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Moderated Posters and Special Session SP14: Young Investigators Award Competition MP01-1 to YIA-06

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S44 Heart Rhythm, Vol 8, No. 5, May Supplement 2011 S44 MODERATED POSTERS MODERATED POSTER SESSION MP01: Lessons Learned from CRT Trials Thursday, May 5, 2011 9:30 - 10:30 a.m. MP01-1 GENDER DIFFERENCES IN CRT RESPONSE: INSIGHTS FROM THE SMART-AV CLINICAL TRIAL Alan Cheng, MD, Michael R. Gold, MD, PhD, Timothy E. Meyer, PhD, Milan Seth, MS, Joshua Rapkin, MS, Kenneth M. Stein, MD and Kenneth A. Ellenbogen, MD. Johns Hopkins University, Baltimore, MD, Medical University of South Carolina, Charleston, SC, Boston ScientiÀc Corporation, St. Paul, MN, Virginia Commonwealth University, Richmond, VA Introduction: Recent large trials including SMARTAV demonstrate that women respond more favorably to cardiac resynchronization therapy (CRT) than men. We sought to understand further these Àndings and determine whether this difference reÁects baseline clinical characteristics or intrinsic differences between men and women with regard to their response to CRT. Methods: 80 patients (68 men, mean age 66 ± 11 years, mean LV(F: 24 ± 7, 4 NYHA Class III) were randomized to 3 treatment arms, which are pooled for this analysis. Data for 846 (86.3) randomized patients with baseline and 6 month left ventricular end systolic volumes (LV(SV) measurements were Àtted to a linear regression model with gender predicting change in LV(SVi (normalized to BSA) and adMusted for all baseline covariates signiÀcantly differing by gender. Results: Women had smaller baseline LV(SV, more LBBB, and less RBBB, ischemic cardiomyopathy, paro[ysmal AF, renal disease, C2PD, and sleep apnea. Women were also less likely to have a history of CAB* or PCI (Table 1). After adMustment for these covariates, women e[hibited greater mean reductions in LV(SVi at 6 months when compared to men (13.4 ml/m2 vs. 8.5 ml/m2, p0.005). Conclusions: These results from the SMARTAV trial suggest women with moderately symptomatic CHF have improved echocardiographic remodeling responses to CRT that are independent of differences in baseline covariates. Further research is needed to understand better this gender difference. MP01-2 IMPACT OF CRT ON HOSPITALIZATIONS IN THE RESYNCHRONIZATION-DEFIBRILLATION FOR AMBULATORY HEART FAILURE TRIAL (RAFT) Anne M. Gillis, MD, FRCP, Charles Kerr, MD, FRCP, Francois Philippon, MD, FRCP, Gary Newton, MD, FRCP, Mario Talajic, MD, FRCP, Michael Froeschl, MD, FRCP, Sandra Froesch, MD, FRCP, Elizabeth Swiggum, MD, FRCP, George A. Wells, PhD and Anthony Tang, MD, FRCP. University of Calgary/Calgary Health Region, Calgary, AB, Canada, St. Paul’s Hospital, Vancouver, BC, Canada, Quebec Heart and Lung Institute, Ste- Foy, QC, Canada, Mt. Sinai Hospital, Toronto, ON, Canada, Université de Montréal-Montreal Heart Institute, Montreal, QC, Canada, University of Ottawa Heart Institute, Ottawa, ON, Canada, Royal Jubilee Hospital, Victoria, BC, Canada Introduction: The RAFT investigators reported that the addition of cardiac resynchronization therapy (CRT) to an implantable deÀbrillator (ICD) reduced the rates of death and hospitalization for heart failure in patients with NYHA Class II/III heart failure (HF), a wide QRS comple[ and left ventricular systolic dysfunction. Methods: This subgroup analysis compares hospitalization rates in the 178 patients randomized to ICDCRT (n84) or ICD (n04). Results: The patients e[periencing hospitalization for any cause was similar in both groups (56). Hospitalization for heart failure was signiÀcantly reduced in the ICDCRT group (1.5) vs the ICD group (26.1). Days hospitalized for any cause were signiÀcantly lower in the ICDCRT group (344; 5 CI 338351 per 100 patient years at risk (PYR)) vs the ICD group (434; 5 CI 427442 per 100 PYR). Days hospitalized for any cardiovascular cause were signiÀcantly lower in the ICDCRT group compared to the ICD group (16; 5 CI 165174 per 100 PYR vs 227; 5 CI 221232 per 100 PYR) and for a HF cause (100; 5 CI 7104 per 100 PYR vs 148; 5 CI 144 153 per 100 PYR). Patients in the ICDCRT group were more likely to be hospitalized for a devicerelated indication (20.0) vs the ICD group (12.2) and spend more days in hospital (47.; 5 CI 45.450.3 per 100 PYR) vs the ICD group (31.5; 5 CI 2.533.6 per 100 PYR) for this indication. Multivariate analysis identiÀed NYHA Class III (2R 2.2 , 5 CI 1.733.03), BUN(2R 1.03 , 5 CI 1.011.06), previous HF hospitalization (2R 1.60; 5 CI 1.232.10), lack of CRT therapy (2R 1.57; 5 CI 1.23 2.02), male gender (2R 1.62; 5 CI 1.132.34), diuretic use (2R 1.81; 5 CI 1.202.73) previous CAB* (2R 1.33; 5 CI 1.031.72), lack of beta blocker therapy (2R 1.51; 5 CI 1.03 2.21) and low platelet count (2R 1.002; 5 CI 1.0001.004) as independent predictors of hospitalization for heart failure. For patients hospitalized once for HF, subsequent hospitalization event rates were similar in both the ICDCRT and ICD groups. Conclusions: CRT therapy signiÀcantly reduces rates of hospitalization for HF and total days in hospital in patients with NYHA II/III HF compared to ICD therapy. CRT therapy does not prevent subsequent HF hospital admissions in the ICDCRT subgroup admitted for HF.
Transcript
Page 1: Moderated Posters and Special Session SP14: Young Investigators Award Competition MP01-1 to YIA-06

S4 4 Heart Rhythm, Vol 8, No. 5, May Supplement 2011S4 4

MODERATED POSTERS

MODERATED POSTER SESSION MP01: Lessons Learned from CRT Trials

Thursday, May 5, 20119:30 - 10:30 a.m.

MP01-1

GENDER DIFFERENCES IN CRT RESPONSE: INSIGHTS FROM THE SMART-AV CLINICAL TRIAL

Alan Cheng, MD, Michael R. Gold, MD, PhD, Timothy E. Meyer, PhD, Milan Seth, MS, Joshua Rapkin, MS, Kenneth M. Stein, MD and Kenneth A. Ellenbogen, MD. Johns Hopkins University, Baltimore, MD, Medical University of South Carolina, Charleston, SC, Boston Scienti c Corporation, St. Paul, MN, Virginia Commonwealth University, Richmond, VA

Introduction: Recent large trials including SMART AV demonstrate that women respond more favorably to cardiac resynchronization therapy (CRT) than men. We sought to understand further these ndings and determine whether this difference re ects baseline clinical characteristics or intrinsic differences between men and women with regard to their response to CRT. Methods: 80 patients (68 men, mean age 66 ± 11 years, mean LV F: 24 ± 7 , 4 NYHA Class III) were randomized to 3 treatment arms, which are pooled for this analysis. Data for 846 (86.3 ) randomized patients with baseline and 6 month left ventricular end systolic volumes (LV SV) measurements were tted to a linear regression model with gender predicting change

in LV SVi (normalized to BSA) and ad usted for all baseline covariates signi cantly differing by gender.Results: Women had smaller baseline LV SV, more LBBB, and less RBBB, ischemic cardiomyopathy, paro ysmal AF, renal disease, C PD, and sleep apnea. Women were also less likely to have a history of CAB or PCI (Table 1). After ad ustment for these covariates, women e hibited greater mean reductions in LV SVi at 6 months when compared to men (13.4 ml/m2 vs. 8.5 ml/m2, p 0.005).Conclusions: These results from the SMART AV trial suggest women with moderately symptomatic CHF have improved echocardiographic remodeling responses to CRT that are independent of differences in baseline covariates. Further research is needed to understand better this gender difference.

MP01-2

IMPACT OF CRT ON HOSPITALIZATIONS IN THE RESYNCHRONIZATION-DEFIBRILLATION FOR AMBULATORY HEART FAILURE TRIAL (RAFT)

Anne M. Gillis, MD, FRCP, Charles Kerr, MD, FRCP, Francois Philippon, MD, FRCP, Gary Newton, MD, FRCP, Mario Talajic, MD, FRCP, Michael Froeschl, MD, FRCP, Sandra Froesch, MD, FRCP, Elizabeth Swiggum, MD, FRCP, George A. Wells, PhD and Anthony Tang, MD, FRCP. University of Calgary/Calgary Health Region, Calgary, AB, Canada, St. Paul’s Hospital, Vancouver, BC, Canada, Quebec Heart and Lung Institute, Ste-Foy, QC, Canada, Mt. Sinai Hospital, Toronto, ON, Canada, Université de Montréal-Montreal Heart Institute, Montreal, QC, Canada, University of Ottawa Heart Institute, Ottawa, ON, Canada, Royal Jubilee Hospital, Victoria, BC, Canada

Introduction: The RAFT investigators reported that the addition of cardiac resynchronization therapy (CRT) to an implantable de brillator (ICD) reduced the rates of death and hospitalization for heart failure in patients with NYHA Class II/III heart failure (HF), a wide QRS comple and left ventricular systolic dysfunction.Methods: This subgroup analysis compares hospitalization rates in the 17 8 patients randomized to ICD CRT (n 8 4) or ICD (n 04).Results: The patients e periencing hospitalization for any cause was similar in both groups (56 ). Hospitalization for heart failure was signi cantly reduced in the ICD CRT group (1 .5 ) vs the ICD group (26.1 ). Days hospitalized for any cause were signi cantly lower in the ICD CRT group (344; 5 CI 338 351 per 100 patient years at risk (PYR)) vs the ICD group (434; 5 CI 427 442 per 100 PYR). Days hospitalized for any cardiovascular cause were signi cantly lower in the ICD CRT group compared to the ICD group (16 ; 5 CI 165 174 per 100 PYR vs 227; 5 CI 221 232 per 100 PYR) and for a HF cause (100; 5 CI 7 104 per 100 PYR vs 148; 5 CI 144153 per 100 PYR). Patients in the ICD CRT group were more likely to be hospitalized for a device related indication (20.0 ) vs the ICD group (12.2 ) and spend more days in hospital (47. ; 5 CI 45.4 50.3 per 100 PYR) vs the ICD group (31.5; 5 CI

2 .5 33.6 per 100 PYR) for this indication. Multivariate analysis identi ed NYHA Class III ( R 2.2 , 5 CI 1.73 3.03), BUN( R 1.03 , 5 CI 1.01 1.06), previous HF hospitalization ( R 1.60;

5 CI 1.23 2.10), lack of CRT therapy ( R 1.57; 5 CI 1.232.02), male gender ( R 1.62; 5 CI 1.13 2.34), diuretic use ( R 1.81; 5 CI 1.20 2.73) previous CAB ( R 1.33; 5 CI 1.03 1.72), lack of beta blocker therapy ( R 1.51; 5 CI 1.032.21) and low platelet count ( R 1.002; 5 CI 1.000 1.004) as independent predictors of hospitalization for heart failure. For patients hospitalized once for HF, subsequent hospitalization event rates were similar in both the ICD CRT and ICD groups.Conclusions: CRT therapy signi cantly reduces rates of hospitalization for HF and total days in hospital in patients with NYHA II/III HF compared to ICD therapy. CRT therapy does not prevent subsequent HF hospital admissions in the ICD CRT subgroup admitted for HF.

