Posters PO 03-01 to 03-115

S217 41, and 24 patients, respectively). The primary endpoint was ventricular rate control (VR) to 100 bpm within 24 hours from initiation of treatment. Secondary ef cacy and safety endpoints included relative HR reduction, time to VR control, conversion to sinus rhythm, length of ICU stay, survival until ICU discharge, and incidence of bradycardia, hypotension, or Torsades de pointes. Results: The primary endpoint was achieved in 85.2 (52/61) of amiodarone patients, 85.0 (35/41) of diltiazem patients, and 87.5 (21/24) of metoprolol patients (P 1.00). The mean relative HR reduction (±SD) was 40.5±13 , 38±16 , and 41. ±12 , in amiodarone, diltiazem, and metoprolol groups, respectively (P 0.52). Conversion to and maintenance of sinus rhythm throughout the study period occurred in 21.3 (13/61) of amiodarone patients, 7.3 (3/41) of diltiazem patients, and 37.5 ( /24) of metoprolol patients (P 0.013). Conclusions: The results of this retrospective study found no difference in achieving the heart rate goal between the three agents. A large randomized controlled trial designed to determine the optimal therapeutic strategy for a heterogeneous cohort of patients with new onset AF with RVR is needed.

PO3-04 CHANGES IN CARDIAC AUTONOMIC TONE DURING NORMAL PREGNANCY Mathias Baumert, PhD, Michal Javorka, MD, PhD, Andrea Seeck, BSc, Renaldo Faber, MD, Prashanthan Sanders, MBBS, PhD and Andreas Voss, PhD. The University of Adelaide, Adelaide, Australia, Comenius University, Martin, Slovakia, University of Applied Sciences Jena, Jena, Germany, University of Leipzig, Leipzig, Germany Introduction: Normal pregnancy affects the cardiovascular system. The aim of this study was to investigate longitudinal changes in cardiac autonomic tone and ventricular repolarisation by means of heart rate variability (HRV) and QT interval variability analysis. Methods: We analysed 30 min high resolution C s recorded monthly in 32 pregnant women starting from the 20th week of gestation. Heart rate and QT variability were quanti ed using detrended uctuation analysis (DFA). Results: DFA of HRV showed signi cantly higher scaling e ponents towards the end of gestation (p 0.0001, Figure 1). DFA of QT interval time series revealed structures signi cantly different from those of HRV. DFA of QT variability was not signi cantly altered during the second half of gestation. Conclusions: In conclusion, pregnancy affects cardiac autonomic tone as measured by HRV. In contrast, QT variability is not altered during the second half of normal gestation, suggesting that ventricular repolarisation is not normal.

PO3-05 RV ONLY PACING CAN PRODUCE A Q WAVE IN LEAD 1 AND AN R WAVE IN V1: IMPLICATIONS FOR BIVENTRICULAR PACING Rutuke K. Patel, PA, Anthony Emmi, RDCS, Yan Wang, RDCS, James N. Kirkpatrick, MD and Joshua M. Cooper, MD. Hospital of the University of Pennsylvania, Philadelphia, PA Introduction: The goal of biventricular (bi v) pacing is to electrically synchronize ventricular activation, seen on 12 lead C as QRS fusion between RV and LV pacing. As RV pacing typically creates an R wave in lead 1 and Q wave in V1, the presence of an initial Q wave in lead 1 (QL1) and/or an initial R wave in V1 (RV1) during bi v pacing might suggest an early contribution to the QRS by a posterolateral LV lead. Methods: In patients (pts) referred to our bi v optimization clinic, we recorded 12 lead C s of RV pacing, LV pacing, native QRS, and bi v pacing with different V V offsets to assess QRS morphology with each type of ventricular activation. An initial QRS de ection greater than 0.1mV and 40ms in duration was de ned as a Q wave or R wave. Results: In a series of 34 pts, RV only pacing produced an initial QL1 in (26 ), an initial RV1 in 17 (50 ), both features in 8 (24 ), and neither feature in 8 (24 ). In 2 pts, the presenting bi v paced QRS was identical to RV only pacing before optimization. After V V optimization, LV timing was advanced in 24 pts, creating a bi v paced QRS with greater LV contribution. There was a trend (p 0.0 ) toward needing a greater advancement in LV pacing in pts with QL1 or RV1 during RV pacing (mean 36ms) compared with pts without these features (mean 22ms). Conclusions: For optimal bi v pacing delivery, LV pacing must contribute signi cantly to ventricular activation. The initial QRS de ection in leads 1 and V1 during bi v pacing may not reliably indicate early LV contribution and therefore the RV and LV only paced QRS morphologies should be compared to the bi v paced QRS morphology in all 12 C leads to determine if a further LV offset is needed to achieve better QRS fusion.

PO3-06 LEFT VENTRICULAR PACING VIA CORONARY SINUS IS ASSOCIATED WITH BETTER REVERSE REDMODELING AND LONG-TERM OUTCOME IN PATIENTS WITH COMPLETE HEART BLOCK POST-TRICUSPID VALVE SURGERY Katherine Fan, MD, Daniel TL. Chan, Dr, MBBS, Lik Cheung Cheng, Dr, FRCS and Wing Hing Chow, Dr, MBBS. Grantham Hospital, Aberdeen, Hong Kong, Queen Mary Hospital, Pok Fu Lam, Hong Kong Introduction: Tricuspid valve repair/replacement (TVR) was indicated in patients (pts) with symptomatic severe tricuspid regurgitation, often secondary to severe right ventricular (RV)

S218 dilatation and severely tethered lea et. The clinical outcome of pacing therapy for complete heart block after TVR were compared between endocardial RV pacing and transvenous lcoronary sinus left ventricular (LV) pacing in our cohort. Methods: From 2002 to 2008, 18 pts underwent permanent pacemaker implantation for complete heart block post TVR (77 with concomitant redo valvular surgery); 10 pts received transvenous RV pacing lead through TV valvuloplasty ring/ bioprosthesis and 8 pts had transvenous LV pacing via coronary sinus branches. Right ventricular volumetric changes were compared before and after TV surgery by CT scan. Results: Baseline demographic and clinical characters were comparable between 2 groups. The mean duration from TVR to pacemaker implantation were 23±8 days and mean follow up period was 58±13 months. The mean capture thresholds remained stable in both groups during follow up. There were signi cant reduction in RV volumes ( 205±60 cm3 vs 128± 35 cm3; p 0.01) and increase in RV e ection fraction ( F) in LV group compared with RV group (12±8 vs 8±5.6 ; p 0.03). ight pts (80 ) in RV group developed progressive right heart failure and worsening TR during follow up, requiring hospitalization. nly 1 pt from LV group developed heart failure secondary to TR recurrence. Conclusions: Transvenous LV pacing via CS can be achieved with long term stable and effective stimulation in pts with complete heart block post TVR. LV pacing was associated with signi cant RV reverse remodeling and better clinical outcome.

PO3-07 EFFECT OF CONSECUTIVE THERMAL EXPOSURES ON CAPTURE THRESHOLD Peter N. Costandi, PhD, Ramez E. Shehada, PhD, Neha B. Butala, MS and Ben A. Coppola, PhD. St. Jude Medical, Sylmar, CA Introduction: ne of the ma or patient safety hazards resulting in the current contraindication of pacemakers in clinical MR systems is lead tip heating, where induced RF currents manifest as heat at the electrode/tissue interface. A proof of safety approach being considered by the IS /I C is currently limited by the unavailability of in vivo data characterizing the effect of elevated temperature doses on myocardial tissue. The ob ective of this study was thus to quantify the change in capture threshold (CT) following successive thermal e posures to 44degC, thereby providing insight to the physiological link required for demonstrating MR safety in the pacemaker patient population. Methods: Si teen adult canines were implanted with a pacer system in the RV ape . ach lead was modi ed to allow for thermal monitoring of the tissue 1mm displaced from the heli where viable myocardium persists. Following a wk maturation period, RF energy was delivered directly to the tissue for 1 hr via the pacing lead to register 44degC. After 2 and 4 wks, a 2nd and 3rd thermal dose was delivered. Bipolar CT was measured weekly for the 14 wk study duration as well as 2 hrs following each thermal dose. CT change was assessed 2 hrs post heating, when the acute cardioprotective effects of thermally stimulated heat shock proteins are not emphasized. Results: f the 16 implants, 2 leads dislodged and 1 canine showed evidence of focal hemorrhage at the heli tip. These 3 cases were then e cluded from analysis. At study end, appropriate heli ation to the endocardial wall, as well as suitable brotic deposition, was veri ed in the remaining 13 canines by gross dissection and light microscopy. The average percent increase in CT 2 hrs following the 1st, 2nd and 3rd thermal e posures was 68 , 81 and 83 , respectively, versus baseline. Furthermore, in 7 of cases the observed post heating increase in CT subsided to within 0.5V of baseline 1 wk

Heart Rhythm, Vol 8, No. 5, May Supplement 2011 following each thermal delivery. Conclusions: CT was found to increase by more than 68 following consecutive thermal e posures, and in most cases returned to baseline within a week. These changes may suggest a modi cation to pacing prescriptions is required prior to MR scanning and may then provide guidance for proof of safety of pacemaker systems in MRI.

PO3-09 COMPARISON OF IEGM CHANGES DUE TO INDUCED ISCHEMIA DURING INTRINSIC VERSUS PACED RHYTHMS Jeffery D. Snell, BA, Nikolai Korsun, PhD, Ryan Rooke, MS, Jay Snell, BS, Bruce Morley, BS, Rupinder Bharmi, MS and Yelena Nabutovsky, MS. St. Jude Medical, Inc., CRMD, Sylmar, CA Introduction: Detection of intracardiac electrogram (I M) ST shifts during ventricular pacing could facilitate early identi cation of ischemia or myocardial infarction in pacer dependent and CRT patients. We directly compared I M changes during acute coronary occlusions between intrinsic and paced rhythms. Methods: Ten canines were implanted with modi ed St ude Medical (S M) Promote® CRT D (3215 36) with RA, RV and LV leads. Baseline I M data was recorded following lead maturation period. Ischemia induced via direct coronary artery occlusion of left anterior descending (LAD) or left circum e (LCX) artery using clamp, in atable cuff, or transvenous balloon, was held for appro imately 4.5 minutes with alternating intrinsic and paced rhythms while recording RVtip Case and LVtip Case I M vectors. The ma imum ST deviation during occlusion was compared to the baseline ST level immediately prior to occlusion. Results: A total of 1 occlusions were analyzed. Ischemia was associated with changes in both sensed and paced I Ms,Fig. For sensed I Ms, the mean ma imum ST segment change during coronary artery occlusion was 1.36 mV which was 73.68 of the R wave amplitude. For paced I Ms, the mean ma imum ST segment change during coronary artery occlusion was 2.14 mV which was 63.16 of the R wave amplitude. Conclusions: I M ST segment changes associated with acute coronary artery occlusions during paced and intrinsic ventricular beats were comparable in canines. These data support the feasibility of ST deviation detection algorithm for ischemia detection during RV or BiV pacing.

S21

Poster Session III

PO3-10 AXILLARY VEIN RUNS AWAY TRYING TO ESCAPE OPERATOR’S PURSUIT; FACTORS CAUSING VASOSPASM AND VESSEL-DISPLACEMENT DURING CARDIAC DEVICE IMPLANTATION PROCEDURE Junichi Saito, MD, Yutaka Kawamura, MD, Natsuko Kamiya, MD, Yasuo Tokoro, MD, Kazuya Iwata, MD, Katsuyuki Kobayashi, MD, Shinsuke Haraguchi, MD, Hideaki Kido, MD, Hideki Takenaka, MD, Masahiko Saito, MD and Masao Nishimura, MD. Ageo Central General Hospital, Ageo, Japan Introduction: It is widely accepted to apply a illary vein puncture for implantation of cardiac devices into the chest. To secure safety and minimize complications such as pneumothora and hemothora , a illary venography is highly useful to con rm anatomical site and direction of the puncture. However, we sometimes fail to make right puncture even utilizing this method. Methods: Two hundred patients (72±12 y.o.) underwent a illary subclavian venography before implantation of cardiac devices. nly patients with normal venography were selected. We applied an e tra thoracic a illary vein puncture method on the 1st rib to safely introduce a guide wire into the a illary vein. Results: In 16 patients, a illary veins were successfully punctured within a few trials (S group). However, in the remaining 31 patients, puncture failed even after several trials (F group). Venography taken immediately after failure disclosed either vasospasm or vessel displacement. Hence, factors such as a body/mass inde , a body weight, a diameter of a illary vein, a width of a illary vein on 1st rib, and a sternoclavicular angle were statistically investigated. All these factors in F group were signi cantly smaller than those in S group (1 ±3 vs 24±4, P 0.0018; 57±11 vs 5 ±13 g, P 0.04; 8.8±1.0 vs 11±3.0 mm, P 0.022; 4.5±3.3 vs 11±3.8 mm, P 0.0001; 113±6 vs 117±5.0 , P 0.015, respectively). Intravenous administration of isosorbide dinitrate did not contribute to immediate improvement of vasospasm and vessel displacement. They were gradually restored by an additional application of local anesthetic into the muscle. In ad usted pooled logistic regression analysis, e istence of ad acent two a illary vein valves at the puncture site and width of a illary veins on 1st rib 4 mm were strongly associated with the high incidence of vasospasm and vessel displacement ( R 18, P 0.0016; R 24, P 0.005 , respectively). Conclusions: tra thoracic a illary vein puncture may be dif cult in slender patients with obtuse sternoclavicular angle and narrow a illary vein having ad acent two vein valves at the puncture site. Careful puncture with suf cient local anesthesia is mandatory to perform successful implantation of the cardiac devices.

PO3-11 USE OF ELECTRONIC MEDICAL RECORD TO IDENTIFY HOSPITAL INPATIENTS ELIGIBLE FOR GUIDELINE BASED HEART FAILURE THERAPIES Nilamkumar Patel, MD, Srinivas Yallapragada, MD, David J. Wilber, MD and Joseph Cytron, MD. Loyola Univ Medical Center, Maywood, IL Introduction: We report a novel way of identifying patients with HF and or LV dysfunction during hospital admission, making minor modi cations in a widely used electronic medical record. Methods: ver a 6 month period from an un 2010, a mandatory 4 item yes or no questionnaire regarding HF was attached to the discharge order sets for all medicine and cardiac surgery patient hospitalizations. This facilitated identi cation

of patients with history of HF and documented F 40 . The charts of these patients, known by their providers to have moderate to severe systolic dysfunction, were reviewed for compliance with appropriate medical and device therapy for HF as recommended in clinical practice guidelines. Results: History of HF was identi ed in 885 patients; of these, 443 had documented F 40 . AC inhibitors or ARBs were prescribed in 74.8 and ß blockers in 87.1 .Ninety patients were readmitted over the 6 month survey. Risk of readmission was signi cantly increased for those not prescribed vasodilators and ß blockers, for women, and for patients with QRS>150ms. In a subset of patients with F 35 , fewer than half had an ICD. Women were signi cantly less likely than men to have an ICD. f 116 patients with F 35 and without ICD, contraindication to ICD was found in 54 (48 ). Contraindications include recent diagnosis of HF or recent PCI/CAB ( 3mo), or MI in last 40d; combined these accounted for 30 of patients without ICD. Cancer, noncompliance, substance abuse or psychiatric disorder accounted for 12 of e clusions. Patient refusal was documented in 14 of cases. In 41 of patients with F 35 and no ICD, no contraindication to ICD could be identi ed. Conclusions: Minor modi cations in an electronic medical record can markedly enhance identi cation of eligible hospital inpatients for guideline recommended therapies. Risk of re hospitalization is signi cantly decreased when providers appropriately apply these guidelines.

PO3-12 CHRONIC BIPOLAR LEFT VENTRICULAR LEADS FOR IMPLANTABLE DEFIBRILLATOR RATE-SENSING Robert H. Hoyt, MD. Iowa Heart Center, Des Moines, IA Introduction: There are multiple options with the Medtronic model 6 4 advisory lead at biventricular implantable cardioverter de brillator (biVICD) battery replacement. A new dual coil ICD lead or right ventricular (RV) rate sensing lead can be implanted, or the 6 4 lead can be re used. Another option may be substitution of the chronic bipolar left ventricular (LV) pacing lead for rate sensing. perience was reviewed in 32 consecutive patients, with both a normally functioning 6 4 lead, and a model 41 4 bipolar LV lead, undergoing biVICD replacement. Methods: isting leads only were used in 17 patients, and new leads were implanted in 15. In 6 cases deliberate reversal of the RV and LV rate sensing leads resulted from moving a 41 4 LV lead into the RV port of the header block, and the IS 1 connector of the 6 4 lead into the LV port. New leads included a model 5076 rate sensing lead implanted in the RV ( patients) or a model 6 47 replacement ICD lead (6 patients). No ICD leads were routinely e tracted. Results: The RV/LV switch was successful in 5 attempts. In one case, the LV electrogram had a far eld atrial signal, and the leads were returned to standard con guration. Implant duration for the LV leads was 57.6 / 6.8 months. The LV sense amplitude was 18.0 / 6.8 mV, with bipolar capture threshold of 1.0 / 0.26V, and impedance of 865 / 282 ohms. Induced ventricular brillation was sensed at 1.2mV by the LV leads, with appropriate de brillation. At follow up of 4.2 / 1.1 months, no lead related problems have been observed in any of the patients. Conclusions: Arrhythmia detection with a biVICD can be done effectively from the LV bipolar lead. For a 6 4 lead with biVICD battery replacement, implantation of a new pace sense lead in the RV eliminates concern about future 6 4 rate sensing fracture, but requires hospitalization, and risk of a new lead. An equivalent outcome may be obtained by switching the RV and

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

LV leads, which effectively replaces the rate sensing function of the 6 4 lead. Since no new leads are implanted, this approach can be used with outpatients. An RV/LV lead switch can also be considered for management of other RV sensing problems, such as diaphragmatic myopotential or T wave oversensing.

COMPARISON OF RIGHT AND LEFT SIDED ICD DEFIBRILLATION EFFICACY AND MORTALITY William W. Brabham, MD, Sherief N. Khalil, MD, Anbukarasi Maran, MD, Frederick W. Funke, Jr., MD, Courtney Cave, MD, Darren S. Sidney, MD, Richard N. Vest, III, MD, Michael L. Bernard, MD, Robert B. Leman, MD, Frank A. Cuoco, MD, J. Lacy. Sturdivant, MD, J. Marcus Wharton, MD and Michael R. Gold, MD. Medical University of South Carolina, Charleston, SC Introduction: Right pectoral implantable cardioverter de brillators (ICD) are infrequently used due to concern of high de brillation thresholds (DFT). Accordingly, right sided implants are most often used in the setting of left sided implant contraindications, many associated with higher morbidity and mortality. While DFT and survival among left sided implants are well described, right sided implants are incompletely de ned. Methods: We performed a retrospective case control analysis of DFT in consecutive patients undergoing transvenous ICD implantation. All patients underwent a uniform, modi ed step down DFT protocol, with an elevated DFT de ned as > 20 . Survival after implantation was evaluated through the Social Security Death Inde . Results: There were 44 right sided and 57 left sided implants. Patients receiving right vs left sided implants were similar with regards to age, gender, race, left ventricular e ection fraction, etiology of heart failure, NYHA class, and baseline medical therapy. There was a higher incidence of diabetes and renal dysfunction in right vs left sided implants (table). In right sided implants, DFT was signi cantly higher with a nonsigni cant higher prevalence of elevated DFT (table). There was a strong trend towards lower mortality with left sided implants aplan Meier analysis (HR 0.5 , p 0.10). Conclusions: The prevalence of elevated DFT in right sided implants is relatively high, and acute testing should be considered. There is a trend towards increased mortality in this population, possibly due to increase in comorbid, noncardiac conditions. Right

Left

63. ± 12.8 63.0 ± 13

P Value 0.65

Male ( )

70.5

73.3

0.73

Ischemic Cardiomyopathy ( )

52.3

53.5

0.50

LV

30.3 ± .4

30.0 ± 12.5 0.78

NYHA Class III/IV

56.8

52.8

0.25

Diabetes

50

34.2

0.05

FR (ml/min/1.73m2) DFT ( ) High DFT (>20 ,

)

Introduction: Patients with severe structural heart disease have increased mortality after implantable cardioverter de brillator (ICD) shocks. Whether this is limited to ICD shock therapy only or e tends also to non shock therapies, such as anti tachycardia pacing (ATP), is unclear. We sought to assess the impact of different ICD therapies on long term outcome among a large cohort of patients with ICDs. Methods: 532 patients undergoing ICD implantation at our Institution from anuary 2001 to ctober 2010 were enrolled. Patients were divided into three groups: roup A patients without any ICD intervention, roup B patients with appropriate ICD shocks, and roup C patients with only ATP interventions. The probability of all cause mortality was evaluated based upon the type of ICD therapy received using multivariable Co proportional analyses. Results: ver a mean follow up of 38 ± 27 months, 52 (10 ) patients received appropriate ICD shocks ( roup B), 46 ( ) received only ATP interventions ( roup C), and 434 (81 ) patients had no ICD intervention ( roup A). verall, 25 (5.8 ) roup A, 11 (21 ) roup B, and 12 (26 ) roup C patients died. At multivariable analysis, ad usted for possible confounding factors (age, indication, type of device, left ventricular e ection fraction) both roup B (hazard ratio [HR 2.6, 5 con dence interval [CI 1.4 to 5.2, p 0.004) and roup C (HR 3.1, 5 CI 1.6 to 5. , p 0.001) had increased mortality compared to roup A. No signi cant difference in mortality was found between roups B and C (p 0.56). Conclusions: Patients with ICD who receive appropriate interventions are at increased risk of mortality. Such risk is not dependent on different types of ICD therapies, such as shocks or ATP. Therefore, our data suggest that in these patients, sustained ventricular arrhythmias per se have negative impact on prognosis rather than modality of ICD therapy.

PO3-15

Right vs Left Sided Implants

ection Fraction ( )

PROGNOSTIC IMPLICATIONS OF DIFFERENT DEFIBRILLATOR THERAPIES IN PATIENTS WITH IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS Gianluigi Bencardino, MD, Pasquale Santangeli, MD, Antonio Frontera, MD, Gemma Pelargonio, MD, Maria Lucia Narducci, MD, Eleonora Russo, MD, Francesca Augusta Gabrielli, MD, Fulvio Bellocci, MD, Antonio Giuseppe Rebuzzi, MD and Filippo Crea, MD. Catholic University of the Sacred Heart, Rome, Italy

PO3-13

Age (years)

PO3-14

4 .2 ± 25.6 70.5 ± 26.8

0.0001

13.4 ± 6.5

11.2 ± 6.

0.038

11.4

7.

