poster session 1

35
S106 Heart Rhythm Vol 4, No.5 May Supplement 2007 Introduction: Thoracic spinal cord stimulation (SCS) has been shown to relieve refractory angina in humans and reduce the incidence of ventricular arrhythmias in post-infarction dogs with heart failure after acute circumflex (Cx) occlusion. This study investigated the effects of chronic SCS on ventricular function in a similar post-infarction canine heart failure model. Methods: In Stage 1 , 30 dogs underwent ICD implantation followed by percutaneous foam embolization of the left anterior descending artery to produce occlusion. After 2 weeks, surviving animals underwent RV pacing (240 ppm) for 3 weeks to produce heart failure. In Stage 2 , animals were randomized to control or SCS groups. The SCS group had an SCS device (Itrel) and epidural stimulation lead implanted with SCS (90% motor threshold, 50 Hz, 200 sec duration) delivered at T4/T5 spinal region for 2 hours TID. All animals were followed for 5 weeks after randomization. In Stage 3 , all animals underwent Cx balloon occlusion for 1 hour. Results: Eight animals died during the acute procedure or initial recovery period prior to randomization. In 11 animals randomized to SCS, LVEF was 65 +/- 5%, 17 +/- 3 %, and 47 +/- 7% at baseline, at Stage 1 end, and at Stage 2 end, respectively. In 11 dogs randomized to Control, LVEF at the same time points was 64 +/- 5%, 19 +/- 5 %, and 28 +/- 3%, respectively. LVEF was significantly improved in the SCS group after 5 weeks (p < 0.001). Additionally, in the SCS group compared to Control after Stage 2 end, body weight change from baseline (3.7 +/- 1.2 vs. 11.4 +/- 2.4%), heart rate (105 +/- 15 vs. 120 +/- 15 bpm), QRS duration (75 +/- 4 vs. 88 +/- 10 ms), and B-type natriuretic peptide levels (216 +/- 82 vs. 653 +/- 337 pg/ml) were significantly less (p < 0.05 for all). The occurrence of ventricular arrhythmias during Stage 3 was also significantly decreased in the SCS group (27%) versus Control (76%; p<0.003). Conclusions: A five-week interval of SCS significantly improved cardiac contractile function and clinical parameters in dogs with healed myocardial infarction and heart failure. It also protected against ventricular arrhythmias during acute ischemia. YI8-6 FIELD STIMULATION PRODUCES FIBRILLATORY ACTIVITY IN A 2-D EXPERIMENTAL MODEL OF CALCIUM OVERLOAD Marvin G. Chang, MS, Linmiao Xu, BS, Connie Y. Chang, BS, Josh Cysyk, PhD, Eduardo MarbÆn, MD, PhD, Leslie Tung, PhD and M. Roselle Abraham, MD. Johns Hopkins University, Baltimore, MD. Introduction: Ca2+ dynamics play an important role in defibrillation success and failure, however the role of Ca overload on response to shocks is unclear. Here, we investigated the effects of field stimulation on reentry and spontaneous activity in a 2D experimental model of Ca2+ overload. Methods: We studied neonatal rat ventricular myocytes (NRVM-only) and co-cultures of skeletal myoblasts and NRVMs. Optical (voltage or calcium) mapping was performed after maturation of calcium handling. Monolayers were superfused with 2.5uM BAYK8644 and 1uM Isoproterenol (BI) to produce Ca2+ overload. Reentries were induced by rapid pacing; monophasic shocks were applied (5.5 & 8.5 V/cm, 25ms) using 2 field electrodes placed in a bath 2.4 cms away from each other and 5mm above the monolayer, with each shock separated by a ~2-sec or 3 min interval. Results: In co-cultures, BI increased the APD restitution slope by 65% (n=13), above the threshold for dynamic instability (delta(APD/CL)=0.5). Reentries were readily induced by rapid pacing. In the absence of Ca2+ overload, field stimulation at 5.5V/cm terminated reentry (n=5). However, in the presence of Ca2+ overload, field stimulation at 5.5 & 8.5 V/cm failed to terminate reentry. Instead, shocks resulted in complex reentries or fibrillatory activity that persisted despite multiple shocks (n=10). This effect was independent of the phase of the reentry cycle at which the shock was delivered. Voltage mapping revealed an isoelectric window following shock, but Ca2+ imaging demonstrated that Ca2+ oscillations persisted throughout the monolayer. Reentry and fibrillatory activity were also induced when field stimulation was applied to spontaneously beating NRVM-only monolayers subjected to Ca2+ overload. Conclusions: Shocks induce complex reentries and fibrillatory activity in the presence of Ca2+ overload. This may result from Ca2+- overload induced gap junctional uncoupling, shock-induced Ca2+ release and/or increased slope of APD restitution. POSTER SESSION 01 Wednesday, May 9, 2007 Session Time: 5:45 PM - 7:00 PM Presenter Available: TBD PO1-1 IMPACT OF A DEDICATED ATRIAL FIBRILLATION CENTER: EXPERIENCE WITH THE FIRST 1000 PATIENTS Liza A. Prudente, MSN, ACNP, Douglas E. Lake, PhD, Yuping Xiao, MS, John D. Ferguson, MD, DDS, John P. Dimarco, MD, PhD, J. Paul Mounsey, MD, PhD, J. Randall Moorman, MD and J. Michael Mangrum, MD. University of Virginia, Charlottesville, VA. Introduction: Patients with atrial fibrillation (AF) are currently managed by a variety of providers (primary care physicians, cardiologists, and EPs). Other disease-based clinics and centers have demonstrated outcome improvements; e.g. CHF clinics, HTN clinics, and chest pain centers. We postulated that a disease-based Atrial Fibrillation Center would have high impact on management of AF patients. Methods: In 9/04 an Atrial Fibrillation Center was established at the University of Virginia. For each referred patient a detailed AF history, based upon the ACC/AHA Clinical Data Standard for AF, was obtained at the initial and subsequent visits. The AF symptom burden was calculated from the frequency and duration of symptoms. Multivariable regression analysis was used to test ideas about determinants for choice of treatment. Results: Between 9/04 and 11/06, 1045 patients, mean age 62 – 14 (67% male) were referred to the AFC. The mean duration of symptoms was 5.2 years and the mean AF symptom burden was 39% . Fifty-three percent had used 1 or more antiarrhythmic (AA) drugs. After initial evaluation, 686 patients received rhythm control therapies (AA drugs, cardioversion, LA catheter ablation), and 262 received rate control therapies (AV blocking agents, AVJ ablation and pacemaker). We made management changes in 76% of cases. Follow-up within 6 months was available for 527 pts. A reduction in symptomatic AF burden was seen in both the rate control pts (from 35% to 15%, p<0.0001) as well as in rhythm control patients (from 35% to 14%, p<0.0001). The major determinants for choice of rhythm control treatment were young age and longer duration of symptoms. HTN, CAD, CHF, the qualifying rhythm, and gender were not significantly different in patients receiving rhythm control management. Conclusions: For patients referred to a dedicated AF center with heart rhythm specialists, there are often treatment changes resulting in a significant reduction in symptomatic AF burden for both rhythm and rate control strategies. PO1-2 ARE BIPOLAR LV LEADS REALLY SUPERIOR? Jeanine K. Murphy, RN, BSN, Richard G. Trohman, MD, Helen K. Suzuki, BA, Kousik Krishnan, MD, Andrew T. Lawrence, MD and Janet M. Haw, RN, BSN. Rush University, Chicago, IL.

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Page 1: Poster Session 1

S106 Heart Rhythm Vol 4, No.5 May Supplement 2007

Introduction: Thoracic spinal cord stimulation (SCS) has been shown to relieve refractory angina in humans and reduce the incidence of ventricular arrhythmias in post-infarction dogs with heart failure after acute circumflex (Cx) occlusion. This study investigated the effects of chronic SCS on ventricular function in a similar post-infarction canine heart failure model. Methods: In Stage 1, 30 dogs underwent ICD implantation followed by percutaneous foam embolization of the left anterior descending artery to produce occlusion. After 2 weeks, surviving animals underwent RV pacing (240 ppm) for 3 weeks to produce heart failure. In Stage 2, animals were randomized to control or SCS groups. The SCS group had an SCS device (Itrel) and epidural stimulation lead implanted with SCS (90% motor threshold, 50 Hz, 200 µsec duration) delivered at T4/T5 spinal region for 2 hours TID. All animals were followed for 5 weeks after randomization. In Stage 3, all animals underwent Cx balloon occlusion for 1 hour. Results: Eight animals died during the acute procedure or initial recovery period prior to randomization. In 11 animals randomized to SCS, LVEF was 65 +/- 5%, 17 +/- 3 %, and 47 +/- 7% at baseline, at Stage 1 end, and at Stage 2 end, respectively. In 11 dogs randomized to Control, LVEF at the same time points was 64 +/- 5%, 19 +/- 5 %, and 28 +/- 3%, respectively. LVEF was significantly improved in the SCS group after 5 weeks (p < 0.001). Additionally, in the SCS group compared to Control after Stage 2 end, body weight change from baseline (3.7 +/- 1.2 vs. 11.4 +/- 2.4%), heart rate (105 +/- 15 vs. 120 +/- 15 bpm), QRS duration (75 +/- 4 vs. 88 +/- 10 ms), and B-type natriuretic peptide levels (216 +/- 82 vs. 653 +/- 337 pg/ml) were significantly less (p < 0.05 for all). The occurrence of ventricular arrhythmias during Stage 3 was also significantly decreased in the SCS group (27%) versus Control (76%; p<0.003). Conclusions: A five-week interval of SCS significantly improved cardiac contractile function and clinical parameters in dogs with healed myocardial infarction and heart failure. It also protected against ventricular arrhythmias during acute ischemia. YI8-6 FIELD STIMULATION PRODUCES FIBRILLATORY ACTIVITY IN A 2-D EXPERIMENTAL MODEL OF CALCIUM OVERLOAD Marvin G. Chang, MS, Linmiao Xu, BS, Connie Y. Chang, BS, Josh Cysyk, PhD, Eduardo Marbán, MD, PhD, Leslie Tung, PhD and M. Roselle Abraham, MD. Johns Hopkins University, Baltimore, MD. Introduction: Ca2+ dynamics play an important role in defibrillation success and failure, however the role of Ca overload on response to shocks is unclear. Here, we investigated the effects of field stimulation on reentry and spontaneous activity in a 2D experimental model of Ca2+ overload. Methods: We studied neonatal rat ventricular myocytes (NRVM-only) and co-cultures of skeletal myoblasts and NRVMs. Optical (voltage or calcium) mapping was performed after maturation of calcium handling. Monolayers were superfused with 2.5uM BAYK8644 and 1uM Isoproterenol (BI) to produce Ca2+ overload. Reentries were induced by rapid pacing; monophasic shocks were applied (5.5 & 8.5 V/cm, 25ms) using 2 field electrodes placed in a bath 2.4 cms away from each other and 5mm above the monolayer, with each shock separated by a ~2-sec or 3 min interval. Results: In co-cultures, BI increased the APD restitution slope by 65% (n=13), above the threshold for dynamic instability (delta(APD/CL)=0.5). Reentries were readily induced by rapid pacing. In the absence of Ca2+ overload, field stimulation at 5.5V/cm terminated reentry (n=5). However, in the presence of Ca2+ overload, field stimulation at 5.5 & 8.5 V/cm failed to terminate reentry. Instead, shocks resulted in complex reentries or fibrillatory activity that persisted despite multiple shocks (n=10). This effect was independent of the phase of the reentry cycle at which the shock was delivered.

Voltage mapping revealed an isoelectric window following shock, but Ca2+ imaging demonstrated that Ca2+ oscillations persisted throughout the monolayer. Reentry and fibrillatory activity were also induced when field stimulation was applied to spontaneously beating NRVM-only monolayers subjected to Ca2+ overload. Conclusions: Shocks induce complex reentries and fibrillatory activity in the presence of Ca2+ overload. This may result from Ca2+-overload induced gap junctional uncoupling, shock-induced Ca2+ release and/or increased slope of APD restitution. POSTER SESSION 01 Wednesday, May 9, 2007 Session Time: 5:45 PM - 7:00 PM Presenter Available: TBD PO1-1 IMPACT OF A DEDICATED ATRIAL FIBRILLATION CENTER: EXPERIENCE WITH THE FIRST 1000 PATIENTS Liza A. Prudente, MSN, ACNP, Douglas E. Lake, PhD, Yuping Xiao, MS, John D. Ferguson, MD, DDS, John P. Dimarco, MD, PhD, J. Paul Mounsey, MD, PhD, J. Randall Moorman, MD and J. Michael Mangrum, MD. University of Virginia, Charlottesville, VA. Introduction: Patients with atrial fibrillation (AF) are currently managed by a variety of providers (primary care physicians, cardiologists, and EPs). Other disease-based clinics and centers have demonstrated outcome improvements; e.g. CHF clinics, HTN clinics, and chest pain centers. We postulated that a disease-based Atrial Fibrillation Center would have high impact on management of AF patients. Methods: In 9/04 an Atrial Fibrillation Center was established at the University of Virginia. For each referred patient a detailed AF history, based upon the ACC/AHA Clinical Data Standard for AF, was obtained at the initial and subsequent visits. The AF symptom burden was calculated from the frequency and duration of symptoms. Multivariable regression analysis was used to test ideas about determinants for choice of treatment. Results: Between 9/04 and 11/06, 1045 patients, mean age 62 ± 14 (67% male) were referred to the AFC. The mean duration of symptoms was 5.2 years and the mean AF symptom burden was 39% . Fifty-three percent had used 1 or more antiarrhythmic (AA) drugs. After initial evaluation, 686 patients received rhythm control therapies (AA drugs, cardioversion, LA catheter ablation), and 262 received rate control therapies (AV blocking agents, AVJ ablation and pacemaker). We made management changes in 76% of cases. Follow-up within 6 months was available for 527 pts. A reduction in symptomatic AF burden was seen in both the rate control pts (from 35% to 15%, p<0.0001) as well as in rhythm control patients (from 35% to 14%, p<0.0001). The major determinants for choice of rhythm control treatment were young age and longer duration of symptoms. HTN, CAD, CHF, the qualifying rhythm, and gender were not significantly different in patients receiving rhythm control management. Conclusions: For patients referred to a dedicated AF center with heart rhythm specialists, there are often treatment changes resulting in a significant reduction in symptomatic AF burden for both rhythm and rate control strategies. PO1-2 ARE BIPOLAR LV LEADS REALLY SUPERIOR? Jeanine K. Murphy, RN, BSN, Richard G. Trohman, MD, Helen K. Suzuki, BA, Kousik Krishnan, MD, Andrew T. Lawrence, MD and Janet M. Haw, RN, BSN. Rush University, Chicago, IL.

Page 2: Poster Session 1

Poster 1 S107

Introduction: Our objective was to compare data from left ventricular (LV) unipolar and bipolar leads in order to determine if use of bipolar leads helps eliminate diaphragmatic stimulation (DS) and improves chronic LV pacing thresholds. Methods: We retrospectively reviewed data from 195 patients implanted with Boston Scientific LV leads and compared the two groups of patients. The Unipolar (UP) Group were implanted with a unipolar LV lead, the EasyTrak. The Bipolar (BP) Group were implanted with a bipolar LV lead, the EasyTrak 2 or 3. We analyzed and compared the incidence of clinically significant DS, the number of device interrogations with reprogramming required to eliminate the DS, the incidence of lead revisions, and the chronic LV pacing thresholds between the two groups. Results: 86 patients were included in the UP group and had a mean follow-up of 693 ± 439 days. 109 patients were included in the BP group and had a mean follow-up of 318 ± 245 days. 11 UP patients (12.8%) and 20 BP patients (18.4%) experienced clinically significant DS (p=NS). The DS was eliminated by reprogramming in 9/11 (81.8%) UP patients and 17/20 (85%) BP patients (p=NS). The median number of visits required to eliminate the DS was 2 in the UP group and 1 in the BP group (p<.05). Chronic LV pacing thresholds were available and were ≤ 2V at 0.5ms in 54/83 patients (65.1%) in the UP group and in 79/99 patients (79.8%) in the BP group (p<.03). Lead revision was required in 3/86 (3.5%) UP patients and 6/109 (5.5%) patients in the BP group (p=NS). One patient in the BP group required a lead revision due to DS. There were 2 patients in each group whose DS could not be totally eliminated. These patients were reprogrammed so that the DS was clinically tolerable. Conclusions: The need for LV lead revision, the occurrence of DS, and the elimination of DS by device reprogramming was similar in both groups. Bipolar leads required fewer reprogramming visits to totally eliminate DS and had superior chronic LV pacing thresholds. The superiority of bipolar LV pacing thresholds has important implications for device longevity and may counterbalance the increased cost of implantation. PO1-3 SHOCK IMPEDANCE TRENDS PROVIDE INFORMATION ON HEART FAILURE Tammi M. Wicks, RN, BSN, Rosemarie T. Hesser, RN and Behzad B. Pavri, MD. Thomas Jefferson University, Philadelphia, PA. Introduction: Implantable cardioverter-defibrillators (ICDs) routinely measure impedance to current flow across the shocking pathway as an assessment of system integrity. This is performed daily by all devices, and some ICDs calculate a weekly average and plot it as a as the Shocking Impedance Trend. This measurement occurs from the RV coil to the ICD can + SVC coil, and incorporates tissues around the heart, including the lung fields. Only one manufacturer provides additional filtering and signal processing based on this data, and reports it as a measure of "lung wetness", but, every ICD is capable of measuring shocking impedance. Methods: NA Results: We have anecdotally noted that in some patients who experienced heart failure (CHF) exacerbations, the shocking impedance trends showed a distinct and easily recognizable "dip" that coincided with the CHF exacerbation (see figure). We have also noted that during hospitalization for diagnoses other than heart failure, such a "dip" in the shock impedance trend was not observed. We report on shock impedance trends in a small series of 8 patients, 4 of whom were admitted for CHF exacerbations, an 4 for non-cardiac diagnoses. The decrease in impedance was estimated at about 5-10 ohms in these 4 patients. Conclusions: Shock impedance trends reported by all device manufacturers, can demonstrate changes that reflect CHF status. Special algorithms (as provided by one manufacturer) may not always

be necessary to obtain this information. This represents a novel application of graphic data reported by many ICDs.

PO1-4 CA2+/CALMODULIN-DEPENDENT PROTEIN KINASE II INHIBITOR ABOLISHES AND PREVENTS TRIGGERED ACTIVITY IN MYOCYTES FROM RYR2R4496C+/-KNOCK-IN MICE Nian Liu, MD, Barbara Colombi, PhD, Carlo Napolitano, MD and Silvia G. Priori, MD, PhD. Molecular Fondazione Salvatore Maugeri, Pavia, Italy. Introduction: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disease characterized by life threatening arrhythmias caused by mutations in the gene encoding the cardiac ryanodine receptor (RyR2). We previously showed that delayed afterdepolarizations induced triggered activity (TA) is the likely mechanism for arrhythmias in CPVT (Liu et al Circ Res 2006). Since recent studies showed that Ca2+/calmodulin-dependent protein kinase II (CaMKII) can increase frequency of calcium sparks directly through RyR2 phosphorylation (Guo et al Circ Res 2006), we hypothesized that CaMKII may play a role in arrhythmogenesis in CPVT. Methods: Isolated ventricular myocytes from wild-type (WT) and knock-in mice harbouring the R4496C mutation (RyR2R4496C+/-) were studied with whole cell patch clamp. Results: Superfusion with caffeine (300 µmol/L) and epinephrine (200 nmol/L) failed to induce TA in WT myocytes, whereas it elicited TA in 67% of RyR2R4496C+/- myocytes (P=0.01). KN-93 (1 µmol/L),a CaMKII inhibitor, completely abolished TA (n=5) and significantly decreased the amplitude of transient inward current (n=5) in RyR2R4496C+/- cells exposed to caffeine and epinephrine (P=0.05). Additionally, when RyR2R4496C+/- cells were pre-treated with KN-93 (1 µmol/L) caffeine and epinephrine could no longer induce TA. Conclusions: We suggest that CaMKII plays an important role in the arrhythmogenesis in CPVT and the inhibition of CaMKII signalling pathway may represent a promising therapeutic strategy in CPVT.

Page 3: Poster Session 1

S108 Heart Rhythm Vol 4, No.5 May Supplement 2007

PO1-5 MODEST REDUCTION IN CARDIAC CALSEQUESTRIN INCREASES SARCOPLASMIC RETICULUM CA2+ LEAK AND RENDERS MICE SUSCEPTIBLE TO VENTRICULAR ARRHYTHMIA Nagesh Chopra, MD, Prince J. Kannankeril, MD, Tao Yang, PhD, Thinn Hlaing, MD, Kristen Ettensohn, BS, Karl Pfeifer, PhD, Brandy Akin, BS, Larry R. Jones, MD, PhD, Clara Franzini-Armstrong, PhD and Bjorn C. Knollmann, MD, PhD. Vanderbilt University, Nashville, TN, Washington Hospital Center, Washington, DC, NICHD/NIH, Bethesda, MD, Krannert Institute of Cardiology, Indianapolis, IN and University of Pennsylvania, Philadelphia, PA. Introduction: Deletion of cardiac calsequestrin (Casq2) causes polymorphic VT in mice akin to humans with CASQ2 mutations. However, other sarcoplasmic reticulum (SR) proteins (e.g. triadin-1 and junctin) are also reduced in homozygous Casq2-/- mice and may contribute to their arrhythmia phenotype. Here, we examined the effect of a less severe loss of Casq2. Methods: Heterozygous (Casq2+/-) mice displaying a 25% reduction in Casq2, but no significant decrease in other SR proteins (triadin-1, junctin, RyR2, SR Ca2+ ATPase) were compared with age and sex matched Casq2+/+ littermates using electron microscopy, Ca2+ fluorescence, cell shortening and L-type Ca2+ current measurements in ventricular myocytes; and ECG recordings during catecholamine challenge and programmed stimulation in vivo. Results: Field-stimulated Ca2+ transients, cell shortening, L-type Ca2+ current and SR volume were not significantly different in Casq2+/- and Casq2+/+ myocytes. However, in presence of isoproterenol SR Ca2+ leak was significantly increased in Casq2+/- myocytes (Casq2+/- 0.18±0.18 Fratio vs. Casq2+/+ 0.11±0.10 Fratio, n=57, 60; p=0.01), resulting in a significantly higher incidence of spontaneous SR Ca2+-releases and triggered beats (Casq2+/- 0.38±0.49 vs. Casq2+/+ 0.12±0.33, n=47, 34; p=0.007). When challenged with isoproterenol in vivo, Casq2+/- mice (n=31) displayed 3-fold higher rates of PVCs than Casq2+/+ mice (n=35; pCasq2+/- mice than in Casq2+/+ mice (episodes/mouse: 17 ± 11 vs. 2 ± 2, n=7, 6; p=0.007). Conclusions: Even isolated modest reductions in Casq2 protein can increase SR Ca2+ leak and cause VT susceptibility. This could explain the increased risk for ventricular arrhythmias in humans heterozygous for CASQ2 mutations.

PO1-6 VISUALIZING 3D CARDIAC ANATOMY MRI DATA WITH PARA-CELLULAR RESOLUTION Christopher E. Goodyer, PhD, Jürgen E. Schneider, PhD, Rebecca A. Burton, MS, Ken Brodlie, PhD and Peter Kohl, MD, PhD. University of Leeds, Leeds, United Kingdom and University of Oxford, Oxford, United Kingdom. Introduction: Homogenous cardiac performance arises from concerted electro-mechanical activity in a highly heterogeneous substrate [1]. Detailed insight into the micro-structural make-up of the heart would be of tremendous utility for understanding the patho-physiological relevance of cardiac heterogeneity. Methods: An interactive visualization tool has been developed, capable of handling high-resolution continuous 3D anatomical MRI data, obtained from a rabbit whole heart [2] (1.5 x 109 voxels, each 26.5 x 26.5 x 24.5 µm). Isosurface and slicing techniques are implemented in an OpenGL application, run on a 7-node cluster powering 28 LCD displays. Surface thresholding and smoothing are precomputed to reduce the dataset to 45 million triangles, thus supporting real time translation, rotation and zooming. Results: Data can be presented on single or multi-panel displays (Fig. 1), allowing users to navigate cardiac anatomy from para-cellular detail to whole-heart. Viewing trajectories can be stored and individual view planes or sequences exported for annotation, analysis or filing, with positional information shown in a 3D cardiac thumbnail. Conclusions: Novel visualization environments are needed to realise the vast potential of modern high-resolution non-invasive imaging modalities. These tools make examination of complex organ structures possible by showing 3D histo-anatomy and allowing superimposition of graphical and textual information, somewhat similar to landscape rendering by 'Google Earth', only the exploration is not limited to outer surfaces.

Page 4: Poster Session 1

Poster 1 S109

Fig. 1: Detail of 53 megapixel display, showing baso-apical inside view of left ventricle with chordae tendinae (CT) projecting �upwards� from papillary muscle (PM); note detail such as free-running Purkinje fibres (PF). [1] Katz AM & Katz PB. Circulation 1989/79:712-717 [2] Burton RAB et al., Ann N Y Acad Sci 2006/1080:301-319 PO1-7 THE ROLE OF EPICARDIUM-DERIVED-CELLS IN ATRIO-VENTRICULAR ISOLATION: IMPLICATIONS FOR AV-REENTRANT TACHYCARDIAS Denise P. Kolditz, MSc, Maurits C. Wijffels, MD, PhD, Arnoud Van der Laarse, MD, PhD, Roger R. Markwald, MD, PhD, Adriana C. Gittenberger-De Groot, PhD and Martin J. Schalij, MD, PhD. Leiden University, Leiden, The Netherlands and Medical University of South Carolina, Charleston, SC. Introduction: During embryonic heart development, the ventricular activation sequence changes from a base-to-apex to an apex-to-base pattern, which reflects maturation of the His-Purkinje system and formation of the annulus fibrosis. The aim of this study was to investigate the role of Epicardium-Derived-Cells (EPDCs) in formation of the isolating fibrous annulus. Methods: In quail embryos, EPDC migration was inhibited by in-ovo microsurgery on the 3rd day of incubation (HH15-18). Ventricular activation patterns were analyzed by extracellular recordings in 40 wild-type (HH38-41) and 8 EPDC-inhibited (HH38-41) post-septated embryonic hearts. Additionally, in-ovo ECGs were recorded in 6 wild-type and 6 EPDC-inhibited hearts. Electrophysiological data was correlated with morphology (MLC2a). Results: While the ventricular apex was the location of earliest ventricular activation in 22/40 (55%) of wild-type hearts (HR 110±18 bpm, AV-interval 77±25 ms), only 2/8 (25%) of EPDC-inhibited hearts (HR 140±36 bpm, AV-interval 73±26ms) showed an apex-first ventricular activation pattern (p=0.039). The vast majority (6/8; 75%) of the EPDC-inhibited hearts showed earliest ventricular activation at the ventricular base. Moreover, the PR-interval in in-ovo ECG recordings was significantly shorter in EPDC-inhibited (53±11 ms) versus wild-type (62±11 ms) hearts (p=0.003). Morphologically, EPDC inhibition was related to marked isolation defects of the annulus fibrosis. Although several small persistent accessory myocardial AV-

connections can still be found in wild-type hearts, these AV-connections were much broader in EPDC-inhibited embryos. Conclusions: Although AV-conduction through small remnants of myocardial AV-connections remains possible in post-septated embryonic wild-type quail hearts at near-hatching (HH44) stages of development, inhibition of EPDC-migration results in marked defects of the annulus fibrosis. These persistent broad accessory AV-connections were related to premature activation of the ventricular base and may provide a substrate for persistent reentrant arrhythmias in later postnatal life. PO1-8 SEIZURES AND TYPE 2 LONG QT SYNDROME (LQT2): EVIDENCE FOR A NOVEL PHENOTYPE-GENOTYPE ASSOCIATION Jonathan N. Johnson, MD, Carla M. Haglund, BA, Nynke Hofman, MSc, Arthur A. Wilde, MD, PhD and Michael J. Ackerman, MD, PhD. Mayo Clinic College of Medicine, Rochester, MN and University of Amsterdam, Amsterdam, The Netherlands. Introduction: Long QT syndrome (LQTS) typically presents with syncope, seizures, or sudden death. Patients with LQTS have been misdiagnosed with epilepsy and treated with anti-epileptic medications. The gene KCNH2, responsible for type 2 LQTS (LQT2), was originally cloned from the hippocampus and encodes a potassium channel active in hippocampal astrocytes. Here, we sought to test the hypothesis that seizures occur more commonly in patients (pts) with LQT2. Methods: Phenotypic data was extracted for 212 consecutive, unrelated pts (144 females, average age at diagnosis, 24 + 16 years, QTc, 466 + 50 ms) clinically evaluated and genetically tested for LQTS at Mayo Clinic between 1998 and 2006. Each pt was classified as either i) Genotype Positive LQTS (N = 109), ii) Genotype Negative LQTS (N = 31), or iii) Normal (i.e. Genotype Negative/Phenotype Negative, N = 72). A positive seizure phenotype was defined as the presence of either a personal or family history of seizures/epilepsy or history of treatment for seizures/epilepsy. Results: Overall, a positive seizure phenotype (personal history in 31, family history in 29, and treatment history in 10) was recorded in 54/212 (25%) pts including 38/140 (27%) with LQTS and 16/72 (22%) Normals (p = NS). Genotype-specific analysis revealed that a positive seizure phenotype was more common in LQT2 (18/43, 42%) than LQT1 (9/48, 19%, p = 0.02). In addition, a personal history of seizures was more common in LQT2 than all other subtypes of LQTS (26% vs 6%, p = 0.008). Among the LQT2 pts, 11 had been diagnosed with seizures and 4 had received anti-epileptic medications. This seizure phenotype/LQT2 genotype association was validated in an independent cohort comprised of 81 unrelated pts with genetically proven LQTS. Conclusions: A positive seizure phenotype was more common in LQT2. Like non-cardiac organ phenotypes observed in other subtypes of LQTS such as LQT1/deafness and LQT3/gastrointestinal symptoms, this novel LQT2-seizure association raises the possibility that LQT2-causing perturbations in the KCNH2-encoded potassium channel may confer susceptibility for true neuro-mediated seizures. PO1-9 MUTATION SCREENING OF PKP2 GENE IN SEVERE FORM OF ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY Elzbieta K. Wlodarska, MD, PhD, Giorgia Beffagna, PhD, Olgierd Wozniak, MD, Elzbieta Czarnowska, PhD, Cristina Basso, MD, FRCP, Kalliopi Pilichou, PhD, Piotr Hoffman, MD, FRCP, Gaetano Thiene, MD, FRCP, Gian Antonio Danieli, MD, FRCP and Alessandra Rampazzo, PhD. Institute of Cardiology, Warsaw, Poland, University of Padua, Padua, Italy and Children's Memorial Health Center, Warsaw, Poland.

