APDs only in 22%. New non-PV triggers were initiated in 18 pts (14%). During mean followup of 31 mos (12 - 87 months) 50 pts (45%) had no AF off antiarrhythmic drugs (AAD); 22 pts (26%) had no AF with AAD; and 14 pts (13%) had >90% AF control with extended monitoring with good symptom control; 24 pts (22%) had recurrent AF.Conclusion: At the time of multiple AF ablation procedure PV triggers initiating AF is common and PV reconnection the rule. New non-PV AF triggers are provoked in small (14%) but significant group of patients. Following repeat antral PVI and targeting of non-PV triggers, without any additional empiric ablation, long term AF control was achieved in 78% of pts. Our findings suggest that attempting to identify and eliminate non-PV triggers and continued whittling away of PV connections are effective in long term control of AF and support the role for 3rd or 4th procedures as needed for AF recurrence.

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RHYTHM-SYMPTOM CORRELATION IN PATIENTS ON CONTINUOUS MONITORING AFTER CATHETER ABLATION OF ATRIAL FIBRILLATIONMassimo Moltrasio, MD, Antonio Dello Russo, MD, Massimo Tritto, MD, Maurizio Landolina, MD, Piergiuseppe De Girolamo, MD, Gianluigi Bencardino, MD, Paolo Della Bella, MD, Emanuele Bertaglia, MD, Alessandro Proclemer, MD, Valerio De Sanctis, MD, Massimo Mantica, MD and Claudio Tondo, MD. Centro Cardiologico Monzino, Milan, Italy, Mater Domini, Castellanza, Italy, San Matteo, Pavia, Italy, San Camillo, Roma, Italy, Policlinico Gemelli, Roma, Italy, Ospedale San Raffaele, Milan, Italy, Ospedale civile, Mirano, Italy, S Maria della Misericordia, Udine, Italy, Istituto s Ambrogio, Milan, Italy

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LOW VOLTAGE AREA IN THE LEFT ATRIUM IS STRONG PREDICTOR FOR ATRIAL FIBRILLATION RECURRENCES FOLLOWING ABLATION: WHO IS MORE SUSCEPTIBLE?Miyako Igarashi, MD, Hiroshi Tada, MD, Yukio Sekiguchi, MD, Hiro Yamasaki, MD, Kenji Kuroki, MD, Takeshi Machino, MD, Yoko Ito, MD, Nobuyuki Murakoshi, MD, Keisuke Kuga, MD and Kazutaka Aonuma, MD. University of Tsukuba, Tsukuba, Japan, University of Fukui, Fukui, JapanIntroduction: The relationship between atrial fibrillation (AF) and left atrial (LA) structural remodeling has been reported. However, there is limited information on the factors for developing arrhythmogenic substrates and their relationship to the clinical outcome following radiofrequency catheter ablation (RFCA).Methods: Using an electro-anatomical mapping system, LA endocardial voltage mapping was performed during sinus rhythm (SR) in 104 AF patients who underwent RFCA. In persistent AF patients (n=49), SR was restored by antiarrhythmic drugs with/without electrical cardioversion before mapping. The presence of a low voltage area (LVA), defined as an area with amplitudes of <1.0 mV and occupying >15% of the LA surface area, was examined.Results: An LVA was found in 25 (24%) patients. The age (OR=1.14; 95% CI=1.04-1.25), AF type (OR=12.03; 95% CI=2.97-48.72) and chronic kidney disease (CKD) (OR=3.3, 95%CI=1.01-10.81) were independent risk factors of the presence of an LVA. On the other hand, the AF-free rate at 18-months follow-up after RFCA was significantly lower in the patients with LVA than that in those without (30.8% vs. 59.0%, p<0.01; See the figure). Furthermore, the presence of an LVA was the only predictor of AF recurrence after RFCA (HR=2.25, 95% CI=1.08-4.72, p<0.05) in the multivariable analysis.Conclusion: Aging, persistent AF and CKD may facilitate the development and progression of an LVA. The presence of an LVA may predict an unfavorable outcome following RFCA.

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AF recurrence. Patients with persistent AF prior to ablation had significantly more recurrences than patients with paroxysmal AF (70.1% vs. 42.0%, p<0.001). Mean LA pressure was significantly higher in patients with recurrence of AF (13.4 ± 7.1 vs. 11.0 ± 5.2 mmHg, p=0.007). Mean LA volume index was enlarged in patients with recurrence (40.1±18.5 vs. 33.0±11.2, p<0.001). In the multivariate analysis, mean LA pressure was predictive in patients with normal or mildly enlarged LA, while AF type was not predictive. For each 1 mmHg increase in LA pressure the risk oft AF recurrence increased by 11% in this subgroup. In patients with moderately or severely enlarged LA, AF type was predictive whereas LA pressure was not.Conclusion: LA pressure, AF type and LA volume index are independent predictors for recurrence of AF after PVI. LA pressure may be helpful especially in patients with small atria, where AF type is not predictive.

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CATHETER ABLATION OF ATRIAL FIBRILLATION IS INDEPENDENTLY ASSOCIATED WITH A LOWER INCIDENCE OF STROKENazem W. Akoum, MD, FHRS, Sameer Ghate, PhD, Leenhapong Navaravong, MD and Nassir Marrouche, MD, FHRS. Comprehensive Arrhythmia Research and Management (CARMA) Center-University of Utah, Salt Lake City, UTIntroduction: Atrial Fibrillation (AF) is a known risk factor for stroke. Catheter ablation (CA) is increasingly used for the treatment of AF. We compared the incident rate of stroke in patients undergoing CA to others with AF not treated with CA.Methods: A retrospective cohort study was conducted using the University of Utah Enterprise Data Warehouse (EDW) between January 2006 and October 2012. We compared AF pts undergoing CA to AF pts not undergoing CA. Pts were followed till the end of study period or date of occurrence of stroke whichever came first. Multivariate analysis was performed to assess the likelihood of stroke in the CA groups, adjusting for CHADS2 score and other comorbidities.Results: A total of 14,850 AF patients were included. CA was performed in 1,099 pts (7.4%). The mean age was lower in the CA group (61.8±14.5 yrs) compared to the no-CA group (66.3±14.7yrs; p<0.01). The CHADS2 score was 0.89±1.1 in the CA group compared to 0.65±89 in the no-CA group. Warfarin use was higher in the CA group (31.57%) compared to the no-CA group (12.36%; P<0.01) post AF diagnosis. During follow up, incident ischemic stroke in the no-CA group was significantly higher (n=1,505; 11.2%) in the no-CA group compared to the CA group (n=40; 3.7%; p<0.01). At the time of stroke, more patients were likely to be on OAC in the CA group (average INR 1.84±1.06) compared to the no-CA group (average INR 1.44±1.32). In multivariate logistic regression analysis, CA was associated with a lower likelihood of stroke (odds ratio [OR], 0.21; [95% CI]= [0.21-0.40]; p<0.01).Conclusion: Catheter ablation for AF is associated with a lower rate of incident stroke compared to no ablation. Patients who had a stroke after ablation did so despite a higher use of warfarin.Regression Analysis for the Occurrence of Stroke

Univariate Analysis

Multivariate Analysis

Odds Ratio p value Odds Ratio p

valueAF ablation 0.30 <0.01 0.21 <0.01CHADS2 score 1.28 <0.01 0.94 0.27Average INR value 0.55 <0.01 0.58 <0.01

Introduction: Aim of the study was to evaluate if Implantable Cardiac Monitor (ICM) is useful to detect the real incidence of AF recurrences and to analyze the relationship between symptoms and recurrences after AF ablation.Methods: Between January 2009 and July 2010, 143 pts who had undergone successful AF ablation and implantation of ICM (Medtronic, Reveal XT) were enrolled by 8 centers. ICMs were programmed to detect AF lasting >6 min to exclude false episodes. Routine follow-up (FU) at 3-month interval was performed.Results: Pts’ mean age was 59±years, 85% were male, 55% with paroxysmal AF. Pulmonary vein isolation was achieved in all pts, with additional left atrium lines in 26% of pts and ablation of inferior cavo-tricuspid isthmus in 41%. Radiofrequency energy was used in 93% of pts and cryothermy in 7%. Sinus rhythm was achieved after ablation in 97% of pts. The ICM was implanted without complications within 2 days after ablation. Mean follow-up was 14±6 months. The symptom-rhythm correlation is reported in the figure.Conclusion: Even if the majority of pts were symptomatic on baseline evaluation, 46% of them became asymptomatic after ablation; 29% of pts still perceived symptoms even without arrhythmia recurrences. Therefore, pts’symptoms are an unreliable means (sensitivity of 53%) of judging clinical status and/or the treatment strategy.

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LEFT ATRIAL PRESSURE AS PREDICTOR FOR RECURRENCE OF ATRIAL FIBRILLATION AFTER PULMONARY VEIN ISOLATIONMarkus Linhart, MD, Nina Karbach, Erica Mittmann-Braun, MD, René Andrié, MD, Christoph Hammerstingl, MD, Georg Nickenig, MD, Thorsten Lewalter, MD, Jan W. Schrickel, MD and Lars M. Lickfett, MD. Department of Medicine - Cardiology, Bonn, Germany, Isar Herzzentrum, München, Germany, Elisabeth-Krankenhaus Rheydt, Mönchengladbach, GermanyIntroduction: Recurrence of atrial fibrillation (AF) after first pulmonary vein isolation (PVI) is a common clinical problem. Reliable identification of risk factors has important implications. Left atrial (LA) pressure is largely observator-independent parameter that can easily be determined on-site after transseptal puncture during PVI. The aim of this study was to investigate the predictive value of LA pressure for AF recurrence after PVI and its relationship to other pre-procedural parameters.Methods: N/AResults: 205 consecutive patients with paroxysmal or persistent AF scheduled for first circumferential PVI were prospectively enrolled. Baseline clinical data were collected. During PVI, LA pressure was determined invasively directly after transseptal puncture. PVI was performed with radiofrequency or cryoenergy. After a mean follow-up of 25±7 months, 105 (51%) patients had

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Little Rock, AR, Cedars-Sinai Hospital, Los Angeles, CAIntroduction: We sought to investigate effect of left ventricular hypertrophy (LVH) on cardiovascular outcomes in atrial fibrillation (AF) patients.Methods: We included 2,115 patients enrolled in AFFIRM trial with available echocardiographic data for left ventricular mass (LVM) calculations per American Society of Echocardiography formula. The cohort was divided in two categories: normal vs. increased LVM & rate vs. rhythm control. Primary endpoint was all-cause mortality (ACM), secondary endpoint was composite of ACM, arrhythmia, stroke, major bleed, myocardial infarction & pulmonary embolism & tertiary endpoint was hospitalization for cardiovascular causes. We did multivariate Cox regression analysis reporting adjusted hazard ratio (HR) with 95% confidence interval.Results: There were 332 (15.7%) deaths & 1,393 cardiovascular hospitalizations over a 6 year period. ACM was significantly higher in patients with severely increased LVM (HR=1.36; 1.03-1.82, p<0.05), which was seen in rhythm control arm (HR=1.61; 1.09-2.37, p<0.05) but not rate control arm (HR=1.06; 0.68-1.64, p=0.8). Secondary endpoint showed similar higher events in rhythm control (HR=1.34; 1.0-1.8, p=0.05) but not rate control arm. Cardiovascular hospitalization rate was also higher in those with increased LVM in rhythm control arm (HR=1.28; 1.01-1.61, p<0.05). HR for ACM per each 10 gram increase in LVM was 1.02; 1.01-1.04, p<0.05, which was also more manifest in rhythm control arm (HR=1.04; 1.01-1.06, p<0.05).Conclusion: Patients with AF & LVH face significantly higher morbidity & mortality when utilizing rhythm control strategy, suggesting a potential hazardous interaction between LVH & use of antiarrhythmic drugs.

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FIVE YEAR FOLLOW UP OF PATIENTS WITH STRUCTURAL HEART DISEASE UNDERGOING CATHETER ABLATION OF PERSISTENT ATRIAL FIBRILLATION USING THE STEPWISE APPROACHDaniel Scherr, MD, Shinsuke Miyazaki, MD, Valerie Aurillac-Lavignolle, RN, MS, Patrizio Pascale, MD, Stephen B. Wilton, MD, Khaled Ramoul, MD, Yuki Komatsu, MD, Laurent Roten, MD, Ashok Shah, MD, Matthew Daly, MD, Amir Jadidi, MD, Michala Pedersen, MD, Sebastien Knecht, MD, Arnaud Denis, MD, Hubert Cochet, MD, Nicolas Derval, MD, Meleze Hocini, MD, Frederic Sacher, MD, Michel Haissaguerre, MD and Pierre Jais, MD. CHU Bordeaux, Hôpital du Haut-Lévêque, Bordeaux, FranceIntroduction: In the BLOC-AF study (Bordeaux Long term Outcome after Catheter ablation of persistent AF) we evaluated long-term success rates and predictors of success after stepwise

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CRYOBALLOON VERSUS RADIOFREQUENCY FOR PULMONARY VEIN RE-ISOLATION AFTER A FAILED INITIAL ABLATION PROCEDURE IN PATIENTS WITH PAROXYSMAL ATRIAL FIBRILLATIONAlexander Romanov, MD, PhD, Evgeny Pokushalov, MD, PhD, Sergey Artyomenko, MD, Vera Baranova, MD, Denis Losik, MD, Sevda Bairamova, MD, Alexander Karaskov, MD, PhD, Jonathan S. Steinberg, MD and Suneet Mittal, MD. Research Institute of Circulation Pathology, Novosibirsk, Russian Federation, The Valley Health System and Columbia University College of Physicians & Surgeons, New York, NYIntroduction: Catheter ablation of paroxysmal atrial fibrillation (PAF) is associated with an important risk of early and late recurrence, necessitating repeat ablation procedures. The aim of this prospective randomized patient-blind study was to compare the efficacy and safety of cryoballoon (Cryo) versus radiofrequency (RF) ablation of PAF after failed initial RF ablation procedure.Methods:Patients with a history of symptomatic PAF after a previous failed first RF ablation procedure were eligible for this study. Patients were randomized to Cryo or RF redo ablation. The primary end-point of the study was recurrence of atrial tachyarrhythmia, including AF and left atrial flutter/tachycardia, after a second ablation procedure at 1 year of follow-up. All patients were implanted with a cardiac monitor (Reveal XT, Medtronic) to continuously track the cardiac rhythm. Patients with an AF burden (AF%) ≤ 0.5% were considered AF-free (Responders), while those with an AF% > 0.5% were classified as patients with AF recurrences (non-Responders).Results: Eighty patients with AF recurrences after a first RF pulmonary vein isolation (PVI) were randomized to Cryo (N = 40) or to RF (N = 40). Electrical potentials were recorded in 77 mapped PVs (1.9 ± 0.8 per patient) in Cryo Group and 72 PVs (1.7 ± 0.8 per patient) in RF Group (p=0.62), all of which were targeted. In Cryo group, 68 (88%) of the 77 PVs were re-isolated using only Cryo technique; the remaining nine PVs were re-isolated using RF. In RF group, all 72 PVs were successfully re-isolated (p=0.003 vs Cryo). By intention-to-treat, 23 (58%) RF patients were AF-free vs 17 (43%) Cryo patients on no antiarrhythmic drugs at one year (p=0.06). Three patients had temporary phrenic nerve paralysis in the Cryo group; the RF group had no complications. Of the 29 patients who had only Cryo PVI without any RF ablation, 11 (38%) were AF-free vs 20 (59%) of the 34 patients who had RF only (p=0.021).Conclusion: When patients require a redo pulmonary vein isolation ablation procedure for recurrent PAF, RF appears to be the preferred energy source relative to Cryo.

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PATIENTS WITH ATRIAL FIBRILLATION AND LEFT VENTRICULAR HYPERTROPHY HAVE SIGNIFICANTLY INCREASED MORTALITY WHEN TREATED WITH RHYTHM CONTROL STRATEGY: A POST-HOC ANALYSIS FROM AFFIRM TRIALNeeraj N. Shah, MD, Nileshkumar Patel, MD, Peeyush Grover, MD, Ankit Chothani, MD, Kathan Mehta, MBBS, Abhishek Deshmukh, MD, Vikas Singh, MD, Ankit Rathod, MD, Hakan Paydak, MD, Valay Parikh, MD, Ghanshyam Savani, MD, George R. Marzouka, MD, Marcin Kowalski, MD, Apurva Badheka, MD, Raul Mitrani, MD and Juan Viles-Gonzalez, MD. Staten Island University Hospital, Staten Island, NY, University of Miami Miller School of Medicine, Miami, FL, Washington Hospital Center, Washington, DC, Drexel University, Philadelphia, PA, University of Arkansas for Medical Sciences,

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with CKD stage ≥3 experienced a significant improvement in CrCl (46.7±9.8 vs 53.0±1.9; p=0.002).Conclusion: Advanced chronic kidney disease is associated with more extensive atrial tissue fibrosis. Restoration of sinus rhythm following catheter ablation of AF results in improved kidney function at 3 months.

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PREDICTING GAPS IN ATRIAL ABLATION LESIONS USING LATE GADOLINIUM CARDIAC MAGNETIC RESONANCE (LGE CMR)James Harrison, MRCP, Christian Sohns, MD, Nick Linton, MRCP, Rashed Karim, PhD, Steven Williams, MRCP, Kawal Rhode, PhD, Jaswinder Gill, FRCP, Michael Cooklin, FRCP, Aldo Rinaldi, FRCP, Matthew Wright, PhD, MRCP, Tobias Schaeffter, PhD, Reza Razavi, FRCP and Mark O’Neill, FRCP. Division of Imaging Sciences and Biomedical Engineering, King’s College London, London, United KingdomIntroduction: Arrhythmia recurrence following catheter ablation for atrial fibrillation (AF) is commonly due to pulmonary vein (PV) reconnection or incomplete block across linear ablation lesions. It has been suggested that LGE CMR can provide a non-invasive method to identify gaps in ablation lesions, prior to repeat catheter ablation for AF or atrial tachycardia (AT). This study assessed this prospectively in patients with recurrent left atrial (LA) arrhythmias.Methods: 17 patients (15 male, 2 female, mean age 58) who had undergone one or more previous catheter ablation(s) for AF/AT, who represented with either paroxysmal AF (n=8) or AT (n=9) underwent pre-ablation LGE CMR. Two expert blinded reviewers independently scored 3D left atrial (LA) LGE CMR reconstructions for the presence/absence of gaps at each PV-LA junction and across the roof and mitral lines (making a total of 102 lesion sets and 204 observations). Electrical integrity of these lesion sets was then assessed at the time of catheter ablation.Results: From the LGE CMR scans, interobserver agreement for detection of a gap at the PV-LA junction or site of previous linear ablation was 85%. However, a correct prediction from the LGE was made for only 42% of lesion sets. The positive predictive value of LGE CMR for gap detection was 58%, whilst the negative predictive value was 24%. Specificity and sensitivity were 46% and 34% respectively.Conclusion: There was a high degree of agreement between two expert reviewers as to the presence or absence of a gap on 3D LA LGE CMR reconstructions. However, the positive predictive value of LGE CMR in determining electrical isolation at the PV-LA junction, roof and mitral isthmus is low.

ablation of persistent AF (PsAF) in patients with structural heart disease (SHD).Methods: 66 consecutive pts (11f, 59±10 years, LVEF 50±14%, 70% long-standing PsAF) with SHD and persistent AF undergoing de novo catheter ablation (stepwise approach: PVI, CFAE ablation, and linear ablation) were included, with the desired procedural endpoint of AF termination. Repeat ablation was performed for pts with recurrent AF/AT after a 1 month blanking period. A minimum follow up (FU) of 30 months with repeated Holter monitoring was performed. Arrhythmia recurrence was defined as AF/AT ≥30 sec.Results: AF was terminated during the index procedure in 50/66 pts (76%). LA diameter, AF cycle length, and duration of continuous AF were predictors of AF termination (All p<0.01). Arrhythmia-free survival rates were 28%, 18%, and 9% after a single procedure, and 69%, 65%, and 56% after 2.2±1.0 procedures at 1, 2, and 5 years FU, respectively. At 5.6±1.4 years of FU, 44 pts (67%) were either free of arrhythmia recurrence (n=35; 53%) or showed clinical improvement (>90% AF burden reduction) under previously ineffective antiarrhythmic drugs (n=9; 14%). Most recurrences occurred over the first 6 months. LA diameter (47±7 mm vs. 57±6 mm; p<0.001), termination of AF during index procedure (68% vs. 13%; p<0.001), duration of continuous AF (14±13 months vs. 45±58 months; p<0.01), and LA cycle length (158±20 msec vs. 146±20 msec; p=0.02) were associated with freedom from arrhythmia recurrence. In multivariate analysis, only termination of AF (OR 10.9; 95% CI 1.6-75.6; p=0.01) and LA diameter <50mm (OR 7.6; 95% CI 1.7-33.3; p<0.01) were independent predictors of freedom from AF/AT during FU. Procedural complication rate (cardiac tamponade, phrenic nerve injury) was 4.1%.Conclusion: In pts with persistent AF and SHD, stepwise ablation with repeat intervention as necessary provides good long-term rhythm outcome. A slow but steady decline of arrhythmia-free survival is noted over 5 years FU. Procedural termination of AF and smaller LA diameter predict long-term arrhythmia-free survival.