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S4 5Moderated Posters

MP01-4

LEFT VENTRICULAR LEAD POSITION AND THE RISK OF VENTRICULAR ARRHYTHMIAS IN THE MADIT-CRT STUDY

Valentina Kutyifa, MD, Michal Gibinski, MD, PhD, Wojciech Zareba, MD, PhD, Jagmeet Singh, MD, PhD, Scott McNitt, MS, Paul Wang, MD, PhD, Amin Al-Ahmad, MD, Bela Merkely, MD, PhD, Arthur J. Moss, MD and Helmut Klein, MD. University of Rochester Medical Center, Rochester, NY, Massachusetts General Hospital, Boston, MA, Department of Medicine Stanford University Medical Center, Stanford, CA, Semmelweis University, Heart Center, Budapest, Hungary

Introduction: Appropriate positioning of the left ventricular (LV) lead for cardiac resynchronization therapy (CRT) is of signi cant importance to increase the response to CRT. However, no data are available regarding the in uence of LV lead position on the risk of ventricular tachycardia (VT) or ventricular brillation (VF).Methods: The position of the LV lead was evaluated by means of biplane coronary venograms and chest X rays (anterior and lateral view) at the time of CRT device implantation in patients enrolled in the Multicenter Automatic De brillator Implantation Trial Cardiac Resynchronization Therapy (MADIT CRT).Results: LV lead was evaluated in 7 patients and positioned at the LV ape in 110 (14 ) patients, in the anterior position in 146 (18 ) patients, lateral position in 450 (56 ) patients and posterior position in 3 (12 ) patients. The lateral or posterior CRT lead location was associated with a signi cantly lower risk of VT/VF than the anterior lead location (Figure). Apical lead position was not arrhythmogenic although associated with increased mortality. After ad ustment for clinical covariates (female, ischemic cardiomyopathy, QRS 150ms, LBBB, RBBB) the lateral or posterior LV lead location was associated with a hazard ratio for VT/VF 0.57 ( 5 CI 0.38 0.85, p 0.007) compared to anterior LV lead location.Conclusions: CRT therapy with posterior or lateral LV lead position is associated with a decreased risk of arrhythmic events in comparison to anterior lead.

MP01-3

DYSSYNCHRONY AND THE RISK OF VENTRICULAR ARRHYTHMIAS IN THE MADIT-CRT TRIAL

Valentina Kutyifa, MD, Michal Gibinski, MD, PhD, Anne-Catherine Pouleur, MD, Dorit Knappe, MD, Paul Wang, MD, PhD, Amin Al-Ahmad, MD, Scott McNitt, MSc, Wojciech Zareba, MD, PhD, Scott Solomon, MD and Arthur J. Moss, MD. University of Rochester Medical Center, Rochester, NY, Cardiovascular Division, Brigham and Women’s Hospital, Boston, MA, Department of Medicine Stanford University Medical Center, Stanford, CA

Introduction: The aim of this study was to investigate the association between the left ventricular (LV) dyssynchrony and the risk of ventricular tachycardia (VT) or ventricular brillation (VF) or death in patients enrolled in the Multicenter Automatic De brillator Implantation Trial Cardiac Resynchronization Therapy.Methods: Transverse dyssynchrony was measured at baseline and at 12 months by speckle tracking echocardiography by assessing the standard deviation of time to peak strain from 12 myocardial regions. The primary end point was VT or VF or death, secondary endpoints included VT or VF, determined based on interrogation of ICDs.Results: Transverse dyssynchrony was evaluated in 416 patients (57 ) in the ICD group and in 661 patients (61 ) in the CRT D group. LV dyssynchrony at baseline before device implantation was not predictive for VT/VF. Decrease in LV dyssynchrony during 12 month follow up was associated with a signi cantly lower risk of subsequent VT/VF or death compared to patients without decrease in LV dyssynchrony (Figure). Hazard ratio after ad ustment for clinical covariates 0.47, 5 CI: 0.27 0.81, p 0.007.Conclusions: Baseline LV dyssynchrony does not re ect the risk of VT/VF in MADIT CRT patients. Improvement in LV dyssynchrony after CRT D implantation is associated with signi cantly reduced risk of VT/VF/Death and VT/VF in mild to moderate heart failure patients.

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S4 6 Heart Rhythm, Vol 8, No. 5, May Supplement 2011

MODERATED POSTER SESSION MP02: Novel Mapping Strategies and Ablation Techniques in SVT

Thursday, May 5, 20113:15 - 4:15 p.m.

MP02-1

DIRECT VISUALIZATION OF THE SLOW PATHWAY USING VOLTAGE GRADIENT MAPPING: A NOVEL APPROACH FOR SUCCESSFUL ABLATION OF AV NODAL REENTRY TACHYCARDIA

Steven J. Bailin, MD and Craig Hoffman, PA. Iowa Heart Center, Des Moines, IA

Introduction: Ablation of atrioventricular nodal reentry tachycardia has become treatment of choice because of a high success and low complication rate. Most ablations are successful utilizing an anatomic approach, but anatomic variance, unusual pathway locations, or multiple pathways may complicate the procedure. Visualization of the slow pathway could e pedite ablation success and enhance safety.Methods: 3 dimensional voltage maps of the atrium were constructed from intracardiac recordings obtained by contact mapping. Voltage values were ad usted until low voltage bridging was observed within the Triangle of och.Results: 2 consecutive patients undergoing ablation for inducible atrioventricular nodal reentry tachycardia, 5 patients with dual AV Nodal physiology without inducible tachycardia, and 5 patients with normal AV nodal physiology, underwent Voltage

radient Mapping. The slow pathway was identi ed in all 34 patients via its corresponding low voltage bridge. Low voltage bridges were not observed in patients without dual AV nodal physiology. Ablation of the slow pathway associated low voltage bridges in 2 patients with tachycardia was successful. Repeat mapping con rmed the absence of low voltage connections previously observed in all 34 patients.Conclusions: Voltage gradient mapping can directly visualize the slow pathway. Ablation of the associated low voltage bridge results in loss of slow pathway function and signi cant changes in the post ablation voltage map. We conclude voltage gradient mapping offers the ability to precisely target the slow pathway for successful ablation.

MP01-5

KIDNEY DISEASE AND CARDIAC REMODELING IN PATIENTS WITH CARDIAC RESYNCHRONIZATION THERAPY: RESULTS FROM THE RESYNCHRONIZATION REVERSE REMODELING IN SYSTOLIC LEFT VENTRICULAR DYSFUNCTION (REVERSE) STUDY

Jehu Mathew, MD, Ronit Katz, PhD, Sanjay Dixit, MD, FHRS, Edward P. Gerstenfeld, MD, FHRS, Martin St. John Sutton, MBBS, Michael R. Gold, MD, PhD, Michael G. Shlipak, MD, MPH, Cecilia Linde, MD, PhD and Rajat Deo, MD. University of Pennsylvania, Philadelphia, PA, University of Washington, Seattle, WA, Medical University of South Carolina, Charleston, SC, University of California, San Francisco, San Francisco, CA, Karolinska University Hospital, Stockholm, Sweden

Introduction: Chronic kidney disease (C D) is associated with changes in cardiac remodeling. We evaluated whether C D affects left ventricular remodeling among patients with cardiac resynchronization therapy (CRT).Methods: R V RS was a randomized, controlled trial evaluating CRT therapy in patients with NYHA Class I/II heart failure. The baseline estimated glomerular ltration rate (e FR) was calculated in all participants, and C D was de ned as an e FR 60ml/min. We compared changes in LV size and function over the course of 12 months between the normal kidney function group and the C D group. We created a linear mi ed model to assess whether kidney function is associated with changes in cardiac remodeling after ad ustment for demographics, comorbidities, medications, cardiomyopathy etiology, and CRT status. Finally, we tested for interactions of e FR with CRT status on 12 month changes in LV size and function using interaction product terms.Results: Among the 561 participants in our study, 160 (2 ) had C D. Participants with normal kidney function were noted to have greater improvements in LV structural parameters than those with C D. These differences in LV remodeling between the two groups were independent of age, gender, race, blood pressure, diabetes, smoking, medications, and the etiology of the cardiomyopathy. In addition there was a signi cant interaction between C D and CRT status for most LV parameters (table 1).Conclusions: CRT improves LV structure and function among people with C D; however, reverse remodeling is attenuated in C D patients compared to those with normal kidney function.

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S4 7Moderated Posters

MP02-3

NOVEL USE OF ATRIAL OVERDRIVE PACING TO RAPIDLY DIFFERENTIATE JUNCTIONAL TACHYCARDIA FROM ATRIOVENTRICULAR NODAL REENTRANT TACHYCARDIA

Jonathan G. Tardos, MD, Ibrahim Almasry, MD, Saverio Barbera, MD, Eric Rashba, MD, FHRS, Sei Iwai, MD, FHRS and Roger Fan, MD. Stony Brook University Medical Center, Stony Brook, NY

Introduction: Distinguishing between unctional tachycardia ( T) and atrioventricular nodal reentry tachycardia (AVNRT) is essential to minimize unnecessary catheter ablation and the risk of heart block during treatment of AVNRT. We investigated whether the tachycardia response to atrial overdrive pacing at a cycle length (CL) slightly shorter than tachycardia CL can differentiate between T and AVNRT. We hypothesized that atrial overdrive pacing would transiently suppress T, whereas it would entrain AVNRT.Methods: Nineteen patients in whom AVNRT was induced and atrial overdrive pacing during either AVNRT or T was attempted were included in the study. We predicted that, upon cessation of atrial overdrive pacing, an atrial His His atrial (AHHA) response would identify T and an atrial His atrial (AHA) response would identify AVNRT ( gure).Results: A total of 8 T and 1 typical AVNRT were induced. Atrial overdrive pacing was attempted in all cases of T and in 14 cases of AVNRT. An AHHA response was observed in 100 of cases (8/8) of T. In 2 cases of AVNRT, atrial overdrive pacing repetitively terminated the tachycardia. In the remaining patients with AVNRT, an AHA response was observed in 100 of cases (12/12). When a response was able to be elicited, atrial overdrive pacing was 100 sensitive and 100 speci c for differentiating T from AVNRT.Conclusions: Atrial overdrive pacing during tachycardia can rapidly differentiate T from AVNRT, which can improve the safety and ef ciency of catheter ablation of these arrhythmias.