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S110 Heart Rhythm Vol 4, No.5 May Supplement 2007

Introduction: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease characterized by fibrofatty replacement and electrical instability of myocardium, both leading to ventricular dysfunction and life-threatening arrhythmias. Many forms of ARVC are due to mutations in genes coding for desmosomal proteins; a high percentage of ARVC patients (pts) was found to carry a mutation in plakophilin-2 (PKP2) gene. The aim of present study was to evaluate prevalence of PKP2 mutations in a series of pts with severe form of ARVC. Methods: Mutation screening of PKP2 gene was performed in 25 (21 males, 4 females) probands with severe form of ARVC (extensive RV damage and/or life threatening arrhythmias) by denaturing high-performance liquid chromatography and direct DNA sequencing. Results: Fourteen unrelated pts (56%) carried a PKP2 mutation. Ten different mutations were identified: two missense (S140F, A372P), two nonsense (R413X, Q638X), two splicing-site (2146-1G>C, 2489+1G>A) and four insertion/deletion (S50fsX110, E257fsX262, W318fsX327, E809fsX826). These nucleotide changes were absent in 200 control chromosomes. Three mutations were found more than once and one proband resulted to carry two different PKP2 mutations. Clinical study in all subjects with PKP2 mutation demonstrated ventricular arrhythmias consisting of ventricular fibrillation/sustained ventricular tachycardia (VTs) in 7 pts, VTs with syncope in 3 pts and non sustained VT/isolated premature ventricular beats in 3 pts. All pts had a severe form of the disease, except one showing moderate intensity of symptoms but with family history of two cases of sudden cardiac death and a first-degree relative with severe form of ARVC. End-stage heart failure leading to heart transplantation was observed in one pt. Left ventricular involvement was present in two cases. Conclusions: 1/Mutations in plakophilin-2 gene can be found in more than half of patients with severe form of ARVC. 2/Severe arrhythmias dominate in a clinical expression of ARVC caused by PKP2 mutations. PO1-10 REGIONAL MYOCARDIAL STRETCH INDUCES COMPARABLE CHANGES IN ECG AND IN TRANSCRIPTIONAL PATHWAYS TO THOSE OF PACING-INDUCED CARDIAC MEMORY Nazira Ozgen, MD, PhD, Alexei N. Plotnikov, MD, Iryna N. Shlapakova, MD, Heather S. Duffy, PhD, Peter Danilo, Jr., PhD and Michael R. Rosen, MD. Columbia University, New York, NY. Introduction: Short-term cardiac memory (CM), induced by 2 hrs of ventricular pacing (VP), initiates degradation of the cAMP response element binding protein (CREB), resulting in a transcriptional decrease of the KChIP2 channel subunit that modulates the transient outward current, Ito. CREB reduction appears to result from down-regulation of protein phosphatase1γ (PP1γ) causing CREB hyperphosphorylation which appears necessary for its subsequent proteosomal degradation. In addition, there is a gradient of change in connexin43 (Cx43) protein which is maximally reduced near the pacing site and may contribute electrotonically to altered repolarization in CM. Hypothesis: Pacing-induced CM results from the effect of altered activation to alter stretch. Methods: A device that alters stretch without affecting activation was sewn to the left ventricular anterior epicardium (n=3) and 4hrs of constant stretch (22% stretch increase) was applied during atrial pacing at 150 bpm. CM was quantified as T wave vector displacement (TVD). Epicardial biopsies were taken before stretch (Ref) and at 4hrs of stretch, near to and far from the site of stretch. CREB and PP1γ protein was measured via western blot in nuclear and cytosolic cell fractions, while whole cell lysates were used to detect total Cx43

levels. Immunofluorescence staining of pCREB was performed using DAPI as a nuclear marker. Results: At 4h stretch, TVD = 22+/-0.6 mV (SE) and nuclear CREB and PP1γ proteins decreased vs. Ref. In immunofluorescence studies pCREB was mainly intranuclear before stretch while at 4hrs stretch, its cytosolic distribution increased. Cx43 was significantly lower in the stretched than the distant site (0.29+/-0.04 vs 0.87+/-0.23 AU, p Conclusions: Stretch-induced changes in TVD, CREB, PP1γ and Cx43 are consistent with those previously found in pacing-induced CM. This result strongly suggests that CM induction results from pacing-induced alter stretch. PO1-11 ELECTRICAL CELL-TO-CELL COUPLING IN PATTERNED PAIRS OF MURINE AND RAT VENTRICULAR MYOCYTES Thomas Desplantez, PhD, Nicolas Geisse, PhD, Lisa Krapf-Renfer, MS, Andreas Werdich, PhD, Kevin K. Parker, PhD and Andre G. Kleber, MD. University of Bern, Bern, Switzerland, Harvard University, Cambridge, MA and Vanderbilt University, Nashville, TN. Introduction: The effect of heterogenous variation of connexin43 (Cx43) expression on electrical coupling between ventricular myocytes (VM) has not yet been analyzed. In this work, we present a new method to analyze the effect of a variation of Cx43 expression on electrical cell-to-cell coupling. Methods: Murine and rat neonatal ventricular myocytes were seeded on an extracellular growth substrate. The patterns of cell pairs were created by a CAD program and transferred to a mask that was subsequently used to fabricate a silicon wafer showing the negative template of required cell structures. High precision silicon elastomer (PDMS) stamps made from the wafer templates by soft-lithography were covered with fibronectin. After 3 to 5 days of growth, cell pairs with the pre-determined cell shape and a common membrane area were obtained. At this stage, the cells showed a marked degree of differentiation as verified by 3-D atomic force microscopy. Intercellular electrical conductance gj,0, voltage dependence of intercellular conductance (half maximal inactivation voltage, Vj,0, minimum conductance gj,min), and single channel conductances were obtained by dual voltage clamp. Results: Normal pairs of rat and murine myocytes showed a gj,0 of 31±4.9 nS (n=9) and 27±7.8 nS (n=3), respectively. Murine Cx43+/+ and Cx43-/- VMs (genetic Cx43 ablation) were mixed at equal quantities. The Cx43+/+/Cx43-/- cell pairs had a gj,0 of 5.6±6.9 nS (n=4) and a typical asymmetrical dependence of gj on transjunctional voltage. In one cell pair, showing a combination of Cx43-/-/Cx43-/- (verified by analysis of single channel conductances) gj,0 was 0.5 nS. Conclusions: 1. Intercellular conductances of normal neonatal VM pairs from rat and mice are closely similar. 2. Intercellular conductance between genetically heterogenous murine cells is largely determined by the cell showing Cx43 ablation. 3. The histograms of single channel conductances in Cx43+/+/Cx43+/+ and Cx43+/+/Cx43-/-

cell pairs are similar, due to the presence of heteromeric connexons in one or both cells, respectively. PO1-12 SHOCK-INDUCED VIRTUAL ELECTRODES IN A MICRO-ANATOMICALLY ACCURATE WEDGE MODEL Thushka Maharaj, MSc, Blanca Rodriguez, PhD, Gernot Plank, PhD, Anton J. Prassl, MS, Tahir Mansoori, MSc, Vicente Grau, PhD, Peter Kohl, MD, PhD, David Gavaghan, PhD and Natalia A. Trayanova, PhD. Oxford University, Oxford, United Kingdom, Johns Hopkins University, Baltimore, MD, Department of Engineering Science, Oxford, United Kingdom and University of Oxford, Oxford, United Kingdom.

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Introduction: Cardiac microstructure has been hypothesized to play a role in defibrillation, however, its contribution has not been fully evaluated yet. Of particular importance is the structure-dependent virtual electrode polarization (VEP) induced by the shock since it gives rise to postshock activations and sets up the stage for shock outcome. The present study examines VEP in a micro-anatomically accurate rabbit ventricular wedge. Methods: A finite-element bidomain microstructure model of LV wedge from rabbit ventricles (0.53x0.53x0.49cm3) was developed (Fig, A) from high-resolution (25µm) MRI scans (11.7 T), segmented to obtain microstructure detail. An octree-based meshing technique was applied. Elements at locations of nonmyocardial tissue were removed from the mesh, and Neumann boundary conditions were enforced in the interstitial space. The region extending above the endocardium was assigned properties of blood. The wedge was paced epicardially, and 10ms truncated exponential shocks were applied via external electrodes (Fig, A). Results: The epicardium is positively polarized due to proximity to the cathode, while the endocardium exhibits complex VEP with positively polarized bridge structures in close proximity to negatively polarized surface layers (Fig. B). Due to sharp transmembrane potential gradients at junctions between tissue base and bridge structures, numerous post-shock activations originate there and spread through negative VEP layers (excitable areas). In contrast, while intramural tissue exhibits significant small scale VEP at tissue discontinuities, transmembrane potential gradients are low, thus activations are less likely to originate intramurally. Conclusions: We suggest a new mechanism for the origin of postshock activations that might hold the key to understanding the delayed appearance of postshock activations on the epicardium.

PO1-13 SUBEPICARDIAL PHASE-0 BLOCK AND DISCONTINUOUS TRANSMURAL CONDUCTION UNDERLIE RIGHT-PRECORDIAL ST-SEGMENT ELEVATION IN BRUGADA SYNDROME BY A NOVEL C-TERMINAL SCN5A MUTATION Marketa Bebarova, MD, PhD, Tom O´hara, MS, Jan L. Geelen, PhD, Roselie J. Jongbloed, PhD, Carl Timmermans, MD, PhD, Yvonne H. Arens, MD, PhD, Luz-Maria Rodriguez, MD, PhD, Yoram Rudy, PhD and Paul G. Volders, MD, PhD. Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands and Massachusetts General Hospital, St. Louis, MO. Introduction: Two mechanisms are considered to explain right-precordial ST-segment elevation in Brugada syndrome (BrS): (1) right-ventricular (RV) subepicardial action-potential shortening and/or loss of dome; (2) RV conduction delay, whether or not due to

concealed structural abnormalities. Both mechanisms favor reentrant excitation. Here we report novel insights from the C-terminal SCN5A mutation F2004L, detected in a Dutch kindred. Methods: Functional consequences of this mutation were studied in transfected Chinese hamster ovary cells by whole-cell patch clamping. Markov models of wild-type (WT) and mutant Na+ channels were incorporated in Luo-Rudy model cells assembled into a transmural RV �wedge�. Results: The proband, a 26-year old male, experienced syncope and had coved-type ST-segment elevations in ECG leads V1 and V2. QRS width was 135 ms. Peak and persistent Na+ current (INa) was decreased by the mutation (to 54% and 56%, respectively; Vhold -120 mV). INa closed-state inactivation was increased (0.30±0.03 vs. 0.16±0.02 in WT), slow inactivation accelerated (tau 12.9±1.6 s vs. 24.6±2.6 s in WT), and recovery from inactivation delayed (fast tau 49±8 ms vs. 20±4 ms in WT at Vhold -80 mV). In the transmural RV wedge model, the excitation wave was decremental from endo- to epicardium, and eventually died out at cycle length (CL) 1000 ms (but not at CL 300 ms). Propagation continued, however, by phase-2 conduction causing long delays of excitation and slow upstrokes at the epicardium. We postulate that the observed transmural decrement and subepicardial phase-0 block was caused by a gradual decrease of INa (slow depolarization → increased closed-state inactivation) and the physiological increase of transient outward K+ current towards the epicardium. Conclusions: Our data explain right-precordial ST-segment elevation on the basis of massive RV transmural voltage gradients during early repolarization caused by discontinuous conduction. Reentry-based tachycardia could be evoked during conditions that exaggerate conduction block in this BrS phenotype. PO1-14 APEX-BASE HETEROGENEITIES OF PHYSIOLOGICAL APD RESTITUTION KINETICS (RK): COMPARISON OF SYMPATHETIC NERVE STIMULATION (SNS) TO PACING Rajkumar Mantravadi, MRCP, Bethann Gabris, BS, Waldo Ortin, DVM, William Degroat, PhD, G. Andre Ng, PhD, FRCP and Guy Salama, PhD. University of Leicester, Leicester, United Kingdom and University of Pittsburgh, Pittsburgh, PA. Introduction: The steepness of APD RK curve and repolarization gradients have been linked to arrhythmia vulnerability. Yet, spatial (apex-base) heterogeneities of �physiological� APD RK [APD vs. diastolic interval (DI) during sympathetic nerve stimulation (SNS) rather than pacing] have not been reported. Methods: APDs were optically mapped from 256 sites on the left ventricle (LV) of isolated rabbit hearts with intact sympathetic innervation using di4ANEPPS. Sympathetic nerves in the spinal cord were stimulated (15 V,15 Hz) until maximum steady state heart rate (HR) was reached and stopped for HR to recover. The hearts were then paced with the identical activation intervals obtained during SNS. APD vs. DI were plotted during SNS and compared to plots obtained by pacing. ∆APD = APDmax - APDmin were averaged for sites at the base and apex of the LV, expressed as Mean ± SEM ;t-test was used to compare apex-base RK. Results: During SNS, HR reached a maximum of 221±7beats/min: at the apex, APD shortened from 206 ±12 to157±6 ms (∆APD =48±7 ms); at the base APD shortened significantly more - 218± 8 to154±8 ms, (∆APD =64±8 ms) (n=6, pKs blocker, HMR 1557 (0.5 µM) abolished RK differences during SNS consistent with reports of IKs current accumulation, especially during beta-adrenergic activation. Conclusions: Differences in RK loops suggest that apex-base heterogeneity are due to a) higher IKs and b) greater sympathetic nerve inputs, at the base than the apex. Both mechanisms would tend to shorten APD at the base more than the apex during SNS, not seen with pacing.

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PO1-15 IKUR BLOCK PROMOTES ATRIAL FIBRILLATION IN �HEALTHY� CANINE ATRIA Alexander Burashnikov, PhD and Charles Antzelevitch, PhD. Masonic Medical Research Laboratory, Utica, NY. Introduction: The ultra-rapid delayed rectified potassium current (IKur), carried by Kv 1.5 channels encoded by the KCNA5 gene, is present in atria, but not ventricles. Block of IKur is thought to be a promising approach for atrial-specific therapy of atrial fibrillation (AF). However, recent reports have associated KCNA5 loss-of-function mutations with familial AF. Our objective in this study was to use low concentrations of 4-aminopyridine (4-AP, 10-50 µM), known to fairly specific for block of IKur, to assess the pro- and antiarrhythmic effects of IKur block in �healthy� and �remodeled� Canine isolated coronary-perfused atria (n=22). Methods: Acetylcholine (ACh, 0.2-0.5 µM) or ischemia/reperfusion were used to acutely �remodel� the atria. Normal atria (�healthy�) display action potentials (AP) with a prominent plateau, whereas remodeled atria display triangular-shaped APs (�remodeled�). Transmembrane action potential and a pseudo-ECG were recorded. Results: In �healthy� atria, 4-AP prolonged AP duration at the level of 20% repolarization (APD20; from 5±3 to 42±19 ms; p90, from 201±17 to 179±12 ms, p90 or ERP in �remodeled� atria (n=14; p=n.s.). Premature electrical stimulation (PES) failed to induce AF in untreated �healthy� atria (0/8), but was successful in inducing non-sustained AF (≤ 3 sec duration) in 50% of atria (4/8) treated with 4-AP (10-50 µM). PES induced non-sustained and/or persistent AF in 11/14 ACh- or ischemia-�remodeled� atria. 4-AP (25-50 µM) did not terminate persistent AF or prevent the initiation of AF in �remodeled� atria. Higher concentrations of 4-AP (100-200 µM), known to also block Ito, prevented and/or terminated AF in 4/6 �remodeled� atria. Conclusions: Our findings suggest that block of IKur can provide the substrate for development of AF in �healthy� Canine atria, presumably via a significant abbreviation of ERP. These observations advance our understanding of why KCNA5 loss-of-function mutations lead to the development of AF.

PO1-16 PIOGLITAZONE, A PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-Γ AGONIST, ATTENUATES ATRIAL FIBROSIS AND ATRIAL FIBRILLATION PROMOTION DUE TO CONGESTIVE HEART FAILURE IN RABBITS Masayuki Shimano, MD, Yasuya Inden, MD, PhD, Yukiomi Tsuji, MD, PhD and Toyoaki Murohara, MD, PhD. Nagoya University, Nagoya, Japan. Introduction: Background: Atrial structural remodeling contributes to the maintenance of atrial fibrillation (AF) in the setting of congestive heart failure (CHF) and angiotensin II (AII) is an important mediator in CHF structural remodeling. We evaluated the effects of pioglitazone on CHF-related structural remodeling and AF promotion and compared with AII type 1 receptor blocker, candesartan (CAN) in an experimental model. Methods: Rabbits were subjected to ventricular tachypacing (VTP, 380-400 bpm for 4 weeks) to create CHF. Rabbits were divided into 5 groups: non-paced controls (CTL, n=15), VTP only (n=15), VTP plus either PIO (5mg/kg/day, n=15) or CAN (2mg/kg/day, n=15), and VTP plus both PIO and CAN (n=15), which started 2 weeks before, and continued during VTP. Electrophysiological studies, atrial fibrosis measurement and atrial cytokine expression studies were performed. Results: Mean duration of burst pacing-induced AF (DAF) was increased after 4 weeks of VTP. Treatment with PIO decreased VTP-induced DAF and attenuated atrial structural remodeling with significant reductions in intra-atrial conduction time and atrial interstitial fibrosis, which were a level comparable to CAN (Table). VTP increased expressions of transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α) and mitogen-activated protein kinases (ERK, p38 and JNK). Treatment with either PIO or CAN significantly reduced TGF-β1, TNF-α and ERK similarly, but neither affected p38 or JNK. The combination of PIO and CAN tended to have additive effects against atrial structural remodeling, AF promotion and cytokine expressions, but not statistically significant. Conclusions: Pioglitazone attenuated CHF-induced structural remodeling and AF promotion in rabbits, equivalent to candesartan. This finding suggests that PPARγ might be a potential therapeutic target for preventing AF substrate in patients with CHF.

*p group CTL VTP PIO CAN PIO&CAN

DAF 0.6±0.1 8.1±0.7* 3.2±0.3*� 2.7±0.3*� 2.4±0.2*�

Intra-Atrial CT 29±1 50±2* 41±2*� 44±2*� 41±1*�

LA-ERP (ms, at BCL 300 ms)

103±3 116±4 113±4 111±3 109±3

%fibrosis in LA 1.6±0.2 16.8±0.8* 10.9±0.7*� 9.4±0.6*� 8.6±0.6*� PO1-17 RANOLAZINE PREVENTS CLOFILIUM-INDUCED TORSADE DE POINTES IN RABBITS Wei-Qun Wang, MD, Edith Munoz, BSc, Arvinder K. Dhalla, PhD and Luiz Belardinelli, MD, PhD. CV Therapeutics, Palo Alto, CA. Introduction: Ranolazine (RAN), a novel anti-ischemic and antianginal agent, has been shown in various pre-clinical models to have anti-arrhythmic effect. RAN has been shown to inhibit late INa and IKr. Specifically, RAN has been shown to suppress EADs and trigger activity in myocytes and Purkinje fibers caused by IKr inhibitors, despite the fact that RAN itself is an IKr inhibitor. This study was undertaken to investigate the effects of RAN on clofilium-induced Torsade de Pointes (TdP) in vivo.

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Methods: Spontaneous TdP was induced with methoxamine (α1-adrenoceptor agonist) followed by clofilium (IKr blocker) in anesthetized rabbits as previously described by Carlsson et al (J.Cardiovas.Pharmacol 1990;16:276-285). RAN was given via iv infusion 10 min prior to clofilium. Arterial pressure (BP), ECG and endocardial monophasic action potential (MAP) were recorded. The QT interval was corrected for heart rate using a formula developed for rabbits: QTc=QT-0.175*(RR-300). Results: Clofilium prolonged QTc (130 ± 4 to 200 ± 18 ms, n=6, P90 (123 ± 6 to 201 ± 21 ms, n=6, P50 values of 10, 15 and 10 µM, respectively. RAN at 25 µM completely prevented the occurrence of TdP (0/6, Pvs vehicle) without a significant effect on heart rate, PR, QRS and QTc intervals (186 ± 9 to 204 ± 10 bpm, 79 ± 2 to 77 ± 1 ms, 32 ± 1 to 33 ± 1 ms and 148 ± 5 to 165 ± 7 ms, n=5, P>0.05, respectively). Because RAN has been reported to have weak α1- adrenoceptor antagonistic activity, we compared the effects of RAN on BP to that of prazosin. While the α1-antagonist prasozin at 5µg/kg/min (n=5) markedly shifted the phenylephrine (α1-agonist) dose-response curve to the right by 6 fold, prasozin (2.5-10µg/kg/min, n=4-6) did not have any effect on clofilium-induced prolongation of QTc and MAPD90 or the occurrence of TdP. RAN, on the other hand, completely suppressed TdP but did not cause any shift in phenylephrine dose-response at the highest dose tested (25µM). Conclusions: The data show that RAN antagonizes the ventricular repolarization changes caused by clofilium and suppresses clofilium-induced TdP in rabbits. PO1-18 INITIAL EXPERIENCE WITH AN 8 MM TIP CRYOCATHETER FOR SLOW PATHWAY MODIFICATION IN AV NODAL REENTRANT TACHYCARDIA (AVNRT) Frederic Dumont, MD, Paul Khairy, MD, PhD, Peter G. Guerra, MD, Mario Talajic, MD, Jean-Francois Roux, MD, Bernard Thibault, MD, Denis Roy, MD, Laurent Macle, MD and Marc Dubuc, MD. Montreal Heart Institute, Montreal, Quebec, Canada. Introduction: Cryoablation is a safe and effective treatment modality for AVNRT. However, concerns over recurrences and procedural times have been expressed with smaller standard-tip catheters. In this pilot study, we tested the safety and feasibility of AV nodal slow pathway modification using an 8 mm tip cryocatheter. Methods: At the Montreal Heart Institute, 30 consecutive patients (age 48.6±13.6 years; 14 women) with typical AVNRT were prospectively enrolled in a protocol assessing cryoablation with an 8 mm tip cryocatheter (Freezor® Max, CryoCath, Montreal, Canada) between March and December 2006. After standard electrophysiology testing confirming the diagnosis of typical AVNRT, an 8 mm tip cryocatheter was initially positioned in the lower third of Koch�s triangle in a combined anatomic and signal-guided approach. The AH interval and effect on slow pathway conduction was closely monitored throughout each cryoapplication. If non-inducibility without AH interval prolongation was achieved, the cryoapplication was pursued for a total of 4 minutes. Results: Acute success was obtained in all 30 patients with a median of 4 cryoapplications that included a median of 2 complete 4-minute lesions, for a median cryoablation time of 9.6 minutes. The median fluoroscopy time was 8.4 minutes and mean procedural duration 1.7±0.8 hours. Thirteen patients (43.3%) had residual slow pathway conduction, with no echo beats in 5 (16.7%) and single echo beats in 8 (26.7%). No patient experienced pain during cryoablation and no complication was noted, with the exception of transient 2:1 AV block in one patient. No patient experienced documented supraventricular tachycardia or recurrent palpitations at a median follow-up of 66 days (range 0 to 206 days). Conclusions: The 8 mm Freezor® Max catheter appears safe and highly effective for ablating typical AVNRT. Long-term efficacy

remains to be compared to standard-tip cryocatheters and conventional RF catheters. PO1-19 UNIQUE ELECTROPHYSIOLOGICAL CHARACTERISTICS OF �IRREGULAR� ATYPICAL ATRIOVENTRICULAR NODAL REENTRANT TACHYCARDIA Kiyoshi Otomo, MD, Kikuya Uno, MD, PhD, Yasutoshi Nagata, MD, Keita Handa, MD and Yoshito Iesaka, MD, PhD. Tsuchiura Kyodo Hospital, Tsuchiura, Japan. Introduction: Atrioventricular (AV) nodal reentrant tachycardia (AVNRT) usually exhibits a constant 1:1 AV relationship. Atypical AVNRT rarely exhibits transient variations in AV relationship during tachycardia; however, the incidence and electrophysiological characteristics of atypical AVNRT exhibiting variable AV relationships have not been fully elucidated. This study was performed to assess the incidence and electrophysiological characteristics of atypical AVNRT with variable AV relationship. Methods: The electrophysiological data were reviewed in 53 consecutive patients (pts) who underwent catheter ablation for atypical AVNRT. Results: Among 67 atypical AVNRTs induced in 53 pts, 8 AVNRTs (12%) induced in 8 pts (15%) exhibited persistent episodes of continuous and simultaneous variations in the A-H, H-A, A-A and H-H intervals (variations: 139±82, 185±132, 94±80, and 232±104 msec, respectively) and Wenckebach A-H block during uninterrupted tachycardia without a change in the retrograde atrial activation sequence (�irregular AVNRT�), while the other 59 AVNRTs (88%) induced in the remaining 45 pts presented a constant AV relationship (�regular AVNRT�: slow-slow/fast-slow=28/31). The tachycardia cycle length (TCL) was significantly shorter (312±74 vs. 380±102 msec; p=0.037) and pts' mean age was significantly younger among those with irregular AVNRT than those with regular AVNRT (35±15 vs. 47±16 years; p=0.024). Catheter ablation (4±3 times) to the earliest retrograde atrial activation site (proximal coronary sinus/left inferoseptum/right inferoseptum=4/1/3 pts) eliminated the retrograde slow pathway conduction in 7 pts (88%) and rendered the tachycardia non-inducible in all 8 pts (100%). Conclusions: The variations in the AV relationship during irregular AVNRT would be attributable to the short TCL that gave rise to unstable conduction in the reentrant circuit and Wenckebach block in the lower common pathway. The left-sided ablation was required to eliminate tachycardia inducibility in about 2/3 of the pts, suggesting that the participation of the leftward AV nodal pathway was common in this entity. PO1-20 PROSPECTIVE RANDOMIZED COMPARISON OF RADIOFREQUENCY ABLATION WITH CRYOABLATION USING AN 8 MM TIP ABLATION CATHETER FOR THE ABLATION OF COMMON ATRIAL FLUTTER (CRYOTIP) Malte Kuniss, MD, Thomas Vogtmann, MD, Rudolfo Ventura, MD, Jürgen Vogt, MD, Gerian Grönefeld, MD, Stefan H. Hohnloser, MD, Bernhard Zrenner, MD, Ali Erdogan, MD, Gunnar Klein, MD, Bernd Lemke, MD, Jörg Neuzner, MD and Heinz F. Pitschner, MD. Kerckhoff-Klinik, Bad Nauheim, Germany, Charité University Hospital, Berlin, Germany, University Hospital Hamburg-Eppendorf, Hamburg, Germany, Heart Center North Rhine-Westphalia, Bad Oeynhausen, Germany, Asklepios Hospital Barmbek, Hamburg, Germany, J.W. Goethe University, Frankfurt, Germany, German Heart Center, Munich, Germany, Justus-Liebig University, Giessen, Germany, University Hospital, Hannover, Germany, Märkische Kliniken, Lüdenscheid, Germany and Klinikum Kassel, Kassel, Germany.