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IMPROVEMENT IN RENAL FUNCTION FOLLOWING CATHETER ABLATION OF ATRIAL FIBRILLATIONNazem W. Akoum, MD, Michel Barakat, MD, Nathan Burgon, BS, Jessiciah Windfelder, ACNP and Nassir Marrouche, MD, FHRS. University of Utah, Salt Lake City, UT, Comprehensive Arrhythmia Research and Management (CARMA) Center-University of Utah, Salt Lake City, UTIntroduction: Chronic kidney disease (CKD) is associated with a higher prevalence of atrial fibrillation (AF) and adverse cardiovascular outcomes. The association of atrial tissue fibrosis with CKD and the effect of AF ablation on kidney function have not been investigated.Methods: Patients presenting for AF ablation at the University of Utah were included. Creatinine clearance (CrCl) was calculated using the MDRD equation. CKD was staged using the National Kidney Foundation guidelines. Late-gadolinium enhanced MRI (LGE-MRI) was performed on all patients prior to catheter ablation and atrial tissue fibrosis was quantified. Patients underwent catheter ablation of atrial fibrillation and were followed up for recurrent AF and kidney functionResults: 463 patients were included in the study, of which 138 (29.8%) had CKD stages I or 244 (52.7%) CKD stage II and 81 (17.5%) had CKD stage ≥3. The average atrial tissue fibrosis was 15.8±10.4% for CKD stage I and II patients compared to 19.1±12.3% for CKD≥3 (p<0.05). Three months following ablation, CrCl remained relatively unchanged in CKD stages I and II (103.6±36.4 vs 100.5±35.7; p=0.24), whereas patients

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INTRAVENOUS FLECAINIDE REDUCES THE EXTENSION OF COMPLEX FRACTIONATED ELECTROGRAM AREAS PRESERVING THEIR SPATIAL LOCALIZATIONAlessandro De Bortoli, MD, Li-Zhi Sun, MD, PhD, Eivind Solheim, MD, PhD, Per Ivar Hoff, MD, Peter Schuster, MD, PhD, Ole-Jørgen Ohm, MD, PhD and Jian Chen, MD, PhD. Institute of Medicine, University of Bergen, Bergen, Norway, Department of Heart Disease, Haukeland University Hospital, Bergen, NorwayIntroduction: Complex fractionated electrogram (CFE) ablation is an accepted strategy for ablation of atrial fibrillation (AF). Flecainide is routinely used intra-procedurally for conversion or modification of AF. We sought to determine the effects of flecainide on CFE extension and distribution.Methods: Twenty-one patients with persistent AF (mean 61 years, 20 men) were enrolled. A CFE map was performed using the CFE mapping tool (NavX system) by sampling 5 s of continuous electrograms from the ablation catheter in order to cover the entire left atrium (LA). A single dose of intravenous flecainide (1mg/kg) was administered after completion of the first map. A second CFE map was created after 30 min (Fig). The LA was divided into 5 segments: anterior, mitral isthmus, posterior, roof and septum. CFE mean was calculated by the system as the average interval of consecutive deflections during the sampling period. CFE areas were defined as regions with a CFE mean <120 ms.Results: The total CFE area in the LA was smaller after flecainide (102 vs 74 cm2; p<0.001). All segments presented increased CFE mean in the second map (p<0.001) resulting in reduction of all CFE areas (p<0.01) except for the mitral isthmus (p=0.06). The largest reduction was observed in the posterior wall (32%) and in the roof (38%). In the second map, 70% of the CFE was located within the CFE areas of the first map. The most stable segments were the septum and roof with 72% and 76% preserved CFE areas, respectively.Conclusion: Flecainide reduces the extension of CFE areas by abolishing functional CFE. The true CFE areas appear to be spatially and temporally stable after flecainide administration. These results may influence the approach to CFE ablation.

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THE PULMONARY VEIN CARINA ABLATION ADJUNCT TO CIRMCUMFERENTIAL PULMONARY VEIN ABLATION RESULTED IN PULMONARY VEIN STENOSIS DURING LONG-TERM FOLLOW-UPDae Lee, MD, Yae-Min Park, MD, Ji-Eun Ban, MD, Jong-Il Choi, PhD, Sang-Weon Park, PhD and Young-Hoon Kim, PhD. Koera University Anam Hospital, Seoul, Republic of KoreaIntroduction: The pulmonary vein (PV) carina ablation as an adjunct to circumferential pulmonary vein ablation (CPVA) has been demonstrated to be effective. However it is little known that the pulmonary vein carina ablation may influence the anatomy

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ATRIAL MYOCARDIAL PROPERTY OF PERSISTENT ATRIAL FIBRILLATION ASSESSED BY SPECKLE TRACKING ECHOCARDIOGRAPHY IMPROVED AFTER ABLATIONShio Ohguchi, PhD, Yasuya Inden, MD, Toshihiko Yamamoto, PhD, Shinjiro Miyata, PhD, Noriko Taguchi, PhD, Masaya Fujita, PhD, Masaya Fujita, PhD, Masaya Fujita, PhD, Kenichiro Yokoi, PhD, Naoki Yoshida, MD, Masayuki Shimano, PhD, Tomomichi Suzuki, MD, Makoto Hirai, MD and Toyoaki Murohara, MD. Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan, Nagoya University School of Health Sciences, Nagoya, JapanIntroduction: Atrial mechanical function can be estimated using speckle tracking echocardiography. In this study, we investigated a reverse process of the left atrial (LA) function before and after catheter ablation between paroxysmal atrial fibrillation (Af) patients and persistent Af patients, using systolic strain (S) and strain rate (SR).Methods: 39 patients (19 paroxysmal Af, 20 persistent Af) were investigated by transthoracic echocardiography before, one day after and 6 months after ablation. Peak S and SR during systole were measured at LA segment.Results: Just after ablation peak S and SR in persistent Af were lower than those in paroxysmal Af (S: 7.0±4.0 vs. 10.6±4.0, p<0.01,SR: 0.57±0.23 vs. 0.71±0.20, p=0.06). In persistent Af patients these parameters increased significantly 6 months after ablation (S: 11.1±5.4, SR 0.70±0.29). In contrast these parameters in paroxysmal Af did not change significantly (S: 13.0±6.2, SR: 0.78±0.34). And at 6 months follow-up, there were no significant differences in systolic S and SR between paroxysmal and persistent Af.Conclusion: Reverse process of atrial myocardial property was shown in persistent Af patients after ablation, and LA reservoir function of persistent Af may be expected to reverse into the near condition of paroxysmal Af under sinus rhythm maintenance.

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migrating ES were 69% RS and 31% FS. Migration of greater than 2 cm occurred with 86% of RS and 6% of FS.Conclusion: Rotor sources were the most common identified mechanism of human atrial fibrillation using phase mapping and a MBC. Rotor sources commonly displayed migration, whereas focal sources did not. Edge sources outside the MBC array of electrodes were common. New catheter designs and/or computational techniques may be needed for more complete identification of AF sources.

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CATHETER-TISSUE INTERACTION THROUGHOUT THE CARDIAC AND RESPIRATORY CYCLESMatthew James. Wright, MBBS, PhD, David Haines, MD, FHRS, Erik Harks, PhD, Harm Belt, PhD, Steven Fokkenrood, MSc, Darrell L. Rankin, MEng, William C. Stoffregen, DVM, PhD, Joseph Nguyen, BS, Vivek Reddy, MD, FHRS and Pierre Jaïs, MD. St. Thomas’ Hospital, London, United Kingdom, Beaumont Heart Center, Royal Oak, MI, Philips Healthcare, Best, Netherlands, Philips Research, Eindhoven, Netherlands, Boston Scientific, San Jose, CA, Mount Sinai Hospital, New York, NY, Hôpital Cardiologique du Haut Lévêque, CHU Bordeaux, Pessac, FranceIntroduction: Catheter stability is key to forming lesions but is difficult to assess. The aim of the study was to assess the contribution of cardiac and respiratory motion on the catheter tip using an integrated RF and ultrasound catheter.Methods: A 7Fr open irrigated RF catheter with a forward facing US transducer and 3 transducers perpendicular to the shaft in the distal electrode was developed. In an in vivo ovine model (n=16) catheter displacement was assessed in 5 consecutive cardiac cycles in both atria, away from the valve annuli (atrial and ventricular diastole, systole) at end inspiration and expiration by 3 blinded operators, during SR, AF and after AV node ablation.Results: 500 data points were examined at 20 positions (10 LA, 10 RA). The mean atrial wall thickness was 3.1 and 4.2mm in atrial diastole and systole. Respiratory motion resulted in a 10% displacement of the catheter in the RA vs 3% in the LA, p=NS, and was the least important contributor to catheter displacement, p<0.05. Atrial contraction had a similar effect on catheter displacement in both the LA and RA compared to baseline with 42% vs 48% difference respectively, p=0.33. Ventricular contraction had a much greater effect on catheter displacement in the RA vs LA 41% vs 7%, p<0.05.Conclusion: Atrial contraction is the major determinant of catheter instability when ablating in the left atrium, with respiratory motion having a negligible effect. In contrast ventricular contraction is the major determinant of catheter instability in the right atrium. The integrated US RF ablation catheter allows the operator to take this into account by directly visualising lesion formation.

of PV. The purpose of this study was to identify the relation between the PV carina ablation and PV stenosisMethods: One hundred-one patients [83 males; mean age: 55.8 +/- 9.6; 43 with paroxysmal atrial fibrillation (AF) and 58 with persistent AF]who underwent redo-catheter ablation were analyzed. Multi-Dimensional computed tomography (MDCT) was performed in all patients prior to first and second ablation procedures, of which time interval between 2 CTs was 18.8 months. A total 183 PVs were evaluated. We measured the difference in the diameter between PV ostium prior to first procedures and that of redo procedure. The severity of stenosis was categorized itno mild (<30%), moderate (30-50%) or severe (>70%).Results:The difference (4.5 +/- 8.2mm) in the diameter of right superior PV after carina ablation was significantly greater than that after CPVA (0.6+/- 2.1mm, P=0.002). The difference in the diameter of left superior PV after carina ablation was also significant l(2.4 +/- 2.5mm vs. 0.8 +/- 4.8mm, P=.0.003). The severity of PV stenosis after carina ablation was mild in 71 PVs (86.6%), moderate in 9 PVs (11%), and severe in 2 PVs (1.1%), whereas that after CPVA was mild in 94 PVs (96.9%), moderate in 3 PVs (3.1%), and severe in 0 PV (0%). The PV stenosis severity was also significantly different between carina ablation and CPVA (P=0.03). In multivariate logistic regression carina ablation of PV was independently related to moderate and severe stenosis of PV, after adjusting multiple variables including age, sex, AF duration, AF type, LA size (P=0.008, Odd ratio=5.0, Confidence intervals: 1.34-18.7). None complained of symptoms related PV stenosis.Conclusion: The PV carina ablation adjunct to CPVA resulted in asymptomatic PV stenosis during follow up.

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CLASSIFICATION AND MIGRATION TRACKING OF AF SOURCES IN HUMAN ATRIAL FIBRILLATION USING PHASE MAPPING AND MULTI-ELECTRODE BASKET CATHETER RECORDINGSJohn R. Bullinga, MD and Jiyue He, MEng. Penn Presbyterian Medical Center, Philadelphia, PAIntroduction: Mechanisms of human atrial fibrillation (AF) remain incompletely understood. Phase mapping is an important technique for identifying potential mechanisms of AF as rotor sources (RS) and focal sources (FS). The migration behavior of RS and FS is unknown. Also, the adequacy of a multi-electrode basket catheter (MBC) to identify sources in the left atrium for PM is unknown.Methods: Ten patients underwent left atrial instrumentation with a MBC in persistent AF at the time of their scheduled AF ablation. Simultaneous 60 second bipolar electrograms (filtered 30-500 Hz) were recorded twice in each patient from all potential bipoles of the MBC. Phase mapping was performed using custom software. RS were defined by phase singularities. FS were defined by centrifugal propagation. Migration of RS and FS locations were measured over time. Edge sources (ES) were defined by sequential propagation from the proximal or distal electrodes of the MBC splines. ES were characterized if they migrated into the MBC array of electrodes as a RS or FS.Results: There was a mean of 3.5 +/- 0.9 potential sources of AF identified at each time epoch. The number of sources varied little within an individual over time and between recordings (standard deviation 0.3 over 60 seconds, mean absolute difference 0.1 on sequential recordings). Source locations and types were highly conserved on sequential recordings in individual patients, but varied between patients. The overall proportions of sources were 46% RS, 11% FS, and 43% ES. ES migrated into the MBC array of electrodes 2% of the time. The

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approaches of electrophysiology and molecular biology.Results: It was found the INa density (-35 mV) was greater in left atrial (n=17, -38.6±4.6 pA/pF) than that in left ventricular (n=35, -24.5±1.3 pA/pF, P<0.01) myocytes. Time constants of activation (τm) and inactivation (τh) of INa was smaller in atrial (0.23±0.02 ms and 1.05±0.04 ms) than those in ventricular (0.48±0.02 ms and 1.67±0.06 ms, P<0.01) myocytes. The V1/2 of INa availability (I/Imax) was more negative in atrial (n=15, -100.3±1.1 mV) than that in ventricular (n=18, -95.1±1.0 mV, P<0.05) myocytes. In addition, recovery of INa from inactivation was slower in atrial than that in ventricular myocytes. Molecular biological experiments revealed that mRNAs and proteins of SCN5A, SCN4A, SCN10A, SCN1B, SCN2B, and SCN3B were homogenously expressed in both atrial and ventricular myocytes. Interestingly, expression of SCN4B was greater (2.8 folds) in ventricular myocytes than that in atrial myocytes. The anti-arrhythmic drug quinidine inhibited INa with IC50 of 2.8 μM in atrial myocytes, while 7.2 μM in ventricular myocytes.Conclusion: Our results demonstrate for the first time to our knowledge that distinctive density and biophysical properties of INa are present in atrial and ventricular myocytes of from rat heart. The less expression of SCN4B in atrial myocytes likely contributes at least in part to the higher density, quicker activation and inactivation, negative potential of inactivation, slower recovery from inactivation of INa, and the more sensitive to inhibition by the anti-arrhythmic drug quinidine. The study further supports the notion that atrial INa may be a target for developing atrial selective anti-atrial fibrillation drug.

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PROPERTIES AND MOLECULAR BASIS OF ATRIAL FIBROBLAST VOLTAGE-DEPENDENT POTASSIUM CHANNELSXiao-Yan Qi, PhD, Hai Huang, PhD, Chia-Tung Wu, MD, Patrice Naud, PhD, Ange Maguy, PhD, Dobromir Dobrev, MD and Stanley Nattel, MD. Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada, University of Duisburg-Essen and University of Heidelberg, Essen/Heidelberg, GermanyIntroduction: Cardiac fibroblasts (FBs) play important roles in arrhythmogenesis by secreting ECM proteins (fibrosis) and by coupling effects on cardiomyocyte bioelectricity. FBs possess voltage dependent K+ (Kv) channels that might contribute to their function, but the nature of these Kv channels is poorly defined. Here, we characterized canine atrial FB Kv currents to define their potential molecular basis.Methods: Freshly isolated atrial FBs were obtained from LA of control (CTL) and congestive heart failure (CHF, 2 wk ventricular tachypacing, 240 bpm) dogs. Kv currents (tight seal patch clamp) and mRNA (qPCR) were quantified.Results: FBs showed robust Kv currents (mean density 13.8±0.9 pA/pF) with time-dependent activation and inactivation (Fig. A). Kv current reversal potential was strongly dependent on [K+]o (slope=41.9 mV/log-mM K+, close to Nernst relationship). Currents were sensitive to TEA (IC50 ~0.6 mM, Fig. B) and 4-AP (IC50 ~49 µM, Fig. C). The degree of inactivation over a 500 ms pulse varied widely but with a monotonic distribution (Fig. D), suggesting a common molecular basis. The Kv1.5 selective blocker DPO-1 (1 µM) reduced Kv current by 85±2% (P<0.001). CHF downregulated Kv current by about 72% (Fig. E) and Kv1.5 mRNA expression by 61%. Kv2.1 mRNA was unchanged by CHF and Kv3.1 was very weakly expressed.Conclusion: Atrial fibroblasts express substantial Kv currents. Based on Kv current properties and PCR data, Kv1.5 subunits are the likely molecular basis, although TEA sensitivity is atypical, suggesting beta subunit modulation. Since FB Kv currents affect cardiomyocyte-FB interactions, better

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RIGHT VENTRICULAR OUTFLOW TRACT ARRHYTHMOGENICITY IS RELATED TO ITS COVERT PACEMAKING PHENOTYPEHeiko Schneider, MRCP, Sunil Jit RJ. Logantha, PhD, Ian P. Temple, MRCP, Mark R. Boyett, PhD, Vaikom S. Mahadevan, MD, Oliver Monfredi, PhD and Halina Dobrzynski, PhD. Cardiovascular Research Group, University of Manchester, Manchester, United KingdomIntroduction: Ventricular tachycardia frequently arises from the right ventricular outflow tract (RVOT). We have investigated the molecular and electrical phenotype of the RVOT in structurally normal hearts to determine whether it has inherently arrhythmogenic features.Methods: Wistar rats (3-months old) were sacrificed according to approved methods. Tissue samples were taken from the right ventricular apex (RV) and the RVOT infundibulum (RVOT1) and ventriculo-arterial junction (RVOT2) (n=8). qPCR was performed on these samples for 96 ion channels and related molecules. Intracellular action potentials from the endocardial surface of RVOT preparations (n=7) were recorded using microelectrodes. Action potentials were also recorded optically after the application of blebbistatin and voltage sensitive dye (RH237) (n=4).Results: Expression of Tbx3 was significantly higher (by ~70%) in the RVOT, suggesting persistence of an embryonic, pacemaker-like phenotype. Expression of Nav1.5 was significantly lower (~50%) in the RVOT, expected to result in an action potential with a lower maximum rate of rise (dV/dtmax) and smaller amplitude. Expression of Kir2.1 and Kir2.2 was significantly lower (~34% and ~10% respectively) in the RVOT, expected to result in a more positive and unstable maximum diastolic potential (MDP). Consistent with this, dV/dtmax of electrically-evoked action potentials was 352±17, 315±20 and 203±16 V/s in the RV, RVOT1 and RVOT2 regions, respectively. Corresponding action potential amplitudes were 106±2, 100±2 and 87±2 mV. However, the MDP was not significantly different. Spontaneous pacemaker activity was recorded from 4 RVOT preparations: optical mapping showed spontaneous action potentials propagating away from the ventriculo-arterial junction (RVOT2) in 2 preparations, and nodal-like pacemaker action potentials (dV/dtmax, 25±7 V/s; amplitude, 44±12 mV; MDP, -41±2) with prominent diastolic depolarization were recorded from a further 3 cells in 2 preparations.Conclusion: The RVOT exhibits anatomical and physiological characteristics similar to the sinoatrial and atrioventricular nodes, including automaticity. This offers a plausible explanation for the propensity towards arrhythmia seen in the RVOT.