0.3 3

LOW-DOSE DOBUTAMINE TEST ASSOCIATED WITH INTER-VENTRICULAR DYSSYNCHRONY: THE NEW GOLD STANDARD FOR IDENTIFYING CRT RESPONSE? DATA FROM THE LODO-CRT PHASE 2 STUDY Maurizio Gasparini, MD, Carmine Muto, MD, Francesco Zanon, MD, Cosimo Dicandia, MD, Giuseppe Distefano, MD, Stefano Favale, MD, Carlo Peraldo Neja, MD, Renato Bragato, MD, Mario Davinelli, ENG, SCD, FHRS, Lorenza Mangoni, ENG, SCD, FHRS and Alessandra Denaro, ENG, SCD, FHRS. IRCCS Istituto Clinico Humanitas, 20089 Rozzano-Milano, Italy, Ospedale S Maria di loreto Mare, Napoli, Italy, Ospedale S Maria della Misericordia, Rovigo, Italy, Anthea Hospital, Bari, Italy, Centro Cuore Morgagni, Pedara Catania, Italy, Policlinico di Bari, Bari, Italy, Ospedale Fatebenefratelli San giovanni Calibita, Roma, Italy, Medtronic Clinical department, Roma, Italy, Medtronic Clinical Department, 200Roma, Italy, Medtronic Clinical Department, Rome, Italy Introduction: CRT is effective in heart failure (HF) pts, but 30 to 50 are non responders. Identifying potential responders remains a challenging task. Aim of the study was the evaluation

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Poster Session III

of the association between left ventricular contractile reserve (LVCR) and clinical and echo long term response to CRT in a multicenter study. Methods: LVCR presence was detected using dobutamine stress echo and de ned as an F absolute increase greater than 5 . 22 pts were enrolled. Clinical response: absence of ma or cardiovascular (CV) events (MC ) (CV death or HF hospitalization); cho response (i.e. reduction of LV end systolic volume > 10 ) after CRT. Results: 80 of pts (177) presented LVCR before CRT. At a mean f.u. of 15±5 mos, 17 (8 ) pts died from HF and 16 (7 ) were hospitalized for HF. Responder pts (no MC ) were 155/180 (88 ) and 33/44 (75 ) (p 0.04) in the groups with and without LVCR, respectively. aplan Meier analysis showed a signi cant difference in MC between pts with and without LVCR. Multivariable analysis identi ed LVCR and inter ventricular dyssynchrony as independent predictors of echo response to CRT. The concomitant presence of both factors showed a very high speci city ( ) and sensitivity (83 ) in detecting responder. n the contrary the concomitant absence of both factors virtually abolished any chance of response ( gure). Conclusions: LVCR presence at baseline predicts both clinical and echo responses to CRT. Concomitant assessment of LVCR and inter ventricular dyssynchrony accurately stratify responder and non responder pts to CRT.

choices were 2LV/1RV (35 pts) 2RV/1LV( pts). There were two self resolved CS dissections no ma or complications. Pre post implant NYHA class echo data are noted in the table. Acute Clinical

chocardiographic Features Pre Post Parameter Implant Implant LV DD (LV end diastolic 63 mm 60 mm dimension) LP P (LV pre e ection period) 153 ms 126 ms DFT/RR

P Value 0.3 0.00001

(diastolic lling time) 45

50

0.002

21

28

0.00001

LV F

Conclusions: The use of trisite pacing to achieve cardiac resynchronization is technically feasible. Trisite ventricular pacing appears to be highly successful acutely, resulting in signi cant improvements in CHF functional class echocardiographic measures of CHF severity dyssynchrony. Trisite pacing, aimed at ma imizing inter lead distances, should be considered to achieve cardiac resynchronization in CRT non responders with persistent dyssynchrony or in pts undergoing de novo implants with multiple dyssynchronous segments.

PO3-17 ACUTE RESPONSE TO TRISITE VENTRICULAR PACING Andrew C. Wickliffe, MD, Thomas Deering, MD, Dan Dan, MD and Serge Cazeau, MD. Piedmont Heart Institute, Atlanta, GA, Hôpital Saint-Joseph, Paris, France

PO3-16 TRISITE VENTRICULAR PACING: A FEASIBLE, CLINICALLY BENEFICIAL & INNOVATIVE NEW TECHNOLOGY TO ACHIEVE CARDIAC RESYNCHRONIZATION Thomas F. Deering, MD, Dan Dan, MD, Andrew C. Wickliffe, MD and Serge Cazeau, MD. Piedmont Heart Institute, Atlanta, GA, Hopital Saint-Joseph, Paris, France Introduction: Despite advances in CRT, the non responder rate remains high partly due to non optimal resynchronization during initial implant. Trisite pacing (TSP) has been proposed as an option to increase responder rates. Methods: Forty si patients (pts) demonstrating multiple dyssynchronous segments by pre implant echocardiographic TDI analysis underwent TSP (16 non responder CRT D upgrades 30 new implants). The 3rd lead position was chosen to ma imize inter lead distance while attempting to pace at the most delayed echo de ned contracting LV segment. Acute pre implant post implant (2 14 days) echo parameters NYHA class were assessed (table). Results: The mean age was 62.5±11.4 years 60. of pts were male. The procedure duration was 174.5 ±5 min, uoroscopy time 25±12.6 min, contrast use 63.7±21. ml. The TSP implantation success rate was 5.6 (44/46). Lead site

Introduction: Despite advances in cardiac resynchronization therapy (CRT) the non responder (NR) rate remains high. Trisite ventricular pacing (TSP) has the potential to improve response rates. Methods: Forty si patients (pts) with LV systolic dysfunction (mean F: 21.7 0.8 ), an average pre implant NYHA class of 3.5 SD and predominant male gender (61. ) underwent TSP. The position of the third lead was chosen to ma imize inter lead distance and pace at the most delayed contracting LV segments (as assessed by echo longitudinal strain). Acute echocardiographic functional data was analyzed before and 7 / 6 days after implantation. Results: Upgrades from CRT NR’s accounted for 2 .3 and new implants (or upgrades from single or dual chamber devices) for 70.7 of pts. Acute pre and post implant echo and clinical data is presented in the table. Conclusions: TSP effectively improves acute clinical and echocardiographic measures of CHF severity. TSP, aimed at ma imizing inter lead distances, should be considered in all pts undergoing resynchronization. Pre implant and acute post implant data Parameter

Pre implant

Post implant

NYHA Class

3.5

1.7

LV DD

63.1mm

61mm

P value 0.001 0.3

LP P (LV Pre e ection period)

14 .1ms 126ms

DFT/RR interval)

45

50

0.002

21

28

0.16

F

(Diastolic lling time/RR

0.001

S222 PO3-18 COMPARISON OF CARDIAC RESYNCHRONIZATION THERAPY OUTCOMES IN PATIENTS WITH NYHA CLASS I/ II VERSUS NYHA CLASS III/IV HEART FAILURE Ariel Rischall, BS, Ryan Gage, BS, Kevin Burns, PhD, Spencer Kubo, MD and Alan J. Bank, MD. St. Paul Heart Clinic, St. Paul, MN Introduction: Several large multicenter randomized trials (R V RS , MADIT CRT, RAFT) have shown that CRT provides signi cant bene ts for patients with New York Heart Association (NYHA) class I/II heart failure (HF). Whether similar outcomes occur in the real world is not well known. This study compares outcomes from patients receiving CRT with NYHA class I/II HF vs those with class III/IV HF. Methods: All patients receiving a rst time CRT device at our institution between 2003 and 2008 with F 35 and QRS duration 120 msec were included. The ef cacy of CRT in the two groups was compared using sub ective clinical response, echocardiographic ( CH ) changes in left ventricular (LV) size and function, survival, and survival free of cardiovascular (CV) hospitalization. Results: Baseline characteristics in class I/II (n 155) and class III/IV (n 512) groups respectively were: age 72±11 vs 68±12 years old, male 74 vs 70 , ischemic etiology 52 vs 60 , QRS duration 158 vs 157 msec, and F 25.6 vs. 24.5 . In both groups over 65 of patients improved clincally without differences between groups. In comparison to the class III/IV group, the class I/II group had a signi cantly larger decrease in LV end diastolic dimension ( 0.55±0.82 vs 0.36±0.7 cm, p .031), while changes in LV systolic dimension ( 0.68±0. 8 vs 0.48±0. 4 cm, p .056) and F (8.1± .5 vs 6.4± .2 ,p .05 ) trended towards signi cance. The class I/II group had a signi cantly higher 5 year survival rate (7 .5 vs 53.7 ) and a greater median time to rst CV hospitalization (58 vs 3 months). Conclusions: In this real world clinical scenario, NYHA class I/ II patients receiving CRT have clinical response rates similar to class III/IV patients. Improvements in LV function and size are as good as, or better than, those in more symptomatic patients. As e pected, 5 year survival and CV hospitalization rates are signi cantly better in NYHA class I/II patients as compared with class III/IV patients.

PO3-19 ACUTE EFFECTS OF BIVENTRICULAR PACING AT VARIOUS LV SITES IN PATIENTS WITH ISCHEMIC HEART FAILURE John P. McKenzie, III, MD, Vincent Splett, MS, Haresh Sachanandani, MS, Brian Yeh, BS and Brien Neudeck, PharmD. Glendale Memorial Medical Center, Glendale, CA, Medtronic, Mounds View, MN, Medtronic, Mission Viejo, CA Introduction: Biventricular (BiV) pacing is an important advancement in the treatment of systolic heart failure (SHF). Retrospective studies have shown a higher response rate for left ventricular (LV) leads placed in a lateral or posterior lateral (PL) vein, but have not compared response at different sites within a patient. This study evaluated acute hemodynamics at multiple LV pacing sites within a speci c patient. Methods: Ten patients with ischemic SHF indicated for BiV pacing were studied. Pacing leads were placed in the right atrium and ventricle (RV). A Millar catheter was placed in the LV for measurement of LV dP/dt ma and LV DP. Target veins for LV pacing were identi ed from venograms. An LV lead was placed into the target veins at up to three sites (basal, mid, and apical). Simultaneous RV LV BiV pacing at each site was

Heart Rhythm, Vol 8, No. 5, May Supplement 2011 preceded and followed by AAI pacing baselines; each period was one minute. Heart rate was maintained constant by atrial pacing at 10 over the sinus rate. Results: Two to 5 coronary veins (4.0±0. ) and 6 to 11 pacing sites (8.4±1.7) per sub ect were evaluated. The mean ma imum change in LV dP/dt ma was 13.7± .7 ; the mean minimum was 4.2±8.0 (P 0.001). Sites with ma imum change were basal (n 4) or mid cavity (n 6) in lateral (n 5) or PL (n 5) veins. Sites in anterior veins were associated with the smallest changes. Apical sites had lower changes in LV dP/dt ma (4.4±10.7 ) than basal (6.2±10.3 ) or mid cavity (4.7±10. ) sites (P 0.05), although 71 of apical sites were still superior to sinus rhythm. Among PL and lateral veins there was considerable variability in the hemodynamic response. At sites in these two veins the difference between the largest and smallest changes in LV dP/ dt ma was 13.6±6.5 . Si sub ects had at least one site in a PL or lateral vein with LV dP/dt ma lower than sinus rhythm. In 7 sub ects there were sites in these two veins with lower increases in LV dP/dt than sites in anterior veins. The optimal response was 5.1±2.3 higher than the response in the corresponding location in the other vein. Conclusions: In ischemic SHF, there is signi cant variability in the acute hemodynamic response to BiV pacing. Anatomical lead placement alone may be insuf cient to produce ma imal bene t.

PO3-20 STIMULUS INTENSITY IN LEFT VENTRICULAR LEADS AND RESPONSE TO CARDIAC RESYNCHRONIZATION THERAPY: PRELIMINARY RESULTS OF THE SILVER-CRT TRIAL Venkata V. Bavikati, MBBS, Jonathan J. Langberg, MD, Michael H. Hoskins, MD, Byron R. Williams, III, MD and Michael S. Lloyd, MD. Emory University, Atlanta, GA Introduction: perimentally, increased left ventricular (LV) stimulus intensity has been shown to improve conduction velocity, myocardial contractility, and cardiac output. However, the clinical bene ts have not been studied and high output LV pacing would shorten battery life of CRT devices. ur prospective randomized, double blind crossover trial analyzed the clinical effects of high output (Hi) versus low output (Lo) LV pacing. Methods: Twenty si patients undergoing CRT implantation with bipolar LV leads were assigned to three months of Hi LV pacing and Lo LV pacing each. The Lo setting was de ned as 1V above the LV tip electrode capture threshold. The Hi setting, to ma imize virtual electrode e pansion, was de ned as 1V above the output required to have simultaneous anodal and cathodal capture of the LV ring and tip electrodes. Si minute walk distance (6MWD), Minnesota living with heart failure score (MLWHF), transthoracic echo parameters, and clinical data were obtained at enrollment and at three and si months of follow up. Results: Mean age was 66.1 8. yrs, mean QRS duration was 156.8 21.4 msec, mean LV e ection fraction ( F) was 30.0 10.5 . The mean pacing output in the Hi arm was 5.6 1. V at 0. 0.3 msec and in the Lo arm it was 2.4 0. at 0. 0.3 msec ( p 0.005). There were no signi cant differences between Lo and Hi LV pacing. The LV F was 33.8 .5 and 33.1 13.4 (p 0.65); LV end diastolic diameter 5.4 1 and 5.6 1.1 cm (p 0.2 ); LV end diastolic volume was 137.7 62.7 and 140.6 56.5 cm3 (p 0.71); 6MWD was 1007.0 377.7 and 1023.7 364.0 feet (p 0.64); MLWHF score was 21.7 21.3 and 20.0 22.8 (p 0.4 ) in the Lo and Hi arms respectively. However, both arms had improvements compared to baseline (Lo arm: all parameters signi cantly improved (p 0.05); Hi arm: F and end diastolic

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dimensions only had trends toward improvement (p 0.1) ). Conclusions: We report the rst randomized clinical trial data comparing high output and low output LV pacing. ur data suggest that low output pacing with a relatively narrow safety margin affords signi cant clinical improvement and is clinically equivalent to high output LV pacing. This supports the safety and bene t of a programming strategy directed towards lengthening battery life in CRT devices.

PO3-21 TARGETED LEFT VENTRICULAR LEAD PLACEMENT USING SPECKLE TRACKING ECHOCARDIOGRAPHY IMPROVES THE ACUTE HAEMODYNAMIC RESPONSE TO CARDIAC RESYNCHRONIZATION THERAPY: A RANDOMIZED CONTROLLED TRIAL Fakhar Z. Khan, MRCP, Munmohan S. Virdee, MRCP, Peter J. Pugh, MRCP, John Hutchinson, BSc, Beverley Smith, BSc, David Begley, MRCP, Simon P. Fynn, MRCP and David P. Dutka, MRCP. Addenbrooke’s Hospital, Cardiology, Cambridge, United Kingdom, Papworth Hospital, Cardiology, Cambridge, United Kingdom Introduction: Left ventricular (LV) lead placement to the latest area of contraction is associated with enhanced response to cardiac resynchronization therapy (CRT). We conducted a randomised controlled trial to compare the effect on acute change in cardiac output (C ) between patients undergoing either echocardiographically guided LV lead placement or standard usual CRT implantation. Methods: A total of 180 patients with left bundle branch block (age 71 ± 8 yrs, NYHA III 2 , F 23 ± 7 , QRS 156 ± ms) were recruited and underwent speckle tracking 2D radial strain at baseline to determine the latest site of activation. Patients were subsequently randomized into one of 2 groups. In group 1 (targeted group TAR) the CRT implanters were aware of the echocardiographic ndings and attempted to position the LV lead to the latest site of activation. In group 2 (control C N) patients underwent standard CRT implantation without echocardiographic guidance. In all patients the LV lead position was de ned by biplane uoroscopy. Patients were classi ed according to the relation of the LV lead to the latest site as: Concordant (C lead position at latest site), Ad acent (A within one segment) or Remote (R 2 or more segments away from latest site). All patients underwent AV and VV delay optimization. Within 24 hours of implantation all patients underwent non invasive C determination using a commercially available system (NIC M) during optimised CRT and with CRT switched off (baseline). The peak improvement in C was compared between the two groups. Results: There were no differences in baseline characteristics between the two groups. There were more C and less R leads in the targeted group (TAR vs. C N: C 68. vs 46.7 p 0.01, A: 24.4 vs. 30.0 p 0.46, R: 6.7 vs. 23.3 p 0.01). There were no differences in C at baseline between the two groups (TAR vs. C N: 4.77 ± 1.1 vs. 4.67 ± 1.1 L/min, p 0.76). C was signi cantly higher during CRT in patients with a targeted LV lead compared to the control group (6.06 ± 1.3 vs 5.57 ± 1.2 L/ min, p 0.021). Conclusions: Targeting LV lead placement to the latest areas of activation using speckle tracking 2D radial strain is associated with a better C response to CRT compared to standard treatment.

PO3-22 EFFECT OF BIVENTRICULAR PACING PERCENTAGE AND FREQUENT OPTIMIZATION IN CARDIAC RESYNCHRONIZATION THERAPY: FREEDOM TRIAL SUBANALYSIS Nilofar Islam, MD, Daniel Gras, MD, William Abraham, MD, Leonardo Calò, MD, Ulrika Birgersdotter-Green, MD, Norber Klein, MD, Christopher Clyne, MD, John Herre, MD, Robert Sheppard, MD, Li-Yin Lee, PhD, Dunja Domazet, MS and Simona Petrutiu, PhD. MidMichigan Physicians Group, Midland, MI, Nouvelles Cliniques Nantaises, Nantes, France, Ohio State University, Columbus, OH, Policlinico Casilino, Roma, Italy, University of California San Diego, San Diego, CA, Universitätklinikum Leipzig, Leipzig, Germany, Hartford Hospital, Hartford, CT, Sentara Cardiovascular Research Institute, Norfolk, VA, The Heart and Vacular Institute of Florida, St. Petersburg, FL, St. Jude Medical, Sylmar, CA Introduction: Previous studies have shown that biventricular (BiV) pacing percentage (Pc ) impacts the response to CRT. Appropriate AV and VV timing can increase BiV Pc . The aim of this analysis was to determine if frequent optimization increased response in patients with lower BiV Pc in the FR D M trial. Methods: Patients (pts) were randomized at enrollment to a standard of care (SoC) or a frequent Quick pt™ optimization ( pt) group and followed at 3, 6, , and 12 month visits. Based on BiV Pc , pts were grouped into a high pacing group (HiPc ) (> 0 BiV pacing) or low pacing group (LoPc ) ( 0 BiV pacing). nly pts with BiV Pc data available at every scheduled follow up were included in this analysis. The freedom from HF hospitalization rates and improvement in NYHA class were compared at 12 months. Results: A total of 550 pts in the SoC (age 67 ± 11 years, NYHA III 5.6 , LV F 24.8 ± 7 ) and 564 pts in the pt group (age 66 ± 11 years, NYHA III 2.4 , LV F 24.2 ± 6.7 ) were included in the analysis. In the SoC group 121 (22 ) pts were LoPc pts and in the pt group 150 (27 ) pts were LoPc pts. Pts with LoPc had similar clinical characteristics between the SoC and pt group. The results are shown in the table below. Conclusions: In the SoC group, pts with a high BiV Pc had better outcomes compared to pts with lower BiV Pc , con rming previous observations. Frequent optimization using Quick pt™ improved CRT outcomes in pts with a lower BiV Pc , to a level comparable to that seen with high BiV Pc . These results suggest that frequent Quick pt™ CRT optimization may mitigate the negative effect of lower BiV Pc and be particularly useful in patients in whom BiV Pc is less than 0 . HiPc SofC N 42 Freedom from HF 3 Hosp NYHA class 58.3

LoPc pt N 414

SofC p value N 121

pt N 150

p value

3

NS

83.2

2

0.04

60.4

NS

53.7

60

NS

PO3-23 THE EFFECTS OF BASELINE TRICUSPID REGURGITATION ON LONG TERM RESPONSE AND PROGNOSIS IN CARDIAC RESYNCHRONIZATION THERAPY PATIENTS Raed A. Abu Sham’a, Sr., MD, Jonathan Buber, MD, Eyal Nof, MD, rafael Kuperstein, MD, Micha Feinberg, MD, David Luria, MD, David Bar Lev, MD, Igor Ariel Lipchenca, MD, Shemy Carasso, MD, Michael Eldar, MD and Michael Glikson, MD.

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Sheba Medical Center, Ramat Gan, Israel, Rambam Medical Center, Haifa, Israel Introduction: CRT is a cutting edge therapy for pts with advanced CHF. The interaction between CRT and TR is currently unknown. In this study we sought to investigate the relationship between baseline TR status and the clinical and echo outcome and survival among these patients. Methods: The study included 184 pts implanted with CRT systems, who underwent complete clinical and echo follow up of at least 1 year. Patients were divided into 2 groups according to baseline TR status. roup 1: no or mild TR and group 2: moderate or severe TR. We compared the baseline characteristics and outcome between the two groups including quanti cation of TR during follow up. Clinical response was de ned as a combined score of NYHA class, quality of life and 6 minute walk scores. ach component was classi ed as improved 1, unchanged 0, or worsened 1. Responders were de ned as pts who had a combined score of >/ 1 who did not die during follow up. cho response was de ned by an absolute increase >/ 5 in LV F and/or relative increase by >/ 10 in LV SV. Results: There were 30 (16.3 ) pts with advanced TR (gr 2). These pts had worse baseline echo parameters, shorter 6 minute walk distance, and higher incidence of a previous pacemaker. There was no signi cant difference in clinical or echocardiographic response to CRT between the two groups. However, patients in group 2 had a signi cantly higher mortality over 3 years ( R 6.5, 5 CI [2.0 21.2 , p value 0.002). Conclusions: The presence of baseline moderate or severe TR is associated with increased mortality without affecting clinical or echocardiographic response to CRT. This may be related to more severe underlying heart disease among these patients. Baseline chracteristics and outcome according to baseline TR status

Methods: In total, 27 patients were enrolled and followed 26 ± 7 days on average. chocardiograms were conducted at enrollment and at 2 week follow up visit. Chronic heart sound (HS) data were collected using an e ternal accelerometer placed at the left pectoral location. S3 measurements were e tracted using a proprietary detection algorithm and compared with the corresponding wave deceleration time ( DT) and wave deceleration slope ( DS) measured from echo. In addition, echo HS pairs from the same patient were compared with each other for a within patient analysis. Results: f 50 echocardiograms collected, 14 were e cluded due to poor data quality. Daily S3 amplitude averaged throughout the calendar day of the echo was signi cantly correlated to DT (r 0.52, p 0.01) and DS (r 0.71, p 0.01). Detection of restrictive diastolic lling ( DT 150ms) was achieved with sensitivity 0.74 and speci city 0.82. Within each patient the direction of S3 amplitude changes (mean±std: 0.6 ±1.13m for DT, p 0.05, and 0.37±1.3m for DS, p 0.22) was opposite to that of DT changes ( 40±2 ms) but the same as DS (0.18±0.15), which was consistent with common understanding of S3 genesis. Signi cant changes in wave deceleration time ( DT >30ms) within patient were detected with a sensitivity 0.42 and speci city 0.84. Conclusions: Automatically measured S3 amplitudes from ambulatory HF patients during activities of daily living showed a signi cant correlation to DS and DT suggesting that S3 amplitudes were indicative of diastolic lling patterns. Within patient analysis demonstrated that S3 amplitudes were moderately sensitive but highly speci c to detect changes in early diastolic lling status. These results support the potential of ambulatory S3 monitoring for assessing HF status.

PO3-25

Variable

No or Mild TR 154 [83.7

Moderate to severe p TR value 30 [16.3

TIMING OF HARDWARE REMOVAL WITH LEAD EXTRACTION AFFECTS IN-HOSPITAL SURVIVAL IN PATIENTS WITH CARDIAC DEVICE INFECTION

LV F,

25 ± 7

22 ± 5

Federico Viganego, MD, Susan O’Donoghue, MD, Zayd Eldadah, MD, PhD, Manish Shah, MD, Mohit Rastogi, MD, Jay Mazel, MD and Edward Platia, MD. Washington Hospital Center, Washington, DC

Degree of MR

0.02

1.3 ± 1

1. ± 1

0.003

45 ± 14

56 ± 14

0.0001

RVFAC

3 ± 10

30 ± 7

0.0001

Upgraded from Pacemaker

23

47

0.007

Baseline 6MW, m

270 ± 220

207 ± 111

0.01

Clinical Response

68

74

0.64

chocardiographic Response

51

48

0.78

Mortality

3.2

20.0

0.0001

stimated SPAP

PO3-24 THIRD HEART SOUNDS MEASURED AT CRT DEVICE IMPLANT SITES ARE CORRELATED TO ECHOCARDIOGRAPHIC FILLING PARAMETERS IN AMBULATORY HEART FAILURE PATIENTS Qi An, PhD, Satya Gupta, MD, Keyur Parikh, MD and Elisa Vireca, BS. Boston ScientiÀc, St Paul, MN, Boston ScientiÀc, Ahmedabad, India, Boston ScientiÀc, Diegem, Belgium Introduction: The third heart sound (S3), caused by abrupt early diastolic lling, is traditionally measured acutely at the cardiac ape . The TRAC HF study aims to evaluate the relationship between chronic S3 measured at CRT implant locations during activities of daily living and underlying hemodynamic status.