MP02-2

INTEGRATED REAL TIME ULTRASOUND LESION MONITORING AND RF ABLATION: PREDICTING STEAM POPS

Matthew J. Wright, MBBS, PhD, Erik Harks, PhD, Szabolcs Deladi, PhD, Fei Zuo, PhD, Steven Fokkenrood, Esq., Mélèze Hocini, MD, Sébastien Knecht, MD, Frédéric Sacher, MD, Michel Haïssaguerre, MD and Pierre Jaïs, MD. Kings College London BHF Centre, Cardiovascular Division, NIHR Biomedical Research Centre, London, United Kingdom, Philips Research, Minimally Invasive Healthcare, Eindhoven, Netherlands, Hôpital Cardiologique du Haut-Lévêque, Bordeaux-Pessac, France

Introduction: Steam pops are a risk of irrigated RF ablation. We used real time ultrasound (US) integrated into a RF ablation catheter to visualise both lesion and intramural gas formation in vivo.Methods: In an in vivo open chest ovine model (n ), 87 epicardial ventricular lesions were performed while monitoring lesion formation. nergy was delivered for 15 60s to achieve lesions with and without steam pops. The US image was compared to a digital audio recording and pathology and histological specimens by blinded observers.Results: 32 lesions resulted in an audible steam pop. For lesions with a steam pop compared to those without the mean power delivered was 7. ±1.7W vs 6.8±2.1W p 0.02, mean lesion depth was 5.4±1.8mm vs 4.6±1.8mm p 0.06, with a mean

impedance drop of 44±10 vs 41±10 p 0.21 respectively. A change in US contrast due to gas formation in the tissue occurred in all lesions that resulted in a steam pop and preceded a rise in impedance. f the 87 lesions, 16 were over myocardial vessels, which were seen on ultrasound at a depth of 0 4mm and a diameter of 0.1 1.7mm. as formation occurred 18±12s following RF delivery, and was clearly discernible from vessels producing a characteristic US re ection. The mean depth of gas formation was 0. ±0.8mm, which correlated with the ma imum temperature predicted by modeling e periments. Changes in US contrast occurred 7±6s before an impedance rise and 7±6s (0.117s) before an audible pop, p 0.01.Conclusions: Integrated US in a RF ablation catheter visualizes gas formation several seconds prior to a steam pop occurring. In addition to real time monitoring of lesion formation, this technology may help prevent complications due to steam pops.

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S4 8 Heart Rhythm, Vol 8, No. 5, May Supplement 2011

Introduction: In radiofrequency ablation for AVNRT a residual ump and a single echo do not seem to substantially modify longterm results; however, in cryoablation procedures their effects are still under evaluation.Methods: Inclusion criteria: acute successful slow pathway cryoablation procedures. clusion criteria: use of a 4 mm tip catheter, no baseline elicitable ump or inducible AVNRT, and unwanted persistent 1st degree AV block at the end of the procedure. Cryoablation ( 80°C for 4 min) was applied after successful cryomapping. AVNRT inducibility was checked 30 min later with and without isoproterenol. Acute success was de ned as AVNRT noninducibility.Results: Among 262 patients (pts) who had undergone cryoablation from May 2004 to March 2010 in our institution, 218 of them ful lled the entry criteria (40±15 years, 115 women, ineffective drugs 1. ±1.3). A 7 F 6 mm tip cryocatheter (CryoCath®) was used in all. Baseline AV nodal effective refractory period ( RP) was 272±4 ms, post procedural

RP 327±54 ms (p 0.001), and the mean of the difference between baseline and post procedural RP was 61±41 ms. A/V ratio at successful site was 1±0.4. Forty eight pts (22 ) had a residual ump at the end of the procedure, and 18 of them had an associated single echo. lobal cryoapplication time was 5±756 sec. During a follow up of 2.5±1.5 years, 40 pts (18 ) had recurrences. Using Co ’s model, univariate predictors of recurrence were residual ump (p 0.02) and global cryoapplication time (p 0.001). At multivariate analysis, only global cryoapplication time was independently signi cant (p 0.001), suggesting that a prolonged cryoapplication time is correlated with more dif cult procedures if a residual ump remains. At 12 months follow up, actuarial rate of recurrencefree pts was 85 in the group without residual ump (170 pts), 70 with residual ump and no echo (30 pts), and 67 with residual ump associated with a single echo (p 0.02 among groups).Conclusions: In patients undergoing AVNRT cryoablation, slow pathway suppression is correlated with a better outcome. A time consuming procedure should be performed in cases with dif cult slow pathway abolition. A single echo is associated with a recurrence risk similar to residual ump without echo.

MP02-4

ELECTROPHYSIOLOGICAL INDICATORS VERSUS VISUAL ASSESSMENT OF RF EFFICACY DURING IN VIVO VENTRICULAR ABLATION

Frederic Sacher, MD, Bryan Wylie, No Degree, Amir Jadidi, MD, Zach Malchano, PhD, Daniel Scherr, MD, Leslie Oley, No Degree, Nicolas Derval, MD, Sebastien Knecht, MD, Meleze Hocini, MD, Pierre Dos Santos, MD, PhD, Michel Haissaguerre, MD, Dave Robinson, No Degree and Pierre Jais, MD. Hopital Cardiologique du Haut Leveque / Universite Bordeaux 2, Bordeaux, France, Voyage Medical, Inc, Redwood City, CA, Hopital Cardiologique du Haut Leveque, Bordeaux, France

Introduction: In vivo assessment options of RF ablation lesions are limited; improved feedback could affect acute procedure outcomes. A novel catheter enabling direct tissue visualization (IRIS) during ablation was compared to a 3.5mm open irrigated tip catheter (TH RM) for endocardial ( ND ) and epicardial ( PI) ventricular RF ablation ef cacy in ovine.Methods: 16 anesthetized sheep (6 ±1yo, 60 ±10kg) underwent percutaneous ND and PI ablation with a ThermoCool (Biosense Webster, USA) or IRIS (Voyage Medical, USA) ablation catheter. RF applications with TH RM were performed using standard indicators of electrode contact ( M amplitude reduction, tactile feed back, uoroscopy) or direct visualization with IRIS to con rm tissue contact. TH RM power was 30 W for 60 sec ma ; IRIS power averaged 21 W (range 10 30 W) for 60 sec ma depending on lesion formation ( ND lesions only).Results: 206 RF applications were performed (80 ND , 80

PI with TH RM; 46 ND with IRIS). At necropsy, 62 of 80 (78 ) applications were identi ed on the ND and 58 of 80 (73 ) on the PI with TH RM versus 45 of 46 ( 8 ) for IRIS (p 0.001 vs TH RM ND ). PI ablation is associated with wider and larger lesions while ND ablation (with TH RM or IRIS) results in deeper lesions probably due to catheter motion on the PI (table) .Conclusions: Despite best efforts using standard assessment of catheter contact, a signi cant portion (22 27 ) of RF applications using a standard open irrigated catheter were not identi ed in ventricular tissue. Direct visualization for in vivo assessment of catheter contact provided a reliable relationship between RF application and tissue lesion formation at 8 of prescribed targets.

RF and lesions characteristics depending on catheters and sites.

ND TH RM ND IRIS p value PI TH RM p value

Power (Watts) 30 ±2 21 ±4 p 0,001 30 ±1 NS

RF duration (seconds) 57 ±14 58 ±15 NS 55 ±13 NS

Percentage of impedance drop at 10 sec ( ) 13 ±8 12 ±3 NS 1 ±10 p 0,001

Lesion Depth (mm) 4,7 ±2,1 4,5 ±1,5 NS 3, ±1,7 p 0,01

Lesion Width (mm) 5,3 ±1,7 5,3 ±1,7 NS 7,2±2,6 p 0,001

Lesion Length (mm) 7,7 ±2,1 ,1 ±4,5 NS ,4 ±3,1 p 0,05

MP02-5

CORRELATIONS BETWEEN LONG-TERM RESULTS AFTER CRYOABLATION FOR AVNRT AND A RESIDUAL JUMP ASSOCIATED OR NOT WITH A SINGLE ECHO

Antonio De Sisti, MD, Joelci Tonet, MD, Fatima Gueffaf, MD, Philip Aouate, MD, Faouzi Touil, MD and Francoise Hidden-Lucet, MD. Cardiology Institute, Rhythmology Unit, Pitié-Salpêtrière Hospital, Paris, France

Page 6: Moderated Posters and Special Session SP14: Young Investigators Award Competition MP01-1 to YIA-06

S4Moderated Posters

VF inductions were performed.Results: The Chronicle ICD with HemoD successfully detected and treated all 30 induced episodes (24 VF, 6 VT) for 100 success ( 5 con dence interval (CI): 88.4 , 100 ). Mean time from VF onset to shock was 10.6±2.3s ( 5 CI: .6s, 11.6s) when initial detection was programmed to 30/40 intervals. RV pulse pressure (PP) and Ma dP/dt during VF were signi cantly reduced compared to baseline (p 0.001). Faster ventricular rates resulted in lower RV PP (Figure). No HemoD rules for delaying or withholding ICD therapy were triggered during VF. The HemoD Pressure Collapse rule, designed to accelerate shock therapy, was satis ed in 5/6 VT and 20/23 VF episodes.Conclusions: The HemoD acute clinical study is the rst prospective evaluation of a tachycardia discrimination algorithm using RV pressure. The study demonstrates no delay in VF treatment and high sensitivity to induced VT/VF with HemoD . This algorithm may be used in future ICDs to reduce inappropriate shocks for hemodynamically stable rhythms.