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DISTINCTIVE DENSITY, BIOPHYSICAL PROPERTIES, AND PHARMACOLOGY OF VOLTAGE-GATED SODIUM CURRENT IN ATRIAL AND VENTRICULAR MYOCYTESGui-Rong Li, PhD, Kui-Hao Chen, MSc and Hai-Ying Sun, BSc. University of Hong Kong, Pokfulam, Hong KongIntroduction: Our earlier study reported that heterogeneous voltage-gated sodium current (INa) in the density and biophysical properties is present in atrial and ventricular myocytes from guinea pig heart (Li et al, J Mol Cell Cardiol 2002;34:1185-1194). However, molecular contribution is not understood for the different properties of INa in atrial and ventricular myocytes of the heart. The present study was designed to investigate the properties, potential molecular contribution, and pharmacology of INa in atrial and ventricular myocytes of rat heart using

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INTERACTION OF WILD TYPE AND MUTANT NAV1.5 α SUBUNITS RESCUES A C-TERMINAL TRUNCATING NAV1.5 MUTATIONAzza Ziyadeh-Isleem, MD, Jerome Clatot, PhD, Sabine Duchatelet, PhD, Estelle Gandjbakhch, MD, PhD, Isabelle Denjoy, MD, Françoise Hidden-Lucet, MD, Alain Coulombe, PhD, Nathalie Neyroud, PhD and Pascale Guicheney, PhD. Inserm U956, Paris, France, Inserm U956,AP-HP, Hôpital Pitié-Salpêtrière, Département de Cardiologie, Paris, France ,Centre de Référence pour les Maladies Cardiaques Héréditaires, Paris, France, Paris, France, Inserm U956,Centre de Référence pour les Maladies Cardiaques Héréditaires, Paris, France,Service de cardiologie, Hôpital Bichat, Paris, France., Paris, France, Inserm U956, AP-HP, Hôpital Pitié-Salpêtrière, Département de Cardiologie, Paris, France, Centre de Référence pour les Maladies Cardiaques Héréditaires, Paris, France, Paris, FranceIntroduction: The Nav1.5 α-subunit, encoded by SCN5A, together with its associated regulatory and anchoring proteins, constitute a macromolecular complex underlying the cardiac Na+ current, INa, which is essential for the generation and transmission of the action potential. INa dysfunction causes life-threatening arrhythmias. Recently, we demonstrated that the Nav1.5 α subunits interact with each other. Here, we characterized a truncating SCN5A mutation, which was identified in a patient with a mixed clinical phenotype of sick sinus syndrome and atrial fibrillation.Methods: Wild type (WT) and mutated Nav1.5 channels were transiently expressed in HEK293 cells and their effects studied by biochemical and patch clamp analysis.Results: The R1860GfsX12 truncating mutation in the Nav1.5 C-terminus causes partial proteasomal degradation of the mutant channel. Nevertheless, some of the mutant channels reach the plasma membrane, as shown by cell surface biotinylation. Patch-clamp recording in cells expressing the mutant channels showed a marked reduction of INa density by 70% compared to cells expressing the WT channels, and impaired biophysical properties. Surprisingly, co-transfection of WT with R1860GfsX12 in a 1:1 ratio almost restored the WT INa. In addition, co-expression of WT and R1860GfsX12 channels increased cell surface and total expression of the mutant channels, suggesting that WT channels allow mutant proteins to escape proteasomal degradation. Moreover, co-immunoprecipitation studies clearly showed that R1860GfsX12 channels still interact with WT channels. Altogether, our results suggest that WT could interact with mutant α-subunits, thus preventing their proteasomal degradation, and that both channels traffic together to the plasma membrane.Conclusion: Multiple mechanisms underlie functional consequences of SCN5A mutations, which could explain why some mutations are responsible for ventricular arrhythmias, while others, such as R1860GfsX12, cause a milder atrial phenotype.

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PATIENTS WITH TYPE 1 LONG QT SYNDROME AND MARKEDLY PROLONGED RECOVERY PHASE QTC VALUES FOLLOWING TREADMILL TESTING HARBOR PKA-INSENSITIVE KV7.1 CHANNELSDaniel C. Bartos, BS, John R. Giudicessi, PhD, Don E. Burgess, PhD, David J. Tester, BS, Seiko Ohno, MD, PhD, Minoru Horie, MD, PhD, Michael H. Gollob, MD, Michael J. Ackerman, MD, PhD and Brian P. Delisle, PhD. University of Kentucky, Lexington, KY, Mayo Clinic, Rochester, MN, Shiga University of Medical Sciences, Ohtsu, Japan, University of Ottawa Heart Institute, Ottawa, ON, Canada

understanding of FB Kv currents may allow for novel therapies of AF in fibrotic conditions like CHF.

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PERSISTENT SODIUM CURRENT IS A THERAPEUTIC TARGET OF RANOLAZINE FOR LETHAL VENTRICULAR ARRHYTHMIAS IN MICE WITH RETT SYNDROMETiannan Wang, MD, PhD, Jose Herrera, BS, Jeffrey L. Neul, MD, PhD, Sridharan Rajamani, PhD, Luiz Belardinelli, MD, PhD and Xander Wehrens, MD, PhD. Baylor College of Medicine, Houston, TX, Gilead Sciences, Fremont, CA, Gilead Science, Fremont, CAIntroduction: Rett syndrome is an X-link genetic disease characterized by developmental reversal, which is caused by Methyl-CpG-Binding Protein 2 (MeCP2) deficiency. About 25% of Rett patients die unexpectedly and suddenly, most likely from ventricular arrhythmias. In a previous study, we reported increased sustained (late) Na current and QT prolongation as the mechanism underlying arrhythmias and sudden cardiac death in MeCP2 null mice, a mouse model of Rett syndrome. Here we tested the hypothesis that ranolazine, an inhibitor of late Na current, could reverse the effects of MeCP2 deficiency in cardiac myocytes.Methods: The electrophysiological properties of ranolazine were characterized in ventricular myocytes isolated from MeCP2 null mice. Patch clamp experiments were performed to study late Na current following 1-s depolarization step pulses to 20 mV. Peak Na current and action potential duration were also measured. TTX, phenytoin and mexiletine were utilized in the study as controls.Results: Ranolazine significantly decreased late Na current with an apparent IC50 of .25 μM, whereas, the peak Na current was not reduced, even at 10-30 μM. Phenytoin (10 μg/ml) also decreased late Na current (from 34.8±4.2 pA/pF to 21.0±2.3 pA/pF), consistent with our previous study. However, mexiletine (100 uM), a class IB antiarrhythmic drug, did not effectively inhibit late Na current in myocytes from MeCP2 null mice. Ranolazine treatment led to shortening of the action potential duration (APD90) from 135.3±30.8 ms to 103±11.23ms.Conclusion: Ranolazine is a promising therapeutic option for arrhythmias in Rett syndrome through blocking late sodium current, shortening of the action potential duration, and reducing QT prolongation propensity and incidence in MeCP2 null mice.

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CI 1.056 - 4.798, p=.036) remained independent predictors for AF recurrence.Conclusion: Left atrial enlargement and the ACE DD polymorphism are independent predictors for AF recurrence after catheter ablation. The association between the ACE DD polymorphism and AF recidivism further supports the use of genetic data for predicting response to AF therapies and highlights the dominant role of fibrosis in AF development.

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EXPERIENCE WITH DIAGNOSTIC AND RESEARCH DRIVEN GENETIC ANALYSIS IN A HIGH VOLUME CARDIOGENETICS CLINICDaniela Husser, MD, Virginia Kootz, RN, Gerhard Hindricks, MD, Dawood Darbar, MD, Dan M. Roden, MD and Andreas Bollmann, MD, PhD. Leipzig University Heart Center, Leipzig, Germany, Vanderbilt University School of Medicine, Nashville, TNIntroduction: With the increasing importance of genetic testing and counselling for inherited arrhythmias and cardiomyopathies, we sought to report the molecular and clinical results of 3 years of cardiogenetic counselling at the Heart Center Leipzig.Methods: By means of candidate gene based sequencing we analyzed all families who presented between 2009 and 2011 with a suspected inherited arrhythmia syndrome including primary electrical diseases, cardiomyopathies, sudden (aborted) unexplained death (SUD) or atrial fibrillation (AF).Results: Since establishment in 2009, 451 patients and family members underwent complete work-up at the department of electrophysiology outpatient clinic, of whom 377 are included in this study (37±19 years old, 55% male, n=164 independent Caucasian families). In 100 families, genetic screening was initiated and lead to identification of a probable disease causing mutation in 49%. Most mutations were found in long QT syndrome (49%), Brugada syndrome (16%), catecholaminergic polymorphic ventricular tachycardias and arrhythmogenic right ventricular cardiomyopathy (12% each) and hypertrophic cardiomyopathy (10%). In the remaining 64 families, genetic testing was withheld because patients did either not consent or a clinical diagnosis could not be established prior to genetic testing. The number of counselled families after SUD was 42. In 62% (n=26) of these families an inherited disease was established (molecular confirmation in n=13, 50%). In total, novel mutations were detected in 6 %. Research-driven genotyping for AF in genes encoding the cardiac sodium channel and associated compounds was performed in 137 patients revealing 3 rare non-synonymous variants in SCN5A, 5 in SCN1B, 1 in SCN4B, 1 in CAV3, 6 in GPD1L, 3 in SNTA1 and 3 in MOG1 (16 %).Conclusion: In this single center experience, a high number of disease causing mutations of patients was detected highlighting the importance of proper clinical phenotyping. Systematic screening of these families identifies many, often asymptomatic, carriers. The role of genetic testing for atrial fibrillation needs to be explored in the future.

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C-REACTIVE PROTEIN AFTER ATRIAL FIBRILLATION ABLATION: IS INFLAMMATION THE HORSE OR THE CART?Omeed Zardkoohi, MD, Li Zhang, PhD, Omar Khatib, MD, Michael Tchou, MD, Peter Hanna, BS, Robert Wirka, MD, Maya Serhal, BS, Edwin T. Zishiri, MD, Patrick Tchou, MD, John Barnard, PhD, David R. Van Wagoner, PhD and Mina K. Chung, MD. Cleveland Clinic Foundation, Cleveland, OH, Oschner Clinic, New Orleans, LA, Stanford University, Stanford, CA, UCSF, San Francisco, CA, Lerner College School of Medicine, Cleveland Clinic Foundation, Cleveland, OH

Introduction:Type 1 long QT syndrome (LQT1) is caused by loss-of-function mutations in the KCNQ1-encoded Kv7.1 pore forming α-subunit. In the heart, Kv7.1 coassembles with KCNE1 to conduct the slowly activating delayed rectifier K+ current (IKs). LQT1 mutations that are resistant to β-adrenergic stimulation of IKs by protein kinase A (PKA) correlate with an increased incidence of life-threatening arrhythmias.Methods:LQT1 patients show paradoxically prolonged QTc values during the treadmill stress test’s recovery phase. Retrospective analyses of treadmill stress testing consisting of a genotype-confirmed LQT1 cohort revealed patients with I235N-KCNQ1 exhibited markedly prolonged recovery phase QTc values. We studied the functional phenotype and PKA sensitivity of I235N-KCNQ1 in vitro and simulated these results using computational modeling of ventricular action potentials (APs) with or without β-adrenergic stimulation.Results:ECG stress testing was evaluated in 10 patients with LQT1 secondary to I235N-KCNQ1. These patients had normal to borderline resting QTc values (445±5ms) that showed marked prolongation (521±10ms) during the recovery phase. We expressed wild-type KCNQ1 (WT) and I235N-KCNQ1 in HEK293 cells. All expression studies included KCNE1. Cells expressing WT or WT + I235N (to mimic the patients’ genotypes) generated currents similar to IKs, but cells coexpressing I235N generated currents that were ~30% smaller (n=11-12 cells, p<0.05). PKA stimulation increased current in cells expressing WT by 64% (n=5, p0.05). Computational modeling of ventricular APs at cycle lengths ranging between 0.3-1s showed that reducing the IKs component by 30% and making it insensitive to PKA increased the APs duration by 1-2%. However, incorporating β-adrenergic stimulation in the simulations increased the APs duration by 6-10%.Conclusion:Functional and computational analyses suggest I235N primarily prolongs the ventricular AP duration during stress testing because it is resistant to PKA. We conclude ECG treadmill stress testing might be useful for identifying patients with concealed, but potentially at-risk, LQT1 secondary to PKA insensitivity.

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GENETIC ACE I/D POLYMORPHISM AND RECURRENCE OF ATRIAL FIBRILLATION AFTER CATHETER ABLATIONLaura Ueberham, Andreas Bollmann, MD, PhD, Arash Arya, MD, Volker Adams, PhD, Gerhard Hindricks, MD and Daniela Husser, MD. Heart Center Leipzig, Leipzig, GermanyIntroduction: The ACE deletion allele, ACE D, is associated with increased cardiac ACE activity, cardiac fibrosis and adverse outcomes in cardiovascular disease and has been linked with failure of anti-AF drug treatment. This study tested the hypothesis that the genetic angiotensin-converting enzyme gene (ACE) insertion/deletion (I/D) polymorphism associates with atrial fibrillation (AF) recurrence after catheter ablation.Methods: In 238 consecutive patients (69 % male, mean age 58 ± 11 years) undergoing catheter ablation of paroxysmal (59 %) or persistent (41 %) AF, the ACE insertion/deletion [I/D] polymorphism was genotyped using real-time polymerase chain reaction followed by gel electrophoresis. After a blanking period of 3 months, AF recurrence (defined as any atrial arrhythmia lasting at least 30s) was detected using serial 7-day-Holter ECG recordings after 3, 6 and 12 months.Results: AF recurrence was observed in 39 % and was associated with persistent AF, longer history of AF, previous antiarrhythmic drug use, previous use of diuretics, increased left atrial diameter, increased left ventricular enddiastolic diameter, additional linear ablation lesions and the ACE DD polymorphism. In multivariable analysis, left atrial diameter (OR 1.111, 95 % CI 1.040 - 1.187, p=.002) and ACE DD genotype (OR 2.251, 95 %

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Ablation injury was quantified by creatine kinase activity (CKA).Results: Seral miR-133a levels were highest in the LA resulting in significant transcardiac (LA vs. CS, p=.016) and transpulmonary (LA vs. PV, p=.008) gradients and cellular miR-133a was also higher in LA compared with PV (p=.03). Cellular miR-29b levels were comparable at different sites while seral miR-29b was not detectable. After ablation seral miR-133a (p=.04) and CKA (p<.001) increased while cellular miR-29b decreased (p=.023) showing a correlation among the parameters (p<.05).Conclusion: The findings of this study (1) reveal substantial miR differences among analyzed samples (serum vs. cells) and sampling sites, and (2) confirm the potential role of miR-133a as marker of myocardial injury. The differential regulation of circulating cellular and seral miR when studied in patients undergoing AF catheter ablation may provide important insights of AF mechanisms and ablation effects but analytical standards are essential.

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THE ROLE OF MACROPHAGE MIGRATION INHIBITORY FACTOR IN THE REGULATION OF CONNEXIN 43 IN ATRIAL MYOCYTESFang Rao, PhD, Chun-Yu Deng, PhD, Yu-Mei Xue, PhD, Qian-Huang Zhang, PhD, Xi-Yong Yu, PhD and Shu-Lin Wu, PhD. Guangdong Cardiovasular Insititue, Guangzhou, ChinaIntroduction: Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Recent findings have demonstrated a mechanistic link between inflammatory and the development of AF.Macrophage migration inhibitory factor (MIF), a pleiotropic cytokine, controls the inflammatory ‘set point’ by regulating the release of other pro-inflammatory cytokines. Recent studies have revealed that Connexin 43 (Cx 43) not only is involved in the electrical conductivity between the cells, but also forms a complex with PKP2 and Na+ channel to affect the sodiumcurrent. The purpose of this study is to observe the role of MIF in the expression of Cx43, and the role of Cx43 in the regulation of calcium channel current in atrial myocytes.Methods: Cx 43 expression in human atrial tissues and HL-1 cells were determined by Western blot and Real time PCR. Whole-cell voltage-clamp recordings and Real time PCR were used to study the regulation and expression of ICa,L and ICa,T in HL-1 cells before and after Cx 43 siRNA knocking down.Results: Expression levels of Cx 43 mRNA and protein are significantly reduced while MIF expression levels were increased in patients with AF. In HL-1 cells, the depression of Cx 43 expression levels induced by rMIF was prevented by ERK 1/2 inhibitor U0126, but not Src inhibitor Genistein and PP1. Both ICa,L and ICa,T are reduced after Cx 43 siRNA knocking down, probably by down-regulation of L type calcium channel α1C subunit and T type calcium channel α1G subunit.Conclusion: These results implicate MIF in the pathological mechanism of AF, probably by decreasing Cx43 expression through the activation of ERK1/2 kinases in atrial myocytes. And ICa,L and ICa,T are regulated directly by Cx43, implicate involvement of Cx 43 in the electrical remodeling.

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POST-CARDIAC ARREST MYOCARDIAL DEPRESSION IS SUPPORTED BY CALCIUM MEMORY AND MITIGATED BY ALDA-1 ACTIVATION OF ALDEHYDE DEHYDROGENASE 2Christopher Woods, MD, PhD, Foad Taghavi, MBChB, Koy Thanaporn, MD, Peter Kohl, MD, PhD, James Spudich, PhD, Daria Mochley-Rosen, PhD and Euan Ashley, MRCP. UCSF,

Introduction: Inflammation and elevated C-reactive protein (CRP) levels have been associated with atrial fibrillation (AF), but whether inflammation is a cause or a consequence of AF is unknown. We tested the hypotheses that CRP levels decrease after successful AF ablation in patients without structural heart disease (SHD) and that baseline CRP and CRP-associated single-nucleotide polymorphisms (SNPs) predict ablation failure.Methods: Subjects enrolled in a biorepository of patients with AF without significant SHD were included if they underwent catheter-based pulmonary vein isolation (PVI). AF recurrence was defined as recurring AF up to 1 year (± 2 months). Baseline and changes in CRP were analyzed using non-parametric tests. CRP-associated SNPs from published literature were tested using additive and dominant models.Logistic regression was used to determine if baseline CRP and CRP SNPs predicted AF recurrence after PVI.Results: Of 367 patients who underwent PVI mean age was 58.1 ± 10.5 yrs and 100 (27%) had AF recurrence. There was no difference in baseline CRP levels between patients with AF recurrence (1.6 mg/L, interquartile range (IQR) 0.8-3.76) mg/L) and patients with no AF recurrence (1.31 mg/L, IQR 0.70-2.88 mg/L), p=0.165. In patients with no AF recurrence at 1 year (n=267), median CRP level did not change significantly from baseline (1.30, 0.70-2.8 mg/L) to 1 year (1.20, 0.60-2.68 mg/L), p=0.872. In multivariate analysis variables associated with AF recurrence were type of AF (long standing persistent vs. persistent vs. paroxysmal), OR 2.14(1.23-3.71), p=0.007; rhythm at time of the procedure (AF vs. sinus), OR 1.91(1.15-3.19), p=0.013; and 2 CRP-associated, tightly linked SNPs, rs780094, OR 1.51(1.08-2.12), p=0.017; and rs1260326, OR1.46 (1.04-2.06), p=0.028, the latter encoding a common missense GCKR (glucokinase receptor) variant associated with metabolic phenotypes, including metabolic syndrome and CRP levels.Conclusion: In a lone AF population, CRP did not significantly change after successful AF ablation, suggesting that AF does not drive inflammation in this group without SHD. AF burden and SNPs associated with metabolic phenotypes, but not baseline CRP, were associated with recurrence, suggesting potential modifiable factors that might enhance PVI success.