Introduction: Cardiac device infections (CDI) including pacemakers and de brillators have been rising worldwide. Antibiotics alone are ineffective, and percutaneous lead e traction (PL ) is required for complete hardware removal. The aim of this study was to evaluate in hospital mortality in a single center population of CDI patients, and to identify its relationship with PL . We hypothesized that clinical presentation may affect the timing of PL , with a potential impact on survival. Methods: Retrospective analysis was performed on 36 consecutive patients with CDI (28 ICDs, 8 pacemakers) who underwent PL at our center from anuary 200 to November 2010. Patients were divided according to clinical presentation ( roup A, bacteremia/endocarditis; or roup B, localized pocket infection only). Students t test was employed for comparison of continuous variables, and Fisher’s e act test was used for comparison of categorical variables. Results: There were 21 patients in roup A and 15 in roup B. The median age was 60 years. Coronary disease, diabetes mellitus, kidney disease, and systolic heart failure were present in 70 , 47 , 48 , and 58 of patients, respectively. Lead vegetation was found in 33 . A laser sheath was employed in 61 of patients, with complete hardware removal in 34 ( 4 ). There was no procedure related mortality. In hospital mortality was 1 , most commonly due to sepsis. Factors associated with in hospital mortality were systolic heart failure (p 0.03) and evidence of lead vegetation (p 0.05). In hospital mortality was

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28 in roup A patients and 6 in roup B patients (p 0.2). PL was performed signi cantly earlier among patients who survived versus those who did not (mean 2. vs. 7.6 days, p 0.02), and in roup B patients versus roup A (1.3 vs 5.7 days, p 0.003). Conclusions: Despite the favorable safety pro le and high success rate of PL , mortality of CDI remains high, particularly in bacteremic patients. Delayed hardware removal with PL may have catastrophic consequences in this subpopulation. A late diagnosis may be due to unsuspected CDI in the setting of nonspeci c symptoms. Physicians should have a high inde of suspicion for CDI, particularly in patients with a high risk pro le and plan for early intervention with PL .

PO3-26 CHARACTERIZATION OF FIBROSIS AT LEAD-TISSUE INTERFACE Mark Harwood, MD, Kristine Rustad, BS, Amin Al-Ahmad, MD, Paul Zei, MD, PhD, Henry Hsia, MD, Paul Wang, MD and Geoffrey Gurtner, MD. Stanford University Hospital, Stanford, CA Introduction: The risk of lead e traction of ICD and pacemaker leads is related to the physical properties of the brous process occur at the lead tissue interface. Relatively little is known about the histological changes involved in the brotic process in humans. Methods: Using speci c stains we e amined the histologic changes from brous tissue attached to the e tracted leads in device patients. Mean patient age was 62 / 14 years. All but one patient had leads removed due to infection. Time from lead implantation ranged 6 months to 11 years. Stains included H , Masson’s trichrome, Picrosirius red, and SMA. Scanning electron microscopy was done on select samples. Results: Masson’s trichrome stain showed a collagen rich matri with low cellularity. Pirocirius red with polarized light revealed the parallel arrangement of densely spaced, smaller collagen bers near the lead interface. SMA stain revealed myo broblasts typical of scar formation. S M showed ingrowth into the ICD coils as early as 6 months after implant. Clockwise from left: S M of coil showing tissue ingrowth, S M of smooth interface at lead tip, Picrosirius red with polarized light showing parallel collagen bers, and SMA staining (red) showing myo broblasts with background DNA stain (blue) Conclusions: Myo broblasts are present in e tracted leads, suggesting on going brotic process; Collagen strands within the brous tissue are arranged in a parallel manner, Ingrowth in to ICD coils occurs rapidly, even within 6 months. Insights into the brotic processes may need to new lead designs that decrease lead brosis, facilitating e traction.

PO3-27 TIME INTERVAL BETWEEN FIRST MYOCARDIAL INFARCTION AND IMPLANTABLE CARDIOVERTER DEFIBRILLATOR IMPLANTATION INFLUENCES INCIDENCE OF VENTRICULAR ARRHYTHMIAS Johannes B. van Rees, MD, Joep Thijssen, MD, C. Jan Willem Borleffs, MD, PhD, Sebastiaan R. Piers, MD, Lieselot van Erven, MD, PhD and Martin J. Schalij, MD, PhD. Leiden University Medical Center, Leiden, Netherlands Introduction: After myocardial infarction (MI), cardiac tissue might become arrhythmogenic over time. In post MI patients identi ed as high risk for sudden cardiac death, the effect of elapsed time from rst MI on future ventricular arrhythmias remains unclear. Methods: Data on 776 consecutive post MI patients (63±11 years, 85 male) receiving an implantable cardioverter de brillator (ICD) at the Leiden University Medical Center were prospectively collected. Date of rst MI, rst ventricular arrhythmia triggering ICD therapy (ATP or shock) and mortality were noted. Patients were allocated to two groups according to median interval from rst MI to ICD implantation. Results: Median interval between rst MI and ICD implantation was 7.7 years (IQR 1.2 15.5 years). After ICD implantation, patients were followed for 2.8±2.2 years during which 173 patients (22 ) received appropriate ICD therapy. Cumulative incidence for appropriate ICD therapy after 5 years was 4 ( 5 CI 40 57 ) for patients in who the rst MI occurred > 7.7 years before ICD implantation and 2 ( 5 CI 22 37 ) for patients with a rst MI 7.7 years before ICD implantation (p 0.001; Figure). Median interval between rst MI and rst appropriate ICD therapy was 12 years (IQR 4.7±17. years). Conclusions: In post MI patients receiving prophylactic ICD treatment, a longer time interval between rst MI and ICD implantation was strongly associated with higher incidence of ICD appropriate therapy during follow up.

PO3-28 HEART-TYPE FATTY ACID-BINDING PROTEIN LEVELS PREDICT THE OCCURRENCE OF APPROPRIATE IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR SHOCKS AND CARDIAC DEATH IN CARDIOMYOPATHY PATIENTS Hyuma Daidoji, MD, Takanori Arimoto, MD, Joji Nitobe, MD, Harutoshi Tamura, MD, Mitsunori Ishino, MD, Daisuke Kutsuzawa, MD, Tetsu Watanabe, MD and Isao Kubota, MD. Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan Introduction: The association between ongoing myocardial damage and outcomes in patients who had received an implantable cardioverter de brillator (ICD) is still unknown. To elucidate this, we measured cardiac speci c cytosolic marker (H FABP, heart type fatty acid binding protein) and myo brillar component (troponin T), and analyzed clinical outcomes in

S226 patients with ICD. Methods: We prospectively enrolled consecutive 102 cardiomyopathy patients (mean age, 65±4 years) with ICD. Myocardial membrane in ury [H FABP (>4.3 ng/mL) and myo brillar in ury [troponin T (>0.01 ng/mL) were de ned by the previous researches. Results: istence of myocardial membrane in ury [45/102 (44 ) and myo brillar in ury [41/102 (40 ) were equally observed in cardiomyopathy patients with ICD. Patients were followed up with an end point of appropriate ICD shock and cardiac death for 1035 days. Univariate predictors of cardiac events were New York Heart Association class, H FABP level, use of angiotensin converting enzyme inhibitors / angiotensin II receptor blocker, and use of amiodarone. Serum H FABP level was signi cant independent prognostic factor of cardiac events with multivariate Co regression analysis (Hazard ratio: 1.1 , 5 con dence interval of hazard ratio: 1.01 to 1.40, p 0.036). Conclusions: ngoing myocardial in ury was commonly observed in patients with ICD. valuation of myocardial damage using H FABP may be a promising tool to predict patient’s outcome in cardiomyopathy patients with ICD.

Heart Rhythm, Vol 8, No. 5, May Supplement 2011 function from baseline at 6 months. Secondary endpoints were change in NYHA class, quality of life score and 6 minute walk test (6 MWT) performance. Results: The baseline characteristics were well matched between the two groups. verall, for all patients the mean age was 71 ± 10 yrs, QRS 161 ± 21ms, NYHA III/IV 1 0/13 and F 23 ± 7 . After 6 months of CRT, the optimization group had a better clinical response with lower NYHA class (2.1±0.8 vs. 2.4±0.8, p 0.048) and quality of life scores (35 ± 18 vs. 42 ± 20, p 0.045) but no differences in 6MWT performance (26 ± 110 vs. 277 ± 114m, p 0.81). chocardiographic response was also better in the optimization group with lower LV end systolic volume (108 ± 51 vs. 126 ± 60 ml, p 0.048) and higher e ection fraction (30 ± 7 vs. 27 ± 8, p 0.01) compared to empiric settings. Conclusions: Device optimization using non invasive measures of C is associated with better clinical and echocardiographic response compared to empiric settings. The validity of these ndings need to be con rmed in a large randomized controlled trial.

PO3-30 PROPHYLACTIC IMPLANTABLE CARDIOVERTER DEFIBRILLATOR TREATMENT IN THE ELDERLY: INCIDENCES OF THERAPY, ADVERSE EVENTS AND SURVIVAL GAIN Johannes B. van Rees, MD, C. Jan Willem Borleffs, MD, PhD, Joep Thijssen, MD, Lieselot van Erven, MD, PhD, Suzanne C.. Cannegieter, MD, PhD, Jeroen J. Bax, MD, PhD and Martin J. Schalij, MD, PhD. Leiden University Medical Center, Leiden, Netherlands

PO3-29 CARDIAC RESYNCHRONIZATION THERAPY OPTIMIZATION USING NON INVASIVE CARDIAC OUTPUT MONITORING Fakhar Z. Khan, MRCP, Munmohan S. Virdee, MRCP, John Hutchinson, BSc, Beverley Smith, BSc, Vikrant Nayar, MRCP, Peter J. Pugh, MRCP, David Begley, MRCP, Simon P. Fynn, MRCP and David P. Dutka, MRCP. Addenbrooke’s Hospital, Cardiology, Cambridge, United Kingdom, Papworth Hospital, Cardiology, Cambridge, United Kingdom Introduction: Non invasive cardiac output monitoring (NIC M) based on bioreactance is a reliable method to assess ventricular function and offers a potential alternative for optimization of cardiac resynchronization therapy (CRT) devices. We compared the effect of NIC M based optimization to no optimization (empiric settings) on CRT outcomes in a single centre observational study. Methods: Two hundred and three patients undergoing CRT were assessed in two consecutive non randomized groups. The rst group (n 54) were programmed to out of the bo ’ settings with a ed AV delay of 120ms and a VV delay of 0ms (empiric group). The second group (n 14 ) underwent ad ustments of both the AV and VV delays according to the greatest improvement in resting C (optimization group). The AV delay was initially ad usted in 20ms intervals (range 80 240ms) and the optimal AV delay selected as the one with the greatest C reading. At this optimized AV delay, the VV delay was ad usted in 10ms increments (range 60 to 60ms) to produce the device settings with the greatest acute haemodynamic bene t. The primary endpoints were improvements in LV volumes and

Introduction: Since mortality risk increases with age, the superior effect of prophylactic ICD treatment might be higher in older patients as compared to younger patients. However, elderly are underrepresented in clinical trials which resulted in inconsistent outcome. The aim of the study was to assess the in uence of age on ICD treatment in the elderly. Methods: All patients treated with an ICD for primary prevention of sudden cardiac death at the Leiden University Medical Center from anuary 1 6 to anuary 200 were included and allocated to 3 groups according to age. Data on adverse events, appropriate ICD shocks and all cause mortality were noted. Survival gain was de ned as the time following rst appropriate ICD shock to death. Results: A total of 13 5 consecutive patients received an ICD (63±11 years, 7 male) of which 705 patients (51 ) were aged 65 years, 4 3 patients (35 ) aged 65 74 years and 1 7 patients (14 ) aged 75 years. Mean follow up was 2. ±2.1 years. ver time, the percentage of patients 75 years receiving an ICD increased from 0 ( 2000) to 15 (>2005). Cumulative incidence of appropriate shocks after 5 years was 1 for patients 65 years, 23 for patients 65 74 years and 13 for patients 75 years (p 0.47; Figure). At 1 year following appropriate shock, cumulative incidence for death was 35 for patients 75 years as compared to 7 for patients 65 years (p 0.05). Conclusions: The percentage of ICD implantations in elderly is increasing drastically. But despite e periencing similar rates of appropriate ICD shocks, more than one third of patients 75 years dies within one year after receiving appropriate shocks as compared to only 7 of patients 65 years.

S228 increases cost. Methods: A nationwide, population based historic cohort study was performed based on data from the Danish Pacemaker Register (DPR) which include all Danish patients who received their rst permanent pacemaker (PM) from 1 7 to 2008 (n 28,820). The DPR holds information on patient related factors, technical and procedural speci cations, as well as complications until the rst outpatient visit after 3 months. Multiple logistic regression was used to estimate ad usted odds ratios (a R) for the association between risk factors and pneumothora treated with a chest tube. Results: The nal study population consisted of 27, 35 patients ( 7 ): male patients, n 15,136 (54 ); median age 77.6 years (25th and 75th percentile: 6 .2 83.8); and dual chamber device, n 17,3 (62 ). A total of 184 patients (0.66 ) were treated for pneumothora . The incidence of pneumothora uctuated from year to year (inter year range 0.22 1.18 ), but declined during the study period (p trend 0.03). The risk of pneumothora was 1.2 when using the subclavian vein for venous access, 0.2 when using the cephalic vein, and 0. when using both the subclavian and cephalic vein. Si risk factors were identi ed: female gender (a R 1.8; 5 CI 1.3 2.4), age >80 y (a R 1.4; 5 CI 1.0 2.0), prior history of chronic obstructive pulmonary disease (a R 3.2; 5 CI 1.2 8.8),venous access via the subclavian vein (a R 7.8; 5 CI 4. 12.5), venous access via both the subclavian and the cephalic vein (a R 5.5; 5 CI 2. 10.6), and implantation in a non university center (a R 2.0; 5 CI 1.5 2.7). Conclusions: Pneumothora treated with a chest tube is still a clinically important problem in device therapy. Both patient related and procedure related risk factors are to be taken into account when deciding the device treatment strategy. The cephalic cut down technique should be applied whenever possible.

PO3-34 IMPACT OF CHRONIC KIDNEY DISEASE STAGES ON PREDICTING LONG-TERM RESPONSE TO CARDIAC RESYNCHRONIZATION THERAPY Shinjiro Miyata, MD, Yasuya Inden, MD, Noriko Taguchi, MD, Masaya Fujita, MD, Seihuku Kyo, MD, Naoki Yoshida, MD, Hiromi Kamiya, MD, Tomohiro Uchikawa, MD, Masayuki Shimano, MD, Kazuhisa Kitamura, MD, Yukiomi Tsuji, MD, Makoto Hirai, MD and Toyoaki Murohara, MD, PhD. Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan, Research Institute of Environmental Medicine, Nagoya, Japan, Nagoya University School of Health Sciences, Nagoya, Japan Introduction: Renal dysfunction was shown to in uence the mortality and morbidity in patients with severe heart failure. However the assessment of cardiac resynchronizaton therapy with de brillator (CRT D) implantation for patients with chronic kidney disease (C D) has not been rmly established. The purpose of this study was to assess whether C D stages before CRT D could predict the clinical response to CRT D. Methods: We studied consecutive 73 advanced HF patients who underwent CRT D in our hospital (67±10 years, New York Heart Association (NYHA) class 3.3±0.7, left ventricular e ection fraction (LV F) 28.2±8.4 , QRS duration 164±2 ms, 4 males). The end point was all cause mortality or HF related hospitalization. Results: During a mean follow up of 1452±156 days, 1 deaths (26 ) and 24 HF hospitalization (32 ) were observed. Baseline C D stages were not related to NYHA class and LV F, but related to the higher risk of reaching the composite the end point (Figure 1). Co multivariated analysis showed higher C D stage

Heart Rhythm, Vol 8, No. 5, May Supplement 2011 was an independent positive predictor of the end point (HR: 1.5 , 5 CI: 1.037 2.43 , P 0.033). Conclusions: Baseline C D stages independently predicted long term mortality and HF hospitalization. Renal dysfunction may be one of the risk factors for nonresponse to CRT D.

PO3-35 IMPROVEMENT IN LEFT VENTRICULAR FUNCTION AFTER CARDIAC RESYNCHRONIZATION IS ASSOCIATED WITH SURVIVAL BENEFIT Ammar M. Killu, MBBS, Brian D. Powell, MD, Raul Espinosa, MD, Samuel Asirvatham, MD, Thomas M. Munger, MD, Peter A. Brady, MD, Robert Rea, MD, David O. Hodge, MS, Heather Wiste, BA and Yong-Mei Cha, MD. Mayo Clinic, Rochester, MN Introduction: Cardiac resynchronization therapy (CRT) has been shown to improve heart failure (HF) symptoms and survival. We hypothesized that a greater improvement in left ventricular (LV) function after CRT is associated with greater survival bene t. Methods: In 520 patients who received CRT P or CRT D, the difference in LV e ection fraction ( F) pre and post CRT was determined, and patients were grouped as non/modest , moderate , or super responders to CRT, de ned as a relative change in LV F of 10 , 10 30 and >30 , respectively. Changes in NYHA class, LV diastolic dimension and mitral regurgitation (MR) grade were assessed for each group. Results: There were 1 8 non/modest , 102 moderate and 220 super responders. Baseline characteristics were essentially the same across groups, with no signi cant difference in the number of patients with dilated cardiomyopathy. However, non/modest responders had shorter QRS duration pre CRT (162.0 ± 33.0, 171. ± 32. , 168.3 ± 33.3ms respectively, p 0.034). After CRT, there was a signi cant difference in improvement in NYHA class ( 0.3 ± 0.8, 0.5 ± 0.8, 1.0 ± 0.8, p 0.001), LV end diastolic diameter ( 0.7 ± 4.8, 2.6 ± 4.5, 4.3 ± 7.6mm, p 0.001), and MR grade ( 0.1 ± 0.6, 0.2 ± 0.6, 0.4 ± 0.6, p 0.001) in the non/ modest , moderate , and super responder groups, respectively. aplan Meier survival analysis ( gure) revealed a signi cant difference between groups; super responders achieved better survival compared to non/modest (p 0.001) and moderate responders (p 0.002). Conclusions: Improvement in HF symptoms and survival after CRT is proportionate to the degree of improvement in LV systolic function.

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PO3-38 ANTI-PLATELET THERAOY AND HEMATOMAS AFTER CARDIAC IMPLNATABLE ELECTRONIC DEVICE REPLACEMENT: INSIGHTS FROM THE REPLACE REGISTRY Marye J. Gleva, MD, Richard Holcomb, PhD, Theofanie Mela, MD, Mina K.. Chung, MD, Venketashewar Gottipaty, MD, Richard Borge, MD, Timothy Shinn, MD, Daniel Z.. Uslan, MD, Dan Dan, MD, Kevin Mitchell, RN and Jeanne E.. Poole, MD. Washington Univ School of Medicine, Saint Louis, MO, none, Minneapolis, MN, Massachusetts General Hospital, Boston, MA, Cleveland Clinic Heart and Vascular Institute, Cleveland, OH, South Carolina Heart Center, Columbia, SC, Abington Medical Specialists, Abington, PA, Michigan Heart, Ypsilanti, MI, David Geffen School of Medicine at UCLA, Los Angeles, CA, Cardiac Disease Specialists, Atlanta, GA, Biotronik, Inc, Lake Oswego, OR, University of Washington, Seattle, WA

PO3-36 WOMEN WITH PRIMARY PREVENTION ICD HAVE SIMILAR ARRHYTHMIC DEATH RATES BUT HIGHER MORTALITY RATES THAN MEN Shriti Masrani, MD, Eric Novak, MS, Jane Chen, MD, FHRS, Mitchell Faddis, MD, PhD, Marye Gleva, MD, Timothy Smith, MD, DPHIL, FHRS and Phillip Cuculich, MD. Barnes-Jewish Hospital/Washington University School of Medicine, Saint Louis, MO Introduction: Meta analyses of randomized trials have not demonstrated survival bene t for women with cardiomyopathy who receive an implantable cardioverter de brillator (ICD) for primary prevention of sudden death (SD). This may be due to a lower rate of SD or dissimilar mortality rates in female patients. This retrospective study evaluated the impact of gender on appropriate ICD therapy and mortality. Methods: 525 consecutive patients with ischemic or nonischemic cardiomyopathy underwent ICD implantation for primary prevention of SD. Demographic, comorbid illnesses and medications were evaluated. Mean follow up was 3.8 years. nd points were mortality and appropriate ICD therapy at 4 years. Results: Baseline characteristics of 121 women (23.1 ) were similar to men in regards to age (women 61 years; men 62.5 years), e ection fraction (25 ), comorbidities and medication use. Signi cant differences included race (81 white male vs. 63 white female, p 0.001), tobacco use (63 male vs. 43 female, p 0.001), and prior coronary bypass surgery (50 male vs. 26 female, p 0.001). There were 160 deaths: 47 of 121 women (38. ) and 113 of 404 men (30.0 ). There were 87 appropriate ICD therapies: 18 of 121 women (14. ) and 6 of 404 men (17.1 ). aplan Meier analysis veri ed a signi cant difference in four year survival (p 0.03 ) but no difference in rate of appropriate ICD therapy (see graphs). Conclusions: Women who received an ICD for prevention of SD had a similar arrhythmic event rate as men. However, the impact of primary prevention ICD therapy is attenuated by increased mortality rate in female patients.

Introduction: Hematoma development after cardiac implantable electronic device (CI D) replacement is problematic. Patients treated with anti platelet agents may be at increased risk of hematoma formation. The relationship between antiplatelet therapy (APT) and the incidence of hematomas after CI D generator replacement was evaluated in the R PLAC Registry. Methods: The R PLAC Registry was a large multicenter prospective study that estimated complication rates out to 6 months after CI D replacement with or without a new lead addition. Medications, including aspirin (ASA) and thienopyridines (TP), were collected at enrollment. All complications including hematomas were prede ned, pre speci ed and ad udicated by a blinded clinical events committee. Hematoma event rates for patients on APT were compared to the hematoma event rate for patients on no APT. Patients on warfarin were e cluded. Statistical analysis included Fisher’s act Test and forward stepwise logistic regression with 5 con dence intervals (CI). Results: The R PLAC Registry enrolled 1030 patients who were not on warfarin. Thirty nine of these patients developed a hematoma. The prevalence of anti platelet medication use and the subsequent hematoma rates are shown in the table. Multivariate logistic regression for TP use demonstrated an odds ratio of 2.4 ( 5 CI 1.3, 4.2). APT and Hematomas Anti Platelet Therapy N( )

Hematoma N( )

p value*

None 335 (32.5)

8 (2.4)

ASA only 512 (4 .7)

17 (3.3)

0.54

Thienopyridine only 6 (6.7)

6 (8.7)

0.02

Both 114 (11.1)

8 (7.0)

0.04

*Compared to no APT Conclusions: TP use with or without ASA was associated with at least a two fold increased risk of hematoma formation after CI D generator replacement. ASA use did not increase hematoma rates. These results further re ne patient speci c risks important in planning CI D replacement procedures.