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Introduction: Recent studies show that pain-free cryoablation is comparable with radiofrequency (RF) ablation regarding clinical success rates and safety in the treatment of common atrial flutter (AFL). Long-term success depends on persistence of bidirectional conduction block (BCB) in the inferior cavotricuspid isthmus (CTI). Aim of this present study is to compare RF ablation to cryoablation with emphasis on acute success rates and persistence of BCB in the CTI. Methods: In this prospective multicenter trial patients were randomly assigned to ablation with RF using an 8-mm tip catheter or cryoablation with 8-mm tip (Freezor®MAX, CryoCath). Acute success rate, clinical long-term success rate and persistence of BCB were defined as primary endpoints. By now data of 163 pts has been analyzed (122m, age 63.5±9.7years). 8 pts had to be excluded, 79 pts were treated with RF, 76 pts with cryo. Cryoenergy was delivered once at each catheter tip site for 240s. The ablation endpoint was defined as complete BCB in the CTI 30 min after last energy delivery. A maximum of 30 Cryo/RF applications were allowed to achieve ablation endpoint. Persistence of BCB in the inferior CTI was controlled by repeat EP study 3 months post ablation. Results: The preliminary data show acute success rates of 92.4% in the RF group (73/79 pts) and of 93.4% (71/76 pts) in the Cryo group, respectively (p>0.05). Repeat EP study was performed in 53/73 pts treated with RF, in 45 pts (84.9%) BCB was persistent, in 8 asymptomatic pts conduction recovered, no clinical recurrence of AFL. In 52/71 pts treated with Cryo repeat EP study was performed showing persistence of BCB in 33 pts (63.5%), p=0.015. In 14 asymptomatic pts conduction recovered, 5 pts developed a recurrence of AFL. Due to a clinical asymptomatic status 20 pts in the RF group and 19 pts in the Cryo group refused repeat EP study. Conclusions: Both energy forms are showing similar acute success rates. Clinical long-term success rate and rate of persistence of BCB were significantly different with reduced efficacy concerning the long term outcome in patients treated with Cryo. PO1-21 HIGH PREVALENCE OF A NOVEL CONDUCTION PATTERN AROUND THE CORONARY SINUS IN CAVOTRICUSPID ISTHMUS DEPENDENT RIGHT ATRIAL FLUTTER Yoshio Yamaguchi, MD, Hiroichi Tsugawa, MD, PhD, Nakaba Fujioka, MD, PhD, Kenichi Kaseno, MD, PhD, Michihiko Kitayama, MD, PhD, Noboru Takekoshi, MD, PhD and Kouji Kajinami, MD, FRCP. Kanazawa Medical University, Ishikawa, Japan. Introduction: We tested our hypothesis that, in atrial flutter (AFL) dependent on the cavotricuspid isthmus (CTI), lower loop reentry (LLR) is the common pathway route at the coronary sinus (CS) posterior site, and thus, dual loop reentry (DLR) is a common circular pattern. Methods: We studied 25 patients with CTI-dependent AFL, 16 with chronic counterclockwise atrial flutter (CCW-AFL) and 9 with clockwise atrial flutter (CW-AFL) and determined the precise reentry circuitry, especially for conduction patterns around the CS orifice, using electroanatomical mapping. We measured postpacing interval and tachycardia cycle length during entrainment from sites within the flutter circuit. Results: In 16 of the 25 CCW-AFL patients, the CS anterior pacing site was within the AFL circuit in 13. The CS anterior pacing site was within the AFL circuit in 6 of the 9 CW-AFL patients. In 8 each of 16 CCW-AFL and 9 CW-AFL patients, both the CS anterior and posterior sites were within the AFL circuit. Results of 3-Dimensional (3D) activation mapping suggest that all of these patients had a DLR circuit, and that CS posterior conduction broke through the eustachian valve/ridge. Conclusions: CS posterior conduction consisted of the flutter circuit and appeared to be critical for maintaining AFL. Almost all AFL patients had DLR formed within the LLR or the superior RA circuit

constituted from CS posterior conduction and in the anterior loop around the tricuspid annulus. PO1-22 CLINICAL BENEFITS OF CURATIVE ABLATION OF ATRIAL FLUTTER IN PATIENTS WITH SEVERE LEFT VENTRICULAR DYSFUNCTION Li-Fern Hsu, MBBS, Isabel Tan, MBBS, Ruth Kam, MBBS, Kah-Leng Ho, MBBS and Bernard Kwok, MBBS. National Heart Centre, Singapore, Singapore. Introduction: Patients with severe left ventricular (LV) dysfunction are at increased risk of sudden death, the prevention of which requires an implantable cardiac defibrillator (ICD). Cure of atrial arrhythmias by catheter ablation has been demonstrated to improve LV function. We evaluated the outcome of atrial flutter (AFL) ablation in a subgroup of patients with severe LV dysfunction (ejection fraction ≤25%). Methods: Patients with AFL presenting with NYHA Class II-III heart failure symptoms and LVEF≤25% were included. Radiofrequency ablation of the cavotricuspid isthmus was performed using either an irrigated-tip or 8mm-tip catheter, with the endpoint of bidirectional conduction block of the isthmus. Echocardiography was performed before ablation, and 6 and 12 months post-ablation for evaluation of LV function. Results: Fifteen patients (14 male, age 58±9 years) with AFL of 16±11 months� duration meeting the above criteria were studied, including 1 patient awaiting cardiac transplantation. Ischemic or valvular heart disease was present in 12 (80%), while 9 (60%) had undergone a previous cardioversion attempt only to recur despite treatment with amiodarone. Heart rate during AFL was 40% in 11 patients and to >50% in 8, eliminating the need for an ICD in these patients, while cardiac transplantation was deemed not necessary for the patient awaiting transplant. Pre-Ablation Post-Ablation P-valueLVEF (%) 19±6 41±14 <0.001

LV end-diastolic size (mm) 65±5 56±6 <0.001

LV end-systolic size (mm) 48±7 39±5 <0.001

LA size (mm) 46±6 42±5 0.04

NYHA Class 2.8±0.6 1.3±0.4 <0.001 Conclusions: Catheter ablation of AFL can be performed rapidly and safely in patients with severe LV dysfunction, leading to significant improvements in LV function. It should be offered as primary therapy in this high-risk subgroup of patients. PO1-23 FUNCTIONAL CHARACTERIZATION OF SITES OF PARASYMPATHETIC INNERVATION IN PATIENTS WITH PAROXYSMAL ATRIAL FIBRILLATION Eric Buch, MD, Nicolas Lellouche, MD, Andrew Celigoj, MD, PhD, Carin Siegerman, BS, David Cesario, MD, PhD, Carlos De Diego, MD, PhD, Aman Mahajan, MD, PhD, Noel G. Boyle, MD, PhD, Isaac Wiener, MD, Alan Garfinkel, PhD and Kalyanam Shivkumar, MD, PhD. University of California, Los Angeles, Los Angeles, CA. Introduction: The functional implications of fractionated left atrial (LA) electrograms (EGMs) in patients with paroxysmal atrial fibrillation (AF) are not well understood. The purpose of this study was to characterize sinus rhythm EGM patterns and their relationship to parasympathetic responses in the LA during catheter ablation.

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Methods: We analyzed 1662 LA ablation sites from 30 patients who underwent catheter ablation for paroxysmal AF. Pre-ablation EGM characteristics (number of deflections, amplitude, and duration) were measured in sinus rhythm. Parasympathetic responses during radiofrequency application (increase of A-H interval by at least 10 milliseconds (ms) or decrease of sinus rate by at least 20%) were assessed at all sites. Classification and Regression Tree (CART) analysis was used to identify characteristics of pre-ablation LA EGMs that best predicted parasympathetic response. Results: A specific pattern of pre-ablation sinus rhythm EGM (deflections at least 4, amplitude at least 0.7 millivolts, and duration at least 40 ms) was strongly associated with parasympathetic responses (sensitivity 73%, specificity 91%). The sites associated with these responses were found to be located mainly in the posterior wall of the LA. Conclusions: Parasympathetic activation during AF ablation is associated with the presence of pre-ablation high-amplitude fractionated EGMs in sinus rhythm.

PO1-24 ADDITIONAL ABLATION OF COMPLEX FRACTIONATED ATRIAL ELECTROGRAMS (CFAE) AFTER PULMONARY VEIN ISOLATION IN PAROXYSMAL ATRIAL FIBRILLATION: RESULTS OF A CONTROLLED RANDOMIZED STUDY Isabel Deisenhofer, MD, Claus Schmitt, MD, Heidi L. Estner, MD, Armin E. Luik, MD, Christof Kolb, MD, Martin R. Karch, MD, Tobias Riexinger, MD, Juergen Schreieck, MD, Gabriele Hessling, MD and Bernhard Zrenner, MD. German Heart Center, Munich, Germany, Staedtisches Klinikum Karlsruhe, Karlsruhe, Germany and Kardiologische Klinik der Universitaet Tuebingen, Tuebingen, Germany. Introduction: Segmental pulmonary vein isolation (PVI) cures paroxysmal atrial fibrillation (AF) in 65-75% of patients (pts). Ablation of complex fractionated atrial electrograms (CFAE) has emerged as an alternative ablation approach. This prospective randomized study evaluates the additional effect of CFAE ablation in pts with paroxysmal AF after PVI. Methods: 98 pts with paroxysmal AF (57±10 years, 74 male) were randomly assigned to undergo PVI (48 pts) or PVI+CFAE ablation (50 pts). Baseline characteristics showed no significant difference between both groups. After PVI, inducibility of sustained AF by atrial burst pacing was tested in all pts. Additional CFAE ablation was performed in patients with inducible AF randomized to the PVI+CFAE group. Primary endpoint was freedom of atrial tachyarrhythmia >30 seconds in a 7 day- Holter ECG at 3 months after one single procedure (off antiarrhythmic drugs). Secondary endpoint was a combined safety endpoint (pericardiac tamponade, thromboembolic accident and PV stenosis). Results: In both groups, 98% of targeted pulmonary veins (PV) were isolated (171/175 PV in PVI alone vs. 181/185 PV in PVI+CFAE ablation). Sustained AF was inducible in 31/48 pts (64%) in the PVI alone group and in 30/50 pts (60%) in the PVI+CFAE ablation group (p=ns). Only in the latter,an additional CFAE ablation was performed. In the intention-to-treat analysis, 36/48 (75%) of pts in the PVI alone and 37/50 (73%) of pts in the PVI+CFAE ablation group were in stable sinus rhythm 3 month after a single procedure (p=ns). In subgroup analysis, best success rates were achieved in pts randomized to PVI alone with non-inducibility of AF (82%; 14/17 pts) and in pts actually treated with combined PVI+CFAE ablation (77%; 23/30 pts). Conclusions: In paroxysmal AF, combination of PVI with ablation of CFAE showed in the intention-to-treat analysis no advantage to PVI alone (73% vs. 75% in sinus rhythm). However, pts without AF inducibility after PVI alone and pts undergoing additional CFAE ablation due to inducible AF showed a trend towards a better rhythm outcome. PO1-25 LIMITED VALUE OF ECG MORPHOLOGY IN PREDICTING LOCATION OF SUCCESSFUL SITE OF OUTFLOW TRACT ARRHYTHMIA Artur Baszko, MD, Krzysztof Blaszyk, MD, Michal Wasniewski, MD, Waldemar Bobkowski, MD, Waldemar Elikowski, MD and Romuald M. Ochotny, PhD, MRCP. Department of Cardiology, Poznan, Poland, Department of Pediatric Cardiology, Poznan, Poland and District Hospital, Poznan, Poland. Introduction: Idiopathic ventricular tachycardia of left bundle block morphology may arise from right (RVOT) or left ventricular outflow tract or aortic coronary sinus (ACS). Several ECG features have been described to predict location of successful ablation site. Methods: We analysed 24 consecutive patients with ventricular arrhythmia successfully ablated at RVOT and 8 patients ablated at ACS (5 - left and 3 - right). Evaluated parameters were as follows: 1)

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QRS duration, 2) axis, 3) R wave amplitude in II, III, aVF, 4) S wave in V5-V6, 5) transitional zone, 6) time to peak of R wave in V1-V4, 7) R/S in V1-V4. All patients with ACS arrhythmia had coronary angiography performed during the procedure. Results: Ablation was complicated by RBBB in 1 case ablated at His bundle proximity. There were no difference between groups with respect to QRS duration. The amplitude of R waves in II and III was significantly higher in ACS arrhythmia than RVOT (2.0±0.5mm vs. 1.3±0.4 mm and 1.8±0.9 mm vs. 1.2±0.5mm). The transition zone was earlier in ACS (100% at or earlier than V3) than RVOT (87% at V3 or later) arrhythmia. R/S amplitude was significantly larger in ACS than RVOT cases (V1: 31±36 vs. 11±8ms, V2: 31±20 vs. 14±8ms, V3: 67±21 vs. 39±26ms). The time to peak of R wave was similar (V1: 48±26 vs. 37±15ms, V2: 52±20 vs. 44±15ms and V3: 76±15 vs 59±18ms). No ECG features could differentiate reliably right ACS from RVOT location. The ECG criteria were predictive only for arrhythmia originating from left ACS. Conclusions: The ECG criteria differentiating ACS from RVOT site of arrhythmia are not reliable. The earlier transition zone and higher amplitude of R wave in inferior leads may suggest ACS origin, however intracardiac mapping is mandatory to confirm the diagnosis. ECG features of arrhythmia from RVOT, right and left ACS

RVOT Right ACS Left ACS

R peak V1 (ms) 39±26 26±4 61±25

R peak V2 (ms) 44±15 44±16 66±19

R peak V3 (ms) 59±18 75±9 76±16

R/S V1 (%) 8±5 6±8 46±39

R/S V2 (%) 13±8 14±5 42±18

R/S V3 (%) 48±31 52±17 77±21

R ampl. II (mV) 1.3±0.4 2.1±0.6 2.0±0.5

R ampl. III (mV) 1.2±0.6 1.6±0.9 2.0±0.9

PO1-26 CHANGES IN THE ISOLATED DELAYED COMPONENT AS AN ENDPOINT OF CATHETER ABLATION IN ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY Akihiko Nogami, MD, Aiko Sugiyasu, MD, Hiroshi Tada, MD, Shigeto Naito, MD, Tatsuya Usui, MD, Shinya Kowase, MD, Yasushi Oginosawa, MD, Shoichi Kubota, MD, Masayuki Igawa, MD, Tetsuo Yamazaki, MD, Naohisa Nakajima, MD, Hajime Aoki, MD, Kazuhiko Yumoto, MD, Toshiyuki Tamaki, MD and Kenichi Kato, MD. Yokohama Rosai Hospital, Yokohama, Japan, Gunma Prefectural Cardiovascular Center, Maebashi, Japan, Nagano Red Cross Hospital, Nagano, Japan and Hiratsuka Kyosai Hospital, Hiratsuka, Japan. Introduction: Ventricular tachycardia (VT) in arrhythmogenic right ventricular cardiomyopathy (ARVC) can be suppressed by radiofrequency catheter ablation (RFCA). Substrate-based mapping and ablation have been reported. However, the endpoint of ablation, other than the non-inducibility, remains undetermined. The aim of this study was to assess the usefulness of a change in isolated delayed components (IDCs) at ablation sites. Methods: Detailed endocardial mapping of the right ventricle (RV) was performed during sinus rhythm in 18 patients (5 women and 13 men, age 48 ± 11 years) with ARVC. An IDC was defined as distinct ventricular electrograms following the QRS separated ≥ 40 msec by an isoelectric interval or very low amplitude signals. Results: During sinus rthythm IDCs were recorded from 18 areas in 16 patients. Of the 18 areas, the latest IDCs in 16 areas were related to the clinical VT circuit. RFCA was carried out in the areas with the IDCs. At the end of the session, the IDC was electrically dissociated in 1, disappeared in 5, exhibited 2nd degree block in 1, and

significantly delayed (≥ 50 msec) in 3. The IDC remained unchanged after the ablation in 6 patients. The change in the IDC was correlated with the change in the type II or III late potentials in the signal-averaged ECG (SAECG). During a follow-up period of 49 ± 37 months, VT recurred in 6 patients. The patients with a changed IDC after the ablation had a significantly lower probability of VT recurrence than those patients with no IDC or an unchanged IDC after the ablation (p < 0.02). The probability of freedom from any VT at 3 years was 100 % for the patients with a changed IDC and 33 % for the patients with no IDC or an unchanged IDC. Conclusions: In patients with ARVC, (1) most IDCs during sinus rhythm were related to the VT ciucuit and can be a target for the ablation; (2) a change in the IDC (block or a delay ≥ 50 msec) after ablation was the strongest predictor for no VT recurrence; (3) termination of VT during ablation or noninducibility of clinical VT after ablation could not be a predictor for no recurrence; and (4) qualitative analyses of the serial SAECGs may be useful for the long-term follow-up. PO1-27 ABLATION OF MALIGNANT, DRUG RESISTANT TACHYARRHYTHMIA IN PREGNANT WOMEN Lukasz J. Szumowski, MD, PhD, Michal Orczykowski, MD, PhD, Ewa Szufladowicz, MD, PhD, Piotr Urbanek, MD, PhD, Pawel Derejko, MD, PhD, Robert Bodalski, MD, Zofia Dangiel, MD, PhD, Joanna Zakrzewska, MD and Franciszek Walczak, MD, PhD. Institute of Cardiology, Warsaw, Poland and Warsaw Medical University, Warsaw, Poland. Introduction: Treatment of tachyarrhytmias in pregnancy is a clinical problem. Pharmacotherapy entails a risk of side effects of the antiarrhytmic drugs, and is unsuccessful in some patients. The goal of this study was to describe mapping and ablation of malignant arrhythmia in pregnant women, with minimum or no X-Ray exposure and the use of electroanatomical system Methods: Mapping and ablation was performed in five women (age 24 to 34 years) at 24 to 38 HbD. Two of them have had incessant AVRT (long RP�), two incessant AT and the last one fast (>240/min) drug resistant, frequent AVNRT. In 4 pts electroanatomical system (CARTO) was used. Results: Two patients underwent an ablation without any X-ray exposure. Total time of fluoroscopy in the remaining three procedures, were 28, 53 and 70 sec mainly due to introduction of the catheters. In three patients, two with incessant AT and one with AVRT-long RP� the EF was reduced (tab).

AT AT AVRT long RP'

AVRT long RP' AVNRT

Age (y) 29 31 27 34 24

Max Heart Rate 250 240 170 170 240

LVEF (%)

41

45

41

58

59

HbD (weeks) 37 24 33 38 35

X-ray (sec.) 70 0 0 28 53

Procedure time(min)

85 67 50 78 51

New born Weight (g)

3800 3850 2540 3530 2860

Number of RF applications

10 1 3 3 2

Total time of RFapplications (s)

356 120 138 222 76

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All patients are free of arrhythmia (FU 13-26 months). There were no early or late complications related to the ablations. The delivery was through natural passages in three of the patients, and cesarean in two - in one due to obstructed labour and in the second due to umbilical cord asphyxia. Three children had 10 Apgar scores, in one (natural delivery, ablation without fluoroscopy), the Apgar score was 9 (impairement of muscular strength). The child with the umbilical cord asphyxia (cesarean delivery), the Apgar score was 3 points in the first minute and 9 points in the 3-rd minute. We do not relate the umbilical asphyxia to the ablation procedure. In that patient (ablation of AVRT) the fluoroscopy time was 28 seconds. Conclusions:Ablation of malignant, drug resistant arrhythmia in pregnant women should be considered as a line of treatment. PO1-28 IS FLUID OVERLOAD A RELEVANT ISSUE IN ATRIAL FIBRILLATION ABLATION WITH AN IRRIGATED TIP CATHETER? Dhanunjaya R. Lakkireddy, MD, Nancy Rogers, RCP, RRT, Loren D. Berenbom, MD, FACC, Rhea Pimentel, MD, FACC, Martin Emert, MD, James Vacek, MD, Diana Newton, NP, Kevin Kreighbaum, RN, Diane Parker, RN, Andrea Coltrain, RN, Debbie McMorris, RN, Penny Words, RCP, RRT, Jayanth Nath, MD and Kamal Gupta, MD. Mid-America Cardiology, University of Kansas, Kansas City, KS. Introduction: Irrigated tip catheter is increasingly used in atrial fibrillation ablation. The ability to achieve greater lesion depth and size at higher powers and relatively less char formation makes it an attractive catheter. Methods: We describe our experience with an open irrigated tip catheter (Thermocool, Biosense Webster Inc) in 52 patients during AF ablation. The cool flow device pumps about 30cc/min of heparinized normal saline during ablation involving >30 W power, 17cc/min with power <30 W and 2cc/min when radiofrequency (RF) is not applied. Results: A total of 52 patients of M:F ratio 7:1, mean age of 57±12 years, LVEF 52±9 %, LA size 4±1 cm underwent pulmonary vein isolation along with selective substrate modification customized to the type of AF (paroxysmal - 38%, persistent - 48% and permanent -14%). Ablation involved an average total procedure time of 254±49 minutes, fluoro time of 92±23 minutes and 4328±1235 ml of saline infusion through the irrigated catheter and other sheaths that are continuously flushed. Patients had a mean 8±3 lb increase in weight over 24 hours. Despite IV diuresis with 2 doses of 40 mg every 12 hours, 25% (13/52) of patients had more than one day (a mean 2.3 days) stay in the hospital due to fluid over related issues. Patients had symptoms of dyspnea (100%), chest tightness (100%), wheezing (25%) and lung crackles (100%). CXRs on all of these patients showed pulmonary vascular congestion (100%), pleural effusion (20%). Eight percent patients had delayed manifestations of fluid overload manifest by lower extremity swelling (25%), orthopnea (100%) and PND (12%) and severe right heart failure (12%) with PAP of 65mm of Hg. It resulted in a 1.8 unplanned visits to the EP clinic and 1.3 visits to the primary care physician's office. One patient had a CT scan for chest symptoms in a local ER which was negative. Conclusions: Irrigated tip catheters have significantly improved the efficiency of ablation with the ability to deliver higher power and achieve greater lesion sizes but add significant volume overload that may increase morbidity, the length of hospital stay, lab draws, radiology work ups and unplanned visits to physician's office.

PO1-29 COOLED INTRA-ESOPHAGEAL BALLOON TO PREVENT THERMAL INJURY OF ESOPHAGEAL WALL DURING RADIOFREQUENCY ABLATION Mauricio I. Scanavacca, MD, PhD, Santos Neto, MD, Cristiano F. Pisani, MD, Wagner Tamaki, MD, Ronaldo H. Santos, MD, Cinthya Guirao, MD, Fernando Piza, MD, Helena Oyama, PhD, Vera Aielo, MD, PhD, Denise T. Hachul, MD, PhD, Adolfo Leiner, PhD and Eduardo Sosa, MD, PhD. InCor, São Paulo, Brazil. Introduction: Atrio-esophageal fistula is a rare, but potentially lethal complication of atrial fibrillation (AF) radiofrequency (RF) catheter ablation. Theoretical mathematical models suggested that esophageal luminal cooling could be effective to prevent thermal injury of the esophageal wall. The aim of this study was to evaluate the protector effect of an esophageal cooled irrigated balloon on the esophageal injury caused by RF. Methods: The study was conducted in four dogs under anesthesia and controlled ventilation. A right thoracotomy was performed, exposing approximately 10 cm of the esophagus. A polyethylene esophageal balloon with 6 cm length and 3 cm diameter was positioned inside the esophageal lumen through an orogastric tube. RF pulses were delivered on the external esophageal surface, by a 4-mm tip catheter, controlled by temperature (between 60 and 85ºC) in three dogs and by power (4 and 8W) in one dog, in two different moments: (A) empty esophageal balloon and (B) cooled (10ºC) saline solution filling the esophageal balloon. Histological measurements of the muscular layer lesion extension (necrosis and edema) were performed using Leica Qwin software. Results: Fifteen esophageal lesions were analyzed. No difference on the thickness of muscular layer (1351±218µm) was observed among the samples. When RF delivery was controlled by catheter tip temperature (mean of 66.9±8.0ºC), the mean power was 3.7±3.8W in the control group (A) and 4.0±3.3W in the cooled balloon group (B) (P=0.89). The depth of muscular layer lesion was higher in cooled balloon group (2262±289µm) when compared to control group (1540±485µm; P=0.035). When RF energy power was controlled (mean of 6.7±1.9 Watts), the mean catheter tip temperature was 80.0±0ºC (A) and 70.4±9.8ºC (B), (P=0.25). No difference was observed in the lesions depth in both groups (A= 2779±311µm vs. B= 2410±405µm; P=0.308). Conclusions: The supposed protector effect against thermal injury by chilling the esophagus during RF delivery was not observed in this study. In fact, it suggests that there is an increase in the lesions depth when RF delivery is controlled by temperature of the catheter tip. PO1-30 FIBEROPTIC VISUALIZATION CATHETER TO ASSESS GAPS WITHIN LINEAR ABLATION LESIONS Bryant Lin, MD, Christopher Eversull, MD, Henry Chen, MD, Paul Zei, MD, PhD, Henry H. Hsia, MD, Paul Wang, MD and Amin Al-Ahmad, MD. Stanford University, Stanford, CA. Introduction: Contiguous linear radiofrequency lesions can be difficult to make. Even with modern navigation tools, it is difficult and challenging to confirm correct placement of lesions. Problems may occur with appropriate tissue contact and power delivery. The assessment of gaps between lesions is a challenge with current technology. Recently the ability to visualize the endocardial surface using a fiberoptic catheter has been described. We describe a new technique utilizing this catheter to visualize and assess gaps between ablation lesions. Methods: Eleven RF lesions were placed on the epicardial surface of an ex-vivo porcine left ventricle using a 4 mm ablation catheter while the heart was placed in a porcine blood bath. Multiple lesion sizes were created and the gap between lesions was randomly varied. After

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formation of each lesion, the distance between lesions was measured using electronic calipers. A fiberoptic video catheter was then used to visualize the lesions. Still images were recorded of each lesion from the catheter. The gap between lesions was estimated by a blinded investigator. A Pearson correlation coefficient between the actual and the estimated gap distance was calculated. Results: The mean actual gap distance was 3.1 +/- 1.8 mm. The mean estimated gap distance was 2.2 +/- 1.1 mm. The mean difference in estimated versus actual gap was 0.9 +/- 1.0 mm. The Pearson correlation coefficient between the actual and estimated gap values is 0.85 (p<0.05). The R Squared is 0.72 and the best-fit linear equation is y = 1.3682x + 0.1427. Conclusions: Using a fiberoptic catheter is a feasible technique for assessing interlesion gap distance. Future studies are needed to assess lesion visualization in-vivo for the purposes of evaluating gaps in lesion placement and potentially to guide lesion placement directly.