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RADIOFREQUENCY CATHETER ABLATION OF ATRIAL FIBRILLATION AS A MODEL FOR THE ANALYSIS OF CIRCULATING MICRO-RNAS - INSIGHTS FROM A PILOT STUDYDaniela Husser, MD, Marvin Leopold, Silke John, MD, Sait Daneschnejad, MD, Sergio Richter, MD, Boris Dinov, MD, Gerhard Hindricks, MD, Volker Adams, PhD and Andreas Bollmann, MD. Leipzig University Heart Center, Leipzig, GermanyIntroduction: Micro-RNAs (miR) are short, noncoding RNAs that are considered stable in circulating blood but there is no consensus on sample acquisition and analysis, i.e. previous studies have used whole blood, serum/plasma or mononucleated cells. Catheter ablation of atrial fibrillation (AF) may be considered an in-vivo model to study differential miR expression as venous, coronary sinus and left atrial access is available and myocardial release due to ablation injury can be studied. Consequently, this pilot study examined cellular and seral miR obtained from different sites before and after ablation.Methods: In 12 patients undergoing radiofrequency catheter ablation of AF, EDTA-blood samples were collected from coronary sinus (CS), left atrium (LA) and peripheral vein (PV) before and from PV 24 - 48 hours following ablation. Muscle-enriched miR-133a and fibroblast-enriched miR-29b were determined from serum and nucleated cells using real-time PCR.

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fibrosis. We tested the efficacy of the PDE5 inhibitor sildenafil, a drug that reduces pulmonary pressure and left ventricle (LV) hypertrophy, in preventing exercise-induced cardiac structural remodelling.Methods:A group of rats (Ex, n=18) underwent high intensity treadmill training for 16 weeks. Sedentary rats (n=20) served as control. Rats were randomized to receive sildenafil (SIL 25 mg/kg/day po) or vehicle. Hypertrophy (wall thickness/body weight) and fibrosis (Red Picrosirius) were assessed in histological slides, mRNA expression by real-time PCR amb plasmatic GMPc by ELISA.Results: Endurance training induced LV and right ventricle (RV) hypertrophy (Fig A) and promoted atrial fibrosis in both atria (Fig B,C). Unchanged βmyosin expression (0.4±0.3 vs 0.4±0.3, p=ns) and absence of myocardial fibrosis (4.3±0.2 vs 4.4±0.3, p=ns) suggested physiological LV hypertrophy as an adaptation in Ex rats. In both atria, ACE and TGFβ (Fig D) were increased in Ex rats. SIL effectively increased plasmatic cGMP (Ex: 1.2±0.9 vs Ex+SIL: 6±2.6 pmol/ml) and blunted LV but not RV hypertrophy (Fig A). Moreover, SIL prevented Ex-induced left atrial (LA) fibrosis (Fig C) and TGFβ-increase (Fig D), but had no effect in right atrium.Conclusion:Endurance exercise induces fibrosis in both atria in a rat model, which may generate a substrate for AF. Chronic treatment with SIL selectively prevented LA fibrosis, possibly by reducing LV hypertrophy and improving hemodynamics. Our results provide new insights into the mechanisms of the atrial arrhythmogenic substrate in athletes.

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REVERSE USE DEPENDENCE OF A QT SHORTENING AGENT: IMPLICATIONS FOR SAFETY AND EFFICACYMoshe Rav Acha, MD, Robert Mills, PhD, Kenta Nakamura, MD, Jordan Leyton-Mange, MD, Stacey Lynch, BS, Patrick Ellinor, MD, PhD, Shiro Baba, MD, PhD, Bruce Conklin, MD, Sean Wu, MD, PhD and David J. Milan, MD. Massachusetts General Hospital, Boston, MA, Massachusetts General Hospital, Charlestown, MA, Gladstone Institute, San Francisco, CAIntroduction: Acquired and congenital forms of long QT syndrome (LQTS) are significant medical problems for which therapies remain suboptimal. The compound, 2MMB, was recently found to rescue a zebrafish LQT model and shorten action potential duration (APD) in human stem cell derived LQTS models. The effect appears to be due to activation of the slow component of the delayed rectifier current (IKs). We sought to characterize the frequency dependent effect of 2MMB in zebrafish and human LQT models.Methods: Breakdance LQT2 mutant zebrafish hearts were

San Francisco, CA, Papworth Hospital, Cambridge, United Kingdom, Stanford, Stanford, CA, Imperial College, London, United KingdomIntroduction: Survival after arrhythmic sudden cardiac arrest (SCA) is limited by post-arrest myocardial depression (PMAD), which is poorly understood.Methods: PMAD was generated by SCA resuscitated using ECMO to restore spontaneous circulation in a rat model. In-vivo and in-vitro contractility were measured using pressure-volume loops and µ-carbon fibers, respectively. Calcium-induced calcium-release (CICR) was measured. Immunoblot analysis against calcium-calmodulin protein kinase II (CAMK) and autophosphorylated CAMK (p-CAMK) was done. Alda-1 was administered prior to SCA.Results: Post-arrest, in-vivo load independent contractility was depressed by ~44% (P<0.05). Cell force, load independent cell end-systolic and end-diastolic length tension relationships were 31%, 60%, 36% depressed in PMAD (all p<0.05). CICR amplitude increased by 290% (p=2e-29) post-arrest, and was called cardiac calcium memory (CCM). Exogenous and endogenous adrenergic activation engendered CCM in-vivo. Immunoblotting confirmed significantly higher p-CAMK post-arrest (p=0.02). Increased CICR was abolished by ryanodine, inhibition of p-CAMK, but not PKA, suggesting that adrenergic activation augments CICR which is maintained by p-CAMK. Alda-1 significantly improved in-vivo and in-vitro contractility, survival (by 50%), while also significantly reducing p-CAMKII and CCM.Conclusion: We present an in-vivo model of PMAD, and demonstrate that isolated cell myofilament calcium insensitivity is responsible for it. CCM develops post-arrest that is triggered by catecholamines, and dependent on p-CAMK. Alda-1 mitigates PMAD myofilament calcium insensitivity, improves survival, and reduces CAMK dependent CCM.

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SILDENAFIL SELECTIVELY PREVENTS LEFT ATRIAL FIBROSIS IN A HIGH INTENSITY EXERCISE RAT MODELCira Rubies Espinalt, MSc, Montserrat Batlle Perales, PhD, Nadia Castillo Machado, BSc, Guasch Casany Eduard, MD, Pablo Ramos Ardanaz, MD, Sitges Carreño Marta, MD, PhD, Brugada Terradellas Josep, MD, PhD and Mont Girbau Lluís, MD, PhD. Experimental Cardiology Laboratory, Arrhythmia Section, Cardiology Department, Thorax Institute, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain, Arrhythmia Section, Cardiology Department, Thorax Institute, Hospital Clínic, Universitat de Barcelona, Barcelona, SpainIntroduction: High intensity endurance exercise increases the risk of atrial fibrillation (AF), partially by promoting myocardial

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risk in all 10 patients. For the 5 patients with appropriate firings, simulations showed that PES from at least 1 endocardial site resulted in VT induction (Fig). All VTs were reentries organized within the GZ. Simulations also correctly predicted that patients with no recorded VT events were non-inducible. Non-inducible patients had lower GZ volumes compared to those with firings (8.7±9.7 cm³ vs 19.2±8.9 cm³, p=.11 ).Conclusion: Simulations with patient-specific MRI-based models of hearts with infarction may provide a unique opportunity to noninvasively predict SCD risk in patients.

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IMAGE-BASED COMPUTATIONAL MODELS OF INFARCTED HEARTS CAN NON-INVASIVELY PREDICT OPTIMAL ABLATION SITEHermenegild J. Arevalo, BS, Heidi Estner, MD, Carolyn Park, MS, Henry Halperin, MD, FHRS and Natalia A. Trayanova, PhD, FHRS. Johns Hopkins University, Baltimore, MDIntroduction: Identification of the optimal ablation site in hearts with infarct-related ventricular tachycardia (VT) remains difficult to do with current catheter-based mapping techniques. The goal of this study was to demonstrate that simulations using subject-specific heart models constitute a novel approach that can successfully predict optimal ablation targets.Methods: VT ablation using traditional mapping techniques and in vivo MRI were performed on 5 pigs with chronic infarcts; ablation failed in 3 (Fig A, example of ablation success). Multiscale, biophysically accurate models were developed from pre-ablation MRI of these pigs, including inexcitable scar and electrically remodeled gray zone (GZ, Fig B). Programmed stimulation, identical to experiment, was simulated to induce VT. To retrospectively predict ablation success or failure, VT ablation at locations identical to experiments was simulated. Optimal ablation target was then determined for each heart.Results: All models were inducible for VT and had mean cycle length of 182ms, in agreement with experiments (186ms). All reentrant VTs were organized around filaments located within GZ (Fig C). Simulations successfully replicated the outcomes of experimental ablation (Fig D). In cases of failure, the simulations revealed that targeting reentry filaments for ablation resulted in

dissected, treated with ivabradine, and optically mapped using di-4 ANEPPS as previously described, or were enzymatically dissociated into clusters for current clamp recordings. IPSC lines were generated froma proband with LQT2 (KCNH2 A422T). Cardiomyocytes (CM) differentiated from these IPSC’s were subjected to whole cell current and voltage clamp recordings.Results: Treatment of LQT2 zebrafish hearts with 2MMB resulted in APD shortening that was greatest at slow heart rates and diminished with increasing rates, as shown by optical mapping (Fig 1a), and current clamp recordings of zebrafish CM (Fig 1b). Isolated iPSC derived LQT2 CM reproduced a frequency dependent shortening of APD with 2MMB application, blunting the normal APD/cycle length relationship (Fig 1c 1d)Conclusion: 2MMB shortens both zebrafish and human LQT2 cardiomyocyte APDs in a reverse rate dependent fashion.This frequency dependent effect may result in favorable safety characteristics. Given the marked reverse use dependence of QT prolonging drugs, a QT shortening agent with reverse rate dependence may provide a unique tool to manage acquired LQTS.

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PATIENT-SPECIFIC MRI-BASED MODELS OF INFARCTED HEARTS CAN PREDICT RISK OF SUDDEN CARDIAC DEATHHermenegild J. Arevalo, BS, Fijoy Vadakkumpadan, PhD, Alexander Jebb, Katherine Wu, MD and Natalia A. Trayanova, PhD, FHRS. Johns Hopkins University, Baltimore, MDIntroduction: ICDs are an effective primary prevention strategy for patients with ischemic heart disease who are at high risk for sudden cardiac death (SCD). Unfortunately, current selection criteria that rely on left ventricular ejection fraction (LVEF) have low specificity, which has led to over implantation of this expensive device. The goal of this study was to demonstrate, in a retrospective analysis, that patient specific, MRI based heart models can be used to predict SCD risk in patients with prior infarction and low LVEF.Methods: MRI and long term clinical follow-up data were acquired from 10 patients with ischemic cardiomyopathy who had ICDs implantated; 5 subsequently had appropriate ICD firings for ventricular tachycardia (VT). Multiscale, biophysically-accurate heart models, including inexcitable scar and electrically remodeled gray zone (GZ), were developed from the MRI. SCD risk was assessed by simulating VT inducibility using programmed electrical stimulation (PES) delivered from 17 different endocardial sites.Results: The simulations successfully predicted arrhythmia

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(10.0±1.1%, p<0.05). In contrast, TH decreased the slope of mSCR (25.5±3.2%/s) and amplitude of DADs (6.3±1.4%) relative to both N and SH (both p<0.05). Conclusion: We reveal a novel mechanism of Ca-mediated arrhythmogenesis associated with severe hypothermia. Our results demonstrate a biphasic relationship between temperature and the rate of spontaneous calcium release, represented as the slope of mSCRs, which may explain the proarrhythmic effect of severe hypothermia and the antiarrhythmic effect of therapeutic hypothermia.

PO04-98

ATRIA ARE MORE SENSITIVE THAN VENTRICLES TO INHIBITION OF LATE SODIUM CURRENT BY GS-458967 BUT BLOCK OF THIS CURRENT IS NOT EFFECTIVE IN SUPPRESSING ACETYLCHOLINE-MEDIATED ATRIAL FIBRILLATIONAlexander Burashnikov, PhD, Jose M. Di Diego, MD, Luiz Belardinelli, MD and Charles Antzelevitch, PhD. Masonic Medical Research Laboratory, Utica, NY, Gilead Sciences, Inc, Foster City, CAIntroduction: The present study tests the hypothesis that an agent that is highly selective for inhibition of the late sodium channel current (late INa), although effective in suppressing ventricular arrhythmias, is relatively ineffective in terminating and suppressing the induction of atrial fi brillation (AF) in an experimental model of AF.Methods: The electrophysiological actions of GS-458967, a potent late INa blocker, were evaluated by recording transmembrane action potentials and pseudo-ECGs in canine coronary-perfused right atrial (n=9) and left ventricular (n=5) preparations. Acetylcholine (ACh, 1 µM) was used to create the substrate for AF (n=9).Results: GS-458967 (10-300 nM) caused signifi cant abbreviation of action potential duration (APD50-90) in atria (consistent with inhibition of late INa), but caused no signifi cant change of APD in the ventricles. GS-458967 (≥100 nM) prolonged the effective refractory period (ERP) in atria due to the development of post-repolarization refractoriness (PRR), but did not alter ERP in the ventricles. The maximum rate of rise of the action potential upstroke (Vmax) was mildly reduced at concentrations ≥100 nM in atria, but not in the ventricles, indicating atrial-selective inhibition of peak INa. Persistent AF was induced in 10/10 atria during exposure to 1 μM ACh. GS-458967 (300 nM) did not terminate ACh-mediated AF in 3 out of 3 atria, but prevented induction of persistent AF in 3 out of 6 atria. This anti-AF effect of the drug was associated with depression of excitability secondary to block of peak INa.Conclusion: In canine coronary-perfused preparations, GS-458967 abbreviates APD, induces PRR, and reduces Vmax in atria, but causes no signifi cant change in these parameters in the ventricles. The small effect of the drug on peak INa account for its lack of effi cacy to suppress ACh-mediated AF at concentrations, previously shown to potently and effectively suppress ventricular arrhythmias.

PO04-99

SIMULTANEOUS OPTICAL MAPPING OF TRANSMEMBRANE AND INNER MITOCHONDRIAL MEMBRANE POTENTIAL REVEAL SPATIOTEMPORAL PATTERNS DURING LOW-FLOW ISCHEMIA IN HUMAN, CANINE, AND RABBIT MYOCARDIUMMatt Sulkin, MS, Fu Siong Ng, MD, PhD, Megan Tetlow, BS and Igor R. Sulkin, PhD. Washington University in Saint Louis, Saint Louis, MO

hearts being non-inducible. In all models, the in-silico determined optimal ablation lesion size was smaller than in experiments (Fig E).Conclusion: Noninvasive prediction of the optimal ablation target can be achieved by in silico analysis of infarct related VT circuits using subject-specifi c heart models.

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ARRHYTHMOGENIC CALCIUM-MEDIATED DELAYED AFTERDEPOLARIZATIONS ARE PROMOTED BY SEVERE, BUT NOT THERAPEUTIC HYPOTHERMIAHidehira Fukaya, MD, PhD, Joseph S. Piktel, MD, Bradley N. Plummer, MS, Kenneth R. Laurita, PhD and Lance D. Wilson, MD. Heart and Vascular Research Center, Metrohealth Campus, Case Western Reserve University, Cleveland, OHIntroduction: Hypothermia causes derangements in cellular calcium (Ca) cycling producing Ca overload. However,the mechanistic relationship between hypothermia-induced dysregulation in Ca cycling and arrhythmias has been never determined. Paradoxically, therapeutic hypothermia is not associated with increased risk of arrhythmia in patients after resuscitation from cardiac arrest. We hypothesized that spontaneous Ca release and delayed afterdepolarizations (DADs) would be promoted by severe hypothermia, but not mild therapeutic hypothermia.Methods: N/AResults: Transmural dual optical mapping of Ca transients and action potentials was performed in canine left ventricular wedge preparations during normothermia (N; 36°C, n=9), therapeutic hypothermia (TH; 32°C, n=9) or severe hypothermia (SH; 28°C, n=4). Multicellular spontaneous Ca release events (mSCRs) and resultant DADs were induced by rapid pacing. Hypothermia produced temperature-dependent slowing of the kinetics of Ca cycling (prolonged Ca transient rise time, duration, and decay, all p<0.01 between groups). The slope (amplitude/rise time) of mSCRs, an important determinant of triggered activity, was signifi cantly higher in SH (74.8±12.3%/s) compared to N (41.5±6.0%/s, p<0.05), associated with signifi cantly higher amplitude of DADs in SH (22.2±2.5%) compared to N

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Results: Figure 1. Drastic differences between available O2 and fNADH were observed for each working condition. The O2 concentration corresponding to the midpoint of fNADH rise for was 70% (BIV), 45% (CONO), and 25% (NCO).Conclusion: NADH imaging provides critical information for defining the relationship between workload and oxygen deprivation that is essential for gauging the severity of ischemic events.

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PLATELET-RICH PLASMA ACTIVATED WITH NANOSECOND PULSED ELECTRIC FIELDS PROMOTES MECHANICAL RECOVERY OF THE LEFT VENTRICLE FROM ISCHEMIA AND RESTORES ELECTRICAL ACTIVITYBarbara Hargrave, PhD, Francis Li, MS, Frency Varghese, MS and Christian Zemlin, PhD. Center for Bioelectrics, Norfolk, VAIntroduction: Myocardial infarction following the occlusion of a coronary artery is a major health concern. We present a modified platelet-rich plasma (PRP) than can be injected into ischemic myocardium to improve the post-ischemic performance of the left ventricle.Methods: Whole blood was taken from New Zealand rabbits and PRP was extracted. The PRP was exposed to either to nanosecond pulsed electrical fields (5 pulses of 30 kV/cm, 300 ns) or bovine thrombin. Both types of exposure have been shown to trigger the release of growth factors, cytokines, and chemokines stored in the alpha granules of platelets. The rabbit heart was excised and placed in a Langendorff perfusion setup. A balloon catheter connected to a transducer was placed in the left ventricle for the measurement of heart rate and systolic and diastolic pressures. Ischemia was induced by stopping perfusion. After 20 to 50 minutes of ischemia, the left ventricle was injected with 600 µl of PRP or saline (control), and ischemia was maintained for 10 minutes. Then the heart was reperfused for 60 minutes.Results: Left ventricular work function, which was calculated by multiplying systolic pressure times heart rate, was greater in the hearts treated with nsPEFs-activated PRP than with thrombin-activated PRP or saline (see Panel A). All hearts (n=5) completely stopped responding to electrical stimulation after 10 to 13 minutes. When PRP was injected, the electrical activity resumed in the vicinity of the PRP injection site in all hearts, even though ischemia was maintained (see Panels B,C).Conclusion: Injection of nsPEF-activated PRP during ischemia substantially improves post-ischemic left ventricular work function and stimulates electrical activity.