S230 PO3-39 THE HAZARD OF SPRINT FIDELIS DEFIBRILLATOR LEAD FAILURE IS HIGHLY DEPENDANT ON AGE Nicolas Girerd, MD, Emilie Nonin, MD, Elodie Morel, PhD, Carine Flys, MSc, Alina Scridon, MD and Philippe Chevalier, MD, PhD. Louis Pradel Cardiology Hospital, Bron, France Introduction: Medtronic Sprint Fidelis (SF) de brillator leads were removed from the market in 2007 because of a high rate of lead failure. Current data do not allow a risk strati cation of the patients with SF leads. We thus sought to determine the predictors of SF lead failure. Methods: Between 2004 and 2007, 26 SF leads were implanted in 258 patients in our center. Variables associated with lead failure were assessed with the aplan Meier method and Co survival model. Results: During a mean follow up period of 2.4 years (ma imum 5.32), we observed 33 SF lead failures (65.6 ±7.5 5 year survival). In univariate analysis, age was the only signi cant predictor of lead failure (Hazard Ratio [HR for a one year increase 0. 7, 5 Con dence Interval [CI 0. 5 0. , p 0.00 ). Underlying heart disease (p>0.10), e ection fraction (p 0.27), subclavicular approach (p 0.83), ape position (p 0. 7), multiples intravascular leads (p 0.86), type of SF lead (p 0. 8) and lead parameters at implantation (p>0.25 for impedance, detection and pacing threshold) were not signi cantly associated with the risk for SF lead failure. atients 62.5 years old (median of the cohort) had a smaller risk for having lead failure when compared to patients >62.5 (HR 0.36, CI 0.17 0.77, p 0,00 ). Survival without failure was 55.6 ±10.4 in patients 62.5 (24/134 leads) versus 78.6 ±8.8 in patients versus in patients >62.5 ( /135 leads). In the subgroup of available patients 62.5 who still had a functioning lead at 3 years (N 53), 8 failures were recorded between 3 and 5 years resulting in a 3 5 years survival of only 68.2 ±12.3 . Conclusions: SF lead failure is much more frequent in younger patients, rising as high as 15 /year 3 years after implantation. Higher mechanical strain due to higher levels of physical activity in younger patients might e plain this e cess of risk. ur results emphasize the need of a close follow up of younger patients with SF leads, possibly using telecardiology. These data also favor the use of a new lead at the time of the generator replacement even if there is no sign of deterioration. Besides, due to the very high lead failure rate in younger patients, prophylactic e plantation might sometimes appear reasonable.

PO3-40 REFERRING PHYSICIANS’ KNOWLEDGE AND BELIEFS REGARDING PRIMARY PREVENTION IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR GUIDELINES Jorge M. Castellanos, MD, Lisa Smith, MPH, Christine Dehlendorf, MD, Paul Varosy, MD and Gregory Marcus, MD. Cedars Sinai Medical Center, Los Angeles, CA, University of California, San Francisco, San Francisco, CA, University of Colorado Denver School of Medicine, Denver, CO Introduction: Based on evidence from controlled clinical trials, the of cial ACC/AHA/HRS uidelines provide clear criteria that should be used in selecting a patient for consideration of a primary prevention ICD (ppICD). However, it is estimated that less than 20 of Americans that meet these criteria actually receive an ICD. In order to test the hypothesis that referring physicians’ awareness of the guidelines may be important, we sought to determine referring physicians’ knowledge and beliefs regarding the ppICD guidelines. Methods: A national sample of three thousand physicians, 1/3rd

Heart Rhythm, Vol 8, No. 5, May Supplement 2011 each specializing in family practice, internal medicine, or general cardiology, were selected from the American Medical Association master le. ach physician was mailed a 34 question survey and a cash gift. Results: 64 of physicians responded, with equal proportions representing each specialty. 10 (interquartile range 0 35 ) of primary care specialists reported managing patients with a depressed e ection fraction ( F) without referral to a cardiologist. 3 5 (28 ) of all respondents never refer patients with the intent of consideration for a ppICD ( 5 CI 25 30 ). Cardiologists (odds ratio [ R 1. , 5 CI 1.2 2.8, p 0.003), those with more patients over age 60 ( R 1.01, 5 CI 1.01 1.02, p 0.001), and those with an electrophysiologist ( P) in their group ( R 1.7, 5 CI 1.3 2.3, p 0.001) were more likely to refer. 487 (34 ) of all respondents did not believe that an F was suf cient to warrant consideration of a ppICD; independent predictors of this response included family practice specialty ( R 2, 5 CI 1.4 2.8, p 0.001), practice in the Western US ( R 1.5 5 CI 1.1 2.1, p 0.02), and having an P in the same group ( R 0.7, 5 CI 0.5 0. , p 0.00 ). 525 (36 ) reported that an F greater than 40 would be an appropriate cut off for considering referral; family practice physicians and those in the Western US were more likely and those with an P in their group were less likely to have this response. Conclusions: Failure to understand the ICD guidelines is common among a national sample of referring physicians. Understanding the predictors of this phenomenon will be important in targeting efforts to enhance ICD guideline adherence

PO3-41 FAMILIAL ATRIAL FIBRILLATION PREDICTS INCREASED RISK OF MORTALITY: A STUDY IN DANISH TWINS Ingrid E. Christophersen, MD, Esben Budtz-Jørgensen, PhD, Stig Haunsø, MD, DMSc, Jesper Hastrup Svendsen, MD, DMSc and Kaare Christensen, MD, DMSc. Laboratory of Molecular Cardiology, dep 9312, the Heart Centre, Copenhagen University Hospital, Copenhagen Ø, Denmark, Department of biostatistics, Institute of Public Health, University of Copenhagen, 1014 Copenhagen K, Denmark, Laboratory of Molecular Cardiology, dep 9312, the Heart Centre, Copenhagen University Hospital, 2100 Copenhagen Ø, Denmark, Danish Twin Register, Institute of Public Health, University of Southern Denmark, 5000 Odense C, Denmark Introduction: Atrial Fibrillation (AF) is a common arrhythmia with increasing prevalence. The estimated lifetime risk for AF in men and women aged 40 years or older is 25 , and patients with AF have an increased mortality. Studies have shown that the disease is associated with mutations and polymorphisms in several genes modulating the electric properties of the myocardium. pidemiologic studies have shown that parental AF is a risk factor for AF in the offspring, and our group have shown a considerable degree of heritability of AF in a twin study. The ob ective of this study was to compare mortality among twins who had a co twin diagnosed with AF, and twins who had an unaffected co twin. Methods: The Danish Twin Registry holds information on 105.427 Danish twins born between 1 anuary 1870 and 1 anuary 2003. We identi ed 1287 twins diagnosed with AF, by merging the Danish Twin Registry, the National Patient Registry and the Central f ce of Civil Registration. For each twin with AF we identi ed 4 control twins without AF, matched on se , zygosity and age, among the twins who were alive at the time of diagnosis of the AF twin . We compared the survival from birth until end of follow up among the co twins of the AF twins and the co twins of the control twins . Survival of co case twins and co control twins were compared using a strati ed Co regression model to allow for the matched design.

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Results: We identi ed 1287 twins with AF, and included their co twins as co cases . 1208 twin pairs were discordant and 7 concordant. We de ned the twin diagnosed with AF rst, as the case. For these cases we identi ed 5106 controls. The co case twins showed a signi cant increase in death rate compared to the co control twins (HR 1.13, 5 CI: 1.03 1.25, p 0,014). We identi ed lone AF in 42 (33.3 ) cases, de ned as no relevant cardiac , pulmonary or endocrine disease diagnosed before or within two years of onset of AF. There was a small, not signi cant difference in death rates when analyzing twins with lone AF compared to co controls (HR 1.06, 5 CI: 0.87 1.2 , p 0.57). Conclusions: The mortality rate is 13 (3 25 ) higher in persons with a sibling with AF. The effect attenuated to 6 (0 2 ) when only lone AF was analyzed.

PO3-42 ASSOCIATION BETWEEN HEART FAILURE AND LACK OF CONTROL OF ATRIAL FIBRILLATION IN A LARGE INTERNATIONAL OUTPATIENT REGISTRY Oleg J. Zharinov, MD, Jim O’Neil, MD, Lisa Naditch-Brule, MD, José S. Cardoso, MD, Jan Murin, MD, Chern-En Chiang, MD, Philippe G. Steg, MD, RealiseAF Investigators. Cardiology and Functional Diagnostics Dpt, National Medical Academy of Postgraduate Education, Kyiv, Ukraine, Midland Regional Hospital, Dublin, Ireland, sanoÀ-aventis, Paris, France, Porto Medical School, Porto, Portugal, 1 Interna Klinika, Bratislava, Slovakia, National Yang-Ming University and Taipei Veterans General Hospital, Taipei, Taiwan, Inserm U-698, Université Paris 7, Paris, France Introduction: There is continued uncertainty regarding the optimal management strategy for atrial brillation (AF) in patients with heart failure (HF). This analysis aimed to evaluate the frequency of AF control (de ned as either sinus rhythm or being in AF with a heart rate 80 bpm at rest) in the subset of HF patients from the RealiseAF registry. Methods: The RealiseAF registry was an international cross sectional registry of AF including 10,546 patients from 831 sites in 26 countries on 4 continents, with at least one episode of AF documented by electrocardiogram ( C ) or Holter monitoring in the last 12 months. Primary analyses included frequency of AF control and description of cardiovascular risk. Results: Mean age was 66.6±12.2 years, 56.4 of patients were male. AF was paro ysmal in 24.8 , persistent in 22.3 and permanent in 46.4 of patients. The prevalence of HF was 45.8 overall. It was 42.8 among patients with controlled AF vs 51.2 in patients with uncontrolled AF (p 0.001). The likelihood of AF control decreased with worsening functional class (Figure). A rhythm control strategy was chosen in 43.5 of patients without HF, 31.1 of patients with NYHA class II and 22.8 of patients with NYHA class III/IV, while rate control was selected in 50.0 , 65.6 and 73. of patients, respectively. Conclusions: HF is highly prevalent among outpatients with AF and is more frequent among patients with uncontrolled AF. These data indicate an association between lack of AF control, choice of a rate control strategy, and worsening functional status.

PO3-43 CHANGES IN THE ELECTROCARDIOGRAM IN OBSTRUCTIVE SLEEP APNOEA PATIENTS DURING EXPERIMENTALLY INDUCED HYPOPNEA Mathias Baumert, PhD, Rajeev Ratnavadivel, MBChB, Daniel Stadler, BSc, Samantha Windler, BSc, Jana Bradley, BSc, Danzil Paul, BSc, Prashanthan Sanders, MBBS, PhD, Doug McEvoy, MD and Peter Catcheside, PhD. The University of Adelaide, Adelaide, Australia, Adelaide Institute for Sleep Health, Adelaide, Australia Introduction: bstructive sleep apnoea syndrome ( SAS) is associated with increased cardiac morbidity and mortality. The underlying mechanisms are incompletely understood. The aim of this study was to investigate changes in the electrocardiogram during e perimentally induced hypopnea. Methods: SAS patients (respiratory disturbance inde >30 events/hr) receiving continuous positive airway pressure (CPAP) treatment underwent overnight polysomnography. To e perimentally induce hypopnea, individual CPAP levels were repeatedly dialled down to 50 , respectively 75 of the baseline pressure until the patient aroused, or for ma imal 2 minutes. High resolution C (512 Hz, lead II) was continuously recorded throughout the procedure. PR, RR, QRS and QT intervals, P and T amplitudes as well as ST levels were measured 4 times: at baseline, 5s after dialdown, 5s before arousal, and immediately before arousal onset. Results: After CPAP dialdown and independent of the level of dialdown, the PR interval and QT intervals were signi cantly prolonged (p 0.05). The QRS duration was unaffected and the RR interval showed a signi cant biphasic change (see gure). P and T wave amplitudes as well as ST levels were all signi cantly elevated after dialdown. Conclusions: Partial upper airway obstruction leads to signi cant changes in atrial and ventricular electrical activity that might contribute to the increased arrhythmias propensity observed in SAS patients.

S232 PO3-44 LEFT ANTERIOR DESCENDING CORONARY ARTERY FLOW IMPAIRED BY RIGHT VENTRICULAR APICAL PACING: THE ROLE OF SYSTOLIC DYSSYNCHRONY Fang Fang, PhD, Zhi-An Li, PhD, Hai-Yan Li, PhD, Ya Yang, PhD and Cheuk-Man Yu, MD. Chinese University of Hong Kong, Hong Kong, P. R. China, China, Capital Medical University, P. R. China, China Introduction: Right ventricular apical (RVA) pacing may affect the myocardial perfusion; however, it remains unknown whether it is related to systolic dyssynchrony induced by RVA pacing. This prospective study was aimed to assess the role of the dyssynchrony in the coronary ow change. Methods: Forty eight non coronary artery disease patients (62±13yrs, 26 male) with sinus node dysfunction were prospectively enrolled. Coronary ow was evaluated by measuring diastolic velocity time integral (VTI) and duration time at the distal portion of left anterior descending coronary artery (LAD) at baseline and at 3 month follow up. Systolic dyssynchrony was assessed with tissue Doppler imaging by time standard deviation to peak systolic velocity of 12 LV segments, Ts SD, cutoff value 33ms). LV lling pressure was estimated by the ration of mitral wave and septal ’. Results: At 3 month, both LAD VTI (11.6±4.5 vs. 10.6±4.3 cm p 0.01) and duration time (540±50 vs. 510±40 ms, p0.05). Interestingly, only the group who developed systolic dyssynchrony at 3 month had signi cant LAD ow deterioration, but remained unchanged in those without dyssynchrony (Table). The accumulative pacing percentage in the past 3 months ( 0.43), systolic dyssynchrony ( 0.50) and the LV septal / ’ ( 0.41) (all p 0.05) were associated with the LAD VTI. Conclusions: RVA pacing disturbs coronary ow, which might be related to the development of systolic dyssynchrony. This may provide additional evidence of the deleterious effect of RVA pacing.

Heart Rhythm, Vol 8, No. 5, May Supplement 2011 clinical course and management of A T in the contemporary era. ur goal was to determine current management strategies for A T including the role of radiofrequency ablation (RFA). Methods: We conducted a retrospective chart review of pediatric patients with A T diagnosed between anuary 2000 and November 2010 at 6 pediatric centers. Charts were reviewed for patient characteristics, clinical presentation, occurrence of TIC, medical and RFA therapy and patient outcomes. Results: We identi ed 145 patients (8 M/56F). The median age at diagnosis was 7. years (1 day 18.1 years). Patients were followed for a median of 1.7 years (7 days 13.5 years). TIC was observed in 26 of patients. Resolution of A T was achieved in 88 of all patients. A T resolved without medical therapy or RFA in 15 patients. Ninety patients received medical therapy with resolution in 2 . Resolution was achieved in 41/45 on medical therapy alone with a median of 2 drug regimens (1 5) over 10.8 months (11 days 137.7 months). Resolution was achieved in 42/45 receiving medical therapy followed by RFA with a median of 2 (1 10) drug regimens over 20.3 months (1 day 106.3 months). Beta blockers alone were the primary therapy for 45 . These patients were more likely to receive RFA than patients receiving other medication regimens (63 vs. 3 , p 0.05). RFA was attempted 104 times in 78 patients at a median 127 days from diagnosis (1 day 12.4 years) with resolution in 2 . RFA with comple mapping was associated with a higher rate of overall RFA success ( 4 vs. 73 , p 0.05) and a lower rate of recurrence (23 vs. 55 , p 0.01) than RFA with standard mapping. Conclusions: A T is managed successfully in most children in the current era with a larger proportion of patients receiving RFA than in previous series. The use of beta blockers as primary therapy is associated with higher rates of RFA. RFA with comple mapping resulted in better outcomes.

PO3-46 BASAL RIGHT VENTRICULAR ENTRAINMENT IS SUPERIOR TO APICAL ENTRAINMENT IN IDENTIFYING MECHANISM OF SUPRAVENTRICULAR TACHYCARDIA Dhaifallah Y. Yahya, MBChB, Batool Al-Mogheer, MSc, Sherif Gouda, MSc, Essam B. Eweis, MD, Mohamed Z. El Ramly, MD and Amir M. AbdelWahab, MD. Electrophysiology Service, Cardiology Department, Cairo University, Cairo, Egypt

PO3-45 MANAGEMENT OF ATRIAL ECTOPIC TACHYCARDIA IN CHILDREN IN THE CURRENT ERA: A MULTI-CENTER EXPERIENCE Kristopher T. Kang, BA, Susan P. Etheridge, MD, Michal J. Kantoch, MD, Michael S. Schaffer, MD, Bryan C. Cannon, MD, David J. Bradley, MD, Robert J. Hamilton, MD, Svjetlana Tisma-Dupanovic, MD, James E. Potts, PhD and Shubhayan Sanatani, MD, FHRS. University of British Columbia, Vancouver, BC, Canada, University of Utah, Salt Lake City, UT, Stollery Children’s Hospital, Edmonton, AB, Canada, Denver Children’s Hospital, Aurora, CO, Mayo Clinic, Rochester, MN, University of Michigan, Ann Arbor, MI, The Hospital for Sick Children, Toronto, ON, Canada, Children’s Mercy Hospital, Kansas City, MO, British Columbia Children’s Hospital, Vancouver, BC, Canada Introduction: Atrial ectopic tachycardia (A T) is an uncommon cause of supraventricular tachycardia. Due to its incessant nature, A T is a common cause of tachycardia induced cardiomyopathy (TIC). There is limited information regarding the

Introduction: Differentiation between AVNRT and AVRT can be sometimes challenging. Apical right ventricular (RV) entrainment can help in differentiation, however it has some fallacies. We thought to compare the accuracy of basal RV entrainment to RV apical entrainment in identifying the mechanism of SVT. Methods: 42 consecutive patients with SVT undergoing catheter ablation were prospectively studied. Apical RV entrainment was performed 20 ms faster than tachycardia cycle length (TCL) initially followed by basal entrainment from the anterosepatal basal RV avoiding His or atrial capture. Postpacing interval (PPI), PPI TCL, corrected PPI TCL and Stim A minus VAwere measured. Results: ntrainment was achieved from both sites of RV in 34 patients (10 men; mean age: 42 ±15 years), 20 with typical AVNRT, 1 with atypical AVNRT, and 13 with AVRT (8 left sided, 4 right sided, and 1 septal APs). PPI TCL, cPPI TCL and SA VA were signi cantly longer with basal entrainment in AVNRT (171±30 vs 153±22 ms (p 0.003), 148±21 vs 131±20 ms (p 0.002) and 145±17 vs 136±15 ms (p 0.005) respectively). Receiver perator Charecteristic (R C) curves showed higher AUC for the above parameters with basal entrainment compared to apical entrainment ( gure). Basal PPI TCL>110 ms had a sensitivity of 100 and a speci city of 84 for diagnosis of AVNRT. Basal cPPI TCL> 5 ms had a sensitivity of 100 and a

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speci city of 3 for diagnosis of AVNRT. Basal SA VA>105 ms had a sensitivity of 100 and a speci city of 3 for diagnosis of AVNRT. Conclusions: Basal RV entrainment from the anteroseptal basal RV is a simple maneuver that is superior to apical ventricular entrainment in identifying the mechanism of SVT.

lacking or limited. The proportion of SPA out of the total SVT related procedures was 2 10 in 73 and >10 in 16 . Diagnostic maneuvers were uniform in terms of catheters used, stimulation and pharmacologic provocation protocols. The threshold for performing SPA in the presence of non inducible SVT was higher for non documented versus documented SVT: no DNP 0 will ablate with non documented versus 5 with documented SVT (p NS); DNP without echo 5 versus 20 (p 0.05); DNP and echo 32 versus 44 (p NS); DNP and 2 echo beats or inducible SVT 64 versus 31 (p 0.017). Signi cant factors in favor of SPA were longer time in practice (r 0.38, p 0.017) and a smaller perceived complication rate (r 0.31, p 0.057). Statistically non signi cant factors were: longer waiting lists (r 0.15, p 0.38); number of procedures booked per day (r 0.11, p 0.51) and type of reimbursement (p 0.24). Initial ablation energy and temperature settings were variable (range 30 60 W; 50 65 C°). 88 of the responders would use lower energy for empiric ablation versus proven tachycardia. Clinical success of SPA, de ned as net bene t to patients, was felt to have occurred in 20 8 (median 80 ) with 1 complication rate. Conclusions: The practice of SPA in cases of non inducible but suspected or documented SVT is highly variable. In absence of an evidence based approach the documentation of arrhythmia was crucial in making a nal decision for SPA. The tendency to ablate empirically is in uenced by the operator’s e perience and complication rate.

PO3-48 PARTICIPATION OF THE LEFT ATRIUM IN ATRIOVENTRICULAR NODAL REENTRANT TACHYCARDIA ASCERTAINED BY THE ANALYSIS OF DUAL CORONARY SINUS POTENTIALS

PO3-47 IS THERE CONSENSUS ON EMPIRIC SLOW PATHWAY ABLATION? INSIGHTS FROM A CANADIAN SURVEY OF ELECTROPHYSIOLOGISTS Avishag Laish-Farkash, MD, PhD, Mohammed Shurrab, MD, Florence Morriello, MD, Irving Tiong, MD, Atul Verma, MD, Guy Amit, MD, PhD, Sheldon Singh, MD, David Birnie, MD, Jeff Healey, MD, Ilan Lashevsky, MD, David Newman, MD and Eugene Crystal, MD. Schulich Heart Centre, Sunnybrook Health Sciences Center, Toronto, ON, Canada, Southlake Regional Health Center, Newmarket, ON, Canada, Soroka University Medical Center, Beer Sheva, Israel, University of Ottawa Heart Institute, Ottawa, ON, Canada, Hamilton Health Sciences, Hamilton, ON, Canada Introduction: Dual nodal physiology (DNP) is a frequent nding in patients with non inducible symptomatic SVT (suspected or documented). mpiric slow pathway ablation ( SPA) is one of the treatment options in these patients. The practice of SPA in the adult population is unknown. We evaluated practices of SPA by Canadian adult electrophysiologists. Methods: A web based questionnaire addressing Canadian adult electrophysiologists. perator e perience, ablation energies, reimbursement models, diagnostic and treatment decisions during electrophysiological study were assessed and based on case scenarios. Results: 41 out of 81 electrophysiologists (50 ) responded. 5 of the responders agreed that the evidence for SPA is

Yoshiaki Kaneko, MD, PhD, Tadashi Nakajima, MD, PhD, Tadanobu Irie, MD, Toshimitsu Kato, MD, Takafumi Iijima, MD, Mio Tamura, MD, Hiroaki Kobayashi, MD, Akihiro Saito, MD, Toshio Ito, MD, Mamoru Manita, MD, PhD and Masahiko Kurabayashi, MD, PhD. Dept Medicine & Biological Science, Gunma Univ Graduate School of Medicine, Maebashi, Gunma, Japan Introduction: The participation of the left atrium (LA) in the critical reentry circuit of atrioventricular nodal reentrant tachycardia (AVNRT) remains controversial. The activation sequence (ACTS) of dual potentials (DP) recorded from the coronary sinus (CS), which consist of a) near eld CS musculature potentials (MP), and b) separate far eld LA electrograms, suggests that conduction between right atrium (RA) and LA (i.e. LAACSMP sequential activation), re ects the activation of LA via Bachmann’s bundle, the interatrial septum, or both, followed by activation of the CSM, whereas a CSMPALA sequence re ects the activation of at least the inferior LA via the CSM. Methods: We analyzed the ACTS of DPCS in 62 patients with slow fast (c AVNRT) and 11 patients with fast slow or slow slow (u AVNRT) during a) tachycardias, and b) right ventricular (RV) and RA burst pacing at a cycle length shorter than the tachycardia. The ACTS of DPCS during c AVNRT was ascertained by uncovering the ventricular electrogram with single ventricular e trastimulation or entrainment pacing. Results: In 32 patients e hibiting a CSMPALA sequence during c AVNRT, the ACTS during RA pacing was the same (CSMPALA) in 14, and reversed (LAACSMP) in 6 patients, while during RV pacing the ACTS was the same as during c AVNRT (CSMPALA) in 20, and reversed (LAACSMP) in a single patient. In 10 patients e hibiting a LAACSMP ACTS during c AVNRT, the ACTS was identical (LAACSMP) in 4, and reversed (CSMPALA) in 4 patients during RA pacing, whereas

S234 during RV pacing, the ACTS was identical (LAACSMP) in 2, and reversed (CSMPALA) in 5 patients. During u AVNRT, observed in 5 patients, the ACTS of DPCS was e clusively in the CSMPALA direction. Conclusions: LA is not involved in the critical reentry circuit in the ma ority of c AVNRT, perhaps because of a) ed conduction block, b) tachycardia dependent RAALA conduction delay, or c) block across Bachmann’s bundle, the interatrial septum or both, during c AVNRT. However, the LA might be involved in the critical reentry circuit in a minority of c AVNRT, in which a fast pathway e its to the LA retrogradely during tachycardia. In some u AVNRT, the slow pathway is not connected to the LA.

