Session 18 S37

ABSTRACT SESSION 18: NONINVASIVE 2: SCD Risk Stratification: The Struggle Goes On Thursday, May 10, 2007 1:30 PM - 3:00 PM AB18-1 KIDNEY DYSFUNCTION IS ASSOCIATED WITH SUDDEN CARDIAC DEATH AMONG WOMEN WITH CORONARY HEART DISEASE Rajat Deo, MD, Feng Lin, MS, Eric Vittinghoff, PhD, Zian H. Tseng, MD, Stephen Hulley, MD, MPH and Michael G. Shlipak, MD, MPH. Johns Hopkins Hospital, Baltimore, MD and University of California, San Francisco, San Francisco, CA. Introduction: Kidney dysfunction has been associated with an increased risk for death, myocardial infarction, stroke, and congestive heart failure among high risk populations. We evaluated whether kidney dysfunction predicted risk of sudden cardiac death. Methods: The Heart and Estrogen Replacement Study (HERS) was a randomized, double-blinded, placebo-controlled trial evaluating the effect of conjugated estrogens plus medroxyprogesterone acetate on coronary heart disease (CHD) event risk among 2763 postmenopausal women with documented coronary artery disease. Kidney dysfunction was categorized by estimated GFR (based on serum creatinine, weight, age and ethnicity) < 40ml/min/1.73m2, 40 to 60ml/min/1.73m2, and >60 ml/min/1.73m2. Results: Of the 2763 women originally enrolled in HERS, there were 136 adjudicated sudden cardiac death events during the 6.8 year follow-up period: 25 events for eGFR>60 ml/min/1.73m2, 37 events for eGFR 40-60 ml/min/1.73m2, and 73 events for eGFR < 40ml/min/1.73m2 (figure). Kidney dysfunction was significantly associated with sudden cardiac death after adjustment for age, race, diabetes, atrial fibrillation, hypertension, smoking, alcohol use, BMI, heart rate variability, left bundle branch block, CHF, CHD, MI, LVH, baseline exercise capacity, HDL, triglycerides, fasting glucose, and medications: [(adjusted HR 1.58; 95% CI 0.98-2.52) for eGFR 40-60 and (HR 2.27; 95% CI 1.22-4.20) for eGFR <40]. Conclusions: Kidney dysfunction is a strong predictor of sudden cardiac death among women with coronary heart disease.

AB18-2 ASSOCIATION OF QRS-DURATION WITH LEFT VENTRICULAR GEOMETRY AND FUNCTION - RESULTS OF THE KORA / MONICA AUGSBURG ECHOCARDIOGRAPHIC STUDY Jan Stritzke, MD, Wolfgang Lieb, MD, Andreas Luchner, MD, Angela Döring, MD, Hans-Werner Hense, MD, Heribert Schunkert, MD and Hendrik Bonnemeier, MD. Universitätsklinikum Schleswig-Holstein, Lübeck, Germany, Universität Regensburg, Regensburg, Germany, GSF Nationales Forschungszentrum für Umwelt und Gesundheit, Institut für Epidemiologie, Neuherberg, Germany and Universitätsklinikum Münster, Münster, Germany. Introduction: In patients presenting with heart failure a prolonged QRS-Duration (QRSd>=120ms) is associated with increased mortality and worse outcome. Although this parameter is also often used as a surrogate parameter for left ventricular asynchrony relative little information about associations between duration of depolarization and left ventricular geometry and function is available. Methods: Subjects (1371 men and women, aged 25 to 74 years) originated from a gender and age stratified random sample of German residents of the Augsburg area (MONICA S3) were examined by standardized echocardiography. Left ventricular mass (LVM), left ventricular enddiastolic diameter (LVEDD), left atrial area (LA), ejection fraction (EF) and ratio of early and late transmitral inflow velocities (e/a) were measured. The QRSd was assessed by high solution ECG. Statistical analysis were performed using tertiles of QRSd (men: 96 - 105ms, >105ms; women: 88 - 97ms, >97ms). Results: Comparing the 1st with the 3rd tertile there was a significant increase in LVM (men: 180+/-44g vs. 200+/-52g, p<0.001; women: 131+/-30g vs. 155+/-42g, p<0.001), LVEDD (49.2+/-4.4mm vs. 51.0+/-4.8mm, p<0.001; 44.8+/-4.0mm vs. 47.1+/-4.2mm, p<0.001) and also in LAA (16.0+/-3.0cm² vs. 17.2+/-3.3cm², p<0.001; 14.5+/-2.6cm² vs. 15.9+/-3.9cm², p<0.001) detectable. In females there was also a significant increase in prevalence of impaired ventricular relaxation (e/a<1) (35.4% vs. 46.5%, OR 1.7, p<0.05) found. EF was equal in both groups. After adjusting for age, gender, height and blood pressure only LVM and LVEDD were significant related to QRSd. Comparing adjusted means there were significant differences found for LVM (181g vs. 189g, p<0.05; 134g vs. 143g, p<0.05) and for LVEDD (49.8mm vs. 50.3mm, p<0.01; 45.4mm vs. 46.3mm, p<0.05). Conclusions: In general population prolongation of QRSd is associated with increase of LVM and LVEDD. Interestingly there was no association between QRSd and EF found. These results may partly explain the high rate of non-responders in patients treated with cardiac resynchronization therapy. AB18-3 MORPHOLOGY OF EXERCISE INDUCED VENTRICULAR ARRHYTHMIAS IS ASSOCIATED WITH MORTALITY Robert E. Eckart, DO, Michael E. Field, MD, Tomasz W. Hruczkowski, MD, Daniel E. Forman, MD, Sharmila Dorbala, MBBS, Marcelo F. Di Carli, MD and William G. Stevenson, MD. Brooke Army Medical Center, San Antonio, TX and Brigham and Women's Hospital, Boston, MA. Introduction: The significance of exercise induced ventricular arrhythmias (EIVA) may be confounded by lower-risk idiopathic right ventricular outflow tract (RVOT) arrhythmias with characteristic left bundle branch block (LBBB) morphology. We sought to determine the prognostic significance of EIVA based on morphology. Methods: Review of consecutive patients undergoing exercise testing with couplets, triplets or multifocal ventricular ectopy during testing. Over 14,000 exercise tests performed with finding of EIVA in 661 tests with 585 tracings on unique patients available for review. We used 2,340 age-gender-risk factor matched patients in a 1:4 ratio with absence of EIVA as controls.

S38 Heart Rhythm Vol 4, No.5 May Supplement 2007

Results: The mean age was 64±11 years. As a function of matching, there were no differences in age, gender, or pre-test identification of hypertension, hyperlipidemia, coronary artery disease or diabetes. Those with EIVA were more likely than those without EIVA to have ST-segment changes during exercise testing (23.6% v 19.4%, p=0.027); although this difference was most often due to non-diagnostic changes. Of those with EIVA, they were a LBBB morphology in 168 (28.7%), a RBBB morphology in 200 (34.2%), and with multiple morphologies in 209 (35.7%). There were 31 deaths in those with EIVA compared to 43 deaths in those without EIVA (5.3% v 1.8%, p<0.0001) during a follow-up of 24±13 months. Of the 114 patients with a LBBB inferiorly directed EIVA that may have been consistent with a RVOT source, there was 1 death (0.9%). There was no difference in survival between those with a LBBB morphology and those without EIVA with a 4-year survival of 96.4% (Log-Rank p=0.93) and no difference between those with a RBBB morphology and those with multiple morphologies of EIVA with a 4-year survival of 89.6% (Log-Rank p=0.49). There was a significant difference in survival between those with LBBB morphology or none and those with RBBB or multiple morphologies (Log-Rank p<0.001). Conclusions: The identification of either isolated RBBB or multiple morphologies of EIVA is associated with increased mortality. Isolated LBBB morphology EIVA is not associated with increased mortality compared to matched controls. AB18-4 SLEEP APNEA PREDICTS SUDDEN DEATH AND VENTRICLAR TACHYARRHYTHMIA IN PATIENTS WITH CHRONIC HEART FAILURE Tsuyoshi Shinozaki, MD, PhD, Koichiro Sugimura, MD, PhD, Shigefumi Fukui, MD, Hiromasa Ogawa, MD, PhD and Hiroaki Shimokawa, MD, PhD. Sendai Medical Center, Sendai, Japan and Tohoku University, Sendai, Japan. Introduction: Sleep apnea predicts mortality of patients with chronic heart failure (CHF). Predictive power of sleep apnea, however, remains unclear for sudden death. We thus aimed to examine whether sleep apnea predicts lethal arrhythmic events in patients with CHF. Methods: Sleep study was performed in 95 consecutive patients with stable CHF (LV ejection fraction, 36 ± 13%). Nocturnal oxygen therapy and continuous positive airway pressure therapy were introduced to 18 among the 27 patients with central sleep apnea and 6 among the 9 patients with obstructive sleep apnea, respectively. Cox-proportional analysis was performed using covariates of age, gender, etiology, brain-natriuretic peptide, LV ejection fraction, LV diameter normalized body-surface area, left atrial diameter normalized body-surface area, medications and apnea-hypopnea index (AHI) > 5/h (after nocturnal respiratory therapy, if introduced). Endpoints included lethal events (overall death or ventricular tachyarrhythmia) and lethal arrhythmic events (sudden death or ventricular tachyarrhythmia). Results: During 29 ± 17 months of follow-up, 18 patients died and 10 ventricular tachyarrhythmia occurred. Predictors of lethal events were AHI > 5/h (hazard ratio, HR:4.1, 95%CI:1.2-13.5) and left atrial diameter normalized body-surface area (HR:1.07, 95%CI:1.01-1.13). Predictors of lethal arrhythmic events were AHI > 5/h (HR:17.5, 95%CI:1.5-197.3), left atrial diameter normalized body-surface area (HR:1.20, 95%CI:1.07-1.34) and LV ejection fraction (HR:0.91, 95%CI:0.85-0.98). The frequency of lethal events and lethal arrhythmic events increased with AHI (lethal events: 10%, 19% and 35%, lethal arrhythmic events: 3%, 14% and 20% in patients with AHI < 5/h, 5/h ≤ AHI< 5/h and 5/h ≤ AHI, respectively. Conclusions: Sleep apnea predicts lethal arrhythmic events independently of hemodynamic parameters in patients with CHF, providing a rationale for management of sleep apnea.

AB18-5 THE CHARACTERISTICS AND DISTRIBUTION OF THE SCAR TISSUE DETECTED BY MAGNETIC RESONANCE IMAGING MAY PREDICT IMPENDING VENTRICULAR TACHYCARDIA IN PATIENTS WITH ISCHEMIC CARDIOMYOPATHY Miki Yokokawa, MD, Hiroshi Tada, MD, PhD, Keiko Koyama, MD, Koji Goto, MD, Kenichi Kaseno, MD, Shigeki Hiramatsu, MD, Shigeto Naito, MD, Shigeru Oshima, MD, PhD and Koichi Taniguchi, MD, PhD. Gunma Prefectural Cardiovascular Center, Maebashi, Japan. Introduction: Late potentials (LPs) represent zones of delayed myocardial activation around unexcitable scar areas. On the other hand, contrast-enhanced magnetic resonance imaging (CMR) identifies nonviable scar tissue as enhanced areas. Methods: A signal-averaged electrocardiogram (SAECG) and CMR were performed in 23 patients with advanced heart failure (dilated cardiomyopathy [DCM]-14, ischemic cardiomyopathy [ICM]-9, 19 males, 69 ± 10 years, EF 23 ± 9 %). In the CMR, the images were scored using a 17-segment model. The transmural extent of the myocardial scar was assessed as the transmurality index (TMI; the sum of 17-segments: 0 = no damage, 4 = transmural damage), transmural scar area (TMA [%]; the percentage of transmural scar segments) and scar volume (%; the percentage of total scar volume: Table). Those parameters and clinical arrhythmic events were compared between the patients with DCM (DCM-Gr) and ICM (ICM-Gr). Results: No significant difference was found in the frequency of positive LPs between the 2 groups (DCM-Gr = 43 % vs. ICM-Gr = 78 %, p = 0.09). In each group, there was no difference in the frequency of positive LPs between the patients with and without sustained ventricular tachycardia (SVT) (Table). The scar volume was lower in the DCM-Gr (5 ± 6 %) than ICM-Gr (39 ± 16 %, p < 0.001). In the DCM-Gr, scar was present mainly in the mid-wall layer, but no transmural scar areas were present. Furthermore, the TMI and scar volume were greater in those with SVT than in those without (Table). In the ICM-Gr, all the CMR-parameters were lower in those with SVT than in those without (Table), indicating that a wider and greater distribution of the non-transmural scar was associated with SVT. Conclusions: CMR is useful to assess the scar characteristics, and may predict an impeding SVT in ICM patients. Positive LPs may not predict an SVT occurrence. Table. SAECG and CMR-parameters in Patients with DCM and ICM

DCM (n = 14) ICM

(n = 9)

SVT (+) SVT (-) p Value SVT (+) SVT (-) p

Value

SAECG

Positive LPs (%)

3/6 (50 %)

3/8 (38 %) 0.64 3/4 (75

%) 4/5 (80 %) 0.86

CMR

TMI 8 ± 4 2 ± 4 < 0.05 21 ± 4* 40 ± 4* < 0.001

TMA (%) 0 0 1.0 10 ± 3* 29 ± 14* < 0.05

Scar volume (%) 9 ± 6 3 ± 5 0.07 25 ± 6* 54 ± 6* <

0.001 CMR= contrast-enhanced magnetic resonance imaging, D (I) CM = dilated (ischemic) cardiomyopathy, LP = late potential, SAECG = signal-averaged electrocardiogram, SVT = sustained ventricular tachycardia. *p < 0.05 vs. DCM.

Session 19 S39

AB18-6 SYMPATHETIC INNERVATION AND RISK OF VENTRICULAR TACHYCARDIA IN GENOTYPED PATIENTS WITH ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY (ARVC-9) Matthias Paul, MD, Michael Schaefers, MD, Peter Kies, MD, Eric Schulze-Bahr, MD, Otmar Schober, PhD, Guenter Breithardt, MD and Thomas Wichter, MD. University of Muenster, Muenster, Germany. Introduction: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically heterogeneous myocardial disease accounting for ventricular tachycardia and sudden cardiac death in a young population. Mutations in the gene encoding for plakophilin-2 (PKP2) have recently been reported by our group as the most common cause of autosomal-dominant ARVC (ARVC-9). In this study, we investigated the potential role of adrenergic dysfunction on the arrhythmia profile in patients (pts) with or without PKP2 mutations with the help of 123I-meta-iodo-benzylguanidin scintigraphy (MIBG-SPECT). MIBG, as a norepinephrine analogue, is a marker of presynaptic sympathetic innervation (uptake-1). Methods: Forty two pts with definite ARVC were divided into those with (PKP2-positive; 17 pts) and without a PKP2 mutation (PKP2-negative; 25 pts). MIBG-SPECT was performed in all pts and compared to results obtained from 10 control subjects (n=10) without identifiable structural heart disease. There were no differences in age or gender between the groups. MIBG images were acquired four hours post injection and analysed for regional 123I-MIBG uptake in a standardized 33-segment bulls eye scheme. Results: Overall, an abnormal tracer uptake was detected in 25 pts with ARVC (59%). There was no difference between PKP2-pos (n=11; 65%) and PKP2-neg (n=14; 56%) pts. During long-term follow-up (9.1±3.8 years), ventricular tachyarrhythmias occurred in 27 pts. However, ARVC pts with an abnormal MIBG-SPECT experienced more often sustained VT when compared to those with a normal sympathetic innervation (PPKP2-pos pts with a reduced MIBG uptake showed a trend to more frequent recurrences of sustained VT than those PKP2-neg pts (P=0.051). Conclusions: An impairment of adrenergic innervation appears to account for a higher risk for VT recurrences in pts with ARVC, and seemingly even more so in pts with a PKP2 mutation. These results indicate a possible role of MIBG-SPECT in terms of an individualized future risk stratification in pts with ARVC. ABSTRACT SESSION 19: NONINVASIVE 3: VT Syndromes: New ECG Insights Thursday, May 10, 2007 1:30 PM - 3:00 PM AB19-1 BODY SURFACE POTENTIAL MAPPING IN PATIENTS WITH ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY: IDENTIFICATION OF NEW ECG-CHARACTERISTICS Matthias Paul, MD, Christian Vahlhaus, MD, Hans-Juergen Bruns, PhD, Christian G. Wollmann, MD, Eric Schulze-Bahr, MD, Lars Eckardt, MD, Guenter Breithardt, MD and Thomas Wichter, MD. University of Muenster, Muenster, Germany. Introduction: Presentation of patients (pts) with arrhythmogenic right ventricular cardiomyopathy (ARVC) and idiopathic right ventricular outflow-tract tachycardias (RVO-VT) may be similar. However, typical ECG features of ARVC are often subtle or absent and therefore do not always allow a clear differentiation between the two entities. Repolarization abnormalities in precordial ECG leads are also characteristic in ARVC. Thus, we analysed potential differences in the

T-wave-integral (TWI) using a 120-channel body surface potential mapping (BSPM). Mutations in plakophilin-2 (PKP2) were identified in pts with ARVC (ARVC-9). Therefore, we additionally assessed the impact of genotype on TWI alterations. Methods: ARVC pts were divided into 2 groups: those with a PKP2-mutation (PKP2-pos; n=5) and those without (PKP2-neg; n=5). In all pts, a BSPM with quantitative signal analyses of the TWI was performed. The results were compared to those obtained in 14 pts with RVO-VT and a control group of 12 healthy subjects. Age, body mass index as well as QRS-axis on surface ECG were not significantly different between the groups. Results: All pts with ARVC had a significantly lower TWI in the right lower anterior region of the torso when compared to both pts with RVO-VT and controls (P<0.00001). These differences were especially pronounced in PKP2-pos in comparison to RVO-VT pts (P<0.00001) with a sensitivity of 91% and a specivicity of 90% respectively (area under curve: 0.98±0.13; P<0.00001). In addition, in PKP2-pos pts, TWI was significantly lower than in PKP2-neg pts (P<0.0001). Reciprocal changes were observed in the left posterior upper region of the torso. In all analyses, there were no significant differences between pts with RVO-VT and controls. Conclusions: Apart from standard ECG lead positions new signal characteristics were identified with the help of BSPM. These allow a reliable differentiation between pts with ARVC and RVO-VT which has important implications for differential diagnosis and risk stratification. The repolarization abnormalities found were even more pronounced in PKP2-pos pts with ARVC. AB19-2 DOES T-WAVE INVERSION IN PATIENTS WITH ARVD CORRELATE WITH RIGHT VENTRICULAR ABNORMALITIES SEEN ON MRI? Henry W. Sesselberg, MD, James P. Daubert, MD, Scott McNitt, MS, Slava Polonsky, MS, David T. Huang, MD, Adam S. Budzikowski, MD, PhD, Ethan Levine, DO, Hugh Calkins, MD, David A. Bluemke, MD, PhD, Frank I. Marcus, MD and Wojciech Zareba, MD, PhD. University of Rochester, Rochester, NY, John Hopkins Hospital, Baltimore, MD and University of Arizona, Tucson, AZ. Introduction: The diagnosis of arrhythmogenic right ventricular dysplasia (ARVD) is based on several major and minor criteria, including T wave inversion (TWI) in leads V2 and V3 (minor criteria) as well as structural RV changes (minor or major depending upon severity). The mechanism of TWI in ARVD remains unexplained and its correlation with the RV changes incompletely characterized. With the advent of newer imaging technology (MRI) we sought to correlate TWI with RV characteristics (dilation and fatty infiltration). Methods: Probands enrolled in the North American ARVD Registry, who had both an MRI exam and also a 12 lead ECG available constitute the study sample. Definite (affected, n=46) and probable (n=21) ARVD patients are included. RBBB patients were excluded. Patients were divided into 3 groups based on the extent of TWI. Results: Of 67 patients who met these inclusion criteria, 30 patients did not have TWI in leads V2-V6, 14 had TWI in V2-V3 (but not beyond) and 23 had TWI beyond V3 (any TWI in V4-V6 in addition to leads V2-V3). Patients with TWI in V2-V3 were to a greater extent female (71%) than those patients without TWI (27%) or TWI beyond V3(43%, p=0.019). Other clinical characteristics were not clearly correlated with TWI on the ECG, although patients with TWI beyond V3 were more often classified as definitely affected by Task Force criteria (p=0.061). By MRI, patients with TWI beyond V3 had lower RVEF and greater RV diastolic and systolic volumes than those patients with TWI in V2-V3 or no evidence of TWI on 12 lead ECG (Table 1). A trend for greater RV abnormality with more widespread TWI is evident.

S40 Heart Rhythm Vol 4, No.5 May Supplement 2007

Conclusions: Patients with TWI in V4-V6 (in addition to V2-V3) had lower RVEFs and greater RV diastolic and systolic dimensions than those with TWI in V2-V3 or absent precordial TWI. TWI beyond V2-V3 may merit consideration as a major criterion for ARVD diagnosis. Table 1: Clinical and MRI characteristics of ARVD Registry patients

No T-wave Inversion in V2-V6

T-wave Inversion in V2-V3 Only

T-wave Inversion Beyond V3

p-value

Number of Patients 30 14 23

Age at Enrollment, mean 42±13 36±12 38±14 0.303

Female, % (n) 27(8) 71(10) 43(10) 0.019

Affected, % (n) 60(18) 57(8) 87(20) 0.061

Prior Arrhythmic Events, % (n) 87(26) 86(12) 87(20) 1.000

RVEF, mean 45±8 51±7 34±14 0.003

RVdiasDiam, mean 40±8 43±9 48±9 0.016

RVsystDiam, mean 31±7 34±8 40±11 0.016

Patients with RV fat, % (n) 53(16) 71(10) 74(17) 0.517

AB19-3 RISK STRATIFICATION OF THE BRUGADA SYNDROME PATIENTS BY THE 12-LEAD ELECTROCARDIOGRAM Juhani Junttila, MD, Josep Brugada, MD, PhD, Pedro Brugada, MD, PhD, Kui Hong, MD, PhD, Andrea Sarkozy, MD, Marc De Zutter, MS, Begona Benito, MD, Juha Perkiomaki, MD, Heikki V. Huikuri, MD and Ramon Brugada, MD. University of Oulu, Oulu, Finland, Hospital Clínic, Barcelona, Spain, Free University of Brussels, Brussels, Belgium, Nanchang University, Jiangxi, China and Montreal Heart Institute, Montreal, Quebec, Canada. Introduction: Brugada syndrome (BrS) is an inherited cardiac disorder that predisposes some subjects to life-threatening ventricular arrhythmias and sudden cardiac death (SCD). Risk stratification between symptomatic and asymptomatic patients with BrS is not well established. Our aim was to study whether12-lead ECG measurements would give useful information for the risk stratification of the BrS patients. Methods: The study population consisted of 464 BrS subjects (62% male). A history of symptoms related to BrS (syncope, documented arrhythmias or SCD) was present in 107 subjects (23%). We determined PR interval, QRS duration, QTc interval, Tpeak-Tend interval from leads II and V2, R/S ratio from lead aVR (aVR sign), and QRS axis from the baseline ECGs. In addition, QRS complex and T-wave morphology parameters were measured by the principal component analysis method. Results: The most prominent difference between the symptomatic and asymptomatic BrS subjects was the QRS duration measured from lead V2 (mean 119 ± 27 ms vs. 101 ± 18ms, p< 0.001). Also aVR sign was significantly higher (p= 0.033) and left axis deviation (LAD) more common among symptomatic BrS subjects (p=0.028). The odds ratio of being symptomatic was 3.0 (95% CI: 1.2-7.4, p= 0.015) for QRS duration ≥100 ms, 2.3 (95% CI: 1.1-4.9, p= 0.031) for aVR sign ≥0.5, and 2.4 (95% CI: 1.1-5.3, p= 0.031) for LAD, respectively. None of the QRS complex or T-wave morphology variables differed between the groups. Conclusions: Prolonged QRS duration in lead V2, higher R/S ratio in aVR and occurrence of left axis deviation in standard ECG seem to

correlate with symptoms and could be useful as additional non-invasive risk markers of life-threatening ventricular arrhythmias in BrS. AB19-4 IS THE PROGNOSIS OF PATIENTS WITH IDIOPATHIC DILATED CARDIOMYOPATHY AND CLASS I OR II OF NYHA AFFECTED BY A BUNDLE BRANCH BLOCK ? Beatrice Brembilla-Perrot, MD, Olivier Marçon, MD, Fabrice Duhoux, MD, Hugues Blangy, MD, Nicolas Sadoul, MD and Yves Juillière, MD. CHU of Brabois, Vandoeuvre les Nancy, France. Introduction: The survival of patients (pts) with idiopathic dilated cardiomyopathy (IDCM) at III, IV stages of NYHA is decreased in those with a bundle branch block (BBB) compared to those without BBB. Less is known on the prognosis of pts at earlier stages of NYHA and who had a left BBB (LBBB) or right BBB (RBBB). The purpose of the study was to evaluate the clinical significance of LBBB or RBBB in pts with IDCM and class I and II of NYHA. Methods: Clinical data, results of noninvasive and invasive studies (surface ECG, Holter monitoring, measurement of left ventricular ejection fraction (LVEF), electrophysiological study, coronary angiography) were collected in 323 pts, 58±12 years old, with IDCM; the pts were in class I or II of NYHA. The studies were indicated for spontaneous wide QRS complex tachycardia (n= 69), syncope (n=103) and nonsustained VT on Holter monitoring (n=151). Eigthy-one of them had a LBBB (group I), 21 a RBBB (group II) and 221 had no BBB (group III). Patients were followed 3±2 years. Results: Mean age was significantly older in group I (61±11 years) and II (63±9) than in group III (57±12) (p<0.01). LVEF was < 40% (mean 29±9 %) and was lower in group I (27±9 %) than in group II (30±9) and III (29±9 (p<0.05). Syncope was more frequent in groups I and II than in group III but the incidence of spontaneous VT was similar. The induction of sustained ventricular tachyarrhythmia (VTA) was similar in the 3 groups (29% in group I, 28.5 % in group II, 32 % in group III). During the follow-up, the incidence of sudden death was similar in 3 groups (2.5 % in group I, 9.5 % in group II, 4 % in group II). The incidence of death related to heart failure and heart transplantation was higher in group I (20.5 %) and II (24 %) than in group III (9 %) (p <0.05). Conclusions: Age was higher and syncope was more frequent in pts with BBB and dilated cardiomyopathy than in those without BBB; mean LVEF was lower in pts with LBBB than in those with RBBB or without BBB. LBBB or RBBB did not increase the risk of spontaneous VT nor the VT induction, did not increase the risk of sudden death, but increased the risk of death related to heart failure and the indications of heart transplantation. AB19-5 A VECTOR APPROACH TO DISTINGUISH RIGHT VENTRICULAR OUTFLOW TRACT FROM AORTIC SINUS CUSP TACHYCARDIA Yanfei Yang, MD, Luis C. Saenz, MD, Paul D. Varosy, MD, Nitish Badhwar, MD, Justin T. Tan, MS, Fethi Kilicaslan, MD, Edmund C. Keung, MD, Andrea Natale, MD, FRCP, Nassir F. Marrouche, MD and Melvin M. Scheinman, MD. University of California, San Francisco, San Francisco, CA, Cleveland Clinic Foundation, Cleveland, OH and Veterans Affairs Medical Center, San Francisco, CA. Introduction: We assessed whether initial vector forces might best distinguish right ventricular (RV) outflow tract (OT) from aortic sinus cusp (ASC) tachycardia (VT). Methods: Among 45 patients (16 males and 29 females with mean age of 41±14 years) with OT-VT, we measured the time from the earliest QRS onset in any lead to local onset and to the first QRS peak/nadir in each surface leads during VT. We compared the earliest phase differences among patients with foci in RVOT (n=32) and in ASCs (n=13) (confirmed by ablation) using unpaired T-tests. We determined the optimum cut-points by analyzing the receiver-operator