Introduction: Inner mitochondrial membrane potential (ΔΨm) dynamics has been implicated in loss of tissue excitability, arrhythmias, and cell death during ischemia-reperfusion (IR). We simultaneously mapped transmembrane potential (Vm) and ΔΨm to precisely link metabolic changes with electrical activity in myocardium during low-flow IR.Methods: We optically mapped left ventricular, transmural wedge preparations from human (n=4; 1 end-stage heart failure (F), 3 non-failing donor rejected (D)) and canine (n=3) hearts as well as the posterior, epicardial surface of rabbit hearts (n=3). Optical recordings were taken every 30 seconds throughout 30 minutes of equilibrium, ischemia, and reperfusion. ΔΨm fluorescence (FΔΨm) was calculated as the relative change in fluorescence from baseline to sequential recordings. Preparations were subjected to 10 μM of blebbistatin to reduce motion artifact and constantly paced at twice the diastolic threshold.Results: Thirty minutes of steady-state recordings revealed stable FΔΨm, where every pixel on the tissue was fit to a first order polynomial through time and then spatially averaged over the surface (D: m=.032±.01, R^2 =.89±.03; F: m= -.043±.02, R^2=.92±.008; Canine: m=.052±.01, R^2 =.93±.009; Rabbit: m=.029±.01; R^2 =.88±.04). Action potential durations were not significantly different (p>.05) during steady-state recordings (at 0, 10, and 30 minutes: D=395.0± 9, 389.9± 14, 401.1±12 ms; F = 413.3, 410, 402 ms; Canine=155.0± 3,162± 8,156.6± 8 ms; Rabbit = 158.8± 7, 161.1± 6, 163.1± 4 ms). During low-flow ischemia in rabbit hearts, FΔΨm decreased uniformly over the epicardial surface of the majority of pixels (80.3±4.1%). Transmural wedges, however, experienced a heterogeneous spatial response to low-flow ischemia in that subendocardial tissue maintained FΔΨm longer compared to mid- and subepicardial tissue. Mid- and subepicardial (F, D, Canine) FΔΨm collapse preceded tissue inexcitability.Conclusion: We developed a system to simultaneously map FΔΨm and Vm in myocardial tissue, which provides a powerful tool for studying fundamental aspects of cardiac function during IR.

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EFFECT OF MYOCARDIAL WORKLOAD AND OXYGEN SUPPLY ON THE DYNAMICS OF NADH FLUORESCENCEAnastasia M. Wengrowski, BS, Rafael Jaimes, III, MS, Sarah Kuzmiak, PhD and Matthew Kay, DSc. The George Washington University, Washington, DCIntroduction: Imaging of NADH fluorescence (fNADH) from cardiac tissue is becoming an important component of new multi-modal optical mapping systems. Interpreting fNADH data within the context of myocardial work load and oxygen supply is not well understood. We conducted studies to reveal the dependence of fNADH levels on workload and oxygen supply during normal sinus rhythm and 1) bi-V working conditions (BIV), 2) contraction only (CONO, Langendorff perfusion), and 3) non-contractile components only (NCO, complete electromechanical uncoupling).Methods: Rabbit hearts (n=6) were perfused via biV working heart (BIV) or Langendorff (CONO and NCO) with modified Krebs-Henseleit at 37ºC. Blebbistatin was used to silence mechanical contractions (NCO). Hearts were illuminated with UV light and epicardial fNADH was imaged with a CCD camera. A second CCD camera imaged the fluorescence of a cytosolic marker (CICF) to remove motion artifact. The fNADH/CICF ratio and aortic pressure were monitored during normal sinus rhythm, pacing (330, 220, and 170ms intervals), and recovery (n=12 runs). Perfusate was then gassed with N2 to stepwise decrease oxygen concentration.

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have led to useful models of heart failure and atrial fi brillation but are unfortunately limited by the diffi culty of molecular-genetic studies in these species. Conversely, chronic pacing studies in small mammals have been limited by the size of existing pacemakers. Here, we present the progression of a design for a fully implantable, miniature pacemaker capable of chronic (>30 days) overdrive pacing in the mouse.Methods: Battery-powered and wireless-powered pacemakers were fabricated from standard electronic components in our laboratory. Both devices produce constant voltage pulses with adjustable pacing rate and pulse width. Mice (n=21) were implanted with endocardial, battery-powered devices (n=16) and epicardial, wireless-powered devices (n=9). Ventricular pulse width thresholds and steady-state (S1S1) effective refractory periods were monitored acutely under isofl urane anesthesia. Thirty-fi ve days after implantation, hearts were explanted for histology.Results: Four out of 16 (25%) mice implanted with battery powered devices survived device implantation. Chronic pacing with the battery-powered device was achieved for a maximum of 6 days before device failure. Consequently, a smaller, wirelessly powered design was conceived and implemented. Seven out of 9 (77.8%) mice implanted with wirelessly powered devices survived device implantation. Acute pacing was achieved in 9 of 16 (56.3%) battery-powered devices and 9 of 9 (100%) of wirelessly powered devices. Ventricular pacing was successfully conducted in 3 mice at 5-day intervals for 35 days before mice were sacrifi ced. Average pulse width threshold was measured as 169.2 ± 64.0 μs for a pacing CL = 100 ms. Stable pacing at rates up to 960 bpm was achieved.Conclusion: Epicardial, ventricular pacing in a mouse for >30 days is possible with our wireless pacemaker design. Wireless pacing controlled by an external transmitter offers a novel tool for mouse model studies of cardiac memory and pacing-induced heart failure.

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CHARACTERISATION OF CATHETER-TISSUE CONTACT FORCE DURING EPICARDIAL RF ABLATION IN AN OVINE MODELMichael CG. Wong, MBBS, Glenn Edwards, BVSc., Jonathan Kalman, MBBS, PhD, Saurabh Kumar, MBBS, Stephen Joseph, MBBS, PhD, Steven Spence, No Degree and Joseph Morton, MBBS, PhD. Royal Melbourne Hospital, Melbourne, Australia, University of Melbourne, Melbourne, Australia, Western Hospital, Melbourne, AustraliaIntroduction: Contact force (CF) during radiofrequency ablation (RFA) is an important determinant of endocardial lesion size with limited data on epicardial RFA and CF. We evaluated CF characteristics using irrigated RFA on the epicardium in an ovine beating heart model.Methods: In 12 sheep a 7F irrigated RFA catheter with CF sensor was introduced via a small pericardial incision onto and in parallel with ventricular epicardium. RFA (30 watts/30 sec duration) with constant CF was applied at 5g, 10g, 20g, 40g and 70g over (a) left and right ventricular (LV/RV) myocardium at sites with or without fat; (b) either directly over or adjacent to a coronary artery; (c) directly over the phrenic nerve (PN) during PN pacing to assess for PN palsy. Each RF lesion size was measured and coronary artery and PN injury assessed.Results: A progressive increase in lesion size and volume with higher CF was observed (p<0.05). Steam pops occurred with high CF. Epicardial fat had an insulating effect on RF penetration into myocardium (p<0.05); however RF lesions were created at sites with >3.5mm epicardial fat. At sites with epicardial fat, each 10g increment in CF led to a 0.6mm increase in myocardial

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CHANGES IN CARDIAC FUNCTION UPON LIGHT-ACTIVATED RELEASE OF NOREPINEPHRINE FROM SYMPATHETIC NEURONS EXPRESSING CHANNELRHODOPSINAnastasia M. Wengrowski, BS, Rafael Jaimes, III, MS, Xin Wang, PhD, David Mendelowitz, PhD and Matthew Kay, DSc. The George Washington University, Washington, DCIntroduction: The release of norepinephrine (NE) from sympathetic neurons plays a major role in cardiac function. β-blockers, which target the β-adrenergic receptors in cardiac cells, have been long used as treatment for cardiac arrhythmias. This study uses an approach that selectively activates sympathetic neurons expressing the light activated protein channelrhodopsin (ChR2) to directly innervate and release NE in the ventricles, to test if optogenic stimulated release of NE alters heart rate and LVP in excised mouse hearts. This approach allows for controlled studies of β-blockers and arrhythmic events that arise from endogenous release of NE and β-adrenergic stimulation.Methods: Mice (Stock# 00860, 012569, Jackson Labs) were crossbred to express ChR2 in catecholaminergic cells. Tail snips from offspring confi rmed expression of ChR2. Hearts (n=3) were excised and Langendorff perfused at 60mmHg with modifi ed Krebs-Henseleit solution at 37°C. A balloon was placed inside the LV to measure left ventricular pressure (LVP). ECG electrodes monitored heart rate. A 470nm LED pulsed at 1 and 2 Hz cycles (5 msec duration) was used to illuminate the epicardium. Heart rate and LVP were measured before and after each illumination (n=9). As a positive control, 1µM isoproterenol was added to the perfusate at the end of each study to measure the sympathetic response of the whole heart.Results: Photoactivation of sympathetic fi bers that express ChR2 resulted in an increase in LVP in all hearts, with as much as a 75% increase in some hearts. Heart rate also increased from approximately 395bpm to 420bpm after optogenic stimulation of sympathetic fi bers. Addition of isoproterenol further increased pressures (~89%) and confi rmed the ability of the sympathetic pathway to be activated.Conclusion: Light pulsing at 470nm increased pressure and heart rate, confi rming the release of norepinephrine from catecholaminergic cells expressing ChR2 in isolated mouse hearts. This study presents a useful model for the study of cardiac arrhythmias that arise from activation of sympathetic fi bers and β-adrenergic stimulation in excised mouse hearts.

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A FULLY IMPLANTABLE PACEMAKER DESIGN FOR MICE: FROM BATTERY TO WIRELESS POWERJacob I. Laughner, MS, Scott B. Marrus, MD, PhD, Carla J. Weinheimer, MS, Erik Zellmer, MS, Matthew R. MacEwan, MS, Jeanne M. Nerbonne, PhD and Igor R. Efi mov, PhD. Washington University, St. Louis, MOIntroduction: Chronic pacing studies in large animal models

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Conclusion: In this model, age-related QTVI increase appears to reflect changes in autonomic control of ventricular repolarization rather than intrinsic electrical instability at a cellular level.

PO04-106

TRANSIENT LINKING DURING AF DEPENDS ON THE AF SUBSTRATE: INSIGHTS FROM HIGH DENSITY MAPPING IN MODELS OF CHRONIC ATRIAL REMODELINGPawel Kuklik, PhD, Dennis H. Lau, MBBS, PhD, Muayad Alasady, MBBS, PhD, Anand N. Ganesan, MBBS, PhD, Rajiv Mahajan, MD and Prashanthan Sanders, MBBS, PhD. Centre for Heart Rhythm Disorders, University of Adelaide, Adelaide, AustraliaIntroduction: Transient linking (TL) of wave conduction has been described in atrial fibrillation (AF). Here, we investigate dependency of TL on the underlying AF substrate.Methods: Electrical activity during induced AF on the epicardial surface of the left (LA) and right (RA) atria was recorded in vivo using rectangular meshes of electrodes in sheep with an established models of hypertension (HT; n=10), myocardial infarction (MI; n=10) and obesity (OB; n=12). First arrhythmia episode longer than 20sec was analyzed. Directions of wave propagation within mapped field were calculated and TLs were identified as groups of activations in which direction of consecutive wave did not deviate more than 25°. Periods of continuous activity within mapped area longer than 300ms were classified as Continuous Electrical Activity (CEA).Results: 64 arrhythmia episodes of length 49±29sec were analyzed. Mean and standard deviation of AF cycle length did not differ between groups but was different between LA and RA (Mean CL: LA:153±26ms, RA:164±25ms, p<0.001; SD of CL: LA:19±10ms, RA:24±11ms, p<0.004). Number of TL episodes per minute was different between groups (HT:20.1±9, MI:11.7±8.8, OB:16.1±11; p<0.044) and chambers (LA:19.2±10.1, RA:12.8±9.4; p<0.006). Percentage of the total time TL was present during arrhythmia was different between groups (HT:50.5±37.7%, MI:16.5±12.6%, OB:36.2±30.4%; p<0.002) and chambers (LA:46.2±28.9%, RA:23.6±22.1%; p<0.001). Number of CEAs was different between groups (HT:3.7±7.2, AMI:15.1±15.3, OB:2.79±7; p<0.007) but not significant between chambers. Percentage of the total time CEA was present during arrhythmia was different between groups (HT:5.4±10.3%, MI:14.1±18.3%, OB:2±4.5%; p<0.036) and not significant between chambers.Conclusion: Transient linking of AF is dependent on the underlying substrate; the HT model showed greatest degree of linking followed by OB and AMI models. Evaluation of AF cycle length alone did not capture differences in AF dynamics whereas TLs and CEAs showed significant differences between the models of chronic atrial remodeling.

PO04-107

CONTINUED CONTRACTION AND FUNCTION OF THE LEFT ATRIAL APPENDAGE AFTER ELECTRICAL ISOLATIONSandeep Panikker, MBBS, H. Tom McElderry, MD, FHRS, Gregory P Walcott, MD and Tom Wong, MD, FRCP. Royal Brompton & Harefield Hospital NHS Foundation Trust, London, United Kingdom, University of Alabama at Birmingham, Birmingham, ALIntroduction: Left atrial appendage (LAA) electrical isolation in addition to a standard ablative lesion set has been reported to improve freedom from atrial fibrillation (AF). The effect of electrical isolation on LAA function and contraction is not fully

lesion depth, while each 1mm of fat reduced lesion depth into underlying myocardium by 0.7mm. The extent of acute coronary injury with direct and indirect RFA, and the occurrence of PN palsy was proportional to CF.Conclusion: CF is a determinant of epicardial RF lesion size, steam pops, acute coronary artery injury and PN injury. Although epicardial fat limits lesion size, RFA with high CF can produce small myocardial RF lesions at sites of thick epicardial fat.

PO04-105

ACTION POTENTIAL AND QT VARIABILITY IN YOUNG AND OLD SHEEP: AGE-RELATED INCREASE IN QTVI IS NOT ASSOCIATED WITH INTRINSIC REPOLARIZATION INSTABILITY.Graeme J. Kirkwood, MBBS and Andrew W. Trafford, PhD. University of Manchester, Manchester, United KingdomIntroduction: QT Variability Index (QTVI) represents the relationship between variability of RR and QT intervals on the surface ECG. It is increased in conditions including ageing, hypertension and heart failure, and a raised QTVI is a powerful predictor of ventricular arrhythmias. The underlying mechanisms remain incompletely understood and there is controversy as to its relationship with cardiac autonomic regulation and action potential restitution. We therefore studied the relationship between QTVI and single-cell action potential variability in an established animal model of ageing.Methods: Young adult (< 1 year) and elderly (> 5 years) Welsh Mountain sheep were used, and all experiments were undertaken in accordance with AAAS guidelines. For in-vivo measurements, 256 second ECG recordings were made in conscious restrained animals under control conditions and following autonomic blockade. Standard HRV analysis was performed in the time and frequency domain, and QTVI was calculated using a modification of Berger’s algorithm as a logarithmic ratio of QT to RR variance. For action potential recordings, myocytes were isolated from the left ventricular free wall and studied using the perforated patch technique. APD90 was recorded at a constant stimulation rate of 0.5Hz and beat-to-beat variability assessed by standard deviation across the time series for each cell. Results are expressed as mean +/- SD, with significant differences by ANOVA at p<0.05.Results: Young and old animals did not differ in HRV measures, but QTVI was significantly higher in old animals (young: -1.68 +/- 0.60, old: -0.69 +/- 0.33, p<0.05). This difference was abolished by autonomic blockade. Age did not affect APD90 (young: 506.9 +/- 173.0ms, old: 407.8 +/- 89.8ms, p=ns) or beat-to-beat variability (young: 16.7 +/- 9.6ms, old: 12.2 +/- 5.8ms, p=ns).

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assigned to calcium channel blocker treatment (amlodipine 10mg daily, n=6), beta-blocker treatment (Atenolol 100mg daily, n=6) and no treatment (HTN control) for a further 16 weeks. Open chest high-density epicardial mapping (160 electrode) study was performed to assess atrial effective refractory period (ERP), conduction velocity (CV), conduction heterogeneity index (CHI) and AF inducibility in both right (RA) and left atrium (LA).Results: The HTN group has a mean systolic blood pressure (SBP) of 154±11 mmHg. 16 weeks of CCB and B-blocker treatment reduced SBP to 133±3 mmHg (p<0.001) and 131±11 mmHg (p=0.007) respectively. Atrial ERP was not altered by either therapy (Table). CCB therapy improved atrial conduction significantly with increased CV and reduced CHI (except for RA). Although B-blocker therapy improved CV (also more than CCB group; P=0.002), CHI remained unchanged. Mean induced AF duration was unchanged between HTN - 30±38 vs. CCB - 30±40 vs. BB - 39±124 s (p=NS).Conclusion: Both CCB and B-blocker therapies demonstrated features of reverse atrial electrical remodeling following reduction in the systolic blood pressure level. At similar blood pressure levels, CCB appears to be slightly superior with additional amelioration of conduction heterogeneity seen in HTN.

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IS ELECTROGRAM MORPHOLOGY & LESION SIZE PREDICTIVE OF CATHETER-TISSUE CONTACT FORCE DURING EPICARDIAL RF ABLATION IN AN OVINE MODELMichael CG. Wong, MBBS, Glenn Edwards, BVSc., Jonathan Kalman, MBBS, PhD, Saurabh Kumar, MBBS, Stephen Joseph, MBBS, PhD, Steven Spence, No Degree and Joseph Morton, MBBS, PhD. Royal Melbourne Hospital, Melbourne, Australia, University of Melbourne, Melbourne, Australia, Western Hospital, Melbourne, AustraliaIntroduction: Contact force (CF) during radiofrequency ablation (RFA) is important for adequate lesion formation with limited data on epicardial RFA & CF. We evaluated epicardial electrogram (EGM) amplitude & lesion volume to determine predictive value for real-time CF using irrigated RFA in an ovine model.Methods: In 12 sheep a 7F irrigated RFA catheter with CF sensor was introduced via a small pericardial incision onto & in parallel with ventricular epicardium. RFA (30 watts/30 sec duration) with constant CF was applied at 5g, 10g, 20g, 40g & 70g over left & right ventricular (LV/RV) myocardium. Baseline & post-RFA EGM amplitude plus lesion volume were correlated with actual CF applied.Results: Increasing lesion volume correlated with higher CF with volume doubling between 5g & 40g of applied CF (r2=0.61,p<0.001). Largest LV lesions were not transmural due to significant baseline wall thickness (mean LV 15.5±3.2mm vs. mean RV 5.6±1.0mm). RV transmural lesions were frequently seen at 70g applications & occasionally at CF 40g. Baseline EGM amplitude & pre-RFA CF correlation was moderately-poor (r=0.24,p=0.008). Sensitivity & specificity for pre-RFA EGM amplitude to predict CF>20g were 41% & 86% respectively.

understood. We studied the mechanical function of the LAA following electrical isolation in a canine model.Methods: Five canines underwent electrical isolation of the LAA using a 4mm open irrigated tip ablation catheter with the aid of a NavX 3D mapping system, following pulmonary vein (PV) isolation. A 20-pole Lasso catheter in the LAA and a 10-pole catheter in the CS were used to assess entrance and exit block. The LAA function was assessed by transesophageal echocardiography (TEE) using pulsed wave Doppler at the LAA ostium and contraction, via direct contrast injection into the LAA, before and after electrical isolation.Results: After a mean RF time of 1154±727 sec at 35W, the LAA in all 5 canines were electrically isolated with entrance and exit block achieved. There was no significant change in LAA flow waveform morphology or peak LAA outflow (0.40±0.11 m/s vs 0.46±0.13 m/s, p=0.25) or inflow (0.78±0.08 vs 0.62±0.14, p=0.08) velocities on TEE. The LAA continued to contract in all cases after electrical isolation as demonstrated by direct LAA angiography.Conclusion: This is the first observation of preserved LAA function and contraction coincident with endocardial silence of the LAA following ablation. The precise mechanism for the observed mechano-electrical dissociation in the LAA requires further elucidation.

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REVERSE REMODELING OF THE ATRIAL SUBSTRATE IN A HYPERTENSIVE OVINE MODEL: A CHRONIC PHARMACOLOGICAL INTERVENTION STUDYShivshankar Thanigaimani, MS, Dennis H. Lau, MBBS, PhD, Anthony G. Brooks, PhD, Pawel Kuklik, PhD, Rajiv Mahajan, MD, Timothy Kuchel, MRCVS, BVSc. and Prashanthan Sanders, MBBS, PhD. Centre for Heart rhythm disorders, University of Adelaide and Royal Adelaide hospital, Adelaide, Australia, SAHMRI-PIRL, Adelaide, AustraliaIntroduction: Hypertension (HTN) is known to result in atrial remodeling leading to increased atrial fibrillation (AF). However, limited information is available on whether conventional hypertensive treatments can reverse the arrhythmogenic substrate.Methods: ‘One-kidney One-clip’ hypertension was induced in 18 sheep for a mean duration of 12 weeks. These were randomly

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(hyper-enhanced on LGE).Conclusion: Thermal ablation lesions undergo complex evolution following the initial thermal damage, which may play an important complementary role in arrhythmia recurrence. MRI has a potential for characterizing the evolution and predicting longer-term ablation outcomes.