PO1-31 INITIAL EXPERIENCE WITH STEREOTAXIS/CARTO INTEGRATION FOR LEFT ATRIAL MAPPING AND ABLATION Spyridon T. Akrivakis, MD, Michael V. Orlov, MD, PhD, Muqtada Chaudhry, MD, Peter Hahn, MD, Jeffrey Mendel, MD, James Armstrong, PA, Juan Andres Merchan, MD, Thomas F. Marchese, BS, Tammee Sweck, BS and Charles I. Haffajee, MD. Caritas St. Elizabeth's Medical Center, Boston, MA. Introduction: Remote Magnetic Navigation System by Stereotaxis, Inc. (RMNS) allows automatic mapping of the left atrium (LA) and adjacent structures. Integration of RMNS and CARTO for ablation of atrial fibrillation (AF) is not well studied. Methods: RMNS was performed in 47 consecutive pts (60±16 years old, 33 males) undergoing mapping and ablation procedure for paroxysmal or persistent AF. Pre-procedure spiral CT was performed in all pts. Segmented LA image was used as the standard for comparison. Via double trans-septal approach an LA �automap� was created by RMNS/CARTO integrated system. Pulmonary veins (PV�s) were identified, their isolation was performed in all pts remotely using a 4 mm magnetic tip catheter (Navistar RMT) and confirmed by Lasso catheter and pacing maneuvers. Additionally, after LA/PV�s isolation,

8 mm nonmagnetic tip catheter was used for manual cavo-tricuspid isthmus ablation and SVC isolation. Results: LA mapping with RMNS was successful in all pts. All PV�s identified by CT were verified by RMNS. �Automap� resulted in 140±64 CARTO points. LA volume by �automap� was 110±31 ml with good correlation with spiral CT. PV isolation was acutely successful in all pts. AF recurred in 11 out of 47 pts (23.4%). Complication rate was 6.4% (1-CVA, 2- late pericardial effusions). Pericardial effusions were considered to be secondary to nonmagnetic catheters, only one of them required percutaneous drainage. Conclusions: RMNS allows accurate mapping of LA. AF ablation by RMNS results in success rates comparable to manual procedures and appears to be associated with lower risk of complications. RMNS was preferred to manual navigation by all operators due to procedural conveniences but future studies will be required to confirm its non-inferiority. PO1-32 ANATOMICALLY DETERMINED FUNCTIONAL CONDUCTION DELAY IN THE POSTERIOR LEFT ATRIUM. RELATIONSHIP TO STRUCTURAL HEART DISEASE Kurt C. Roberts-Thomson, MBBS, Irene H. Stevenson, MBBS, Peter M. Kistler, MBBS, PhD, Haris M. Haqqani, MBBS, John Goldblatt, MBBS, Prashanthan Sanders, MBBS, PhD and Jonathan M. Kalman, MBBS. Royal Melbourne Hospital, Melbourne, Australia and Royal Adelaide Hospital, Adelaide, Australia. Introduction: The posterior left atrium plays an important role in the initiation and maintenance of atrial fibrillation. We characterized the conduction properties in this region in patients with different forms of structural heart disease undergoing cardiac surgery. Methods: This study included 34 patients having elective cardiac surgery. Four groups included patients with: normal LV function having coronary artery bypass grafting (CABG); severe LV dysfunction (LVEF < 35%) and CABG (LVF); normal LV function and severe mitral regurgitation (MR); normal LV function having aortic valve replacement (AS). Epicardial mapping of the posterior LA was performed in sinus rhythm and during pacing at 600 and 400ms from different sites. Activation patterns, regional conduction velocity (CV), conduction heterogeneity (CH), anisotropy, and total plaque activation time (TAT) were assessed. Results: Activation mapping demonstrated the presence of a line of functional conduction delay in all patients in a consistent anatomic location in the posterior left atrium running vertically between the pulmonary veins. These changes resulted in circuitous wavefront propagation. Conclusions: We have demonstrated the presence of a line of functional and anisotropic conduction block in a consistent anatomic location in the posterior left atrium in patients with structural heart disease. This is most marked in conditions associated with significant chronic atrial enlargement and leads to circuitous wave-front propagation suggesting a potential role in arrhythmia substrate.

CABG LVF MR AS P value

LA diameter (mm) 39±7 47±7 54±6 42±6 p<0.05

Extent of line (CV 0-20cm/s) as a % of plaque Pacing CL 600ms

6.5±6.2 10.4±5.2 10.8±7.9 6.7±4.9 p<0.05

Extent of line (CV 0-20cm/s) as a % of plaque Pacing CL 400ms

6.3±6.1 12.5±7.2 13.0±7.1 8.0±5.8 p<0.05

CH index 600ms 2.7±1.4 3.7±1.2 3.1±1.5 3.6±1.9 p=0.07

Anisotropy index (600ms) 1.8±0.4 2.1±0.4 2.7±0.9 1.6±0.4 p<0.05

TAT at pacing CL 600ms (ms) 46.2±13.4 55.1±10.9 53.5±12.7 44.5±8.9 p<0.05

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PO1-33 COMPLEX FRACTIONATED ELECTROGRAM DISTRIBUTION AND TEMPORAL STABILITY IN PATIENTS UNDERGOING ATRIAL FIBRILLATION ABLATION Jean-Francois Roux, MD, Sattar Gojraty, BS, Rupa Bala, MD, Christopher Liu, MD, Mathew D. Hutchinson, MD, Sanjay Dixit, MD, Francis E. Marchlinski, MD and Edward P. Gerstenfeld, MD. University of Pennsylvania, Philadelphia, PA. Introduction: Targeting of complex fractionated electrograms (CFEs) has been described as an approach for catheter ablation of atrial fibrillation (AF). The distribution and temporal stability of CFE regions remains poorly defined. Methods: We performed 2 consecutive left atrial (LA) CFE maps using the NaVX system prior to AF ablation. Bipolar electrograms were acquired during AF from a circular mapping or ablation catheter. At each point, mean AF cycle-length (CL) was calculated automatically by averaging the interval between deflections over a 2-second window. Sites with mean CL ≤ 120 ms were considered CFE+ sites. The 2 maps were compared qualitatively and quantitatively. For the qualitative analysis, the LA was divided in 21 regions (distal PV (n=4), PV-anterior LA junction (n=4), PV-posterior LA junction (n=4), hi-mid-low posterior LA (n=3), hi-mid-low septum (n=3), roof (n=1), LA appendage (n=1), mitral annulus (n=1) ) and the CFE distribution for the 2 maps was compared. For the quantitative analysis, the CFE data were exported to Matlab and the correlation (r) and %-difference ([A - B]2 /A2) between maps was calculated. Results: A total of 12 pts. (83% male, age 54 ± 6.9 years) undergoing AF ablation (5 paroxysmal, 7 persistent) were studied. The two maps were separated in time by 32 ± 7 mins. There was no significant difference in the mean AF CL (136 ± 19 ms vs. 139 ± 13 ms; p=NS) or number of CFE+ regions (10.8 ± 2.9 vs 10.0 ± 2.9; p=NS) between the 2 maps. The majority of CFE regions were located at the PV-anterior LA junction (29.1%) and the atrial septum (14.5%), whereas only 4% were located distally inside the PVs. The presence of CFEs in both maps was concordant for 80.2% and discordant for 19.8% regions. There was a significant correlation between maps (r=0.38 ± 0.22, range 0.14 to 0.86; P < 0.001) with a %-difference of 10.2 ± 5.0%. Conclusions: During AF, most CFE regions are found in the vicinity of the PVs or over the interatrial septum. There is a significant correlation between two CFE maps constructed 32 minutes apart with 80% concordance of CFE sites. This likely represents stability of the underlying atrial substrate and/or �drivers� of AF. PO1-34 WHAT IS THE SIGNIFICANT ROLE OF LINEAR ABLATION ON THE STRUCTURAL REMODELING OF LEFT ATRIUM, LEFT ATRIAL APPENDAGE AND PULMONARY VEINS AFTER CATHETER ABLATION OF ATRIAL FIBRILLATION ? Chin-Chou Huang, MD, Hsuan-Ming Tsao, MD, Mei-Han Wu, MD, Ching-Tai Tai, MD, Yenn-Jiang Lin, MD, Shih-Lin Chang, MD, Li-Wei Lo, MD, Wanwarang Wongcharoen, MD and Shih-Ann Chen, MD. Taipei Veterans General Hospital, Taipei, Taiwan. Introduction: The regression of left atrium (LA) size after restoration of sinus rhythm has been documented in atrial fibrillation (AF) patients. However, the impact of aggressive catheter ablation on the morphological changes of LA, LA appendage ( LAA ) and pulmonary veins (PVs) remains to be elucidated. Methods: 72 patients ( 51±11 years) with drug-refractory paroxysmal atrial fibrillation underwent circumferential isolation of 4-PVs under the guidance of a three-dimensional electroanatomic mapping system (NavX system) and the circular catheter. Patients with positive inducibility test ( AF longer than 1 minute after high current 5X

threshold, long pulse duration 8 msec, 250-150 pacing cycle length from the distal coronary sinus ) after PV isolation received linear ablations on the mitral isthmus and/or LA roof. All the patients received baseline and post-ablation MDCT to evaluate the morphologies of PVs, LA and LAA. Results: Group I : 29 patients received additional linear ablations. Group II : 43 patients received only PV isolation. The post-ablation MDCT was done at a mean follow-up of 160± 95 days. The ostial diameters of superior PVs, volume of LA and size of LA appendage (LAA) ostium showed significant decrease in the two groups without AF recurrence. Furthermore, the percentage of decrease was similar between the two groups. Regarding the patients with AF recurrence, Group I ( 12 of the 29 patients ) were associated with more significant LAA dilatation (LAA ostial size post/pre-ablation ratio: 1.22±0.44 vs 0.84±0.19, p=0.009) and borderline increase of LA volume (ratio: 1.03±0.30 vs 0.82±0.12, p=0.06) compared to Group II (14 of 43 patients ). However, the degrees of morphological changes of PVs were similar between the two groups. Conclusions: Both the PV isolation and additional linear ablation show significant reverse remodeling of LA, LAA and superior PVs in patients without recurrent AF. However, additional linear ablation could not stop the progressive morphological remodeling of LA and LAA in patients with recurrent AF. PO1-35 ATORVASTATIN PREVENTS ATRIAL FIBRILLATION IN PATIENTS WITH IMPLANTATION OF A PACEMAKER: A PROSPECTIVE RANDOMIZED TRIAL Chia-Ti Tsai, MD, PhD, Yi-Chih Wang, MD, Ling-Ping Lai, MD, PhD and Jiunn-Lee Lin, MD, PhD. National Taiwan University Hospital, Taipei, Taiwan. Introduction: Increasing evidence suggests that AF is an inflammatory disease. Statins is an anti-inflammatory agent. Statin therapy may provide an effective treatment strategy for AF. We conducted a prospective randomized trial to test the efficacy of atorvastatin to prevent paroxysmal atrial fibrillation (PAF) or atrial high rate episodes (AHEs) in patients with implantation of a pacemaker. Methods: The effect of atorvastatin on time to the first attack of significant AF or AHE (≥180/min and ≥10 minutes), which were accurately detected by pacemaker interrogation, was evaluated in an open-label prospective randomized design. Results: Fifty-two patients (23 males, 70±13 years old) were randomized to the statin group (atorvastatin 20 mg/day) and 54 (25 males, 72±13 years old) to the non-statin group. Around 70 % of the patients had sick sinus syndrome and the remaining atrioventricular block. Three patients did not complete the follow-up and the remaining patients completed the followed-up for one year. Significant AHE occurred in 3 of 50 patients (6.0%) in the statin group, and 10 of 53 patients (18.9%)(odds ratio=0.27; 95% confidence interval [CI] 0.05-0.96, p=0.03) in the non-statin group. Patients in the non-statin group were more likely to develop significant AHE that those in the statin group (log-rank p=0.028). In the multivariable Cox model, atorvastatin treatment was associated with a 67% reduction in risk to develop significant AHE (HR 0.33, 95% CI 0.14 to 0.79, P=0.015). Conclusions: The present study clearly and accurately demonstrated the efficacy of atorvastatin to prevent significant AF in patients with implantation of a pacemaker.

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PO1-36 AUTONOMIC TRIGGER PATTERNS AND ANTI-ARRHYTHMIC TREATMENT OF PAROXYSMAL ATRIAL FIBRILLATION: DATA FROM THE EURO HEART SURVEY Cees B. De Vos, MD, Robby Nieuwlaat, MS, Harry J. Crijns, MD, PhD and Robert G. Tieleman, MD, PhD. University Hospital Maastricht, Maastricht, The Netherlands. Introduction: The autonomic nervous system can generate atrial fibrillation (AF) by increasing vagal or adrenergic tone in patients with an arrhythmogenic substrate. The clinical history is used to identify the kind of autonomic predominance that is responsible for the development and maintenance of AF. There are no data on the frequency of autonomic triggers in AF, nor on the clinical importance of recognition of these triggers. Methods: In 2003 and 2004, 1517 patients with paroxysmal AF were enrolled in the Euro Heart Survey on AF in 35 ESC countries. The physicians reported possible triggers for the arrhythmia. We identified patients with autonomic AF, categorized into 2 trigger patterns: adrenergic (initiation of AF associated with exercise, emotion or during daytime and absence of vagal triggers) and vagal (postprandial, night time only). Results: One or more triggers were found in 640 patients (42%). An autonomic trigger pattern according to our definition could be identified in 376 patients (25%). In autonomic AF, the disease was vagally mediated in 147 patients (10%) and adrenergic in 229 patients (15%). Patients with vagal AF had similar occurrence of concomitant heart disease. Although dissuaded by the ACC/AHA/ESC guidelines for the management of patients with AF, 72% of the patients with a vagal trigger pattern were treated with inappropriate drugs, mostly beta-blockers. In patients with a vagally mediated form of paroxysmal AF inappropriate treatment was associated with a shift to persistent or permanent AF in 18% of the patients at one year follow-up, compared to only 4% in the appropriately treated group (p=0.08). Conclusions: The Euro Heart Survey is the first large observational study to provide a complete picture of AF triggers, autonomic trigger patterns, its management and outcome. An autonomic trigger pattern was frequently seen in paroxysmal AF patients. In contrast to the general opinion, we observed that vagal AF is not restricted to the young and healthy. The high percentage of inappropriate treatment suggests insufficient appreciation for autonomic triggers of AF. This may lead to aggravation of the arrhythmia. PO1-37 WHAT IS THE TRUE AF BURDEN AFTER CATHETER ABLATION OF ATRIAL FIBRILLATION? A PROSPECTIVE RHYTHM ANALYSIS IN PACEMAKER PATIENTS WITH CONTINUOUS ATRIAL MONITORING Daniel Steven, MD, Thomas Rostock, MD, Boris Lutomsky, MD, ScD, Helge Servatius, MD, Hanno U. Klemm, MD, ScD, Rodolfo Ventura, MD, Imke Drewitz, MD and Stephan Willems, MD. Universitaeres Herzzentrum Hamburg, Hamburg, Germany. Introduction: Current success evaluation after catheter ablation of atrial fibrillation (AF-Abl) is widely based on long-term ECG, tele-ECG or on patients symptoms after AF-Abl. In this study we analyzed continuous atrial recordings from pacemaker with a Holter function before and after AF-Abl. Methods: Between August 2005 and August 2006 a total number of 310 patients underwent AF-Abl in our institution. Twenty-five (mean age 65.4±11.1 years, 13 (52%) male) of them had prior pacemaker implantation of devices with an atrial Holter function. Holter data were collected and correlated to the patients′ symptoms prior to and three monthly after AF-Abl. AF recurrence was defined as an episode with an atrial frequency of more then 200bpm lasting longer then 30 seconds. Patients with paroxysmal atrial fibrillation (AF) (n=14)

underwent pulmonary vein isolation (PVI) Patients with persistent or inducible AF after PVI as well as patients with a history of long-lasting persistent AF (n=11) an additional substrate modification by means of atrial defragmentation was performed. Procedural endpoint in persistent AF was AF termination by ablation. Results: The mean AF burden prior to ablation was 25.18 % during a monitoring period of 8.4±3.5 months. During the follow up after AF-Abl (7.6±3.7 months) the AF burden was reduced to 1.9%. In 11 of 14 patients (78%) with paroxysmal AF no AF episode was detected after AF-Abl (AF-burden 0%). In patients with persistent AF the AF-burden decreased from 47,9% to 5,2% (p= 0,009). In our population the freedom of symptoms correlated well with the documented freedom of AF. Conclusions: Continuous atrial monitoring revealed a complete AF freedom in 78% of patients with paroxysmal AF and a significant reduction of the AF-burden in patients with persistent or chronic AF. There was a close association between clinical symptoms and documented arrhythmia episodes in this patient cohort. These data demonstrate that symptomatic freedom of AF correlates well with the actual freedom of AF after AF-Abl with electrophysiological procedure endpoints (i.e. PVI and AF termination). PO1-38 REENTRANT CIRCUIT IS TOTALLY CONFINED TO ATRIOVENTRICULAR NODE IN HALF OF ATYPICAL ATRIOVENTRICULAR NODAL REENTRANT TACHYCARDIAS Kiyoshi Otomo, MD, Kikuya Uno, MD, PhD, Yasutoshi Nagata, MD, Keita Handa, MD and Yoshito Iesaka, MD, PhD. Tsuchiura Kyodo Hospital, Tsuchiura, Japan. Introduction: There are still controversies as to the precise location of the reentrant circuit (RC) in atypical AV nodal reentrant tachycardia (AVNRT), especially whether or not the perinodal atrium is involved in the RC. This study was performed to assess whether the perinodal atrium is involved in the RC of atypical AVNRT. Methods: Among 19 patients (pts) with 25 atypical AVNRTs (slow-slow: 11, fast-slow: 14) induced during electrophysiological study, overdrive pacing was performed from the high right atrium during atypical AVNRT to assess whether the tachycardia was reset when the perinodal atrium (coronary sinus (CS) and His bundle site (HBS)) was antidromically captured by overdrive pacing. The tachycardia was considered to be reset when the H-H interval was shortened by >10 msec. Results: Fourteen atypical AVNRTs (56%; slow-slow/fast-slow=7/7) induced in 10 pts (53%) were not reset by overdrive pacing even when all the perinodal atrium, including the earliest retrograde atrial activation site (ERAAS) during the tachycardia (CS ostium/proximal CS/HBS=3/10/1), was antidromically captured and pre-excited 15-40 msec earlier than expected. Among them, 4 tachycardias (16%) induced in 4 pts (21%) presented ventriculo-atrial (VA) dissociations during the tachycardia, including transient VA block in 2 and variable H-A interval during constant H-H interval in the remaining 2 pts. In the other 11 tachycardias (44%; slow-slow/fast-slow=4/7; the ERAAS: CS ostium/proximal CS=9/2) induced in the other 9 pts (47%), the tachycardia was not reset by atrial overdrive pacing when HBS was antidromically captured 10-40msec earlier than expected, but reset only when both HBS and the ERAAS were antidromically captured. Conclusions: All the atypical AVNRTs were not reset even when the atrium at the HBS was pre-excited, suggesting that atrial myocardium near the HBS would not be involved in the RC of atypical AVNRT. All the perinodal atrium could be preexcited without tachycardia reset in 56% of atypical AVNRTs, suggesting that the perinodal atrium would not be involved in the RC in about half of atypical AVNRTs.

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PO1-39 RAPID ASSESSMENT OF AV NODAL CONDUCTION AFTER CATHETER ABLATION OF POSTEROSEPTAL ACCESSORY PATHWAYS Gi-Byoung Nam, MD, PhD, Kyoung-Min Park, MD, Kee-Joon Choi, MD and You-Ho Kim, MD. University of Ulsan, Seoul, Republic of Korea. Introduction: After successful ablation of posteroseptal accessory pathway(AP), retrograde conduction through the atrioventricular(AV) node could mimic residual AP conduction when it exits through the coronary sinus(CS) region. Para-Hisian pacing(PHP) is often difficult to interpret due to the overlap of the His bundle activity in the ventricular electrogram. We propose a new algorithm simply measuring stimulus to atrial interval after pacing the ventricle at the para-Hisian (PHP) and posteroseptal (pacing near the CS ostium, PSP) regions for a rapid identification of residual AP conduction vs. conduction through the AV node. Methods: We performed PHP and PSP in patients with AV nodal reentrant tachycardia(AVNRT, n=27) or atrioventricular reentry tachycardia using posteroseptal AP(n=17). Interval from the stimulus to the high right atrial(HRA) activity was measured after para-Hisian ventricular myocardial capture(PHP-VM), para-Hisian His bundle capture(PHP-HB), and posteroseptal ventricular myocardial capture(PSP-VM). Results: 1. In patients with AVNRT, the stimulus to HRA (SA) interval was prolonged significantly by 55±17 ms during PHP-VM than during PHP-HB. In patients with posteroseptal AP, SA interval was prolonged only by 13±19 ms during PHP-VM than during PHP-HB. 2. The difference in the SA intervals between PHP-VM and PHP-HB > 35ms excluded presence of AP conduction. 3. In patients with AVNRT, SA interval during PSP-VM was 29±19 ms longer than the SA interval during PHP-VM. In patients with posteroseptal AP, SA interval during PSP-VM was 29±30 ms shorter than the SA interval during PHP-VM. 4. Difference in PHP SA intervals (PHP-VM minus PHP-HB) >25 ms and SA interval during PSP-VM longer than during PHP-VM successfully identified AV nodal from posteroseptal AP conduction. Conclusions: 1. Marked (>35mm) prolongation of the PHP SA interval alone could predict AV nodal conduction suggesting loss of posteroseptal AP conduction. 2. SA interval during PHP, when combined with PSP could be used for a rapid and simple identification of residual posteroseptal AP from AV nodal conduction. PO1-40 GENETIC PREDISPOSITION TO POST-MYOCARDIAL INFARCTION LONG QT INTERVALS AND TORSADE DE POINTES Guido D. Pollevick, PhD, Antonio Oliva, MD, Sami Viskin, MD, Tabitha Carrier, BS, Alejandra Guerchicoff, PhD and Charles Antzelevitch, PhD. Masonic Medical Research Laboratory, Utica, NY and Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel. Introduction: The early post-myocardial infraction (MI) period (days 2-11) is associated with a slight QT prolongation in most patients. In some, the post-MI electrical remodeling results in prominent prolongation of the QT interval, negative T waves throughout the precordium and the development of Torsade de Pointes (TdP) arrhythmias. The present study examines the hypothesis that long QT mutations or polymorphisms predispose to the development of TdP in the days immediately following an MI. Methods: Of 434 consecutive admissions for acute MI, 8 patients displayed progressive QT prolongation resulting in typical TdP (QTc=492 ± 57 ms)(Halkin et al JACC 38:1168-74, 2001). Genomic DNA from these 8 patients and from 14 others with acute MI and normal QT, were prepared from peripheral blood lymphocytes. All known exons of KCNQ1, KCNH2, KCNE1, KCNE2 and SCN5A

genes, previously linked to LQTS, were amplified using intronic primers and sequenced. Results: No mutations in the long QT genes were uncovered in any of the patients. However, 6 out of 8 patients who presented with QT prolongation and TdP had a heterozygous K897T polymorphism in KCNH2, with a frequency of 0.625 (K) and 0.375 (T). In the group with uncomplicated MI and normal QT, 3 out of 14 were heterozygous for the K897T polymorphism with a frequency of 0.89 (K) and 0.11(T). This frequency did not significantly deviate from the normal population frequency of 0.84 (K) and 0.16 (T). Genotype frequencies from QT affected patients were not in Hardy-Weinberg equilibrium (X2= 4.49 pK897T vs WT is expressed. Population-based studies have found the KCNH2-K897T polymorphism to be associated with both prolonged and abbreviated QT intervals. Conclusions: Our findings lend support to the hypothesis that this form of acquired long QT and TdP occurring post-MI has a genetic predisposition. PO1-41 CLINICAL CHARACTERISTICS AND EFFICACY OF ADDITIONAL THERAPY IN PATIENTS WITH LQT1 AND LQT2 SYNDROME REFRACTORY TO Β-BLOCKER THERAPY Yuuko Yamada, MD, Koji Miyamoto, MD, Satoko Kitamura, MD, Hideo Okamura, MD, Takashi Noda, MD, PhD, Kazuhiro Satomi, MD, PhD, Kazuhiro Suyama, MD, PhD, Takashi Kurita, MD, PhD, Naohiko Aihara, MD, Shiro Kamakura, MD, PhD and Wataru Shimizu, MD, PhD. National Cardiovascular Center, Suita, Japan. Introduction: β-blockers significantly reduce cardiac events (CE) including syncope, Torsade de Pointes (TdP) and cardiac arrest in patients (pts) with congenital long QT syndrome (LQTS). However, CE continue to occur in some pts on β-blockers. The aims of this study were to assess the clinical and electrocardiographic characteristics in genotyped LQTS pts, who were refractory to β-blocker therapy, and to evaluate the efficacy of additional therapy for CE. Methods: The study population consisted of 74 genotyped LQTS pts (35 LQT1 and 39 LQT2), who were treated with β-blockers, among 170 genotyped LQTS pts (97 LQT1 from 35 families, 73 LQT2 pts from 38 families). The 74 pts were divided into 2 groups; 20 pts who had experienced recurrence of CE on β-blockers (CE (+) group) and 54 pts without recurrence (CE (-) group). Results: The recurrence rate of CE on β-blockers was comparable between LQT1 and LQT2 pts (8 (23%) of 35 LQT1 pts vs. 12 (31%) of 39 LQT2 pts; p=0.43). There were no LQTS-related deaths, but ventricular fibrillation or cardiac arrest occurred in 4 LQT1 pts and 1 LQT2 pt. No significant differences were observed in age at first CE (12±7 vs. 16±14 y.o.), previous history of syncope (85% vs. 81%), cardiac arrest (25% vs. 22%), and percentage of proband (70% vs. 74%) between the CE (+) group and CE (-) group. The CE (+) group had higher TdP documentation (85% vs. 37%; p=0.0005), longer baseline QTc interval (526±44 ms vs. 496±41 ms; p=0.0055), and higher incidence of pore mutations (85% vs. 39%; p=0.0005) than the CE (-) group. Transient withdrawal of β-blockers triggered CE in 5 of the 8 LQT1 pts, and β-blocker dose-up suppressed subsequent CE in all 8 LQT1 pts. In contrast, β-blocker dose-up (n=6) and additional pharmacological therapy with mexiletine (n=6), verapamil (n=8) and/or potassium supplement (n=9) failed to prevent subsequent CE in 10 of the 12 LQT2 pts. ICD was implanted in 2 LQT1 and 5 LQT2 pts. Conclusions: LQTS pts with documented TdP, longer QTc, and pore mutations were more refractory to β-blocker therapy, especially in LQT2 pts. Additional pharmacological therapy and/or ICD were more frequently required in LQT2 pts.