Session 20 S41

characteristics curves, and derived an algorithm to discriminate ASC from RVOT foci. The ECGs from both groups were analyzed using standard published criteria by an expert blinded to the clinical results. Results: Earliest onset in V2 (29/32 [88%] vs 4/13 [12%], p = 0.0001), earlier initial peak/nadir in III (93±16 vs 110±19 ms, p = 0.0026) and V2 (42±19 vs 75±26 ms, p < 0.0001) favored RVOT-VT. The V2 onset criterion was strongly predictive of an RVOT focus (sensitivity 91%; specificity 69%; positive predictive value 88%; negative predictive value 75%; c = 0.80). After determining the optimum cut-points for each, we combined these parameters to form a four-point (0-3) score and compared the patients with ASC vs RVOT foci (p < 0.001). Twenty-eight of 30 patients with a score of 0 had RVOT-VT, and 2/2 patients with a score of 2 had an ASC focus. The table shows the sensitivity, specificity, positive and negative predict value using different cut-off score. The sensitivity and specificity using this vector approach were superior to the current ECG criteria for distinguishing the origin of OT-VT (sensitivity of 85% vs 64%, specificity of 88% vs 50%).Conclusions: In OT-VT, the earliest onset or first peak/nadir in V2 and early initial peak/nadir in III suggest a RVOT focus. Table - Sensitivity, Specificity, Positive and Negative Predict Value by

Scores (c = 0.87)

Score Sensitivity (%)

Specificity (%)

Positive Predict Value (%)

Negative Predict Value (%)

1 85 88 73 93

2 15 100 100 74 AB19-6 CHARACTERISTICS OF PREMATURE VENTRICULAR CONTRACTIONS INITIATING LIFE-THREATENING VENTRICULAR TACHYARRHYTHMIA IN PATIENTS WITH ISCHEMIC HEART DISEASE AS REVEALED BY CONTINUOUS 12-LEAD ECG MONITORING Yu-Ki Iwasaki, MD, PhD, Yasushi Miyauchi, MD, PhD, Yasuhiro Hirasawa, MD, Kenji Yodogawa, MD, PhD, Koji Katoh, MD, PhD, Takeshi Yamamoto, MD, PhD, Naoki Sato, MD, PhD, Keiji Tanaka, MD, PhD, Yoshinori Kobayashi, MD, PhD, Takao Katoh, MD, PhD and Teruo Takano, MD, PhD. Nippon Medical School, Tokyo, Japan. Introduction: Premature ventricular contraction (PVC) with short coupling interval has been considered as a high-risk sign for development of life-threatening ventricular arrhythmias (VT/VF) especially in ischemic heart disease (IHD). However, because of its infrequent nature, the characteristics of the PVC that trigger VT/VF have not been characterized in detail by 12-lead ECGs. Methods: This study consisted of 9 patients (age 71±7) with IHD and poor LV function (EF 29±7%), in whom the onset of VT/VF could be recorded by continuous 12-lead ECG monitoring. Patients within 48 hours from the onset of acute myocardial infarction were excluded. Results: In all patients, VT/VF was initiated by single or couplet of PVCs. In 8 patients, such PVC exhibited RBBB and either left axis (n=3), northwest axis (n=3), or right axis deviation pattern (n=2) with relatively narrower QRS (138±22ms), suggesting that they originated from the Purkinje systems either in left posterior or anterior fascicular region. In all patients, PVCs with different QRS morphology that did not trigger VT/VF could be also recorded. The QRS duration of such non-triggering PVC was significantly longer (183±30 ms, p<0.01) than that in the triggering PVC. Unexpectedly, there was no significant difference in the coupling interval between the triggering PVCs and non-triggering PVCs (430±158 vs. 396±38 msec, p=NS). In 4 of 9 patients, the VT/VF could be controlled by pharmacologic therapy. In the remaining 5 patients resistant to anti-arrhythmic drugs, radiofrequency catheter ablation (RFCA) of the triggering PVCs was effective. In all such patients Purkinje potential preceding the onset of QRS was appreciable at the successful site.

Conclusions: The PVCs originating from the Purkinje system could initiate the VT/VF more easily than those from the ventricular muscle regardless of the coupling interval. The origin of the PVC, rather than the coupling interval, is an important determinant of whether it triggers VT/VF in patients with IHD. ABSTRACT SESSION 20: PEDI/ADULT CONGENITAL HEART DISEASE 1: Device Therapy in Children and Adults with CHD Thursday, May 10, 2007 1:30 PM - 3:00 PM AB20-1 BIPOLAR LUMENLESS LEAD PERFORMANCE CHARACTERISTICS IN CHILDREN AND ADULTS WITH CONGENITAL HEART DISEASE Marcos Daccarett, MD, Nathan M. Segerson, MD, Rakesh K. Pai, MD, Moeen Abedin, MD, David Bradley, MD, Roger A. Freedman, MD and Elizabeth V. Saarel, MD. University of Utah, Salt Lake City, UT. Introduction: Due to small size and anatomic variation, implantation of endocardial atrial (A) and ventricular (V) leads for permanent pacing in congenital heart disease (CHD) remains a challenge. The 4.1F bipolar lumenless SelectSecure deflectable catheter-delivered lead offers advantages in this population due to the small, isodiametric diameter, increased tensile strength and novel method of placement. Methods: A retrospective descriptive analysis of all patients at a single center implanted with the Medtronic 3830 model lead was performed. Results: Over 6 months, 27 patients were implanted. The mean age was 15±7 years, 60% male. D-transposition of the great vessels and ventricular septal defects were the most prevalent CHD diagnoses. A total of 26 A leads and 16 V leads were implanted. The mean procedure time was 149±85 min, with fluoroscopy time of 19±14 min and a total radiation dose of 557 mGy (CI95%, 256 - 984). Implant capture and sensing thresholds were excellent (Table I), and phrenic nerve stimulation could be avoided by precise lead position in all patients. Pacing and sensing thresholds remained stable during the 90±52 day follow-up (Table I). No acute lead-related complications, lead failures or extractions were observed. Utilizing a multivariate longitudinal ANOVA, no statistically significant differences in sensing/pacing trends were found when comparing the performances for A and V locations.

Table I. SelectSecure Model 3830 Lead Performance Characteristics. (Mean±SD)

Atrial lead Performance

Visit N Voltage Threshold (V) Sensed A/V (mV)

Impedance (Ω)

Pre-Discharge 26 1.2±0.8 4.1±2.7 839±354

7±2 days 17 0.8±1.1 3.2±1.2 591±105

69±31 days 10 0.8±0.3 3.2±1.8 565±76

131±38 days 2 0.7±0.3 1.7±0.1 616±68

Ventricular lead Performance

Pre-Discharge 16 0.8±0.5 12.1±4.9 803±282

7±2 days 11 1.1±1.7 9.8±1.9 540±78

69±31 days 7 0.9±0.3 8.8±3.5 545±86

S42 Heart Rhythm Vol 4, No.5 May Supplement 2007

Conclusions: In our single-center experience this novel lumenless, catheter-directed bipolar lead appears to be safe and effective for A and V pacing in the acute and subacute post-implant periods. Extended performance trends will be required to determine long-term efficacy. AB20-2 LOW-TECH LEAD EXTRACTION IN PEDIATRIC AND CONGENITAL EP PRACTICE David J. Bradley, MD, Susan P. Etheridge, MD and Elizabeth V. Saarel, MD. Primary Children's Hospital, Salt Lake City, UT and University of Utah, Salt Lake City, UT. Introduction: A variety of techniques have been described for the extraction of non-functioning endocardial pacing and defibrillator leads. The preservation of venous routes to the heart is a priority in young patients, who will require many pacing systems. While few reports of extraction exist in the pediatric cardiology literature, major extraction complications are occasionally described, particularly with the use of laser and electrosurgical extraction sheaths. We report our experience with extraction using techniques other than laser and electrosurgical sheaths in a representative group of young patients. Methods: We reviewed pacemaker lead extraction records from the electrophysiology database at our institution over the past 4 years. Results: Over the study period, 31 patients (median age 17.1, range 5.1-31.1) underwent extraction of 39 leads (5% ICD). Seventeen (55%) had normal anatomy, 14 had repaired or palliated congenital heart disease (CHD). Simple traction (T) was used for 12 (31%) leads, extraction by sheaths using the superior approach (SA) for 4 (10%), femoral approach using gooseneck snares (GNS) for 11 (28%), and dedicated extraction snares (ES) for 12 (31%). Extraction success overall was 85%, with 3 partial extractions (8%) and failure with 3 leads (8%). Extraction success using femoral approaches (GNS and ES) was 91%. There were no serious complications. Minor complications included fracture and embolization of a lead tip, requiring retrieval, and damage to a second functioning lead, requiring replacement. No transfusions were required. No evidence of valve injury was suspected or demonstrated by echo in any patient. Conclusions: Pacemaker lead extraction using sheaths and snares is safe and effective in the pediatric and CHD population. The femoral approach, adopted over the course of this series, has the highest success rate and can be adapted to patient size and anatomy. AB20-3 PATTERNS OF REVERSE REMODELING IN CHILDREN RECEIVING CARDIAC RESYNCHRONIZATION THERAPY Elizabeth B. Fortescue, MD, Charles I. Berul, MD, Mark E. Alexander, MD, Edward P. Walsh, MD, John K. Triedman, MD, Elizabeth D. Blume, MD, Kevin Pachucki, BS, David W. Brown, MD and Frank Cecchin, MD. Children's Hospital Boston, Boston, MA. Introduction: Cardiac resynchronization therapy (CRT) has been demonstrated to significantly improve cardiac function in children with heart failure. The pattern and time-course of reverse remodeling of the left ventricular (LV) myocardium in children receiving CRT has not been well described. Methods: All pts receiving CRT at Childrens Hospital Boston to date were reviewed. Inclusion criteria were: (1) LV ejection fraction (EF) <45% on echo prior to CRT; (2) 2-ventricle physiology with a morphologic LV in the systemic position; and (3) at least 1 pre-CRT and 3 post-CRT echos suitable for quantitative analysis. Paired t-tests were used to compare echo measurements over time for statistical significance. Results: Of 10 eligible patients, median age at CRT implant was 2.7 yrs (range 0.4-19.8). Cardiac diagnoses included isolated dilated

cardiomyopathy (5), coarctation (2), and D-TGA (3). Median duration of follow-up after CRT was 15.6 months (range 2.4-51.2). With CRT, LVEF improved from mean 23±11% before CRT to 48±19% on most recent echo (p=0.002). LVEDV Z score decreased from mean 11.5 ±10.0 to 6.0 ±6.9 (p=0.17), and LVESV Z score decreased from mean 27.8 ±23.2 to 11.2 ±14.5 (p=0.07). The largest gains in EF were made in the first month after implant, but further improvements continued through 2 years of follow-up. The Figure shows a box and whisker plot of EF over time. The columns mark medians and 25-75 percentiles, the vertical lines show min/max values, and the line connecting the plots marks the mean value.

Conclusions: In this cohort of young pts, CRT was associated with echocardiographic evidence of reverse LV remodeling. These data suggest that reverse remodeling in children receiving CRT is a chronic process, with the largest effect occurring acutely. These data may aid in interpreting echo measurements and guiding therapy in children receiving CRT. AB20-4 ELEVATED DEFIBRILLATION THRESHOLDS IN CHILDREN AND ADOLESCENTS WITH IMPLANTABLE CARDIOVERTER DEFIBRILLATORS (ICDS): A RETROSPECTIVE REVIEW Eric S. Silver, MD, Leonardo Liberman, MD, Henry M. Spotnitz, MD, Allan J. Hordof, MD and Robert H. Pass, MD. New York Presbyterian Hospital, Columbia University, New York, NY. Introduction: The incidence and characteristics of children and adolescents with elevated defibrillation thresholds (DFTs) are not well described. Methods: All patients < 21 years of age who received an ICD at our institution from 1/98 -9/06 were analyzed, including age, sex, diagnosis, body surface area (BSA), medications at the time of ICD placement, and echocardiographic data. All patients who required the placement of a subcutaneous patch or array (SUBCUA) for elevated DFTs were identified and compared to those with an acceptable DFT. Elevated DFTs were defined as a DFT with less than 10J safety margin from the devices maximum output. Results: Sixty-eight patients met the study criteria. The majority of patients had a diagnosis of hypertrophic cardiomyopathy (23 patients, 34%), positive ventricular stimulation study (12 pts, 18%), dilated cardiomyopathy (10 pts, 15%), long QT syndrome (10 pts, 15%), or congenital heart disease (8 pts, 12%). 12 of 67 (18%) required a SUBCUA due to elevated DFTs, while one patient received a

Session 20 S43

prophylactic SUBCUA without DFT testing. SUBCUA's were successful in lowering the DFTs to an acceptable level in all 12 (100%). There were no associated complications with their use. Patients with dilated cardiomyopathy (DCM) had a higher incidence of elevated DFTs compared with all other groups (6/10, p=0.002). All other diagnoses, patient age, sex, BSA, use of amiodarone, or a low shortening fraction were not associated with elevated DFTs. Four of the 12 patients (33%) who required a SUBCUA prior to hospital discharge had acceptable DFTs at the time of ICD implantation, with elevated DFTs at pre-discharge testing. Conclusions: We found an 18% incidence of elevated DFTs requiring SUBCUA. Patients with a diagnosis of DCM were more likely to have elevated DFTs at or soon after device placement requiring the implantation of a SUBCUA. Preparation for elevated DFTs in pediatric patients with DCM should be considered. AB20-5 ELECTRICAL STORM IN CHILDREN WITH AN IMPLANTABLE CARDIOVERTER DEFIBRILLATOR: CLINICAL FEATURES AND OUTCOME Michael J. Wolf, MD, Ilana J. Zeltser, MD, Jack Salerno, MD, Juan Villafane, MD, Jane Crosson, MD, William Scott, MD, Bertrand Ross, MD, Lori Seaman, MD, Elizabeth Stephenson, MD, Thomas Paul, MD, Yung Lau, MD, Ulhas Pandurangi, MD, Larry A. Rhodes, MD, Jonathan R. Kaltman, MD, Ronn E. Tanel, MD, Victoria L. Vetter, MD, Karen Buck, RN and Maully J. Shah, MBBS. University of Pennsylvania, Philadelphia, PA, Dallas Children's Hospital, Dallas, TX, Seattle Children's Hospital, Seattle, WA, Children's Heart Specialists, Louisville, KY, Johns Hopkins University, Baltimore, MD, King Daughters Children's Hospital, Norfolk, VA, Hospital for Sick Children, Toronto, Ontario, Canada, Georg-August University, Gottingen, Germany, Alabama Children's Hospital, Birmingham, AL, Madras Medical Mission, Chennai, India, West Virginia University, Morgantown, WV and Children's Hospital of Philadelphia, Philadelphia, PA. Introduction: Electrical Storm (ES) is arbitrarily defined as ≥ 2 ventricular arrhythmia (VA) events resulting in ICD activation in 24 hours. Data are lacking regarding ES in children. Methods: A multi-institutional retrospective study was conducted with patients (pts) from 11 pediatric centers to evaluate clinical features, and outcome of ES. Pts ≤ 21 years with ICD and ≥ 1 ES from 1995 to 2006 were included. Clinical, ICD data and stored electrograms were analyzed. Results: Of 223 ICD recipients, 23 (10 %) had ES over a follow up of 3.6 ± 2.6 yrs. ES patients had long QT syndrome (n=8), hypertrophic cardiomyopathy (HCM) (n=7), catecholaminergic VA (n=2), restrictive cardiomyopathy (n=1), non compaction cardiomyopathy (n=1), Tetralogy of Fallot (n=1) and idiopathic VA (n=3). Seven (30%) ES pts had aborted cardiac arrest prior to ICD. Age at ICD implant of ES pts was 10 ± 4.5 yrs. Age at 1st ES was 11.7 ± 4.6 yrs. Time from ICD to 1st ES was 1.55 ± 1.78 yrs. Eight (34%) patients (50% had HCM) had ≥ 1 ES (2ES in 8, 3 ES in 3 and 4 ES in 2 patients). Twenty two (96%) pts were on antiarrhythmic drugs at time of ES with reported non-compliance in two. Overall, 426 ICD shocks (median 6 /patient, range 2-148) were delivered during ES. VA triggering ES were ventricular fibrillation in 61%, polymorphic ventricular tachycardia (VT) in 30% and monomorphic VT in 9% of patients. ES occurred at rest in 8(34.8%), with exertion in 11(48%), mild activity in 2 (8.6%), and sleep in 2 (8.6%). During ES, ICD was unsuccessful in defibrillation in 6 (26%) pts culminating in 1 death, VA self termination in 3 and external defibrillation rescue in 2 patients. After ES, 16 (69%) pts were hospitalized and 19 (83%) had medication change or dose increase. Morbidity from ES included psychological trauma in 8 (35%), neurological impairment in 1 (4%), heart transplant in 2 (8.6%) and ICD battery depletion in 2 (8.6%) pts.

Conclusions: The consequences of electrical storms can be devastating in children. Optimizing antiarrhythmic treatment, ICD programming and external defibrillation back up may be necessary to improve outcome. The true prevalence and predictors of ES need to be defined with a larger study. AB20-6 FINITE ELEMENT MODELING OF NOVEL DEFIBRILLATION APPROACHES IN CHILDREN AND ADULTS Matthew Jolley, MD, Jeroen Stinstra, PhD, David Weinstein, PhD, Steve Pieper, PhD, Raul San Jose Estepar, PhD, Frank Cecchin, MD, Dana H. Brooks, PhD, Rob Macleod, PhD and John K. Triedman, MD. Children's Hospital Boston, Boston, MA, University of Utah, Salt Lake City, UT, Brigham and Women's Hospital, Boston, MA, NorthEastern University, Boston, MA and Scientific Computing Institute, University of Utah, Salt Lake City, UT. Introduction: ICD implants in children are complicated by size and anatomy. Creative ad hoc implant techniques are utilized but have not been fully validated. We used subject-specific, image-based finite element models (FEMs) to compare electric fields and expected defibrillation thresholds (DFTs) using standard and novel electrode locations. Methods: FEMs were created by segmenting normal torso CT scans of 2 children and 1 adult[ages 2, 10, and 29years] into tissue compartments, meshing and assigning tissue conductivities. FEMs were modified by interactive placement of ICD electrodes in a variety of reported and anatomically feasible locations. The critical mass hypothesis was used to define effective defibrillation. Potentials, electric fields, and currents were computed and interactively visualized using SCIRun. Results: Computed DFTs for standard transvenous configurations in the adult were similar to published results. Thoracic subcutaneous electrodes resulted in high but clinically feasible DFTs, and generated more homogenous electric fields than electrodes close to the heart. Contralateral extracardiac placement of can and electrode predicted lower DFTs than ipsilateral. Differences in lead placement and patient anatomy produced significant variation (e.g., up to 100% DFT variation with a four rib difference in lead placement). Transvenous and epicardial leads had lower DFTs but greater field variance and very high (>60V/cm) local myocardial voltage gradients in some orientations. Conclusions: Image based FEMs provide insight into clinical defibrillation scenarios. Extracardiac ICDs are predicted to be effective in both children and adults. Our method, developed using open source tools, may aid ICD development and patient-specific optimization of electrode placement in patients with small and/or unusual anatomy.

S44 Heart Rhythm Vol 4, No.5 May Supplement 2007

ABSTRACT SESSION 21: PEDI/ADULT CONGENITAL HEART DISEASE 2: Pediatric Arrhythmias: New Insights and Therapies Thursday, May 10, 2007 1:30 PM - 3:00 PM AB21-1 ACCESSORY ATRIOVENTRICULAR MYOCARDIAL CONNECTIONS IN THE DEVELOPING HUMAN HEART, RELEVANCE FOR PERINATAL SUPRAVENTRICULAR TACHYCARDIAS Nathan D. Hahurij, MSc, Nico A. Blom, MD, PhD, Denise P. Kolditz, MSc, Maurits C. Wijffels, MD, PhD, Regina Bökenkamp, MD, Roger R. Markwald, PhD, Martin J. Schalij, MD, PhD, Robert E. Poelmann, PhD and Adriana C. Gittenberger-De Groot, PhD. Leiden University, Leiden, The Netherlands and Medical University of South Carolina, Charleston, SC. Introduction: Fetal and neonatal atrioventricular reentrant tachycardias can be life threatening but resolve in most cases during the first year of life. Temporary presence of accessory atrioventricular (AV) myocardial connections during the normal process of AV junction isolation may explain this phenomenon. Methods: We studied 44 human embryonic (n=6), fetal (n=34) and neonatal (n=4) sectioned hearts with an age range of 4 to 36 weeks of development. We used immunohistochemical markers to identify myocardium and connective tissue including antibodies against MLC-2a, HHF-35, collagenVI and periostin. Accessory AV myocardial connections were quantified and categorized according to their specific location and 3D AMIRA reconstructions were made. Results: Up to 6 weeks of development, atrial and ventricular myocardium was continuous at the AV junction. Between 6 and 10 weeks, numerous AV myocardial connections were observed at the left (45%), right (35%) and septal (20%) region of the AV junction. Whereas most right sided connections were identified as distinct myocardial strands, left sided connections comprised larger areas of myocardium. Between 10 and 20 weeks, all AV connections consisted of discrete myocardial strands that gradually decreased in number. Majority of AV connections (67%) were observed at the right AV junction, mostly located at the lateral aspect (45%) in close contact with the so-called right atrioventricular ring bundle. At the left AV junction and the septal area only 17% and 16% of the AV connections were observed, respectively. 3D reconstructions of the AV nodal area at these stages also showed several myocardial AV connections related to the developing AV node. From 20 weeks until birth and in neonatal hearts no accessory connections were observed anymore. Conclusions: Isolation of the AV junction is a gradual and ongoing process and particularly right lateral AV connections are commonly found at later stages of normal human cardiac development. These transitory accessory myocardial connections may act as substrate for atrioventricular reentrant tachycardias in the fetus or neonate. AB21-2 BRUGADA SYNDROME IN THE PEDIATRIC POPULATION Andrea Sarkozy, MD, Tim Boussy, MD, Gian-Battista Chierchia, MD, Sergio Richter, MD, Marc De Zuter, RN, Joseph Brugada, MD, PhD, Ramon Brugada, MD, PhD and Pedro Brugada, MD, PhD. Free University of Brussels, Brussels, Belgium, University of Barcelona, Barcelona, Spain and Montreal Heart Institute, Montreal, Quebec, Canada. Introduction: The characteristics and prognosis of BS in the pediatric population have not been systematically investigated. Methods: In this study we included 113 patients from our BS database who were evaluated for BS at age ≤ 18 years between 1991 and 2006 (age: 10.6 ± 5 years, 58 males). Four patients presented as symptomatic probands, and 109 children were evaluated during the

family screening of 38 adult probands. SCN5A mutation was identified in 9 individuals from 5 families. Results: Seventy-four children (group I) had a negative class I antiarrhythmic drug (AAD) test. Three of these patients were silent SCN5A mutation carriers. Ten children (group II) had baseline normal ECG and were asymptomatic, but due to their young age (3.2 ± 3y, p<0.001) no class I AAD test was performed. In eight asymptomatic children (group III), the result of the class I AAD test was questionable. Three of these children were carriers of an SCN5A mutation. Fifteen asymptomatic children (group IV) had a positive class I AAD. Six patients (group V) had a positive class I AAD test and had syncope. Interestingly, four of the 6 patients in group V also had evidence of sick sinus syndrome and atrial fibrillation/flutter (p<0.001) and four of the 6 patients had intermittent spontaneous coved type I ECG documented (p<0.001). During the mean follow up period of 60.2 ± 38 months, 2 patients suffered sudden death and one patient aborted sudden death. The two patients who died suddenly were from group V. In Kaplan Meier survival analysis the presence of syncope (p=0.036), SSS/atrial arrhythmias (p=0.014) and spontaneous type I ECG (p=0.014) predicted a significantly shorter survival. Conclusions: In our study, symptomatic BS occurred rarely in children. These patients frequently presented with sick sinus syndrome and atrial arrhythmias in the presence of spontaneous type I ECGs. The medium term prognosis of these children was unfavorable. In contrast, the medium term prognosis of the asymptomatic children is favorable. AB21-3 UTILITY OF SIGNAL-AVERAGED ELECTROCARDIOGRAPHY IN PEDIATRIC ARVC Robert M. Hamilton, MD, Joel A. Kirsh, MD, Gil J. Gross, MD, Angie Basciano, Laura De Souza and Elizabeth A. Stephenson, MD. Hospital for Sick Children, Toronto, Ontario, Canada. Introduction: Signal-averaged electrocardiography (SAECG) is reported to have a moderate sensitivity (SENS) and high specificity (SPEC) for ARVC in adults. We sought to identify SENS and SPEC of SAECG in children. Methods: Patients presenting with LBBB VT or a family history of ARVC underwent noninvasive assessment for Task Force (TF) criteria for ARVC, including SAECG. Those identified with an additional ARVC criterion underwent invasive assessment. SAECGs were filtered at 40-250Hz. Z values for filtered QRS duration (QRSDf), high frequency low amplitude signal duration (HFLA) and root-mean-square voltage of the terminal 40 msec (RMS40) were calculated based on published regression equations from a group of 139 normal children aged 5-15 years, who were also used to assess SPEC of individual and combined SAECG criteria. Where ARVC patients had sequential SAECGs during follow-up, changes in Z value were calculated on a per year interval (∆Z). Outcomes of death or appropriate defibrillator shock (DEATH/SHOCK) were identified. Results: SAECGs were available in 36 children aged 4.8 to 18.0 (13.9±3.2) years who met TF criteria for ARVC. Average noise was 0.26 ±0.09 µV. SAECG parameters were ≥ 2 S.D. for QRSDf in 9/36 (25%),≥ 2 S.D. for HFLA in 11/36 (31%) and ≤ -2 S.D. for RMS40 in 9/36 (25%). Any abnormal SAECG parameter was present in 17/36 (47%) children, including 6 who had normal unfiltered QRS duration (QRSDu) on standard ECG. Only 11/139 (8%) control children had any abnormal SAECG parameter. DEATH/SHOCK occurred in 4/36 patients, and was predicted by a more prolonged HFLA (Z value = 3.99±4.36 vs. 1.65±2.11, p<0.02) and lower RMS40 (Z value = -2.33±1.85 vs. -1.16±0.98, p<0.01) Patients with DEATH/SHOCK tended to have a more rapid negative change (∆Z) in RMS40 (-0.58±1.23 vs. -0.03±0.21, p=0.1)