PO3-49 TACHYARRHYTHMIA CHARACTERISTICS AND RESULTS OF CATHETER ABLATION IN PATIENTS FOLLOWING A SURGICAL ATRIOTOMY: IMPORTANCE OF CAVOTRICUSPID ISTHMUS ABLATION Miyako Igarashi, MD, Hiroshi Tada, MD, Yukio Sekiguchi, MD, Hiro Yamasaki, MD, Kenji Kuroki, MD, Takeshi Machino, MD, Yoshihisa Naruse, MD, Yoko Ito, MD, Emi Nakano, MD, Fusanori Kunugida, MD, Takashi Kaneshiro, MD, Kentaro Yoshida, MD, Keisuke Kuga, MD and Kazutaka Aonuma, MD. University of Tsukuba, Tsukuba, Japan Introduction: A variety of supraventricular tachyarrhythmias may occur in patients after undergoing a surgical atriotomy, which may require a repeat ablation procedure for the appearance of a new arrhythmia that had not been previously found. However, few studies have e amined the time course and characteristics of the arrhythmias after cardiac surgery or the role of linear ablation of the cavo tricuspid isthmus (CTI) for atrial utter (CTI AFL) in those patients. Methods: Radiofrequency catheter ablation (RFCA) using an electro anatomical mapping system (CART ) was performed in 23 patients with arrhythmias after a surgical atriotomy ( women; 44±18 years; congenital heart disease 17, valvular disease 5, and dilated cardiomyopathy 1). The clinical course and results of the ablation were evaluated. Results: The mean duration from the surgical atriotomy to the rst ablation procedure was 14.8±12.4 years. In 6 out of 7 patients (85.7 ) who underwent a linear ablation at the CTI for CTI AFL, an atriotomy scar related AT occurred 20.5±16.4 months later. Conversely, in a patient who had undergone RFCA for a scar related AT, common AFL occurred 6 months later. n the other hand, dual loop atrial tachycardias (ATs) that included a CTI AFL combined with reentry related to the atriotomy scar were identi ed in 5 patients. In another 5 patients, a CTI AFL and scar related AT both presented clinically and were induced during the procedure. In those 10 patients, linear lesions were created from the scar to the inferior vena cava (Scar IVC) and at the CTI. In the remaining 5 patients who had scar related ATs or common AFL, linear lesions were created at the Scar IVC and CTI simultaneously. In the patients who underwent RFCA in only 1 region (scar related site or CTI; n 8), 7 (87.5 ) had AT recurrences. However, in the patients who underwent RFCA at both the scar related site and CTI (n 15), only 3 had recurrences (20 , p 0.01). Conclusions: After a surgical atriotomy, CTI AFL occurred frequently (78 ), even after the ablation of a Scar AT. Catheter ablation at both the CTI and isthmus of the Scar AT may be indispensable for a cure.

Heart Rhythm, Vol 8, No. 5, May Supplement 2011 PO3-50 ELECTROANATOMICAL MAPPING AND TEMPERATURE MONITORING OF THE ESOPHAGUS IN CIRCUMFERENTIAL PULMONARY VEIN ISOLATION Xiao qing Liu, MD, Xu Zhou, MD, Yanbin Li, MD, Gang Yang, MD and xinchun Yang, MD. Beijing Chaoyang Hospital, Beijing, China Introduction: During left atrial (LA) catheter ablation, an atrioesophageal stula can develop as a result of thermal in ury of the esophagus during ablation along the posterior LA. No studies have e amined the relationship of the lumen temperature of esophagus and the distance between the esophagus and the posterior wall of LA. ur study was to designed to demonstrate it and to describe a new method to avoid in uring of esophagus. Methods: A virtual reconstruction of the geometry of the esophagus was produced using an electroanatomical mapping system and a specially designed catheter in 20 consecutive patients undergoing circumferential pulmonary vein isolation. The course of the esophagus, its pro imity to the predicted lines of application of radiofrequency energy to the left atrium and its inner side temperature were evaluated. Results: 14 (55 ) were located centrally (i.e. >10 mm from the ostium), 5 (30 ) laterally (i.e. 10 mm from the ostium) and 1 (5 ) obliquely. No movements larger than 5 mm occurred during the procedure. Three typies of lesion points on the posterior wall could be disdinguished according to their monitored temperature in different areas. The temperature of typeIlesion increased rapidly to 38.5°C within 30 seconds during delivery of radiofrequency energy. TypeII lesion increased more slowly than typeI,never e ceeded 38.5°C in 60 seconds. And no obvious changes were observed in type III lesion. The distances were measured between the esophagus geometry to the posterior wall of LA labeled with the lesion points. The distance of typeIlesion was 7.0±1.0 mm, type II 11.1±4.0 mm, type III 18.5±10.7mm (P 0.001). Conclusions: sophageal 3D geometry provides the e act location of the esophagus during CPVI in a simple and well tolerated way. According to the distances between the esophagus to the posterior wall we can stratify the ablation risk to avoid in uring esophagus. We can change the course of the ablation lines to bring them further from the esophagus and reduce the power of ablation in the dangerous areas. Consequently, electroanatomical mapping and temperature monitoring of the esophagus can be a helpful and easy method to avoid atrioesophageal stula in CPVI.

PO3-51 ADENOSINE TRIPHOSPHATE - INDUCED ATRIAL FIBRILLATION: THE CLINICAL SIGNIFICANCE AND RELEVANCE TO CLINICAL ATRIAL FIBRILLATION Susumu Tao, MD, Yasuteru Yamauchi, MD, Shingo Maeda, MD, Hiroyuki Okada, MD, Toru Obayashi, MD and Mitsuaki Isobe, MD. Musashino red cross hospital, Tokyo, Japan, Tokyo Medical and Dental University, Tokyo, Japan Introduction: Adenosine triphosphate (ATP) is useful to unmask the left atrium pulmonary vein (PV) dormant conduction after PV isolation, and sometimes induce atrial brillation (AF). However, clinical signi cance of ATP induced AF is less understood. So we prospectively investigated the incidence of AF induced by ATP and the relevance between spontaneous AF and ATP induced AF. Methods: We performed PV isolation to 81 patients with AF (64 with paro ysmal AF, and 17 with persistent AF), and accessory pathway ablation to 44 patients with atrioventricular reciprocating tachycardia (AVRT). Before PV isolation, we searched triggering

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site of spontaneous AF. Then we in ected ATP 20mg and investigated triggering site of ATP induced AF. In patients with AVRT, we in ected ATP 20mg after successful accessory pathway ablation. Results: In 24 (2 .6 ) of 81 patients with AF, AF was provoked by ATP in ection. ctopic beats triggering AF originated from PV in 22 patients and from right atrium in 2 patients. Moreover, in 13 (54.2 ) of 24 patients with ATP induced AF, spontaneous AF were also documented to arise from the same triggering site as ATP induced AF. In 48 patients (5 .3 ), only ectopic beats were documented by ATP in ection, and in 13 (27.1 ) of them spontaneous AF arose from the same site as ATP induced ectopic beats. Inversely, among 34 patients whom spontaneous AF initiation was documented, AF was provoked by ATP from the same site as spontaneous AF in 14 patients(41.2 ), and similarly only ectopic beats were provoked in 13 patients(38.2 ). In only 2 (4.5 ) of 44 patients with AVRT, AF was provoked by ATP in ection. Conclusions: ATP induced AF is strongly associated with clinical AF, and ma ority of ATP induced AF originate from PV. ATP in ection is useful to identify arrhythmogenic PV.

PO3-52 THERAPY DIRECTED AT STRETCH REDUCES THE FREQUENCY OF CLINICAL ATRIAL FIBRILLATION: A LONG TERM STUDY IN PATIENTS WITH MITRAL STENOSIS John Roshan, MD, Purendra K. Pati, MD, George Joseph, MD, Sunil Chandy, MD, Jacob V. Jose, MD, Paul V. George, MD, Oommen K. George, MD, Prashanthan Sanders, MD, PhD and Bobby John, MD, PhD. Christian Medical College Vellore, Vellore, India, Royal Adelaide Hospital, Adelaide South Australia, Australia Introduction: Atrial brillation[AF is a common sequel to untreated rheumatic mitral stenosis [MS . Atrial remodeling in MS is associated with left atrial (LA) enlargement, loss of myocardium and scaring with widespread and site speci c conduction abnormalities. We have recently demonstrated that balloon mitral valvotomy [BMV is associated with immediate and late atrial reverse remodeling. However, it is unknown if this translates to long term decrease in the incidence of AF. Methods: We studied 446 patients (Mean age:33 ± .5 years ; 163 Male ) with severe MS [mitral valve area(MVA) less than 1.2cm2 in sinus rhythm who underwent a successful BMV and were followed up for 1 14 (mean 8.46 ± 3) years. The LA size, mitral valve score (MVS), pulmonary artery pressure (PAP), mitral valve area (MVA) were measured before and immediately after BMV. chocardiographic parameters were repeated at follow up. Results: Following BMV, 35 patients remained in sinus rhythm while 87[1 .5 patients developed AF. Patients who developed AF were at baseline,older [34.74 ± .27 vs 30. 6 ± .8,p .001 , had longer duration of symptoms[48.5 vs 34.4 months p .007 , larger left atrial size [48.57 ± 7 vs 44.08 ± 6.5mm in parasternal long a is view on echocardiography p .0001 , higher MVS [7.8 ± 1.5 vs 7.25 ±1.42 p .002 , higher pulmonary artery pressures [40.84 ± 15.48 vs 33.71 ± 15.3 p .001 , severe tricuspid regurgitation [p .005 and smaller MVA [.77 ± .17 vs .83 ± .1 p .01 . Additionally, the post procedure MVA was smaller [1. ± 0.26 vs 2 ± 0.28, p 0.002 and at follow up they had larger LA dimension [50 ± 6 vs 44 ± 5.7 p .0001 and higher restenosis rate [18.5 vs .05 p 0.0001 . Multivariate logistic regression analysis identi ed duration of symptoms [p .01 , New York Heart Association[NYHA class at presentation [p .02 , LA size at presentation [p .01 and at follow up [p .0001 as predictors of AF. Conclusions: BMV has reduced the incidence of AF [1 .5 , 5 Con dence Interval 15.84 23.1 when compared

to reported series [40 of patients with similar baseline characteristics who were not sub ect to the intervention. Patients with longer duration of symptoms, higher NYHA class and larger LA at presentation were more likely to develop AF despite the intervention.

PO3-53 HETEROGENEITY IN ATRIAL REFRACTORINESS PREDICTS CAVOTRICUSPID ISTHMUS-DEPENDENT ATRIAL FLUTTER DURING ATRIAL FIBRILLATION ABLATION Michael M. Shehata, MD, Tong Liu, MD, PhD, Jaime Molden, MD, Allen Amorn, MD, Xiushi Liu, MD, Sumeet S. Chugh, MD, FHRS and Xunzhang Wang, MD. The Heart Institute, CedarsSinai Medical Center, Los Angeles, CA Introduction: Particularly in patients undergoing radiofrequency ablation (RFA) for atrial brillation (AF), a simple test to determine need for pre emptive cavotricuspid isthmus atrial utter (AFL) ablation would be of signi cant utility. We hypothesized that the occurrence of AFL is dependent on a critical difference in atrial effective refractory period (A RP) between the high right atrial septum (HRAS) and the coronary sinus ostium (CS ), in contrast to AF that may result in more uniform shortening of A RP at the 2 sites. Methods: We prospectively studied 61 consecutive patients (mean age 60±12 yrs, male 85 ) referred for RFA of AF or AFL. Patients were divided into three groups according to a history of AFL ablation and the atrial arrhythmias encountered during RFA: roup 1: Patients for AF RFA with inducible AFL or previous ablation for AFL (n 15); roup 2: Patients for AF RFA without inducible AFL and no previous ablation for AFL (n 21); roup 3: Patients for AFL RFA without inducible AF or a previous history of AF (n 25). Programmed stimulation was performed following RFA to obtain A RP at the HRAS and CS with pacing at twice the diastolic threshold with a single drive cycle length of 500ms. Results: There were no signi cant differences in se , age, left atrial diameter and left ventricular e ection fraction among the three groups. There were signi cant differences in the absolute delta A RP [(HRAS RP) (CS RP) among the three groups. The delta A RP in roup 1 was higher than roup 2 (47±14 vs. 18±16 ms, p 0.001), and there was no difference compared with roup 3 (47±14 vs. 33±24 ms, p 0.06). Compared with roup 2, roup 3 also had higher values of delta A RP (33±23 ms and 18±16 ms, p 0.001). A delta A RP greater than 30 ms appeared predictive of the presence or history of typical atrial utter. Conclusions: AFL was associated with a critical heterogeneity of A RP between the HRAS and CS not observed in AF only patients. This may constitute a simple test for decision making regarding pre emptive cavotricuspid isthmus ablation in patients undergoing RFA for AF.

PO3-54 REGIONAL ATRIAL SUBSTRATE REMODELING OF THE RIGHT ATRIUM IN ATRIAL FIBRILLATION PATIENTS MAY RESULT IN SINUS NODE DYSFUNCTION Hung-Yu Chang, MD, Yenn-Jiang Lin, MD, Li-Wei Lo, MD, Shih-Lin Chang, MD, Yu-Fung Hu, MD, Kazuyoshi Suenari, MD, Cheng-Hung Li, MD, Tze-Fan Chao, MD, Shuen-Hsin Liu, MD, Beny Hartono, MD, Ambrose Kibos, MD and Shih-Ann Chen, MD. Cheng-Hsin General Hospital, Taipei, Taiwan, Veterans General Hospital-Taipei, Taipei, Taiwan Introduction: Previous study showed the poor right atrial substrate is observed in sinus node (SN) dysfunction patients. It remained unclear that if regional atrial substrate of certain area

S236 of the right atrium (RA) in patients with AF may relate to the SN dysfunction. Methods: The study consisted of 23 consecutive patients (56±10 y/o, 14 males) who underwent catheter ablation for symptomatic paro ysmal AF. All antiarrhythmic drugs were discontinued for at least 5 half lives before procedure. lectroanatomic maps (NavX, St ude, USA) during sinus rhythm were performed in the right atrium (mean mapping sites 222±71). Sinus node dysfunction was de ned as corrected sinus node recovery time (CSNRT) longer than 550 msec with different pacing cycle length 500, 450, 400 and 300 ms. Regional atrial substrate analysis (voltage, total activation time, and refractory period) of the RA was investigated in patients with ( roup 1) and without SND ( roup 2) Results: The mean bipolar voltage of the entire RA, total activation time, and atrial refractory period were similar between 2 groups. Regional analysis showed that the mean bipolar voltage of the SN region (within 1cm diameter of the earliest activation site of sinus rhythm, average mapping sites 11±4) had a lower bipolar voltage in roup 1 (1.11±0.3 vs 2.1±0.7 mV, p 0.02). In contrast, the electrogram properties during SR were similar in the other anatomic regions of the RA between 2 groups. Conclusions: In AF patients, only atrial remodeling near the SN origin of the RA was associated with the SN dysfunction.

Heart Rhythm, Vol 8, No. 5, May Supplement 2011 Results: Four pts met inclusion criteria (age 54±5, 3 men). All recorded AF episodes were longer than 6 hr. Mean AFR was 2 0±21 fpm during the 1st hr and 320±37 fpm during 6th hr (p 0.05). In all pts, AFR increased during the rst 3 hrs of AF and then reached a plateau during the 4th to 6th hrs (see e ample in Fig A). Fig B shows AFR normalized to the mean values of AFR during the plateau phase (4 6 hr) in all 4 patients. Conclusions: We provide rst in human evidence on the time course of electrical remodeling during spontaneous AF paro ysms. AFR acceleration occurs during the initial three to four hrs and then reaches a plateau, which may have implications for the interpretation of AFR values early in the course of AF.

PO3-56 THE IMPACT OF RADIOFREQUENCY ABLATION AROUND RIGHT PULMONARY VEIN AND SUPERIOR VENA CAVA ON AUTONOMIC NERVE FUNCTION Shinsuke Iwai, MD, Junichi Nitta, MD, PhD, Kensuke Ihara, MD, Akira Sato, MD, Miki Kanoh, MD, Mitsutoshi Asano, MD, Kenichi Muramatsu, MD, Tsunehiro Yamato, MD, Yutaka Matsumura, MD, PhD, Kazuyasu Takei, MD, Kihiro Asakawa, MD and Mitsuaki Isobe, MD, PhD. Saitama Red Cross Hospital, Saitama, Japan, Tokyo Medical and Dental University, Tokyo, Japan

PO3-55 ATRIAL FIBRILLATORY RATE ACCELERATES DURING FIRST HOURS OF SPONTANEOUS ATRIAL FIBRILLATION: FIRST IN HUMAN EVIDENCE OF THE TIME COURSE OF ELECTRICAL REMODELING USING IMPLANTABLE LOOP RECORDER Pyotr G. Platonov, MD, PhD, Martin Stridh, PhD, Mirko De Melis, PhD, Lubos Urban, MD, Jonas Carlson, PhD, Giorgio Corbucci, PhD and Fredrik Holmqvist, MD, PhD. Skåne University Hospital and Center for Integrative Electrocardiology at Lund University (CIEL), Lund, Sweden, Center for Integrative Electrocardiology at Lund University (CIEL), Lund, Sweden, Medtronic BRC, Maastricht, Netherlands, The National Institute of Cardiovascular Diseases, Bratislava, Slovakia Introduction: Atrial brillatory rate (AFR) can predict outcome of therapeutic interventions for atrial brillation (AF), however AFR behavior at initiation and during the rst hours of spontaneous AF episodes have been reported only in e periment and during induced AF in humans. The aim of our study was to assess AFR during spontaneous AF episodes in pts with paro ysmal AF. Methods: Consecutive pts with paro ysmal AF (n 14, age 57±7, 12 men) received implantable loop recorder (ILR) for AF detection (Reveal XT, Medtronic). ne month after implantation, C monitoring was initiated with a dedicated Holter communicating with ILR and storing 46 hr ILR C through telemetry. The Holter C was reviewed for the presence of AF 1 hr with AF onset captured. AFR was measured in brillations per minute (fpm) using spatiotemporal QRST cancellation and time frequency analysis. Mean AFR per 10 min and per 1 hr were then used for analysis of AFR behavior.

Introduction: It is well known that radiofrequency catheter ablation (RFCA) around pulmonary veins (PVs) modi es the autonomic nerve function. However, the different effect on the heart rate variability (HRV) in the different RFCA regions around the left atrium is still unclear. This study assessed the relation between HRV after RFCA of atrial brillation (AF) and the ablated sites. Methods: ne hundred and eleven patients who underwent RFCA of AF ( 2males, age 58.7±11.1) were included. PV isolation was performed for only the left PVs in 21 patients ( roup I), and for the right PVs with/without the LPVs in 67 patients ( roup II). The other 23 patients underwent superior vena cava(SVC) isolation in addition to the RPV isolation with/ without the LPV isolation ( roup III). HRV was analyzed using 24 hour Holter monitoring performed on average 4 (early period) and 17 months (late period) after the RFCA. Mean heart rate (MHR), time domain (standard deviation of NN intervals (SDNN)) and frequency domain (low frequency (LF), high frequency (HF) and LF/HF ratio) were estimated. These parameters were also compared with those of 50 age and gender matched normal sub ects (Control group). Results: There was no signi cant difference in HRV between the group I and control group. The group II had higher MHR and signi cant decrease in SDNN(p 0.005) and LF(p 0.04) as compared to the group I. Moreover, the group III had even higher MHR(p 0.04) and lower SDNN(p 0.005) than the group II. Signi cantly lower LF/HF ratio was seen in the group III than group I(p 0.002) and group II(p 0.001). In the group II, there was no difference in HRV between the patients that underwent the LPV isolation and those who did not. In the group I, there was no change about HRV between early and late period. In contrast, the roup II and III showed signi cant, but not

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complete recovery of HRV. Conclusions: PV isolation for the RPVs induced a signi cant reduction in the autonomic nerve function, and the additional SVC isolation further suppressed the autonomic nerve function especially in the sympathetic tone. n the other hand, RFCA around the LPVs had little effect on HRV. These alterations in HRV tended to continue over a year.

PO3-57 INCIDENCE AND SIGNIFICANCE OF EARLY RECURRENCES ASSOCIATED WITH DIFFERENT ABLATION STRATEGIES FOR AF: INSIGHTS FROM THE MULTICENTRE STAR AF TRIAL Laurent Macle, MD, Paul Khairy, MD, Jason Andrade, MD, Yaariv Khaykin, MD, Roberto Mantovan, MD, Giuseppe De Martino, MD, Jian Chen, MD, Carlos A. Morillo, MD, Paul Novak, MD, Vittorio Calzolari, MD, Peter G. Guerra, MD, Girish Nair, MD, Esteban G. Torrecilla, MD and Atul Verma, MD. Montreal Heart Institute, Montreal, QC, Canada, Southlake Regional Health Center, Newmarket, ON, Canada, Ospedale Regionale di Treviso, Treviso, Italy, Casa di Cura Santa Maria, Bari, Italy, Haukeland University Hospital, Bergen, Norway, Hamilton Health Centre, Hamilton, ON, Canada, Royal Jubilee Hospital, Victoria, BC, Canada, Hospital General Universitario Gregorio Maranon, Madrid, Spain Introduction: arly recurrences ( R) are common after catheter ablation for AF, yet the impact of different ablation strategies is unknown. Data on R associated with three different ablation approaches was prospectively collected in the multicentre STAR AF trial. Methods: The STAR AF trial randomized 100 patients with paro ysmal or persistent AF to ablation of comple fractionated electrograms (CF ) alone, pulmonary vein isolation (PVI) alone, or PVI CF . Patients were followed for 12 months. R was de ned as any recurrence of AF, atrial tachycardia, or utter (AT/ AFL) >30 sec during the rst 3 months. Late recurrence (LR) was de ned as any recurrence of AF, AT/AFL >30 sec between 3 and 12 months. Results: Forty nine patients (4 ) e perienced R (3 AF; 10 AT/AFL). R rates were similar with PVI vs PVI CF (43. vs 41.3 , P 0.83). In contrast, a trend towards higher R rates was noted with CF alone vs PVI with or without CF (63.3 vs 42. , P 0.06). No signi cant predictor of R was identi ed. Thirty three of 4 (67 ) patients with R and 16 (31 ) of 51 patients without R had LR (P 0.0001; Figure 1). Among patients with R, the type of arrhythmia (AF vs AT/AFL) was not predictive of LR. In contrast, in those with R, CF alone was associated with a higher risk of LR (8 .5 vs 53.3 , P 0.01). Conclusions: R is common following any AF ablation strategy, with non signi cantly higher rates if PVI is not performed. R is strongly associated with LR, particularly with CF alone, as only 10 remain arrhythmia free during long term follow up.