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PO1-42 NON-INDUCIBILITY OF VENTRICULAR TACHYCARDIA DOES NOT PREDICT LOW LIKELIHOOD OF APPROPRIATE THERAPY IN PATIENTS WITH ARVD Adam S. Budzikowski, MD, PhD, James P. Daubert, MD, Henry W. Sesselberg, MD, Melvin M. Scheinman, MD, N. A. Mark Estes, III, MD, Scott McNitt, MS, Hugh Calkins, MD, Wojciech Zareba, MD, PhD and Frank I. Marcus, MD. University of Rochester, Rochester, NY, University of California, San Francisco, San Franciso, NY, Tufts-New England Medical Center, Boston, MA, Johns Hopkins Hospital, Baltimore, MD and University of Arizona, Tucson, AZ. Introduction: The prognostic significance of inducibility of VT during programmed ventricular stimulation (PVS) was recently challenged in postinfarction patients and in dilated cardiomyopathy patients, but there are limited data regarding the predictive value of inducibility in patients with ARVD. We hypothesized that VT inducibility at PVS can be used to stratify patients for future arrhythmic events and provide a guide to ICD therapy. Methods: We studied 67 probands (mean age 38±14 years; 39% females) enrolled in the North American ARVD Registry who underwent PVS and had an implanted ICD. Inducibility was defined as sustained VT or VF using up to 3 extrastimuli at 2 sites and isoproterenol. ICD follow-up events were adjudicated at a core lab to determine the incidence of appropriate therapy for VT/VF. Results: Inducibility was found in 30 (45%) of 67 patients. During median 1.2-year follow-up, 20 (30%) patients experienced one or more appropriate ICD therapy. At 1 year, 26% non-inducible and 36% inducible patients received appropriate ICD therapy. More inducible patients received appropriate ICD therapies but that difference did not reached statistical significance (hazard ratio=1.64 (95%CI: 0.74-3.66, p-value=0.23) (Fig1). Non-inducible ARVD patients had a high: (26% at 1 year and 39% at 2 years) risk of arrhythmic events. There were no differences in outcome with respect to the site of VT induction. Conclusions: Non-inducible ARVD patients with ICD have a high risk of arrhythmic events, thus questioning the prognostic significance of EP inducibility testing in these patients.

PO1-43 ELECTROPHYSIOLOGICAL EFFECTS OF CARVEDILOL ADMINISTRATION IN PATIENTS WITH DILATED CARDIOMYOPATHY. A PROSPECTIVE, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY Emmanuel M. Kanoupakis, MD, Emmanuel G. Manios, MD, Hercules E. Mavrakis, MD, Eleftherios M. Kallergis, MD, George M. Lyrarakis, MD and Panos E. Vardas, MD, PhD. Heraklion University Hospital, Heraklion, Crete, Greece. Introduction: Several studies suggest the clinical efficacy of carvedilol in reducing atrial and ventricular arrhythmias in patients with left ventricular dysfunction (LVD) due to congestive heart failure (CHF) or following myocardial infarction. However, the mechanisms supporting its antiarrhythmic efficacy have been derived from experimental studies. In this prospective, placebo-controlled trial we examined the electrophysiological effects of a high oral dose of carvedilol in patients with CHF and LVD due to non-ischemic dilated cardiomyopathy. Methods: Thirty one patients underwent an electrophysiological study and were randomly assigned to treatment with carvedilol or placebo. After two months of treatment the study was repeated. Results: Carvedilol prolonged almost all conduction times. In the same group atrial (AERP) and ventricular (VERP) effective refractory periods were significantly prolonged (fig. 1), while the parameters of repolarization remained virtually unchanged. The prolongation of refractoriness was most pronounced in the atrium. The change in ventricular refractoriness was correlated with ejection fraction (r= 0.94, p<0.01) suggesting that patients with more preserved left ventricular function responded to treatment with greater prolongation. Conclusions: Even after a short period of administration, carvedilol has marked and diffuse electrophysiological effects that would be beneficial for patients with CHF and may contribute to the positive outcome of clinical trials

PO1-44 SINUS NODE DYSFUNCTION IN ORTHOTOPIC HEART TRANSPLANT RECIPIENTS Jeffrey Luebbert, MD, Forrester A. Lee, MD and Lynda E. Rosenfeld, MD. Yale University, New Haven, CT. Introduction: Sinus node dysfunction (SND) is a well known early complication of orthotopic heart transplantation (OHT). Its incidence over the lifetime of transplant recipients is less well characterized. The goal of this study was to determine the incidence and timing of SND in a large cohort of OHT recipients. Methods: The databases of the Yale University Heart Transplant and Electrophysiology Services were reviewed and cross referenced. Patients who received pacemakers for SND were identified for analysis. Results: A total of 241 patients underwent OHT using biatrial anastamoses from 1984 to 2006. Of these, 216 patients survived >5

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days post OHT and were included in the analysis. Fifty eight women and 158 men underwent OHT at a mean age of 49±13 years. Patients were followed in the Yale Heart Transplant Clinic and had yearly ECGs and 24 hour ambulatory monitoring. Of these patients, 24 (4 female, 20 male, mean age at transplant 49±12 years) developed SND and received a pacemaker. Thirteen patients received pacemakers within 30 days post OHT; 11 patients received pacemakers 248 to 4329 days post OHT:

Conclusions: Although frequently seen as an early complication of OHT, SND remains a risk throughout the lifetime of OHT recipients. Whether this risk can be reduced by newer techniques such as bicaval anastamoses remains to be established. PO1-45 REASONS FOR IMPLANTATION OF PERMANENT PACEMAKERS IN YOUNG PATIENTS AND LONG TERM FOLLOW-UP Najib Z. Al-Rawahi, MD, Rafeeq Samie, MD, David Farwell, MD, Michael H. Gollob, MD, Robert Lemery, MD, Martin S. Green, MD, Anthony S. Tang, MD and David H. Birnie, MD. Ottawa Heart Institute, Ottawa, Ontario, Canada and University of Ottawa Heart Institute, Ottawa, Ontario, Canada. Introduction: The reasons young patients receive permanent pacemakers (PPM) are not well defined. Also, PPM have significant device related long-term morbidity. There are some data to suggest this morbidity is higher in younger patients. Study aims: i) To examine reasons for permanent pacing in young patients ii) To assess incidence of idiopathic Sinus Node Dysfunction (SND) or Heart Block (HB) which may have a genetic basis iii) To assess long-term morbidity The study was done in the sole implant center serving a catchment area of 1 million. Methods: The device clinic database was examined for patients who had initial PPM implant at age ≤ 45 years between 1988 and 2004. The database and individual patient charts were examined and all original data including ECGS and Holter strips were reviewed. Subsequent surgeries were recorded. Results: 71 patients were included with an average age at implant of 25.4±10.8 years. Reasons for implantation of PPM were: post cardiac surgery or ablation in 29 patients (40.8%), idiopathic HB or SND in 16 patients (22.5%), congenital HB in 11 patients (15.5%), vasovagal syncope in 7 patients (9.9%) and miscellaneous causes in 8 patients (11.3%). The estimated incidence of idiopathic HB and SND is 1 in 1.125 million.

Patients have been followed for an average of 12.1±6.3 years. 25 patients (35.2%) required 37 subsequent PPM related surgeries for reasons other than routine pulse generator changes (PGC) (Figure 1). Lead failure was the most common reason for subsequent surgeries (18 surgeries (48.6%)) Conclusions: i) The most common reason for implantation of PPM in young patients is after cardiac surgery or ablation. ii) PM implantation for idiopathic SND or HB is the second most common indication. However the diagnosis is rare with an estimated incidence of 1 in 1.125 million. iii) Young pacemaker patients have considerable device related morbidity in follow-up.

PO1-46 BACHMANN�S BUNDLE PACING HAS ADVANTAGE OVER RIGHT ATRIAL APPENDAGE PACING OF AVOIDING HEMODYNAMIC PERTURBATION ASSOCIATED WITH RIGHT-TO-LEFT ATRIAL CONTRACTION DELAY Tomoyuki Suzuki, MD, Toshiyuki Osaka, MD, PhD, Eriko Yokoyama, MD, Yoshio Takemoto, MD and Itsuo Kodama, MD, PhD. Shizuoka Saiseikai General Hospital, Shizuoka, Japan and Nagoya University, Nagoya, Japan. Introduction: Right atrial pacing (RAp), usually performed at the appendage (RAA), causes a delayed electrical and mechanical activation of the left atrium (LA) that may compromise transmitral inflow during late diastole and impede left ventricular (LV) preload. RAp at the septum might be preferable without causing such a delayed LA activation. Methods: The study included 18 patients with a permanent pacemaker implanted for tachycardia-bradycardia syndrome with normal AV conduction (PQ=175±15 ms); atrial lead was positioned in RAA in 9 and RA septum near the Bachmann�s bundle (BB) in 9. During sinus rhythm (SR) and RAp (AAI mode), we measured intervals from the onset of the P wave in the ECG to the onset of atrial filling wave (A-wave) in the pulse Doppler echocardiography at the tricuspid (At) and mitral (Am) valve. Time difference between P-Am and P-At (TD) was estimated as RA-to-LA contraction delay. Myocardial performance index (Tei index) was calculated as the sum of isovolumic contraction time (ICT) and isovolumic relaxation (IRT) divided by ejection time (ET). Results: RAAp and BBp increased and decreased P wave duration by 45.1±21.3% and 6.3±8.1%, respectively, compared with SR. TD was 16±18 ms during SR. RAAp increased TD by 15±15 ms. The A-wave was interrupted by the following LV contraction in all the patients during RAAp. Compared with SR, RAAp increased rate-adjusted ICT, ET, IRT by 75.9±56.8, 9.1±8.2, 33.1±16.1%,

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respectively, leading to a significant increase in Tei index by 28.2±17.2% (p<0.001). LV filling time (interval from the onset to the offset of transmitral flow) was decreased by 10.0±3.4%. BBp decreased TD by 27±14 ms without causing A-wave cutoff in any patient. BBp increased ICT, ET, IRT only by 11.6±14.8, 4.6±4.7, 6.3±4.4%, respectively, leaving Tei index unaffected (3.6±2.9% increase; P=0.08). The decrease in LV filling time remained in 6.6±2.9%. Conclusions: RAAp results in an interruption of transmitral inflow in association with RA-to-LA contraction delay. BBp has advantage over RAAp to minimize hemodynamic perturbation caused by LA activation delay with RAp. PO1-47 COMPARISON OF TWO ALGORITHMS DESIGNED TO REDUCE VENTRICULAR PACING IN PACEMAKER PATIENTS Helmut Pürerfellner, MD, J. Brandt, MD, Carsten W. Israel, MD, Todd Sheldon, MS, James W. Johnson, MS and G Milasinovic, MD. Krankenhauses der Elisabethinen, Linz, Austria, University Hospital, Lund, Sweden, J.W. Goethe-Universität, Frankfurt, Germany, Medtronic, Inc., Minneapolis, MN and Clinical Center of Serbia, Belgrade, Serbia and Montenegro. Introduction: Managed Ventricular Pacing (MVP) and Search AV+ (SAV+) are two pacing algorithms designed to reduce ventricular pacing. MVP promotes conduction by operating in AAI/R mode with backup ventricular pacing during AV block (AVB). SAV+ operates in DDD/R mode with a nominal AV extension of 290 ms during atrial sensing and 320 ms during atrial pacing. A comparison of the reduction of ventricular pacing achieved with these two algorithms in pacemaker patients (pts) has not been performed. Methods: The EnRhythm and EnPulse clinical studies were two separate pacemaker studies that assessed the percentage of ventricular pacing (%VP) after 1-month using the MVP and SAV+ algorithms, respectively. In each study the pt demographics and AVB status was assessed at baseline by clinicians. Each pt�s AV block status was assigned using the following hierarchical categories: persistent 3rd degree AVB (p3AVB), episodic 3rd degree AVB (e3AVB), 2nd degree AV (2AVB), 1st degree AVB (1AVB), and no AVB (nAVB). No pts were excluded from analysis based on their AV block status. The %VP was retrospectively tabulated for each AVB status category and for each algorithm in the two clinical trials. Results: One hundred and twenty-nine and 193 pts completed 1-month of follow-up with complete data for MVP and SAV+, respectively. Baseline demographic differences were observed. EnRhythm had a higher % of males (p=.01), beta blocker (p < .01), ACE inhibitor (p < .01) and calcium channel blocker (p =.04) usage and lower % of pts with coronary artery disease (p = .04). The distribution of AV block was different between the two studies (p=.03). The table shows the number and % of pts in each AV block category, median %VP and the % of pts with less than 40% VP. The p-value comparisons after adjustment for patient demographic differences are provided. Conclusions: MVP resulted in a reduction in %VP across all pt groups except persistent third degree AV block. The greatest reduction in %VP was observed in patients with mildly impaired AV conduction.

Number (% of Pts) Median %VP % of Pts < 40% VP AVB Degree MVP SAV+ MVP SAV+ P-

value MVP SAV+ P-value

p3AVB 13 (10%)

27 (14%) 98.9% 100% 1.00 8% 4% 0.36

e3AVB 25 (19%)

22 (11%) 1.2% 42.2% .02 72% 45% .02

2AVB 25 (19%)

31 (16%) 37.6 99.3% .002 56% 16% .0002

1AVB 10 (8%) 35 (18%) 0.9% 80.6% <.0001 100% 37% .004

nAVB 56 (44%)

78 (40%) 0.3% 2.9% <.0001 98% 88% .04

PO1-48 IS QRS CONFIGURATION DURING RIGHT VENTRICULAR PACING A RELIABLE INDICATOR OF THE OPTIMUM RIGHT VENTRICULAR PACING SITE ? Yoshio Takemoto, MD, Toshiyuki Osaka, MD, PhD, Eriko Yokoyama, MD, Tomoyuki Suzuki, MD and Itsuo Kodama, MD, PhD. Shizuoka Saiseikai General Hospital, Shizuoka, Japan and Nagoya University, Nagoya, Japan. Introduction: Right ventricular (RV) apical pacing is detrimental to left ventricular (LV) function since abnormal intraventricular conduction produces dyssynchronous LV contraction. RV septal pacing or bifocal RV pacing has been performed as an alternative. However, information is still limited as to the reliable indicator of the optimum RV pacing site. Methods: The study included 10 patients with normal QRS duration and AV conduction at sinus rhythm. We assessed in acute hemodynamic studies QRS duration in the ECG, electrical axis of the QRS complex, maximum rate of increase and decrease in LV pressure (LVdp/dtmax, -LVdp/dtmax) during 3 AV sequential pacings (AV delay = 100 ms): right atrial (RA)-RV apex (RVAp), RV septum where to produce QRS duration as short as possible (RVSp), and bifocal RV (apex and outflow tract) (RVbifp). Values during RA pacing alone (RAp) were employed as controls. Results: Compared with RAp, RVp caused a significant increase in QRS duration at all pacing sites tested; QRS duration during RVAp was longer than during RVSp and RVbifp. QRS duration during RVbifp was longer than during RVSp. QRS axes during RVAp and RVbifp were deviated to the left compared with RAp, whereas no difference was obtained during RVSp. RVp decreased LVdp/dtmax at all pacing sites; the value for RVAp was lower than for RVSp and RVbifp, whereas the values for RVSp and RVbifp were comparable. RVAp and RVSp decreased -LVdp/dtmax compared with RAp, whereas no difference was obtained during RVbifp. Conclusions: Despite a significant prolongation of QRS duration with a left axis deviation compared with RVSp, RVbifp attenuates RVAp-induced deterioration of LV systolic performance to a similar extent to RVSp without compromising the diastolic performance. QRS configuration alone may not be a reliable indicator of LV mechanical synchronization during RV pacing.

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ECG and Hemodynamic Parameters

RAp RVAp RVSp RVbifp

QRS duration (ms) 83±19 155±21* 121±8*, # 141±15*, #, +

QRS axis (degrees) 58±21 -76±7* 64±27# -18±62*, #, +

LVdp/dtmax (mmHg/s) 1579±471 1370±347* 1491±481*, # 1478±425*, #

-LVdp/dtmax (mmHg/s) 2029±433 1808±385* 1738±288* 1912±466

* p # p+ p

PO1-49 THE PREVALENCE OF METHICILLIN RESISTANT ORGANISMS AMONG PACEMAKER AND DEFIBRILLATOR IMPLANT RECIPIENTS David J. Rodriguez, MD, Rudolph F. Evonich, MD and David E. Haines, MD. Beaumont Hospital, Royal Oak, MI. Introduction: Pacemaker and defibrillator infections are an uncommon, but catastrophic complication of device implantation. We previously reported an increasing incidence of methicillin-resistant (MR) pathogens among device infections. Of 5,188 device implants/generator changes/system revisions, infection rate was 1.06%. MRSA was identified in 3/20 (15%) culture positive infections prior to 6/30/2002, but 11 of 21 (53%) infections after that date. The present study examined the prevalence of MR organism colonization in patients undergoing device implants and determine any comorbidities or cofactors that may predispose to this colonization. Methods: Sixty-four patients undergoing pacemaker/defibrillator device implantations or generator replacements were enrolled in the study. Clinical data were obtained prospectively. Prior to the procedure, the nares were swabbed, and the samples were cultured and analyzed for presence of coagulase positive staphylococcus aureas (SA). If present, the samples were tested for methicillin sensitivity. Results: There were 41 men and average age was 73 yo. Devices were new implants in 88%, generator changes in 11% and system modifications/upgrades in 11%. 29/64 pts (45%) were hospitalized for 1 day and 35 patients (55%) were inpatients for a mean of 6.3 days. Other clinical characteristics included diabetes (30%), chronic kidney disease (17%), cancer history (14%) and steroid use (6%). A total of 8 pts (14%) had positive cultures for SA: 1.5 % with MRSA; 9.3% with methicillin sensitive SA; 3.1% of patients grew coagulase negative SA (CNS). 86% of the nasal cultures were negative for any growth after 48 hours. No predictors of SA colonization were identified among the clinical variables collected. Conclusions: MRSA is a common pathogen among device-related infections. Colonization with MSSA and MRSA is present in a non-selected cohort of device implant patients. Antibiotic selection prior to pacemaker procedures directed towards MRSA may be appropriate in select patients identified by surveillance cultures. PO1-50 DUAL CHAMBER PACING WITH IMPLANTABLE DEFIBRILLATORS COMPARED WITH SINGLE CHAMBER DEVICES IS NOT ASSOCIATED WITH WORSENING HF IN OCTOGENARIANS AND NONAGENARIANS AT HIGH RISK OF SUDDEN DEATH Sandeep Sagar, MD, PhD, Win-Kuang Shen, MD, Yasir M. Quershi, MBBS, Atul Singla, MBBS, Sabeeh Siddiqui, MD, Gabe Fuque, David J. Bradley, MD, PhD, Paul A. Friedman, MD and Arshad Jahangir, MD. Mayo Clinic, Rochester, MN.

Introduction: Recent trials have shown a detrimental effect of right ventricular apex pacing on cardiac function and survival in patients with implantable cardioverter-defbrillators (ICD). The mean age of patients in these trials has been in mid sixties and it is not clear whether such a deleterious effect is also observed in advanced-elderly (≥80 years) patients with a more limited life span. Methods: We evaluated medical records of all patients 80 years and older who underwent ICD implantation at the Mayo Clinic between 1994 and 2006 for the development of new or worsening heart failure (HF) and overall survival. Results: Of 257 pts (mean age 83±3 yrs, range 80-94 yrs, 54% male), 171 (67%) had ICD implanted for secondary prevention of sudden death (SD). Patients were divided into those receiving ICDs with ventricular (SC= 118 pts) or atrioventricular (DC = 139 pts) pacing capabilities. There was no significant difference in baseline left ventricular ejection fraction (EF= 25±10 vs. 28±13%) and HF severity in the two groups. During the mean follow up of 2.6±2.2 yrs (longest 10 yrs) after ICD implant, more patients (64%) with DC ICDs were paced ventricularly ≥70% than SC ICDs (28%, p<0.01). Worsening of HF occurred in 142 pts and was more frequent in those with SC devices (41% vs. 27%, P=0.007), who also had more frequent post-implant atrial fibrillation (AF= 6 vs 1%, P<0.001). All cause mortality was not significantly different between the two groups (35% in DC vs 41% in SC, p=0.12). Predictors of worsening HF included EF prior to ICD implant, prior renal failure, mitral valve prolapse and history of chest pain. SC pacing and post-implant AF were predictors of worsening HF within 6 months of implant. Conclusions: In the older-elderly patients at high risk of SD, dual chamber pacing with ICD compared with SC devices is not associated with worsening HF. SC ventricular pacing is associated with increased incidence of post-implant AF and HF. The impact of pacing on worsening heart failure may vary dependent on the age and the underlying substrate. PO1-51 ROLE OF NT-PROBNP, HS-CRP, AND IL-6 IN IDENTIFYING PATIENTS ON CARDIAC RESYNCHRONIZATION THERAPY AT RISK OF SUDDEN DEATH Giuseppe Ricciardi, MD, Roberta Frandi, MD, Paolo Pieragnoli, MD, Francesco Sofi, MD, PhD, Andrea Colella, MD, Anna Maria Gori, BS, Francesca Pirolo, BS, Anna Lucia Caldini, BS, Maria Cristina Porciani, MD, Rosanna Abbate, MD, Luigi Padeletti, MD and Antonio Michelucci, MD. University of Florence, Florence, Italy and Azienda Ospedaliero-Universitaria Careggi, Florence, Italy. Introduction: It is not established if baseline blood levels of inflammatory markers and of natriuretic peptides may identify patients (pts) on cardiac resynchronization therapy (CRT) at risk of sudden death (SD, including the first life-threatening episode in pts with also defibrillator). Methods: We studied prospectively 140 pts (112 M; 28 F, median age of 75 (range: 49-93 years), NYHA III-IV class, EF = 29.9 ± 9.6 %, left bundle branch block, on optimized medical therapy, intraventricular dyssynchrony) who underwent CRT with (n=86; 61.4%) or without defibrillator (n=54; 38.6%). We evaluated in each patient just before CRT: NT-proBNP (Roche Diagnostics, USA), high-sensitivity C-reactive protein (hs-CRP, Dade Behring, Marburg, Germany), interleukin-6 (IL-6, Amersham Biosciences; UK), EF, left ventricular end-diastolic and end-systolic volumes (LVVs). Results: SD (follow-up: 14.1 ± 6.3 months), as the first episode, was observed in 40 patients (28.6 %). No differences were observed between pts with and without SD for age, EF, NYHA class, LVVs, hsCRP and IL-6 whereas only NT-proBNP proved to be significantly (p3558.1 pg/mL) and performed a regression analysis which showed a significant association between the highest tertile of NT-pro-BNP and SD (OR: 6.3; 95%CI 1.6-24.2; p=0.008). Moroever, at a Cox

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regression analysis, after adjustment for possible confounders, the highest tertile of baseline NT-pro-BNP resulted to be a significant predicting variable for SD (HR: 4.9; 95%CI 1.6-15.1; p=0.004). Conclusions: NT-proBNP, but not hsCRP and IL-6, is able to predict SD in CRT patients. PO1-52 EFFECT OF PHYSICAL EXERCISE ON THE DEVELOPMENT OF CARDIAC DYSSYNCHRONY IN PATIENTS WITH DEPRESSED LEFT VENTRICULAR FUNCTION Robert Blank, MD, Michael Kühne, MD, Beat Schär, MD, Peter Ammann, MD, Stefan Osswald, MD and Christian Sticherling, MD. University Hospital, Basel, Switzerland and Kantonsspital, St.Gallen, Switzerland. Introduction: Patients (pts) with depressed left ventricular ejection fraction (LVEF) and left bundle branch block benefit from cardiac resynchronization therapy (CRT). Little is known about the effect of physical exercise on mechanical dyssynchrony measured by echocardiography. Methods: Pts with LVEF 65ms and IVMD as a difference between aortic and pulmonic preejection times of > 45ms. A test was considered positive if the patient developed measurable signs of dyssynchrony, in both, IVMD and SLWMD. Results: 42 pts on optimized medical treatment for heart failure (37 male, 60 +/-14 years, 21 ischemic and 21 non-ischemic cardiomyopathy) were studied. 11 pts (26%) had a positive test (group A), 31 had a negative test (group B). In group A, IVMD increased significantly during exercise from 26 ±14ms to 57 ±12 ms (p<0.001), whereas IVMD remained unchanged in group B (14 ±13 ms and 12 ±16 ms, respectively, p=NS). There was no significant difference in SLWMD between the the two groups at rest (p<0.37). It increased significantly from 28 +/-22 ms to 80 +/-13 ms (p< 0.001) in group A, but not in group B (21+/-45ms to 30+/-46ms, p=NS). SLWMD after exercise became significantly longer in group A (p<0.01). The QRS duration at rest was significantly longer in group A (mean 153ms±21) than in group B (mean 121±32ms; p<0.007) and remained unchanged in both groups after exercise. 6/11 pts. (55%) with a positive test received a CRT and all were responders. Conclusions: The evaluation of cardiac dyssynchrony including measurement of SLWMD and IVMD at rest and during exercise may be a new tool to identify potential candidates for CRT. QRS-duration at rest seems to be predictive for the development of mechanical dyssynchrony under physical exercise. PO1-53 A NOVEL APPROACH TO DETERMINE OPTIMAL LV LEAD POSITION IN CRT USING EPICARDIAL MAPPING WITH A SUBXIPHOID APPROACH Jad D. Swingle, MD, Ann C. Garlitski, MD, Scott A. Bernstein, MD, Ashish B. Patel, MD, Anthony Aizer, MD, Douglas S. Holmes, MD, Neil E. Bernstein, MD and Larry A. Chinitz, MD. New York University, New York, NY. Introduction: CRT has been proven effective in improving symptoms in severe CHF. The optimal site for placing the LV lead has not been well studied due to limitations of the coronary venous anatomy. Epicardial pace mapping is a novel method to define optimal left ventricular pacing site. Methods: Three patients with a conventional indication for CRT and no previous cardiac surgery were enrolled. Through a transcutaneous subxiphoid puncture, access to the epicardial space was achieved. Using Endocardial Solutions, Inc. NavX mapping system a three

dimensional anatomic, voltage and activation map of the epicardial surface of the heart was created. The epicardial surface of the LV was divided into seven regions (anterior base, anterior mid, lateral base, lateral mid, posterior base and posterior mid, and apex). Sequential A-V biventricular pacing through a roving epicardial mapping catheter and an endocardial RV apex catheter was performed from each of the seven identified regions. During pacing at each site a transthoracic echocardiogram was performed to measure aortic VTI as a measure of acute hemodynamic response to pacing. Results:

Aortic Velocity Time Integral During Pacing From LV Sites

Patient

Baseline

RV Only Pacing

#1 Anterior Base

#2 Lateral Base

#3 Posterior Base

#4 Anterior Mid Ventricle

#5 Lateral Mid Ventricle

#6 Posterior Mid Ventricle

#7 Apex

1 15.5 16.4 SCAR 17.5 15.5 15.2 15.8 16.4 17.8

2 19.9 16.3 16.5 20 19.2 14.4 22.9 19.1 SCAR

3 12.2 13.3 12.3 13.9 13.4 13.1 13.6 12.3 13.0

Conclusions: Epicardial pace mapping is technically feasible and safe. Epicardial mapping allows evaluation of the entire LV without the limitations of coronary venous anatomy. There are significant hemodynamic differences between the seven tested sites in the LV. The site that resulted in the best acute hemodynamic improvements was not the same in all patients. In some patients, pacing the LV in specific sites may worsen acute hemodynamic response. This study suggests mapping different regions of the LV identifies areas of scar and may identify an optimal pacing site specific to an individual heart failure patient and lead to greater symptomatic improvement. PO1-54 EPICARDIAL VS. CORONARY SINUS LEAD PLACEMENT FOR CARDIAC RESYNCHRONIZATION THERAPY IN THE TREATMENT OF HEART FAILURE Henri Roukoz, MD, Firas El Sabbagh, MD, Anbazhagan Prabhakaran, MD, Penny L. Houghtaling, MS, Lillian Batizy, MS, Jose Navia, MD, Patrick J. Tchou, MD and Mina K. Chung, MD. Cleveland Clinic, Cleveland, OH. Introduction: Minimally invasive left ventricular (LV) epicardial (EPI) leads may offer an alternative after coronary sinus (CS) lead placement failure in cardiac resynchronization therapy (CRT). We sought to compare patients undergoing CRT with EPI leads vs. CS