Session 22 S45

Conclusions: In these children, SAECG has a 47% SENS and 92% SPEC for ARVC, and identified additional children with ARVC whose QRSDu on standard ECG is normal. SAECG is feasible in children being assessed for ARVC, with SENS and SPEC approaching that seen in adults assessed for ARVC. In this limited sample size, SAECG parameters and their trends appear to predict outcome. AB21-4 QUALITY OF LIFE IN PEDIATRIC PATIENTS WITH THE LONG QT SYNDROME Jonathan R. Kaltman, MD, Ryan Tomlinson, BS, Linda Hurd, MSN, CRNP, Ronn E. Tanel, MD, Maully J. Shah, MBBS, Victoria L. Vetter, MD, David Shera, PhD, Anne Kazak, PhD, Gil Wernovsky, MD and Bradley S. Marino, MD. The Children's Hospital of Philadelphia, Philadelphia, PA. Introduction: Children with the Long QT syndrome (LQTS) live with the risk of sudden death, activity restrictions, and the need for daily medications. This study evaluates quality of life (QOL), behavior, and cross-informant variance between patients (pts) with LQTS and their parents. Methods: QOL (Pediatric QOL Inventory [PedsQL]) and behavioral (Achenbach) inventories were completed by pts with LQTS and their parents. The PedsQL has a total score and two subscales (Physical and Psychosocial). Pts' clinical charts were reviewed. Comparisons were made to published data for healthy children using t-tests. Multivariate modeling used linear regression. Results: 43 pts with LQTS were evaluated (mean age 13.8 ± 3.0; male 50%) with a mean QTc of 0.48 ± 0.03. Total QOL score was significantly lower in LQTS pts compared to healthy children (77.8 ± 16.1 vs. 83.0 ± 14.8; p = 0.03). The Psychosocial score was lower in LQTS pts compared to normal (76.1 ± 16.7 vs. 82.4 ± 15.5; p = 0.01) while the Physical score was similar (80.9 ± 17.0 vs. 84.4 ± 17.3; p = 0.21). Assessment of parental perception of their childs QOL revealed Total QOL (76.0 ± 17.2 vs. 87.6 ± 12.3; p < 0.001), Psychosocial (73.9 ± 18.9 vs. 86.6 ± 12.8; p < 0.001) and Physical (80.1 ± 17.9 vs. 89.3 ± 16.4; p < 0.001) scores that were all lower than parents perception of healthy children. Lower QOL scores for LQTS pts were associated with higher levels of anxiety/depressive symptoms (p = 0.03) and somatic complaints (p = 0.01). QOL was not associated with cardiac symptoms, an implantable device or a genetic diagnosis. Lower total scores for parental perception of QOL were associated with higher perceived levels of internalizing symptoms (p = 0.01) and lower perceived overall competency (activities, school, social settings; p = 0.04). Conclusions: Pts with LQTS have a lower QOL than normal children, associated primarily with psychological factors. Parents also perceive a lower than normal QOL for their children but, unlike their children, relate lower QOL to both physical and psychosocial functioning. Physicians and families caring for children with LQTS should increase focus on the psychological well-being of these pts in an effort to improve their quality of life. AB21-5 BASELINE HEART RATE AND THE EFFICACY OF Β-BLOCKER THERAPY FOR THE PREVENTION OF LIFE THREATENING CARDIAC EVENTS IN PATIENTS WITH THE CONGENITAL LONG QT SYNDROME Ilan Goldenberg, MD, Arthur J. Moss, MD, Scott McNitt, MS, Wojciech Zareba, MD and Jennifer L. Robinson, MS. University of Rochester, Rochester, NY. Introduction: Increased sympathetic activity is a risk factor for cardiac events in patients with the congenital long QT syndrome

(LQTS). We hypothesized that a faster resting heart rate may identify LQTS patients who benefit from β-blocker therapy. Methods: Cox proportional hazards regression modeling was used to assess the efficacy of time-dependent β-blocker therapy for the prevention of aborted cardiac arrest or sudden cardiac death in 2245 LQTS patients, aged 10-20 years, who did not receive medical therapy at the time of the baseline ECG recording. Results: In multivariate analysis, upper quartile resting heart rates (RR interval <720 msec) and QTc durations (≥530 msec) at the baseline examination were associated with a respective 2.5-fold and 1.9-fold increase in the risk life threatening cardiac events in study patients (p<0.001 for both parameters). β-blocker therapy was associated with a 63% reduction in the risk of life threatening cardiac events in the overall study population (p=0.002). However, the benefit of β-blocker therapy was more pronounced among patients who exhibited upper quartile resting heart rates (HR = 0.30 [95% CI 0.13 - 0.70]; p = 0.005) than among patients with slower resting heart rates (HR = 0.48 [95% CI 0.21 - 3.68] p = 0.42). By contrast, upper quartile QTc duration did not identify patients with a more pronounced β-blocker effect (HR = 0.58 [95% CI 0.27 - 1.25]; p=0.17). Conclusions: Our findings suggest that assessment of resting heart is useful to identify high-risk LQTS patients who may benefit from medical therapy with β-blockers. ABSTRACT SESSION 22: SPECIAL SESSION 1: Clinical Reports with ICD and CRT Therapy Thursday, May 10, 2007 1:30 PM - 3:00 PM AB22-1 DIALING-IN" THE RIGHT VENTRICULAR LEAD TO OPTIMIZE RESYNCHRONIZATION THERAPY" Ryan G. Aleong, MD, Anshul Patel, MD, E. Kevin Heist, MD, PhD, Francois B. Tournoux, MD, Annabel A. Chen, MD, Mary Orencole, RN, CNP, Jeremy N. Ruskin, MD, Warren Harthorne, MD and Jagmeet Singh, MD, PhD. Massachusetts General Hospital, Boston, MA. Introduction: Cardiac resynchronization therapy (CRT) has been shown to improve left ventricular function, patient symptoms and survival in appropriate heart failure patients. Lack of response to CRT may be due to variability in coronary sinus (CS) anatomy, LV electrical activation and the impact of right ventricular (RV) pacing. We describe optimization of CRT by repositioning the RV lead along the inter-ventricular septum relative to the fixed LV lead position to maximize electrical and anatomic separation. Methods: N/A Results: A 79 yr. male with ischemic cardiomyopathy (LVEF 30%), NYHA class III symptoms, left bundle branch block (QRS 152 ms), and mechanical dyssynchrony (Ts-SD of 44ms) underwent implantation of a CRT device. Rotational coronary venous angiography was performed, capturing 120 frames over a 4-sec period from LAO 55 to RAO 55. The LV lead was placed in a postero-lateral CS branch (Figure A). Continuous cardiac output (CO) was monitored using a novel lithium indicator (LiDCO) method. The CO increased from a baseline 3.63 to 4.33 L/min during biventricular pacing with a septal RV lead position (Figure A), and further increased to 5.25 L/min with moving the lead to the RV apex with BiV pacing (Figure B). Moving the RV pacing site from the septal to apical region also increased the RV to LV electrical delay from 88 ms to 130 ms. The patient responded well at 3 months with functional improvement (NYHA I, increase in 6-min walk distance from 800 to 1050 feet and improvement in MLWHF score from 73 to 26), reduction in mechanical dyssynchrony (Ts-SD of 27ms) and an increase in his LVEF to 42%.

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Conclusions: RV lead site selection relative to the final LV lead position may increase electrical and physical separation between the two leads, translating into a better acute hemodynamic and long-term clinical response. However, this dialing-in the RV lead strategy needs to be evaluated prospectively.

AB22-2 DIRECT HIS BUNDLE PACING IN A PATIENT UNDERGOING DUAL CHAMBER ICD IMPLANTATION Ahmad Abdul-Karim, MD, Robert Lobel, MD and Daniel L. Lustgarten, MD, PhD. University of Vermont, Burlington, VT. Introduction: Adverse effects associated with conventional RV apical (RVA) pacing have led to the use of alternative pacing sites in patients requiring ventricular pacing. Direct His bundle pacing (DHBP) maintains physiologic ventricular activation and has been shown to be feasible, safe, and effective. DHBP may not be considered an option for patients needing an ICD since the RV apex is preferred for optimal defibrillation. Herein we present a novel approach to providing both DHBP and RVA defibrillation. Methods: N/A Results: The pt is a 78 yo male with HOCM and CHF presenting with syncope. Previously he had an ablation for typical AFL where he was noted to have a PR interval of 360 ms. On Holter he had confluence of atrial and ventricular activation during exercise due to PR prolongation. We decided to implant a CRT-D with a view toward providing DHBP via the LV pacing port. Using a deflectable delivery sheath, an exposed screw lead (Medtronic 3830) was fixed at the anteroseptal RV where a His potential was identified (HV≈45ms). Pacing showed 40 ms latency from the stim artifact to the ECG QRS onset. Ventricular activation on the DHBP lead occurred 200 ms after the stim artifact. The paced and native QRS complexes were identical. A defib lead was placed in the RVA and an atrial lead placed at Bachmann's bundle. The leads were connected to a CRT-D device using the LV pacing port for the DHBP lead. The RV defib lead was set below capture threshold. The end result was AV synchronous pacing over the normal His-Purkinje system with physiologic AV delay (see Fig). Conclusions: We present a novel approach to providing both permanent ventricular pacing and ICD therapy preserving physiologic ventricular activation. We used a CRT device using the LV port to

achieve DHBP. This approach should be broadly applicable given the advent of deflectable lead delivery systems and individually programmable ventricular channel outputs.

AB22-3 SAFETY OF ICD IMPLANTATION IN A PATIENT USING AN EXTERNAL PNEUMATIC AIRWAY CLEARANCE DEVICE Mathew D. Hutchinson, MD, Nehal N. Mehta, MD, Sandhya Dhruvakumar, MD, Sen Ji, MD, PhD and Joshua M. Cooper, MD. University of Pennsylvania, Philadelphia, PA. Introduction: The use of defibrillators in young patients and those with comorbid medical conditions presents challenges in ensuring proper device function while preventing spurious therapies. Specific interactions with many medical devices are not known. We present a case of device implantation in a patient with cystic fibrosis (CF) who uses an external pneumatic airway clearance system. Methods: NA Results: A 22 year old man with CF, ventricular noncompaction and LV dysfunction (EF 30%) was referred for implantation of a single chamber ICD for primary prevention of sudden death. Due to his copious mucus production, he was treated with an external pneumatic compression device (The VestTM, Model 104; Hill-Rom). The vest is applied to the chest with Velcro straps and connected to an external air pulse generator, which inflates and deflates against the chest up to twenty times per second causing dislodgement of mucus from smaller airways and facilitating expectoration. We were concerned about both mechanical interactions of the pneumatic compressions against the ICD pocket and the electric generator creating artifact on the ICD lead. No previous experience was available either in the medical literature or from the device manufacturer. Given the elevated risk of sudden death in patients with left ventricular noncompaction and low EF, implantation of a single chamber ICD was performed in our patient. We performed a device interrogation while the patient used The VestTM 24 hours after ICD implantation. We found no electrical artifact present on the ventricular or shock electrograms either during or after use (Figure). Conclusions: The external pneumatic compression device The VestTM causes no apparent interference with ICD function. It appears safe to resume treatments with The VestTM as soon as 24 hours after implantation provided that customary activity restrictions are observed.

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AB22-4 DEFIBRILLATOR MALFUNCTION REQUIRING EMERGENT EXPLANTATION OF ICD GENERATOR: A DEVICE FLAW RESULTING IN REPEATED INAPPROPRIATE HIGH ENERGY THERAPIES Mark A. Mitchell, DO, Joseph G. Akar, MD, PhD, David J. Wilber, MD and Peter Santucci, MD. Loyola University, Maywood, IL. Introduction: 68 yr old man with an ICD implanted 8/04 for recurrent VT was transferred for multiple inappropriate high-energy therapies. He had been discharged from a community hospital 2 days earlier after a series of 4 shocks, but returned with recurrent shocks. Methods: N/A Results: In the ER, telemetry confirmed NSR during therapy delivery. Attempts by a Boston Scientific (BSX) field technician to deactivate tach detection failed to prevent further shocks. No abnormalities were seen on CXR. Repeated interrogation revealed that the Guidant model T177 ICD autonomously reactivated detection & therapy. As a result of a device fault, reversion to a Safety Fallback Mode (SFM) repeatedly reprogrammed the pulse generator (PG) to single zone detection & therapy with limited programmability. The device could retain any reprogramming only briefly before reverting to SFM. No EGMs or event markers could be obtained. The inability to prevent inappropriate shocks mandated the immediate replacement of the PG. During the replacement procedure, all lead connections were inspected. Intra-op device measurements & lead parameters were normal. During follow-up analysis, BSX engineers reproduced the clinically observed error message in the lab environment. Evaluation of the ICD confirmed a device reset resulting in the observed error message. Following the reset, the PG reverted to a SFM with minimal programmability. X-ray imaging of the device failed to reveal anomalies. The analog integrated circuit (AIC) was removed & tested showing normal behavior. When the AIC was reconnected to the PG, repeated interrogations failed to recreate the error codes noted clinically & in the lab environment. Conclusions: The speculative conclusion for the ICD malfunction was a faulty solder joint resulting in an incomplete connection between the AIC & the body of the device. The connection was corrected once the AIC was replaced during testing & resoldered to the device. This malfunction is the first reported occurrence of its kind,

and shows an example of a serious & potentially dangerous PG anomaly. AB22-5 NOVEL METHOD OF ATRIOVENTRICULAR PROGRAMMING IN ATRIAL FLUTTER CAUSES IMPROVEMENT IN PATIENTS WITH BIV-PACEMAKER- A CASE SERIES Tasneem Z. Naqvi, MD and William Barnett, BA. Cedars-Sinai Medical Center, Los Angeles, CA and Medtronics, Inc., Los Angeles, CA. Introduction: Atrial flutter is a common cause of exacerbation of congestive heart failure (CHF). In this report we describe novel method of atrioventricular (AV) pacemaker optimization in 4 patients (pts) with atrial flutter and CHF who had not derived significant symptomatic benefit post biventricular pacemaker implantation. Methods: All patients (age 71-84 yrs) had atrial flutter on interrogation and adjustment of AV delay and post ventricular atrial refractory period (PVARP) was performed to enable sensing of every 2nd to fourth atrial flutter beat by the atrial lead. Once sequential early and adequate late diastolic filling was seen on mitral inflow pulsed wave (PW) Doppler, further adjustment of AV delay and PVARP was performed until the highest and broadest atrial velocity occurred on mitral inflow PW Doppler (white arrows, Figure). Mode switch was turned "OFF" in all pts and upper and lower rate limits were set at 100 and 50 bpm. Results: All pts developed improvement in aortic ejection duration and peak ejection velocity - both echocardiographic surrogates of cardiac output, at the time of AV optimization. Repeat EKG in all pts at 8 months, 7 days and 3 days post optimization showed persistent atrial flutter and no change in EKG P and QRS relationship. All pts developed improvement in CHF symptoms post echo-guided biv pacemaker optimization. Conclusions: Our findings suggest that by adjusting PVARP and AV delay in pts with CHF and stable atrial flutter, atrial mechanical contribution to cardiac output and improvment in cardiac output can be achieved without complications. These findings highlight the value of echo-guided pacemaker optimization in symptomatic patients with atrial flutter post biventricular pacing.

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ABSTRACT SESSION 23: SPECIAL SESSION 2: Mapping and Ablation of Ventricular Arrhythmias: Cases from the EP Lab Thursday, May 10, 2007 1:30 PM - 3:00 PM AB23-1 LEFT CARDIAC SYMPATHETIC DENERVATION FOR CATECHOLAMINEGIC POLYMORPHIC VENTRICULAR TACHYCARDIA Mario Facchini, MD, Lia Crotti, MD, Chiara Ferrandi, BSc, Giuseppe Celano, MD, Zahurul A. Bhuiyan, MD, PhD, Attilio Odero, MD, Arthur A. Wilde, MD, PhD and Peter J. Schwartz, MD. IRCCS Istituto Auxologico Italiano, Milan, Italy, IRCCS Fondazione Policlinico San Matteo/University of Pavia, Pavia, Italy and University of Amsterdam, Amsterdam, The Netherlands. Introduction: Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), a genetic disorder caused by mutations in the ryanodine receptor gene RyR2, manifests itself with life-threatening arrhythmias (LTAs) occurring especially during physical stress. Its management is difficult. Most patients are protected by beta-blockers (BB), but many continue to have VT on effort and often receive an ICD. As fast VTs occur even with modest physical effort, the ICD repeatedly shocks many of these patients, greatly limiting their physical activities. We explored the possibility that left cardiac sympathetic denervation (LCSD) might reduce these stress-induced adrenergically-mediated LTAs and the need for ICD implant. Methods: We report the outcome of 2 CPVT patients not protected by BB who underwent LCSD. Their RyR2 mutations were identified by DHPLC and direct sequencing. Results: Patient 1 carries a novel missense mutation, F4511L, absent in his relatives and in 117 controls. Since age 10 he had frequent syncope and at age 17 a polymorphic VT was documented during exercise stress testing at 50 watt. Despite propranolol (240 mg) he had a cardiac arrest due to documented ventricular fibrillation. In 1988, at age 18, he underwent LCSD. During the following 18 years he remained completely asymptomatic. VT can still be induced by exercise but only at 120 watt. Patient 2 carries a novel missense mutation, E4076K, strongly segregating within the family and absent in 100 controls. She became symptomatic at age 10 and despite full dose BB therapy she continued to have complex arrhythmias at minimal workloads. In 2005, at age 17, she underwent LCSD. During the following 12 months she remained asymptomatic and ventricular arrhythmias appear only at high workloads. Conclusions: These two single cases provide proof-of-concept for the possibility of managing CPVT patients not protected by BB by performing LCSD. The antiarrhythmic effect of LCSD is also accompanied by a major improvement in the quality of life of these young patients who are no longer terrified at the idea of moving and exercising. LCSD does not preclude the possibility of resorting to an ICD, if necessary. AB23-2 DEVELOPMENT OF DELAYED POTENTIAL IN ENDCARDIAL ELECTROGRAM OF THE RIGHT VENTRICULAR OUTFLOW TRACT IN A PATIENT WITH THE BRUGADA SYNDROME Yasuaki Tanaka, MD, Mitsuhiro Nishizaki, MD, Noriyoshi Yamawake, MD, Takashi Ashikaga, MD, Hiroyuki Fujii, MD, Shingo Maeda, MD, Tatsuya Hayashi, MD, Saori Niki, MD, Harumizu Sakurada, MD and Masayasu Hiraoka, MD. Yokohama Minami Kyosai Hospital, Yokohama, Japan, Tokyo Metropolitan Hiroo Hospital, Tokyo, Japan and Tokyo Medical and Dental University, Tokyo, Japan. Introduction: It has been reported that the abnormal potential was observed from epicardial electrogram mapping in the right ventricle outflow tract (RVOT) in patients with Brugada syndrome. However,

there are no previous reports that electrical abnormality has been demonstrated by endocardial mapping in electrophysiological study (EPS). Methods: N/A Results: A 59 year-old male was admitted to our hospital because of abnormal electrocardiogram (ECG). His 12 leads ECG showed incomplete right bundle branch block with saddleback type ST-segment elevation in the right precordial leads. He had no symptoms. However, his son has been diagnosed as Brugada syndrome, and has been implanted implantable cardioverter-defibrillator (ICD). In oral glucose tolerance test, the ST elevation was enhanced. During infusion of pilsicainide (Pil), the morphology of ST-segment elevation was changed to coved type. In EPS, ventricular fibrillation was induced by programmed ventricular stimulation from RVOT with 2 extrastimuli. Furthermore, Pil provocation test was performed again. In the mapping catheter placed at the endocardium of the free wall at the RVOT (figure1), a distinct local electrogram was recorded after termination of the QRS complex after Pil (figure2, arrows). The ST-segment elevation was also augmented by 0.2mV at the J point in V2 lead and the duration of the local electrogram at RVOT from J point was prolonged from 36ms to 61ms (figure2). He underwent implantation of ICD. Conclusions: To the best of our knowledge, this is the first case of Brugada syndrome, in whom delayed potential was seen after QRS complex in the endcardium of RVOT after sodium channel blocker. The findings suggest that development of electrical abnormality in endocardial mapping may reflect increased voltage gradient due to further decrease in INa in the epicardium.

AB23-3 ROLE OF THE POSTERIOR PAPILLARY MUSCLE AND PURKINJE SYSTEM IN THE MECHANISM OF VENTRICULAR FIBRILLATION IN HUMAN: ELECTROPHYSIOLOGIC AND HISTOPATHOLOGIC FINDINGS Akihiko Nogami, MD. Yokohama Rosai Hospital, Kanagawa, Japan. Introduction: Recently, experimental studies revealed that radiofrequency catheter ablation (RFCA) of Purkinje system in the posterior papillary muscle (PPM) terminated ventricular fibrillation (VF) and prevented VF induction. We examined autopsy specimens from a patient who underwent successful RFCA of ischemic VF.

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Methods: A 61-year-old man with ischemic cardiomyopathy, renal failure, and an implantable cardioverter/defibrillator presented during an electrical storm. Results: ECG showed frequent, ventricular premature contractions (VPCs) with right bundle branch block (RBBB) and superior axis (VPC#1), and VPCs with RBBB and inferior axis (VPC#2). While VPC#1 initiated VF or nonsustained polymorphic VT (NSPVT), VPC#2 initiated NSPVT only. During VPC#1, diastolic Purkinje potentials (-50 msec) were recorded at the left ventricular mid-septum. RFCA at this site abolished VPC#1 and VF. However, frequent NSPVT triggered by VPC#2 was still observed. At the second session, VPC#2 and NSPVT were eliminated by RFCA to the proximal site where left bundle (LB) potential was recorded during sinus rhythm (Figure 1). Pacing from this site at the different cycle lengths reproduced the QRS configurations of VPC#1 and VPC#2. He died of pneumonia 1 month after ablation, and an autopsy was performed. RFCA sites for VPC#1 and VPC#2 were macroscopically observed (sites A and B in Figure 2, respectively). At the ablation site of VPC#2 the fibromuscular bands that connected the left ventricular septum and the PPM were observed (arrows in Figure 2). Microscopic analysis confirmed the presence of Purkinje cells in the fibromuscular band (Figure 3) and the PPM. Conclusions: Purkinje system in the fibromuscular bands and the PPM may play an important role in the initiation and perpetuation of VF in humans.