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CALMODULIN-DEPENDENT PROTEIN KINASE II INHIBITOR REDUCES MALIGNANT ARRHYTHMIA RISK IN THE HEART POST MYOCARDIAL INFARCTIONJulie A. Wolfram, PhD, Ian D. Greener, PhD, Xiaoping Wan, PhD and J. Kevin. Donahue, MD, PhD. MetroHealth Campus of Case Western Reserve University, Cleveland, OH, University of Illinois-Chicago, Chicago, ILIntroduction: Calmodulin-Dependent Protein Kinase II Inhibitor (CaMKIIn) is a peptide inhibitor of CaMKII, a regulatory protein important for calcium homeostatsis and signaling. CaMKII activity and expression are increased in heart failure, hypertrophy and arrhythmias. Since electrical remodeling after myocardial infarction has been associated with arrhythmic risk and CaMKII expression is increased after infarction, we hypothesized that CaMKII inhibition would reduce arrhythmia risk in the post MI heart.Methods: Swine (25-30kg, n=5) underwent 2.5 hr LAD occlusion to develop a MI. After 4 weeks, animals with inducible ventricular tachycardia (VT) were infused with CaMKIIn adenovirus and sacrificed after 1 week. Outcomes included electrophysiology study before and after gene transfer, optical mapping, patch clamp analysis and molecular analysis of CaMKII-related protein expression.Results: Inhibition of CaMKII reduced the number of distinct VT morphologies per animal. The monophasic action potential at 90% was significantly longer in the scar and border zone of the apex (235±18 ms at baseline vs. 275±17 post gene transfer, p=0.02). The effective refractory period trended longer after gene transfer compared to post MI recordings (p=0.054). In isolated myocytes, peak Na+ current increased (-64.18±4.3, -36.88±7.5 INa at -20mV pA/pF, p=0.02) and the maximum IKs tail current decreased (0.95±0.09, 0.37±0.06 IKs at -20mV pA/pF, p=0.038). However, IKr and IK1 did not change. We saw multiple effects on Ca handling and sarcomere dynamics: decreased sarcomere shortening (6.2%±0.4, 3.27%±0.2, p<0.0001), decreased Ca transient amplitude (0.28±0.02, 0.22±0.01, p=0.0012), increased Ca transients (44.74±2.31, 71.66±4.09, p<0.0001) and elongated the T-P segment (153.8±5.94, 191.14±5.77, p=0.0002). The action potential duration at 90% was increased compared to non-infarcted controls (264±10, 330±20, p=0005). Quantitative PCR confirmed transgene expression in the active treatment group and not controls.Conclusion: CaMKIIn expression post MI caused a decrease in VT and reduced electrical remodeling which would overall lead to decreased arrhythmia risk.

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THE DIFFERENCE BETWEEN AMIODARONE AND BEPRIDIL IN CONTROLLING ATRIAL FIBRILLATION AND ATRIAL REMODELING IN HYPERTENSIVE RATSMiyako Igarashi, MD, Nobuyuki Murakoshi, MD, DongZhu Xu, MD, Yoko Ito, MD, Yukio Sekiguchi, MD, Tomoko Ishizu, MD, Yoshihiro Seo, MD, Hiroshi Tada, MD and Kazutaka Aonuma, MD. University of Tsukuba, Tsukuba, JapanIntroduction: Amiodarone and bepridil are both multi-channel blockers and effective in restoring and maintaining sinus rhythm

Increasing EGM amplitude at higher CF trended towards significance (p=0.052). Lesion volume correlated at low (<25%) & moderate (25-75%) EGM amplitude change (p=0.041) but not with >75% change (p=0.15). EGM amplitude change was not significantly different with increasing CF (p=0.448).Conclusion: Epicardial lesion volume is strongly related to increasing CF. EGM amplitude has only modest correlation with CF demonstrating its limited value in predicting real-time CF during epicardial RFA in this model.

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ACTIVE POST-ABLATION LESION FORMATION CHARACTERIZED BY THREE DIMENSIONAL HIGH-RESOLUTION MAGNETIC RESONANCE IMAGINGBenu Sethi, MASc, Andriy Shmatukha, PhD, Mohammed Shurrab, MD, Jennifer Barry, BA, Graham Wright, PhD and Eugene Crystal, MD, FRCP. Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, Arrhythmia Services, Schulich Heart Centre, Sunnybrook Health Sciences Centre, Toronto, ON, CanadaIntroduction: Thermal ablations are used in cardiac electrophysiology. Electrical measurements confirm successful cessations of arrhythmias acutely after ablations, but recurrences occur at variable frequencies after all ablations. This may be due to post-ablation lesions evolution. We report observations of thermal ablation lesion formation in a model allowing high-resolution (HR) MRI.Methods: 32 lesions were created in back muscles of 8 rabbits using standard catheters, power and time settings. 3D HR T1-weighted (T1w), T2-weighted (T2w) and Late Gadolinium Enhancement (LGE) MRI was acquired (and compared to histology) immediately after ablations (8 les.), immediately and 2 wks after ablations (12 les.) and immediately, 2 and 4 wks after ablations (12 les.).Results: On MRI and histology, shapes, sizes and internal compositions of ablation lesions underwent tremendous changes during the first 2 wks after ablations. The acute lesions were round with unclear ill-defined borders. At 2 wks, the lesions were elliptic with sharp well-defined borders. At 4 wks, the shapes became more irregular and borders more fuzzy, which was attributed to lesion healing. Overall lesion area reduction at 2wks (as compared to acute) was ~ 65, 25 and 53 % as reported by T2w, T1w and LGE respectively. The acute lesions’ cores consisted of prominent hemorrhage and coagulation necrosis. At 2 wks, minor hematoma substituted the hemorrhage and prominent fibrosis surrounded the coagulation necrosis. They were all successfully discriminated by T1w. In acute, the edema extended beyond the contraction band necrosis (forming the lesion borders) and adjacent to it minor inflammation further into the normal tissue. At 2 wks, it was constricted to the border. Fibrosis, coagulation and contraction band necrosis were successfully discriminated by T2w. As depicted by LGE, the lesion core within the contraction band necrosis rim stayed ischemic and was surrounded by a prominent inflammation

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ridge between the LAA and LSPV were assessed. Image quality was scored by two independent reviewers based on a scale of 1 (not visible) to 5 (high quality).Results: Image quality was higher in 3D volumetric mode compared to 2D: (LAA: 3.5±1.4 vs 2.5±1.2, p<0.01; LSPV: 3.8±1.1 vs 2.1±1.2, p<0.01, LIPV: 4.1±1.0 vs 2.9±1.0, p<0.01, RSPV: 4.1±1.2 versus 3.4±1.2, p=0.03, RIPV: 4.3±1.2 versus 3.7±1.3, p<0.01). 3D VICE mode revealed excellent visualization of the LAA ridge (Figure 1) in all patients (100%). Importantly, 50% of patients had at least one PV or the LAA with a score ≤ 2/5 in 2D mode (poorly/not visible) but had a score of 5/5 in 3D VICE mode (excellent visualization).Conclusion: This is the first clinical experience with a 3D VICE system demonstrating significantly enhanced accuracy in assessing the true geometry of LA structures relevant for AF ablation and provides unique views otherwise unobtainable by 2D mode

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IMAGING “AF BEGETTING AF”: NONINVASIVE ECGI DEMONSTRATES ELECTROPHYSIOLOGICAL CHANGES IN HUMANS WITH PAROXYSMAL AF WHICH IS ASSOCIATED WITH AF RECURRENCE AFTER PVIPhillip Cuculich, MD, Ramya Vijayakumar, MS and Arpit Agrawal, MD. Washington University in Saint Louis, Saint Louis, MO, Barnes-Jewish Hospital, Saint Louis, MOIntroduction: Atrial fibrillation (AF) causes and perpetuates with a remodeling process. There is no noninvasive method to study this process in humans.Methods: Noninvasive Electrocardiographic Imaging (ECGI) was performed during sinus rhythm on 20 subjects with a history of paroxysmal AF prior to pulmonary vein isolation (PVI) procedure after drug washout. Total atrial and left atrial conduction times (TACT and LACT, electrical remodeling) and left atrial posterior wall voltage (LAPW, structural remodeling) were measured. One year drug-free PVI outcomes were recorded.Results: Adverse electrical remodeling was imaged with ECGI early in AF and was progressively worse with longer AF duration (Figure). Structural remodeling was present largely in subjects with > 5 years of paroxysmal AF (Figure). PVI success (n=14) was associated with shorter TACT (90 vs. 113ms, p<0.005), higher LAPW voltages (0.50 vs. 0.20mV, p=0.012) and was independent of age and left atrial size.Conclusion: Noninvasive electrical imaging of advanced atrial remodeling was associated with worse PVI outcomes in this small study. If replicated, ECGI may help guide treatment decisions through better understanding of patient-specific atrial physiology.

in patients with persistent atrial fibrillation (AF). However, there is little information about the mechanisms of them on inhibiting AF.Methods: A total of 36 Dahl salt-sensitive hypertensive rats were divided into a 0.3%-NaCl-fed normotensive group and 8%-NaCl-fed hypertensive group. The 0.3%-NaCl-fed rats were orally administered with a vehicle as a control (Control), and the 8%-NaCl-fed rats were also orally administered with a vehicle (HT), amiodarone (Amio), and bepridil (Bepri). After a 4 week-treatment, we assessed and compared the results of the electrophysiologic study, histological analysis and Western blotting among the 4 groups.Results: The induced AF duration was significantly prolonged in the HT-group, and equally shortened in the Amio and Bepri groups (control: 23±17, HT: 45±36, Amio: 18±16, Bepri: 20±21 [sec]; p<0.05). The degree of interstitial fibrosis was greater in the HT-group than that in the Control-group and it was equally suppressed in the Amio and Bepri groups (control: 4.1, HT: 13.0, Amio: 7.0, Bepri: 6.5 [%]; p<0.01). The hyperphosphorylation of p53 in the HT-group was significantly suppressed only in the Amio-group. On the other hand, hyperphosphorylation of CaMKII in the HT-group was significantly suppressed only in the Bepri-group. These findings suggested that amiodarone could be more effective for inhibiting cardiac hypertrophy or apoptosis, and bepridil may be more related to calcium handling.Conclusion: Amiodarone and bepridil were both effective for inhibiting AF perpetuation in hypertensive rats through different mechanisms.

PO04-113

INITIAL CLINICAL EXPERIENCE WITH 3D VOLUMETRIC INTRACARDIAC ECHOCARDIOGRAPHY FOR ASSESSMENT OF LEFT ATRIAL ANATOMYTeferi Mitiku, MD, Neil R. Brysiewicz, MS, Paras Bhatt, MD, Mustapha Al-Shaaraoui, MD, Jude F. Clancy, MD, Mark A. Marieb, MD, Kamran Haleem, MD, Lissa Sugeng, MD and Joseph G. Akar, MD, PhD. Yale University School Of Medicine, New Haven, CTIntroduction: Traditional, intracardiac echocardiography is limited to imaging in 2D planes, which does not reproduce an accurate, detailed 3D geometry of the left atrium (LA). This study explores the possible benefits of real-time 3D volumetric ICE (3D VICE) imaging in assessing LA anatomy.Methods: An ACUSON AcuNav V 10F phased-array ultrasound catheter was coupled with an SC2000 imaging system (Siemens Healthcare, Mountain View, CA) to obtain simultaneous 2D and 3D volumetric image sequences of LA structures in ten patients (9 males, age 66±2 years) undergoing LA ablation.The LA appendage (LAA), left superior and inferior (LSPV, LIPV), right superior and inferior (RSPV, RIPV) pulmonary veins, and the

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TISSUE ACTIVATION FREQUENCY IDENTIFIES ROTOR DENSITY IN MULTI-WAVELET REENTRYBryce E. Benson, BS, Nicole Habel, MD, Richard T. Carrick, BS, Philipp Bielau, No Degree and Peter S. Spector, MD. University of Vermont, Burlington, VTIntroduction: Perpetuation of atrial fibrillation can be caused by either multi wavelet reentry or a mother rotor with fibrillatory conduction. Optical mapping studies have demonstrated that regional variation of tissue activation frequency (TAF) can be caused by a single high frequency rotor with fibrillatory conduction. We propose that TAF can identify regions of high rotor density during multi wavelet reentry.Methods: Using a custom computer model we created a two-dimensional sheet of tissue comprised of 80x80 cells. Action potential duration (APD) randomly varied between 125 and 135ms. A 25x25 cell patch with shorter APD (80 ± 5ms) was placed on the tissue to create regional heterogeneity. Twelve episodes of AF were initiated by burst pacing (at 12 different locations). TAFs and rotor density were identified over 10s during each episode. The tissue was divided into 100 areas and mean TAF and rotor density were calculated for each region.Results: We found a strong correlation between TAF and rotor density (r2 = 0.8659). There was a statistically significant difference between TAF in and out of the high rotor density region (for example region 1 vs 2 in figure (9.6 ± 0.1 Hz vs. 10.9 ± 0.3 Hz respectively, p < 0.001)).Conclusion: Tissue activation frequency identifies regions of high rotor density in multi-wavelet reentry and can therefore serve as a target for map-guidance during ablation.

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FOCAL ACTIVATION SITES IN THE LEFT ATRIUM OF PATIENTS WITH ATRIAL FIBRILLATION: PREVALENCE, DISTRIBUTION AND RELATIONSHIP TO SCARMoloy Das, MBBS, Sigfus Gizurarson, MD, PhD, Rupin H. Dalvi, MSc, Behnaz Ghoraani, PhD, Andrew Ha, MD, Adrian M. Suszko, MSc, Sridhar Krishnan, PhD and Vijay S. Chauhan, MD, FRCP. Toronto General Hospital, Toronto, ON, Canada, Ryerson University, Toronto, ON, CanadaIntroduction: The pathophysiology of AF maintenance is not well understood, but may depend on structural remodeling and the presence of focal activation sites (FAS). We aimed to evaluate the existence and spatial location of FAS and their relationship to LA scar.Methods: In 32 patients undergoing AF ablation (56.7±8.3 yrs, 84% persistent AF, AF duration 4.5±3.9 yrs), bipolar EGM recordings of 2.5 sec were made at multiple sites in the LA with a 20-pole circular catheter during AF. The presence of FAS was based on near-simultaneous (within 50 ms) local activation in 7 of 10 bipoles for at least 3 consecutive cycles (Figure 1). The FAS site was approximated to the centre of the circular catheter. LA scar was defined by bipolar voltage <0.1 mV.Results: After exclusion of non-contact points, 231±76 bipolar EGMs per patient (from a total of 452±112 EGMs) were used in the analysis. FAS were identified in 78% of patients (3.0±3.8 FAS per patient) with a CL of 168±21 ms. Most FAS (94%) were transient with a duration of 660±271 ms. The majority of FAS (75%) were located in the PV ostium/antral region (RIPV > LIPV > LSPV > RSPV). The anterior wall was the most common non-PV site (14%). Scar size was 12±11% of total LA area. Almost all FAS (93%) were located in normal LA voltage regions (>0.1 mV) and there was a significant inverse correlation between LA scar size and number of FAS per patient (r= -0.373, p=0.036).Conclusion: Focal activity is highly prevalent during predominantly persistent AF but is usually very transient (<1 sec). Most FAS are found in the region of the PVs within normal atrial tissue. The paucity of FAS in heavily scarred LA may imply alternative, more diffuse mechanisms in the maintenance of AF which may limit the success of catheter ablation.

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INTRA-TISSUE ABLATION & VISUALIZATION SYSTEM TO MONITOR LESION FORMATION TO MINIMISE EXTRACARDIAC ABLATIONMatthew James. Wright, MBBS, PhD, David Haines, MD, FHRS, Erik Harks, PhD, Fei Zuo, PhD, Frank Budzelaar, MSc, William C. Stoffregen, DVM, PhD, Darrell L. Rankin, MEng, Joseph Nguyen, BS, Vivek Reddy, MD and Pierre Jais, MD. St. Thomas’ Hospital, London, United Kingdom, Beaumont Heart Center, Royal Oak, MI, Philips Healthcare, PC Best, Netherlands, Philips Research, Eindhoven, Netherlands, Boston Scientific, San Jose, CA, Mount Sinai Hospital, New York, NY, Hôpital Cardiologique du Haut Lévêque, CHU Bordeaux, Pessac, FranceIntroduction: Ablation beyond the cardiac boundary can have devastating consequences. We developed an RF ablation catheter with multiple ultrasound (US) transducers to monitor in real time atrial wall thickness, extra-cardiac tissue and visualise lesion formation in real time. The aim of the present study was to differentiate between tissue types and visualise ablation of cardiac and extra-cardiac tissue.Methods: 16 sheep were used in this study with a total of 104 attempts of lesion formation in the atria. Lesions were made using a 7Fr open irrigated RF ablation catheter with 4 US transducers in the 5.3mm ablating electrode to assess in real time the atrial wall boundary and lesion formation. Mean power delivery was 32 ± 4W, with RF delivered between 13-120 seconds. Lesion geometry and US images were blindly assessed by a pathologist or 3 operators respectively.Results: Characteristic atrial contraction was seen at all sites where lesion delivery was attempted. RF delivery resulted in 69 (66 %) lesions detectable at pathology, 61 of which were transmural, and were correctly seen on US in 73% of cases. In 53 lesions the lung was within 0.9±0.7 (0.2-2.8) mm of the cardiac boundary as assessed by US. Ablation of the adjacent lung occurred in 29 lesions and was identified by US in 82%. When the lung was not visualised on US there were no adjacent lung lesions.Conclusion: US integrated into a RF ablation catheter can accurately differentiate between tissue types based upon reflection and contraction patterns. This allows lesions to be delivered safely, minimising extra cardiac damage.

Figure Legend: Voltage map of a snapshot of multi-wavelet reentry (A), rotor density map (B) and corresponding TAF map (C). TAF plotted against rotor density (D).

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VISUALIZATION OF THE LEFT ATRIAL APPENDAGE BY PHASED ARRAY INTRACARDIAC ECHOCARDIOGRAPHY FROM THE PULMONARY ARTERY IN PATIENTS WITH ATRIAL FIBRILLATIONTakahiko Nishiyama, MD, Yoshinori Katsumata, MD, Kohei Inagawa, MD, Takehiro Kimuta, MD, PhD, Nobihiro Nishiyama, MD, PhD, Kotaro Fukumoto, MD, Yoko Tanimoto, MD, PhD, Yoshiyasu Aizawa, MD, PhD, Kojiro Tanimoto, MD, PhD, Keiichi Fukuda, MD, PhD and Seiji Takatsuki, MD, PhD. Keio University school of Medicine, Tokyo, JapanIntroduction: The left atrial appendage (LAA) represents one of the major sources of cardiac thrombus formation in patients with atrial fibrillation (AF). Transesophageal echocardiography (TEE) is known to be the gold standard to detect the thrombus in the LAA, however, which can be a painful examination. Recently, the phased-array intracardiac echocardiography (ICE) has been available.Methods: We aimed to study the feasibility of the ICE for visualization and evaluation of LAA in patients with AF undergoing catheter ablation. Forty-seven patients with AF undergoing catheter ablation (male 40, 58±9 years) were included.Results: TEE and ICE were performed on the previous day of the catheter ablation and just before the transseptal puncture during catheter ablation, respectively. ICE catheter was advanced up to the pulmonary artery (PA) from the femoral vein which could visualize the LAA from the apex. In all patients, the LAA was clearly and entirely visualized with manipulating ICE catheter. The LAA flow velocity measured by the ICE showed a good correlation with that measured by TEE (R=0.414, p=0.004). No patients developed any complications.Conclusion: The ICE utilized in PA is feasible for making observation and evaluation of the LAA. ICE might be a substitute for TEE in the low risk AF patients undergoing catheter ablation to rule out the accidental thrombus formation in the LAA.