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leads in terms of survival and effect on ventricular function and QRS duration. Methods: Patients who underwent CS lead placement attempts for CRT between 9/98 and 8/05 were identified from a prospectively collected clinical database. Patients who failed CS lead placement and subsequently underwent minimally invasive LV EPI lead placement were compared to patients with successful CS lead placement. Clinical, electrocardiographic, and echocardiographic data were collected at baseline, 1, 3, 6, 12 and >12 months post-procedure. Data were analyzed using a parametric hazard model and propensity analysis. Results: CRT devices were placed in 442 patients (78% male, mean age 67 years, 62.4% ischemic cardiomyopathy, LVEF 18.9±7.1%, QRS duration 175.8±27.3 ms). CS leads were successfully placed in 384 pts (87%) and 58 (13%) patients had EPI lead placement. ICDs were placed in 65% and pacemakers in 35%. Age, sex, history of MI, diabetes, NYHA class, use of β-adrenergic blockers and baseline EF and QRS were similar in both groups. Propensity modeling showed EPI patients were more likely to have an ICD, have less tobacco use, and less use of ACE inhibitors or thiazides. For the longitudinal repeated measurements analysis of EF and QRS, there were no differences in EF (p=.18), percent change in EF (p=.2), QRS (p=.6) or percent change in QRS (p=.9). Baseline EF (p<.0001) and QRS (P<.0001) had more impact on EF and QRS at follow-up, respectively. Results were similar after adjusting for the propensity score. Survival analysis using a parametric hazard model showed no difference in the groups. After adjusting for the propensity score there was still no difference in mortality. Conclusions: Compared to CS leads, minimally invasive LV epicardial leads used for CRT appear to have a similar effect on EF, QRS duration and survival. They are an acceptable alternative to CS leads for CRT in heart failure patients. PO1-55 LONG-TERM EFFECTS OF CRT IN PATIENTS WITH NARROW QRS: THE INSYNC/INSYNC ICD ITALIAN REGISTRY Maurizio Lunati, MD, Maurizio Gasparini, MD, Massimo Santini, MD, Augusto Achilli, MD, Maurizio Landolina, MD, Luigi Padeletti, MD, Antonio Curnis, MD, Giovanni B. Perego, MD, Alessandra Denaro, MS and Mario Davinelli, PhD. Niguarda Hospital, Milan, Italy, Istituto Humanitas, Milan, Italy, S. Filippo Neri, Rome, Italy, Belcolle Hospital, Viterbo, Italy, S. Matteo, Pavia, Italy, Careggi Hospital, Florence, Italy, Spedali Civili, Brescia, Italy, Istituto Auxologico, Milan, Italy, Medtronic Italy, Rome, Italy and Medtronic Italia, Rome, Italy. Introduction: Cardiac resynchronization therapy (CRT) is recommended for patients with symptomatic heart failure presenting QRS>120ms, as marker of ventricular dyssynchrony. The effects of CRT in narrow QRS patients (QRS≤120ms) are still controversial. Aim of this study was to evaluate the effects of CRT in patients with QRS≤120ms (nQRS) with respect to patients with QRS>120ms (lQRS). Methods: The study population consisted of 1971 patients (217 nQRS) consecutively implanted with biventricular devices. They were enrolled in the InSync/InSync ICD Italian Registry and underwent baseline evaluation and periodical follow-up visits. We estimated the clinical outcome after 12-month of CRT, and the mortality data. Results: After 12 months of CRT, NYHA Class significantly improved in both groups (lQRS: from 2.9±0.6 to 2.1±0.7; nQRS: from 2.9±0.6 to 2.0±0.7), ejection fraction increased (lQRS: from 26±8% to 34±11%; nQRS: from 28±8% to 37±11%), left ventricular end-diastolic diameter decreased (lQRS: from 69±9mm to 66±10mm; nQRS: from 68±9mm to 66±9mm), as well as left ventricular end-systolic diameter (lQRS: from 59±11mm to 54±12mm; nQRS: from 57±8mm to 54±10mm). At a median follow-up of 16 months, the all-cause mortality resulted similar in the two groups (log-rank test p=0.678).

Conclusions: Our results indicate that CRT induced similar benefits in both groups at long-term follow-up, resulting in comparable effects on mortality.

PO1-56 EFFECTS OF CARDIAC RESYNCHRONIZATION THERAPY IN PATIENTS WITH MILD SYMPTOMS OF HF WITH RESPECT TO SEVERELY SYMPTOMATIC HF PATIENTS: THE INSYNC/INSYNC ICD ITALIAN REGISTRY Maurizio Landolina, MD, Maurizio Lunati, MD, Maurizio Gasparini, MD, Massimo Santini, MD, Luigi Padeletti, MD, Augusto Achilli, MD, Stefano Bianchi, MD, Francesco Laurenzi, MD, Antonio Curnis, MD, Antonio Vincenti, MD, Alessandra Denaro, MS and Anna Maria Varbaro, MS. S. Matteo, Pavia, Italy, Niguarda Hospital, Milan, Italy, Istituto Humanitas, Milan, Italy, S. Filippo Neri, Rome, Italy, Careggi Hospital, Florence, Italy, Belcolle Hospital, Viterbo, Italy, Fatebenefratelli, Rome, Italy, S. Camillo Hospital, Rome, Italy, Spedali Civili, Brescia, Italy, S. Gerardo dei Tintori, Monza, Italy, Medtronic Italy, Rome, Italy and Medtronic Italia, Milan, Italy. Introduction: The effects of cardiac resynchronization therapy (CRT) in NYHA class II patients are still controversial. Aim of this study was to evaluate the effects of CRT in NYHA II with respect to NYHA III and IV patients. Methods: We evaluated the clinical outcome after 12-month of CRT, and the long-term survival of 952 patients (188 in NYHA class II) consecutively enrolled in a national observational registry. Results: The NYHA II group experienced lower all-cause mortality (log-rank test p=0.018) and less major cardiovascular events (CVe) compared to the NYHA III/IV patients (rate 13.0 vs. 23.0 per 100 patient-years of follow-up, p< 0.001). The percentage of patients who improved the NYHA class after 12 months of CRT was lower in NYHA II than in NYHA III/IV patients (34% Vs. 69%, p< 0.001), while the absolute increase of ejection fraction was similar in the two groups (8±9% Vs. 9±11%, p=NS), as well as the reduction of end-diastolic diameter (-3±8mm Vs. -3±8mm, p=NS) and end-systolic diameter (-4±10mm Vs. -6±10mm, p=NS). In both groups, the patients with major CVe during follow-up exhibited less or no reverse remodeling compared to those with better long-term clinical outcome (Figure, *= p<0.05). Conclusions: Our results indicate that CRT induced similar improvements of ventricular function in both groups, whereas the improvement in functional status was significantly lower for NYHA II than for III/IV patients. A positive effect of CRT on cardiac dimensions was associated with long-term beneficial effect on disease progression in NYHA II patients

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PO1-57 CARDIAC CONTRACTILITY MODULATION BY NON-EXCITATORY ELECTRICAL CURRENTS IMPROVES ACUTELY DIASTOLIC FUNCTION IN PATIENTS WITH CHRONIC SYSTOLIC HEART FAILURE Turgut Brodherr, MD, Thomas Lawo, MD, Matthias Vogt, BSc, Netanel Eizenberg, MS, Benny Rousso, PhD and Andreas Mügge, MD, PhD. University Hospital Bergmannsheil, Bochum, Germany and Impulse Dynamics Ltd., Haifa, Israel. Introduction: Cardiac Contractility Modulation (CCM) by application of non-excitatory currents is an effective therapy for patients with chronic systolic heart failure (CHF) and uncompromised interventricular conduction. Altered transsarcolemmal calcium transients and, in the long term, a modified myocardial gene expression seem to contribute to the observed contractile benefit. Due a maladaptive fetal gene program in the failing heart, CCM could theroretically worsen diastolic function by increased calcium transients. Therefore we analysed the acute effect of CCM on diastolic function focussing on active isovolumetric relaxation. Methods: 26 patients with CHF had a CCM-stimulation device (Optimizer II/III) implanted, data of 22 patients were suitable for analysis. The acute effects of CCM on contractility (dP/dtmax), relaxation (dP/dtmin) and preload (left ventricular end-diastolic pressure (LVEDP)) were determined by LV pressure changes acquired with a micromanometer during implantation. Subsequently raw data were smoothed to minimize undesirable artifacts and futher analysed. Results: The mean baseline values for dP/dtmax and dP/dtmin were 1047 mmHg/s and -1005 mmHg/s, respectively. After activation of CCM a significant gain was achieved simultaneously in contractility as well as in active relaxation (maximum change of dP/dtmax at 1114 s and dP/dtmin at 1103 s; p = 0.35). These beneficial effects were detected both by raw data analysis (∆dP/dtmax: +8.9%, p < 0.0001; ∆dP/dtmin: + 6.0%, p < 0.0001) and after applying smoothing functions (∆dP/dtmaxs: +7.2% , p < 0.0001; ∆dP/dtmins: +4.2%, p < 0.0001). The documented slight increase of LVEDP under CCM-conditions may contribute to the beneficial clinical effects as a surrogat of elevated preload (∆LVEDP : +1.6 mmHg, p = 0.005). Conclusions: Though the acute beneficial effect of CCM-stimulation is thought to be mediated by enhanced systolic calcium transients, an increase of diastolic capacity in terms of active relaxation was detected. Local CCM-stimulation may affect global preload as an additional mode of action.

PO1-58 ELECTRONIC INTERFERENCE OF IMPLANTABLE DEVICES INDUCED BY CARTO� MAPPING SYSTEMS Peter Hahn, MD, Patricia Pacetti, NP, Susan McAllister, NP, Seun Ajayi, BS, Thomas Marchese, BS, Muqtada Chaudhry, MD, Michael V. Orlov, MD, PhD and Charles I. Haffajee, MD. Hospital of St. Elizabeth, Boston, MA. Introduction: Magnetic mapping systems are increasingly employed in EP procedures as adjuncts to standard fluoroscopic navigation. As the number of pts with implantable devices increases, so does the risk of unforeseen interactions with magnetic systems such as Carto� (Biosense Webster). Methods: 24 pts with implantable devices (13 PPMs, 10 ICDs, and 1 Reveal� [ILR]) participated in this study. The devices tested were manufactured by Biotronik, Boston Scientific (Guidant), ELA, Medtronic, St. Jude Medical, and Vitatron. The pts were positioned supine on a table above the Carto magnet. The devices were interrogated before and during activation of the Carto electromagnetic field. Any interference was documented, and the devices were re-interrogated outside the EP lab. Results: 11 out of 24 (46%) of the devices experienced interference that terminated telemetry and prevented any response programming commands. One device (Figure 1) recorded intense electrogram noise prior to termination of telemetry. There were no interactions documented when the Carto field was inactive. The susceptibility of different devices was highly variable: Biotronik (0/1 ICD, 1/1 PPM), Boston Scientific (0/3 ICD, 3/3 PPM), ELA (1/1 PPM), Medtronic (0/4 ICD, 0/5 PPM, 1/1 ILR), St. Jude Medical (2/2 ICD, 2/2 PPM), and Vitatron (1/1 PPM). None of the devices were reset or placed into �magnet mode� by the active Carto magnetic field, nor were any device programs altered. Conclusions: Implantable devices are susceptible to external electromagnetic interference, including exposure to the magnetic field generated by Carto. In this series of 24 pts, although none of the devices failed to deliver pacing therapy, 46% were affected by interference that prevented telemetry and reprogramming. Further research into the mechanism of interference and inability to program devices in such environments is clearly needed.

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PO1-59 UNLEADED: THE FLUOROLESS 3D LEAD IMPLANT Toby Markowitz, BS, Phillip Falkner, DVM, Chad Giese, BS, K. Evan Nowak, BS, Brian McDonald, BS, Marina Jovanovic, BS, Brian Craig, MS and Victoria Interrante, PhD. Medtronic, Inc., Minneapolis, MN and University of Minnesota, Minneapolis, MN. Introduction: Intraoperative fluoroscopy during cardiac pacing lead implantation presents an occupational hazard to implanting physicians and their staff, both through cumulative radiation exposure and the orthopedic burden of wearing protective lead (Pb) garments. We assessed feasibility of anatomic mapping and device lead implantation using a novel non-fluoroscopic 3D imaging system based on bio-impedance. Methods: A 44 kg. swine was anesthetized with isoflurane. Eight device implanting physicians were scheduled and presented to the operating suite. They were proctored briefly (range 8 to 15 minutes) by an experienced veterinarian implanter (PF) who used a deflectable sheath (modified C304, Medtronic) and Swan-Ganz Bipolar Pacing Catheter (D97120F5, Edwards Lifesciences) to map the heart. The 3D image was cleared allowing the physicians to map the heart and implant a right ventricular lead (3830, Medtronic). The map image was again cleared and mapping repeated. All work was performed without fluoroscopy or wearing of lead (Pb) garments. Results:

Prior Experience � Minutes to perform Threshold & R-wave Measurements Implanter

Swine Deflectable sheath 1st Map Implant 2nd

Map

Volts@ 0.4 mS.

mVolts

1 5 2 14.8 3.0 * 0.8 6.9

2 4 2 7.0 4.5 3.0 0.9 9.2

3 4 4 10.0 3.0 5.5 3.2 10.1

4 2 1 5.5 2.0 3.0 2.0 5.1

5 4 1 6.5 2.5 4.8 3.5 3.0

6 5 2 5.0 1.0 5.0 5.5 3.8

7 2 1 8.8 1.8 7.5 3.0 8.9

8 4 3 8.0 1.5 5.0 2.2 8.3

Mean±S.D. 3.7±1.1 1.9±1.1 8.2±3.1 2.4±1.1 4.8±1.6 2.6±1.5 6.9±2.7

* schedule did not allow 2nd map. � 1= Experienced, 5= Inexperienced. All implanters created a map and implanted a pacing lead in the right ventricle. Stimulation and sensing parameters were measured immediately following initial implant and were generally acceptable. The protocol did not allow repositioning. Second mappings took a mean of 2.8 minutes (32%) less than the first. No complications were observed. Conclusions: Although the physicians were unfamiliar with swine anatomy, the deflectable sheath and the visualization system, all successfully implanted leads in a swine without fluoroscopy. Self-reported physician experience with swine and the deflectable sheath did not appear to affect the results. The Swan-Ganz catheter and deflectable sheath combination allowed safe exploration of cardiac structures. Time reduction for the second mappings suggests further time savings may be realized. This demonstration using novel bio-impedance based 3D imaging suggests the feasibility of reducing occupational hazards in the electrophysiology laboratory while ensuring safe device implantation. Further exploration is warranted.

PO1-60 DEFIBRILLATOR IMPLANT TESTING: APPROPRIATE USE OF 10 JOULE SAFETY MARGIN REQUIRES A STANDARDIZED TEST PROTOCOL AND ALLOWS REDUCTION OF IMPLANT TESTING BURDEN Karel F. Smits, MSc. Bakken Research Center, Maastricht, The Netherlands. Introduction: Aim is to study the role of the test protocol on outcome of Defibrillation Threshold (DFT) implant testing. Methods: A 2-parameter (E50,C) Dose-Response (DR) curve represents the relation between probability of defibrillation success and shock energy E. E50 is the energy at 50% success. C is the steepness of the curve. P(success) = (E/E50)^C / (1+(E/E50)^C) Computer modeling estimated the parameter distributions from a test population of 654 DFT's from the Painfree RX II study. Simulated DR curves were subjected to clinically current test protocols resulting in success/failure, DFT, sensitivity of detecting High Risk (HR) patients, number of device delivered shocks and cumulative shock energy. A failed test had a less than 10 Joule Safety Margin. A High Risk patient required > 20J to obtain 80% defibrillation success. Results: Of the test population 4.8% was a High Risk patient. The table below shows the results for various test protocols: Simulated test protocol

P(fail test)

Sensitivity HR pt

Nr shocks

Cum. energy

1/1 at 15 J .082 .67 1 15

2/2 at 20 J .063 .64 2 40

+if failed, 1 repeat 2/2 .025 .43 2.06 41.1

+if failed twice, repeat 2/2 .016 .32 2.08 41.6

Step Down-start at 20 J .037 .41 4.8 57

Step Down-start at 14J .010 .19 4.5 42

SD+ 1 confirm (=DFT+) .019 .36 5.8 54

SD+ 2 confirm (=DFT++) .028 .50 7.0 66

Binary Search-start at 12J .011 .22 3.2 30

Conclusions: 1. Sensitivity of detecting High Risk patients with E80 > 20 Joule ranged from 19-64% for various protocols while requiring 2 successful VF terminations at 10 Joule Safety Margin. 2. Standardization of DFT implant test protocol is necessary to obtain a standard sensitivity of detecting High Risk patients. 3. A 1/1 @ 15 Joule protocol could be considered as a standard test protocol as it yields the highest sensitivity at the lowest number of shocks and the lowest cumulative test energy. PO1-61 A NOVEL LEAD DESIGN REDUCES FAR FIELD R-WAVES (FFRWS) AND DECREASES THE INCIDENCE OF INAPPROPRIATE AUTOMATIC MODE SWITCH EPISODES Ralph S. Augostini, MD, Scott L. Beau, MD, David Henderson, MD, W. Ben Johnson, MD, Stephen P. Chough, MD, Charles Athill, MD and John P. McKenzie, III, MD. Riverside Methodist Hospital, Columbus, OH, Arkansas Heart Hospital, Little Rock, AR, Florida Hospital Ormond Memorial, Ormond, FL, Iowa Heart Center, Des Moines, IA, Midwest Heart Foundation, Lombard, IL, Sharp Memorial Hospital, San Diego, CA and Glendale Memorial Hospital, Glendale, CA.

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Introduction: FFRWs are sensed in approximately one-third of patients with DDD pacemakers and represent the primary reason for inappropriate automatic mode switch (AMS). We hypothesized that decreasing the atrial lead anode to cathode tip-to-ring electrode spacing reduces FFRW sensing. The OptiSense® 1699T Lead Study was a prospective, multi-center, randomized trial designed to evaluate ability of a 1.1mm bipolar tip-to-ring spacing to attenuate FFRW signals and decrease inappropriate AMS. Methods: Patients with standard indications and without chronic atrial fibirillation received a St. Jude Medical DDD(R) pacemaker, a market-released RV lead, and a right atrial lead with either a 1.1mm electrode spacing, (OptiSense 1699T, treatment) or 10.0 mm electrode spacing (Tendril® SDX 1688T lead, control) and were followed for 3 months. Atrial far field signals (with ventricular paced and intrinsic events), AMS episode stored electrograms, and atrial sensing and pacing thresholds were evaluated at the discharge, 1 and 3 month visits. Results: Of 122 patients enrolled, the mean age was 73.7 ± 11.5 years, 53% were male and 73% had a history of hypertension. No adverse safety issues were observed. Variable (all at 3 months)

OptiSense (1.1 mm)

Tendril SDX(10.0 mm) p-value

Pts with Paced FFRWs < 0.1mV 90.9% 40.9% < 0.0001

Pts with Intrinsic FFRWs < 0.1mV 95.5% 86.4% 0.39

Atrial Sensing Threshold (mV) 2.64 ± 1.44 2.83 ± 1.31 0.47

Atrial Pacing Threshold (V @ 0.5msec) 0.59 ± 0.16 0.85 ± 0.26 < 0.001

% Pts with Inappropriate AMS Episodes 6.9% 25.7% 0.03

% Stored EGMs with Inappropriate AMS 3% 49% 0.009

Conclusions: The occurrence of sensed FFRWs is higher with paced ventricular beats than intrinsic events. Close (1.1mm) atrial bipolar electrode spacing significantly reduced paced FFRW signals, which resulted in a highly significant reduction in the incidence of inappropriate AMS. These data indicate that the OptiSense lead may improve overall pacemaker performance and reliability of AMS episodes. PO1-62 SAFETY AND EFFICACY OF A LEFT VENTRICULAR LEAD (LV) WITH DEPLOYABLE LOBE FIXATION Stuart Adler, MD, George Crossley, MD, Gery F. Tomassoni, MD, Satish Goel, MD, Andrew Rosenblum, MD, Gregory Botteron, MD, Hardwin Mead, MD, Derek V. Exner, MD, MPH and Model 4195 Lead Clinical Investigators. St. Paul Heart Clinic, St. Paul, MN, Mid-State Cardiology, Nashville, TN, Central Baptist Hospital, Lexington, KY, Baptist Medical Center, Jacksonville, FL, West Michigan Heart, PC, Grand Rapids, MI, Metro Heart Group of St. Louis, Creve Coeur, MO, Cardiovascular Medicine & Cardiac Arrhythmias, Inc., Palo Alto, CA and University of Calgary, Calgary, Alberta, Canada. Introduction: Achieving a stable LV pacing site within the coronary sinus (CS) is problematic in some patients. This report summarizes the experience with an investigational 5 Fr, steroid-eluting, unipolar LV lead with deployable lobes (Model 4195), designed to provide enhanced passive fixation within the CS. Methods: A total of 296 patients were enrolled in a prospective, multi-center cohort (25 centers) and followed for up to 24 months. Patients with NYHA class III or IV symptoms, a QRS > 130 ms, and an ejection fraction (EF) < 35% were included. Data from previous LV lead studies were used to define the primary endpoints: Safety: Freedom from Model 4195 lead-related complications > 80% at 3 mo; Efficacy: Mean LV voltage threshold at 0.5ms, < 2.5 volts at 3 mo.

Results: Of 296 subjects enrolled, 284 had an LV lead attempt and were included in the safety analysis. Subjects had a mean age of 70 yrs, 27% were female, and 94% had NYHA class III limitation. Mean intrinsic QRS width was 157 ms and mean LV EF was 23%. Of the 284 subjects, 273 had a Model 4195 lead attempt, and 259 of these (95%) were successful. Follow-up ranged from 0 to 24 (median 12 mo). At 3 mo there were 10 Model 4195 lead-related complications in 9 subjects, yielding a freedom from first LV lead-related complication rate of 96.5%. Complications included lead dislodgement (3), loss of capture (2), and extra-cardiac stimulation (5). Following 2 dislodgements early in the study, lead placement guidelines were developed. No further dislodgements occurred when guidelines were followed. The mean LV threshold at 3 mo was 1.3 V (Figure 1).

Conclusions: The Model 4195 lead demonstrates a low rate of lead dislodgement (1.2%), good safety performance, and stable pacing thresholds. These results, combined with the novel fixation of this lead, indicate that this lead provides a new alternative for LV lead placement via the CS. PO1-63 �MINVPACE�: A STUDY COMPARING MINIMAL VENTRICULAR PACING AND PREVENTIVE AF ALGORITHMS IN THE TREATMENT OF PAF Anita Arya, MRCP, Rick A. Veasey, MRCP, John Silberbauer, MRCP, Carey P. Edwards, MRCP, Guy W. Lloyd, MD, FRCP, Nikhil R. Patel, MD, FRCP and A. Neil Sulke, MD, FRCP. East Sussex Hospitals NHS Trust, Eastbourne, United Kingdom. Introduction: The beneficial effects of atrial pacing on paroxysmal atrial fibrillation (PAF) may be negated by increased ventricular pacing. This was a prospective randomised study evaluating the effect of pacing algorithms that minimise ventricular pacing (MVP) with and without anti-AF algorithms, on AF burden (AFB) in patients with PAF. Methods: Using a single blind three-way cross-over design, patients with AF burden 1-70% with or without intermittent high grade AV block (AVB), implanted with pacemakers with MVP capability were enrolled. Three devices were assessed: Ela Symphony, Vitatron T70 and Medtronic Enrhythm. Patients were randomised to MVP with or without preventive AF algorithms or DDDR (AV delay (AVD) 150ms) for 2 months per phase. The primary outcome measures were AFB

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and AF episodes/day. Secondary outcome measures examined the effect of ventricular and atrial pacing on AF burden. Results: 65 patients were enrolled, of these, 32 (mean age 74.5 +/- 7.8, 62.5% males) had an AF burden of 1-70% during the induction phase and completed all phases. Pacing indications were SSS in 82 % and intermittent AVB in 18% of patients. There was no significant difference in AFB or AF episodes/day between the control phase DDDR, 14.0±17.7% 2.3±2.6, and MVP, 14.7±17.7% 2.9±5.0, or MVP + AF algorithms, 13.1±17.5% 4.3±8.2, p=0.85 and 0.84. Ventricular pacing was significantly higher during the DDDR (AVD150) phase, 82±21%, than in MVP 16±27% and MVP+algorithms 25±33%, p=<0.001. Atrial pacing was greater during MVP+algorithms, 70±25% versus 57±27% in DDDR and 45±27% in MVP alone, p=0.004. There was no significant correlation between V pacing and AF burden, p=0.88. Conclusions: Minimal ventricular pacing algorithms are highly effective in reducing ventricular pacing but do not reduce AFB in the short term. No additional benefit or adverse outcome was found with preventative anti-AF algorithms in combination with minimal ventricular pacing algorithms. PO1-64 IMPACT OF ATRIAL PACING ON AF BURDEN: LONG TERM ANALYSIS FROM THE SAFARI STUDY Atul Prakash, MD, Michael R. Gold, MD, PhD, Charles I. Haffajee, MD, Bharati Manda, MS and Shelby Li, MS. St. Joseph's Regional Medical Center, New Jersey, NJ, Medical University of South Carolina, Charleston, SC, St. Elizabeth's Medical Center, Boston, MA and Medtronic, Inc., Minneapolis, MN. Introduction: SAFARI was a multicenter, prospective, randomized, study including pts with paroxysmal AF (PAF) and bradycardia, designed to evaluate the safety and efficacy of AF Prevention Pacing Therapies (PPTs)with standard DDD pacing. Pts were required to have at least 2 episodes of AF in the 3 mos prior to implant. All pts received a Selection 9000 pacemaker (Vitatron, NL) and underwent a 4mo �run-in� period of DDD pacing. Only pts with documented AF during this period were randomized to PPT ON/OFF . The percentage of patients with no AF during the 4mos run-in period has been reported (204 of 485 patients, 42%). We now report the long term impact of DDD pacing alone on AF burden in all pts with PPTs OFF over 10 mos follow up. Methods: Pts with FFRW sensing issues, deaths, withdrawals, missing data, and those randomized to PPTS ON were excluded from analysis leaving 296 pts that were treated with DDD pacing. Of these, 170 had no AF burden at time of randomization while 126 pts had AF burden. AF burden was compared during the 4mos run-in period and 10 mos in these two groups and correlated with % A and % V pacing. Results: At 10 mos a total of 31% (93 pts) had no AF burden. Of pts with AF at randomization only 8.7% (11) remained AF free at 10 mos (Figure 1). Of pts without AF at randomization, 48% (82) continued free of AF at 10 mos (p=0.0002 by logistic regression). % A pacing was 68% in pts with no AF and 58% in pts with AF during follow-up. Both % A pacing and % V pacing were similar in the two groups. Conclusions: In pts with PAF and a pacemaker indication, a significant proportion (31%) are rendered AF free by dual chamber pacing alone for at least 10 mos. Early AF recurrence within 4 mos of pacer implant predicts significantly higher AF burden over long term. This may reflect either electrical remodeling or a population at higher risk for AF. These pts may be considered for further therapies i.e PPTs, antiarrhythmic drugs,or ablation.