MP03-3

A RANDOMIZED-CONTROLLED PILOT STUDY COMPARING ICD IMPLANTATION WITH AND WITHOUT INTRA-OPERATIVE DEFIBRILLATION TESTING IN PATIENTS WITH HEART FAILURE AND SEVERE LEFT VENTRICULAR DYSFUNCTION: A SUB-STUDY OF THE RAFT TRIAL

Jeffrey S. Healey, MD, Lorne J. Gula, MD, David H. Birnie, MD, Lawrence D. Sterns, MD, John Sapp, MD, Eugene Crystal, MD, Chris Simpson, MD, Derek V. Exner, MD, Bernard Thibault, MD, Francois Philippon, MD, George A. Wells, MD and Anthony SL. Tang, MD. Hamilton Health Sciences, Hamilton, ON, Canada, University of Western Ontario, London, ON, Canada, University of Ottawa, Ottawa, ON, Canada, Royal Jubilee Hospital, Victoria, BC, Canada, Dalhousie University, Halifax, NS, Canada, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, Queen’s University, Kingston, ON, Canada, University of Calgary, Calgary, AB, Canada, Montreal Heart Institute, Montreal, QC, Canada, Universite Laval, Quebec City, QC, Canada, University of Ottawa Heart Institute, Ottawa, ON, Canada

Introduction: Debate continues regarding the need to perform intra operative de brillation testing (DT) at the time of ICD insertion. bservational studies suggest that: serious complications related to DT are rare; the success of clinical shocks is similar for patients regardless of testing and that patients not having DT are at higher risk of death. However; all of these data are observational and sub ect to bias.

MODERATED POSTER SESSION MP03: Risks and Predictors of ICD Shocks

Friday, May 6, 20119:30 - 10:30 a.m.

MP03-1

INCREASED RISK OF HEART FAILURE AND DEATH AFTER ICD SHOCK IN ICD AND CRT-D PATIENTS IN THE MADIT-CRT TRIAL

John C. Evans, MD, Paul J. Wang, MD, Scott McNitt, MS, Arthur J. Moss, MD, Wojciech Zareba, MD, PhD and Amin Al-Ahmad, MD. Stanford, Palo Alto, CA, University of Rochester, Rochester, NY

Introduction: Prior ICD trials have shown that patients who survive an appropriate ICD shock are at increased risk for subsequent mortality. The Multicenter Automatic De brillator Implantation Trial Cardiac Resynchronization Therapy (MADITCRT) trial demonstrated that CRT D reduces the risk of heart failure (HF) event or death. It is not known if CRT D therapy reduces the subsequent risk of death or heart failure after a successful ICD shock.Methods: MADIT CRT enrolled ischemic NYHA class I or II and nonischemic NYHA class II cardiomyopathy patients with e ection fraction 30 and QRS duration >130 ms. The clinical outcomes and occurrence of shocks were recorded in the implantable cardioverter de brillator (ICD) arm and the resynchronization with de brillator (CRT D) arm of the trial. The risk of death and combined risk of death or HF event were compared in the patients with and without shocks in each arm of the trial.Results: Among 1,820 patients in the trial, 271 patients (15 ) received at least one ICD shock. The occurrence of any shock was predictive of subsequent death (HR 1. 5, p 0.004) and combined HF/death (HR 1. 1, p 0.001) during subsequent follow up. As shown in Table below, ICD shock was associated with similar increase in the risk of subsequent end points in both ICD only and in CRT D arms.Conclusions: In heart failure patients enrolled in MADIT CRT who receive ICD shock, there is an increased risk for subsequent death and the combined end point seen during follow up in both arms of the trial. CRT D showed reduction in the risk of primary end points in patients after ICD shock that was similar to the risk reduction in patients never e periencing ICD shocks.

MP03-2

PROSPECTIVE EVALUATION OF A NOVEL ICD ALGORITHM USING RIGHT VENTRICULAR PRESSURE

Stephen A. Fahrig, MD, Arun N. Kumar, PhD, W. Ben Johnson, MD, Paul A. Friedman, MD, Robert H. Hoyt, MD, Nicole M. Wood, BS and Teresa A. Whitman, PhD. Saint Thomas Hospital, Nashville, TN, Medtronic Inc, Mounds View, MN, Iowa Heart Center, West Des Moines, IA, Mayo Clinic, Rochester, MN

Introduction: Incorporation of hemodynamic data into ICD detection algorithms may reduce inappropriate shocks. The HemoD acute study prospectively evaluated the ef cacy of a new single chamber ICD algorithm that uses right ventricular (RV) pressure to augment ICD detection.Methods: Patients (n 27) undergoing ICD or CRT D implant were studied. A standard ICD lead and a Medtronic 4328A pressure sensing lead (PSL) were placed in the RV. A Medtronic Chronicle ICD with the HemoD algorithm was implanted and connected to the ICD lead and PSL. An additional lead or P catheter was used to rapidly pace the RV to simulate VT. VT and

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S500 Heart Rhythm, Vol 8, No. 5, May Supplement 2011

After ad ustment for multiple covariates (amiodarone use, any previous pre ICD revascularization, and LV F), number of transmural scar segments remained strongly associated with the occurrence of appropriate ICD therapy (HR per segment 1.48;

5 CI 1.18 1.84; p 0.001).Conclusions:In this pilot study, the e tent of myocardial scar, characterised by L CMR, was signi cantly associated with the occurrence of spontaneous ventricular arrhythmias. We hypothesise that scar quanti cation by L CMR may prove a valuable risk strati cation tool for the occurrence of ventricular arrhythmias, which may have implications for patient selection for ICD therapy.

MP03-5

INTRACARDIAC T-WAVE ALTERNANS PREDICTS IMMINENT VENTRICULAR TACHYARRHYTHMIAS IN ICD PATIENTS

Charles Swerdlow, MD, Theodore Chow, MD, Mithilesh K. Das, MD, MBBS, Anne Gillis, MD, Xiaohong Zhou, MD, Athula I. Abeyratne, PhD and Raja N. Ghanem, PhD. Cedars-Sinai Medical Center, Los Angeles, CA, Heart & Vascular Associates, San Jose, CA, Methodist Hospital, Indianapolis, IN, University of Calgary, Calgary, AB, Canada, Medtronic, Inc., Moundsview, MN

Introduction: T wave alternans (TWA) increases before spontaneous ventricular tachycardia or brillation (VT/VF), but its short term predictive accuracy for imminent VT/VF remains unknown when measured using ICD electrograms ( Ms).Methods: In 63 ICD patients, TWA was computed from

Ms before spontaneous VT/VF and from 4 types of control recordings: stored Ms before spontaneous supraventricular tachycardia (SVT) and real time Ms in baseline rhythm, in rapid pacing (105 bpm), and in ambulatory telemetry Holter recordings matched to the time of day at which VT/VF occurred. Real time control Ms were analyzed using sequential windows of 8 pairs of beats. Logistic regression and a Receiver

perating Characteristic (R C) curve were used to assess the accuracy with which M TWA predicts VT/VF.Results: In follow up, 28 patients had 166 episodes of VT/VF. M TWA was greater before VT/VF (62. ±3.1 μV, n 28) than during baseline rhythm (12.8±1.8 μV, P 0.0001, n 62), rapid pacing (14.5±2.0 μV, P 0.0001, n 52), SVT (27.5±6.1 μV, P 0.0001, n ) or time matched controls (12.3±3.5 μV, P 0.0001, n 16). The odds of VT/VF increased by 2.2 fold ( 5 con dence interval: 2.0 2.4, p 0.0001) for each 10 μV increment in TWA (range: 0 218 μV). Ad usted for multiple episodes per patient, the area under the R C curve was 0. 16 (Figure). A threshold of 31 μV corresponded to an ad usted speci city of 5 and sensitivity of 66 .

Conclusions: Intracardiac TWA predicts imminent VT/VF in ICD patients. ICDs that monitor TWA continuously may warn patients and initiate pacing therapies to prevent VT/VF.

Methods: During the last year of enrolment in the RAFT Trial (Resynchronization for Ambulatory Heart Failure Trial), patients were offered participation in a randomized sub study of DT. In the DT arm, the goal was to achieve at least one success at 25 .Results: Among 252 patients screened, 145 were enrolled; 75 randomized to DT and 70 to no DT. Those assigned to DT and to no DT were similar in terms of: age (65. ± .3 yrs vs. 67. ±8. yrs); LV F (24.7±4.6 vs. 23.6±4.6 ), QRS width (154.8±23.5 vs. 155.8±23.6 msec) and history of atrial brillation (5 vs. 6 ). f 68 patients in the DT arm tested according to protocol, 6 had a successful DT without system modi cation and the

remaining 4 had a successful DT with polarity reversal and/or right ventricular lead repositioning. Intra operative complications were rare and not signi cantly different between groups. Four percent of patients in the DT arm e perienced intra operative hypotension requiring vasopressors or inotropes for > 15 minutes, compared to none in the no DT arm (p 0.25). No patient in either group died or e perienced stroke, myocardial infarction, heart failure, need for intubation or CPR or unplanned ICU stay. Hospital length of stay was not prolonged in the DT group: 20.2±26.3 hrs vs. 21.3± 23.0 hrs p 0.7 . During followup, the composite outcome of heart failure hospitalization(HF) or all cause mortality occurred in 1 of patients in the DT arm and 10 of patients in the no DT arm (p 0.14). No patient suffered an arrhythmic death. Patients in the no DT arm had a nonsigni cantly lower risk of HF hospitalization or death: HR 0.53, 5 CI: 0.21 1.31).

Conclusions: In this randomized trial of DT, peri operative complications were uncommon regardless of DT. Patients in the no DT arm did not have a measurable increase in their risk of long term adverse clinical outcomes.

MP03-4

THE EXTENT OF LV SCAR QUANTIFIED BY LATE GADOLINIUM ENHANCEMENT MRI IS ASSOCIATED WITH SPONTANEOUS VENTRICULAR ARRHYTHMIAS IN ICD RECIPIENTS

Paul A. Scott, MBChB, John Morgan, MD, FRCP, Nicola Carroll, BSc, David Murday, MBBS, Paul Roberts, MD, FRCP, Charles Peebles, MBBS, Stephen Harden, MBBS and Nick Curzen, PhD, FRCP. Wessex Cardiothoracic Unit, Southampton, United Kingdom

Introduction: Characterisation of sudden cardiac death (SCD) risk remains a challenge. Late gadolinium enhancement cardiac magnetic resonance imaging (L CMR) can accurately identify myocardial scar. We performed a retrospective single centre observational study, evaluating the association between the e tent and distribution of LV scar, quanti ed using L CMR, and the occurrence of ventricular arrhythmias, in patients with coronary artery disease and ICDs.Methods:All patients included (2006 200 ) had undergone LCMR prior to ICD implantation. Scar (de ned as myocardium with a signal intensity 50 of the ma imum in scar tissue) was characterised in terms of percent scar, scar surface area, and number of transmural LV scar segments. The end point was appropriate ICD therapy.Results:Si ty four patients (average age 66±11 years, 51 male) were included. During 1 ±10 months follow up, appropriate ICD therapy occurred in 1 patients (30 ). In univariate Co regression analyses both percent scar scar (hazard ratio [HR per 10 1.75; 5 con dence intervals [CI 1.0 2.81; p 0.02) and number of transmural scar segments (HR per segment 1.40; 5 CI 1.15 1.70; p 0.001) were signi cantly associated with

the occurrence of appropriate ICD therapy. Notably, in univariate analyses LV F (p 0.86), QRS width (p 0.13), and scar surface area (p 0.15) were not associated with the study end point.