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during continuous vagal stimulation (20Hz). AF could be induced reproducibly (5-6 times) in the same animal by repeating the stimulation procedure after a 5 min rest. The effects of drugs (iv bolus) on the inducibility and termination of AF was tested in the presence of drugs given starting at 1 min after initiation of AF. Results: In control rats, AF induced by burst stimulation lasted for 4.9 ± 0.06 min while the vagal nerve stimulation was maintained (5 min). TPNQ, FLEC, E-4031 and RAN dose-dependently terminated AF, shortened mean AF duration (AFD) and prevented the induction of AF. The potencies (EC50) of TPNQ, FLEC, RAN and E-4031 to terminate AF were 0.005, 0.7, 6 and 15 µM (plasma concentration) and the AFD at highest doses of TPNQ (0.024 µM), FLEC (2.9 µM), RAN (19 µM) and E-4031(18 µM) was 1.1 ± 0.13, 1.3 ± 0.74, 1.5 ± 0.39 and 2.8 ± 0.97 min, respectively.Conclusion: TPNQ, FLEC, E-4031 and RAN prevented and terminated AF in a dose-dependent manner. As expected, the IKAch blocker TPNQ was more potent than other compounds, indicating that IKAch plays an important role in vagatonic AF. FLEC was more potent than RAN, suggesting that blocking peak INa is an important contributor to the anti-AF effects of these drugs. E-4031 was the least effective among these ion channel blockers, consistent with the fact that IKr does not play an important role in atrial action potential repolarization in the rat. The potencies of the drugs to terminate AF are in agreement with previous clinical and experimental reports, suggesting that this AF model can be used to predict the anti-AF effect of new agents.

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COMPASSIONATE USE OF LARIAT DEVICE FOR PERCUTANEOUS EPICARDIAL EXCLUSION OF ANATOMICALLY CHALLENGING LEFT ATRIAL APPENDAGESMehul Patel, MD, Mossaab Shuraih, MD, Mihail G. Chelu, MD, Nilesh Mathuria, MD, Ali Massumi, MD, Mehdi Razavi, MD, Abdi Rasekh, MD and Jie Cheng, MD, PhD. The Texas Heart Institute/St. Luke’s Episcopal Hospital, Houston, TXIntroduction: Percutaneous left atrial appendage exclusion (LAAE) with the LARIAT closure device is used to reduce stroke risk in patients with nonvalvular atrial fibrillation (AF) and contraindication to oral anticoagulation (OAC). However, a sizable number of such patients may get excluded due to unfavorable anatomies such as large left atrial appendage (LAA) width >40 mm, superior LAA orientation, LAA apex directed behind the pulmonary artery (PA), and large bilobed/multilobed LAA. We report the safety and feasibility of using LARIAT device for patients with such unfavorable LAA anatomies in the hybrid operating room (hOR).Methods: Between January 2010 and November 2012, 86 patients with persistent/permanent AF, CHADS score ≥ 2 and contraindication(s) for OAC were evaluated for LAAE with LARIAT device. LAA anatomy was examined with 3D CT angiography in multiple views. 22 patients were initially excluded due to unfavorable anatomic features. Of these, 7 patients underwent LARIAT device closure; all had major intolerance including life-threatening bleeding from OAC with a compelling indication to prevent stroke due to high CHADS scores.Results: A total of 7 patients, mean age 67.1 ± 7y, three females, with unfavorable LAA anatomy, underwent successful LAAE using LARIAT device in hOR, with surgical back-up. All patients had large LAA (>40mm, range 45 to 58mm); additional variations included: bilobed in 3, long C shaped lobe prolapsing behind the PA in 1, and a large multilobed cauliflower-like LAA in 1. The LARIAT delivery device was able to deliver the suture percutaneously and completely capture the LAA at the

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LEFT ATRIAL APPENDAGE CLOSURE FOLLOWED BY SIX WEEKS ANTITHROMBOTIC THERAPY - A PROSPECTIVE SINGLE CENTER EXPERIENCEKyong Ryul Chun, MD, Stefano Bordignon, MD, Alexander Fuernkranz, MD, Melanie Gunawardene, Verena Urban, MD, Britta Schulte-Hahn, MD, Bernd Nowak, MD and Boris Schmidt, MD, FHRS. CCB - Cardioangiologisches Centrum Bethanien, Frankfurt a.M., GermanyIntroduction: The concept of left atrial appendage (LAA) closure has been introduced as a treatment alternative for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). Currently, two different LAA closure systems are available but lacking comparative data.Objective: To prospectively compare procedural data and patient outcome for both LAA closure systems.Methods: Consecutive patients (pts) with NVAF, high risk for stroke and either contraindication or not willing to accept long term oral anticoagulation (OAC) were prospectively allocated to 2 groups: Watchman™, Boston Scientific (group A) or Cardiac plug™, St. Jude Medical devices (group B) were implanted. LAA dimensions were calculated from TEE and angiography. All patients received dual antiplatetet therapy (aspirin/clopidogrel) or OAC (HASBLED<3) for 6 weeks followed by TEE re-assessment. If eligible, switch to aspirin alone performed.Results: A total of 80 pts were prospectively enrolled in this study. There was no statistical difference between group A (n=40) and B (n=40): CHA2DS2VASC: 4.2±1.5 vs. 4.4±1.8, HASBLED: 3.3±1.1 vs. 3.0±1.1, respectively. Acute LAA occlusion was achieved in 79/80 (99%) pts (group A: 39/40, 98%,) and in (group B: 40/40, 100%), respectively. Procedure- and fluoroscopy-time were not different (group A vs. B: 50±17 min vs. 47±15 min and 6.5±5.0 min vs. 7.5 ± 4.4 min, respectively. Procedural complications included one ST elevation and one delayed tamponade in each group. At 6 weeks F/U one device dislodgment (group B) and four device related thrombi were noticed (group A: n=3, group B n=1). During a mean follow of 313±178 days no stroke or systemic embolism was observed. Two patients died from heart failure, one from GI bleeding under aspirin alone. Switch to aspirin alone was enabled in 99 % of patients (80% after 6 weeks).Conclusion: Implantation of LAA closure devices can be performed with high success rates in high-risk patients. Postprocedural 6 weeks antithrombotic therapy followed by ASA appears to be safe and feasible.

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A SMALL ANIMAL MODEL OF ATRIAL FIBRILLATION PREDICTS CLINICAL EFFICACY OF ANTI-ARRHYTHMIC AGENTSWei Qun Wang, MD, Xiao-Jun Li, PhD, Arvinder K Dhalla, PhD and Luiz Belardinelli, MD. Gilead Sciences, Inc., Fremont, CAIntroduction: Experimental models of atrial fibrillation (AF) commonly use large animals, which are expensive and not easily available. We describe a new, reliable and reproducible AF model in rats to determine the anti-AF effect of drugs. We evaluated the anti-AF effects of various ion channel blockers including inhibitors of peak INa (flecainide, FLEC), IKr (E-4031), IKAch (tertiapin-Q, TPNQ) and late and peak INa (ranolazine, RAN) in this model.Methods: Male SD rats (n=29) were anesthetized and a quadripolar electrocatheter was placed into right atrium (RA) to record atrial electrograms and to electrically stimulate the atrium. Sustained AF was induced by burst stimulation (50Hz) to the RA

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MD and Atsushi Takahashi, MD. Yokosuka Kyosai Hospital, Yokosuka, JapanIntroduction: Although long-term efficacy of catheter ablation in atrial fibrillation (AF) patients without structural heart disease (SHD) has been reported, that of AF patients with valvular heart disease (VHD) remains unclear. Methods: This study included 2,369 AF patients without any indication of valve surgery or other SHD (mean age 60.8±10.3 years, paroxysmal AF: 1,899 patients, persistent AF: 470 patients). All patients underwent extensive pulmonary vein isolation (EPVI), and focal and/or linear ablation was performed if needed. The ablation results in the VHD patients (group-1, n=314) were compared with those of non-VHD (group-2, n=2,055).Results: The group-1 patients were significantly longer history of AF and larger left atrial dimension compared to the group-2 patients. EPVI was successfully achieved in all patients. The arrhythmia-free survival rate after a single ablation procedure was significantly lower in group-1 than group-2 with a mean follow-up of 33±24 months without any antiarrhythmic drugs (57% vs 69%, P=0.0002). However, the difference in the arrhythmia-free survival rate between the 2 groups became smaller at a mean follow-up of 35±25 months after the last ablation session (group-1: 78% vs. group-2: 81%, P=0.033).Conclusion: In a large cohort of AF patients with VHD, an acceptable long-term efficacy could be achieved by an EPVI based ablation with repeat sessions.

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COMPARISON OF BALLOON CATHETER ABLATION TECHNOLOGIES FOR PULMONARY VEIN ISOLATION - THE LASER VERSUS CRYO STUDYStefano Bordignon, MD, Kyong Ryul Julian. Chun, MD, Melanie Gunawardene, MD, Alexander Fuernkranz, MD, Verena Urban, MD, Britta Schulte-Hahn, MD, Bernd Nowak, MD and Boris Schmidt, MD, FHRS. CCB Markuskrankenhaus Frankfurt Germany, Frankfurt a.M., Germany, CCB - Cardioangiologisches Centrum Bethanien, Frankfurt a.M., GermanyIntroduction: Balloon catheters have been developed to facilitate pulmonary vein isolation (PVI) in patients with drug-refractory paroxysmal atrial fibrillation (PAF).Objective: To compare the safety and efficacy of the cryo-balloon (CB) and the laser-balloon (LB) for PVI in patients with PAF.Methods: One hundred and forty patients with drug refractory AF were prospectively allocated in a 1:1 fashion to undergo a PVI procedure with the 28 mm CB or the LB and were followed for a minimum of 12 months in 3 months intervals thereafter using 3 day Holter ECG recording. The primary efficacy end point was a documented AF recurrence ≥ 30 seconds between 90 and 365 days after the index ablation.Results: In total, 269/270 PVs (99.6%) and 270/273 PVs (98.9%) were acutely isolated in the CB and LB group, respectively. Mean procedural time was 136 ± 30 minutes for the CB group and 144 ± 33 minutes for the LB group (p=0.13). Mean fluoroscopy time was longer in the CB group (21 ± 9 minutes versus 15 ± 6 minutes; P<0.001). During 12 months follow-up, 37% of patients in the CB group and 27% in the LB group experienced an AF recurrence (p=0.18). Phrenic nerve palsies occurred in 5.7% (CB) and 4.2% (LB) of patients, respectively.Conclusion: Balloon catheters are a viable option to safely perform a PVI procedure in patients with drug-refractory PAF. Ninety-nine per cent of PVs may be acutely isolated with a single balloon catheter. The AF free survival rate after a single ablation procedure was not statistically different in both groups.

ostium in all patients. Two patients required minimally invasive thoracotomy; one due to inability to release the LARIAT snare from a long C-Shaped LAA and the other due to preexisting adhesions requiring surgical window to access the pericardial space. The mean length of stay was 4.57 ± 2.1 days. There were no major complications or peri-procedural deaths.Conclusion: Percutaneous LAAE with LARIAT device is safe and feasible in patients previously excluded due to unfavorable LAA anatomy. However, such cases may be best performed with close surgical backup in the hOR.

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COMPARISON OF LONG-TERM OUTCOME BETWEEN LASER BALLOON, CRYOBALLOON AND IRRIGATED RADIOFREQUENCY ABLATION OF PAROXYSMAL ATRIAL FIBRILLATIONGaetano M. Fassini, MD, Antonio Dello Russo, MD, Osama Al-Nono, MD, Stefania Riva, MD, Massimo Moltrasio, MD, Fabrizio Tundo, MD, PhD, Benedetta Majocchi, MD, Moussa Mansour, MD, Conor D Barrett, MD, Kevin E Heist, MD, PhD, Jeremy N. Ruskin, MD and Claudio Tondo, MD. Cardiac Arrhythmia Research Centre, Centro Cardiologico Monzino IRCCS, Milan, Italy, MGH Heart Center, Cardiac Arrhythmia Service, Massachusetts General Hospital, Boston, MAIntroduction: Radiofrequency (RF) is still the most widespreadly used energy source of ablation for symptomatic drug-refractory paroxysmal atrial fibrillation (PAF). Cryoballoon and laser balloon are promising alternatives. The aim of the study is to compare the long-term outcome between the three different ablation technologies.Methods:We compared 20 patients (pts) with PAF who underwent pulmonary veins isolation with the laser balloon to 35 matched pts with cryoballoon ablation and 80 patients with conventional RF ablation. All patients underwent regular follow up with 7-day-Holter-ECG recording and outpatient clinic evaluation every 3 months for > 1 year after ablation procedureResults:There was no significant difference between the three groups regarding patients’ characteristics and procedure parameters including the left atrial dimensions (22.4 ± 5.5, 23.2 ± 4.8, 24.7 ± 9.1 cm2 respectively), left ventricular ejection fraction (62.9 ± 7.2, 62.8 ± 5.1, 57.6 ± 16.2 % respectively) and the fluoroscopy time (33 ± 10.4, 56.3 ± 26.8, 49 ± 22.3 min respectively) except for the longer procedural times in the laser and the cryoballoon groups (210.3 ± 53.8, 193.1 ± 52, 161.7 ± 53.2 min respectively) which was statistically different compared to the RF group (P= 0.003 and 0.006 respectively). The overall long-term success in the laser balloon and the RF groups was 85% whereas it was 77.2% in the cryoballoon group with no statistically significant difference (p= 0.56). The study showed more incidence of pericardial effusion in the laser balloon group, one case of transiet ischemic attack and one case of reversible phrenic nerve palsy in the cryoballoon group.Conclusion:PAF ablation by means of the laser balloon or cryoballoon is feasible and seems to have a similar long-term success rate in comparison to conventional RF ablation. Procedure times of the laser balloon and cryoballoon ablation were significantly longer than in RF ablation.

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LONG-TERM EFFICACY OF CATHETER ABLATION OF ATRIAL FIBRILLATION IN PATIENTS WITH VALVULAR HEART DISEASEKatsumasa Takagi, MD, Taishi Kuwahara, MD, Kenji Ohkubo, MD, Masateru Takigawa, MD, Yuji Watari, MD, Emiko Nakashima, MD, Naohiko Kawaguchi, MD, Kazuya Yamao,

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NECESSITY AND CHARACTERISTICS OF REPEAT PROCEDURES IN THE CONTEXT OF A NEWLY ESTABLISHED PROCEDURAL ENDPOINT OF UNEXCITABILITY ALONG THE ABLATION LINE FOR PULMONARY VEIN ISOLATIONDaniel Steven, MD, Arian Sultan, MD, Jakob Lüker, MD, Boris Hoffmann, MD, Thomas Rostock, MD, Benjamin Schäffer, MD, Doreen Schreiber, MD, Helge Servatius, MD, Jana Nuehrich, MD, Mathias Knoll, MD, Gregory F. Michaud, MD and Stephan Willems, MD. Universitaeres Herzzentrum Hamburg, Hamburg, Germany, University Hospital Mainz, Hamburg, Germany, Robert Bosch Krankenhaus, Stuttgart, Germany, Brigham and Women’s Hospital, Boston, MAIntroduction: Electrical pulmonary vein isolation (PVI) is an established endpoint for catheter ablation for paroxysmal atrial fibrillation (PAF). However, reconnection of the PVs during follow-up (FU) frequently occurs. An additional endpoint of non-excitability along the line may help to improve long-term outcomes and avoid PV reconnection in a randomized trial comparing conventional ablation (group1) to ablation using this additional endpoint (group 2). We report on frequency and periprocedural parameters of repeat procedures during this trial.Methods: Between August 2009 and August 2011, 74 patients (pts) with PAF were enrolled in the study at our institution. Of those, 37 pts were randomized to PVI using a conventional ablation approach. The second arm (n=37 pts) additionally underwent continuous ablation beyond PVI to achieve unexcitability along the ablation line (2mV @ 10ms). Pts and procedural characteristics were evaluated. Endpoints consisted of time to repeat procedures, radiofrequency (RF) energy, number of reconnected PVs and location of PV reconnection as assessed by three-dimensional mapping.Results: During the course of follow-up (18±6 months) 15 repeat procedures in 15 patients were performed (1/pts; 20%). According to higher recurrence rates, pts in group 1 had a significant higher number of repeat procedures (n=12 vs. n=3, p=0.01). Procedural characteristics did now show significant differences between groups. Main areas of RF application during repeat procedure consisted of (1) the ridge between left superior PV and left atrial appendage and (2) LA roof towards the right superior PV. However, pts in group 2 showed a trend towards a higher number of reconnected PVs (2.1 vs. 2.7 PVs) possibly indicating more complex anatomical circumstances.Conclusion: Pts undergoing PVI with the additional endpoint of non-excitability have significantly better outcomes after a single procedure resulting in significantly fewer repeat procedures. Anatomical challenges may be considered as the main reason. Further technical improvement such as contact force measurement may be helpful to overcome this limitation.

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PHOTON BEAM RADIATION INDUCED HEART BLOCK IN LANGENDORFF-PERFUSED PORCINE HEARTS: FEASIBILITY OF EXTRACORPOREAL ABLATION OF ARRHYTHMOGENIC TISSUEH Immo Lehmann, MD, Limin Song, PhD, Juna Misiri, MD, Jack Cusma, PhD, Kay Parker, Susan B. Johnson, BS, Samuel J. Asirvatham, MD, Suraj Kapa, MD, Daniel J. Ma, MD, Robert C. Miller, MD, Michael G. Herman, PhD and Douglas L. Packer, MD. Mayo Clinic, Rochester, MNIntroduction: External radiation beam therapy delivered to arrhythmogenic locations of the heart may be a promising non-invasive treatment for cardiac arrhythmias. In an ex situ model of

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INTEREST OF REAL-TIME CONTACT FORCE SENSING FOR PULMONARY VEIN ISOLATION - MID-TERM OUTCOME AFTER PAROXYSMAL ATRIAL FIBRILLATION CATHETER ABLATIONJean-Paul Albenque, MD, Samia Fazaa, MD, Eloi Marijon, MD, Benoit Guy-Moyat, MD, Abdeslam Bouzeman, MD, Frederic Treguer, MD, Nicolas Combes, MD, Stephane combes, MD and Serge Boveda, MD. Clinique Pasteur, Toulouse, FranceIntroduction: We hypothesized that the use of continuous sensing contact force (CF) technology during pulmonary vein isolation (PVI), in the setting of paroxysmal atrial fibrillation (AF) was associated to a significant reduction of AF recurrence at mid-term.Methods: Eligible patients with symptomatic paroxysmal AF were enrolled in this prospective non-randomized study (NCT01630031). PVI (anatomic approach-linear antral catheter ablation guided by CARTO® 3 System, Biosense Webster, Inc.) was performed by a same experienced operator, using either the THERMOCOOL® SMARTTOUCHTM Catheter (Biosense Webster, Inc.) (CF group), or THERMOCOOL® SF or EZ STEER® THERMOCOOL® Catheters (Biosense Webster, Inc.) (control group). Except for CF information (with an objective of at least 10 g), ablation procedures were carried out using identical approaches in both groups. In case of incomplete PVI, additional ostial lesions (electrophysiological approach-then guided by a Lasso catheter) were performed to finally achieve complete PVI. The primary endpoint was the proportion of AF recurrence (free of any antiarythmic treatment), after a single catheter ablation procedure, assessed during a 12-month standardized follow-up (including a 3-month blanking period) with Holter ECG monitoring at 3, 6 an 12 months.Results: Of the 60 patients enrolled in the study (30 patients in each group), all patients achieved a complete 12-month follow-up. Demographic, cardiovascular and anatomic characteristics were similar in both groups. Effective PVI was achieved in all patients, using an exclusive anatomic approach in 83.3% in CF group vs. 38.3% in control group (P<0.0001). After a 12-month follow-up, 12 patients (20%) demonstrated at least one AF episode after a mean period of 5.6±3 months. The proportion of AF recurrence was 10.5% (95% CI, 0.0-22.4) in the CF group, compared to 35.9% (95% CI, 12.4-59.4) in the control group (Log Rank test, P=0.04). After adjustment on potential confounding factors, the use of CF catheter was found to be independently associated to a lower AF recurrence during follow-up.Conclusion: Our findings emphasize the potential interest of real-time CF sensing technology, to finally reduce AF recurrence burden after PVI for paroxysmal AF.