AB23-4 ABLATION OF PREMATURE VENTRICULAR COMPLEXES WITHIN THE MIDDLE CARDIAC VEIN Sujoya Dey, MD, Fred Morady, MD and Frank M. Bogun, MD. University of Michigan, Ann Arbor, MI. Introduction: Frequent ventricular ectopic activity may be incapacitating for some patients and may cause significant reduction in cardiac function if left untreated. Epicardial ablations have been described for sustained monomorphic VT in patients without heart disease. We present a unique case of successful ablation of premature ventricular complexes (PVC) within the middle cardiac vein. A 44 year-old male was referred to the electrophysiology laboratory because of palpitations from symptomatic PVCs in a left bundle superior axis pattern. Echocardiogram revealed normal left ventricular function while cardiac catheterization revealed normal coronary angiogram. A Holter showed a PVC burden of 25%. Methods: N/A

Results: Programmed ventricular stimulation was performed with and without isoproterenol from the right ventricular apex. No sustained arrhythmia was inducible. The patient had frequent, monomorphic PVCs occurring in a trigeminal pattern with a left bundle superior axis. Activation mapping was performed at the septal aspect of the right and left ventricle with the earliest activation mapped to the infero-apical septum. Multiple radiofrequency (RF) energy lesions were delivered in this area from the right and from the left side which were equally premature (local activation preceding the PVCs by -15 to -19 msec ). These applications failed to eliminate the PVCs. Finally, the catheter was placed into the middle cardiac vein where the earliest activation of -26 msec was located. RF delivered through an irrigated tip catheter immediately eliminated the PVC at an output of 10 watts. After the RF lesion was applied, contrast was injected through the irrigated tip catheter confirming its location in the middle cardiac vein. No complications occurred. Conclusions: Epicardial arrhythmia foci often require a trans-pericardial ablation procedure in order to eliminate the arrhythmia. Since the PVCs originated from the middle cardiac vein, a trans-pericardial procedure was not necessary. This unusual site of origin of PVCs should be considered prior to a trans-pericardial ablation approach. AB23-5 CATHTER ABLATION OF RECURREMT ISCHEMIC VENTRICULAR TACHYCARDIAS GUIDED BY LATE EPICARDIAL POTENTIALS IN SINUS RHYTHM Eduardo B. Saad, MD, Fernanda Ferreira, MD, Ieda Prata, MD, Fabiola Veronese, RN, Paulo Maldonado, MD and Luiz Eduardo Camanho, MD. Hospital Pró-Cardíaco, Rio De Janeiro, Brazil. Introduction: Catheter ablation of ischemic ventricular tachycardias can be a challenging procedure, especially when only fast, non-mappable tachycardias are induced. Other ways of locating the critical regions of the reentrant circuits should be utilized. Methods: N/A Results: A 46 year old male presented with acute anterior wall MI 11 years ago treated with IV Streptokynase. He gradually developed severe LV dysfunction (EF 18%) in the presence of anterior wall akinesis and no significant coronary artery obstructions. A single chamber ICD was implanted 6 years ago due to inducible VT. In 2004 he presented with appropriate ICD firing despite combination of Amiodarone (600 mg/day) and Mexiletine. At EP study only VF could be induced. Conventional endocardial mapping was performed but no areas of low voltage were found in the LV. No ablation was perfomed and an upgrade to a biventricular device was perfomed. One year later he presented with multiple episodes of near-fainting. Device interrogation revealed 89 episodes of ventricular arrhythmias in the last 3 months: 72 successfully treated by ATPs, 3 by electrical shocks and 14 self-terminating VTs. The EP study was repeated but again only polymorphic VT and VF could be induced. No areas of low voltage were found in the endocardial LV. Epicardial access was obtained percutaneously by a subxyphoid approach and mapping was performed in sinus rhythm with a 4mm tip catheter. An extensive area recording low voltage potentials was found in the anterior and lateral LV, where late (diastolic) potentials were recorded. RF applications (total of 28; 50W, 60º) were performed, with complete elimination of those potentials. Amiodarone (200 mg/day) was maintained. After 9 months of follow up the pt remained asymptomatic with no further episodes of ventricular arrhythmias recorded by the device. Conclusions: The scar area caused by MI can be confined to the epicardial region. Catheter ablation using conventional mapping techniques guided by late potentials in sinus rhythm can be an effective strategy when only non-mappable VTs are present.

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AB23-6 PATHOLOGIC FINDINGS AFTER ABLATION FOR VENTRICULAR TACHYCARDIA IN DILATED CARDIOMYOPATHY: CORRELATION WITH BIPOLAR VOLTAGE MAPPING Paveljit S. Bindra, MD, HZ Kimbrell, MD, Fiorenzo Bendotti, RN, Mariell Jessup, MD, David Lin, MD, Edward P. Gerstenfeld, MD and Francis E. Marchlinski, MD. University of Pennsylvania, Philadelphia, PA. Introduction: We have reported that electroanatomic voltage map abnormalities and VT origin in dilated cardiomyopathy (DCM) have a peri-annular distribution most dramatic in the lateral LV. Few reports exist of pathologic correlation with such maps. Methods: N/A Results: A 61-year old male presented with ventricular tachycardia (VT) in 1991 partially suppressed with amiodarone. A biventricular ICD was implanted for EF of 20%, QRS duration of 168 ms and heart failure (HF). In August 2005, he underwent VT ablation for multiple ICD shocks (Fig 1A). LV voltage mapping revealed a basolateral scar (Fig 1B). Ablation in this region rendered the VT non-inducible. He developed progressive HF but no VT, and was admitted 1 year later and underwent orthotopic heart transplantation. The explanted heart revealed a fibrotic transmural parenchyma focus measuring 0.9 x 0.6 x 0.6 cm in the posterior basolateral LV (Fig 1C) and patchy scar throughout the lateral LV. Hematoxylin/elastin stains of the endocardium (Figure 1D) and epicardium (Fig 1E) and trichrome stains (Fig 2F, 2G) highlighted focal areas of interstitial fibrosis and myocyte hypertrophy correlating with the scar on the map (area=15.8 sqcm). Microscopic evaluation of the anterior LV also revealed fibrosis (Fig 2H) not evident on the map (Fig 2I). The patient has done well post-transplant. Conclusions: This case report is the first to correlate human cardiac pathology with voltage mapping in DCMP. It illustrates that although bipolar voltage maps have a reasonable correlation with gross pathology and marked fibrosis; diffuse microscopic fibrotic changes in dilated cardiomyopathy may not be fully represented by the voltage map. Whether these additional areas of microscopic fibrosis serve as a sufficient substrate for VT will require additional study.

ABSTRACT SESSION 24: ALLIED PROFESSIONALS 2: Allied Professionals: Interesting Case Presentations Friday, May 11, 2007 10:30 AM - 12:00 PM AB24-1 REVERSIBLE SOFTWARE ELECTRICAL RESETS IN IMPLANTABLE DEFIBRILLATORS CAUSED BY COSMIC RADIATION DURING AIR TRAVEL Aileen M. Ferrick, ACNP-C, Anthony Aizer, MD, Neil E. Bernstein, MD, Douglas S. Holmes, MD, Jane M. Smyth-Melsky, RN and Larry A. Chinitz, MD. New York University, New York, NY. Introduction: Cosmic Radiation (CR) is well known to electrical engineers as a potential source of disruption to the integrity of electrical circuits. An industry alert was announced in 2005 (St. Jude Medical) in reference to specific implantable defibrillator (ICD) models that were at risk for a hardware reset secondary to CR resulting in loss of pacing and defibrillation. We report on 2 cases of reversible software resets resulting from presumed exposure to CR. The intensity of CR is related to altitude and geological latitude with CR levels being least at the equator and increasing with travel to either pole. Air and space travel is a well known risk for electrical resets from CR due to the loss of atmospheric protection from ambient CR. The level of CR in air travel may be as much as 300 times greater than sea level. Methods: N/A Results: CASES In our patients the ICDs were manufacured by Medtronic Inc.(Models 7289/Insync and D154/Entrust). In both cases, the devices reverted to nominal pacing and defibrillation settings. The times of reset coincided with transatlantic air flights in both individuals. One of the patients had previously been programmed to biventricular pacing for treatment of heart failure and his device reverted to VVI pacing at 40 bpm (nominal setting) with a subsequent loss of biventricular pacing. Originally programmed to 3 zones for tachycardia therapy, it reset to 1 zone for VF therapy only. The second device was prophylactic and the nominal values were only marginally different from those programmed after implant. That patient was psychologically traumatized however, by this unintended device reset. Audible alarms were triggered following both patients' electrical reset episodes. Conclusions: Electrical resets of a software variety are possible from exposure to ambient CR. Air travel is a significant risk factor for these software resets. While correctable, they may have important clinical and psychological ramifications. AB24-2 ANODAL CAPTURE IN CRT-D SYSTEM WITH AN INTEGRATED BIPOLAR ICD LEAD AND SEPARATE RV PACE/SENSE LEAD Mary-Lee Mattei, MSN, NP, RN, Karen Rofino, RN, Karen A. Rose, MSN, NP, RN, Jason Rashkin, MD, Dionyssios Robotis, MD and Lawrence Rosenthal, MD, PhD. University of Massachusetts, Worcester, MA. Introduction: Some cardiac resynchronization therapy (CRT) devices can utilize various LV pacing vectors, including an 'extended bipolar' configuration (LV cathode, RV anode). Inadvertent stimulation at the anodal site may result. Due to the large surface area of the RV coil, anodal capture (AC) is unlikely in CRT-D systems with an integrated bipolar shocking lead. However, if a separate RV pace/sense lead is used, AC can occur since the RV ring becomes the anode in extended bipolar configurations. Methods: n/a

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Results: A 63-yr-old m with a CRT-D (Guidant H210) returned for a lead revision due to noise on the RV egram channel, reproducible with pocket manipulation. A new bipolar pace-sense lead (St. Jude 1688TC) was placed in the RV apex and the IS-1 pin of the ICD lead (Guidant 0158) was capped. The RV egram showed no noise with the new lead, pace thresholds were acceptable (0.4 V at 0.5 msec). The LV threshold was 1.3 V at 0.5 msec in an extended bipolar pacing configuration. Two weeks later, the RV threshold was 0.5 V and the LV was 0.6 V. During LV threshold testing, AC was noted with LV pacing with an LVring-to-RVring extended bipolar pacing configuration (LV ring = cathode, RV ring = anode). Figure 1A shows the AC threshold at 2.8 V. AC is seen in the first two beats (simultaneous capture of the RV and LV). In the third beat, intrinsic RV activation is approx160 msec after the LV pace marker, representing inter-ventricular conduction time from left-to-right. The surface ECG shows two distinct QRS morphologies. Figure 1B shows eventual loss of LV capture in the third beat and a return to intrinsic activation on the RV and LV channels. Conclusions: Anodal capture can complicate threshold testing. When a separate RV pace/sense lead is used with a Guidant CRT-D system, extended bipolar configurations use the RV ring as the anode rather than the RV coil on the shock lead. In such a configuration, AC may occur.

AB24-3 A NOVEL SOURCE OF ELECTROMAGNETIC INTERFERENCE CAUSING INAPPROPRIATE THERAPY FROM AN IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR Jane M. Smyth Melsky, RN, Neil E. Bernstein, MD, Anthony Aizer, MD, Aileen M. Ferrick, ACNP-C, Ann C. Garlitski, MD, Jad D. Swingle, MD, Ashish B. Patel, MD, Scott A. Bernstein, MD, Douglas S. Holmes, MD and Larry A. Chinitz, MD. New York University, New York, NY. Introduction: N/A Methods: N/A Results: A 68 year old gentleman with a history of nonischemic cardiomyopathy (diagnosed in 1999) and paroxysmal atrial fibrillation presented to the arrhythmia clinic after receiving a shock from his ICD. He underwent ICD implantation in 1999 and subsequent battery change in 2005 to a Maximo DR ICD model 7278 (Medtronic Inc., Minneapolis, MN, USA.) At the time of the shock, the patient reports

pumping gas in the rain. Upon touching his car, he felt a transient numbness and withdrew his hand from the car. He then attempted to pump the gas again and was shocked and fell to the ground. Device interrogation revealed Electromagnetic Interference (EMI) consistent with 50-Hz alternating current on both atrial and ventricular channels. There were two distinct EMI episodes, therapy was aborted after the initial sensed event and then delivered seven seconds later when the second EMI event occurred. It was later found that the gas pump had an electrical short in it, requiring electrical rewiring. Conclusions: Electromagnetic Interference can happen in many settings, often unexpectedly, and can be facilitated by electrical conduction with water. Patients with implantable devices need to be educated to take care when handling any electrical machinery, particularly when wet.

AB24-4 CASE REPORT: RESOLUTION OF PACEMAKER SYNDROME WITH DVIR PACING Melanie T. Gura, MSN, NP, RN, Philip H. Keyser, MD, Joseph Redle, MD, Michael A. Pelini, MD and Jason K. Smith, MD. Northeast Ohio Cardiovascular Specialists, Hudson, OH. Introduction: Pacemaker syndrome (PS) refers to adverse hemodynamic or electrophysiologic consequences associated with an electrically normal pacing system. Persistent or intermittent PS induces symptoms ranging from minor to severe, or may limit the patients ability to achieve optimal functional status. PS may occur in the setting of intact ventriculoatrial (VA) conduction in dual-chamber pacing if parameters are suboptimally programmed. Methods: NA Results: We report a case of a 74 year-old male, with sick sinus syndrome and a dual chamber-pacing system, with symptoms

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consistent with PS when programmed to DDDR, lower rate 70 ppm, upper rate limit 120 ppm, auto PVARP, paced AV interval 150 ms, sensed AV interval 120 ms. Consistent VA conduction was exhibited with VVIR pacing, DDD pacing, long AV intervals and rate-adaptive pacing. Chest x-ray revealed normal lead placement. Atrial and ventricular pacing stimulation and sensing thresholds were appropriate. The pacemaker was reprogrammed to DDI at 60 ppm without consistent VA conduction. At one week follow-up, he reported a significant improvement in quality of life (QOL), with the ability to rake leaves and clean gutters with SOB only at peak activity. ECG revealed intact VA conduction following occasional atrial premature depolarizations with VAT pacing. The pacemaker was reprogrammed to the DVIR mode. At two and four weeks post reprogramming, the patient reported significant improvement in QOL with an increase in exercise tolerance and no SOB. Conclusions: PS is an array of cardiovascular and neurologic symptoms and signs resulting from a disruption of AV synchrony due to suboptimal pacing, inappropriate programming of pacemaker parameters, or upper-limit behavior of AV synchronous pacing. This case demonstrates that PS may occur with different pacing modalities that result in permanent or temporary disruption of AV synchrony, and resolution of PS with DVIR pacing. DVIR pacing is a unique strategy to optimize pacing therapy to manage PS. Reprogramming of the pacemaker should be individualized to the patient to achieve the optimal effect. AB24-5 BI-VENTRICULAR PACING: A THERAPY NOT A PANACEA CASE REPORT FROM A CARDIAC RESYNCHRONIZATION CLINIC Mary-Lee Mattei, MSN, ACNP, Karen A. Rose, MSN, ACNP, Lawrence S. Rosenthal, MD, PhD and Dionyssios Robotis, MD. University of Massachusetts Memorial Health Care, Worcester, MA. Introduction: Cardiac resynchronization therapy (CRT) has become standard of care for patients with advanced heart failure; however, post-implant management remains critical to its success. Methods: Case: This case exemplifies the need to integrate medical management and device therapy for optimal outcomes. An 82 year-old male with ischemic cardiomyopathy (ICM), ejection fraction (EF) of 10-15%, NYHA class III-IV heart failure, LBBB and QRS of 144 ms was referred to our specialized CRT clinic for evaluation. Results: Prior to implant, dyssynchrony echo, six minute walk (6mw) and quality of life (QOL) tests were performed. Findings: dyssynchrony echo positive for interventricular and negative for intraventricular dyssynchrony, 6mw 425 feet, QOL 75, BNP 440. He underwent implantation of a biventricular (Bi-V) ICD and was subsequently managed in the CRT clinic. At his 6 week visit he had no clinical improvement with 6mw 200 feet, QOL score 73, BNP 1150. AV optimization (AV opt) was not possible due to frequent PAC's/ PVC's and paroxysms of AF with rapid ventricular response resulting in vetricular sensed events greater than 50%. Aggressive medical management with addition of digoxin and titration of beta-blocker was implemented over several weeks with return to sinus rhythm (SR). A subsequent visit revealed SR with 99% Bi-V pacing, hypovolemia likely related to increased response to diuretics, systolic BP 72, QOL score 73, BNP 156. Walk test was not performed secondary to hypotension. Normal saline was administered, diuretics discontinued, and AV opt performed. AV delay was reset from100 ms to 160 ms sensed, 180 ms paced. Follow-up to AV opt revealed 99 % Bi-V pacing, EF 30%, euvolemia off diuretics and QOL score 55, NYHA Class II.

Conclusions: Frequent follow-up visits and meticulous device programming, ideally in the setting of a CRT clinic, leads to improved outcomes and is pivotal to the success of CRT. AB24-6 BRUGADA SYNDROME ONLY IN PRESENCE OF FEVER- WHAT IS THE TREATMENT? Colleen A. Wolford, RN, BSN and Luna Bhatta, MD. Upstate Medical University, Syracuse, NY. Introduction: N/A Methods: N/A Results: A 53-year-old previously healthy man presented to the ER with flu-like symptoms. His ECG was felt to be consistent with an acute anteroseptal MI(Figure 1). He underwent cardiac catheterization which showed normal coronary arteries. Upon review the patients ECG was consistent with Brugada type pattern. ECG normalized once his fever subsided. He denied history of palpitations/syncope or family history of sudden death. The patient was referred to an electrophysiologist. The available data and lack of uniform recommendations were discussed with patient and family. With their consent, he underwent pharmacological and electrophysiology testing. Procainamide infusion did not show ECG changes. EP testing was done with the protocol recommended by Brugadas group. Polymorphic VT was induced. After discussion with the patient and family, a single chamber ICD was implanted. The patient was referred for genetic testing. Brugada syndrome is characterized by ECG showing right bundle branch block pattern and ST segment elevation in leads V1 to V3 with documented VT or history of sudden cardiac death. Patients who present with this characteristic ECG may be asymptomatic but are at risk of sudden cardiac death. Management of asymptomatic patients with Brugada type ECG is controversial especially when the Brugada pattern is only seen with fever. Brugada et al has suggested asymptomatic patients with typical Brugada pattern ECG are at risk of sudden cardiac death and therefore should undergo EP testing. Those with inducible ventricular arrhythmia should receive ICD. Patients who present with Brugada type ECG only during febrile state have not been studied and are difficult to risk stratify. We presented the available evidence and lack of clear answer to the patient and family and decided our approach according to their decision. Conclusions: N/A

Session 25 S53

ABSTRACT SESSION 25: BASIC/TRANSLATIONAL SCIENCE 5: Autonomic, Functional, and Age-Related Arrhythmias Friday, May 11, 2007 10:30 AM - 12:00 PM AB25-1 COMBINED SYMPATHO-VAGAL STIMULATION STABILIZES ROTORS DURING STRETCH-RELATED AF AND FAVORS ITS PERSISTENCE AFTER ABOLISHING TRIGGERED ACTIVITY Masatoshi Yamazaki, MD, Sharon Zlochiver, PhD, Matthew Klos, BS, Haruo Honjo, MD, Itsuo Kodama, MD, Omer Berenfeld, PhD, José Jalife, MD and Jérôme Kalifa, MD. SUNY Upstate Medical University, Syracuse, NY and Nagoya University, Nagoya, Japan. Introduction: Combined sympatho-vagal stimulation (SVS) has been shown to favor maintenance of atrial fibrillation (AF) by an electrophysiological mechanism that remains unexplored. Here, we endeavored to differentiate between reentrant and triggered discharge mechanisms during stretch-related AF (SRAF) in the setting of SVS. Methods: Optical imaging of AF dynamics was carried out using an SRAF model in the isolated sheep heart (n=7). We mimicked SVS by perfusing 1 µM acetylcholine and 0.03 µM isoproterenol (ACh+ISO). Next, ryanodine (10-40 µM, RYA) was added to abolish triggered activity in response to Ca release. Movies of the left atrial appendage (LAA), together with electrograms on the LAA, left atrial roof (LAR) and right atrial appendage (RAA) enabled characterization of dominant frequency (DF) distribution. Results: SRAF was maintained by both LAA breakthroughs and meandering, short-lived reentrant wavefronts (92.7±1.0 and 7.3±1.0%, respectively). Maximum DF (DFmax) distribution was LAR: 7.8±0.8, LAA:5.6±0.4, RAA:4.1±0.4 (mean±SEM, p<0.05). After SVS, DFmax increased at all locations and DF dispersion (DFmax- DFmin) decreased from 4.2±0.8 to 2.3±0.8 (p<0.02). In the presence of SVS, RYA perfusion led to an increased number and lifespan of rotors (125.8±29.7 to 508.3±168.9 ms /(sec-AF), p<0.04) and none of the AF episodes terminated (figure). In contrast, in the absence of SVS or after ACh+ISO washout, RYA terminated SRAF in all animals. Conclusions: Without SVS, abolishing triggered activity with RYA led to eventual rotor extinction and AF termination. However, in the presence of SVS, RYA was ineffective because of very stable and long lasting rotors. Therefore, the predominance of triggered versus reentrant mechanisms during SRAF is governed by SVS, which tends to stabilize left atrial rotors.

AB25-2 PULMONARY VEIN REGION ABLATION IN EXPERIMENTAL VAGAL ATRIAL FIBRILLATION: ROLE OF AUTONOMIC GANGLIA ABLATION IN EFFICACY Kristina Lemola, MD, Denis Chartier, BSc, Yung-Hsin Yeh, MD, Marc Dubuc, MD, Raymond Cartier, MD, Andrew Armour, PhD, Michael Ting, PhD, Masao Sakabe, MD, PhD, Akiko Shiroshita-Takeshita, MD, PhD and Stanley Nattel, MD. Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada. Introduction: Pulmonary vein (PV) encircling radiofrequency ablation is effective in vagal AF. There is evidence that PVs are a favored site for reentrant and focal mechanisms caused by cholinergic stimulation. PV ablation procedures also have the capacity to affect left atrial autonomic ganglia situated near the PV ostia. Thus, efficacy could be due to a primary role of the PVs themselves or to a key role for left atrial ganglia. Aim: To compare effects of PV elimination (PVE) versus ablation of autonomic ganglia (AAG) overlying PV ostia on vagal AF. Methods: Atrial effective refractory period (AERP) and AF duration were measured with and without vagal stimulation before and after PVE by circumferential radiofrequency PV ablation in morphine/chloralose anesthetized dogs (PVE group, n=6) and before and after radiofrequency ablation targeting all PV-ostial ganglia (AAG, n=6). Local dominant frequency (DF) was assessed by FFT of unipolar electrogram recordings. Results: AERP (CL 300 ms) decreased with vagal stimulation from 116±16 to 78±29** ms (p<0.001**) before and from 132±19 to 80±25** ms after PVE (p=NS for PVE effect). PVE disconnected all PVs, but sustained AF (>20 mins) was induced by vagal stimulation in all dogs both before and after ablation. AF maintenance was associated with persistence of high-frequency driver regions: maximum DF (DFmax) averaged 19±4 Hz before versus 19±3 Hz (P=NS) after PVE. Vagal stimulation reduced AERP by 52±7 ms at baseline; AAG reduced the AERP response to 7±2** ms. Vagal AF >20 mins was induced in 7/7 dogs before and 0/7** after AAG, which reduced mean AF duration to 92±21s. AAG reduced DFmax from 21±1 to 11±0.3 Hz (P<0.05). Bilateral AAG was essential for efficacy: sustained AF was inducible in all dogs after unilateral AAG, which did not significantly alter DFmax (19±1 before vs 16±1 Hz after left PV AAG; 23±2 before vs 16±2 Hz after right PV AAG). Conclusions: 1. Intact PVs are unnecessary for vagal AF maintenance; 2. AAG suppresses vagal AF. 3. Suppression of vagal responses by ablation of the autonomic ganglia overlying PV ostia may contribute importantly to the clinical efficacy of PV ablation for vagal AF. AB25-3 ACETYLCHOLINE INFUSION AND ABNORMAL INTRACELLULAR CALCIUM DYNAMICS PROMOTE BOTH REENTRANT AND NON-REENTRANT ACTIVITIES IN THE PULMONARY VEINS IN A CANINE MODEL OF HEART FAILURE Chung-Chuan Chou, MD, Bich Lien Nguyen, MD, Po-Cheng Chang, MD, Hui-Ling Lee, MD, Fun-Chung Lin, MD, San-Jou Yeh, MD, Michael C. Fishbein, MD, Shien-Fong Lin, PhD, Delon Wu, MD, Ming-Shien Wen, MD and Peng-Sheng Chen, MD. Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan, Cedars-Sinai Medical Center, Los Angeles, CA, Chang Gung Memorial Hospital/Chang Gung University, Taipei, Taiwan and University of California, Los Angeles, Los Angeles, CA. Introduction: Acetylcholine (ACh) shortens action potential and reduces excitability; however, ACh may also help induce late phase 3 early afterdepolarizations. We hypothesized that in a heart failure