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S501Moderated Posters

MP04-2

OPTICAL PACING OF THE ADULT RABBIT HEART

Michael W. Jenkins, PhD, Yves T.. Wang, BS, Michiko Watanabe, PhD, Yuanna Cheng, MD, PhD and Andrew M.. Rollins, PhD. Case Western Reserve University, Cleveland, OH, Cleveland Clinic, Cleveland, OH

Introduction: Although cardiac electrophysiology and pacing have greatly contributed to combating arrhythmias, electrical pacing does suffer from several drawbacks including low spatial precision, stimulation artifacts in electrode recordings, interference from magnetic elds and the requirement of tissue contact. Here, we test an alternative approach. Recently, we have demonstrated that infrared optical pulses can noninvasively pace an embryonic quail heart without introducing e trinsic agents into the tissue. Building on this work we set out to demonstrate optical pacing in the adult rabbit heart.Methods: Four rabbit hearts were e cised and Langendorffperfused. Laser light was delivered via optical ber to either the right or left atrium. Brief on off on sequences of pulses were delivered to demonstrate the feasibility of pacing. An C signal was recorded from electrodes on the left ventricle along with the trigger signal from the laser to validate the success of pacing.Results: The gure shows typical results of an on off on pacing e periment. The blue trace is the C and the red trace is the trigger from the pulsed laser. When the laser was turned on the heart rate increased ~30 to 2.5 Hz and followed the pulses in a one to one fashion. All four hearts were successfully paced in on off on e periments. The laser was able to pace the heart by stimulating various locations in the right and left atria.Conclusions: We have demonstrated, for the rst time, optical pacing of an adult heart. We have demonstrated reproducible pacing in multiple hearts in both the left and right atria. Future studies will aim to optimize the technique and determine the safety of the procedure.

MP04-3

ACTION POTENTIAL PROPAGATION IN HUMAN MONOLAYERS MADE FROM INDUCED PLURIPOTENT STEM CELL DERIVED CARDIOMYOCYTES

Luqia Hou, MS, Matt Klos, PhD, Alexandra Bizy, MS, Guadalupe Guerrero-Serna, PhD, Jianhua Zhang, PhD, Timothy Kamp, MD, PhD, Jose Jalife, MD and Todd Herron, PhD. University of Michigan, Ann Arbor, MI, University of Wisconsin Medical School, Madison, WI

Introduction: Successful reprogramming of human adult broblasts allowed the creation of induced pluripotent stem

cell derived cardiomyocytes (iPS CM). Initial characterization of human iPS CM was accomplished in heterogeneous embryoid bodies and at the single cell level. However, their integrated behavior as organized electrical syncytia has not been investigated. The ob ective was to demonstrate that iPSCMs can form electrically coupled monolayers showing rhythmic pacemaker activity, with uniform conduction velocity (CV), action potential duration (APD) restitution, and Ca2 dynamics.Methods: iPS CMs were derived from the 1 11T cell line using directed differentiation. Monolayers were immunostained for conne in40 (C 40), C 43, actinin, MHC, MHC, and N cadherin. ptical mapping (Di 8 AN PPS, 40 μM, 200

MODERATED POSTER SESSION MP04: Advances in EP Technology

Friday, May 6, 20113:15 - 4:15 p.m.

MP04-1

CARDIAC OPTOGENETICS: VALIDATION OF A CELL DELIVERY SYSTEM FOR CONTROL OF CARDIAC FUNCTION BY LIGHT

Emilia Entcheva, PhD, Zhiheng Jia, MSc, Virgilijus Valiunas, PhD, Hong-Zhang Wang, PhD, ZhongJu Lu, PhD, Huilin Liu, MSc, Harold Bien, MD, PhD, Barbara Rosati, PhD, Peter R.. Brink, PhD and Ira S.. Cohen, MD, PhD. SUNY - Stony Brook, Stony Brook, NY

Introduction: ptogenetics combines light and e pression of light sensitive ion channels to control electrical activity in e citable tissues. After rapid growth of neuroscience applications, optogenetics found its way to cardiac applications very recently. ur group was the rst to demonstrate a nonviral approach to cardiac optogenetics, where non e citable cells carry e ogenous light sensitive ion channel(s), and when coupled to cardiomyocytes (CM), produce optically e citable heart tissue. Here we validate this approach for optical control of neonatal and adult ventricular myocytes and e amine the role of gap unctional coupling in the process.Methods: As a proof of principle, we developed a stable H cell line e pressing Channelrhodopsin2 (ChR2). Its functionality was validated using voltage clamp in single cells and in heterologous cell pairs (H with adult canine CM or neonatal rat CM), as well as using optical mapping in cardiac syncytium made of H and neonatal rat CM. Cell cell coupling was perturbed by 0.2 to 0.5mM carbeno olone (CBX).Results: We demonstrate robust creation of optically e citable cell pairs or large scale syncytium when ChR2 H cells couple to CM (adult or neonatal). Minimal electrical coupling (about 1.5nS) is suf cient for functionality of the proposed method, while complete CBX uncoupling reversibly abolishes optical responsiveness of the syncytium, Fig 1.Conclusions: ur results con rm feasibility to control e citation and contraction in cardiac tissue by light and validate a new non viral optogenetics approach, potentially suitable for in vivo applications of cardiac optical pacing and cardioversion.

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S502 Heart Rhythm, Vol 8, No. 5, May Supplement 2011

Neither VNA nor 24 hour average heart rate changed during LL VNS. In roup 2 dogs, the frequency of PAF and PAT episodes during active LL VNS were 1.4±2.5/d and 8.0±5.8/d, respectively, signi cantly fewer than during sham stimulation ( .2±6.2/d, P 0.01 and 22.0±4.4/d, P 0.001, respectively). The tyrosine hydro ylase positive nerve structures in the left stellate ganglion of roup 1 dogs were less dense in LL VNS dogs (N 6, ,684±22,257 μm2/mm2) than normal control dogs (N 5; 186,561±11,383 μm2/mm2, P 0.01).Conclusions: Chronic LL VNS suppresses S NA and reduces tyrosine hydro ylase positive nerve structures in the left stellate ganglion. It also decreases the paro ysmal atrial tachyarrhythmias in ambulatory dogs. The structural and functional remodeling changes in the left stellate ganglion underlie the antiarrhythmic mechanisms of LL VNS.

MP04-5

OPTICAL IMAGING OF INTRAMURAL SPREAD OF ELECTRICAL ACTIVATION

Richard D. Walton, PhD, Christopher D.. Lawrence Xavier, MSc and Olivier Bernus, PhD. University of Leeds, Leeds, United Kingdom

Introduction: Cardiac arrhythmias are often caused by ectopic beats originating from intramural sites. Current techniques to map intramural activation patterns using plunge electrodes or optrodes have limited in plane spatial resolution. A recent computational study provided proof of principle for a novel optical imaging technique to visualize and determine the depth of the intramural wave front, but e perimental validation of this technique was still lacking.Methods: Coronary perfused left ventricular slab preparations (14.3±1.4 mm thick) isolated from pigs (N 3) were stained with DI 4 ANBDQBS. We utilized an alternating illumination approach that involved comparing pairs of simultaneously recorded broadeld epi uorescence and transillumination images produced

during alternating L D illumination (660 nm) of the epi ( PI) and endocardium ( ND ). Recordings were taken simultaneously with two CCD cameras imaging the PI and ND surfaces at an effective frame rate of 750Hz. Phantoms imitating the optical properties of myocardial tissue with ellipsoidal uorescent sources of varying sizes embedded at known depths were imaged for calibration.Results: In phantoms (20 mm thickness) we showed that we were able to reliably estimate the depth of uorescent boundaries ranging from 3 to 15 mm with respect to the imaged surfaces. Mean percentage error for determining the intramural e tent of the sources was 8±6 . In ventricular slabs, intramural pacing was achieved at two depths: 5 and 8mm from PI. We were able to localise the origin of intramural e citation waves with a precision of ±1. mm. The technique allowed measuring the anisotropic rates of wave propagation before breakthrough at either surface. The apparent transmural e pansion conduction velocities following intramural pacing were found to be 0.15±0.1 mm/ms towards PI and 0.27±0.12 mm/ms towards ND . Rate dependency of wave front e pansion showed increased rates of e pansion with decreased pacing cycle length (1Hz, 0.12±0.07 mm/ms vs 4Hz, 0.22±0.0 mm/ms).Conclusions: Alternating illumination imaging enables the reconstruction of intramural activation patterns providing a potential means for imaging ectopic beats.

fps) and confocal Ca2 imaging (10μM Fluo 4, 150 fps) were performed 3 5 days after plating.Results: iPS CM monolayers e pressed C 43, MHC,

actinin, and n cadherin, but C 40 and MHC were absent. Di 8 AN PPS revealed heterogenous distribution of myocyte t tubule structures in the monolayers; some myocytes had well de ned t tubules while other cells lacked t tubule structures. Functionally, iPS CM monolayers displayed spontaneous electrical activity at 1.01±0.17Hz, n 13; p 0.05 (mean ± SD; Student’s t test); carbachol 0.1 M slowed the spontaneous frequency to 0.56±0.14 Hz (n 5). iPS CM APD80 was similar to human adult ventricular myocytes (251±6.76 ms). However, all13 monolayers displayed pronounced APD80 alternans at basic cycle lengths (BCLs) of 1000 (long AP, 352±30.3 ms; short AP, 267±1 .5 ms; p 0.05) and 500 ms (long AP, 326±14.5 ms; short AP, 2 7 ± 10.7 ms; p 0.05). CV was rate dependent: 16.2 ± 1.34 cm/s at BCL 1000 ms vs. .78 ± 0.73 cm/s at BCL 350 ms. Ca2 transient amplitude alternans was also observed in some myocytes, which may underlie the APD alternans.Conclusions: iPS CM monolayers generate spontaneous and e ternally driven action potentials that propagate at uniform CVs. In addition, their APD restitution and Ca2 dynamics are similar to neonatal rat cardiomyocyte monolayers. iPS CM monolayers are a powerful new model to investigate mechanisms of normal and abnormal human cardiac impulse propagation.