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or persistent (27%) AF. INR for WARF group was 2.2±0.4. Baseline characteristics were similar among the groups (see Table). There were 2 TE events (asymptomatic cerebral emboli and TIA) and 7 bleeding events (hematoma n=3; pericardial effusion n=3; persistent hematuria n=1) with no significant difference in complications among groups (LtoW vs. WARF vs. NOAC; 5% vs. 3% vs 4%; P=NS).Conclusion: In this group of AF patients undergoing catheter ablation, use of dabigatran or rivaroxaban peri-procedure did not lead to an increase in bleeding or TE complications.

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LONG-TERM OUTCOME FOLLOWING PULMONARY VEIN ISOLATION (PVI) FOR MANAGEMENT OF ATRIAL FIBRILLATION (AF): AN UPDATED ANALYSIS OF A LARGE PROSPECTIVE COHORTRachel Palekar, BA, Tina Sichrovsky, MD, Richard E. Shaw, PhD, Dan Musat, MD, Aysha Arshad, MD, Mark Preminger, MD, Suneet Mittal, MD, FHRS and Jonathan Steinberg, MD, FHRS. Valley Hospital, Ridgewood, NJIntroduction: PVI is the cornerstone of AF ablation. Although AF is eliminated in most patients (pts), we and others have reported a significant rate of very late recurrence (VLR), defined as recurrence after being AF-free off antiarrhythmic drugs ≥ 12 months. The goal of this analysis was to determine: 1) long-term efficacy of PVI in a larger prospective cohort with longer follow-up; 2) risk factors for VLR; 3) patterns of VLR and need for treatment; and 4) efficacy of re-ablation after VLR.Methods: AF ablation pts were invited to join a prospective registry if there were no obstacles to long-term follow-up. All pts free of AF for 1 year post ablation are the focus of this analysis.Results: A total of 432 pts (age 63.5±10.6, 320 male) were followed for 68.6 ±34.6 months. 79 of 432 pts (18.3%) had VLR at 35.3 ±16.8 months post-ablation. There was a steady attrition rate reaching 17% and 29% at 5 and 10 years, respectively (Fig.). By multivariate analysis, persistent AF (HR= 2.5, p <0.0001), hypertension (HR= 2.1, p=.007), and hyperlipidemia (HR=2.6, p=.021) were independent risk factors for VLR. There were 2 distinct patterns of recurrence: isolated/limited without significant symptoms (n=23, 29%) and prolonged/persistent requiring treatment (n=51, 65%). 40 of the latter (78%) were re-ablated, and 38% became AF-free again off drugs.Conclusion: This large prospective study found that the majority of PVI pts maintain a long-term complete response, although a portion had VLR years after successful ablation. VLR was more likely in pts with persistent AF, hypertension or hyperlipidemia. VLR occurred in distinct patterns and a portion of these required re-ablation.

a Langendorff perfused porcine heart, we evaluated the effects of high dose photon radiation on AV node function as a feasibility basis for intact animal studies.Methods: Six hearts were isolated from (30-50 kg) pigs and perfused with 37ºC, modified Krebs-Henseleit-Buffer via 2 cannulas in the coronary ostia. Perfusion pressure was set to 70-80 mmHg. Fiducials were placed in the ostium of the CS and in the anterior wall of the PA. Hearts were fixed in the perfusion beaker. For 2 hearts, a 2 mm multidetector (MD)-CT was acquired and a treatment plan, targeting the AV node area developed. A posterior anterior radiation approach with a target size of 15x15 mm was chosen. On the couch of the photon accelerator, matching of the implanted fiducial clips with an AP and lateral X-ray image to the planning CT scan, ensured concordance in positioning. Photons were delivered in a single-fractionated dose of up to 200 Gray (Gy). An ECG was constantly acquired during delivery.Results: High dose photon radiation was delivered to 2 hearts. After isolation, spontaneous SR with a mean rate of 74±5 bpm was recorded. In the first heart, complete heart block occurred after delivery of 62 Gy. During continuation of photon delivery, a ventricular escape rhythm of 40 bpm organized. Cumulative dose of 120 Gy led to further degeneration into a slow ventricular rhythm of 12 bpm. RV pacing after completion of 200 Gy did not reveal retrograde AV node conduction, persisting until study-termination. In a second isolated heart, photon delivery created first degree AV block. None of the hearts without radiation delivery (n=4) exhibited AV block.Conclusion: High dose photon radiation appears to have acute effect on myocardium and can be used to induce acute heart block. The mechanism behind this effect and the translation into alteration of electrical tissue properties remains unclear. These data may have important implications for future non-invasive photon based therapies of cardiac arrhythmias, potentially replacing catheter-based ablation. Establishing actual dose response relationships will require additional investigation.

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SAFETY OF NEW ORAL ANTICOAGULANTS FOR PATIENTS UNDERGOING ATRIAL FIBRILLATION ABLATIONGevorg Stepanyan, MASc, Nitish Badhwar, MBBS, Randall J. Lee, MD, PhD, Gregory M. Marcus, MD, Byron K. Lee, MD, Zian H. Tseng, MD, Vasanth Vedantham, MD, PhD, Jeffrey Olgin, MD, Melvin M. Scheinman, MD and Edward P. Gerstenfeld, MD. UCSF, San Francisco, CAIntroduction: The new oral anticoagulants (NOAC), dabigatran and rivaroxaban, have been demonstrated to be at least equivalent to warfarin for preventing thromboembolism (TE) in patients with atrial fibrillation (AF). However, there is limited data with use around ablation procedures. We evaluated the risk of bleeding or TE complications associated with NOAC use during AF ablation.Methods: Patients underwent AF ablation between 1/2011 and 12/2012. Patients were grouped based on peri-procedural anticoagulation regimen: 1) lovenox transition to warfarin (LtoW), 2) ablation on warfarin with therapeutic INR (WARF) or 3) NOAC (dabigatran (67%) or rivaroxaban (33%)). NOACs were held for a minimum of 24 hours (dabigatran) or 36 hours (rivaroxaban) prior to the procedure. Heparin infusion was initiated 6 hours post procedure for LtoW and NOAC groups; NOAC was resumed the morning after the procedure. PVI was performed with an irrigated 3.5mm ablation catheter with activated clotting time maintained >300 seconds. TE or bleeding complications during ablation and through 30 days were tracked.Results: 196 patients underwent ablation for paroxysmal (73%)

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LONG-TERM SUCCESS FROM FIRM ABLATION IS MAINTAINED EVEN IF ACUTE ENDPOINT IS NOT ACHIEVEDAysha Arshad, MD, Suneet Mittal, MD, Dan Musat, MD, Mark Preminger, MD, Tina Sichrovsky, MD, Sanjiv M. Narayan, MD and Jonathan S. Steinberg, MD. The Valley Hospital, Ridgewood, NJ, UCSD Medical Center, San Diego, CAIntroduction: It has recently been reported in the CONFIRM trial that atrial fibrillation (AF) may be sustained by localized sources that when successfully eliminated (focal impulse and rotor modulation [FIRM]) results in improved outcomes. We report on the largest experience of FIRM patients independently performed outside of the founding center.Methods: Over a 6-month period, we enrolled 8 patients in a prospective open-label registry of FIRM-guided ablation. Patients had history of resistance to prior ablation attempts and/or longevity of continuous AF. After mapping, localized sources were targeted for ablation. Acute endpoints included termination of AF or slowing of AF cycle length > 10%. Clinical success was defined as AF-freedom >= 6 mos post-ablation after a 3-month blanking period.Results: The 8 patients were 62 ± 10 years, 50% longstanding persistent AF and 50% persistent AF; with EF 45 ± 10 % and LA diameter 4.9 ± 0.8 cms. Patients had failed a median of 2 AADs, 4 CV, 2 prior ablations, and had total AF duration of 1315 ± 951 days. During mapping, 1.6 ± 0.8 localized rotors were detected: RA only in 3, RA and LA in 4 and LA only in 1 patient. One patient had atrial tachycardia mapped and ablated at a LA site that was identical to previously mapped and ablated rotor. Of the 12 targeted rotors, 6 were confirmed to be eliminated; the remaining 6 rotors were transient or unstable after ablation and could no longer be targeted. Overall, only 3/8 patients (37%) had acute procedural success; AF was then cardioverted if present. During follow-up of 154 ± 63 days 7/8 patients were newly able to maintain sinus rhythm, although 6/7 remained on previously ineffective medication. Of the 3 patients with acute success, 2 were in sinus rhythm. Of 5 patients without acute success, 4 maintained sinus rhythm with 1 spontaneously transitioning from AF to atrial tachycardia to sinus soon after ablation.Conclusion: In this independent series of advanced AF patients, FIRM-guided ablation yielded long-term benefit despite absence of acute procedural success in the majority. It is conceivable that the rotors when successfully mapped and targeted may not consistently acutely terminate AF but make it difficult to maintain AF long-term, possibly by forcing organization into unstable or targetable microreentrant atrial tachycardia.

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INCIDENCE OF PERIPROCEDURAL CARDIAC TAMPONADE ACCORDING TO THE LEVEL OF ACTIVATED CLOTTING TIME DURING ATRIAL FIBRILLATION ABLATIONKyoung Jeong Ko, RN, CCRN, Hyun Soo Lee, MPH, MA, Jeong Hoon Chae, RN, Ra Seung Lim, RD, Ju Yong Sung, RN, Ji-Eun Ban, MD, Yae Min Park, MD, Jong-Il Choi, MD, Hwan-Cheol Park, MD, Sang Weon Park, MD and Young-Hoon Kim, MD, PHD, FHRS. Korea University Cardiovascular Center, seoul, Republic of KoreaIntroduction: Atrial fibrillation (AF) expert consensus statement and guideline recommends that heparin should be administered prior to or immediately following transseptal puncture and adjusted to achieve and maintain ACT of 300s and 400s. We questioned the rate of periprocedural complications is not the

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UTILITY OF REPEATED AF ABLATION AT LARGE REFERRAL CENTERS AFTER 1-2 PRIOR INTERVENTIONS: IS THE ADDITIONAL INTERVENTION WORTH THE RISK?Siu Han Jo Jo Hai, MBBS, Kristi H. Monahan, RN, Janice M. Haroldson, RN, Kelly J. Wock, RN, Paul A. Friedman, MD, Yong-Mei Cha, MD, Samuel J. Asirvatham, MD, Thomas M. Munger, MD, Peter A. Brady, MD, David J. Bradley, MD, Robert F. Rea, MD and Douglas L. Packer, MD. Mayo Clinic, Rochester, MNIntroduction: While multiple procedures may be required to eliminate atrial fibrillation (AF), the merits of a third or fourth procedure remain unclear both from the standpoint of efficacy and safety.Methods: The outcomes of 2699 patients who underwent AF ablations in a large academic medical center were prospectively reviewed. Patients who had their third or fourth ablations after undergoing prior procedures elsewhere, were identified and outcomes compared with those undergoing their first and second ablation procedures performed at the institution. All patients underwent repeat WACA ablation followed by CAFE intervention or aggressive linear ablation in the setting of persistent/longstanding persistent.Results: 66 patients (mean age 56 ± 9 years, male 78%) were included in the analysis. Of these patients, 35% had paroxysmal and 65% had persistent or long-standing persistent AF, and the mean duration of AF was 6.5 ± 5.8 years. 88% of them were found to have underlying heart diseases with left ventricular ejection fraction less than 40% and 52% had severe left atrial enlargement. At a mean follow-up duration of 4.2 ± 1.7 years after initial ablation at Mayo, 64% of these patients remained free from AF without anti-arrhythmic drugs, as compared to 66% of the 619 patients who underwent their second ablations, and 75% of the 2019 patients who underwent their first ablation (p=0.88 and p=0.09 respectively). 79% of them remained in sinus rhythm with at least one anti-arrhythmic drug, compared with 83% of those who had two ablations, and 88% of those who had one ablation (p=0.47 and p=0.04 respectively). No difference in risk was experienced.Conclusion: These data suggest that the success rate with a third or forth AF ablation is at least at high as the second procedure and is comparable in terms of AF elimination with the first procedure, without an apparent increase in complication rate. Repeated ablation therefore merits considerations when performed with appropriate level of care and aggressiveness.

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S342 Heart Rhythm, Vol. 10, No. 5, May Supplement 2013

pairs of VO2 max, the rhythm/AADs status was maintained or improved, i.e. SR restored and/or AADs discontinued. These beneficial outcomes were independently associated with VO2 max improvement with regression slope coefficients of +2.3±0.3 and +2.8±0.4 ml/kg/min for SR restoration and AADs withdrawal, respectively (multivariate p<0.00001 for both).Conclusion: The functional improvement after ablation for LSPAF is significantly potentiated when arrhythmia-free outcome can be achieved without AADs.Change in VO2 max (ml/kg/min)

AADs continued AADs withdrawn

No change in rhythmn=2250.4 ± 4.3p=0.19

n=493.5 ± 4.9p<0.00001

SR restorationn=2892.4 ± 4.7p<0.00001

n=994.7 ± 4.9p<0.00001

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LEFT ATRIAL CATHETER ABLATION OF ATRIAL FIBRILLATION VIA TRANSSEPTAL ACCESS IN PATIENTS WITH ATRIAL SEPTAL CLOSURE DEVICES: A NEW SUBSTRATE FOR ATRIAL TACHYCARRHYTHMIASJong-Il Choi, MD, PhD, Chun Hwang, MD, Hong Euy Lim, MD, PhD, Sang Weon Park, MD, PhD and Young-Hoon Kim, MD, PhD. Korea University Medical Center, Seoul, Republic of Korea, Utah Valley Regional Medical Center, Provo, UTIntroduction: Atrial fibrillation (AF) is not uncommon in patients who underwent closure of atrial septal defect (ASD) by percutaneous device, which may be one of the arrhythmogenic substrates and result in developing atrial tachyarrhythmias within both atria. However, left atrial (LA) catheter ablation via transseptal puncture (TSP) is considered to be challenging in those patients. We sought to investigate influence of ASD device closure on efficacy of LA catheter ablation through TSP and its arrhythmogenic mechanism in patients with AF.Methods: Thirty three consecutive patients (56±9 years old, 50% male) with obliteration of ASD secundum by percutaneous closure device (96.9% Amplatzer, 3.1% Gore Helex) who underwent LA catheter ablation for drug-refractory AF were studied. In 26 of 33 patients, AF occurred following the ASD device closure, whereas AF had already existed in 7 patients (21.2%) prior to the closure of ASD. The common successful TSP site was the inferoposterior margin of the closure device.Results: LA catheter ablation through the TSP were performed at 17.5±13.7 months after the closure of ASD. In patients with AF onset before the ASD closure, compared with those with AF onset after the ASD closure, incidence of coexisting atrial flutter (AFL) or atrial tachycardia (AT) was higher (71.4% vs. 23.1%, p=0.027) and rate of AF termination was lower (71.4% vs. 80.8%, p<0.001). The rate of AF termination was significantly higher in patients with trigger or reentry originated from septum and associated with the closure-device (n=6) compared to those without association with the closure-device (n=27) (83.3% vs. 77.8%, p<0.001). However, during the mean 27.5±13.7 months, there was no significant difference in the freedom from recurrence of atrial tachyarrhythmia after the procedure between two groups. There was no procedure-related complication.Conclusion: The ASD closure device may play a role as a substrate for trigger or reentry mechanism of atrial tachyarrythmias. Therefore, these closure-device should be considered as one of the potential targets during the catheter ablation in patients with AF.

same between ACT of 300s to 350s and 350s to 400s.Methods: Total 278 patients (M:F=222:56, mean age: 56.4±10.9 years, Paroxysmal AF:Persistent AF=135:143) who underwent radiofrequency catheter ablation (RFCA) of AF were analyzed. Adequate systemic anticoagulation has been maintained for at least 4 weeks prior to RFCA. RFCA was performed on uninterrupted warfarin therapy in all patients. We divided the patients into two groups according to mean ACT level during RFCA procedure, group 300s-350s (group I, n=180) and group 350s-400s (group II, n=98). The incidence of cardiac tamponade, major and minor bleeding, systemic thromboembolism (STE), and vascular complications were compared.Results: Initial heparin bolus dose (IU) (8041±2572 vs. 7376±2693, p=0.044) was higher in group II. ACT (406±88s vs 368±74s, p<0.001) after initial loading dose of heparin and mean ACT (380±37s vs 336±27s, p<0.001) during procedure in group II were significantly higher than those in group I. The incidence of cardiac tamponade in group II (9, 9.2%) was significantly higher than that of group I (5, 2.8%, p=0.02), which occurred more common in female group with statistical significance (7, 12.5% vs 7, 3.2%, p=0.004). However, the rate of major or minor bleeding, STE, and vascular complications did not differ between two groups.Conclusion: Compared to group with ACT 300s and 350s, RFCA while maintaining ACT of 350s and 400s resulted in higher incidence of cardiac tamponade without differences in STE or other periprocedural complications. Prospective randomized controlled study is warranted to confirm this result.

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SINUS RHYTHM RESTORATION AND ANTIARRHYTHMIC DRUGS WITHDRAWAL INDEPENDENTLY PREDICT FUNCTIONAL IMPROVEMENT AFTER CATHETER ABLATION FOR LONG-STANDING PERSISTENT ATRIAL FIBRILLATIONMartin Fiala, MD, PhD, Dan Wichterle, MD, PhD, Libor Sknouril, MD, Veronika Bulkova, MSc, Renata Nevralova, MD, Ondrej Toman, MD, PhD, Miroslav Dorda, MD, Jakub Pindor, MSc, Jaroslav Januška, MD and Jindřich Spinar, MD, PHD, FHRS. Nemocnice Podlesi, Department of cardiology, Trinec, Czech Republic, Department of Cardiology, Institute for Clinical and Experimental Medicine, Prague, Prague, Czech Republic, International Clinical Research Center – Department of Cardiology, St. Anne’s University Hospital Brno, Brno, Czech Republic, Department of Cardiology, University Hospital, Brno, Masaryk University, Brno, Czech RepublicIntroduction: This prospective study investigated functional improvement of patients after catheter ablation for long-standing persistent atrial fibrillation (LSPAF).Methods: Extensive radiofrequency ablation (1.7±0.8 procedures per patient) for LSPAF was performed in 201 consecutive patients (59±9 years, 45 F). Echocardiography, exercise tolerance and laboratory tests were routinely performed at baseline, at 6 and 12 months after the initial ablation, and 3-6 months after delayed repeat ablation in subset of 54 patients. Improvement in maximum oxygen consumption (VO2 max) was assessed in pooled 723 within-patient pairs of examinations and categorized according to corresponding change in current rhythm status and presence of antiarrhythmic drugs (AADs) therapy defined as ≥1 AAD including beta-blocker.Results: At the end of 47±14 month follow-up, 92% patients were in stable SR (75% off AADs). As compared to baseline, the final examination showed improvement in left atrial appendage outflow velocity (44±20 vs. 58±24 cm/s), LVEF (53±10 vs. 60±5%), NT-proBNP (1139±894 vs. 288±287 pg/ml), and VO2 max (20.3±6.3 vs. 23.7±8 ml/kg/min); all p<0.001. In 622 / 723


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