PO1-65 IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR THERAPY BY GENOTYPE IN LONG QT SYNDROME PATIENTS Wojciech Zareba, MD, PhD, Ilan Goldenberg, MD, Arthur J. Moss, MD, James Daubert, MD, Scott McNitt, MS and Slava Polonsky, MS. University of Rochester, Rochester, NY. Introduction: Implantable cardioverter-defibrillators (ICDs) are increasingly used in long QT syndrome (LQTS) patients. There are limited data regarding clinical course of LQTS patients with ICDs by genotype. Methods: We analyzed data from 88 LQTS patients, who received an ICD at the discretion of their cardiologists and who were genotyped. There were 34 LQT1 patients, 45 LQT2 patients, and 9 LQT3 patients. Results: Clinical characteristics of three subgroups were similar. For LQT1, LQT2, LQT3, respectively: age at ICD implantation: 28+/-17, 30+/-16, and 23+/-18 (p=0.549); females: 79%, 78%, and 44% (p=0.114); baseline QTc: 512+/-55, 518+/-71, 527+/-63 (p=0.822); aborted cardiac arrest 15%, 27%, and 11% (p=0.400); aborted cardiac arrest or syncope: 65%, 62%, and 33% (p=0.258); beta-blockers: 94%, 93%, 89% (p=0.869). Median follow-up was resepctively: 4.9, 4.7, and 2.7 years (p=0.546). Appropriate therapy occurred in 9% of LQT1, 27% of LQT2, and none of LQT3 patients (p=0.040). Figure shows cumulative probability of appropriate ICD therapy by genotype. At 4 years event rates were 3% for LQT1, 21% for LQT2 and none for LQT3 patients. Conclusions: LQT2 patients have high risk of recurrent arrhythmias despite beta-blocker treatment. LQT2 genotype should be considered as a risk factor when evaluating LQTS patients for ICD therapy.

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PO1-66 PRIMARY PREVENTION ICDS IN THE SETTING OF CHRONIC KIDNEY DISEASE: A DECISION MODEL ANALYSIS Mitesh S. Amin, MD, Aaron D. Fox, MD, Gautham Kalahasty, MD, Richard K. Shepard, MD, Mark A. Wood, MD and Kenneth A. Ellenbogen, MD. Virginia Commonwealth University, Richmond, VA. Introduction: Primary prevention ICD trials have excluded patients with chronic kidney disease (CKD). Co-morbidities and lower life expectancy in patients with CKD make the benefit of ICD implantation uncertain. We used decision analysis modeling to estimate survival benefit for primary prevention ICDs in this patient group. Methods: A decision analysis model was constructed to evaluate the risks and benefits of ICD implantation versus no implantation in patients with CKD who met current criteria for a primary prevention ICDs. Published data and life-tables were used for event rates, infection risks, and overall survival in CKD patients with and without ICDs. Variables included patient age (40-80 years), GFR and stage of CKD (0-5), probability of SCD (6-22%/year), and device implantation mortality (0.3-1.2%/implant). All cause survival was the primary endpoint. Results: The benefits of an ICD for primary prevention in patients with CKD hinges primarily on the patient age and stage of kidney disease. With stages 1 and 2 (GFR>=60), ICD implantation benefits a majority, regardless of age. However, in patients with higher stages of CKD (GFR<60), the benefit is less significant and dependent on patient age. This is attributed to patients having a high procedural risk and limited life expectancy with advanced renal disease. At an average procedure mortality of 0.5% death/procedure, ICD implantation is favored at ages<75 for stage 3 (GFR 30-59), ages<70 for stage 4 (GFR 15-29), and ages<55 for stage 5 (GFR<15 and hemodialysis). As procedural mortality increases, age thresholds decrease. Conclusions: Our model shows the benefit from primary prevention ICDs is determined by patient age and stage of renal disease. Physicians need to consider the degree of CKD in determining the appropriateness of ICD therapy. This theoretical analysis can help design prospective clinical trials.

PO1-67 DFT FOR A SUBCUTANEOUS IMPLANTABLE DEFIBRILLATOR (S-ICD®) SYSTEM: EXPERIENCE FOR THE FIRST 150 PATIENTS Margaret A. Hood, MD, Warren M. Smith, MD, Andrew A. Grace, MD, PhD, Simon P. Fynn, MD, FRCP, Derek L. Connelly, MD, Jay Wright, MD, Ian G. Crozier, MD, Iain C. Melton, MD, Andrey Ardashev, MD, PhD, Johannes Sperzel, MD, Jörg Neuzner, MD, Stefan G. Spitzer, MD, Riccardo Cappato, MD and Gust H. Bardy, MD. Auckland City Hospital, Auckland, New Zealand, Papworth Hospital, Cambridge, United Kingdom, Glasgow Royal Infirmary, Glasgow, United Kingdom, Cardiothoracic Center, Liverpool, United Kingdom, Christchurch Hospital, Christchurch, New Zealand, Burdenko Hospital, Moscow, Russian Federation, Kerckhoff-Klinik, Bad Nauheim, Germany, Klinikum Kassel, Kassel, Germany, Ambulantes Herz-Zentrum, Dresden, Germany, San Donato Hospital, Milan, Italy and University of Washington, Seattle, WA. Introduction: The S-ICD® system offers an opportunity to significantly streamline ICD surgery. Here we summarize the mean DFT data for the first 150 patients tested with an S-ICD® system demonstrating the viability of an S-ICD® system to defibrillate reliably. Methods: All patients were tested with an S-ICD® system following informed consent. In the first 52 patients various configurations were tested to determine the feasibility of subcutaneous defibrillation. These data were used to design 5 within-subject studies to optimize system configuration, capacitance and polarity as well as compare DFTs for the S-ICD® system. All DFT testing used a step-down, skip-up test protocol. Results: A total of 40 system configurations were tested in the first 52 patients. Of these, 18 reliably defibrillated patients (mean DFT = 14-60J). The results from these patients were used to test a limited number of system configurations in separate within-subject studies. A total of 98 patients were enrolled in 5 studies and a total of 989 VF inductions and defibrillation shocks were delivered using the S-ICD® test system. There was only one failure to defibrillate a patient. The mean DFT ranged from 29-50J for all tested configurations. A total of 403 inductions were tested for a lateral can/parasternal electrode configuration with the mean DFT consistently in the 34-37J range across the 5 studies. Conclusions: Numerous system configurations for the S-ICD® system reliably defibrillate patients. A limited number of configurations satisfy the a priori criteria of reliable defibrillation and uncomplicated surgical placement using anatomical landmarks without fluoroscopy. Based on the DFT data from the first 150 patients it appears that the final preferred S-ICD® system configuration can reliably defibrillate patients. This would allow for a device with an output between 60-80J including consideration for a suitable safety margin. PO1-68 INCIDENCE AND CAUSES OF SINGLE VENTRICULAR BACKUP PACED BEATS PRIOR TO VT/VF IN A PACING MODE THAT PROMOTES AV CONDUCTION Todd Sheldon, MS, James W. Johnson, MS, Linda L. Ruetz, MS and Michael O. Sweeney, MD. Medtronic, Inc., Minneapolis, MN and Brigham and Women's Hospital, Boston, MA. Introduction: Managed Ventricular Pacing (MVP) is an enhanced AAI-based pacing mode that provides backup ventricular pacing (VP) during loss of AV conduction. VP can be triggered by true AV block, ventricular undersensing, or by rules to provide VP during potential electrical crosstalk (ventricular sense occurring immediately after an atrial pace). We investigated the incidence and causes of single VPs immediately prior to VT/VF episodes in the EnTrust Trial where MVP was the primary pacing mode.

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Methods: All VT/VF episodes with pre-storage EGM enabled were analyzed and episodes during MVP operation were examined for single VPs prior to VT/VF onset. Results: A total of 351 VT/VF episodes occurred during MVP operation in 421 patients followed for 5.3 ± 3.9 months. Single VPs were observed in 16/351 (4.6%). Of these, 13/16 (81%) were triggered by VPDs creating a pacing facilitated short-long-short sequence terminated by a single VP. The specific causes for the single VPs were: 10/16 (62.5%) were due to �pseudo-crosstalk� triggered by VPDs in the crosstalk window, 3/16 (18.8%) by true AV block, 2/16 (12.5%) by functional ventricular undersensing (VPD blanked by post atrial pace ventricular blanking) and 1/16 (6.2%) by far-field R wave oversensing. No true electrical crosstalk was observed. Conclusions: VT/VF episodes were rarely preceded by single VPs. The majority of single VPs were unnecessary and triggered by a VPDs in the crosstalk window. Future enhancements to MVP may involve more sophisticated rules for further eliminating unnecessary VPs.

PO1-69 BRADYCARDIA PACING INDUCED SHORT-LONG-SHORT SEQUENCES AT THE ONSET OF VENTRICULAR TACHYARRHYTHMIAS: A POSSIBLE MECHANISM OF PROARRHYTHMIA? Michael O. Sweeney, MD, Linda L. Ruetz, MS, Paul Belk, PhD, Thomas J. Mullen, PhD, James W. Johnson, MS and Todd Sheldon, MS. Brigham and Women's Hospital, Boston, MA and Medtronic, Inc., Minneapolis, MN. Introduction: Abrupt changes in ventricular cycle lengths (short-long-short, S-L-S) may initiate ventricular tachycardia (VT)/fibrillation (VF). S-L-S sequences may be passively permitted or actively facilitated by bradycardia pacing. Onset patterns of VT/VF in ICD patients were

analyzed to characterize interactions between pacing mode and VT/VF initiation. Methods: Initiating sequences of 1,356 VT/VF episodes in PainFree Rx II (634 patients) and EnTrust Trial (421 patients) were analyzed using stored electrograms and by pacing mode (DDD/R, VVI/R, and Managed Ventricular Pacing [MVP]). Results: Single VPDs without S-L-S initiated 73.7% of all VT/VF; 26.3% of VT/VF episodes were initiated by pacing permitted pauses (S-L-S sequences without ventricular pacing) or pacing facilitated pauses (S-L-S sequences actively facilitated by ventricular pacing including the terminal beat following a pause; Figure). Pacing permitted S-L-S VT/VF accounted for 25.6% (VVI/R), 20.0% (MVP), and 6.4% (DDD/R) of all VT/VF by mode. Pacing facilitated S-L-S VT/VF accounted for 14.8% (DDD/R), 9.4% (VVI/R), and 8.2% (MVP) of all VT/VF by mode. Pacing facilitated S-L-S VT/VF occurred in 5.2% (DDD/R), 3.3% (VVI/R), and 2.6% (MVP) of patients with episodes and was the sole initiating sequence in ~1-2% of patients. Pause durations during pacing facilitated S-L-S differed between modes (DDD/R 793 ± 172 ms vs. MVP 865 ± 278 ms vs. VVI/R 1180 ± 414 ms, p=0.002). The majority of these episodes were monomorphic VT. Conclusions: VT/VF in some ICD patients may be initiated by S-L-S sequences that are actively facilitated by bradycardia pacing operation and may constitute an important mechanism of ventricular proarrhythmia. Enhancements to bradycardia pacing operation to reduce the possibility of ventricular proarrhythmia merit investigation.

PO1-70 APPROPRIATE SHOCKS AFTER PLACEMENT OF IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR IN ORTHOTOPIC HEART TRANSPLANT SURVIVORS Vivian Tsai, MD, Joshua M. Cooper, MD, Hasan Garan, MD, Andrea Natale, MD, FRCP, Kenneth C. Civello, MD, Ross Downey, MD, Leon Ptaszek, MD, PhD, Sharon Hunt, MD, Paul Zei, MD, PhD, Henry H. Hsia, MD, Paul Wang, MD and Amin Al-Ahmad, MD. Stanford Hospital and Clinics, Stanford, CA, University of Pennsylvania, Philadelphia, PA, Columbia Hospital, New York, NY, Cleveland Clinic, Cleveland, OH and Massachusetts General Hospital, Boston, MA. Introduction: Sudden cardiac death among orthotopic cardiac transplant (OHT) recipients is poorly described and documented. The

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role for implantable cardioverter-defibrillators (ICDs) in this population is unknown. Methods: We retrospectively analyzed the records of all OHT survivors who had implantation of an ICD after transplant from January 1995 to December 2005 at The Cleveland Clinic Foundation, Columbia University, The University of Pennsylvania, and Stanford University. We examined demographic variables, presence and severity of graft atherosclerosis, ejection fraction, electrocardiographic characteristics, indications for ICD implantation, and delivery of shocks after ICD implantation. Results: Thirty-five patients had OHT and subsequent ICD implantation. The mean age at OHT was 44 years, the majority (n=28) male. The mean ejection fraction was 46%. The average age at ICD implantation was 52 years, with the average time from OHT to ICD implant 10.9 years. Graft atherosclerosis was present in the majority of patients (25/34 (74%)), of which 36% (9/25) had left ventricular dysfunction (mean ejection fraction, 35%). Of these patients with graft atherosclerosis, 68% (17/26) experienced syncope prior to ICD implant, versus 22% (2/9) of patients without graft atherosclerosis (p=0.03). The most common indications for ICD implantation included: syncope and graft atherosclerosis (68%), ventricular tachycardia (14%), and ventricular fibrillation (14%). 20 shocks were delivered to 26% (9/26) of patients, of whom 7 (78%) received 10 appropriate shocks. In 3 (9%) of 35 patients, 10 shocks were inappropriate. Graft atherosclerosis was present in 100% (9/9) of patients who received shocks, compared with 65% (17/26) without shocks (p=0.04). Conclusions: Use of ICDs may be appropriate in select OHT patients. Further studies are needed to clarify a proper prevention strategy in this population. PO1-71 POST-PROCESSING, EXPERT SYSTEM AUTOMATICALLY IDENTIFIES ICD-DETECTED VT/VF EPISODES THAT WARRANT CLINICIAN REVIEW Bruce D. Gunderson, MS, Amisha S. Patel, MS, Mark L. Brown, PhD and Charles D. Swerdlow, MD. Medtronic, Inc., Minneapolis, MN and Cedars-Sinai Medical Center, Los Angeles, CA. Introduction: Clinicians review ICD-detected episodes of VT/VF to identify misclassified supraventricular tachyarrhythmias (SVT) and guide appropriate reprogramming. Reviewing all episodes to identify the minority that correspond to inappropriate detection of SVT is time-consuming and requires expert knowledge. We tested a post-processing, expert-system algorithm that automatically identifies misclassified SVT and flags ICD interrogations with SVTs for review. Methods: The expert-system algorithm uses the ratio of atrial to ventricular rate, electrogram morphology, chamber of onset, interval regularity, response to anti-tachycardia pacing (ATP), and AV association to classify episodes as VT/VF, SVT, or Unknown. Evaluation of the algorithm was performed using a randomly-selected subset of 121 dual-chamber ICD interrogations (72 patients (pts)) with VT/VF detections from a large clinical study. Interrogations were flagged for review if the algorithm classified any episode as either SVT or Unknown. All episodes were adjudicated by at least 2 electrophysiologists. Results: Overall, there were 469 ICD-detected VT/VF episodes. Physician reviewers classified 306 (65%) as true VT/VF and 163 (35%) as true SVT. The algorithm correctly diagnosed 372 of 376 episodes (99%) from 62 pts as SVT or VT/VF (Table). The algorithm could not diagnose 20% (93/469) of the episodes (i.e. Unknown) from 30 pts. Overall, the algorithm correctly classified at least 1 episode as SVT or Unknown in all 60 interrogations that included a true SVT episode. It correctly did not classify any episode as SVT or Unknown in 77% (47/61) of interrogations that included only true VT/VF episode(s). Conclusions: A novel, post-processing, expert system diagnosed 80% of ICD-detected VT/VF episodes with an accuracy of 99% and

flagged for review all interrogations with inappropriate detection of SVT. Implementing the algorithm in a programmer or internet-based server could expedite review of ICD-detected VT/VF episodes and ensure review of inappropriate detections of SVT. Algorithm Classification

Truth SVT VT/VF Total SVT 118 1 119

VT/VF 3 254 257

Total 121 255 376 PO1-72 ELECTRICALLY INDUCED CHEST CONSTRICTIONS PRODUCE BLOOD FLOW DURING VENTRICULAR FIBRILLATION VIA THORACIC-ONLY PUMP MECHANISM Byron L. Gilman, MS, Mark W. Kroll, PhD, Paul Wang, MD, Kai W. Kroll, MS and James W. Berry, RD. Galvani, Ltd., Minneapolis, MN and Stanford University, Palo Alto, CA. Introduction: An electrical CPR method (E-CPR) has been developed to deliver a train of externally-applied pulses to produce chest constrictions. It has recently been reported that E-CPR produced blood flow equivalent to that produced by Manual Chest Compressions (MCC). E-CPR pulse trains can be designed with pulse waveforms to specifically constrict skeletal or cardiac muscle. It was hypothesized that, E-CPR may be shown to produce blood flow equivalent to that produced by MCC and using appropriate waveforms, to function as a thoracic-only pump method. Methods: Swine (n=5) were anesthetized and maintained on a ventilator, micro-manometer tipped pressure catheters were placed in the ascending aorta and the right ventricle to continuously monitor pressures, and blood flow was measured using two Doppler ultrasound probes, to measure ejection velocity and to provide images of the aortic and mitral valves as well as left ventricular function. A Skeletal Muscle Con-striction Protocol (SMCP) was defined as a 150 ms pulse train comprising 15 equally-spaced 0.15 ms pulses at a rate of 60 pulse trains per minute for 15 seconds. A constriction protocol was applied during electrically induced ventricular fibrillation, Doppler data were recorded, and Time-Velocity-Integrals (TVI) were calculated. Following initial protocol evaluations (n=175), the skeletal musculature of a swine was paralyzed using pancuronium administered intravenously at 60 µg/kg, and the constriction protocols were then re-evaluated (n=4). Results: SMCPs produced significant blood flow when applied without pancuronium TVI = 8.1 �± 5.4 (n=9). In contrast the blood flows of NSR = 16.9 �± 3.6 (n=8) and MCC=7.4 �± 8.9 (n=5). Following pancuronium, SMCP produced no flow (TVI = 0) and therefore no cardiac constriction. Conclusions: SMCP were shown to produce blood flow during ventricular fibrillation and flow greater than MCC. The absence of flow after administering pancuronium shows this protocol to be a thoracic-only pump mechanism. Additional work is needed to determine optimal pulse trains for specific thoracic-only pump performance. PO1-73 IN ISCHEMIC CARDIOMYOPATHY WITH MODERATELY REDUCED EJECTION FRACTION, QRS DURATION IS MORE EFFECTIVE FOR RISK STRATIFICATION THAN T-WAVE ALTERNANS Daniel P. Morin, MD, MPH, Eran S. Zacks, MD, Andreas C. Mauer, MD, Matthew Janik, MD, Shaun Ageno, MD, Steven M. Markowitz, MD, Sei Iwai, MD, Bindi K. Shah, MD, Bruce B. Lerman, MD and Kenneth M. Stein, MD. Cornell University, New York, NY.

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Introduction: T-wave alternans (TWA) has been used for risk stratification for sudden death in pts with low LVEF. We hypothesized that other factors may be more useful than TWA for risk stratification in patients with only moderately reduced EF. Methods: We evaluated 170 pts (142 M, 66±11 years) with CAD, NSVT, and LVEF 31-40% who were referred for risk stratification for sudden death. TWA was determined during atrial pacing and interpreted using standard criteria. Based on prior studies, positive and indeterminate TWA were grouped together as nonnegative ("TWA-nonneg"). Follow-up for the endpoint of VT, VF, or death was conducted through chart review, device interrogation, and query of the Social Security Death Index. Results: The average LVEF was 36±3%. 97 (57%) pts tested TWA-nonneg. Compared with pts who were TWA-negative, those who were TWA-nonneg had longer QRS (100±16 ms vs 109±23 ms, p<0.01) and were less likely taking beta blockers (93% vs 81%, p=0.04), but had similar age, LVEF, and prevalence of left bundle branch block and previous coronary revascularization (all p=NS). Usage rates of ACE inhibitors, calcium channel blockers, nitrates, digoxin, aspirin, statins, and clopidogrel were similar (all p=NS), as was ICD implantation rate (50% vs 59%, p=0.35). Over follow-up of 2.9±1.4 years, events occurred in 54 (32%) pts (17 of 73 [23%] TWA-neg, 37 of 97 [38%] TWA-nonneg). There were 22 arrhythmic events and 32 deaths. In univariate analysis, nonneg TWA predicted events (HR 1.87, p=0.03). In multivariate analysis correcting for factors differing between TWA groups and the presence or absence of an ICD, only QRS duration remained an independent predictor (HR per 10-ms increment in QRS: 1.16, 95% CI 1.04-1.29, p=0.006), and TWA was no longer significantly associated with events (HR 1.50, p=0.18). Conclusions: In patients referred for risk stratification due to NSVT and ischemic cardiomyopathy with moderately depressed LVEF, TWA is effective for risk stratification. However, in this population, TWA�s predictive value is confounded by QRS duration, which is a more potent predictive indicator of VT, VF, or death. PO1-74 COMPARISON OF MODIFIED MOVING AVERAGE AND SPECTRAL ANALYSIS FOR DETECTING MICROVOLT T WAVE ALTERNANS IN AMBULATORY ECG RECORDINGS Raja J. Selvaraj, MD and Vijay S. Chauhan, MD, FRCP. University of Toronto, Toronto, Ontario, Canada and University Health Network, Toronto, Ontario, Canada. Introduction: The Modified Moving Average (MMA) algorithm is commonly used to measure T wave alternans (TWA) in ambulatory ECG recordings, but the spectral algorithm (SA) may have better signal to noise discrimination because it uses frequency domain analysis. We compared the accuracy of these two algorithms to measure TWA in synthetic and ambulatory ECG recordings in the presence of noise. Methods: Simulated TWA (0 - 20 µV) was added to synthetic ECGs and ambulatory ECGs from normal subjects (n = 18). White noise (0 - 100 µV) and periodic noise (50 µV at 0.01 - 0.49 cpb) were added to synthetic ECGs. TWA magnitude was measured with MMA and SA using a 64-beat sampling window. The difference between measured TWA and added TWA was defined as the measurement error (ME). An MMA ratio (TWA magnitude / intraclass variability) and k value were used to discriminate TWA from white noise, as measured by MMA and SA, respectively. Results: With no added TWA, MMA falsely detected TWA in synthetic ECGs with white noise (ME 1 - 12.5 µV) and in ambulatory ECGs (ME 3.7 ± 1.9 µV). In contrast, false detection of TWA did not occur with SA (ME 0 µV). An MMA ratio > 1.2 eliminated false detection of TWA in ambulatory ECGs. In the presence of low TWA magnitude, TWA was overestimated by MMA and underestimated by SA in proportion to the white noise level. With higher magnitude TWA, the ME was similar between MMA and SA. The accuracy of the MMA

ratio in discriminating TWA from noise in ambulatory ECGs was similar to the k value based on their respective ROC curve areas (0.77 vs. 0.86, p = 0.13). In the presence of 0.26 to 0.49 cpb periodic noise without added TWA, TWA was falsely detected in synthetic ECGs using MMA (ME 2.9 ± 3.9 µV), but not using SA (ME 0 µV). In the presence of periodic noise of 0.26 to 0.49 cpb and added TWA (10 µV), ME was larger in synthetic ECGs with MMA compared to SA (1.9 ± 1.9 vs. 1.1 ± 0.9 µV, p = 0.056). Conclusions: In the presence of white noise in ambulatory ECGs, MMA performs comparably to SA in measuring TWA, provided the MMA ratio is used to avoid false TWA detection. SA is more robust than MMA in discriminating TWA from periodic noise due to its frequency domain analysis. PO1-75 CIRCADIAN RHYTHM OF DECELERATION CAPACITY Axel Bauer, MD, Petra Barthel, MD, Raphael Schneider, MSc, Elisabeth Arnoldi, MD and Georg Schmidt, MD. Deutsches Herzzentrum München, Munich, Germany and Universität München, Munich, Germany. Introduction: Deceleration Capacity (DC) of heart rate is a novel, Holter-based risk predictor after myocardial infarction which has been shown to be superior to conventional measures of heart rate variability (HRV). DC quantifies deceleration-related (quasi-)periodicities of heart rate over 24 hours and is thought to be a measure of vagal activity. If so, circadian rhythm of DC should differ from that of global measures of HRV. Methods: The study enrolled 1,455 survivors of acute myocardial infarction. PCI was performed in 90% of the patients. In all patients, 24-hour Holter recordings were performed during the second week after index infarction. During median follow-up of 22 months, 70 patients died. DC as well as standard measures of HRV were assessed over 24-hours as well as for 3-hour periods. Results: Of all variables tested, low 24-hour values of DC showed the strongest association with mortality (p<0.0001 for comparison of DC with standard measures of HRV). DC exhibited a clear circadian pattern with maximum values during the night and in the early morning and minimum values in the afternoon. This pattern was present in both survivors and non-survivors (left panel shows median values; p<0.0001). In contrast, global measures of HRV such as SDNN or HRV-index exhibited maximum values in the morning (right panel; p<0.0001). RMSSD (reflecting vagally mediated short-term variability) exhibited a pattern similar to DC, but was only moderately associated with mortality. Conclusions: These findings support the hypothesis that DC is a specific measure of vagal function which differs from global measures of HRV