MP04-4

CHRONIC LOW-LEVEL VAGUS NERVE STIMULATION REDUCES PAROXYSMAL ATRIAL TACHYARRHYTHMIAS IN AMBULATORY CANINES BY INDUCING STRUCTURAL AND FUNCTIONAL REMODELING OF THE LEFT STELLATE GANGLION

Mark J. Shen, MD, Tetsuji Shinohara, MD, PhD, Hyung-Wook Park, MD, PhD, Kyle Frick, BS, Daniel S. Ice, MD, Eue-Keun Choi, MD, PhD, Seongwook Han, MD, PhD, Rahul Sharma, BS, Changyu Shen, PhD, Micahel Fishbein, MD, Lan S. Chen, MD, Douglas P. Zipes, MD, Shien-Fong Lin, PhD and Peng-Sheng Chen, MD. Krannert Institute of Cardiology, Indianapolis, IN, Division of Biostatistics, Indiana University, Indianapolis, IN, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, Department of Neurology, Indianapolis, IN

Introduction: Low level vagus nerve stimulation (LL VNS) has been shown to reduce ventricular tachyarrhythmias in ambulatory animals. However, the antiarrhythmic mechanism of LL VNS remains unclear. Moreover, whether LL VNS can reduce atrial tachyarrhythmias in ambulatory animals is unknown.Methods: We implanted neurostimulators for left LL VNS and radiotransmitters for continuous recording of left stellate ganglion nerve activity (S NA), left thoracic vagal nerve activity (VNA) and electrocardiograms in 6 ambulatory, conscious dogs ( roup 1). roup 2 dogs (N 6) underwent both LL VNS and intermittent rapid atrial pacing to facilitate the development of paro ysmal atrial tachyarrhythmias. Paro ysmal atrial tachyarrhythmia is de ned as a tachycardia with a rate of >160 bpm that lasted for >10 sec, with the irregular ones being called paro ysmal atrial brillations (PAF), the regular ones paro ysmal atrial tachycardias (PAT).Results: In roup 1 dogs, integrated S NA was signi cantly reduced during LL VNS (7.8±1. mV s vs. .4±2.3 mV s at baseline, P 0.05).The reduction was most apparent from 7 to AM, (31 reduction, 10.8±2.5 mV s versus 15.6±2. mV s at baseline, P 0.01). The average heart rate from 7 to AM was also signi cantly reduced during LL VNS (P 0.05).

S NA induced heart rate acceleration averaged 107. ± .0 bpm during LL VNS and 12 .2± .3 bpm at baseline (P 0.05).

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S503Moderated Posters

MP05-2

THROMBOEMBOLIC RISK EVALUATION IN PATIENTS WITH ATRIAL FIBRILLATION USING A MODIFIED CHADS2 SCORING SYSTEM

Myung-jin Cha, MD, Gyu-chul Oh, MD, Seokyung Hahn, PhD, Eue-Keun Choi, MD, PhD and Seil Oh, MD, PHD, FHRS. Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea, Republic of, Medical Research Collaborating Center, Seoul National University Hospital, Seoul, Korea, Republic of

Introduction: Antithrombotic recommendations for relatively low risk patients with atrial brillation (AF) are not well established. We sought to evaluate the thromboembolic risk in AF patients with (1) a CHADS2 score of 1 with minor risk factors and (2) a CHADS2 score of 0 but CHA2DS2 VASc score of 2.Methods: A total of 6 5 patients with AF that were followed for 12 months (median 65.6 months, range 12 138 months), were

analyzed retrospectively. The modi ed CHADS2 score (MCS) was applied as follows. ach CHADS2 score group was divided into two groups, A and B (i.e. MCS 0A vs. 0B, and MCS 1A vs. 1B) according to the number of non ma or risk factors (female gender, chronic kidney disease, coronary artery disease, age 65 to 74 years). roup A had 0 or 1, and group B had 2 or more non ma or risk factors.Results: In patients with a CHADS2 score of 1, there were 13 thromboembolic events (3.8 ) in 343 MCS 1A patients, and 12 thromboembolic events (11.1 ) in 108 MCS 1B patients. Thromboembolic risk was signi cantly higher in the MCS 1B compared to the MCS 1A patients (p 0.006). In patients with a CHADS2 score of 0, the thromboembolic risk of MCS 0B was similar to that of MCS 0A (p 0.0 5) although their CHA2DS2VASc score was 2.Conclusions: Patients with MCS 1B had a higher thromboembolic risk than patients with MCS 1A. Antithrombotic strategies for patients with a CHA2DS2 VASc score of 2 but a CHADS2 score of 0 need further investigation.

MP05-3

INCIDENCE OF ASYMPTOMATIC EMBOLIC EVENTS FOLLOWING PULMONARY VEIN ISOLATION PROCEDURES: COMPARISON BETWEEN DIFFERENT ABLATION DEVICES

Claudia Herrera Siklody, MD, Thomas Deneke, MD, Mélèze Hocini, MD, Heiko Lehrmann, MD, Dong-In Shin, MD, Shinsuke Miyazaki, MD, Susanne Henschke, MD, Jochen Schiebeling-Roemer, MD, Michel Haissaguerre, MD and Thomas Arentz, MD. Herz Zentrum Bad Krozingen, Bad Krozingen, Germany, Krankenhaus Porz am Rhein, Cologne, Germany, Hopital Cardiologique du Haut-Lévèque, Bordeaux-Pessac, France

Introduction: New devices speci cally designed to ease pulmonary vein isolation (PVI) procedures have been recently

MODERATED POSTER SESSION MP05: Atrial Fibrillation and Thromboembolism

Saturday, May 7, 20119:30 - 10:30 a.m.

MP05-1

THE TEMPORAL RELATIONSHIP OF ATRIAL TACHYARRHYTHMIAS AND THROMBOEMBOLI BASED ON STORED DEVICE DATA: A SUBGROUP ANALYSIS OF TRENDS

Emile G. Daoud, MD, Taya V. Glotzer, MD, D. George Wyse, MD, PhD, Michael D. Ezekowitz, MD, PhD and Paul Ziegler, BS. Ohio State University, Columbus, OH, Hackensack University Medical Center, Hackensack, NJ, Libin Cardiovascular Institute of Alberta, Calgary, AB, Canada, Lankenau Institute for Medical Research, Philadelphia, PA, Medtronic Inc., Minneapolis, MN

Introduction: The temporal relationship between atrial tachyarrhythmias [tachycardia (AT) and brillation (AF) and thromboembolic events (T ) is unknown. This study evaluated this relationship utilizing stored AT/AF diagnostic data from implanted devices.Methods: The TR NDS study was a prospective, observational study to evaluate the relationship between device detected AT/AF and T . TR NDS enrolled 2486 pts requiring a dual chamber device, and 1 stroke risk factor. The current study focuses on the 40 pts (1.6 ) who e perienced T (ad udicated by 3 neurologists).Results: The mean age was 75 (28 males), mean CHADS2 score of 2.5, and 32 pts with a diagnosis of AF. AT/AF was detected prior to T in only 50 (20/40) pts. ther than mean and ma imum daily AT/AF burden, there were no signi cant clinical differences between pts with vs. without AT/AF prior to T . For the 20 pts with AT/AF detected before T , during the 30 days prior to T , the mean ma imum AT/AF burden on a single day was ± 11 hours, and the mean cumulative AT/AF burden was 151 ± 252 hours; however, 14 of these 20 pts with AT/AF detected prior to T were not in AT/AF at diagnosis of T . The last episode of AT/AF in these 14 pts was 168 ± 1 days (range: 3 642 days) before T . Also, of the 20 pts with AT/AF prior to T did not have any AT/AF in the 30 days before T . Therefore, of the 40 pts with T in this population, 2 /40 (73 ) pts had zero AT/AF burden within the 30 days prior to T .Among the 20 pts without AT/AF detected prior to T , 6 patients (30 ) had AT/AF recorded 181 ± 143 days after T .Conclusions: This study represents the largest series of pts with T and device detected AT/AF and offers 3 insights: (1) the ma ority of T in this population did not occur pro imally (within 30 days) of any AT/AF episodes. These data imply that the mechanisms of T in pts with implantable devices may importantly involve mechanisms other than cardioembolism due to atrial tachyarrhythmias,(2) 70 of the pts with AT/AF detected prior to T were not in AF with the T implying that the rhythm at T diagnosis is not indicative of AF contributing to the T , (3) A new diagnosis of AT/AF after T has implications for ongoing studies assessing the etiology of cryptogenic T utilizing implantable recorders.

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S504 Heart Rhythm, Vol 8, No. 5, May Supplement 2011

based on CHADS2 score and not AF burden. We sought to gain insight into late stroke events and their relationship to AF recurrence, use of AC, and CHADS2 score.Methods: We reviewed our single center e perience of 1, 0 patients (pts) who underwent PV antral isolation and then followed for a minimum of 1 year (average 4 2 months). Prior to stopping AC in pts with a CHADS2 score >1 we routinely performed transtelephonic C monitoring for at least 3 weeks and taught all pts to twice daily assess heart rate and stability of pulse. In CHADS2 score 1 pts, any arrhythmia documentation or inability to perform pulse assessment typically precluded stopping AC. Late additional C monitoring was routinely performed at 6 18 months and with symptoms when stopping AC.Results: AC was stopped in 1031/1 0 (52 ) of pts: 546/840 (65 ) with CHADS2 0; 384/7 6 (48 ) with CHADS2 1 and 101/354 (40 ) with CHADS2 2; p 0.0001). 16 late strokes occurred (0.2 per pt year). Five strokes (0.5 ) occurred in pts with CHADS2 0, all off AC; 5 strokes (0.62 ) in pts with CHADS2 1, 1 off and 4 on AC; and 6 strokes (1.51 ) in pts with CHADS2 2, 2 off and 4 on AC. 13/16 stroke pts (7 ) had documented AF. In patients off AC, there was no difference in stroke rate/yr strati ed by CHADS2 score (CHADS2 0: 0.28 ; CHADS2 1: 0.07 ; CHADS2 2: 0.50 ; p NS). There was no difference in stroke risk on AC versus off AC among those pts with either CHADS2 1 (0.48 vs 0.07 ) or CHADS2 2 (0.3 vs 0.50 ). The risk of ma or bleeding per pt yr for

those remaining on AC after ablation was greater than those off AC (13/1138 (1.14 ) versus 1/832 (0.1 ); p 0. 016).Conclusions: In the post AF ablation pt population with AC use guided by e tended C monitoring and pulse assessment: 1) verall stroke rate risk is very low and risk appears to be due to recurrent AF and not CHADS2 score. 2) AC can be stopped in over 40 of pts with CHADS2 2 with acceptably low stroke risk and avoidance of hemorrhagic risk. AC guidelines post AF ablation should be modi ed to emphasize individual pts arrhythmia burden and risk assessment and not based solely on CHADS2 score.