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(HF) model, ACh facilitates both reentry and triggered activity to perpetuate atrial fibrillation (AF). Methods: We used optical mapping to simultaneously map intracellular calcium (Cai) and membrane potential (Vm) in isolated pulmonary vein (PV)-left atrium preparations from 10 dogs with pacing-induced HF. Atrial arrhythmias were induced by pacing and mapped at baseline, during ACh (1µmol/L) infusion, followed by ryanodine (2 µmol/L) and thapsigargin (1 µmol/L) infusion. Anti-cholineacetyltransferase (ChAT) staining and Periodic acid-Schiff (PAS) staining were used to identify parasympathetic nerves and specialized conduction cells, respectively. Results: Focal discharge (FD) could be induced from PVs by S1S2 pacing (2/10 at baseline; 6/9 with ACh) and burst atrial pacing (8/10 at baseline; 9/9 with ACh) protocols. In 43 beats of FDs, 17 (40%) showed the rise of Cai was prior to Vm elevation, and preceded by the formation of a Cai sinkhole (low Cai surrounded by high Cai). Ryanodine and thapsigargin infusion suppressed the induction of FD in 6/6 dogs. The spatial distribution of dominant frequency (DF) was changed to a focal source pattern with the highest DF colocalized with the PV FD site in 35/37 cholinergic AF episodes (95%, n= 8). Both PV-left atrium reentry and bursts of PV FD were present during AF. The incidence of PV FD during AF was increased by ACh from 2.4±0.6 beats/sec (n=4) to 6.5±2.2 beats/sec (n=8) (p=0.003). Within the firing PVs, the sites of FD have more ChAT (+) nerves and thicker layers of PAS (+) cells than non-FD parts of the PVs (15±10.5% vs 0%, p=0.0001, and 0.132±0.058 mm vs 0.0464±0.06 mm, p=0.0001, respectively). Conclusions: We conclude that ACh promotes both reentry and FD through spontaneous (voltage-independent) Cai release from a Cai sinkhole. The sites of FD are characterized by abundant parasympathetic innervation and specialized conduction cells. AB25-4 DOES FREE RADICAL SCAVENGING PREVENT ISCHEMIC FOCAL VENTRICULAR TACHYCARDIA Dezhi Xing, MD and James B. Martins, MD. University of Iowa and VAMC, Iowa City, IA. Introduction: Focal ventricular tachycardia (VT) in acute myocardial ischemia is closely related to triggered activity (TA). Lovastatin blocks both focal VT and TA possibly by free radical scavenging. Our study was to analyze the effects of acutely administered free radical scavenger-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) on VT and TA. Methods: Forty-two alpha chloralose anesthetized dogs with coronary artery occlusion were included. 3-D activation mapping helped to locate the origin of focal or reentrant VT. TEMPO (30mg/kg, iv) or saline was given when VT was reinducible. Focal endocardium excised from the site of origin of VT was studied using standard microelectrode techniques with normal Tyrodes solution. Results: Reentry (10/11) and focal (11/12) VT induction were both highly reproducible in vehicle treated groups. TEMPO (n=19) blocked focal VT in 5 of 10 dogs (p=0.055), but 9 of 9 dogs with reentrant VT continued to have VT re-induced after TEMPO (p=0.02 vs focal VT). TEMPO did not alter effective refractory period (168±3 to 171±3 ms), mean blood pressure (88±3 to 81±3 mmHg, p=0.06), or size of ischemia. In vitro, TEMPO (10-3M, n=9) produced no change in resting membrane potential (81±6 vs 80±6 mV), action potential amplitude (91±5 vs 87±5 mV), APD90 (250±15 vs 257±13 ms) and APD50 (171±7 vs 178±7 ms). Nevertheless, sustained TA facilitated by isoproteronol (5x10-7M) was attenuated to 0-5 complexes with TEMPO (n=8, p<0.05) including excised foci of VT. In Dose response testing (10-2-10-4M, n=6), 5 of 6 tissues with TA were blocked with TEMPO at 10-2 M, but in 0 of 6 tissues with vehicle alone (p<0.01). Reversibility to sustained TA also occurred after TEMPO washout. Conclusions: These results suggest that free radical scavengers can prevent triggered activity which caused focal VT during myocardial

ischemia. Antioxidant therapy may play an important role in VT blockade under the conditions of myocardial ischemia. AB25-5 KCNQ DELETION IN THE DROSOPHILA HEART INCREASES THE AGING-RELATED CARDIAC ARRHYTHMIA - AN AGING MODEL OF CARDIAC ARRHYTHMIA H. S. Vincent Chen, MD, PhD, Karen Ocorr, PhD and Rolf Bodmer, PhD. University of California, San Diego, San Diego, CA, The Burnham Institute, La Jolla, CA and The Burnham Institution, La Jolla, CA. Introduction: The genetic basis of cardiac arrhythmias associated with aging is poorly understood. The relatively long lifespan of mammalian systems precludes a simple approach to elucidate the aging-related factors on the genesis and facilitation of arrhythmic disorders. The average lifespan for the fruit fly, Drosophila, is 5-7 weeks and, as in humans, wild-type (WT) flies develop arrhythmias at advanced ages (>3 weeks). A simple fly heart preparation with short lifespan provides a valuable model for studying genes and modifiers involved in aging-related arrhythmogenesis. Methods: Semi-intact Drosophila heart preparations at 1 week (young) and 5 weeks (old) of ages were generated and monitored with high speed digital movies (~160 frames/s) for contractile functions, as well as with intracellular and field potential recordings for arrhythmic activities (Ocorr et al., PNAS, 2007). Results: Examination of WT fly heart preparations showed significant declines in KCNQ RNA levels and increases in cardiac arrhythmia with age (> 3 folds). The KCNQ gene in humans encodes the slowly activating potassium (IKs) current and reduced IKs currents by mutations or drugs would prolong cardiac action potential and lead to fatal arrhythmias. Deletion mutants in the single KCNQ gene of Drosophila are viable but show 6-fold increase of arrhythmic activities in young flies that resemble those seen in older WT flies. External stimulation at 2X the intrinsic heart rate (5Hz) produced sustained arrhythmias similar to what is seen in humans. Additional blockade of KCNQ mutant hearts with Ibutilide (0.1-1 µM), a blocker of rapid-activating K+ currents (IKr), further exacerbated age-dependent arrhythmias. Conclusions: These results suggest that Drosophila hearts use similar K+ channels for cardiac repolarization as human hearts. Reduced IKs and IKr currents are involved in age-related increase of cardiac arrhythmias. Because genetic and pharmacological manipulations can be easily combined on the Drosophila heart, this system provides a powerful model for studying the mechanisms underlying age-dependent increase in cardiac arrhythmias. ABSTRACT SESSION 26: BASIC/TRANSLATIONAL SCIENCE 6: Basic Approaches to Ventricular Arrhythmias Friday, May 11, 2007 10:30 AM - 12:00 PM AB26-1 AUTONOMIC NERVE ACTIVITY AFTER ACUTE MYOCARDIAL INFARCTION IN AMBULATORY DOGS Kenzaburo Kobayashi, MD, Masahiro Ogawa, MD, PhD, Anita Phan, MD, Juan Song, PhD, Michael C. Fishbein, MD, Lan S. Chen, MD and Peng-Sheng Chen, MD. Cedars-Sinai Medical Center, University of California, Los Angeles, Los Angeles, CA and Children's Hospital, University of Southern California, Los Angeles, CA. Introduction: It is generally accepted that acute myocardial infarction (MI) increases both sympathetic nerve activity and arrhythmia, and that these two are causally related to each other. However, a recent clinical trial (COMMIT) showed that beta blocker therapy given within 24 hrs after MI adversely affects the outcome.

Session 26 S55

Methods: We implanted data sciences international (DSI) transmitters to record left stellate ganglion nerve activity (SGNA), left thoracic vagal nerve activity (VNA) and subcutaneous ECG in ambulatory dogs 24 hrs a day, 7 days a week. After two weeks of continuous ambulatory monitoring, acute MI was created by percutaneous balloon occlusion of the left anterior descending (N=2) or circumflex coronary arteries (N=2) for one hour. Results: There was a circadian variation of sympathetic nerve activity but not vagal nerve activity at baseline. Acute MI results in an abrupt increase of 10-s integrated SGNA from 38509±10953 uV/day at baseline to 59129±19264 uV/day (p 30 s) atrial or ventricular tachycardia episodes (N=23), the amplitude of the SGNA (20.3±18.3 uV/30s) was not different than at times without arrhythmias (14.8±14.9 uV/30s, P=NS). Conclusions: SGNA, but not VNA, increases within 24 hrs after acute MI. However, there was no temporal relationship between SGNA and cardiac arrhythmias during that period. These data suggest that beta blocker therapy may not be antiarrhythmic when given within 24 hrs after acute MI. AB26-2 AUTONOMIC CONTROL OF HCN2-BASED BIOLOGICAL PACEMAKERS Iryna N. Shlapakova, MD, Richard L. Verrier, PhD, Peter J. Danilo, PhD, Richard B. Robinson, PhD, Ira S. Cohen, MD, PhD, Peter R. Brink, PhD, Michael R. Rosen, MD and Alexei N. Plotnikov, MD. Columbia University, New York, NY, Harvard University, Boston, MA and Stony Brook University, Stony Brook, NY. Introduction: A potential advantage of biological pacemakers (BP) based on the HCN2 channel isoform over electronic pacemakers (EP) is their autonomic regulation. We studied autonomic regulation of murine HCN2-based BP using adult human mesenchymal stem cells (hMSC) as a delivery platform in left ventricular anterior wall (LV) and an adenoviral vector (Ad) in left bundle branch (LBB). We tested vagal and sympathetic control via Poincare plots (PP) of R-RN against R-RN1 intervals to characterize heart rate variability (HRV). Methods: Complete atrioventricular block (AVB) was induced in 6 dogs via RF ablation and an EP was implanted (VVI 35 bpm). On day 2 after inducing AVB, hMSC containing HCN2 cDNA were implanted subepicardially in LV (n=4) or Ad-HCN2 was implanted in LBB (n=2). Pace-mapping was performed to confirm origin of rhythms and 24h ECG and PP shape were analyzed. Results: During sinus rhythm PP had a complex shape consistent with respiratory sinus arrhythmia based on sympathetic and parasympathetic innervation of sinus node (Fig A). At 1w and 6w, all hMSC dogs had a torpedo PP pattern: reduced HRV reflected predominantly sympathetic control. We subdivided all rhythms in hMSC dogs into those that did/did not pace-map to implantation site. BP rhythms at LVA had a narrow PP with low variability (SDNNi = 27±6ms) (Fig B); spontaneous rhythms at other sites had wider PP and more scatter (Fig C), reflecting higher HRV (SDNNi = 56±5ms, p<0 05). In LBB implants, PP showed even more variability (Fig D). Conclusions: Because narrow PP reflect predominant sympathetic control and more variable PP reflect increased parasympathetic input, we conclude: (1) BP as well as spontaneous rhythms throughout LV have substantial sympathetic responsiveness, (2) BP in LBB manifest more vagal control than in LVA, consistent with vagal innervation patterns, (3) the extent of autonomic control of BP is determined by implantation site.

AB26-3 HUMAN MESENCHYMAL STEM CELL TRANSPLANTATION IN CANINE MYOCARDIAL INFARCTION MODEL INDUCES NGF-ß EXPRESSION BY PARACRINE ACTION RESULTING IN SYMPATHETIC NERVE SPROUTING AND PROARRHYTHMIA Hui-Nam Pak, MD, PhD, Hong-Euy Lim, MD, PhD, Jin Seok Kim, MD, Gwang Il Kim, MD, PhD, Yun Shin Yeo, BSc, Yong Hu Fang, MD, Byung Soo Kim, MD, PhD, Chun Hwang, MD, Peng-Sheng Chen, MD and Young-Hoon Kim, MD, PhD. Korea University, Seoul, Republic of Korea, Pochon CHA University, Pochon, Republic of Korea, Utah Valley Medical Center, Provo, UT and Cedars-Sinai Medical Center, Los Angeles, CA. Introduction: Although both cardiac resynchronization therapy and mesenchymal stem cell (MSC) transplantation improves heart failure, we previously reported that combined left ventricular (LV) epicardial pacing (EpiP) and human MSC (hMSC) transplantation to caine heart has a risk of sudden cardiac death (SCD) without immune rejection. We hypothesized that hMSC transplantation induces NGF-ß expression by paracrine action resulting in sympathetic hyper-innervation and proarrhythmia. Methods: We compared the effects of hMSC to NGF-ß expression (rt-PCR) and cardiac sympathetic nerve sprouting (immunohistochemistry with tyrosine hydroxylase, TH) in vivo canine model (n=17, 1x107 in 1 mL, 5 sites 15 mm apart from electrode) with or without acute myocardial infarction (AMI: LCX ligation) or LV EpiP (DDD, minimal AV delay, 3.5V, open chest) and in vitro pacing of hMSC culture (n=5, 6x106 cells, 2.5 V, 80 bpm for 5 days). We analyzed stored ICD egm in hMSC+EpiP+AMI (n=5), hMSC+EpiP (n=5), hMSC only (n=5), and sham operation (n=2) groups after 4 weeks survival. Results: 1. 80% of hMSC+EpiP+AMI group, 60% of hMSC+EpiP group, 40% of hMSC only group, and none of control revealed spontaneous ventricular tachyarrhythmia (VT) episodes in stored ICD egm. 2. The hMSC transplanted hearts expressed higher densities of TH positive cardiac sympathetic nerves compared with control dog (0.32±0.28 % area vs. 0.00±0.02 % area, p<0.001). 3. hMSC transplanted hearts expressed 121.4±79.4 fold and 4.7±2.0 fold higher expression of NGF-ß and VEGF than sham operation group, respectively. In contrast, in vitro hMSC did not increase NGF-ß or VEGF expression after electrical stimulation (p=NS). Conclusions: hMSC transplantation to canine model with or without AMI or EpiP induced NGF-ß expression in paracrine action, results in cardiac sympathetic hyper-innervation, ventricular arrhythmia, and SCD. Cardiac sympathetic nerve may contribute not only to the improvement of ventricular function, but also ventricular arrhythmias through paracrine action after hMSC transplantation.

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AB26-4 INTRACARDIAC ELECTROPHYSIOLOGY STUDIES IN TRANSGENIC RABBITS Malcolm Kirk, MD, Michael Brunner, MD, Peem Lorvidhaya, MD, Manfred Zehender, MD, Tammy Donahay, BS, Leonard Chaves, BS, Patricia Mastrofrancesco, BA, Alfred E. Buxton, MD, Xuwen Peng, MD and Gideon Koren, MD. Brown University, Providence, RI, University of Freiburg, Freiburg, Germany, Pennsylvania State University, Hershey, PA and Rhode Island Hospital, Brown University, Providence, RI. Introduction: We have created two lines of transgenic rabbits overexpressing pore mutants of the human KvLQT1 (KCNQ1) and KCNH2 (HERG) in the heart. These rabbits show specific inhibition of IKs (LQT1) and IKr (LQT2), respectively. We have previously reported frequent sudden death due to polymorphic ventricular tachycardia (VT) in LQT2, but not LQT1, rabbits. We performed comprehensive electrophysiology (EP) studies in these rabbits to establish normal values, and assess the effect of IKs and IKr inhibition on these values. Methods: Male rabbits, (10 LQT1, 6 LQT2, and 11 littermate controls), age 98 ± 24 weeks were orally intubated and anesthetized with isofluorane. Electrode catheters were placed transvenously at the RV, His bundle and right atrium An EP study was performed in the baseline state and after infusion of isoproterenol to increase the heart rate by 20%. Results: Spontaneous second degree AV block was observed under anesthesia in 5 of 6 LQT2 rabbits. The His bundle recordings, and ventricular pacing showed infra-His block, not due to ventricular refractoriness. Isoproterenol abolished AV block in all cases. AV Wenckebach cycle length (AVWCL) was significantly longer in LQT2 (253 ± 38 ms) than controls (194 ± 37 ms) or LQT1 (166 ± 26 ms), and ventricular effective refractory period (ERP) was longer in LQT2 rabbits (183 ± 24ms) than controls (146 ± 16 ms), or LQT1 (146 ± 22 ms). (p< 0.05, one-tailed t test). These differences were all abolished by isoproterenol. Sustained ventricular arrhythmias were induced with up to 3 ventricular extrastimuli in 4/11 controls, 1/10 LQT1, and 0/6 LQT2. Conclusions: Intracardiac EP studies demonstrate abnormalities of repolarization and conduction in LQT2 rabbits. Programmed stimulation results did not correlate with risk of spontaneous arrhythmias, but dispersion of repolarization may explain the propensity of LQT2 rabbits to have spontaneous VT. LQT2 rabbits demonstrated spontaneous infra-His block, suggesting a role for IKr in the rabbit His-Purkinje system. AB26-5 REDUCTION OF DISPERSION OF REPOLARIZATION AND PROLONGATION OF POSTREPOLARIZATION REFRACTORINESS EXPLAIN THE ANTIARRHYTHMIC EFFECTS OF QUINIDINE IN A MODEL OF SHORT QT SYNDROME Peter Milberg, MD, Regina Tegelkamp, MS, Gerold Moennig, MD, Günther Breithardt, MD, Wilhelm Haverkamp, MD and Lars Eckardt, MD. Westfaelische Wilhelms University, Muenster, Germany and Virchow Clinic, Charite, University Medicine, Berlin, Germany. Introduction: Short QT syndrome (SQTS) is a newly described ion channelopathy, characterized by a short QT interval, associated with sudden cardiac death due to ventricular fibrillation. Since therapeutic options in SQTS are still controversial, we examined antiarrhythmic mechanisms in an experimental model of SQTS. Methods: Pinacidil, an IK-ATP channel opener administered in increasing concentrations (50-100µM) in 48 Langendorff-perfused rabbit hearts, led to a significant reduction of QT interval, thereby mimicking SQTS. Eight simultaneously recorded monophasic action potentials demonstrated an increase in dispersion of repolarization, especially between the left and the right ventricle.

Results: During programmed stimulation, pinacidil significantly increased the inducibility of ventricular fibrillation (one of 48 hearts under baseline conditions, 29 hearts during pinacidil administration; p=0.0001). Additional treatment with the IKr blocker sotalol (100µM) and the class-I antiarrhythmic drugs flecainide (2µM) and quinidine (0.5µM) randomly assigned to three groups of 16 hearts led to prolongation of repolarization as well as of the refractory period. Sotalol or flecainide did not reduce the rate of inducibility of ventricular fibrillation (p=0.63; p=0.219). However, quinidine reduced the inducibility of ventricular fibrillation by 73% (p=0.008) as compared to controls. The antiarrhythmic potential of quinidine was associated with a significantly greater prolongation of MAP duration, refractoriness and postrepolarization refractoriness as compared to sotalol and flecainide. Moreover, quinidine reduced dispersion of repolarization. Conclusions: Pinacidil mimics short QT syndrome, thereby facilitating inducibility of ventricular fibrillation. Quinidine demonstrates superior antiarrhythmic properties in the treatment of ventricular fibrillation in this model as compared to sotalol and flecainide due to its effects on refractoriness, postrepolarization refractoriness and by reducing dispersion of repolarization. AB26-6 BISOPROLOL REGULATE SODIUM CHANNEL SUBTYPES MRNA EXPRESSION AND FUNCTION IN THE LEFT VENTRICULAR CARDIOMYOCYTE OF THE VOLUME-OVERLOADED RATS Geru Wu, MD, PhD, Yutao Xi, MD, PhD, Yuan Du, PhD and Aiqun Ma, MD, PhD. 1st Hospital of Xian Jiaotong University, Xi'an, China and Texas Heart Institute, Houston, TX. Introduction: Beta-blockers can reduce sudden cardiac death, which caused ventricular tachycardia/fibrillation (VT/VF) in heart failure patients, but their role in ion channel components, in particular sodium channels expression and function, has not been defined. Methods: Volume-overload rat models were created by 8 week aorto-caval fistula (ACF) and treated with bisoprolol (ACF-T) (0.8mg/kg·d) for 4 weeks. The hemodynamics and EKG parameters were studied in sham-operation (SO), ACF and ACF-T. The mRNA levels of various sodium channel subtypes were evaluated by real time RT-PCR. Sodium channel gating was studied using patch-clamp techniques. Results: The left ventricular in ACF and ACF-T dilated and the constriction function decreased, compared with SO (pvs.205±29 ms in ACF, pv1.5 mRNA level was decreased by 80% in ACF (0.20±0.03 in ACF vs. 1.00±0.08 in OS,pv1.6 was increased 1.9 fold; (1.91±0.20 vs. 1.01±0.08,pNaT density decreased in ACF compared to SO, (-14.4±4.0 pA/pF vs. -19.7±6.7 pA/pF, pNaL increased (-1.03±0.17 pA/pF vs. -0.75±0.22 pA/pF, pNaT shifted to more positive voltages (V0.5: -74.4±4.1 mV vs. -93.0±7.5 mV, pNaL: -0.29±0.09 pA/pF; V0.5: -95.4±3.8 mV; τ: 69±16 ms). Incubating Bisoprolol with ACF ventricular cardiomyocytes also improved sodium channel function (INaL: -0.61±0.09 pA/pF; V0.5: -95.7±2.1 mV; τ: 70±16 ms), but bisoprolol didnt effect INaT density in vivo and vitro. Conclusions: Our results suggested that Bisoprolol could reduce neuronal Na1.6v mRNA levels and its function in vivo and vitro, and suggested one of molecular mechanism of bisoprolol in heart failure patients.

Session 27 S57

ABSTRACT SESSION 27: BASIC/TRANSLATIONAL SCIENCE 7: Mechanisms of Cardiac Alternans in Health and Disease Friday, May 11, 2007 10:30 AM - 12:00 PM AB27-1 SPONTANEOUS VENTRICULAR FIBRILLATION TRIGGERED IN AGED HEARTS SUBJECTED TO OXIDATIVE STRESS Norishige Morita, MD, PhD, Norihiko Ono, MD, Hideki Hayashi, MD, Masahiro Ogawa, MD, Shien-Fong Lin, PhD, Peng-Sheng Chen, MD, James N. Weiss, MD and Hrayr S. Karagueuzian, PhD. Cedars-Sinai Medical Center, Los Angeles, CA and University of California, Los Angeles, Los Angeles, CA. Introduction: Oxidative stress and aging are known to alter intracellular Ca2+ (Cai

2+) dynamics. However, their combined role in the genesis of ventricular fibrillation (VF) is poorly understood. Methods: We studied Langendorff-perfused rat hearts using simultaneous dual optical Cai

2+-voltage mapping and glass microelectrode recordings in 6 young (3-4 month) and 8 old (24-27 month) rats. Results: The pro-oxidant H2O2 (50-100 µM) promoted spontaneous VF in 7 of 8 old rats, but in none of the 6 young rats (P<0.05). VF started with a short run of monomorphic ventricular tachycardia (VT) that arose from a focal source at the base of the heart where the rate of Cai

2+ removal (τ) was slower than at mid/apical sites (τ =115±16 vs. 99±5 ms; P<0.05). VT propagated initially as single wavefronts but within few seconds degenerated into multiple wavelets signaling the onset of VF. Microelectrode recordings from the base of the heart showed that the focal tachycardia was compatible with early afterdepolarization (EAD)-mediated triggered activity. EADs emerged from a membrane potential of -55 to -68 mV when the diastolic Cai

2+

level was at 27±11% of the peak systolic Cai2+ transient amplitude

(Figure). During triggered activity, discordant action potential and Cai

2+ transient amplitude alternans emerged leading to wavebreak and VF. In young rats, τ of Cai

2+ transient was significantly faster (P<0.05) than old rats, and was little affected by H2O2. Pretreatment with antioxidant trolox (2 mM) reduced the frequency of H2O2-mediated VF (P<0.05). Old rats had significantly greater ventricular interstitial fibrosis (15% vs. 0.4%, P<0.001) and reduced immunodetectable SERCA2a than young rats (P<0.05). Conclusions: Oxidative stress induced by H2O2 interacts with underlying fibrosis in aged rat ventricles to promote VF with an onset mechanism compatible with EAD-mediated triggered activity

AB27-2 CELLULAR MECHANISM FOR SUSCEPTIBILITY TO ARRHYTHMOGENIC ALTERNANS IN HEART FAILURE Lance D. Wilson, MD, Tamer H. Said, MD, Darwin Jeyaraj, MD, Xiaoping Wan, MD, PhD, Gregory S. Hoeker, BS, Haiyan Lui, MD, Isabelle Deschenes, PhD, Kenneth R. Laurita, PhD and David S. Rosenbaum, MD. MetroHealth Campus, Case Western Reserve University, Cleveland, OH. Introduction: Action potential alternans (APD-ALT) is closely associated with reentrant arrhythmogenesis. Although sudden cardiac death usually occurs in patients with heart failure (HF), the mechanism underlying susceptibility to APD-ALT in failing myocytes is unclear. We hypothesize that impaired sarcoplasmic reticulum (SR) calcium (Ca) reuptake associated with decreased SERCA2a expression, which contributes importantly to contractile dysfunction in HF, also explains increased susceptibility to APD-ALT. Methods: High resolution optical mapping was used to map action potentials and Ca transients from 256 sites spanning the transmural surface of canine wedge preparations from normal (N) and HF hearts produced by rapid pacing (each n=7). Results: HF significantly (p<.001) lowered the heart rate threshold for APD-ALT (from 247±27 to 171±13 bpm) and Ca-ALT (from 239±27 to 169±15 bpm). Increased susceptibility to APD-ALT in HF was associated with a slower time constant of Ca transient decay (τ) and decreased SERCA2a expression (Fig). Regions that were most susceptible to APD-ALT (endo- and mid-myocardium) exhibited 33±16% slower τ and 28±19% less SERCA2a expression (both p<.01) vs. resistant regions (epicardium), supporting downregulation of SERCA2a as a molecular basis for increased susceptibility to APD-ALT. Moreover, when stimulating isolated myocytes using an action potential clamp, HF lowered the threshold for Ca-ALT (from 233 to 171 bpm), reaffirming that susceptibility to APD-ALT arises from impaired Ca cycling, not HF-induced changes in the action potential. Conclusions: These functional and molecular data suggest that HF-induced impairment of SR Ca reuptake enhances susceptibility to APD-ALT. APD-ALT may be a mechanism linking contractile dysfunction to arrhythmogenesis

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AB27-3 CALSEQUESTRIN-MEDIATED MECHANISM OF CALCIUM TRANSIENT ALTERNANS WITHOUT SARCOPLASMIC RETICULUM CONTENT ALTERNANS Juan G. Restrepo, PhD, Alain Karma, PhD and James N. Weiss, PhD. Northeastern University, Boston, MA and University of California, Los Angeles, Los Angeles, CA. Introduction: The cellular origin of alternans remains unclear despite the recognized important arrhythmogenic role of this phenomenon. Some studies suggest that a steep dependence of the amount of calcium released from the sarcoplasmic reticulum (SR) on the SR content can cause calcium transient alternans (CTA). However, this mechanism does not appear to explain recent observations of CTA without SR content alternans. Here we pinpoint a new mechanism of CTA without SR content alternans based on a numerical study of a physiologically detailed model of calcium cycling that includes luminal gating of calcium release channels (RyRs) by calsequestrin (CSQ). Methods: Calcium release was modeled with a large number (~10,000) of calcium release units (dyads) spatially distributed throughout the cell with a 50-100 ratio of RyRs to L-type calcium channels (LCC) per dyad. In addition, a fully stochastic Markov model of both LCC and RyR kinetics was used. For the latter, the transition rate from closed to open states is lower (higher) when CSQ is bound (unbound) to luminal auxiliary proteins (triadin/junctin) that regulate the sensitivity of RyRs, and the transition rates between CSQ-bound and CSQ-unbound open or closed states is controlled by the free calcium concentration in the junctional SR. The model was paced with a periodic action potential clamped waveform. Results: For pacing rates below a critical threshold, calcium transient alternans developed without SR content alternans. These alternans were associated with an alternation of the fraction of CSQ-bound RyR/triadin/junctin complexes. Conclusions: CSQ-mediated changes of relative RyR refractoriness can explain calcium transient alternans without SR content alternans. AB27-4 FIBROBLASTS POTENTIATE CARDIAC ALTERNANS AND CONDUCTION BLOCK: A SIMULATION STUDY Yuanfang Xie, PhD, Alan Garfinkel, PhD, James N. Weiss, MD and Zhilin Qu, PhD. University of California, Los Angeles, Los Angeles, CA. Introduction: It has been shown experimentally that gap junctions form between fibroblasts and myocytes, which can facilitate slow conduction in cardiac tissue. Despite its effects on conduction, how fibroblast insertion in cardiac tissue affects the dynamics of arrhythmogenesis remains to be elucidated. Methods: We carried out computer simulations of one-dimensional cables of coupled myocytes and fibroblasts. The Luo-Rudy model was

used for the myocytes while the fibroblast was modeled as an inexcitable cell with a chloride current maintaining its resting potential at around -50 mV. Fibroblast volume was chosen to be 1/5 of that of a myocyte. Two models were studied: in the first model, a segment of fibroblasts were inserted in the middle of the cable. In the second model, fibroblasts were either periodically or randomly inserted between myocytes. Periodic pacing at one end of the cable was used to investigate the dynamical effects of fibroblast. Results: In the first model, successful conduction along the cable occurred if the segment of fibroblast was shorter than 300 µm. A maximum conduction delay of 30 ms was observed, which agrees with experimental observations in cultured monolayers. In the second model, alternans and conduction failure occurred at slower pacing rate than without fibroblasts (Figure). This effect depended on the conductance of fibroblast cells and on the coupling strength between fibroblast and myocytes. Conclusions: In addition to slowing conduction velocity, fibroblasts may also potentiate cardiac alternans to promote an arrhythmogenic substrate.