PO3-58 SOMATIZATION IS ASSOCIATED WITH SYMPTOM SEVERITY IN ATRIAL FIBRILLATION Anil Gehi, MD, Neeta Goli, BS, Samuel Sears, PhD, Eugene Chung, MD, Kathryn Wood, PhD, Jennifer Cohen, MD, Kimberly Guise, MSN, ACNP, Jennifer Walker, MSN, ACNP and J. Paul Mounsey, MD, PhD. University of North Carolina at Chapel Hill, Chapel Hill, NC, Eastern Virginia Medical School, Norfolk, VA, East Carolina University, Greenville, NC, Duke University, Durham, NC Introduction: Somatization, referring to a personal tendency to magnify the presentation of physical complaints as a result of health an iety, has been associated with increased medical costs and worsened health outcomes. We e amined the effects of somatization on atrial brillation (AF) symptom presentation in outpatient AF patients (pts). Methods: In 158 pts with AF presenting to an P clinic, questionnaires regarding their general health and well being, including the Toronto AF Symptom and Severity Checklist (AFSS) and the Whitely Inde , a 14 item screening tool for somatization (e.g. pts asked Are you afraid of illness? ) were completed. The association between somatization and AF symptom severity, ad usting for potential confounders, was assessed using analysis of covariance. Results: Among 158 pts, mean age was 61.2 yrs, 65.8 of pts were male, 87.5 Caucasian, and AF was paro ysmal in 46 . Comorbidities included HTN (52.6 ), DM (1 .7 ), CHF(15.8 ), and previous MI(5.3 ). Whitely Inde (scored 0 14, mean 3.8) was subdivided into three categories: 2 (no somatization, n 61), 3 6 (possible somatization, n 67), 7 (probable somatization, n 30). Unad usted AFSS symptom severities for the 3 groups were .6, 14.5, and 18.6, respectively (p 0.0001). After ad usting for potential confounders (age, gender, persistent vs. paro ysmal AF, HTN, DM, AF burden, smoking), Whitely scores were 11.1, 14.3, and 17. , respectively (p 0.0022) (Fig). Conclusions: In AF patients, worsened somatization was associated with increased severity of AF symptoms. Clinical attention to the effects of this type of health an iety is needed to improve chances of patient relief of AF symptoms.

PO3-59 ATRIAL FIBRILLATION IN INDIGENOUS AUSTRALIANS: RACE SPECIFIC DIFFERENCES Christopher X. Wong, MBBS, Yi Han Cheng, No Degree, Michelle T. Sun, No Degree, Dennis H. Lau, MBBS, Darryl P. Leong, MBBS, Anthony G. Brooks, PhD, Nicholas J. Shipp, PhD, Muayad Alasady, MBBS, Han S. Lim, MBBS, Hany S. Abed, MBBS and Prashanthan Sanders, MBBS, PhD. Royal Adelaide Hospital, Cardiovascular Research Centre, Dept of Cardiology, Adelaide, Australia

S238 Introduction: The prevalence of atrial brillation (AF) varies according to race. Information on differing disease burdens in racial groups is important in helping clinicians monitor, evaluate and manage these patients. Furthermore, such information may yield important insights into the pathogenesis of AF. Previous reports have suggested that AF is less prevalent in African Americans compared to Caucasians. However, there is a paucity of data from indigenous groups. Methods: ver a 10 year period (2000 200 ), we identi ed all Indigenous and Caucasian hospitalizations for AF at a single tertiary university hospital. Results: f 13,217 Indigenous hospitalizations, 350 (2.7 ) were for a primary or secondary diagnosis of AF. Indigenous AF patients were younger than non Indigenous AF patients (53.6 vs 74.7 yrs, p 0.0001). Whilst most Indigenous AF patients were 50 5 yrs, most non Indigenous AF patients were over 80 yrs. For principal Indigenous AF diagnoses, common comorbidities were hypertension (13.2 ), smoking (5.3 ), hyperlipidemia (3.3 ) and coronary artery disease (2.6 ). For secondary Indigenous AF diagnoses, common principal diagnoses were coronary artery disease (12.2 ), valvular heart disease (4.3 ), unspeci ed chest pain (4.3 ) and angina (3.6 ). Whilst the mean length of stay for Caucasian patients with a principal AF diagnosis decreased from 3.4 to 2.0 days, the mean length of stay in Indigenous patients remained at appro imately 3 days. Furthermore, principal Indigenous AF diagnoses as a percentage of all Indigenous AF hospitalizations increased from 7.1 to 24.1 . Conclusions: Indigenous Australians have signi cantly greater rates of AF at an earlier age than their Caucasian counterparts, accounting for an increasing number of their hospitalizations. The burden of AF in this racial subgroup is substantial and likely to contribute to their early morbidity and mortality. These ndings suggest there is a need for further studies e ploring the racial differences in AF prevalence and pathogenesis.

PO3-60 THE USEFULNESS OF CHADS2 AND CHA2DS2-VASC SCORES TO PREDICT CARDIOVASCULAR EVENTS IN THE PATIENTS WITH ATRIAL FIBRILLATION AFTER CATHETER ABLATION Tze Fan Chao, MD, Yenn-Jiang Lin, MD, Shih-Lin Chang, MD, Li-Wei Lo, MD, Yu-Feng Hu, MD and Shih-Ann Chen, MD. Taipei Veterans General Hospital, Taipei, Taiwan Introduction: Atrial brillation (AF) was associated with increased risk of cardiovascular events, including stroke, coronary artery disease, peripheral thromboembolism and mortality. However, the data about the predictors of cardiovascular events in the patients of AF after catheter ablation was limted. The aim of this study was to evaluate the usefulness of CHADS2 and CHA2DS2 VASc scores for the risk strati cation in patients after catheter ablation. Methods: Total 580 AF patients (453 patients were paro ysmal and 127 patients were non paro ysmal AF) who received ablation were enrolled. The mean age was 54.4 ± 12.4 years old and 423 patients were male. ach patient received standard follow up after catheter ablation. The composite endpoint includes all cause mortality, stroke, acute coronary syndrome, pulmonary embolism, and other peripheral thomboembolism events required hospitalization. Results: During the follow up of 38.8 ± 22.7 months, 3 patients (6.7 of the study population) suffered from cardiovascular events. In the multivariate Co regression analysis, the independent predictors were LA diameter, recurrence after catheter ablation, CHADS2 and CHA2DS2 VASc scores. The areas under the curve of the R C curves based on the CHADS2

Heart Rhythm, Vol 8, No. 5, May Supplement 2011 and CHA2DS2 VASc scores to predict cardiovascular events were 0.736 and 0.750, respectively. Conclusions: Both the CHADS2 and CHA2DS2 VASc scores were useful scoring systems of risk strati cation for AF patients who received catheter ablation. Multivariate Co regression analysis for predictors of cardiovascular events after catheter ablation Variable HR 5 CI P value HR 5 CI P value AF (non paro ysmal)

1.042 0.450 2.413 0. 23

1.1 5 0.523 2.730 0.673

Final recurrence after ablation

1.465 1.022 2.101 0.038

1.360 0. 41 1. 67 0.102

LA diameter (mm)

1.037 1.001 1.074 0.046

1.034 0.

LV F ( )

0.

0.

CHADS2 score

1.4 5 1.17 1.8 6 0.001

CHA2DS2 VASc score

3 0. 52 1.305 0.734

8 1.071 0.061

1 0. 50 1.033 0.657

1.430 1.167 1.754 0.001

PO3-61 LEFT ATRIAL APPENDAGE OCCLUSION WITH THE WATCHMAN-DEVICE IN PATIENTS WITH ATRIAL FIBRILLATION AND WARFARIN CONTRAINDICATIONS Gunnar G. Klein, MD, Johannes Hartung, MD, Marcelo Tallone, MD, Dieter Fischer, MD, Philipp Röntgen, MD, Ajmal Gardiwal, MD and Arnd Schaefer, MD. Hannover Medical School, Hannover, Germany Background: PR T CT AF shows, that left atrial appendage occlusion (LAA occlusion; Watchman) is not inferior to warfarin regarding stroke and bleeding in patients with atrial brillation (AF) eligible for warfarin therapy ( AC). Methods: In PR T CT AF patients were under AC during the rst 6 weeks after LAA occlusion. However, in daily practice clinicians need an alternative to AC for patients with AC contraindications. Thus, we studied safety and ef cacy of Watchman Device implantation in patients with contraindications to AC, who received dual antiplatelet therapy during the rst 6 weeks after device implantation. Results: ur cohort shows typical characteristics of chronic AF patients (see table 1). Patients with AC contraindications were of similar age, suffered more often from coronary artery disease (CAD) and stroke. However, HASBL D Score was even lower in patients with AC contraindications. LAA occlusion followed by dual antiplatelet therapy in those patients with AC contraindication was safe and effective. We observed one early device embolisation during the procedure and one late (>24h) pericardial effusion without hemodynamic compromise. During FU one ischemic stroke occurred 82 days after device implantation in one of the patients with dual antiplatelet therapy. He was switched to aspirin only after T showed adequate device position 6 weeks after implantation. Notably, this one and only stroke did not occur during the rst 6 weeks under dual antiplatelet therapy. Conclusions: Watchman Device implantation followed by early dual antiplatelet therapy is safe and effective in patients with atrial brillation ineligible for AC.

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Parameter (mean ± SD) Age (years) CHADS2 Score CHA2DS2 Vasc Score HASBL D Score Paro ysmal AF ( ) CAD ( ) Hypertension ( ) Diabetes ( ) H of Stroke ( ) Device Size (mm) Fluoroscopy Time (min.) vents during proc. (n; ): Pericardial tamponade Pericardial effusion Device embolisation Stroke Follow Up (FU; days) vents during FU (n; ): Stroke TIA Ma or Bleeding

AC All Patients AC contraindication N 27 N 7 N 20 72±7 72±8 73±6 2.5±1 2.5±1.2 2.7±0.8 3.8±1. 3.6±1.4 4.3±1.1 2. ±1.0 2. ±1.1 3.3±0.8 11 10 14 41 45 2 3 5 86 33 40 14 37 35 43 27±3 27±4 28±2 11±6 10±5 15±6 1; 3.7 1; 5 0;0 0;0 0;0 0; 0 1; 3.7 1; 5 0; 0 1; 3.7 1; 5 0; 0 0; 0 0; 0 0; 0 207 212 1 2 1; 3.7 1; 5 0; 0 1; 3.7 1; 5 0; 0 0; 0 0; 0 0; 0 0; 0 0; 0 0; 0

PO3-62 EARLY RECONNECTIONS ACROSS MITRAL ISTHMUS ABLATION LINES ARE COMMON AND PREDICTS MITRAL ANNULAR DEPENDENT FLUTTERS FOLLOWING PULMONARY VEIN ISOLATIONS FOR ATRIAL FIBRILLATION William W. Chik, FRACP, Toon Wei. Lim, FRACP, Choon Hiang Koay, RN, Valerie A. See, BSc, Rebecca McCall, BA, Robert Zecchin, RN, Karen Byth, PhD, Liza Thomas, MBBS, PhD, David L. Ross, FRACP and Stuart P. Thomas, MBBS, PhD. Westmead Hospital, Cardiology Department, Westmead, 2145, N.S.W., Australia, National University Hospital, Cardiac Department, Singapore, 119074, Singapore, Westmead Private Hospital, Westmead, 2145, N.S.W., Australia, Westmead Hospital, Westmead, 2145, N.S.W., Australia, Liverpool Hospital, Liverpool, NSW, 2170, Australia Introduction: Recurrent macro reentrant atrial tachyarrhythmias following radiofrequency ablations are often due to reconnections across ablation lines. Inability to create durable and transmural linear lesions predisposes to future arrhythmogenicity. We e amined the incidence and clinical impact of mitral isthmus line (MIL) reconnections in patients returning for a second procedure (redo) after pulmonary vein isolation (PVI). Methods: 220 consecutive patients with atrial brillation (AF) underwent PVI ablation. MIL ablation was randomly assigned to half the patients. All were followed with 7 day Holter monitoring and clinically at 3, 6 and 12 months, for 2.2±0.8 years. We studied all 8 patients who underwent a redo after an average of 283±18 days for recurrent AF (42 ), atrial utter (40 ) and both (18 ). 52/ 8 (53 ) patients had been randomized to MIL ablation. Results: MIL was con rmed intact at the initial procedure in 28/52 (54 ) patients. At redo, 8/28 (2 ) initially intact MIL had reconnected, and of these 3/8 (38 ) had inducible mitral annular (MA) utter. In contrast, the 24 with failed MIL ablation at the rst procedure had a higher probability of inducible MA utter at the redo procedure ( /24 [38 vs. 3/28 [11 , p 0.02). Hence, 12 of 32 with incomplete or reconnected MIL had inducible MA utter while none of the 20 patients with intact MIL had inducible

utter at redo (p 0.002). Additionally, 13/46 (28 ) initially randomized to no MIL had inducible utter at redo compared to 12/52 (23 ) assigned to MIL ablation at the rst procedure (p 0.56). Logistic regression analysis revealed longer ablation times for MIL (14.3±8.1 for patients who had reconnection of a previously intact MIL vs. .3±6.1 mins for those without a reconnection; p 0.03) at the initial procedure was a positive predictor for future MIL reconnection. Conclusions: Reconnections of 1/3 mitral isthmus line occurs early after an initial PVI procedure in patients requiring a second procedure; Incomplete lines were associated with higher risk of mitral annular utter than complete lines at the rst procedure; Reconnected or intact lines are not associated with more mitral utter than no lines; Longer ablation times predict increased risk of future reconnection.

PO3-63 EFFECT OF THE RADIOFREQUENCY CATHETER ABLATION OF ATRIAL FIBRILLATION ON THE FUTURE ACUTE CORONARY ARTERY EVENTS IN PATIENTS WITH A PRIOR HISTORY OF CORONARY ANGIOPLASTY Ta-Chuan Tuan, MD, Yenn-Jiang Lin, MD, PhD, Tao-Cheng Wu, MD, PhD, Shih-Lin Chang, MD, Li-Wei Lo, MD, Yu-Feng Hu, MD, Ching-Tai Tai, MD, Kazuyoshi Suenari, MD, Cheng-Hung Li, MD, Tzu-Fan Chao, MD and Shih-Ann Chen, MD. Taipei Veterans General Hospital, Taipei, Taiwan Introduction: Atrial brillation (AF) is associated with increased risk of coronary artery disease (CAD). However, it is unclear if successful catheter ablation of AF improves the occurrence of future acute coronary events. Methods: This study included 100 symptomatic AF patients who underwent catheter ablation of AF with a prior history of coronary angioplasty, and 152 age/se matched control patients with documented AF (with angioplasty but without ablation). The patients were followed for any acute coronary syndrome, including unstable angina (UA) or myocardial infarction (MI) requiring hospitalization/ R visits. We tested the predictive value of various risk factors for AF and coronary artery disease in this cohort. Results: The clinical characteristics were similar between the two groups (Table). With a follow up duration of 36±24 months, hospitalization due to acute coronary syndrome occurred in 4.8 of the patients with ablation (median duration: 1 .7 months after the procedure, including 75 with UA and 25 with MI), and .1 with antiarrhythmic drug control ( .1 , median duration since enrollment: 6.8 months, including 80 with UA and 20 with MI, P 0.001). In the multivariate Co regression analysis, the independent predictors were an ablation procedure ( R 0.21, 5 CI 0.10 0.43, P 0.001, Figure), and smoking ( R 4.1, 5 CI 1.3 14.6, P 0.016). Conclusions: In AF patients with prior coronary angioplasty, radiofrequency ablation reduced the occurrence of future coronary artery events, as compared with the antiarrhythmic medication treated control patients.

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Heart Rhythm, Vol 8, No. 5, May Supplement 2011 (Amio (HR 1.13, p .23, R HR 1.14, p .14) risk dissipated. Conclusions: 1. CVH are frequent in AF pts occur early; this may relate to AF recurrence rates. 2. While both rhythm strategies increase CVH, A disease variables contribute to Amio risk AAD.

PO3-65 RIGHT ATRIAL SUBSTRATE REMODELING AND ATRIOVENTRICULAR NODE CONDUCTION PROPERTY IN ATRIAL FIBRILLATION PATIENTS Beny Hartono, MD, Hung-Yu Chang, MD, Yenn-Jiang Lin, MD, Shih-Lin Chang, MD, Li-Wei Lo, MD, Yu-Feng Hu, MD, Kazuyoshi Suenari, MD, Cheng-Hung Li, MD, Tze-Fan Chao, MD, Shuen-Hsin Liu, MD, Kibos Ambrose, MD and Shih-Ann Chen, MD. Division of Cardiology - Taipei Veteran General Hospital, Taipei, Taiwan, Cheng-Hsin General Hospital., Taipei, Taiwan

PO3-64 CARDIOVASCULAR HOSPITALIZATIONS VARY WITH RECURRENT ATRIAL FIBRILLATION: INSIGHTS FROM THE AFFIRM TRIAL April E. Slee, MS, Sanjeev Saksena, MBBS, FHRS, Ankush Verma, MS and Tina Liu, MS. Electrophysiology Research Foundation, Warren, NJ Introduction: Cardiovascular hospitalizations (CVH) have been proposed as endpoints in atrial brillation (AF) clinical trials but are not well understood. Methods: We e amined disease, clinical treatment characteristics as well as recurrent AF events as related to the rst CVH in the AFFIRM study in 3 pt cohorts based on initial antiarrhythmic drug (AAD) selected. Results: Amiodarone (Amio,n 735) pts had more advanced CAD heart failure than other rhythm ( R, n 12 8) rate control (Rate, n 2027) pts. Time to rst CVH was shorter for Amio R compared to Rate (p .001). At 2 mos, CVH occurred most often in R (16 ) or Amio (12 ) than Rate (8 , p .0001 ).At rst CVH, ventricular rate >100 bpm was more common with Rate (p . 02), 60 bpm with Amio (p .005) interventions with Amio Rate (p . 02). AAD discontinuation was higher with R (35 ) than Amio (14 ) or Rate (20 , p .001). Cardioversion with R (38 ) e ceeded Amio (31 ) Rate (15 , p .001)). Risk varied with recurrent AF frequency. In pts with AF > 75 of followup (FU) time, Amio (Hazard ratio HR 1.5, p .006) R (HR 2.18, p .0001) increased risk. In pts with AF at 75 25 of FU time, modest risk persisted with Amio (HR 1.3, p .023) R (HR 1.34, p .001). In pts with infrequent AF e.g. 25

Introduction: It is not clear whether atrial remodeling affect the atrial input to the atrioventricular node (AVN) and cause AVN dysfunction. We aimed to investigate the correlation between right atrial (RA) substrate and AVN function in patients with atrial brillation (AF). Methods: The study consisted of 22 consecutive patients (57±10 y/o, 14 males) who underwent catheter ablation for symptomatic AF. lectroanatomic bipolar voltage mapping (NavX, St ude, USA) was performed in the RA (mean mapping sites 221±73). Mean biopolar voltage of the entire RA and och area were obtained, and the low voltage zones (LVZs) were de ned as peak to peak bipolar voltage of less than 0.5 mV. Poor antegrade AVN function was de ned as incapability of AV 1 to 1 conduction with paced cycle length 400ms; poor retrograde AVN function was de ned as presence of VA dissociation with paced cycle length 500ms. Results: Five patients (23 ) had antegrade AVN dysfunction, 12 patients (55 ) had poor retrograde AVN function and 3 (14 ) had both. These patients were characterized by lower mean bipolar voltage of the RA (both antegrade and retrograde AVN dysfunction), lower bipolar voltage of the och’s triangle area (antegrade AVN), presence of LVZ (antegrade AVN), and longer total RA activation time (antegrade AVN), when compared to other patients with normal AVN function. Conclusions: Diffuse remodeling of the RA substrate in patients with AF may affect the e it from retrograde AVN conduction, while localized atrial remodeling in the och area may affect atrial input to the antegrade AVN. Further study is needed to clarify the role of atrial substrate remodeling in the AVN dysfunction in patients with AF.

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PO3-66 HUMAN AND ANIMAL FEASIBILITY STUDY OF INVESTIGATIONAL 3D GEOMETRY ACQUISITION SOFTWARE E. Kevin Heist, MD, PHD, FHRS, Stephan Danik, MD, Fadi Chalhoub, MD, Florian Koci, MD, Conor Barrett, MD, Francesco Perna, MD, Christopher Houghtaling, MS, Dennis Morgan, MS, Claudio Tondo, MD, Jeremy Ruskin, MD and Moussa Mansour, MD. Massachusetts General Hospital, Cardiac Arrhythmia Service, Boston, MA, St. Jude Medical Corp, Waylan, MA, Centro Cardiologico Monzino, Milan, Italy Introduction: Current 3D mapping systems have dif culty rendering comple cardiac structures. The interpolation between mapped points results in distortion of the maps requiring signi cant post acquisition processing. New mapping software was designed to improve the delineation of closely spaced structures without the need for post processing. Methods: In vivo mapping of the left and right atria and the aorta was performed in 6 pigs. Left atrial and pulmonary vein (PV) mapping was also performed in 6 patients undergoing catheter ablation for atrial brillation. The created maps were analyzed with current (St. ude Medical nSite NavX™ Technology) versus investigational (St. ude Medical) software and dimensions of cardiac chambers were compared to pre procedural CT scans to determine the relative accuracy of the maps. Results: Maps created with the investigational software provided greater sub ective detail of comple cardiac structures compared to current software in both animals and humans (Figure). Analysis of the left atrial/pulmonary vein maps from the human study with the CT scan as reference demonstrated signi cantly less error in measurement of PV ostial long and short a is dimensions and ridge width (left PV to left atrial appendage) with investigational vs current software (measurement error: PV long a is 0.88 0. 5mm vs 3.42 3.51mm p 0.001, PV short a is 0.88 0.74 vs 3.33 3.51 mm p 0.002, ridge 0.50 0.54 vs 1.67 0.82 mm p 0.016). Conclusions: The investigational mapping software produces maps which are more accurate in rendering comple cardiac structures compared to currently available software, and without the need for post acquisition processing.

PO3-67 3D ESOPHAGYC RECONSTRUCTION WITH MULTI SLICE 64 COMPUTED TOMOGRAPHY (MSCT-64) AND PASSIVE FUSION WITH ESOPHAGUS SHELL IN PATIENTS UNDERGOING AF ABLATION Fernando A. Scazzuso, MD, Santiago Rivera, MD, Gaston Albina, MD, Alberto Giniger, MD, Ruben Laiño, MD and Matias Kamlofsky, PhD. Instituto Cardiovascular de Buenos Aires, Buenos Aires, Argentina Introduction: Catheter ablation (CA) has proven as standard procedure for patients with drug refractory atrial brillation (AF). Atrioesophageal stula (A F) has been described as an infrequent but lethal complication of this procedure. Several approach and different techniques were described to avoid this tremendous complication. The aim of this study is describe a new technique to determinate the accuracy of tridimensional esophagic reconstruction from MSTC 64 to determine its feasibility and reproducibility as a methodological approach to avoid (A F) complication in a huge cohort. Methods: Single center prospective analysis of consecutive patients who underwent ablation of atrial brillation and received a MSCT 64 prior to ablation from May 200 to ctober 2010. We performed the tridimensional reconstruction of the esophagus to determinate the relation with the pulmonary vein ostium (PV ). We designed the left atrium shell. The esophagus shell was designed advancing a quadripolar catheter inside the esophagus and pulling back towards the pharynges. We performed the fusion of the left atrium with the MSCT 64 using Verismo® tool. We obtain the ducially points from the pulmonary ostia and transport passively the esophagus shell. Results: 83 patients were included with a mean age 61± .7 yrs, 0 male and a mean BMI of 26.5±6.4 kg/m2. 78 ( 3. 7 ) patients were in sinus rhythm at time of MSCT 64. We determine the esophagus tract in 7 patients ( 5.18 ). In 7 patients it was impossible to perform the reconstruction because of technique problems in image acquisition. The accuracy obtained was of 62.02 ( t between tridimensional reconstruction and esophagus shell) when MSCT was performed more than 48hs prior to procedure. When we discriminate studies performed less than 48 h we have obtained 83.82 of accuracy (p value 0.05). The range of mismatch between each structure after fusion was 6 mm ± 10 mm. Conclusions: The passive fusion technique of the esophagus has a high accuracy to determinate the esophagus position if the MSCT is performed during the last 48h before the procedure. This allows avoid this critical structure during AF ablation and lets us modify the strategy during ablation procedure.