MP05-5

SUCCESSFUL CATHETER ABLATION OF ATRIAL FIBRILLATION REDUCED THE RISK OF CARDIOVASCULAR EVENTS BEYOND THE CONVENTIONAL CHADS2 IN ATRIAL FIBRILLATION PATIENTS AT HIGH RISK

Yenn-Jiang Lin, MD, Shih-Lin Chang, MD, Li-Wei Lo, MD, Yu-Feng Hu, MD, Ta-Chuan Tuan, MD, Ching-Tai Tai, MD, Kazuyoshi Suenari, MD, Cheng-Hung Li, MD, Tzu-Fan Chao, MD and Shih-Ann Chen, MD. Taipei Veterans General Hospital, Taipei, Taiwan

Introduction: Catheter ablation is a potentially curative treatment for atrial brillation (AF). However, it is unclear if successful catheter ablation of AF improves the long term outcome of the total mortality and thromboembolic (T ) events.Methods: A total of 271 consecutive symptomatic AF patients (52±10 yrs, roup I) at high risk (CHADS2 1) undergoing catheter ablation were compared to 322 age/gender matched controls (52±11 years, roup II) without catheter ablation of documented AF in the contemporary period. ver a mean follow up of 34 months (2 113), the patients were followed for AF recurrences ( roup: Ia: no recurrence after ablation, roup: Ib: AF recurrence after ablation), total mortality, stroke, coronary syndrome, and pulmonary emboli, and other peripheral T events requiring hospitalization.Results: verall 60 of the AF ablation patients were free of AF without drugs. In the ablation patients, 0 of the vascular

introduced. We aimed to compare the safety of these devices through screening for subclinical cerebral embolic events after PVI with either an irrigated radiofrequency catheter (RF) or a cryoballoon or a multi electrode duty cycled RF ablation catheter (PVAC).Methods: This multicentric study included patients (pts) with symptomatic paro ysmal or short persistent atrial brillation referred for PVI. Ablation was done using either one of the previously cited catheters. Cerebral magnetic resonance imaging (MRI) was performed before and after ablation. All pts were continuously anticoagulated around the procedure according to each center’s usual practice. In every case, intravenous heparin was administrated during ablation aiming an ACT > 300 seconds.Results: 74 pts (61± years old, 62 paro ysmal AF) were included in the study: 27 in the RF group, 23 in the cryoballoon group and 24 in the PVAC group. Total procedure times were 1 8±50 min, 174±35 min and 124±32 min respectively (p 0.001 for PVAC against RF and cryoballoon). Neurological e amination was normal in all pts before and after ablation. The incidence of new embolic lesions in post procedural MRI was 7.4 (2 /27) in the RF group, 4.3 (1/23) in the cryoballoon group (single lesions) and 33.3 (8/24, 2.75±1. 1 lesions/patient) in the PVAC group (p 0.008 for PVAC against cryoballoon and RF).Conclusions: The PVAC catheter presents a strikingly higher incidence of embolic events than RF or cryoablations. Further technical improvements aiming to optimize the safety of PVAC ablations seem to be mandatory.

MP05-4

RISK OF STROKE AFTER ATRIAL FIBRILLATION ABLATION: AF BURDEN VERSUS CHADS2 SCORE IN PATIENTS WITH ORAL ANTICOAGULANT USE GUIDED BY ECG MONITORING AND PULSE ASSESSMENT

Michael P. Riley, MD, PhD, Erica Zado, PA, Kurt Schillinger, MD, PhD, Marc Deyell, MD, Edward P. Gerstenfeld, MD, David J. Callans, MD, Mathew Hutchinson, MD, David Lin, MD, Joshua Cooper, MD, Ralph Verdino, MD, Rupa Bala, MD, Fermin Garcia, MD, Wendy Tzou, MD and Francis E. Marchlinski, MD. Hospital Of The Univ Of Pennsylvania, Philadelphia, PA

Introduction: Current recommendations dictating use of oral anticoagulant ( AC)following atrial brillation (AF) ablation are

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S505Young Investigators Awards Competition

SPECIAL SESSION SP14: Young Investigators Award Competition

Thursday, May 5, 20111:30 - 3:30 p.m.

YIA-01

SERCA2A AS A NOVEL MECHANISM AND THERAPEUTIC TARGET FOR ARRHYTHMOGENIC CARDIAC ALTERNANS IN HEART FAILURE

Michael J. Cutler, DO, PhD, Xiaoping Wan, MD, PhD, Bradley N. Plummer, BS, Isabelle Deschenes, PhD, Kenneth R. Laurita, PhD, Roger J. Hajjar, MD and David S. Rosenbaum, MD. MetroHealth Medical Center, Case Western Reserve University, Cardiology, Cleveland, OH, Mount Sinai Heart, Mount Sinai Medical Center, New York, NY

Introduction: Beat to beat alternation of the cardiac action potential (Vm Alt) attributable to alternation in cellular calcium cycling (Ca Alt) is a recognized mechanism of ventricular brillation (VF). Recently, we reported that S RCA2a, the

pump responsible for re uptake of cytosolic calcium during diastole, plays a central role in the molecular mechanism of cardiac alternans. Heart failure (HF) is associated with impaired myocardial calcium handling, de cient S RCA2a, and increased susceptibility to cardiac alternans. Therefore, we hypothesized that targeting de cient S RCA2a will signi cantly reduced cardiac alternans in the failing heart.Methods: All studies were performed in adult guinea pigs that were divided into 3 groups: 1) Control, 2) HF (thoracic aorta constriction), and 3) HF S RCA2a overe pression (AAV .S RCA2a). lectrophysiological studies were performed in isolated myocytes and Langendorff perfused hearts using standard patch clamp and optical mapping techniques, respectively.Results: HF resulted in a decrease in LV fractional shortening (25±2 vs. 50±2 , p 0.01) when compared to control. Isolated HF myocytes demonstrated slower SR calcium uptake, decreased Ca release and increase diastolic Ca compared to controls (p 0.05). Moreover, S RCA2a, RyR2 and NCX protein e pression were decreased in HF when compared to control (p 0.05). As predicted, HF increased cardiac alternans as evidenced by decreased heart rate thresholds for both Vm ALT (2 0±12 bpm vs. 388±8 bpm, p 0.01) and Ca ALT (230±15 bpm vs 370±13 bpm, p 0.01) compared to controls. In vivo gene transfer of AAV .S RCA2a increased LV fractional shortening and S RCA2a protein e pression compared to HF alone (p 0.01). Importantly, S RCA2a overe pression in HF suppressed cardiac alternans compared to both HF alone (p 0.001) and control (p 0.05).Conclusions: These data provide new evidence that reduced S RCA2a in HF modulates susceptibility to arrhythmogenic cardiac alternans. Moreover, therapies targeting S RCA2a can improve contractile dysfunction and reduce arrhythmia substrate in HF.

events/deaths occurred > 3 months after the procedure. The incidence of the total mortality was 0.35 , 0.50 , and 1.58

per year, and total vascular events was 0.60 ,1.73 , and 2.78 per year in roups Ia, Ib, and II, respectively (P 0.01). In the multivariate Co regression analysis, the independent predictors of all events were a recurrence of AF ( R: 2.88, 5 CI 1.6 5.2, P 0.001) and CHADS2 score of >2 ( R: 1.57, 5 CI 1.2 2.1, P 0.001), but not anticoagulation use.Conclusions: Catheter ablation in high risk AF patients reduced the T events and overall mortality. The AF burden (based on a symptom based follow up) predicted the future T events and all cause mortality after the catheter ablation, in addition to the conventional CHADS2.

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YIA-02

MECHANISM OF PREGNANCY-RELATED LONG QT SYNDROME RISK: ESTROGEN ACCELERATES HUMAN CARDIAC REPOLARIZATION BY ENHANCING KCNH2 MEMBRANE TRAFFICKING VIA HEAT-SHOCK-PROTEIN INTERACTION

Lars Anneken, MD, Stefan Baumann, MD, Peter Biliczki, MD, Zenawit Girmatsion, PhD, Ina Takac, ScD, Ralf P. Brandes, MD, Thomas Klingenheben, MD, Eric Schulze-Bahr, MD, Stanley Nattel, MD, Stefan H.. Hohnloser, MD and Joachim R. Ehrlich, MD. Universitätsklinikum Erlangen, Erlangen, Germany, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany, Institut für Kardiovaskuläre Physiologie, Fachbereich Medizin der Goethe-Universität, Frankfurt am Main, Germany, Universitätsklinikum Münster, Münster, Germany, Montreal Heart Institute and Université de Montréal, Montréal, QC, Canada

Introduction: Women with Long QT Syndrome (LQTS) 2 have mildly reduced event risk during pregnancy but high risk postpartum. ffects of gonadal hormones (gon horm) on human QTc are controversial and related cellular mechanisms modulating repolarization in LQTS 2 unknown. This study assessed the regulation of human QTc by gon horm and elucidated cellular mechanismsMethods: on horm and QTc were measured in 21 women (5 LQTS 2 [ CNH2 R752P during the menstrual cycle, 11 probands with hormonal stimulation, 5 with pregnancy). Mutagenesis, heterologous e pression, patch clamp, real time PCR, protein biochemistry, confocal microscopy were usedResults: In all 3 groups, higher estradiol ( 2) levels correlated with shorter QTc (p 0.001; A B). Progesterone or 2/progesterone ratio were not correlated. 2 stimulation (60 pM, 48h) enhanced I CNH2 (C) via estrogen receptor ( R) dependent increases in CNH2 membrane traf cking (p 0.001) with no effect on CNQ1. R activation did not affect I CNH2. Heat shock protein (Hsp) is known to enhance CNH2 traf cking. Transcription/translation of CNH2, R or chaperones (Hsp70, Hsp 0, STIP 1, DNA A1, rp 4) were unchanged. 2 enhanced

CNH2 interaction with Hsp70 and Hsp 0 (D). eldanamycin (Hsp 0 inhibitor) decreased 2 mediated CNH2/Hsp interaction and abolished I CNH2 increaseConclusions: levated 2 levels abbreviate ventricular repolarization in female LQTS 2 patients and healthy women.