AB27-5 ELECTRICAL RESTITUTION AND ALTERNANS OF MONOPHASIC ACTION POTENTIALS IN PATIENTS WITH AND WITHOUT SYSTOLIC DYSFUNCTION Jason Kim, BS, Gautam Lalani, MD, Ashwani Sastry, MD, Michael R. Franz, MD, PhD and Sanjiv M. Narayan, MD, PhD. University of California and VA Medical Center, San Diego, CA, Cornell University, New York, NY and VA Medical Center, Washington, DC. Introduction: Alternans of action potential duration (APD) may lead to unidirectional block and reentrant arrhythmias. The restitution hypothesis states that a steep slope of the APD/diastolic interval (DI) relationship (restitution) may cause alternans, but is not established in humans. We tested this hypothesis in patients with and without reduced left ventricular ejection fraction (LVEF). Methods: We studied 42 study patients (LVEF 28+8 %) and 18 controls (LVEF 58+12 %). At electrophysiologic study, we recorded monophasic action potential (MAP) duration at 90 % repolarization (MAPD90) in the right (n=52) or left (n=8) ventricle during extrastimuli and steady-state pacing. In each patient, the maximum slope of

Session 28 S59

MAPD90 restitution was considered steep if >1 using best-fit lines (fig A). MAPD90 alternans was 'positive' if present for > 50 % beats. We followed patients for 806+473 days for sustained ventricular arrhythmias and all-cause mortality (events). Results: Study and control patients did not differ in slope (1.1+0.7 vs 1.3+0.7, p=NS) or numbers with slope > 1 (38% each), and slope was similar for left and right ventricle (p=0.28). Nevertheless, MAPD90 alternans was more prevalent (48 % vs 24 %, p+13 vs 24+17 beats, p=0.059) in study than control patients, although its amplitude did not differ (11+15 vs 7+8 ms, p=0.30). Steep slope did not predict MAPD90 alternans in either group. Patients with events (n=28) had MAPD90 alternans of greater duration (37+12 vs 22+15 beats; p+18.2 vs 6.2+8.9 ms, p=0.05) than those without (fig B).

Conclusions: MAPD alternans is more prevalent and of longer duration in patients with reduced LVEF than controls, and in those who suffered events. However, we found no relationship between steep restitution and alternans of MAP duration at the sampled site. AB27-6 ACTION POTENTIAL ALTERNANS AS A PRECLINICAL MARKER OF DRUG-INDUCED PROARRHYTHMIA Tamer H. Said, MD, Lance D. Wilson, MD, Xiaoping Wan, MD, PhD, Anthony Fossa, PhD and David S. Rosenbaum, MD. MetroHealth Campus, Case Western Reserve University, Cleveland, OH and Pizer Global Research and Development, Groton, CT. Introduction: Sudden cardiac death (SCD) from Torsades de Pointes (TdP) is a devastating complication of therapeutic drugs which block HERG and represents a major impediment to drug development. Prolongation of the ECG QT interval is a primary marker used to screen drugs for proarrhythmic risk; however, it poorly predicts drug-induced TdP. T wave alternans, a powerful marker for SCD, is secondary to cellular action potential alternans (APD-ALT) and can be induced by HERG blocking drugs. We hypothesized that APD-ALT is a better preclinical marker for proarrhythmia than QT interval. Methods: High resolution optical action potentials were recorded from 256 sites across the epicardium of Langendorff-perfused guinea pig hearts (n=25) at baseline and after perfusion with one of four HERG-blocking drugs that either are associated with clinical TdP (TdP+: Bepridil and E4031) or are not (TdP-: Risperidone and Verapamil). Results: QT prolongation was observed with both TdP+ and TdP- drugs and could not differentiate the two groups (Fig). APD-ALT (difference in action potential duration between two consecutive beats) was induced by stepwise increase in pacing heart rate. TdP+ drugs significantly enhanced (p<.01) APD-ALT while TdP- drugs did not affect or significantly suppressed (p<.001) APD-ALT (Fig). Discordant alternans (Dis-ALT), linked to a mechanism of VF, was enhanced only by TdP+ drugs (Dis-ALT threshold decreased by 20-30 ms, p≤.05).

Conclusions: In contrast to nonspecific QT prolongation, drug-induced augmentation of APD-ALT was induced by TdP+ but not TdP- drugs. These data suggest that APD-ALT is a novel pre-clinical marker to assess potential proarrhythmic risk during drug development.

ABSTRACT SESSION 28: BASIC/TRANSLATIONAL SCIENCE 8: Syndromes and Genomics Friday, May 11, 2007 10:30 AM - 12:00 PM AB28-1 EXPANDED MUTATIONAL ANALYSIS OF THE CARDIAC RYANODINE RECEPTOR IN GENOTYPE NEGATIVE PATIENTS REFERRED FOR LONG QT SYNDROME GENETIC TESTING Melissa L. Will, BS, David J. Tester, BS and Michael J. Ackerman, MD, PhD. Mayo Foundation, Rochester, MN. Introduction: Type 1 catecholaminergic polymorphic ventricular tachycardia (CPVT1) is caused by pathogenic mutations in the RYR2-encoded cardiac ryanodine receptor. Since concealed type 1 long QT syndrome (LQT1) and CPVT mimic each other, we sought to determine the spectrum and prevalence of RYR2 mutations in a large cohort of unrelated, LQTS genotype negative patients referred specifically for LQTS genetic testing. Methods: Using PCR, DHPLC, and direct DNA sequencing, we previously performed a targeted RYR2 analysis involving the 23 previously published exons (8, 14-15, 44-47, 49, 83, 87-91, 93-94, 97, 100-105) implicated in CPVT1 for 269 LQTS genotype-negative referral cases (180 females, average age at diagnosis 25 years, and average QTc, 470 ms). Here, we expand our analysis to include 19 additional exons to give an overall analysis of 42 RYR2 exons (8-15, 37-49, 83-105). Results: Overall, 22 distinct mutations were seen in 23 individuals. Fifteen mutations (12 novel) localized to the original 23 exons while 7 novel mutations were in the expanded screen. One patient harbored two separate mutations (F329L and A4510T). None of the mutations were present in 200 ethnic-matched reference alleles. Three mutations localized to the calstabin-2 binding domain. Detailed clinical data was available for 18 cases. All had had a positive history of exertional syncope or near drowning and 11 had a family history of sudden cardiac death.

S60 Heart Rhythm Vol 4, No.5 May Supplement 2007

Conclusions: With this expanded RYR2 scan in our unrelated cohort of 541 patients referred explicitly for LQTS genetic testing, nearly as many CPVT1-susceptibility mutations have been identified as LQT3-causing mutations and far more than LQT4-10 combined. To our knowledge, compound heterozygosity involving RYR2 is reported for the first time. AB28-2 THE EFFECT OF MUTATION CLASS ON QTC IN UNRELATED PATIENTS REFERRED FOR THE FAMILIONTM GENETIC TEST FOR LONG QT SYNDROME David J. Tester, BS, Benjamin A. Salisbury, PhD, Janet L. Carr, PhD, Carole Harris-Kerr, PhD, Carol R. Reed, MD and Michael J. Ackerman, MD, PhD. Mayo Clinic, Rochester, MN, PGxHealth, LLC, New Haven, CT and Cogenics, Inc., New Haven, CT. Introduction: Long QT syndrome (LQTS) genetic testing became clinically available in 2004. Given the veracity of the molecular/functional evidence, LQTS-mutations are annotated as 'probable'- (class I) or 'possible'- (class II) deleterious mutations. Class III genetic variants represent common polymorphisms occurring in >0.5% of the general population. Here, we examined the effect of genotype and mutation class on the heart rate corrected QT interval (QTc). Methods: From August 2004 to August 2006, 574 consecutive, unrelated patients (62% females, 86% white, average age, 23 ± 16 years, and average QTc, 464 ± 54 ms) were referred to PGxHealth for the FAMILIONTM LQTS genetic test. Patients were classified as Genotype Positive (LQT1, LQT2, LQT3, LQT5, or LQT6) or Genotype Negative. Non-synonymous variants were classified as either class I, II, or III and the QTc was compared between genotypes and mutation classification. Results: Overall, 219 patients (84 LQT1, 77% class I; 82 LQT2, 65% class I; 24 LQT3, 79% class I; and 21 Multiples, 81% class I) were genotype positive. Among the genotype negative cases, 313 (88%) hosted ≥ 1 class III variants, similar to the frequency in healthy controls. The average QTc was significantly longer among genotype positive cases (484 ± 52 ms), LQT1 (484 ± 42 ms), LQT2 (485 ± 60 ms), and multiples (512 ± 67 ms) compared to the genotype negative cases (453 ± 50 ms, p value < 0.0001). The QTc (477 ± 62 ms) for patients with a possibly deleterious LQTS mutation (class II) was similar to patients with a class I mutation (483 ± 52 ms) and significantly greater than genotype negative patients with common polymorphisms (454 ± 49 ms, p value < 0.003). Conclusions: Over 75% of genotype positive patients have probable (class I) LQTS-susceptibility mutations. Although the remaining 25% with class II variants are vulnerable to the possibility of being a "false positive", overall there was a significant QT prolonging effect in patients with class II mutations compared to patients with a negative genetic test regardless of the number of common polymorphisms present. AB28-3 INTRONIC BRANCH POINT MUTATIONS MAY CONTRIBUTE TO THE CURRENT FAILURE OF IDENTIFYING MUTATIONS IN PATIENTS AFFECTED BY THE LONG QT SYNDROME Lia Crotti, MD, Marzena A. Lewandowska, BSc, Matteo Pedrazzini, BSc, Roberto Insolia, BSc, Giuseppe Celano, MD, Federica Dagradi, MD, Erica Bussani, BSc, Franco Pagani, MD, PhD and Peter J. Schwartz, MD. IRCCS Policlinico San Matteo, Pavia, Italy and International Centre for Genetic Engineering and Biotechnology, Trieste, Italy. Introduction: Genetic screening of Long QT Syndrome (LQTS) does not identify a clear disease-causing mutation in almost 30% of

affected probands. So far, molecular screening and investigators attention has focused mainly on obvious exonic disease-causing mutations or on substitutions at canonical splice-sites. This leaves uncharacterised many intronic variants that could affect splicing regulatory elements and lead to different types of splicing abnormalities. Predicting which intronic variants are functionally significant is quite difficult to determine from nucleotide sequence alone and pose a diagnostic challenge. Methods: N/A Results: A three-generation LQTS family was investigated. Nine members exhibited QTc prolongation with notched T waves. One member died suddenly in the post-partum period following a telephone ring. Seven other members were asymptomatic with normal QTc. Molecular screening of LQTS genes failed to identify an obvious disease-causing mutation. However, we discovered a novel A to G branch point substitution in KCNH2 intron 9 (IVS9-28A/G), which co-segregates with the clinical phenotype and was absent in 400 reference alleles. A hybrid minigene splicing assay demonstrated that the mutation induced intron retention with selection of upstream cryptic 3 splice site. Conclusions: We demonstrated the LQT2 disease-causing role of a novel branch point mutation in KCNH2. This mutation induces intron retention, an aberrant splicing event difficult to be predicted without a functional splicing assay. The present finding represents proof of concept that intronic mutations affecting pre-mRNA processing may contribute to the failure of traditional molecular screening in identifying a disease-causing mutation in patients with Long QT Syndrome and offers a strategy to reduce the number of genotype-negative cases. AB28-4 SEVERITY OF CONDUCTION DISEASE AND DEVELOPMENT OF CARDIAC STRUCTURAL ABNORMALITIES IN SODIUM CHANNEL DISEASE DEPENDS ON GENETIC BACKGROUND Carol Ann Remme, MD, PhD, Markus A. Engelen, MD, Sandra Van Brunschot, BSc, Antoni C. Van Ginneken, PhD, Charly N. Belterman, BSc, Harold V. Van Rijen, PhD, Arthur A. Wilde, MD, PhD, Marieke W. Veldkamp, PhD, Jacques M. De Bakker, PhD and Connie R. Bezzina, PhD. Department of Experimental Cardiology, Amsterdam, The Netherlands, University Medical Center, Utrecht, The Netherlands and University of Amsterdam, Amsterdam, The Netherlands. Introduction: Reduced penetrance and variable expression is a common feature in primary arrhythmia syndromes including cardiac Na+ channel disease. We hypothesized that this variability may be due, at least in part, to differences in genetic background. We studied the effects of the SCN5A mutation 1798insD, equivalent to human 1795insD, in mice of two distinct inbred strains. Methods: The mutation was transferred from the 129P2 strain (129P2-Scn5a1798insD/+, mut 129P2), onto the FVB/N strain by >6 generations of backcrossing, to generate FVB/N-Scn5a1798insD/+ (mut FVB/N) mice. Mice were analyzed by ECG and echocardiography. Epicardial mapping was performed on isolated Langendorff perfused hearts, followed by Picro Sirius Red staining of cardiac tissue. Results: Adult mut 129P2 mice (2-3 months) showed more severe PQ-prolongation (mean 48.4 ± SEM 0.8 ms vs wildtype (WT) 40.2±0.8, n=12) as compared to FVB/N (mut 35.4±0.8 vs WT 31.9±0.6, n=11; p<0.01). After administration of flecainide, increase in QRS-duration was more than 3-fold higher in mut 129P2 (11.3±0.8 ms, n=7) compared to mut FVB/N (3.4±0.7 ms, n=6; p<0.0001). Epicardial mapping showed that total activation time in the right ventricle (RV, which was more affected than the left ventricle) was increased in mut 129P2 (14.7±2.0 ms, n=9) compared to mut FVB/N (10.6±1.7 ms, n=10; p<0.05). In 10 out of 11 (91%) old mut 129P2 mice (18-20 months) arrhythmias were induced in the RV as opposed to 6 out of 14 (43%) old mut FVB/N, and old 129P2 mice developed

Session 29 S61

more severe myocardial fibrosis. On echocardiography, old mut 129P2 mice showed decreased cardiac contractility and more severe RV dilatation (RV diameter 0.097±0.01 cm, n=5) compared to old mut FVB/N (0.045±0.01 cm, n=5; p<0.05). Conclusions: In Scn5a1798insD/+ mice, severity of conduction disease, arrhythmia inducibility and structural degeneration depends on genetic background, providing evidence that genetic modifiers play a role in the variability of clinical expression in cardiac Na+ channel disease. Our congenic mice provide a relevant tool for future identification of genes modulating cardiac conduction. AB28-5 VARIANTS IN CARDIAC SODIUM CHANNEL (SCN5A) ASSOCIATED WITH ATRIAL FIBRILLATION Dawood Darbar, MD, Gayle Kucera, RN, Tanya Stubblefield, RN, Janey Wang, MS, Alfred L. George, MD and Dan M. Roden, MD. Vanderbilt University, Nashville, TN. Introduction: Family-based genetic studies have identified ion channel gene variants associated with atrial fibrillation (AF), the most common arrhythmia in clinical practice. Here we tested the hypothesis that vulnerability to AF is associated with genetic variation in SCN5A, the gene encoding the cardiac sodium channel. Methods: We resequenced the SCN5A coding region (>6 kb) in 188 subjects with lone AF, 257 with AF + associated heart disease, and 188 anonymous ethnically-defined controls. Results: In addition to common, previously-reported polymorphisms, 19 rare missense variants were identified in 22 probands (5.9%). All variants were verified by repeat PCR and bidirectional resequencing, and all probands were heterozygous. In 6 families with >1 affected member, the variant cosegregated with AF. All variants affect highly conserved residues in the SCN5A protein and 16/19 substitutions are non-conservative including 5 that add, remove or reverse side chain charge. Of the 19 variants, 8 were novel: not previously published or deposited in publicly-accessible databases, and not found in the population controls. The remaining 11/19 have been previously associated with inherited arrhythmia syndromes (long QT syndrome syndrome [LQTS], Brugada syndrome). Conclusions: Mutations or rare variants in SCN5A may predispose patients with or without underlying heart disease to AF. In addition, AF may represent part of the spectrum of LQTS and Brugada Syndrome. The findings of the present study expand the clinical spectrum of disorders of the cardiac sodium channel to include AF, and represent important progress toward molecular phenotyping and directed rather than empiric therapy for this common and morbid condition. AB28-6 Β-ADRENERGIC RECEPTOR POLYMORPHISM PREDICTS VENTRICULAR ARRHYTHMIA AFTER SUBARACHNOID HEMORRHAGE J. Michael Frangiskakis, MD, PhD, Masaki Tanabe, MD, Marilyn Hravnak, RN, PhD, Elizabeth A. Crago, RN, MSN, Michael B. Horowitz, MD, John Gorcsan, III, MD and Barry London, MD, PhD. University of Pittsburgh, Pittsburgh, PA. Introduction: Subarachnoid hemorrhage (SAH) leads to significant death and disability. Cardiac morbidity and mortality after SAH are attributable to myocardial infarction (MI), decreased ventricular function, and ventricular arrhythmias (VA), with a likely stimulus being catecholamine surge. β-adrenergic receptor (β-AR) polymorphisms affect cardiac outcomes, but their role in arrhythmia after SAH is unknown. Consequently, we tested the association of 5 β-AR polymorphisms with VA in the setting of SAH. Methods: In 253 patients admitted for acute, aneurysmal SAH, EKG parameters, 24-hour Holter monitors (VA = 3° heart block; ventricular

couplets, tachycardia, and fibrillation), and echocardiograms (ejection fraction, [EF]) were examined. Genotypes were obtained using TaqMan SNP Genotyping Assays for the following gene polymorphisms: β1-AR (S49G, R389G) and β2-AR (G16R, Q27E, T164I). Results: Initial QTc (iQTc) was 462 ± 50 ms (mean ± SD, n=245) and ≥470 ms in 93 patients (38%). QTc decreased at follow-up (≥7 days, 440 ± 30 ms, n=91, p=0.003). VA were present in 47/159 patients (30%), iQTc was longer in patients with VA (480 ± 51 vs. 453 ± 41 ms, p=0.001), and iQTc correlated with VA incidence (p=0.001; R2=0.899; Figure). For β1 S49G, genotyping yielded 100 SS, 32 SG, and 4 GG individuals. The G allele was associated with VA, particularly in those not taking β-blockers, but was not associated with iQTc (Table). This association was still significant using a multivariate analysis including sex, age, and EF (p=0.048; N=136). No other β-AR polymorphism was associated with VA or iQTc. Conclusions: These data demonstrate a significant association between the β1 S49G polymorphism and arrhythmias in the setting of SAH. The β1-AR S49G polymorphism modulates the cardiac effects of the catecholamine surge in SAH and prophylactic β-blockade may be useful in this population.

ABSTRACT SESSION 29: CATHETER ABLATION 4: Ablation of AF: Safety First Friday, May 11, 2007 10:30 AM - 12:00 PM AB29-1 HIGH INCIDENCE OF ASYMPTOMATIC ESOPHAGEAL ULCERATION AFTER PULMONARY VEIN ANTRUM ISOLATION IN PATIENTS WITH ATRIAL FIBRILLATION Hiroshi Nakagawa, MD, PhD, Kenneth A. Seres, MD, Katsuaki Yokoyama, MD, PhD, Jack Collier, MD, Vikram Katari, MD, Deborah J. Lockwood, MBChB, Sunny S. Po, MD, PhD, Adriana Slobodova, MD, Lisa Herring, RN, Jody Olsen, RN, Ralph Lazzara, MD, Richard F. Harty, MD, Karen J. Beckman, MD and Warren M. Jackman, MD. University of Oklahoma Health Sciences Center, Oklahoma City, OK. Introduction: Esophageal (Eso) ulceration and LA-Eso fistula are thought to be rare complications of atrial fibrillation (AF) ablation. The purpose of this study was to examine the incidence of Eso injury after AF ablation using endoscopy and the relationship between Eso temperature during ablation and Eso injury. Methods: 30 AF patients undergoing pulmonary vein (PV) antrum isolation plus ganglionated plexi ablation (general anesthesia) were studied. Eso was localized using both intracardiac echocardiography and a thin, flexible pediatric Eso temperature probe. For each RF application close to Eso, the Eso temp probe was positioned at the level of the ablation electrode to record Eso temp. During ablation close to Eso, RF power was limited to 20-25 Watts for 30 sec and RF application was terminated immediately when Eso temp increased just 0.2°C. A 0.2°C increase in Eso temp occurred in 20/30 pts. Eso

S62 Heart Rhythm Vol 4, No.5 May Supplement 2007

endoscopy was performed 1 day after ablation in 16/20 pts with Eso temp rise. If Eso ulcer was present, the patient was treated with proton pump inhibitor (omeparzaol 80 mg/day) and sucralfate (1g/10ml, 4 times per day) and follow-up endoscopy was performed at 2 weeks. Results: Endoscopy 1 day after ablation found an Eso ulcer (4-12 mm width) in 9/16 pts. There was no significant difference between 9 pts with Eso ulcer and 7 pts without Eso injury in: 1) number of RF applications with >0.2°C increase in Eso temp (1-7, median 5.5 vs 2-8, median 6); 2) peak increase in Eso temp (including overshoot after RF termination, 0.5-3.0°C, median 1.0°C vs 0.4-1.7°C, median 1.1°C); 3) total number of RF applications (median 62 vs 74); 4) LA size (median 4.4 cm vs 4.6 cm); or 5) mild possible esophageal symptoms (1/9 pts vs 2/7 pts). Follow-up endoscopy at 2 weeks was performed in 7/9 pts with acute Eso ulcer and showed almost complete healing in 7/7 pts. At follow-up of 1-5 (median 1.5) months, none of 20 patients developed Eso perforation, LA-Eso fistula, or significant Eso symptoms. Conclusions: Even with low RF power (20-25 Watts) applications and only tiny increases in Eso temp, the incidence of asymptomatic Eso ulcer is high. Eso ulcers heal with conservative therapy. AB29-2 PAIN DURING RADIOFREQUENCY APPLICATION IS ASSOCIATED WITH ESOPHAGEAL TEMPERATURE RISES DURING CATHETER ABLATION OF ATRIAL FIBRILLATION Arash Aryana, MD, E. Kevin Heist, MD, PhD, Ivan Ho, MD, Anshul Patel, MD, Ryan Aleong, MD, Stephan B. Danik, MD, Theofanie Mela, MD, André D' Avila, MD, Jeremy N. Ruskin, MD and Moussa C. Mansour, MD. Massachusetts General Hospital, Boston, MA. Introduction: Atrioesophageal fistula is an uncommon but devastating complication of catheter-directed pulmonary vein isolation (PVI) for treatment of atrial fibrillation. Esophageal temperature rise (ETR) has been previously documented during radiofrequency (RF) applications around the pulmonary veins from inside the left atrium as a possible marker for esophageal injury. The aim of this study was to investigate the possible relationship between pain during RF applications and ETR in patients undergoing PVI. Methods: We prospectively recorded the presence and absence of pain during each RF application along with continuous esophageal temperature monitoring in patients undergoing PVI. When present, pain intensity was classified as mild, moderate, or severe. Esophageal temperature was measured using an esophageal temperature probe. Patients were maintained under mild conscious sedation throughout the ablation procedure. Results: Data from 19 consecutive patients (mean age: 57 ± 10) were analyzed. All pulmonary veins were isolated in all patients. The number of RF applications delivered per patient was 103 ± 27 (range: 58 - 154). Fifteen of 19 patients had at least one ETR, and 18 of 19 patients experienced at least one episode of pain during RF application. For the entire group, there were a total of 1,960 RF applications resulting in 126 (6.4%) ETRs and 145 (7.4%) episodes of pain. Eighty percent of RF applications causing pain corresponded to ETR (p<0.001). In contrast, only 1% of pain-free RF applications were associated with ETR (p<0.001). In this cohort, the predictive value of pain for presence of ETR was 92%, and the predictive value of lack of pain for absence of ETR was 98%. Conclusions: Presence of pain during left atrial RF application in patients undergoing PVI was frequently associated with a temperature rise in the esophageal lumen. Conversely, lack of pain was a strong predictor of absence of ETR. If validated in future studies, presence/absence of pain during RF application may prove to be a useful predictor of the likelihood for esophageal injury during PVI.