S242 PO3-68 WHAT KIND OF ATRIAL FIBRILLATION PATIENTS DEVELOP ATRIAL REMODELING WITH A VOLTAGE REDUCTION? Miyako Igarashi, MD, Hiroshi Tada, MD, Yukio Sekiguchi, MD, Hiro Yamasaki, MD, Kenji Kuroki, MD, Takeshi Machino, MD, Yoshihisa Naruse, MD, Yoko Ito, MD, Emi Nakano, MD, Fusanori Kunugida, MD, Takashi Kaneshiro, MD, Kentaro Yoshida, MD, Keisuke Kuga, MD and Kazutaka Aonuma, MD. University of Tsukuba, Tsukuba, Japan Introduction: A nding reported for atrial remodeling in patients with atrial brillation (AF) is a reduction in the left atrial (LA) endocardial voltage. However, few studies have attempted to clarify the predictors of developing an LA voltage reduction in AF patients. Methods: This study included 80 AF patients (persistent AF 42) who underwent radiofrequency catheter ablation. In the persistent AF patients, sinus rhythm was restored by electrical cardioversion and/or antiarrhythmic drugs before mapping. LA endocardial voltage mapping with electro anatomical mapping system (CART ) was performed during sinus rhythm before ablation. The average LA voltage and proportion of the low voltage area with amplitudes of 1.0 mV in the LA were e amined. Results: Hypertension, diabetes mellitus, hyperlipidemia and low left ventricular e ection fraction ( 50 ) were not related to the presence of low voltage areas. However, the AF type (persistent AF) was a signi cant predictor of the presence of a low voltage area ( dds ratio [ R 4. 51; 5 con dence interval [CI 1.355 12.113; p 0.05). The proportion of the low voltage area in persistent AF was signi cantly greater (20.4 of total LA surface area) than that in paro ysmal AF (5.2 ; p 0.001), and the average LA voltage was signi cantly lower in persistent AF than in paro ysmal AF (1.2 vs. 1.7 [mV ; p 0.001). Furthermore, aging was associated with the presence of a low voltage area ( R 1.0 6; 5 CI 1.025 1.172; p 0.01). A signi cant negative correlation between aging and the average LA voltage was observed (r 0.53, p 0.001). n the other hand, diabetes mellitus was associated with a broad low voltage area (>20 of the total LA surface area) ( R 6.424; 5 CI 1.082 38.142; p 0.05), and the proportion of the low voltage area (35.0 ) was greater in patients with diabetes mellitus than in those without (10.5 ; p 0.01). Among the patients with persistent AF, that lasted for >3 years was signi cantly associated with a low voltage area ( R 5.50 ; 5 CI 1.008 30.108; p 0.05), while the sustained AF duration itself was not related. Conclusions: A very long lasting persistent AF, old age, and diabetes mellitus, all were strongly associated with the presence of low voltage areas in the LA.

PO3-69 EVALUATION OF ESOPHAGEAL DISPLACEMENTS DURING PULMONARY VEIN ISOLATION IN PAROXYSMAL ATRIAL FIBRILLATION ABLATION Fernando A. Scazzuso, MD, Santiago Rivera, MD, Gaston Albina, MD, Ruben Laiño, MD, Alberto Giniger, MD and Matias Kamlofsky, PhD. Instituto Cardiovascular de Buenos Aires, Buenos Aires, Argentina Introduction: Catheter ablation represents a substantial achievement in AF treatment but this technique is not free from complications. Atrioesophageal stula has been reported. The outcome of this infrequent complication in most cases is fatal. Several approach and different techniques were described to avoid this tremendous complication. We describe

Heart Rhythm, Vol 8, No. 5, May Supplement 2011 a new technique to assess esophagus displacement during pulmonary veins isolation (PVI). The aim of this study is describe esophagus position shifts during PVI using the Verismo tool in nSite Nav X system using the Shadow Function to avoid Atrioesophageal stula complication. Methods: Single center prospective analysis of consecutive patients who underwent ablation of atrial brillation and received a MSCT 64 prior to ablation between May 200 and ctober 2010. We performed the tridimensional reconstruction of the esophagus to determinate the relation with the pulmonary vein ostium (PV ) and posterior wall. We designed the left atrium shell and the esophagus position with a quadripolar P catheter inside the esophagus lumen. We performed the fusion of the left atrium with the MSCT using Verismo® tool. We obtain the ducially points from the pulmonary vein ostium and transport passively the esophagus acquired points obtained during shell construction. If sophagus tract t with 3D esophagus reconstruction its position was assessed by using the Nav X Shadow tool during the entire procedure. Signi cant displacements were de ned as those presenting more than 3mm shift between the 3D reconstructed esophagus and the `in vivo´ position determined by the shadow function. Results: 86 patients were included with a mean age 61± .7 yrs, 0 male and a mean BMI of 26.5±6.4 kg/m2. Seventy eigth ( 3. 7 ) patients were in sinus rhythm at time of MSCT 64. We determine the esophagus tract in 7 patients ( 5.18 ). Signi cant displacements were observed in 12 patients (15.18 ) and 66 (84,81 ) showed no signi cant position shifts (p value 0.05) Conclusions: The present study suggests that the sophagus does not present signi cant position shifts during PVI. Shadows tool con rm that initial assessment of esophagus position after 3D reconstruction is safe and precisely to guide PVI procedure.

PO3-70 CARTOSOUND AND FAST ANATOMICAL MAPPING UNDERESTIMATE LEFT ATRIAL VOLUME WHEN COMPARED TO CT ANGIOGRAPHY Joshua Skibba, MD, Latoya N. Linton-Frazier, MD, Raman Moradkhan, MD, Javier E. Banchs, MD, Erica D. PennyPeterson, MD, Soraya M. Samii, MD, PhD, Deborah L. Wolbrette, MD, Gerald V. Naccarelli, MD and Mario D. Gonzalez, MD. Penn State University / Milton S. Hershey Medical Center, Hershey, PA Introduction: 3 D reconstruction of the left atrium identi es critical anatomical landmarks and facilitates catheter navigation during ablation of atrial brillation. The accuracy of left atrial volume determination using new imaging modalities is unknown. In the present study we compared left atrial volumes measured by CartoSound (IC ) and Fast Anatomical Mapping (FAM) versus CT angiography. Methods: Left atrial volumes were measured in 12 consecutive patients (mean age 61±7 years) referred for catheter ablation of atrial brillation. All patients had a prior CT angiogram. IC and FAM images were acquired during the procedure. Left atrial appendage and pulmonary vein volumes were e cluded from analysis. Calculated left atrial volume with CartoSound and FAM was obtained as a sum of virtual pyramids created between the center of the map and the virtual image surface. CartoSound was gated to atrial activation (end diastole), while FAM is an average of catheter position over 1 second. Results: IC and FAM left atrial volumes were similar (10 ±45 cm² vs.112±45 cm², NS, respectively), but smaller than left atrial volumes determined by CT angiography (150±43 cm²; p 0.05).

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prolonged electrograms, multiple de ection, and higher DF value as AF nests were responsible for appro imately 10 of the sites wave fractionation during AF. The ma ority of the CF s during AF were functional, and degree of CF depends on the activation rhythm.

PO3-72 RESPIRATORY COMPENSATION IMPROVES THE ACCURACY OF ELECTROANATOMIC MAPPING OF THE LEFT ATRIUM AND PULMONARY VEINS DURING ATRIAL FIBRILLATION ABLATION Roy Beinart, MD, Rajesh Kabra, MD, Kevin E. Heist, MD, PhD, Dan Blendea, MD, PhD, Conor D. Barrett, MD, Stephan B. Danik, MD, Ryan Collins, BS, Jeremy N. Ruskin, MD and Moussa Masnour, MD. Massachusetts General Hospital, Boston, MA, Biosense Webster, Diamond bar, CA Conclusions: IC and FAM underestimate left atrial volumes when compared to CT angiography. Although both IC and FAM calculate volume in a similar manner, each imaging modality has its own inherent limitations. IC provides real time image acquisition, but may underestimate atrial contours. FAM provides a rapid reconstruction of the left atrium, but is not gated with the cardiac cycle.

PO3-71 CAN WE IDENTIFY COMPLEX FRACTIONATED ELECTROGRAMS DURING SINUS RHYTHM IN NONPAROXYSMAL ATRIAL FIBRILLATION? Wenchin Tsai, MD, Yenn-Jiang Lin, MD, Li-Wei Lo, MD, ShihLin Chang, MD, Yu-Feng Hu, MD and Shih-Ann Chen, MD. Buddhist Tzu-Chi General Hospital, Hualein, Taiwan, Taipei Veterans General Hospital, Taipei, Taiwan Introduction: Spectral analysis can be used to identify AF nests and abnormal atrial substrates in sinus rhythm (AF nest) in patients with paro ysmal atrial brillation (AF). However, the role of AF nests during AF remains unclear, as well as the relationship to the high dominant frequency (DF) sites and comple fractionated electrograms (CF s) during AF. Methods: This study enrolled 20 persistent AF patients (age 48±11 years) who underwent 3D mapping (NavX, St. ude Medical, USA). The analysis of the substrate characteristics included the degree of fractionation (based on the mean fractionation interval, FI), and fast Fourier Transformation (Recti ed, resolution 0.14 Hz, sampling rate 1200 Hz). Abnormal SR electrograms were identi ed by spectral analysis (> 70 Hz), which was observed after cardioversion to SR. Results: A point by point comparison of the electrogram characteristics during SR and AF were performed in a total of 1016 sites (51 ± 12 sites/patients in LA). A total of .4 sites with abnormal SR electrograms (AF nest) were identi ed, which were characterized by prolonged electrograms, multiple de ections, and the positive spectral analysis result (73.1 ± 7. vs. 37.5 ± 8.3 Hz, P 0.001). During AF, sites with AF nest were all located within the CF area (100 , with fractionation interval 120 msec), and sites without nest may manifest CF s during AF (52.6 , P 0.04, compared to AF nest). The DF value during AF was similar in both groups (7.1 ± 1.20 vs. 7.21 ± 1.25 Hz, respectively, P NS). During AF, the higher degree of CF s correlated with the presence of AF nest (higher DF value during SR (35±8. Hz, 40±11 Hz, 48±14 Hz, in non CF s (FI>120), variable CF s (FI 60 120), and continuous CF s (FI 60), respectively, P 0.001). Conclusions: Abnormal SR electrograms characterized by

Introduction: The creation of accurate electroanatomic maps ( AM) of the left atrium and pulmonary veins is important for AF ablation to guide ablative lesions and improve the safety and ef cacy of the procedure. Respiratory motion of the heart and the pulmonary veins affects the accuracy of these maps. We assessed the changes in the left atrial and pulmonary venous anatomy due to respiration and their implication for AM acquisition. Methods: Two separate AM were created using the CART 3 mapping system in 22 consecutive patients (63 males, mean age 63 ± 8 years) undergoing AF ablation at our center: a non respiratory compensation (RC) map in which endocardial points were collected irrespective of respiratory phase, and an RC map in which the points were collected during end e piration only. These maps were compared to pre procedural cardiac CT/MRI images. Results: Non RC mapping required 3.2 ± 1.0 minutes versus 7.8 ± 2.1 minutes for the maps with RC. In comparison to the pre procedural CT/MRI images, maps without RC signi cantly over estimated the dimensions of the pulmonary veins ostia compared to maps with RC in both long a is and short a is (Figure 1). Distances between the pulmonary veins were not signi cantly different when comparing non RC to RC mapping at the left atrial roof or oor. Conclusions: Respiratory compensation at the time of AM acquisition during AF ablation more accurately represents the true anatomical dimensions of the pulmonary vein ostia. The resulting more accurate maps may improve the safety and ef cacy of atrial brillation ablation.

S244 PO3-73 THREE DIMENSIONAL RECONSTRUCTED VOLUME OF EPICARDIAL FAT IS ASSOCIATED WITH THE PERPETUATION OF ATRIAL FIBRILLATION AND A POOR PROGNOSIS AFTER CATHETER ABLATION Yasuo Okumura, MD, PhD, Ichiro Watanabe, MD, PHD, FHRS, Masayoshi Kofune, MD, PhD, Koichi Nagashima, MD, Hiroaki Mano, MD, Kimie Ohkubo, MD, PhD, Toshiko Nakai, MD, PhD, Toru Hiratsuka, MD, Nobuyuki Fujii, MD and Atsushi Hirayama, MD, PhD. Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan Introduction: picardial fat contains abundant ganglionic ple i contributing to the occurrence of atrial brillation (AF). Methods: We evaluated the total epicardial adipose tissue volume ( AT) and AT volume around the left atrium (LA AT) in 20 patients with AF (paro ysmal: n 12; persistent: n 8) who underwent catheter ablation and in 15 controls by 320 row multi detector computed tomography. The AT was measured by assigning Houns eld units from 50 to 200 to fat, and the 3 dimensional (D) volume of the total AT was reconstructed by the a ial images from the bifurcation of the pulmonary artery to the coronary sinus. Thereafter, the 3D reconstructed LA AT volume was manually segmented. Results: The 3D volume of the total AT and LA AT gradually increased from that in the controls, to that for those with paro ysmal AF to that for those with persistent AF ( AT: 13 ±47 vs. 156±36 vs. 26 ±132 cm3, P 0.001, LA AT: 38±16 vs. 42±13 vs. 80±50 cm3, p 0.030). After ad usting for the possible factors related to AT (age, se , body surface area, hypertension, hyperlipidemia, diabetes mellitus, and coronary artery disease), the 3D total AT volume remained related to the presence of AF (p 0.006). Nine of the 20 AF patients e perienced a recurrence of AF after ablation. The 3D AT and LA AT volume was signi cantly greater in the recurrence group than in the non recurrence group ( AT: 25 ±127 cm3 vs. 154±38 cm3, p 0.017, LA AT: 76±4 vs. 41±13 cm3, p 0.033). Conclusions: The 3D reconstructed epicardial fat tissue is increased in paro ysmal and persistent AF patients independent of the traditional risk factors. The 3D AT volume might be useful for predicting a recurrence of AF after ablation.

Heart Rhythm, Vol 8, No. 5, May Supplement 2011 MBBS, PhD. Cardiovascular Research Centre, Department of Cardiology, Royal Adelaide Hospital and the Disciplines of Medicine and Physiology, University of Adelaide, Adelaide, Australia, Department of Thoracic Medicine, Royal Adelaide Hospital and Adelaide University, Adelaide, Australia Introduction: bstructive sleep apnea ( SA) is increasingly recognized as a risk factor for atrial brillation (AF); however, its contribution to the atrial substrate is not known. Methods: 40 pts undergoing ablation of paro ysmal AF and in sinus rhythm for 48hrs (20 with moderate severe SA (AHI> 15) and 20 with no SA (AHI 15) by overnight polysomnography) were studied. Multipolar catheters were positioned at the lateral right atrium (RA), coronary sinus (CS), crista and RA septum : RP (high/low lateral RA, pro imal and distal CS, septal ); conduction time along the RA and CS ; number and duration of fractionated signals (FS>50ms) along the crista; and sinus node function (CSNRT) were measured . lectroanatomic maps of the LA and RA were created to determine voltage, conduction and distribution of FS. Results: See table. The groups had no differences in the prevalence of established risk factors for AF. Pts with SA had the following compared to those without SA: no difference in RP; prolonged conduction times; greater number and longer duration of FS along the crista; longer P wave duration (PWD); longer CSNRT; lower atrial voltage; slower atrial conduction velocity; and more widespread FS in both atria. Conclusions: SA is associated with signi cant atrial remodeling characterized by atrial enlargement, loss of myocardium, site speci c and widespread conduction abnormalities and impaired sinus node function. These features may in part e plain the association between SA and AF. Results N Age

SA

51±3.8

M D RAT / S V R SA

P

55±3.3

ns

AHI

8.7±0.

38±5.

PWD RA/LA volume

11 . ±14.5 8 ±7/83±3

137.7±8.2 111± /116±11

0.01 0.04/0.01

Mean RP

228±54

226±82

ns

Conduction time CS/LAT RA (ms)

45.1± . /51.2±10

51±7/58.3± .7

0.02 0.003/0.03

Crista FS (No./dur)

2±1.8/44±18

5±1/62±10

Voltage RA/LA (mV)

2.4±0.2/2.4±0.1

1.5±0.1/1.6±0.2

Conduction velocity RA/LA (m/s)

1.2±0.1/1.2±0.0

0.8±0.0/0. ±0.0

Comple electrograms ( )

11±2

22±2

0.0001

0.001/ 0.001 0.001/ 0.001 0.001

PO3-75 NOVEL ALGORITHM TO DETECT REAL TIME BEAT-TOBEAT CYCLE LENGTH REGULARITY DURING ATRIAL FIBRILLATION

PO3-74 CHRONIC OBSTRUCTIVE SLEEP APNEA CAUSES ATRIAL REMODELING: IMPLICATIONS FOR ATRIAL FIBRILLATION Hany Dimitri, MBBS, Michelle Ng, BSc, Pawel Kuklik, PhD, Anthony Brooks, BS, Martin Stiles, MBBS, PhD, Andrew Thornton, PhD, Ral Antic, MBBS and Prashanthan Sanders,

Seungyup Lee, MS, Kyungmoo Ryu, PhD, Albert Waldo, MD, Celeen Khrestian, BS, Dominique Durand, PhD and Jayakumar Sahadevan, MD. Case Western Reserve University, Cleveland, OH, Cardiac Rhythm Management Division, Sylmar, CA, Louis Stokes Cleveland VA Medical center/ University Hospitals Case Medical Center/Division of Cardiology, Cleveland, OH, University Hospitals Case Medical Center/Division of Cardiology, Cleveland, OH, Louis Stokes Cleveland VA Medical center/ University Hospitals Case Medical Center /Division of Cardiology, Cleveland, OH Introduction: ne mechanism of atrial brillation (AF) is due to 1 or more atrial driver(s) causing brillatory conduction. The

S245

Poster Session III

dominant frequency (DF) of atrial electrograms (A s) is a method used to identify these driver regions characterized by regular activation during AF. However, DF correlates poorly with beat to beat A cycle length (CL). To identify regions of regular activation, we developed a CL variability detection (CLVD) algorithm to generate a CL regularity map (CLRM). We tested the hypothesis that this algorithm would accurately and rapidly identify beat to beat regularity. Methods: We analyzed 10 episodes of AF in 10 dogs (sterile pericarditis model) due to a regular reentrant rhythm in the left atrium (LA) determined by activation sequence mapping. A s were recorded simultaneously from 400 420 electrodes on both atria. CLVD was applied to all bipolar A s, and compared to manual measurements. A CLRM was generated using the CL standard deviation (SD) at each site. Results: The accuracy of identifying regular sites using CLVD analysis was 2.7 in real time, and 100 of ine. The gure shows an e ample of a CLRM with a region in the LA (SD 2 ms) corresponding to location of a stable reentrant driver (black arrows), and a regular region on the right atrium of 1:1 activation from the driver. Areas of regularity (SD 4ms) identi ed by CLVD included the location of a reentrant circuit. Conclusions: The CLVD algorithm provides a new method of accurately and rapidly identifying beat to beat regularity in AF. The generated CLRM was accurate in locating the driver region and areas with 1:1 activation from the driver.

a single reentrant circuit and unstable reentrant circuits, all of which produce brillatory conduction causing AF. We restudied the VNS AF model using high density mapping to determine the AF mechanism. Methods: During pacing induced AF with VNS (2 7.5mA) in 8 dogs, 488 unipolar atrial electrograms (A s) were recorded simultaneously from both atria, along with 12 24 electrodes between the pulmonary veins. Activation sequence maps were produced from sustained ( 5 min) episodes of AF during VNS in each dog. Consecutive 50 0 ms activation windows were analyzed over a period of 0.5 1.06 seconds. Also 4 second segments of each bipolar A were sub ected to a beat to beat cycle length (CL) variability detection algorithm. Results are shown as the mean CL ± the standard deviation (SD). Results: During AF with VNS, multiple foci (5 10) of short (mean 107±18.5 ms), regular (mean SD 8.5±3.5 ms) CLs were present in both atria. The predominant locations of focal activity were in the crista terminalis, border of the inferior vena cava (IVC), and posterior left atrial free wall (85 of all episodes). All episodes had focal activity at the IVC border. A minimum of 3 foci were ring simultaneously. These foci produced uniform activation patterns, collision of wavefronts and brillatory conduction. No reentrant circuits were present. Conclusions: In contrast to the prediction of the multiple wavelet hypothesis, during VNS, multiple foci of short, regular CL drive the atria, thereby maintaining AF. These foci are widely distributed over the atria. The crista terminalis, IVC, and posterior left atrial free wall areas showed greatest focal activity.

PO3-77 THE USE OF TRANSESOPHAGEAL ECHOCARDIOGRAPHY AND INTRACARDIAC ULTRASOUND TO GUIDE INSERTION OF A LEFT ATRIAL APPENDAGE OCCLUSIVE DEVICE Gery F. Tomassoni, MD, Jennifer Isaccs, RN, CCRN, Melody Muir, RN, CCRN, Melissa Franklin, RN, BSN, Marciana Beall, RDCS, Aaron Hesselson, MD and Paula Hollinsworth, MD. Lexington Cardiology Consultants, Lexington, KY, Central Baptist Hospital, Lexington, KY, Biosense Webster, Diamond Bar, CA

PO3-76 HIGH DENSITY MAPPING OF THE MOE MODEL OF ATRIAL FIBRILLAION - STUDIES DURING VAGUS NERVE STIMULATION IN THE IN VIVO CANINE HEART Seungyup Lee, MS, Jayakumar Sahadevan, MD, Celeen Khrestian, BS, Dominique Durand, PhD and Albert Waldo, MD. Case Western Reserve University, Cleveland, OH, Louis Stokes Cleveland VA Medical center/ University Hospitals Case Medical Center/Division of Cardiology, Cleveland, OH, University Hospitals Case Medical Center/Division of Cardiology, Cleveland, OH Introduction: Moe, et al. hypothesized that multiple reentrant wavelets (random reentry) was the mechanism of atrial brillation (AF) on the basis of vagal nerve stimulation (VNS) studies. However, recent studies have demonstrated various driver mechanisms of AF, including a single focus, multiple foci,

Introduction: The insertion of a left atrial appendage (LAA) occlusive device in patients with atrial brillation (AF) has recently been shown to be effective in the prevention of thromboembolic events. Presently, the procedure is guided by transesophageal echocardiography (T ) which is cumbersome and adds an additional risk. We report our initial e perience inserting the WATCHMAN LAA device using T and intracardiac ultrasound (IC ). Methods: 17 patients (72 ± 8 yrs old, LV F 57 ± 5 , CHADS score mean of 3) with AF (8 permanent, paro ysmal) underwent insertion of the WATCHMAN LAA occlusive device (Atritech, Inc). The procedure was guided by both T IC . The LAA device was inserted through a 13 Fr sheath via a transseptal puncture. IC images (8 Fr Acuson catheter, Siemens) were obtained from the LA using an 8.5 Fr sheath with a second transseptal puncture. Measurements of the LAA ostium, device position, device stability, and color doppler for residual ow post implant were recorded for both T IC . Results: All 17 patients received a successful implant. Standard T views at 0°, 45°, 0°, 135° were obtained in all 17 pts. Comparable IC views were obtained from the LA septum, LA roof, the level of the mitral valve underneath the LAA, and directly in front of the LAA . There was no signi cant differences in the LAA measurements pre post implant between T IC images. The total procedural uoroscopic times were 76 ± 22 min and 17 ± 6 min respectively. No thromboembolic events or device dislodgements were seen.