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PO1-76 DECELERATION CAPACITY IN PATIENTS WITH DIABETES MELLITUS Georg Schmidt, MD, Petra Barthel, MD, Axel Bauer, MD, Raphael Schneider, MSc, Elisabeth Arnoldi, MD and Kurt Ulm, PhD. Deutsches Herzzentrum Munich, Munich University of Technology, Munich, Germany and Munich University of Technology, Munich, Germany. Introduction: Post-infarction patients suffering from diabetes mellitus (DM) have a high risk of subsequent mortality. This study was performed to prospectively investigate the predictive value of Deceleration Capacity (DC), a novel risk predictor (Lancet 2006). Methods: 242 consecutive diabetic post-infarction patients were included. They were 75 years of age or younger and presenting with sinus rhythm. Primary endpoint was total mortality. Mean follow up was 22 months. DC was determined according to the published methodology (DC categories: 0 (DC > 4.5 ms), 1 (DC 2.5-4.5 ms), 2 (DC <= 2.5ms)). Cox-proportional hazard analyses were performed with respect to age, history of previous infarction, mean heart rate, HRV index and arrhythmia count during 24-h Holter monitoring, QRS duration and LVEF, all with prospectively defined dichotomies. Results: During follow up period 12% of the patients died. Patients DC category 2 had a significantly higher 2-year mortality rate (37%) than patients in DC category 1 (14%) or DC category 0 (5%). In multivariate analysis, DC2 was the strongest risk predictor (hazard ratio 6.5), followed by age (hazard ration 3.1), LVEF (hazard ration 2.7), and DC1 (hazard ratio 2.5). Conclusions: In diabetic post-infarction patients, DC allows both identification of low-risk patients (in whom further diagnostic workout is not warranted), and of high-risk patients (who likely to benefit from intensified therapy). PO1-77 SIMULTANEOUS CHANGES OF AUTONOMIC ACTIVITY AND CARDIAC CONTRACTILITY LEADING TO TILT INDUCED SYNCOPE Antonio F. Folino, MD, PhD, Giulia Russo, MD, PhD, Alberto Porta, PhD, Gianfranco Buja, MD, Sergio Cerutti, MS and Sabino Iliceto, MD. University of Padua, Padua, Italy, University of Milan, Milan, Italy and Polytechnic of Milan, Milan, Italy. Introduction: In our study we evaluated the modifications of autonomic activity, and their correlations with the correspondent changes of cardiac contractility, occurring before tilt induced syncope. Methods: Twenty-three patients (mean age 43 yrs) with unexplained syncope were studied during upright tilt test (60° for 20 minutes, followed by sublingual nitrate administration) by means of tissue Doppler echocardiography and heart rate variability analysis. Data collection for both examinations were performed at baseline and after 15 minutes of tilt. Tissue Doppler was sampled on the anterior and inferior wall of the left ventricle, considering the amplitude of systolic (Sw) and atrial diastolic (Aw) waves. Measurements of left atrial diameter and volume were also obtained. The power spectrum for heart rate was estimated using the autoregressive technique, and was decomposed in components labeled as low frequency (LF, 0.04-0.15Hz) and high frequency (HF, centered around the breathing rate). Results: A positive response was induced in 15 patents (65%). These subjects evidenced during the test a significant increase of LF (from 48,45 to 65,49nu; p<0.05) and a decrease of HF (from 40,08 to 25,67nu; p<0.05). Moreover, they had a relevant decrease of Aw either on inferior (from 8,61 to 7,08cm/sec, p <0.005) and anterior (from 6,52 to 4,94cm/sec, p<0.001) walls, but a not significant increase of Sw on both sites. On the contrary, negative patients showed not significant changes of LF and HF during Tilt , but a

significant increase of Sw on inferior wall (from 8,62 to 10,06cm/sec, p= 0.030) and not significant modification of Aw at both sites sampled. Patients with positive and negative test, had a similar significant reduction of left atrial area and volume. Conclusions: Our results seem to indicate that in patients with tilt induced syncope the increase of sympathetic activity, induced by passive orthostatism, is not accompanied by a proportional enhancement of ventricular performance. In contrast, it is associated with a reduction of atrial contractility, that probably plays a contributing role in the pathogenesis of neurally mediated syncope. PO1-78 BRUGADA SYNDROME AND AUTONOMIC NERVOUS DYSFUNCTION Anna Kostopoulou, MD, George N. Theodorakis, MD, Maria Koutelou, MD, Efthimios G. Livanis, MD, Athanassios Theodorakos, MD, Themistoklis Maounis, MD, Dimitrios T. Kremastinos, MD, PhD and Dionyssios V. Cokkinos, MD, PhD. Onassis Cardiac Surgery Center, Athens, Greece. Introduction: The purpose of this study was to evaluate autonomic function in patients (pts) with Brugada syndrome with a head-up tilt-test (HUT) and sympathetic innervation of the heart assessed by I-123 metaiodobenzylguanidine (MIBG) single photon emission tomography (SPECT). Methods: The study included 15 pts with the Brugada syndrome, mean age 40±7.7 years. Thirteen pts had syncopal and/or presyncopal episodes (5 pts had 1.4±2.4 syncopal episodes and 8 reported presyncope) and 2 pts were totally asymptomatic. Eleven pts had inducible ventricular tachycardia/fibrillation and had a defibrillator implanted at a VVI 30 bpm mode. All pts underwent a HUT with clomipramine challenge whereas the I-123 MIBG test was performed in 13. The myocardium uptake was studied in 6 segments (anterior, posterior, inferior, septum, lateral from the short axis and apex from long vertical axes) using a 5-point scale (0=normal, 1=moderately diminished, 2=intermediately diminished, 3=severely diminished and 4=no uptake). Results: Ten pts (66.67%) had a positive HUT during the 8.6±4.3 min of the test. Eight of the 13 pts with syncope/presyncope and the two asymptomatic pts had a positive HUT. The response of the test was mixed in 7, cardioinhibitory in 1 and vasodepressive in 2. All pts with a positive HUT had an abnormal uptake of I-123 MIBG with a mean score of 6.3±2.5. Reduced uptake was noted mainly in the inferior, posterior wall and apex. Five pts (33.3%) had a negative HUT and their MIBG score was 1.8±2.9 (ANOVA p=0.015 when compared with the positive HUT group). Conclusions: Autonomic abnormalities expressed as abnormal responses to head-up tilt testing and areas of sympathetic denervation in the left ventricle are present in a subgroup of pts with the Brugada syndrome. It is therefore possible, that many syncopal episodes in pts with Brugada syndrome could be pathophysiologically related to abnormalities of autonomic nervous function. PO1-79 MULTIPLE CLINICAL PHENOTYPE IN PATIENTS WITH THE LQT3 SYNDROME DUE TO A HOT SPOT MUTATION, E1784K, IN SCN5A GENE Wataru Shimizu, MD, PhD, Koji Miyamoto, MD, Yuko Yamada, MD, Satoko Kitamura, MD, Shigeyuki Ueda, MD, Hideo Okamura, MD, Takashi Noda, MD, PhD, Kazuhiro Satomi, MD, PhD, Kazuhiro Suyama, MD, PhD, Takashi Kurita, MD, PhD, Naohiko Aihara, MD, Minoru Horie, MD, PhD and Shiro Kamakura, MD, PhD. National Cardiovascular Center, Suita, Japan and Shiga University, Otsu, Japan.

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Introduction: Mutations in SCN5A encoding the cardiac sodium channel α subunit are associated with the LQT3 subtype of long-QT syndrome (LQTS), Brugada syndrome, cardiac conduction defect (Lenegre syndrome), sinus node dysfunction, and atrioventricular block. Some specific SCN5A mutations may cause multiple clinical phenotype (overlap syndrome), however, correlations between SCN5A mutations and clinical characteristics are hardly unknown. Methods: We identified 26 LQT3 patients (9 families) among 227 genotyped LQTS patients (103 LQT1, 87 LQT2, 26 LQT3 and 11 LQT7) from 95 families in our hospital. Among the 26 LQT3 patients, 10 patients (38%) from 4 families (44%) were found to have identical missense mutation, E1784K, indicating a mutational hot spot in SCN5A gene in LQT3 syndrome. We investigated clinical manifestation in patients with the specific E1784K mutation. Results: The mean age of the 10 patients (6 men) was 25±16 years. The corrected QT interval was considerably prolonged (513 ± 32 ms), but all patients were asymptomatic. Three (30%) of 10 patients showed Brugada ECG, which was spontaneously observed in 2 patients and induced by pilsicainide in one patient (Figure, arrow), among whom one patient had 2nd degree of atrioventricular block and sinus node dysfunction. T wave alternans was documented in 3 (30%) patients, but neither Torsade de pointes nor notched T wave were seen. Two patients were treated with mexiletine, and the remaining 8 patients had no medications. During follow-up period (2.2 ± 2.2 years), no cardiac events occurred in any patients. Conclusions: The E1784K mutation is a mutational hot spot in SCN5A gene in patients with LQT3 syndrome, and some patients with the specific mutation shows multiple clinical phenotypes.

PO1-80 PREDICTING PULMONARY VEIN ISOLATION RESPONDERS BY USING P WAVE DURATION ON SURFACE ECG Aslam Khan, MD, Andrew D. Choi, BA, Dan Musat, MD, Sripal Bangalore, MD, MPH, Apurva Badheka, MBBS, Suneet Mittal, MD, Jonathan S. Steinberg, MD and Kataneh Maleki, MD. St. Luke's Roosevelt Hospital Center, New York, NY and The George Washington University, Washington, DC. Introduction: Atrial fibrillation (AF) is associated with atrial electrical remodeling resulting in a prolonged duration of the P wave. Sustained sinus rhythm may reverse remodeling and is presumed to be advantageous for sinus rhythm maintenance. We hypothesized that

evidence of reverse electrical remodeling on ECG predicted response to ablation of AF using pulmonary vein isolation (PVI). Methods: P wave duration was manually measured by 2 blinded cardiologists from lead II on 12 lead-ECGs recorded in sinus rhythm (after cardioversion) pre (1.8 ± 2.1 mos) and post (2.0 ± 1.0 mos) PVI. Twenty patients (57 ± 13 yrs) with persistent AF (duration 7 ± 8 yrs despite 1.4 ± 1.1 antiarrhythmic drugs) were included. Results: The pre-PVI P wave duration of 129.4 ± 23.4 ms decreased to 113.0 ± 28.2 ms after PVI ( p ≤0.0001). An 18 % decline in P wave duration was observed in 8 (40%) patients. The 15 (75%) patients free of AF recurrence at 6 month follow-up demonstrated a mean 14% decrease in P wave duration from 123.5 ± 20.9 ms to 106.3 ± 23.1ms (p ≤ 0.0001), whereas the 5 patients with AF recurrence had a much smaller change (8%) in P wave duration from 144.0 ± 26.1 ms to 133 ± 35.3 ms (p = NS). A shortening of P wave duration by 18 % was associated with absence of AF recurrence (p=0.035) with a positive predictive value of 100%. Conclusions: Reverse atrial remodeling after PVI is demonstrated by a shortening of the P wave duration on the 12 lead ECG. A decrease in P wave duration is predictive of a successful PVI. PO1-81 SUDDEN ARRHYTHMIC DEATH SYNDROME-DIAGNOSTIC YIELD OF CLINICALLY SCREENING THE FIRST DEGREE RELATIVES IN A BRITISH SPECIALIST CLINIC Pier D. Lambiase, MD, PhD, Juan C. Kaski, MD, Eileen Firman, RN, Perry M. Elliott, MD, Akbar K. Ahmed, MBBS, Anthony W. Chow, MD, Mary Sheppard, MD, Martin D. Lowe, MD, PhD and William J. McKenna, MD. Heart Hospital, UCL, London, United Kingdom. Introduction: Sudden arrhythmic death syndrome (SADS) arises through disorders of ion channel function or structural heart disease. It accounts for over 400 deaths in the UK per annum. The role of family screening is becoming increasingly recognised in the primary prevention of SADS. To date there has been no comprehensive analysis of the diagnostic yield and efficacy of a family screening approach in SADS index cases where the post mortem heart is structurally normal after expert pathological review. Methods: 118 SADS families where the SADS victim died between 1 and 35 years of age were evaluated in a systematic family screening programme between 2003-2006. All SADS index cases had a structurally normal heart after expert review of all available tissue. All studied relatives underwent resting, signal averaged ECG, 24h Holter, exercise ECG with V02 max, transthoracic echocardiography and an ajmaline challenge test after initial clinical screening. Results: The most common modes of death were rest in 28%, sleep in 25% and exercise in 18%. An inherited electrical cause of SADS was identified in 41 of the 118 families (35%)-20 Brugada, 18 Long QT Syndrome (LQTS), 3 Catecholiminergic Polymorphic Ventricular Tachycardia (CPVT). Structural heart disease was identified in 5 ARVC & 2 DCM families. 26 ICDs have been implanted in affected family members-4 LQTS, 7 Brugada, 2 CPVT, 2 ARVC, 2 DCM and 9 on clinical grounds without a definitive diagnosis. The ECG (37%) and ajmaline challenge test (49%) had the highest diagnostic yield in families with a positive diagnosis. Conclusions: A systematic screening approach in relatives of SADS victims has a high diagnostic yield of 35% despite the index case having a structurally normal heart at post mortem. Electrical causes of SADS predominate in these families. These findings demonstrate that a systematic clinical screening programme in SADS families is both achievable and effective. The full impact of gene testing upon diagnostic yield is awaited.

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PO1-82 EVOLUTION OF CARDIAC AUTONOMIC NERVOUS ACTIVITY FROM THE ACUTE TO THE CHRONIC PHASE IN PATIENTS WITH TRANSIENT LEFT VENTRICULAR APICAL BALLOONING Jasmin Ortak, MD, Melanie Barantke, MD, Iris K. Wilke, MD and Hendrik Bonnemeier, MD. University Luebeck, Luebeck, Germany. Introduction: Transient left ventricular apical ballooning (AB), a clinical entity characterized by acute but rapidly reversible left ventricular (LV) systolic dysfunction is emerging. Even though recent findings suggest catecholamine-mediated myocardial stunning due to enhanced sympathetic outflow, the time course of cardiac autonomic nervous activity has not yet been investigated from the acute to the chronic phase. Methods: We prospectively enrolled 37 consecutive patients (35 women, median age 68 years) with transient left ventricular AB. Heart rate variability (HRV) was determined from 24-hour-Holter-ECGs, recorded (I) directly on hospital admission, (II) on day 2 after admission, (III) on day 3 after admission, and (IV) 3 month after hospitalisation. Results: Within 48 hours after hospital admission, parameters of HRV were significantly depressed (SDNN 94.1±23ms; SDNNi 43.0±15ms; rMSSD 23.1±9ms; SDANN 81.7±25ms; TI 24.9±7ms). All parameters of HRV significantly increased within the subacute phase (day 3) and exhibited complete normalization after 3 month follow up (SDNN 124.7±24ms; SDNNi 45.1±8ms; rMSSD 27.2±11ms; SDANN 118.5±27ms; TI 31.2±8ms; all p<0.001). Furthermore, there was a constant increase of mean RR-intervals from the acute to the chronic phase of AB (861±125ms to 898±98ms, p<0.001). Conclusions: In patients with AB, there is a significant depression of cardiac vagal modulation in the phase of acute left-ventricular dysfunction, followed by a consecutive constant improvement of autonomic modulation from the subacute to the chronic phase. The rapid restoration of parasympathetic function may in part explain the favourable prognosis of AB patients

PO1-83 STILLBIRTHS IN CONGENITAL LONG QT SYNDROME Michael J. Ackerman, MD, PhD, Brian C. Brost, MD, Jennifer Robinson, MS, Wojciech Zareba, MD, PhD and Arthur J. Moss, MD. Mayo Clinic College of Medicine, Rochester, MN and University of Rochester, Rochester, NY. Introduction: Although long QT syndrome (LQTS) most commonly presents with syncope, seizures, and sudden death during the first decade in males and second and third decade in females, events can occur at any age including infancy. Case reports have described in-utero presentations of LQTS hallmarked by fetal bradycardia and sudden death. However, the stillbirth frequency among women with clinically diagnosed and/or genetically proven LQTS is unknown. Methods: Reproductive history was analyzed retrospectively using the International LQTS Registry comprised of 1274 probands and 13,586 family members. Annual follow-up and updates (most recent, 03/2006) are maintained on 7779 of the registry participants. The stillbirth frequency was compared between women of child-bearing years classified clinically as affected, borderline, or unaffected. Subset analysis for women confirmed as positive or negative for the two most common genotypes (LQT1 and LQT2) was also performed. Results: Overall, 509 stillbirths were recorded for 317 women. The majority (> 90%) occurred at < 30 weeks estimated gestational age. Among women who have had any pregnancies, stillbirths occurred in 124/854 (14.5%) female probands and female relatives clinically diagnosed with LQTS compared to 56/444 (12.6%) with borderline LQTS, and 93/790 (11.8%) women classified as unaffected. This trend did not achieve statistical significance (p = 0.1). For the two most common LQTS subtypes, stillbirths occurred in 35/243 (14.8%) LQT1-positive probands and relatives compared to 18/141 (12.7%) LQT1-negative female relatives and 21/161 (13%) LQT2-positive versus 18/173 (10.4%) LQT2-negative women. Conclusions: There appears to be a non-significant trend toward increased stillbirths among women with clinically suspected or genetically proven LQTS. Given that each fetus of an LQTS positive mother has only a 50% chance of inheriting her LQTS-susceptibility mutation, the observed trends merit additional scrutiny. The hypothesis that cardiac channelopathy represents an etiologic cause of early intrauterine fetal demise in some of the 14,000 unexplained stillbirths occurring in the United States annually requires further investigation. PO1-84 EXERCISE TESTING FOR RISK ASSESSMENT IN PEDIATRIC WOLFF-PARKINSON-WHITE SYNDROME Robin S. Bershader, Charles I. Berul, MD, Frank Cecchin, MD, John K. Triedman, MD, Edward P. Walsh, MD and Mark E. Alexander, MD. Boston University, Boston, MA and Children's Hospital Boston, Boston, MA. Introduction: Recent data may support pre-emptive ablation for asymptomatic patients with Wolff-Parkinson White (WPW). Some insurers may not approve this procedure without risk assessment or documented SVT. We examine the assertion that persistent pre-excitation during maximal exercise testing represents a proxy for more rapid antegrade conduction. Methods: Retrospective medical record review of all WPW patients >4yo between 2004-2006. Results: Exercise testing was performed in 74 pts with manifest WPW who also underwent intracardiac EP study (14.3±4.1, 42% with pre-procedure SVT). Abrupt loss of pre-excitation during exercise was documented in 12 (16%), with the remainder having progressive fusion with persistent delta wave at peak heart rate (193±15). They were compared to 90 pts with WPW who underwent EP study (12.5±5, p< 300msec ranging from 33% in those studied without

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exercise, 27% in those with persistent delta wave and 8% in those with loss of delta wave. Fewer patients with exercise testing had SVT induced during EP study (53%) compared to those without prior exercise testing (69%, p=0.03). There was no difference in the percentage of pathways with retrograde characteristics that could support ORT (92% overall). Neither pathway location, clinical presentation, age, gender, second arrhythmia substrate or the presence of cardiomyopathy or CHD influenced exercise results. Conclusions: Exercise testing adds little to decision making in pediatric patients with WPW. A minority of pts with WPW have abrupt loss of pre-excitation on exercise testing. There is poor correlation between exercise-inferred and clinical antegrade conduction. Even pts with loss of delta wave may have potentially dangerous conduction characteristics. PO1-85 CLINICAL OUTCOMES OF FONTAN REVISION SURGERY WITH AND WITHOUT ASSOCIATED ARRHYTHMIA INTERVENTION Kazuhiro Takahashi, MD, Francis Fynn-Thompson, MD, Frank Cecchin, MD and John K. Triedman, MD. Children's Hospital Boston, Boston, MA. Introduction: The use of surgical revision w/wo Maze in Fontan patients(pts) for hemodynamic/ arrhythmia indications remains controversial. This study reports perioperative mortality / morbidity and late outcomes in revisions from a single institute. Methods: 40 consecutive pts undergoing Fontan revision 1/1990 to 8/2006 were retrospectively reviewed. Median age at revision was 19 yrs, and follow-up period was 3.9 yrs. Fenestration was instituted in 22. Pts were divided into arrhythmia surgery group (GI, n=21), and no arrhythmia surgery group (GII, n=19). Clinical characteristics, mortality, and morbidity were compared. Results: GI pts were older at revision (25.2 vs17.1yrs; p=0.004) with longer interval between the revision and primary surgery (17.2 vs10.1yrs; p<0.001), and pre-existing atrial tachycardia (AT) was more prevalent (95% vs. 42%; p<0.001). Total mortality rate was 12.5% (4 periope, 1 early postope and 0 late death). Survival curves for both Gs were similar. Major perioperative adverse events occurred in 14/40 (35%) pts (renal failure, seizure, thrombosis, intracranial hemorrhage). These were more frequent in GI, but median hospital stays were not different.14 pts underwent cath >3 mos postoperatively for nonurgent indications (fenestration closure 8, ablation 3). Filling pressures were unchanged from preop (RA pressure change 16.8 to 13, p = 0.07, ventricular EDP change 9.3 to 9.9, ns). Cardiac index was unchanged (2.2 to 2.6 l/min/m2;p=0.09) at the cost of reduction of SaO2 (92% to 88%; p=0.10). Sustained AT prevalence at follow-up (>3 months) was 37% in GI and 53% in G II (p = 0.34). The severity of AT decreased in GI (AT score 7.3 +/- 2.6 preop vs 3.3 +/-3.0 postop, p<0.05). Improvement of AT severity score were observed at incidence of 72% of GI and 30% of GII. Conclusions: Mortality and morbidity of Fontan revision were significant in this series, but limited to the perioperative period and were not increased by performance of concomitant Maze surgery. No significant changes in hemodynamics in postoperative hemodynamics. Despite some AT recurrence, concomitant arrhythmia surgery improved the arrhythmia status in pts with pre-existing AT.

PO1-86 DOFETILIDE: DOES IT HAVE A ROLE IN MANAGMENT OF ARRHYTHMIA IN ADULTS WITH CONGENITAL HEART DISEASE? Ronald S. Wells, MD, Seshadri Balaji, MBBS, Paul Khairy, MD, PhD, Louise Harris, MD and Christopher Anderson, MD. Oregon Health and Science University, Portland, OR, Montreal Heart Institute, Montreal, Quebec, Canada, Toronto General Hospital, Toronto, Ontario, Canada and Northwest Pediatric Cardiology, Spokane, WA. Introduction: Little is known about the use of dofetilide (DE, class 3 antiarrhythmic approved for adult atrial flutter/fibrillation [AFL/AF]) in patients with congenital heart disease (CHD). Concerns about safety and efficacy have limited its use in this population. We present the experience of four centers using DE in CHD. Methods: CHD patients given DE from November 2000 to April 2006 were reviewed. Results: Fifteen patients (age 19-53y, mean 30 at DE initiation) were reviewed. CHD diagnoses: Truncus arteriosus (2); stenotic bicuspid aortic valve (1); Tetralogy (2); transposition (2); tricuspid atresia (3); pulmonary atresia (2); and single ventricle (3). All had at least 1 prior cardiac surgery (range 1 to 6; mean 2.6 ± 1.1) including Fontan operation in 8. Arrhythmia diagnoses: incisional-atrial reentrant tachycardia/atypical AFL (10); AF (2); AFL/AF (2); recurrent VT (1). An average of 3.4 ± 1.2 antiarrhythmics were tried pre-dofetilide, including ibutilide in 3. Eleven had prior catheter ablations attempts (average 1.7 ± 0.6/patient), either unsuccessful or initially successful with subsequent relapse. Two had prior arrhythmia surgery (Maze at Fontan revision); AFL recurred in both. Four had a pacemaker; 3 had an AICD. QTc increased from baseline of 440 ± 32 to 490 ± 46 following dofetilide initiation. No patient required dosing adjustment for renal impairment. Two had torsades/VF requiring cessation of therapy. See Figure for other responses.

Conclusions: DE successfully converts to/maintains NSR in most CHD patients with AFL/AF. The risk of proarrhythmia is significant and mandates adherence to prescribing and monitoring guidelines. DE is reasonably safe and effective in patients with CHD and refractory AFL/AF but needs to be used with care.

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S140 Heart Rhythm Vol 4, No.5 May Supplement 2007

PO1-87 EFFECT OF VARYING DART SEPARATION ALONG THE CARDIAC AXIS ON VENTRICULAR ARRHYTHMIA INDUCTION DURING TASER APPLICATION Dhanunjaya R. Lakkireddy, MD, James Vacek, MD, Donald Wallick, PhD, William Kowalewski, BS, David O. Martin, MD, MPH, Jagdish Butany, MD, Andrea Natale, MD, FRCP and Patrick Tchou, MD. Mid-America Cardiology, University of Kansas, Kansas City, KS, Cleveland Clinic, Cleveland, OH and Toronto General Hospital, Toronto, Ontario, Canada. Introduction: Previous studies have shown the stun gun application close to the heart is more prone for arrhythmia induction. The size of the electrical vector and its ability to capture the myocardium determines its arrhythmogenecity. The specifics effect of separation distance along the cardiac axis is unknown. Methods: In 7 pigs, the effect of varying dart distance along the sternal notch (SN) - point of maximum impulse (PMI) on myocardial capture ratio/VF induction with a popular stun gun model (TASER® X-26, TASER International, Scottsdale, AZ) was assessed. The SN-PMI axis distance averaged 15.8±1.65 cm. One dart was fixed at either the upper (SN) or lower (PMI) spot and the second dart was then moved towards the other at distance intervals of approximately 2.5cm along this axis and V-capture was studied at x1 standard application. Results: There was no V-capture at 2.5 cm separation either from the SN or from the PMI in all 7 pigs. At 5 cm separation from the PMI there was an average of approximately 5:1 capture and the capture decreased to 3:1 at the maximum separation of around 15 cm indicative of more rapid myocardial capture. When the SN dart was fixed and the other dart separated at 5 cm, there was capture in only 4 of the 7 pigs yielding an average capture ratio of 28:1 (0.036 on the graph). With greater separations, the capture ratio decreased quickly to 3:1 at the 15 cm separation. No VF induction was seen during any of these TASER applications. Conclusions: Myocardial capture ratio tends to decrease with increasing dart separation up to 15 cm in the cardiac axis. Shorter dart separations tend to cause less rapid myocardial capture probably related to current jump across shorter distances and the relative differences in current density. However even in the closest possible application along the cardiac axis no VF was induced with TASER current application.

PO1-88 VIRTUAL CARDIAC SYMPOSIA: A SERIES OF I NTERNET BASED, EDUCATIONAL FORUMS FOR CARDIOLOGISTS WORLD WIDE Sergio Dubner, MD, DMSc, Arthur J. Moss, MD, Edgardo Schapachnik, MD, Andres R Perez Riera, MD, Li Zhang, MD, Woijciech Zareba, MD, MPH and John Camm, MD. Swiss Medical, Buenos Aires, Argentina, University of Rochester, Rochester, NY, Hospital Argerich, Buenos Aires, Argentina, Universidad de Sao Paulo, San Pablo, Brazil, LDS Hospital, Salt Lake City, UT and St. George�s Hospital, London, United Kingdom.

Introduction: The Internet is an extremely powerful media for the transmission of data and knowledge. The International Society for Holter and Noninvasive Electrocardiography (ISHNE) has taken a novel educational approach since 2002 by conducting a series of cardiology-related educational activities in the format of a web-based, internet, virtual symposiums. Objective: To demonstrate the significance of world wide internet-based cardiology educational activities after entered the 21 Century Methods: Six free of charge cardiology virtual symposia were organized by each of the subject committee, starting on 2002, they were the First Virtual Brugada Syndrome Symposium (April 2002), the First Virtual International Long QT Syndrome Symposium (April 2004), the First Virtual International Arrhythmogenic Right Ventricular Dysplasia Symposium (April 2005), ISHNE World Wide Internet Symposium on Atrial Fibrillation (October 2005), the ISHNE World Wide Internet Symposium on Heart Failure (March 2006), and the ISHNE World Wide Internet Symposium on Sudden Cardiac Death (October 2006). All of them were presented in English with translation into Spanish and Portuguese, and the last 2 were also translated into Chinese and Russian and offered CME credits. Results: There has been a dramatic and progressive increase in the number of registrants, the number of countries represented, and the number of lectures downloaded with each subsequent virtual symposium during the past 4 years, BRUGADA LQTS ARVD AF HF SCD

Honorary President

P. Brugada

A. Moss

F. Marcus - G. Fontaine

J. Camm A.J.Moss D.

Zipes

Registrants 1821 2,716 3,147 7,245 11899 14087

Countries 22 48 75 94 108 123

Duration (days) 30 30 15 30 30 30

Downloaded lectures No data 23811 28736 33891 50634 64939

Submitted questions 99 245 151 368 197 200

Top lecture downloaded 916 No

data 5980 7574 5051 11251

Conclusions: The progressively increasing numbers of cardiologists from around the world who are involved in these web-based, virtual symposia suggest that this approach is answering an unmet professional education need. This approach adds an important, new, low-cost dimension to continuing medical/cardiologic education. PO1-89 BIGGER DEFIBRILLATOR LEAD CONTRIBUTES TO LOWER DEFIBRILLATION ENERGY REQUIREMENT Uma N. Srivatsa, MD and Stephen Stark, MD. University of California, Davis, Sacramento, CA. Introduction: Defibrillation thresholds (DFT) are variable due to physiologic factors. A 10 Joule (J) safety margin is recommended for programming the ICD. High DFTs are noted in about 6 to 10% of patients at the time of implantation. It has been shown to be related to side of implant, body size, coil to RV apex distance, and amiodarone use. In this situation high energy device, subcutaneous coil, elimination of SVC from circuit, additional coils in central veins or epicardial patches are used to decrease DFT. We report two cases where replacing a 7 French by 9 French defibrillator lead reduced the DFT. Methods: n/a Results: Patient 1 is a 23 year old female with dilated cardiomyopathy, NYHA class II and BMI 36.6. She received an ICD