AB29-3 MECHANISM OF PHRENIC NERVE INJURY DURING HIGH INTENSITY FOCUSED ULTRASOUND BALLOON ABLATION OF RIGHT-SIDED PULMONARY VEINS AND THE SUPERIOR VENA CAVA Yasuo Okumura, MD, PhD, Mark W. Kolasa, MD, Susan B. Johnson, BS and Douglas L. Packer, MD. St. Marys Hospital, Mayo Clinic & Foundation, Rochester, MN. Introduction: The phrenic nerve can be injured with catheter-based treatment of atrial tachyarrhythmias. However, the impact of high intensity focused ultrasound (HIFU) on tissue temperature surrounding the phrenic nerve during balloon catheter ablation remains unclear. Methods: The impact of HIFU ablation on the phrenic nerve was studied in eight dogs. Thermocouples were implanted on the epicardial right atrial surface along the phrenic nerve via a right-sided thoracotomy. The right phrenic nerve was paced from the SVC at 10-20 mAmps during HIFU ablation performed at the right superior pulmonary vein (RSPV) or superior vena cava (SVC) for 40 sec at 32 watts using a 20 mm balloon catheter. Results: Seventeen intentional phrenic nerve injuries occurred during 59 HIFU ablations (RSPV: 51, SVC: 8). A sudden loss of the phrenic nerve capture was observed in 5 of 17 phrenic nerve injuries, with a gradual loss or weakness in phrenic capture in 12 injuries. The phrenic nerve temperatures at the beginning of injury in sudden loss and gradual loss/weakness injuries were similar: 64.0 ± 15.7 ºC vs. 58.8 ± 15.1 ºC, p=ns. However, the time required for phrenic nerve dysfunction was significantly shorter in sudden loss than in gradual loss/weakness injuries (16.3 ± 8.4 sec vs. 31.2 ± 3.8 sec, p<0.001), resulting in a steeper gradient of temperature rise in sudden loss than in gradual loss/weakness injuries (2.2 ± 1.6 vs. 0.6 ± 0.5, p<0.01). The steep gradient temperature rise was highly dependent on the relationship to focused zone of HIFU delivery (2.6 ± 0.9 mm vs. 6.4 ± 3.6 mm from the center of the focused zone, p<0.05). No sudden loss injuries recovered after HIFU ablation, whereas gradual loss/weakness injuries recovered without apparent residual pacing threshold increases. Conclusions: The threshold of phrenic nerve injury with HIFU was 45-48 ºC. More rapid temperature increments produce permanent injury while gradual change is reversible. Excess temperature elevation can also occur at a distance during HIFU delivery. AB29-4 LONG-TERM NEUROLOGIC OUTCOMES IN ACUTE THROMBOEMBOLIC EVENTS ASSOCIATED WITH ABLATION FOR ATRIAL FIBRILLATION Shane M. Bailey, MD, Marilou Ching, MD, Kenneth C. Civello, MD, Anthony J. Furlan, MD, Walid Saliba, MD, Robert A. Schweikert, MD, J. David Burkhardt, MD, Maurico Arruda, MD and Andrea Natale, MD, FRCP. Cleveland Clinic Foundation, Cleveland, OH. Introduction: Cerebral thromboembolism (CTE) is a rare complication of ablation for atrial fibrillation (AF). We sought to determine the neurologic outcome of patients who experienced this complication. Methods: Between January 2000 and June 2006, 3060 patients underwent ablation for AF. All patients with persistent or permanent AF underwent transesophageal echocardiography prior to ablation or were treated with warfarin for 3 weeks prior to ablation. We report on the clinical outcome of patients who experienced CTE associated with AF ablation as well as the vascular distribution of embolic events. Neurologic outcome was measured by the Barthel Index (BI) scaled over a 100-point range, with 100 representing complete independence and 0 corresponding to complete dependence.

Session 29 S63

Results: Of 3060 patients, 19 patients (0.6%) experienced acute stroke within 48 hours of the procedure. All events were thromboembolic. Persistent or permanent AF was present in 16 (85%) and paroxysmal in 3 (15%). At least one stroke risk factor was present in 10 patients. The vascular distribution of cerebral embolic events was: right anterior circulation - 5 patients (26%), left anterior circulation - 5 patients (26%), posterior circulation - 3 patients (16%), and two or more territories - 6 patients (32%). Four patients underwent mechanical thrombectomy, 1 patient was treated with systemic tPA and the remaining patients were treated conservatively with anticoagulation when appropriate. After an average follow-up of 42 ± 23 months, 1 patient who underwent thrombectomy died within one month, 1 patient died 4 years after the procedure, 2 were lost to follow-up but not listed in the social security death index and 15 were assessed for functional status. Average Barthel Index for these patients was 98 (range from 75-100). Conclusions: Acute stroke in the setting of ablation for AF is a rare complication with potential for significant morbidity and mortality. In our series of patients, CTE was more common in patients with persistent or permanent AF. No preferential vascular territory for embolic events was observed. The majority of patients experienced full neurologic recovery. AB29-5 POST CARDIAC INJURY SYNDROME WITH SEVERE PULMONARY CAPILLARY LEAKAGE- A COMPLICATION FOLLOWING EXTENSIVE RADIOFREQUENCY CATHETER ABLATION FOR ATRIAL FIBRILLATION Reinhold Weber, MD, Gerd Bürkle, MD, Claudia Herrera, MD, Thomas Blum, MD, Jan Minners, MD, Jochem Stockinger, MD, Dietrich Kalusche, MD and Thomas Arentz, MD. Herz-Zentrum Bad Krozingen, Bad Krozingen, Germany. Introduction: Treatment of permanent atrial fibrillation (AF) may require extensive radiofrequency catheter ablation (RFA) in the left atrium (LA) . We describe a new complication following extensive ablation in the left atrium for long lasting AF. Methods: Between 2000 and 2006 432 patients (50+/-11 years, 125 women) with drug refractory AF (paroxysmal 332, persistent 86, permanent 14) were treated in our centre by RFA. Segmental ostial isolation of the PVs was performed in 312 and circumferential ablation around both PVs in 120 patients. Additional substrate modification was carried out with linear lesions in 22 and ablation of complex fractionated potentials (CFP) in 9 patients using an irrigated tip catheter with a maximum power of 30 to 35 Watts. Results: Four male patients (aged 53+/-8 years) developed dyspnoea 38+/-14 hours after the procedure. Significant oedema (weight gain 5.4+/-1.5 kg) and fever (38.8+/-0.4oC) were the dominant clinical signs. Chest X-ray revealed severe pulmonary oedema with transthoracic echocardiography showing normal left ventricular function and normal pulmonary pressures. Leucocytosis (14075+/-4216/ µl) and an elevated CRP (17.7+/-8 mg/ dl) but normal procalcitonine and negative blood cultures were noted. CT ruled out PV stenosis. All patients were treated conservatively with one patient needing non-invasive CPAP ventilation for 24 hours. Oedema regressed in all patients within 3 days. In addition to circumferential PV isolation, substrate modification had been performed in 2 (roof line and/or ablation of CFP) of the 4 patients. The RF time was slightly longer when compared to patients without this complication (4116+/-1250 vs. 3262+/-2024 sec.; p=0.1). None of the patients treated with segmental ostial PV-isolation only developed pulmonary oedema. Conclusions: We describe a post cardiac injury syndrome with severe pulmonary leakage after extensive ablation in the LA. The precise mechanism remains elusive, but the accompanying systemic inflammatory syndrome favours a specific immunologic/ autoimmunologic reaction induced by RFA in the LA.

AB29-6 OPEN IRRIGATION ABLATION CATHETER FAILS TO ELIMINATE CIRCULAR CATHETER ELECTRODE CHARRING IN PATIENTS UNDERGOING EGM-GUIDED PULMONARY VEIN ISOLATION FOR AF Mauricio Arruda, MD, Shane M. Bailey, MD, Walid Saliba, MD, Mandeep Bhargava, MD, J. David Burkhardt, MD, David O. Martin, MD, MPH, Jennifer E. Cummings, MD, Thomas Dresing, MD, Mohamed H. Kanj, MD, Oussama M. Wazni, MD, Robert A. Schweikert, MD and Andrea Natale, MD, FRCP. Cleveland Clinic, Cleveland, OH. Introduction: Current AF ablation approaches include electrical isolation of the pulmonary veins (PVI), often guided by a circular catheter. The ablation tip-electrode inevitably touches the small electrodes on the circular catheter resulting in high current density, tissue overheating, local char formation and possibly thromboembolic events. This phenomenon had been previously minimized by RF power titration guided by micro-bubble on intracardiac echocardiography (ICE), which is not applicable while utilizing an open irrigation catheter for ablation. Purposes: We prospectively evaluated the incidence of electrode char formation using an open irrigation catheter for PVI. Methods: Fifteen pts underwent PVI guided by two commercially available circular catheters. Both studied catheters utilized 1 mm wide ring electrodes, mounted on an approximately 3 Fr, 10 electrodes (10 pts) or 6 Fr, 20 electrodes (5 pts). PVI was obtained by RF current delivery (up to 45W) via a 7 Fr, 3.5mm open irrigation tip-electrode catheter. At the end of the procedure the catheters were inspected for thrombus or char. Results: The ablation tip electrode was consistently free of thrombus or char. However, both circular catheters showed adherent char. The 3Fr catheter, with smaller surface area, typically exhibited char on most electrodes in all 10 pts, often covering the entire electrode circumference. ICE identified thrombus (retrieved successfully by aspiration) in one of these pts. The catheter with larger electrode surface area exhibited char in 3 of 5 pts. Typically on fewer electrodes and located at the lateral and backwards facing aspect of the electrode. None of the pts developed any clinically significant thromboembolic events. Conclusions: Char is commonly present on the electrodes of circular catheters used to guide Pulmonary Vein Isolation despite the use of an open irrigation catheter for ablation. Char formation is inversely proportional to the surface area of the recording electrode on the circular catheter. Whether possible char microembolization has clinical implication remains to be demonstrated. ABSTRACT SESSION 30: CATHETER ABLATION 5: AF Ablation: Long-Term Outcomes Friday, May 11, 2007 10:30 AM - 12:00 PM AB30-1 SAFETY OF ORAL ANTICOAGULATION WITHDRAWAL AFTER SUCCESSFUL ATRIAL FIBRILLATION ABLATION: RESULTS OF A MULTICENTER STUDY WITH A LONG-TERM FOLLOW-UP Andrea Corrado, MD, Sakis Themistoclakis, MD, Pierre Jaïs, MD, Erica Zado, PAC, MPH, Antonio Rossillo, MD, Robert A. Schweikert, MD, Walid Saliba, MD, Jennifer E. Cummings, MD, J. David Burkhardt, MD, Oussama M. Wazni, MD, Aldo Bonso, MD, David J. Callans, MD, Michel Haïssaguerre, MD, Francis E. Marchlinski, MD, Antonio Raviele, MD and Andrea Natale, MD, FRCP. Cleveland Clinic Foundation, Cleveland, OH, Umberto I Hospital, Venice, Italy, Hôpital du Haut-Lévèque, Bordeaux, France and University of Pennsylvania, Philadelphia, PA.

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Introduction: Atrial fibrillation is associated with an increased risk of thromboembolic events (TE) and often requires oral anticoagulation therapy (OAT). Pulmonary vein isolation (PVI) is considered an effective treatment for atrial fibrillation. However, up to now the effect of OAT discontinuation on the incidence of TE, after successful PVI, is still unclear. The aim of this multicenter study was to evaluate the safety of discontinuation of OAT after apparently successful PVI. Methods: We studied consecutive patients (pts) that underwent successful PVI from January 2001 to December 2005 and discontinued OAT 3-6 months after the ablation. A minimum follow-up of at least 6 months after OAT discontinuation was required before the enrollment. Results: The study population consisted of 2436 pts [1935 (79%) male, mean age 57±11 years]. AF was paroxysmal in 1575 (65%), persistent in 396 (16%) and permanent in 460 (19%) pts. The average duration of AF prior to ablation was 45±34 months. Structural heart disease was present in 884 (36%) patients (mean LVEF 55±8%, mean LA diameter 43±8 mm). A CHADS2 risk score for TE was ≥2 in 282 (11%) pts, equal to 1 in 646 (27%) pts and equal to 0 in 1508 (62%) pts. During a mean follow up of 31±17 months only 1/2436 (0.04%) pt had a cerebrovascular accident (CVA) one year after PVI. The CVA occurred in a pt with CHADS2 risk score 0 while in sinus rhythm. Repeat monitoring after the CVA revealed asymptomatic paroxysmal atrial fibrillation one week later. No pts with CHADS2 risk score equal to 1 or ≥2 had TE (Table). Conclusions: In this large study population discontinuation of OAT after a successful PVI appears to be safe also in patients at high risk for thromboembolic events. Incidence of TE in pts with different CHADS2 risk score CHADS2 score Patients n (%) TE n (%)

CHADS2 =0 1508 (62) 1 (0.07)

CHADS2=1 646 (27) 0

CHADS2≥2 282 (11) 0 AB30-2 IMPACT OF PRESENTING AF TYPE OF LATE RECURRENCES AT LONG-TERM FOLLOW-UP (>18 MO) AFTER AF ABLATION Anita Wokhlu, MD, David O. Hodge, BA, Kristi H. Monahan, RN, Jan Haroldson, RN, Samuel J. Asirvatham, MD, Paul A. Friedman, MD, Thomas M. Munger, MD and Douglas L. Packer, MD. Mayo Clinic, Rochester, MN. Introduction: Ablation has been shown to be effective for eliminating atrial fibrillation (AF) in studies with follow-up limited to 12 months. Over long-term follow-up (>18 mo), however, underlying disease or other factors may promote recurrences. The impact of late recurrences on the durability of AF therapy is unknown. Methods: 774 patients with AF (55% paroxysmal (PAF), 45% persistent or permanent (PeAF)) undergoing RFA (44% wide area circumferential ablation, 55% pulmonary vein isolation) were examined for long-term recurrence after 2 months post-procedure. Results: First-time recurrences are demonstrated in Kaplan-Meier analysis in Fig. 1. 23% of these occur within 6 months, and an additional 8% by 12 months. Thereafter, first-time recurrences occur from 18 to 30 months at a rate of 10% / year. A histogram (Fig. 1) of total recurrences over time demonstrated that patients with PeAF had increased recurrence rates. At 24 months, 20% of PeAF patients had late recurrences vs.11% in those with PAF (p=0.02). PeAF, as well as diabetes, early recurrences within first two months independently predicted first-time AF recurrence, and diabetes was the strongest predictor of any or multiple late recurrences. At last follow-up (1.7 + 1.5 yrs), AF control was achieved in 474 patients (73%, 10% requiring AADs) with a redo ablation rate of 10.5%. At 24 months, AF control

was achieved in 176/224 (79%) of patients with PAF compared with 116/170 in patients with PeAF (p=0.02) Unlike PAF where recurrence plateaus from 12 to 24 months to 11% , recurrence rate rises in PeAF group from 14% to 20%. Conclusions: Long term follow-up demonstrates first time recurrences beyond 18 months, as well as a modest increment in arrhythmia burden over time. Underlying diseases including those that contribute PeAF may result in additional substrate-mediated arrhythmia that may not be modifiable by ablation alone.

AB30-3 RECURRENCE OF PERSISTENT BUT NOT PAROXYSMAL ATRIAL FIBRILLATION AFTER CATHETER ABLATION CONTINUES TO INCREASE DURING LONG TERM FOLLOW-UP N. Raj Subramanian, MD, Matthew Huffman, MD, Liza A. Prudente, MSN, ACNP, Heather Greenbaum, BS, Glenn Brammer, MD, J. Michael Mangrum, MD, J. Randall Moorman, MD, John D. Ferguson, MD, John P. Dimarco, MD, PhD and J Paul Mounsey, MD, PhD. University of Virginia, Charlottesville, VA. Introduction: Early recurrences of AF after ablation are not thought to be significant; late attrition is increasingly recognized. To assess the magnitude of the problem, we measured the recurrence rate in a cohort of patients post AF ablation. Methods: We studied 210 consecutive pts who had pulmonary vein isolation; 109 pts received additional linear lesions and/or ablation of complex fractionated electrograms; 54 pts had more than one ablation. F/u data was obtained by chart review and scripted interviews. Recurrence after the last ablation was defined as documented AF or AFL, or prolonged palpitations that the pt attributed to AF. The number of patients with recurrent AF was assessed at each of the following time-points: 0-1, 1-3, 3-6, 6-12, 12-18, 18-24, 24-36 months. Results: Complete f/u was obtained for 182 patients (87% of 210); 59% had PAF and 41% were persistent. Among pts with PAF (persistent AF): 46% (59%) had HTN, and 17% (27%) had one or more of DM, CAD, DCM, or valvular disease. After a mean f/u of 20 +/- 7 mo, 60% of pts were free of any recurrence (64% of PAF pts; 52% of persistent AF pts). Among PAF pts who were arrhythmia free at 1 year (after a 3 mo healing period), only 11% had recurrence over the next yr whilst 33% of pts with persistent AF who were arrhythmia free at one yr recurred over the next year. The Figure demonstrates

Session 30 S65

incidence of recurrence over each time period. At the 18-24 mo time period, the rate of recurrence in PAF pts plateaus at 19%. By contrast there was a steady rise in the rate of recurrence in persistent AF that achieves 47% at 18-24 mo (p=0.02). The presence of structural heart disease, age, gender, and the lesion set were not predictive of recurrence. Conclusions: Amongst patients with paroxysmal AF, freedom from recurrence at 6-12 mo after ablation suggests a good long term result. In persistent AF late recurrence is common.

AB30-4 CATHETER ABLATION FOR ATRIAL FIBRILLATION: TRENDS IN PATIENT PROFILES, CLINICAL OUTCOMES AND COSTS IN COMMUNITY HOSPITALS SINCE 2003 Matthew R. Reynolds, MD, Robert S. Fishel, MD, Phillip P. Brown, MD, Lynn G. Tarkington, RN, April W. Simon, RN, MSN and Steve D. Culler, PhD. Beth-Israel Deaconess Medical Center, Boston, MA, Florida Electrophysiology Associates, Atlantis, FL, HCA CCMN, Nashville, TN, Cardiac Data Solutions, Inc., Atlanta, GA and Emory University, Atlanta, GA. Introduction: The objective of this analysis was to identify trends in patient profiles and outcomes in atrial fibrillation (AF) patients undergoing radiofrequency catheter ablation (RFA) in community hospitals since 2003. Methods: The Hospital Corporation of Americas (HCA) Casemix Database, an administrative database from all HCA hospitals, was utilized to evaluate AF patients undergoing an RFA from January 2003 thru June 30, 2006. The study population consists of 2,028 AF patient admissions undergoing RFA in 51 HCA hospitals. Exclusion criteria included diagnosis of atrial flutter, Wolff-Parkinson-White syndrome, or nonparoxysmal AV nodal tachycardia; prior PPM or ICD; the implantation of a PPM or ICD or an open surgical ablation during the hospitalization. Procedural complications were identified using ICD-9-CM codes. Results: The number of AF patients treated with RFA increased rapidly from 257 in 2003 to 546 in the first half of 2006 (Table). The study population was mostly male (68%) with an average age of 60.7 years. The only in-hospital complication rates above 1% overall were for cardiac perforation (2.8%), cardiac perforation with

pericardiocentesis (1.97%), and vascular complications (8.48%). The overall in-hospital mortality rate was 0.7%. Mean length-of-stay varied from 3.1 to 3.6 days and mean hospital costs varied from $20,085 to $26,635. Conclusions: The number of AF patients being treated with RFA in community hospitals is growing rapidly while morbidity and mortality outcomes remain low.

All Patients 2003 2004 2005

2006, Q 1 & 2

Patients 2,028 257 526 699 546

Number of Hospitals 51 30 33 51 43

Male, % 68.0 65.4 70.7 67.1 67.9

Age 60.7 60.0 61.4 60.6 60.5

Discharged Home,% 95.8 92.2 96.6 95.4 97.3

Death, % 0.69 1.56 0.19 1.00 0.37

Stroke, % 0.28 1.56 0.0 0.14 0.18

New Onset Hemodialysis, % 0.49 1.56 0.0 0.29 0.73

Infection, % 0.15 0.39 0.0 0.29 0.0

Mechanical Complication, % 0.15 0.0 0.0 0.29 0.18

Cardiac Perforation, % 2.81 3.11 2.66 3.15 2.38

Cardiac Perforation & Pericardiocentesis, % 1.97 3.50 1.90 1.72 1.65

Pneumothorax, % 0.59 0.0 0.95 0.29 0.92

Pneumothorax & Chest Tube, % 0.44 0.0 0.38 0.72 0.37

Vascular Complication, % 8.48 6.61 10.84 8.15 7.51

Accidental Puncture or Laceration, % 0.74 1.17 0.76 0.86 0.37

Length of Stay (Days) 3.3 3.3 3.6 3.4 3.14

Cost (current $s) 23,366 20,085 23,342 26,635 20,748

AB30-5 LONG-TERM AUTONOMIC EVALUATION IN PATIENTS UNDERGOING SELECTIVE VAGAL DENERVATION TO TREAT PAROXYSMAL ATRIAL FIBRILLATION Cristiano F. Pisani, MD, Denise Hachul, MD, PhD, Milena Macatrão-Costa, MD, PhD, Sissy Lara, MD, PhD, Cesar Grupi, MD, PhD, Carina Hardy, MD, Francisco C. Darrieux, MD, PhD, Eduardo Sosa, MD, PhD and Mauricio I. Scanavacca, MD, PhD. São Paulo University, São Paulo, Brazil. Introduction: Vagal tone is a trigger to Atrial Fibrillation (AF) in a subset of patients. A new approach aiming selective ablation of the left atrium autonomic ganglia has been described. Conventional AF ablation leads to a transient autonomic system modification. Direct ablation of Ganglionated Plexi could lead to a more persistent modification. Methods: Nine patients with paroxysmal and predominantly vagal induced AF underwent RF ablation of epicardial and endocardial atrial sites were high frequency stimulation (HFS) elicited vagal reflex. The endpoint of the procedure was the abolition of all vagal reflexes evoked by HFS. Holter monitoring was performed before (median -2 days), soon after (median 1 day), late after (median 146 days) and long-term after (median 542 days) ablation. Heart rate (HR), time and frequency-domain HR variability (HRV) were analyzed from Holter monitoring and used as an indicator of autonomic activity. All antiarrhythmic drugs were suspended 5 days before evaluation and amiodarone 30 days before. Unpaired t-test was used to compare the values.

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Results: Minimal (40.9±6.8 to 54.6±8.1; P=0.005) and average HR (65.9±6.2 to 78.9±3.7; P=0.0005) remained significantly increased at long-term evaluation when compared to before ablation parameters. No difference was observed on maximum HR (116.3±25.8 to 127±13.7; P=0.351). Time-domain HRV parameters also remained significantly and persistently modified: SDNN (170.3±11.2 to 117.7±31.8; P=0.003); pNN50 (30.3±21.9 to 4.48±5.70; P=0.033) and rMSSD (57.5±27.0 to 21.6±10.3; P=0.027). The LF band of time-domain HRV and power spectral analysis showed no difference when compared to before ablation parameters (LnLF: 5.9±0.9 to 5.6±1.3ms2; P=0.133) but HF band remained significantly decreased (LnHF: 6.0±0.5 to 4.2±0.5ms2; P=0.034) at long-term evaluation. A discrete difference was observed on autonomic balance (LF/HF: 1.6±0.3 to 2.1±0.3; P=0.051) Conclusions: Autonomic modification persisted after long-term outcome when selective atrial vagal denervation guided by evoked vagal reflex was performed to treat paroxysmal AF. AB30-6 PREDICTIVE VALUE OF ATRIAL TACHYARRHYTHMIA INDUCIBILITY Warangkna Boonyapisit, MD, Siddharth Mukerji, MD, Carol Chen-Scarabelli, MSN, NP, RN, Rita McLemore, MSN, NP, RN, Frank Pelosi, Jr., MD, Hakan Oral, MD, Frank M. Bogun, MD, Aman Chugh, MD, Eric D. Good, MD, Ranjan Thakur, MD, Fred Morady, MD and Krit Jongnarangsin, MD. University of Michigan, Ann Arbor, MI, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI and Michigan State University, Lansing, MI. Introduction: Atrial fibrillation (AF) inducibility after left atrial catheter ablation has been shown to be associated with higher recurrences of AF and poorer clinical outcome. However, the predictive value of AF inducibility on the development of AF in patients with no prior history of AF is unknown. Methods: We prospectively studied 41 patients (mean age 66±11, 41male) with no prior history of AF or atrial flutter (AFL) who underwent implantation of devices with electrogram storing capability for high atrial rate detection (12 pacemakers, 27 ICDs, and 2 biventricular ICDs). The mean left ventricular ejection fraction and left atrial diameter were 37±18% and 43±8 cm, respectively. Electrophysiologic study was performed at the implantation. Atrial tachyarrhythmia (ATR) inducibility protocol consisted of left atrial pacing via the coronary sinus for 10 seconds at 300 ms, 250 ms and 200 ms. Pacing was attempted 3 times on each cycle length. If ATR was still noninducible, the above pacing protocol was then repeated in the right atrium. Inducible ATR was defined as induced AF or AFL that lasted >60 seconds. Patients were routinely followed in the device clinic and via transtelephonic monitoring. Intracardiac electrograms were reviewed if high atrial episodes were detected. Results: ATR was induced in 32 (78%) patients. During the mean follow up of 172±94 days, 2 of 32 patients (6%) with ATR inducibility and 1 of 9 patients (11%) without ATR inducibility developed ATR longer than 10 minutes (p=0.535). Conclusions: ATR inducibility is common in patients without prior ATR and does not increase the risk of development of ATR in comparison to patients without ATR inducibility.