2 acts via R mediated Hsp 0 interaction with CNH2 to augment CNH2 traf cking and enhance I r. These results provide mechanistic and potential therapeutic insights into LQTS occurrence and control, particularly in women

YIA-03

CONNEXIN GENE TRANSFER PRESERVES CONDUCTION VELOCITY AND PREVENTS ATRIAL FIBRILLATION

Tomonori Igarashi, MD, PhD, J.Emanuel Finet, MD, Ayano Takeuchi, MS, Yoshihisa Fujino, MD, PhD, Maria Strom, PhD, Ian D. Greener, PhD, Gary P. Pawlowski, BS, David S. Rosenbaum, MD and J. Kevin Donahue, MD. MetroHealth campus, Case Western Reserve University, Cleveland, OH, MetroHealth Campus, Case Western Reserve University, Cleveland, OH, Department of Biostatistics, School of Public Health, The University of Tokyo, Tokyo, Japan, Department of Preventive Medicine and Community Health, University of Occupational and Environmental Health School of Medicine, Kitakyushu, Japan

Introduction: Alterations of gap unction proteins ( P) are associated with conduction delay and arrhythmogenesis in atrial brillation (AF). We hypothesized that atrial speci c gene transfer with P would improve conduction, eliminate reentry, and prevent AF.Methods: 30 Yorkshire swine were randomized into two groups: sinus rhythm (SR, n 15) and AF (n 15). ach group had the following subgroups: sham operated controls and gene therapy with adenovirus e pressing conne in (C ) 40 (AdC 40 animals) or C 43 (AdC 43 animals), with 5 animals in each subgroup. In vivo gene transfer was performed using the epicardial gene painting method with polo amer F127 (20 ), trypsin (0.5 ), and indicated virus (1 10 pfu/ml). In addition, the AF group had atrial pacemakers implanted for burst pacing. Animals were monitored daily for rhythm. All animals underwent terminal study on day 7.Results: Conduction time was signi cantly prolonged in AF control animals (75.5 msec., p 0.05 vs. SR control animals). Conduction time improved in AF AdC 40 (55.6 msec.) and AF AdC 43 animals (60.2 msec.) compared to AF control animals (p 0.05). ptical mapping corroborated the in vivo measurements. Statistical analysis using generalized estimating equations showed signi cant increases of SR percentages in AdC 40 animals (relative risk; 2.16, 5 con dence interval; 1.07 to 4.36, p 0.05) and AdC 43 animals (relative risk; 3.6 , 5 con dence interval; 1. 7 to 6. 3, p 0.01) compared

to AF control animals. In contrast to AF animals, in vivo electrophysiological study and e vivo optical mapping showed that SR animals had no detectable change in atrial conduction with either AdC 40 or AdC 43 gene transfer. Western blot analysis demonstrated successful transgene e pression in each of the gene transfer groups. For the AF control group, total and phosphorylated C 43 were decreased relative to SR controls (p 0.01 vs. SR control animals). ene therapy with C 43 completely restored e pression of both total and p C 43 in the AF animals to SR levels.Conclusions: Atrial speci c gene therapy with C 40 and C 43 preserved atrial conduction and prevented AF. Targeted gene therapy will provide us a novel therapeutic approach for AF based on selective alteration of atrial substrates.

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S507Young Investigators Awards Competition

for catheter ablation received a D MRI prior to the procedure. LA enhancement was calculated using an algorithm based on LA wall pi el intensity distribution. We then compared the degree of LA enhancement with different clinical characteristics, demographics, structural parameters and other co morbidities. Patients were categorized based on the percentage of pree isting LA enhancement seen on D MRI: Utah Class I (05 LA enhancement), Utah II (5 20 ), Utah III (20 35 ), and Utah IV (>35 ).Results: In univariate analysis, patients with e tensive AF burden (p 0.01), hypertension (p 0.48) and diabetes (p 0.42) had signi cantly more LA remodeling. Based on results from multivariate analysis, AF burden was shown to be the most important predictor for pre procedure enhancement (p 0.005). There were signi cant differences between Utah Class and AF burden (months) (p 0.005): Utah I 2 . / 46.8; Utah II 60.6

/ 87.7; Utah III 4.5 / .8; Utah IV 12 . / 118.7. There were also signi cant differences between Utah Class and LA volume (cm3), (p 0.005): Utah I 7. / 34.2; Utah II 8.0 / 3 .7; Utah III 107. / 42.3; Utah IV 130.6 / 4 .3.Conclusions: The duration of time spent in AF is the most powerful predictor of LA structural remodeling as assessed with D MRI. LA dilation is associated with increased LA enhancement seen on D MRI.

YIA-06

INCIDENCE AND PREDICTORS OF APPROPRIATE ICD THERAPY IN PATIENTS WITH ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA (ARVD) UNDERGOING ICD IMPLANTATION FOR PRIMARY PREVENTION

Aditya Bhonsale, MD, Cynthia A. James, PhD, Crystal Tichnell, MS, Brittney Murray, MS, Dmitri Gagarin, MD, Darshan Dalal, MD, Binu Philips, MD, Ryan Tedford, MD, Harikrishna Tandri, MD, Daniel P. Judge, MD and Hugh Calkins, MD. Johns Hopkins Hospital, Baltimore, MD

Introduction: Patients with a diagnosis of ARVD often receive implantable de brillator for prevention of sudden death. The purpose of this study was to de ne the incidence and predictors of appropriate ICD therapy in ARVD patients following placement of an ICD for primary prevention.Methods: The study population consisted of 84 patients with a diagnosis of ARVD who underwent ICD implantation for primary prevention. Detailed phenotypic, genotype, and ICD event information was obtained and appropriate ICD therapies were ad udicated based on intracardiac electrograms. aplanMeier analysis was used to determine freedom from appropriate therapy for VT and fast VT/VF (CL 240msec).Results: f the 84 ARVD patients, 46 were men and 64 were probands. ver a mean follow up of 4.7 3.4 years, 40 (48 ) patients had an appropriate shock of which 16 (1 ) were potentially fatal fast VT/VF episodes. Freedom from appropriate ICD therapy at 1, 2 and 5 years was 73 , 64 , 37 and from

YIA-04

CHARACTERISATION OF FRACTIONATED ATRIAL ELECTROGRAMS CRITICAL FOR MAINTENANCE OF AF: A RANDOMISED CONTROLLED TRIAL OF ABLATION STRATEGIES (THE CFAE AF TRIAL).

Ross J. Hunter, MRCP, Ihab Diab, MD, FRCP, Muzahir Tayebjee, MD, FRCP, Laura Richmond, MSc, Simon Sporton, MD, FRCP, Mark J. Earley, MD, FRCP and Richard J. Schilling, MD, FRCP. Barts and The London NHS Trust and QMUL, London, United Kingdom

Introduction: Whether ablation of comple fractionated atrial electrograms (CFA ) modi es AF by eliminating drivers or atrial de bulking remains unknown. This randomised study aimed to determine the effect of ablating different CFA morphologies compared to normal electrograms (i.e. de bulking normal tissue) on the cycle length of persistent AF (AFCL).Methods: After pulmonary vein isolation CFA were targeted systematically throughout the left then right atrium, until termination of AF or abolition of CFA prior to DC cardioversion. 10s electrograms were classi ed according to a validated scale, with rade 1 being most fractionated and grade 5 normal. Patients were randomised to have CFA grades eliminated sequentially, from grade 1 to 5 (group 1) or grade 5 to 1 (group 2). Because grade 5 electrograms were considered normal, only 5 were ablated. Lesions were regarded as individual observations, and an increase in AFCL (mean of left and right atrial appendage) > 5 ms was regarded as signi cant. The randomised strategy rstly controlled for any cumulative effect of ablation on AFCL, and secondly allowed assessment of the order of ablation on the number of CFA lesions required.Results: 68 CFA were targeted in 20 patients. AFCL increased after targeting 50 of grade 1 CFA , 34 of grade 2, 13 of grade 3, 33 of grade 4, and 8 of grade 5 (p 0.0001 for grades 1, 2, and 4 versus 5, 3 versus 5 not signi cant). Binary logistic regression con rmed the effect of CFA grade on the proportion of lesions causing cycle length prolongation, but showed no effect of electrogram amplitude, location in the left or right atrium, or the order in which CFA were targeted.

limination of the most fractionated electrograms rst reduced the number of grade 3 and 4 CFA encountered (group 1 versus group 2 both p 0.01), translating to fewer CFA targeted per patient in group 1 compared to group 2 (37 ± 14 and 58 ± 18 respectively; p 0.015).Conclusions: Targeting CFA is not simply atrial de bulking. Ablating certain grades of CFA increases AFCL, suggesting they are more important in maintaining AF.

YIA-05

FACTORS INFLUENCING LEFT ATRIAL STRUCTURAL REMODELING IN ATRIAL FIBILLATION PATIENTS AS ASSESSED WITH DELAYED-ENHANCEMENT MRI

Troy J. Badger, MD, Nazem Akoum, MD, Yaw A. Adjei-Poku, MD, Nathan S. Burgon, BSc, Thomas S. Haslam, BSc, Michael Barakat, BSc, Rory Carrera, BSc, Anthony Petersen, BSc, Chankevin Tek, No Degree, Christopher J. McGann, MD and Nassir F. Marrouche, MD. Comprehensive Arrhythmia and Research Management (CARMA) Center, University of Utah School of Medicine, Salt Lake City, UT

Introduction: Atrial brillation (AF) has been shown to result in left atrial (LA) structural remodeling that leads to more progressively diseased state. We used delayed enhancement MRI (D MRI) to assess which clinical parameters are most in uential in the LA remodeling process.Methods: 487 patients who presented to the University of Utah

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S508 Heart Rhythm, Vol 8, No. 5, May Supplement 2011

ICD therapy for fast VT/VF was 3 , 83 , and 7 . Univariable analysis identi ed proband status (HR 6.4, 5 CI 2.3 18.2, P 0.001), inducibility at P study (HR 3.1, 5 CI 1.4 6. , P 0.005), presence of nonsustained ventricular tachycardia (NSVT) (HR 3.8, 5 CI 1. 7.6, P 0.001) and Holter PVC count >1000/24hrs (HR 3.1, 5 CI 1.1 8.3, P 0.024) as signi cant predictors of appropriate ICD therapy. Inducibility at P study (HR 4.5, 5 CI 1.37 14. 6, P 0.013) and NSVT (HR 10.54,

5 CI 2.40 46.18, P 0.002) alone remained as signi cant predictors on multivariable analysis. Proband status (p 0.026) and/or inducibility at P study (p 0.024) was signi cantly associated with fast VT/VF occurrence. None of the family members with non inducible P study (N 18) e perienced fast VT/VF during follow up.Conclusions: Inducibility at P study and presence of NSVT are independent strong predictors of appropriate ICD therapy in ARVD patients receiving ICDs for primary prevention. Mutation status, electrocardiographic variables and ma or structural abnormalities do not appear to affect this risk. Family members of ARVD probands with no documented NSVT or PVC> 1000 on Holter, and who are non inducible at P study appear to be at low risk for life threatening VT/VF and may not require ICD implantation.


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