ABSTRACT SESSION 31: CATHETER ABLATION 6: Experimental Methods in Ablation: A Potpourri Friday, May 11, 2007 10:30 AM - 12:00 PM AB31-1 CHRONIC AF TERMINATION BY CATHETER ABLATION IS ASSOCIATED WITH A BETTER CLINICAL OUTCOME Mark D. O'Neill, MD, Kang-Teng Lim, MBBS, Pierre Jaïs, MD, Seiichiro Matsuo, MD, Sébastien Knecht, MD, Leonardo Arantes, MD, Yoshihide Takahashi, MD, Anders Jonsson, MD, Sathish Kodali, MD, Frédéric Sacher, MD, Jacques Clémenty, MD, Mélèze Hocini, MD, Nicolas Derval, MD, George J. Klein, MD and Michel Haïssaguerre, MD. Hôpital Cardiologique du Haut-Lévèque, Bordeaux, France. Introduction: Termination of long lasting persistent AF (CAF) can be performed by catheter ablation targeting thoracic veins and multiple left atrial sites. This study describes the clinical outcome and subsequent arrhythmia recurrence depending on the achievement of acute AF termination in a cohort of consecutive patients. Methods: 178 consecutive patients, 147 (83%) men and 31 (17%) women, mean age (56±10 yrs) underwent ablation of CAF (25±42months) using a sequential catheter ablation approach involving isolation of pulmonary veins, ablation of coronary sinus and all left atrial areas showing rapid/heterogeneous activity, and linear lesions at the roof and mitral isthmus. Activation mapping was performed after conversion to atrial tachycardias (AT) until restoration of sinus rhythm. At 1, 3, 6 and 12 months after ablation, patients underwent clinical review and 24-hour ambulatory ECG monitoring to identify asymptomatic arrhythmia. Repeat mapping and ablation was performed in patients with persistent arrhythmia. Results: AF was terminated in 149 patients (84 %), directly to sinus rhythm in 23 or via ablation of intermediate AT in 126 pts. AF could not be terminated without DC or pharmacological cardioversion in 29 patients (No Term 16%). The amount of delivered RF energy did not differ between groups (Term 86±27 vs 96±28min; p=0.08). Following the index ablation, sustained arrhythmia recurrence was documented in 79 pts with a lower incidence in Term (64 pts, 44%) compared to No Term groups (15 pts, 50%, p=0.4). Most importantly, AT was the dominant mode of recurrence in Term pts (56/64) whereas AF was the most common arrhythmia observed in No Term pts (8/15; p=0.0015). Re-ablation of recurrent arrhythmia was limited in the former and extensive in the latter group. Among the total cohort after repeat ablation, sinus rhythm was maintained in 95% (Term) vs 57% (no Term) of patients during a follow-up of 10.5±6 months. Conclusions: Acute CAF termination during catheter ablation is predictive of subsequent maintenance of sinus rhythm. However, repeat procedures are commonly required for arrhythmia recurrence which takes the form of AT in Term pts and of AF in no term pts. AB31-2 CRYOABLATION LESION SIZE DECREASES WITH PHYSIOLOGIC FLOW AND INCREASES WITH TRABECULATION Thomas A. Pilcher, MD, J. Philip Saul, MD and Dieter Haemmerich, PhD. Medical University of South Carolina, Charleston, SC. Introduction: Cryoablation has now become an alternative to treat many cardiac arrhythmias and may be the treatment of choice in some patient populations. We hypothesized that cryo-lesion size is strongly affected by convective warming at the ablation site. Methods: Fresh porcine hearts were sectioned and placed in a temperature-controlled saline bath (37 o C) with varying directed flow rates (0, 1, 2 and 3 L/min). Cryoablation (9 Fr, 8mm tip) was performed for 4 minutes on 40 tissue pieces with temperature controlled at -80oC. Cryoablation was also performed for 8 minutes on 12 tissue pieces at flow rates of 0 and 3 L/min. Flow rates were

Session 31 S67

randomized between applications. Time to reach -80oC and trabeculation depth were recorded. The ablation site was marked on each tissue piece and the pieces were placed in culture media for 24hrs. The pieces were then sectioned along the direction of flow and stained with nitro blue tetrazoleum. Lesion depth and width were measured, and lesion volume calculated as a partial oblate ellipsoid. Results: Lesion size varied significantly with flow, such that higher flow rates produced smaller lesions (mean volumes: 1119 ± 292, 972 ± 227, 875 ± 225 and 543 ± 217 mm3 for 0, 1, 2 and 3 L/min flow rate respectively, poC decreased (r= -0.78), and trended towards being larger with 8 than 4 min applications (p=0.08). Conclusions: In contrast to radiofrequency ablation, cryo-ablation lesion size is smaller at high flow rates and larger at low flow rates, due to the warming effects of local convective flow. The effects of high flow are reduced in areas of trabeculation, and the time to reach -80oC predicts lesion size. Local convective warming strongly affects cryo-lesion size.

AB31-3 PATIENTS WITH POSTOPERATIVE ATRIAL FIBRILLATION HAVE A MORE THAN DOUBLED LONG-TERM RISK OF DEATH DUE TO STROKE, HEART FAILURE AND MALIGNANT ARRHYTHMIAS Anders Ahlsson, MD, Lennart Bodin, PhD, Espen Fengsrud, MD and Anders Englund, MD, PhD. Department of Cardiothoracic Surgery, Orebro, Sweden, Department of Medical Statistics and Epidemiology, Orebro, Sweden and Department of Cardiology, Orebro, Sweden. Introduction: Postoperative atrial fibrillation (AF) is a risk factor for early morbidity and mortality after coronary bypass surgery. Its long term consequences have, however, not been well studied. Methods: Between 1st Jan 1997 - 30th June 2000 1588 patients underwent primary CABG at our institution. All patients who were in preoperative sinus rhythm and had no history of AF or pacemaker treatment were included (n=1461). Any presence of AF during the postoperative days 1-5 defined the patient as belonging to the AF group. After a median follow up of 8.0 years, all patients were screened in the Swedish National Epidemiological Registry for mortality and cause of death. Cox regression analysis was used to define risk factors for late mortality. Results: 423/1461 pat (29.0%) developed postoperative AF. The AF patients were older (69.2 ± 8.1 vs. 64.9 ± 9.5 years, p < .001) but had similar left ventricular ejection fractions (55.8% ± 14.8% vs. 57.4% ±

14.5%, p = 0.242) . At follow up, mortality in the AF group was 143/423 (33.8%) compared to 213/1038 (20.5%) in the no AF group (p < .001). Risk factors for death in the regression analysis were age (Hazard Ratio 1.06 [95% Confidence Interval 1.05 - 1.08]), postoperative AF (HR 1.46 [1.18 - 1.81]) and diabetes (HR 1.75 [1.36 - 2.25]. Death causes more common in the postoperative AF group were cerebral infarction (4.3% vs. 1.3%), myocardial infarction (7.8% vs. 4.1%) sudden death (2.6% vs. 0.9%) and heart failure (6.6% vs. 3.1%). Conclusions: An episode of postoperative atrial fibrillation is an age independent risk factor for late mortality after coronary surgery. The increased mortality is mainly explained by an increased incidence of thromboembolic disease, arrhythmia and heart failure. AB31-4 FEASIBILITY OF REAL-TIME COMPUTED TOMOGRAPHY GUIDANCE FOR CATHETER NAVIGATION AND RADIOFREQUENCY ABLATION Timm-Michael Dickfeld, MD, PhD, Martin Engelhardt, MD, Katrina Read, MSc, Amir Nader, MD, Anthony Johnson, MD, Chris Kocher, MD, Jagan Akella, MD, Magdi M. Saba, MD, Stephen Shorofsky, MD, PhD and Thorsten Fleiter, MD. University of Maryland, Baltimore, MD. Introduction: Recent ablation strategies for complex arrhythmias such as atrial fibrillation or ischemic ventricular tachycardia are increasingly based on anatomic considerations. While fluoroscopy and 3D-mapping systems are most widely used to guide these ablations, they are limited by poor soft tissue visualization or the lack of real-time anatomic data. Therefore, we sought to evaluate if real-time computed tomography (RT-CT) could overcome these limitations and guide catheter navigation and ablation. Methods: Catheter manipulation was evaluated in a swine model using a 40-slice RT-CT scanner. First, catheter navigation was attempted from the femoral vein to the great cardiac vessels, and from the right atrium across the tricuspid valve to the right ventricle. In a second step, traversing of the inter-atrial septum and placement of predefined RF ablations in the lateral left atrial appendage (LAA) and left superior pulmonary vein (LSPV) were attempted under RT-CT guidance. Necropsy was performed to assess for possible complications and to evaluate the location of the ablation sites. Results: Using only real-time CT guidance, catheter navigation was successfully performed in the great cardiac vessels and from the femoral vein to the right atrium and ventricle and confirmed by electrical recordings. The scan plane was adjusted in real-time to visualize the catheter tip and adjacent segments to determine the curvature and rotation of the catheter and to enable anatomic catheter guidance . RT-CT successfully guided the catheter across the inter-atrial septum to the predefined ablation sites in the left atrium, where RF energy was successfully delivered under CT guidance. Contrast-injection allowed additional 3D-reconstruction of detailed cardiac anatomy. At necropsy, no complications were seen. RF lesion at the LSPV ostium and the lateral LAA correlated well with the real-time CT images (position error <2mm). Conclusions: In this feasibility study, real-time CT provided soft tissue visualization and instantaneous anatomic data. Its ability to guide catheter navigation/ablation suggests a possible role to facilitate RF procedures.

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AB31-5 NEW NON-INVASIVE THERAPY FOR CARDIAC ARRHYTHMIAS USING STEREOTACTIC RADIOSURGERY: INITIAL FEASIBILITY TESTING Arjun Sharma, MD, Patrick Maguire, MD, Douglas Wong, MD, Thilaka Sumanaweera, PhD, James Steele, DVM, Philip Peterson, BS, Luis Fajardo, MD, Patricia Takeda, MD and Thomas Fogarty, MD. Sutter Memorial Hospital, Sacramento, CA, CyberHeart, Portola Valley, CA, The Community Medical Center, Fresno, CA, Stanford University, Palo Alto, CA and Regional Cardiology, Sacramento, CA. Introduction: Catheter based techniques for arrhythmia ablation require intravascular intervention with attendant limitations and potential complications. We examined the feasibility of using externally focussed sterotactic radiation to alter cardiac electrophysiologic properties, as this could be used to ablate arrhythmias. Methods: Externally focussed radiation of atrial tissue was studied in Hanford-Sinclair mini swine (n=5)(40-70kg). The radiation (x-rays, 20-60 Gray) was targeted using a computer controlled robotic arm, directing a linear accelerator (Cyberknife). Radiosurgery enables radiation to be precisely delivered over 1-2 fractions. The target was determined using either a surgically implanted fiducial, or 16 slice CT scan. Cardiac and respiratory motion compensation was used. Four to eight weeks post radiation the animals underwent cardiac assessment with CT, TEE and Cardiac mapping with CARTO (Biosense). The animals were then sacrificed and pathology specimens taken. Results: All animals survived treatment. Radiation effects appeared to be time and dose dependent. Radiation directed at the left superior pulmonary vein resulted in uniform attenuation of signal amplitude, with the remaining signal appearing to be residual far field. Similar signal attenuation was seen in the inferior venacava-tricuspid isthmus in 1 animal which had radiation there. No pulmonary vein stenosis was seen, and there was no damage to valves, nearby ventricular and pulmonary tissue, or esophagus. Limitations: These animals did not have any spontaneous arrhythmias and thus efficacy of this technique in clinical therapy is unknown, although loss of electrical activity is usually corellated with success of ablation. The longest follow up was 3 months. Conclusions: External sterotactic radiosurgery produces focussed electrophysiologic changes with minimal changes in surrounding tissue. With CT guidance the technique can be wholly non-invasive. The therapy is rapid and can be done in one hour with the energy directed to any cardiac tissue with 1-2 cm accuracy. This new methodology is potentially applicable to any cardiac arrhythmia. AB31-6 A NOVEL TECHNOLOGY TO ENHANCE RFCA FOR ATRIAL FIBRILLATION: ELECTRODE-TISSUE CONTACT ASSESSMENT BASED ON IMPEDANCE PHASE ANGLE Douglas S. Holmes, MD, Hong Cao, PhD, Saurav Paul, PhD, Harry A. Puryear, PhD and Larry A. Chinitz, MD. New York University, New York, NY and St. Jude Medical, Minnetonka, MN. Introduction: Electrode-tissue contact is critical in creating lesions and mitigating complications during RF catheter ablation (RFCA) treatment of AFib. We describe a novel technology that measures impedance phase angle (IPA) changes relative to the electrode tissue contact. It has the potential to greatly enhance the safety and efficacy of RFCA AFib treatment. An in vivo evaluation of the potential clinical utility of IPA is presented. Methods: A custom-built device monitored in vivo phase angle changes prior to and during RF ablation in 5 pigs. The catheter was maneuvered to multiple sites in RA and LA using fluoroscopy and nonfluoroscopic navigation system. Power mode RF ablations were

performed at 20W, 30s and various IPA values. Ablation sites were marked on 3D chamber geometries. Lesions were identified post mortem and correlated with the IPA values. Results: A total of 60 ablations were performed. FIGURE A indicates that the optimal IPA for successful lesion creation is between phase angle values of 4° to 9°. Lower phase angle results in unsuccessful ablation due to inadequate tissue contact. Higher phase angle results in high temperature shut-downs even at such short-duration, low-power settings. FIGURE B shows a strong correlation between IPA and maximum electrode temperature during ablation. The optimal IPA values correspond to temperatures required to create successful lesions and avoid tissue charring or coagulum formation. Conclusions: IPA reliably monitors in vivo electrode-tissue contact necessary for RF catheter ablation. The technology allows users to assess the degree of tissue contact and thus facilitates rational choices for RF power settings. This study demonstrates that IPA helps optimize lesion creation and may improve the safety and efficacy of RF catheter ablation.

ABSTRACT SESSION 32: CATHETER ABLATION 7: SVT: Mechanisms and Clinical Outcomes Friday, May 11, 2007 10:30 AM - 12:00 PM AB32-1 THE ANTERIOR LINE: AN ALTERNATIVE LINEAR LESION IN LEFT ATRIAL FLUTTER Armin E. Luik, MD, Isabel Deisenhofer, MD, Heidi L. Estner, MD, Cristof Kolb, MD, Tilko Reents, Agathe Konietzko, MD, Andreas Pflaumer, MD, Gabriele Hessling, MD and Bernhard Zrenner, MD. Universität München, Munich, Germany and Deutsches Herzzentrum München, Munich, Germany. Introduction: Left lateral mitral isthmus line has been suggested to prevent or treat left atrial flutter (LAFL). However, severe complications may occur due to need for energy delivery in distal CS. We evaluated the safety and feasibility of an alternative anteriorly placed line in 122 patients (P). Methods: 122 P (age 57.8±8.9 years, 89 men) with LAFL (n=51) or atrial fibrillation (AF; n=71) were treated with an anterior line. The anterior line was drawn from the superior mitral valve to the ostium of the left superior PV (panel 1) compassing anteriorly the left atrial appendage (LAA). Efficacy of the line in terminating LAFL, ease of validation of line completeness and safety of the ablation were analyzed. Results: LAFL was the presenting arrhythmia in 51/122 P and occurred during AF ablation in 35/71 P. Perimitral flutter or peri left PV reentry was found in 71/86 P with LAFL. A mean of 84±29 RF applications were needed including PV isolation and additional lines. Procedure time was 323±90 minutes. No major complication including neurological failure, stroke and pericardial effusion occurred.

Session 32 S69

Line completeness was assessed (1) with an activation map while stimulating in the LAA, (2) by continuous stimulation via the map catheter while moving from laterally over the line to the anteriorly: the CS activation sequence switched from distal to proximal pattern (stimulation lateral to the line) to proximal to distal pattern while stimulating anterior to the line (panel 2). Successful ablation using the anterior line could be performed in 57/71 P suffering from perimitral LAFL or flutter around the left PV. 12 patients had to undergo reablation because of recurrence of LAFL. Conclusions: The anterior line is a safe and technically easy strategy to prevent or treat perimitral LAFL or reentry around the left PV. Line validation is easy to perform, even without 3d mapping systems.

AB32-2 PREVALENCE AND ACTIVATION CHARACTERISTICS OF FOCAL ATRIAL TACHYCARDIAS ORIGINATING FROM SEPTAL AND PARA-SEPTAL STRUCTURES Javier E. Banchs, MD, Gregory W. Woo, MD, Sherry J. Saxonhouse, MD, Erica D. Penny-Peterson, MD, Soraya M. Samii, MD, Deborah L. Wolbrette, MD, Gerald V. Naccarelli, MD and Mario D. Gonzalez, MD. Pennsylvania State University, Hershey, PA and University of Florida, Gainesville, FL. Introduction: Atrial tachycardias (AT)s originating from septal and para-septal structures such as fossa ovalis, perinodal tissue, and mitral annulus-aorta junction activate the right and left atria in a non uniform fashion. Determination of the focal source of the arrhythmia can be challenging in these patients. Methods: Ninety-seven consecutive patients found to have a focal AT during electrophysiology study were included. Detailed mapping of the right and left atria during tachycardia was performed when early activation in the right atrium was localized in one or more of the following regions: fossa ovalis, His bundle, coronary sinus, or Bachman's bundle. The earliest activation site in relation to the onset of the P wave was documented in each chamber. Results: Nineteen of the 97 patients (20%) were found to have origin of the tachycardia from septal or para-septal structures (Figure). Sixteen patients were women (age 54±18), 7 had a previous ablation attempt, and 17 had structurally normal hearts.

Mapping of both atria demonstrated that the AT originated from the mitral annulus-aorta junction in 11 patients (58%), from perinodal tissue in 5 (26%) and from the fossa ovalis in 3 (16%). Earliest activation recorded from the right atrium preceded the onset of the P wave by 33±14 ms in 17 patients (89%) even though the source was located on the left in 10 of them. When the earliest sites from each side were compared in all patients, the activation gradient was 24±18 ms. Conclusions: Septal and para-septal structures account for 20% of focal ATs. The inter-atrial activation gradient suggests that most of these AT are not septal, but rather originated from para-septal structures. Despite this gradient, activation in the right atrium preceding the onset of the P wave is observed in most patients with a left-sided para-septal focal AT.

AB32-3 RAPID DISTINCTION OF LEFT AND RIGHT ATRIAL FLUTTER BY ENTRAINMENT MAPPING FROM THE ANTERIOR RIGHT ATRIUM Hernán Roa, MD, Rafael Peinado, MD, PhD, José L. Merino, MD, PhD, Ester Macía, MD, Oscar Quintero, MD and Mar Gonzalez-Vasserot, MD. Hospital La Paz, Universidad Autonoma, Madrid, Spain. Introduction: Atrial flutters (AF) can be located in the left or right atrium and localization often requires extensive activation and entrainment mapping. Rapid distinction of the likely region of interest would simplify the mapping and ablation procedure. This study was aimed to develop a simple method for predicting the atrium in which the successful ablation region was located by using entrainment mapping from the right atrium. Methods: We retrospectively studied 52 patients (31 male, age 62 ± 16 years) undergoing successful RF catheter ablation of AF in which entrainment mapping was used to delineate the tachycardia circuit. Thirty-four patients had structural heart disease. The location of the AF circuit was determined by mapping and ablation. AF were grouped depending on the location of the successful ablation region in two groups: Group 1 (right atrial flutter, RAF) included common AF (n=25), lower loop AF (n=5), fossa ovalis AF (n=4) or superior vena cava AF (n=1). Group 2 included left atrial (LAF) flutter (n=17). The difference between the postpacing interval and tachycardia cycle length (PPI-TCL) was calculated at the cavotricuspid isthmus (CTI), anterior right

S70 Heart Rhythm Vol 4, No.5 May Supplement 2007

atrium (ARA), high right atrium (HRA), high and low right atrial septum (HRAS, LRAS), proximal coronary sinus (PCS) and distal coronary sinus (DCS). We compared the PPI-TCL at these sites between the two groups, and developed a simple criterion to predict AF origin. Results: The mean PPI-TCL at the different sites of entrainment mapping in the group 1 and 2 where: CTI: 27±41 vs 96±80, p< 70 ms at the ARA distinguished RAF from LAF. This criterion had a sensitivity and positive predictive value of 96 %, specificity and negative predictive value of 92 % for predicting the location of successful ablation region in the right atrium. Conclusions: Simple analysis of PPI-TCL from the ARA can rapidly suggest the AF circuit location in the right or left atrium to guide more detailed mapping of one atrial chamber. AB32-4 ABLATION OF POSTEROSEPTAL ACCESSORY PATHWAYS GUIDED BY LEFT ATRIUM-CORONARY SINUS MUSCULATURE ACTIVATION SEQUENCE Róbert Pap, MD, Attila Makai, MD, Gábor Bencsik, MD, Vassil B. Traykov, MD and László Sághy, MD. University of Szeged, Szeged, Hungary. Introduction: Some posteroseptal accessory pathways (APs) can be ablated on the tricuspid annulus or in the coronary venous system, while others require a left sided approach. Predicting which APs are amenable to ablation from the right side is very important to prevent unnecessary instrumentation of the left heart. During retrograde AP conduction fragmented or double potentials can be recorded in the coronary sinus (CS), with a low amplitude, blunt component originating from left atrial (LA) myocardium, and a larger, sharp one from the CS musculature itself. Methods: Thirty-seven patients with posteroseptal AP were included. Intracardiac recordings by a decapolar catheter placed in the CS were assessed by an electrophysiologist blinded to the results of ablation. The LA-CS activation sequence was determined at the earliest site during retrograde AP conduction. Results: Eleven APs (30%) were successfully ablated on the tricuspid annulus (right endocardial), 7 (19%) inside the coronary venous system (epicardial), and 19 (51%) on the mitral annulus via transseptal puncture (left endocardial). A fragmented or double potential was recorded in all patients inside the CS at the earliest site during retrograde AP conduction. Sharp potential from the CS preceded the LA blunt component (sharp/blunt) in all patients with an epicardial AP, and in 10 of 11 (91%) patients with a right endocardial AP. A reversed sequence (blunt/sharp) was recorded in 17 of 19 (89.5%) patients with a left endocardial AP. A sharp/blunt sequence of potentials at the earliest site in the CS predicted successful ablation from the right side with 94% sensitivity and 89.5% specificity. Conclusions: During retrograde AP conduction the LA-CS musculature activation sequence recorded at the earliest site identifies posteroseptal APs amenable to ablation without left heart access. AB32-5 HOW TO SUCCEED IN WPW ABLATION AFTER A PRIOR FAILURE? A 1999-2006 MULTICENTER EXPERIENCE Frédéric Sacher, MD, Matt J. Wright, MD, PhD, Usha Tedrow, MD, Mark D. O'Neill, MD, Pierre Jaïs, MD, Meleze Hocini, MD, Rosie MacDonald, MD, Jacques Clementy, MD, Laurence M. Epstein, MD, Nicholas S. Peters, MD, FRCP, William G. Stevenson, MD and Michel Haïssaguerre, MD. Universite Bordeaux II / CHU de Bordeaux, Bordeaux-Pessac, France, St. Mary's Hospital, London, United Kingdom and Brigham and Women's Hospital, Boston, MA. Introduction: Catheter ablation for Wolff-Parkinson-White syndrome (WPW) can be challenging and is associated with failure in ~1-5% of cases. We analysed the reasons for failure to achieve a permanent

result. Methods: We analyzed all repeat ablation procedures for an accessory pathway (AP) with manifest pre-excitation (1999 to 2006) performed in 3 centers after a prior procedural failure (1.8 ±0.8 procedures). Results: Eighty-nine patients (61males, 28 ±16yo) were studied, 82 of whom had otherwise normal hearts (See Table; a cavo-tricuspid and a left anterior AP were also present and ablated successfully). The repeat procedure was successful in 81 (91%). Multiple (2.7 ±0.9) or large APs were seen in 13 patients. For left lateral APs, inaccurate mapping and lack of transseptal access during the index procedure accounted for failure (n=15). An irrigated catheter was required for deep APs (n=7). In addition 7 postero-septal APs deep in the septum required biatrial and coronary sinus applications to succeed. For parahisian and midseptal APs, RF was cautiously titrated from 5 to 30W, eliminating the AP in 3. Cryoablation was then used in 7 with acute success in 6 but delayed recurrences in 3 (within one month). The procedure was abandoned in 2 young patients (one with RF and the other with RF and cryo) due to an excessive risk of AV block. For patients with middle cardiac vein APs, RF at the endocardium was ineffective and irrigated ablation in the CS was crucial to deliver adequate power. For anteroseptal, anterior and right lateral APs, a successful outcome was achieved with long sheaths (n=5) or a left subclavian approach (anteroseptal n=4). Conclusions: Ablation of left sided APs in WPW syndrome requires familiarity with the transseptal and retrograde aortic approaches. In case of left inferior WPW, a middle cardiac vein AP should be ruled out. For right lateral to antero-septal pathway long sheaths and a left subclavian approach should be used.

Procedure characteristics depending on the localization of the pathway

Left lateral(n=22)

Postero-septal (n=12)

Para-hisian or Mid-septal (n=11)

Middle Cardiac Vein (n=10)

Right anterior and antero-septal (n=10)

Right lateral(n=9)

Multiple or large pathways (n=13)

p-value

Acute Success

20 (91%)

9 (75%)

9 (82%)

10 (100%)

10 (100%)

9 (100%)

12 (92%) 0.27

Number of previous procedure

1.9 ±1.0

1.4 ±0.8

3.5 ±0.7

2.0 ±0.2

2.4 ±0.6

1.5 ±0.6 1.5 ±0.7 0.04

Radiofrequency duration (min)

5.5 ±5.8

19.3 ±24.1

3 ±1.4

9.3 ±9.9

9.3 ±5.2

14.1 ±8.3 17 ±16 0.17

Fluoroscopy duration (min)

23 ±20 30 ±25 19 ±6 31

±45 31 ±18

20 ±13 33 ±23 0.92

Transseptal 22 (100%)

3 (25%)

0 (0%)

2 (20%) 0 (0%) 0

(0%) 5 (38%) <0.001

Irrigated tip catheter

20 (91%)

12 (100%)

3 (27%)

10 (100%)

6 (60%)

7 (70%)

12 (92%) 0.34

Energy used 22 RF 12 RF

10 RF 7 Cryo

10 RF 3 Cryo 10 RF 9 RF 13 RF 0.85