S246 Conclusions: Comparable T views and LAA measurements needed for successful insertion of a LAA occlusive device can be safely obtained using LA IC images via a second transseptal puncture. Larger studies are needed to determine if IC can become the primary imaging modality for insertion of LAA devices.

PO3-78 BI-LEVEL POSITIVE AIRWAY PRESSURE (BIPAP): THE NEW UTILITY METHOD IN CATHETER ABLATION OF ATRIAL FIBRILLATION USING THE NAVX SYSTEM Mitsuru Takami, MD, Akihiro Yoshida, MD, Asumi Takei, MD, Satoko Tanaka, MD, Mitsuaki Itoh, MD, Kimitake Imamura, MD, Ryudo Fujiwara, MD, Atsushi Suzuki, MD and Ken-ichi Hirata, MD. Kobe university hospital, Kobe, Japan Introduction: The changes of respiratory motion, apnea and o ygen desaturation were commonly seen in catheter ablation of atrial brillation (AF) with conscious sedation. These events caused the instability of the catheter positioning on the 3 dimensional electroanatomical mapping using the nSite NavX system. We hypothesized that the use of the bi level positive airway pressure (BiPAP) decrease the frequency of those adverse events than the use of the conventional o ygen mask (C M) in catheter ablation of AF using the nSite NavX system. Methods: Fifty eight patients who underwent catheter ablation of AF with conscious sedation were divided into two groups (BiPAP group, n 2 , C M group, n 2 ). All patients received intravenous administration of de medetomidine to achieve sedation. Additional bolus in ection of propofol was given during catheter ablation if needed. During each catheter ablation, we compared the frequency of the o ygen desaturation events (Sp 2 5 ) and the change of the respiratory motion events which were estimated by the nSite NavX system between the two groups. Results: The frequency of the o ygen desaturation event (0.07 vs. 1.00, p 0.004) and the change of the respiratory motion (8.0 vs. 13.5, p 0.04) were signi cantly lower in the BiPAP group than the C M group. No patient in BiPAP group was intolerant of the positive pressure ventilation. In N M group, four patients changed from the C M to the BiPAP during ablation procedure due to the large respiratory motion or signi cant o ygen desaturation. Their conditions improved after using the BiPAP. Conclusions: The BiPAP group reduced the events of o ygen desaturation and the changes of respiratory motion during catheter ablation of AF than the C M group. Using the BiPAP facilitates AF ablations with the nSite NavX system and enhances the safety of the procedure.

PO3-79 RENAL DYSFUNCTION WAS ASSOCIATED WITH DIFFERENT ATRIAL SUBSTRATE AND POOR OUTCOME AFTER CATHETER ABLATION IN THE PATIENTS WITH PAROXYSMAL ATRIAL FIBRILLATION Tze Fan Chao, MD, Yenn-Jiang Lin, MD, Shih-Lin Chang, MD, Li-Wei Lo, MD, Yu-Feng Hu, MD and Shih-Ann Chen, MD. Taipei Veterans General Hospital, Taipei, Taiwan Introduction: Renal dysfunction was associated with high recurrence rate after electric cardioversion of atrial brillation. The aim of this study was to investigate the associations of renal function with atrial substrate and the outcome of catheter ablation in paro ysmal AF patients. Methods: Total 232 paro ysmal AF patients who received catheter ablation were enrolled. The estimated FR was

Heart Rhythm, Vol 8, No. 5, May Supplement 2011 calculated using the Cockcroft aut equation normalized by body surface area and the patients were divided into 3 groups according to their FR (group 1 : > 0 mL/min/1.73m2, group 2 : 60 0 mL/min/1.73m2 and group 3 : 60 mL/min/1.73m2). The atrial voltage and activation time were collected before pulmonary vein isolation. All patients received standard follow up after catheter ablation. Results: The baseline characteristics and bi atrial electrophysiological properties of the study population were shown in Table 1. The LA voltage became lower and the activation time became longer when the FR decreased from the group 1 to group 3. During the follow up of 25.4 ± 13.3 months, 15. of the study population suffered from AF recurrence. The recurrence rates of these 3 groups were 6. , 14.5 and 38. , respectively. The LA dimension, LA voltage and the groups of renal function were identi ed to be the independent predictors of AF recurrence in the multivariate analysis. Conclusions: Decreased FR was associated with poor LA substrate and high recurrence rate of catheter ablation in patients with paro ysmal AF.

PO3-80 CRYOBALLOON IN AF ABLATION: IMPACT OF PV ANATOMY? Martin Schmidt, MD, Uwe Dorwarth, MD, Michael Wankerl, MD, Manuel Oberecker, MD, Juergen Krieg, MD, Florian Straube, MD, Sebastion Reif, MD, Alexander Leber, MD, Ulrich Ebersberger, MD and Ellen Hoffmann, MD. Klinikum Bogenhausen, Munich, Germany Introduction: Cryoballoon ablation is a promising tool in AF therapy. Complete occlusion of the pulmonary veins (PV) is key for successful PV isolation. Despite 2 cryoballoon sizes (23 and 28mm) a complete occlusion (de ned as 4/4 by PV contrast in ection) may hardly be achieved in any PV. The impact of the PV ostial anatomy on cryoballoon PV occlusion grading and AF recurrence rates has not been investigated yet. Methods: PV ostial diameter were analyzed in 81 consecutive patients (54 men, 60± years, 53 paro ysmal and 28 persistent

S248 Conclusions: The duration of persistent AF strongly predicts the clinical success of persistent AF ablation. Procedural AF termination was critical for the maintenance of sinus rhythm only in the patients with shorter AF duration. In the patients with longer AF duration, further e tensive ablation to terminate AF may not be warranted.

PO3-83 DOES ADDITIONAL LINEAR ABLATION AFTER CIRCUMFERENTIAL PULMONARY VEIN ISOLATION IMPROVE CLINICAL OUTCOME IN PATIENTS WITH ATRIAL FIBRILLATION? PROSPECTIVE RANDOMIZED STUDY Hee-Sun Mun, MD, Boyoung Jeoung, MD, PhD, Jong Youn Kim, MD, Jae Min Shim, MD, Hye Jin Hwang, MD, Moon Hyung Lee, MD, PhD, Sung Soon Kim, MD, PhD and Hui-Nam Pak, MD, PhD. Yonsei University Health System, Seoul, Korea, Republic of Introduction: Although circumferential pulmonary vein isolation (CPVI) has been considered to be the cornerstone for radiofrequency catheter ablation (RFCA) in patients with atrial brillation (AF), there are still substantial amount of recurrence. Therefore, we evaluated the ef cacy of additional linear ablation to left atrial (LA) roof (Roof), Roof posterior inferior line (PostBo ), and Roof PostBo anterior line (AL) in patients with AF. Methods: This study enrolled 275 patients (187 paro ysmal AF (PAF) vs. 88 persistent AF (PeAF), male 78.5 , 56.0±10.8 years old) who underwent RFCA for AF. We compared CPVI (n 64), Roof (n 52), and PostBo (n 71) in 187 patients with PAF as a prospective randomized study. AL was done in 64 patients with PeAF. The bidirectional block rates of CPVI, Roof, PostBo , and AL were 100.0 , 78.4 , 66.7 , and 48.8 , respectively. Results: Both total procedure time (177.4±42.2min vs. 1 3.4±2 .3min, 1 8.2±52.3min, or 241.3±65. min, respectively; p 0.001) and ablation time (4172.2±12 1.4sec vs. 5436.1±783.8sec, 5267.8±1678. sec, or 6 27.8±178 .1sec, respectively; p 0.001) were the shortest in CPVI compared with Roof, PostBo , or AL. During 8.2±4.1 months follow up, the recurrence rates after 3rd month RFCA were 6.2 (31.0 under AAD) in CPVI, 13.5 (31. under AAD) in Roof, 1 .7 (35.5 under AAD) in PostBo , and 21. (63.6 under AAD) in AL. Within PAF patients, clinical outcome after CPVI alone was better than that after PostBo (p 0.01 ). In the patients with the achievement of complete bidirectional block, there was no signi cant difference in the recurrence rates (CPVI; 6.2 (31.0 under AAD), Roof; 10.3 (28.0 under AAD), and PostBo ; .4 (25. under AAD), p 0.750). verall clinical recurrence rates after 3rd months RFCA were not different in PAF group (13.4 ) and PeAF group with AL ablation (21. , p 0.113). Conclusions: In patients with PAF, additional linear ablations to CPVI did not improve clinical outcome in spite of longer procedure or ablation time, regardless of bidirectional block achievement. However, the additional linear ablation including anterior line in patients with PeAF resulted in comparable clinical outcome of PAF ablation.

PO3-84 ATRIAL TACHYCARDIA FOLLOWING ABLATION OF PERSISTENT ATRIAL FIBRILLATION: ACUTE SUCCESS OF CATHETER ABLATION DEPENDS ON TACHYCARDIA MECHANISM Jinjin Wu, MD, Tilko Reents, MD, Stephanie Fichtner, MD, Sonia Ammar, MD, Clemens Jilek, MD, Heidi L. Estner, MD, Pinjun Zhu, MD, Christof Kolb, MD, Gabriele Hessling, MD and Isabel Deisenhofer, MD. German Heart Center, Munich, Germany

Heart Rhythm, Vol 8, No. 5, May Supplement 2011 Introduction: Atrial tachycardia (AT) is a common nding during or after ablation of persistent atrial brillation (pAF). We investigated if acute success of AT ablation is depending on tachycardia mechanism. Methods: This study included 111 AT forms in 60 ablations of 56 patients (mean age 64±11 years, 13 females). PAF ablation included pulmonary vein (PV) isolation and ablation of comple fractionated atrial electrograms. AT occurred either acutely during pAF ablation (n 43) or after a mean of 8.7± .8 months (n 17). The tachycardia mechanism was macroreentry (MR, perimitral or roof dependent), localised reentry (LR) or focal AT (FAT). The location sites of LR and FAT were distributed to 5 pre divided atrial segments (Table1). A linear ablation of the critical isthmus (anterior line, mitral isthmus line or roof line) was performed for MR, the local reentrant site ablated for LR and earliest activate site ablated for FAT. Acute success was de ned as termination of all occurring AT forms to sinus rhythm or to another form of AT. Results: As shown in Table 1, the underlying mechanism of 111 AT forms (mean cycle length 265±54ms) was found MR in 53 forms (48 ), LR in 57 forms (51 ) and FAT in 1 form (1 ). f the 53 MR forms, 50 forms ( 4 ) were stopped by ablation (anterior line n 30, mitral isthmus line n 4 and roof line n 28), whereas only 36 of 57 LR forms (63 ) were stopped by ablation (P 0.0001). The only form of FAT was successfully ablated. Conclusions: During or after pAF ablation, AT due to LR is as common as MR. FAT is rarely found. The acute success rate of catheter ablation for MR was signi cantly higher than for LR. Table 1: Atrial tachycardia mechanism, location and success rate of ablation Atrial Forms, Tachycardia (AT) N Mechanism

Successfully Ablated Location Forms, N ( )

Forms, N

Successfully Ablated Forms, N( )

Macroreentrant 53 AT

50 ( 4)

Perimitral

28

25 ( 4)

Roof dependent

25

25 (100)

Left atrium (LA) septum

1

12 (63)

Localized reentry

Focal AT

57

1

36 (63)

1 (100)

LA roof (PV regions and 16 free posterior LA)

12 (75)

Anterior LA (including left atrial appendage)

7 (78)

Right atrium (RA) 6

3 (50)

Inferior LA (mitral ring and mitral isthmus)

2 (100)

2

Unknown

5

0 (0)

RA

1

1 (100)

PO3-85 PULMONARY VEIN STENOSIS AFTER CATHETER ABLATION; COMPARISON BETWEEN RADIOFREQUENCY AND IRREVERSIBLE ELECTROPORATION Fred H M. Wittkampf, PhD, Vincent J. van Driel, MD, Harry van Wessel, BSc, Peter Loh, MD, PhD and Pieter A. Doevendans, MD, PhD. Div Heart and Lungs, Univ Medical Center, Utrecht, Netherlands Introduction: Pulmonary vein (PV) stenosis is a potential problem after radiofrequency (RF) catheter ablation inside PV ostia. The reaction of the PV ostium to catheter ablation with irreversible electroporation (IR ) is unknown. Methods: In 5 si months old pigs (60 75 kg), the response of PV ostia to IR and RF catheter ablation was compared. Biplane PV angiograms were made before ablation. After NavX

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reconstruction of left atrial geometry, catheter ablation with IR was performed using a custom de ectable 20mm circular octopolar ablation catheter. Ten consecutive non arcing, non barotraumatic 200 oule shocks were delivered at different positions 0.5 to 1.5 cm inside 1 of the 2 PV ostia. Thereafter, circular PV ostial ablation was performed at the same depth inside the other ostium using sequential 30 watts RF applications via a standard irrigated 4mm ablation electrode. Selection of the energy source for each of the 2 PV ostia was alternated between animals. Biplane PV angiograms were made directly after ablation and after 3 months survival. PV ostial diameter and heart size were measured using the diameter of the contrast catheter as caliper. Results: With RF ablation, PV ostial diameters decreased 25±20 directly after ablation and remained 23±20 smaller after 3 months when compared with pre ablation diameters. With IR ablation, PV ostial diameter decreased 18±5 directly after ablation, but had increased 18±1 after 3 months when compared with pre ablation diameters. Corrected for the increase in heart size during growth of the animal from 6 to months, PV ostia in which RF ablation had been performed showed a signi cant 38±17 decrease in diameter (p 0.01), while PV ostia in which IR ablation had been performed showed a non signi cant 5±15 decrease in diameter after 3 month survival. (p 0.44) Conclusions: In this porcine model, RF ablation inside PV ostia causes signi cant PV stenosis after 3 months. In contrast, IR ablation at the same level does not affect PV ostial diameter.

PO3-86 CLINICAL SIGNIFICANCE OF INDUCED ATRIAL FIBRILLATION AFTER TERMINATION OF CHRONIC, PERSISTENT ATRIAL FIBRILLATION DURING STEPWISE APPROACH Yasutsugu Nagamoto, MD, Park Jae-Seok, MD, PhD, Daniel Tanubudi, MD, Yiu-Kwan Ko, MD, Ji-Eun Ban, MD, PhD, HwanCheol Park, MD, Jong-Il Choi, MD, PhD, Hong-Euy Lim, MD, PhD, Sang-Weon Park, MD, PhD and Young-Hoon Kim, MD, PhD. Korea University, Cardiovascular Center, Division of Electrophysiology, Seoul, Korea, Republic of Introduction: Atrial brillation (AF) termination has been used as the endpoint of catheter ablation of long lasting persistent AF (PeAF). It has not been evaluated whether an inducibility testing of AF after achieving AF termination in these patients is bene cial or not. The aim of this study was to evaluate the role of inducibility test of AF in predicting clinical outcomes during follow up. Methods: In 128 long lasting PeAF (> 1 year) patients underwent catheter ablation (pulmonary vein isolation, multiple linear ablations, defragmentation, and bidirectional block of cavotricuspid isthmus), inducibility was tested by rapid atrial pacing at the end of ablation procedure after AF termination. Induced AF was de ned as one lasting longer than 5 minutes. Results: f 128 patients, induced AF was lasted longer than 5 minutes in 52 patients ( roup 1) and induced AF was spontaneously terminated within 5 minutes in 76 patients ( roup 2). During 38±18 months of follow up, AF recurrence rate in roup 1 (n 20, 38 ) was tended toward higher than that in roup 2 (n 8, 24 ), but there was no signi cance difference. The incidence of atrial tachycardia (AT) as a recurred arrhythmia was also similar between two groups (6 in roup 1 vs 12 in roup 2, NS). Conclusions: AF which is inducible after termination of PeAF is not related to clinical AF or AT recurrence during follow up. Non inducibility of AF at the end of procedure is not predictive of maintenance of sinus rhythm after catheter ablation of long lasting PeAF.

PO3-87 LESION DEPTH WITH CIRCULAR IRREVERSIBLE ELECTROPORATION ABLATION Fred H M. Wittkampf, PhD, Vincent J. van Driel, MD, Harry van Wessel, BSc, Paul F. Gründeman, MD, PhD, Aryan Vink, MD, PhD, Pieter A. Doevendans, MD, PhD and Peter Loh, MD, PhD. Div Heart and Lungs, Univ Medical Center, Utrecht, Netherlands, Dept of Pathology, Univ Medical Center, Utrecht, Netherlands Introduction: Irreversible electroporation (IR ) may be a novel non thermal ablation modality for fast electrical pulmonary vein (PV) antrum isolation. However, lesion depth, continuity, and their relationship with shock magnitude still are unknown. Methods: In this pilot study in three 60 75 kg pigs, median sternotomy was performed and the pericardium was opened. The heart was raised to e pose the base of the left ventricle (LV). A custom device with a 20 mm circular decapolar ablation hoop was sutured to the basal LV. The device included a circular spacer above the ablation electrodes to keep the pericardium at 10 mm distance from the ablation area. After ation of the device, the heart was lowered into the pericardial sac and the pericardium was lled with heparinized blood to immerse the ablation area completely. Non arcing, non barotraumatic, IR ablation was performed between all 10 electrodes shunted together and a large indifferent skin patch electrode under the animal. Two more ablations were performed around the LV base without overlap between lesions. The ablations were performed in random sequence: 50 oule ( ), 200 , and 5 times 200 . Then, the thora was closed and the animal was allowed to recover and survive for 3 weeks. Thereafter, the heart was removed and sections of the lesion areas were histologically studied to measure width, depth and continuity of the lesions. Results: 50 applications resulted in small, separate, half spherical lesions under each electrode without continuity between lesions. Average lesion depth was 3.0±0.5 mm. At 200 , lesions had fused resulting in continuous circular lesions in all animals. Lesion transmurality was reached in 2/3 lesions. This, together with tissue shrinkage complicated measurement of lesion depth. Lesion depth was estimated to be .8±0.7 mm. Five successive applications of 200 also resulted in transmurality of 2/3 lesions. stimated average lesion depth was 7.1±0. mm. Vessels, when present in the lesion, did not appear to affect e tension of the lesion, which is in agreement with the non thermal character of IR ablation. Conclusions: A 200 application via a 20 mm circular decapolar catheter may result in continuous circular lesions, apparently deep enough for PV antrum isolation.

PO3-88 ELECTRICAL PULMONARY VEIN ISOLATION BY IRREVERSIBLE ELECTROPORATION Fred H M. Wittkampf, PhD, Vincent J. van Driel, MD, Harry van Wessel, BSc, Peter Loh, MD, PhD and Pieter A. Doevendans, MD, PhD. Div Heart and Lungs, Univ Medical Center, Utrecht, Netherlands Introduction: Catheter ablation by irreversible electroporation (IR ) is a promising new technology for pulmonary vein (PV) antrum isolation in patients with atrial brillation. Methods: In this porcine study (7 pigs, 60 75 kg), electrical PV antrum isolation was compared between conventional irrigated radiofrequency (RF) ablation and circular IR ablation. These animals have 2 PV ostia; one inferior and one on the right side with its ostium very close to the fossa ovalis. After left atrial and PV reconstruction with NavX, PV ostial IR ablation was

S250 performed with a non arcing, non barotraumatic, circular 200 application, delivered via a custom 20 mm octopolar ablation catheter. The other PV ostium was electrically isolated using sequential 30 watts RF applications delivered via a standard 4mm irrigated catheter electrode. Both isolations were performed as pro imal as technically possible inside the ostia. A large skin patch on the back served as indifferent electrode for both energy sources. The type of energy for both ostia was alternated between animals and ablation continued until complete electrical isolation was achieved with an observation time of 30 minutes. After ablation, the animals were allowed to recover and survive for 3 months. Results: PV potentials were present in 13/14 ostia, thus 13 ostia were targeted. Seven PV ostia were electrically isolated by IR ablation and 6 by sequential RF applications. n average, RF ablation took 786±205 sec of RF delivery while IR ablation took 1.4±0.8 applications of 6ms duration per ostium. For both technologies, the right PV ostium was most problematic because of its very close pro imity to the transseptal puncture site; the inferior PV ostium was always isolated with a single IR application. All animals will be restudied after 3 months survival. Complications did not occur. Conclusions: IR catheter ablation allows for fast electrical PV isolation with very promising results, at least acutely.

PO3-89 UPREGULATION OF SMALL-CONDUCTANCE CALCIUM-ACTIVATED K+ CURRENT IN FAILING RABBIT VENTRICULAR CELLS IS DUE TO INCREASED SENSITIVITY TO CYTOSOLIC CA2+ Po-Cheng Chang, MD, Isik Turker, MD, Su-Kiat Chua, MD, Mitsunori Maruyama, MD, PhD, Mark J. Shen, MD, Zhenhui Chen, PhD, Michael Rubart-von der Lohe, MD, John C. Lopshire, MD, PhD, James N. Weiss, MD, Shien-Fong Lin, PhD, Peng-Sheng Chen, MD and Tomohiko Ai, MD, PhD. Indiana University School of Medicine, Indianapolis, IN, Department of Medicine (Cardiology), UCLA, Los Angeles, CA Introduction: Small Conductance Calcium Activated Current, or apamin sensitive current (I AS), is important in atrial but not ventricular repolarization in normal hearts. We investigated whether I AS density is altered in failing ventricular cells. Methods: We used a rabbit model of pacing induced heart failure (HF) for this study. The left ventricular (LV) function was evaluated by echocardiography. Left ventricular cardiomyocytes were isolated enzymatically, and I AS was measured using whole cell patch clamp techniques at 36°C with various free Ca2 concentrations in the pipette. RT PCR was performed to evaluate mRNA of S 2 channels, which carries the ma ority of I AS. Results: All HF rabbits showed LV systolic dysfunction ( F 31 ± 5 ). Failing ventricular cardiomyocytes showed signi cantly larger I AS density than the normal ventricular cells (I AS at 0 mV with [Ca2 i of 863 nM: 8.3 ± 1.00 pA/pF, n 6 cells from 5 failing rabbits, vs. 2.83 ± 0.87 pA/pF, n 6 cells from 4 normal rabbits, p 0.01). The steady state Ca2 response of I AS was leftward shifted in the failing cells compared with the normal cells. The data were tted with a Hill equation, yielding d of 232 ± 5 nM for failing, and 553 ± 78 nM for normal cells (p 0.002). S 2 mRNA levels in failing ventricles (N 5) averaged 118±8.5 compared to normal ventricles (p 0.3 ). Conclusions: In a rabbit model of pacing induced HF, I AS in the ventricles was signi cantly upregulated due to increased Ca2 sensitivity. Increased I AS may play a signi cant role in ventricular repolarization in HF. Its potential role in electrical remodeling and arrhythmogenesis warrants further evaluation.

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

PO3-90 MOLECULAR SIGNALLING UNDERLYING CONSTITUTIVE ACETYLCHOLINE-CURRENT ACTIVATION IN ATRIAL FIBRILLATION Samy Makary, PhD, Chia-Tung Wu, PhD, Niels Voigt, MD, Ange Maguy, PhD, Dobromir Dobrev, MD, PhD and Stanley Nattel, MD. Montreal Heart Institute/Université de Montréal, Montreal, QC, Canada, University of Heidelberg, Mannheim, Germany Introduction: AF causes atrial tachycardia remodelling (ATR), with enhanced constitutive acetylcholine regulated current (I AChc) playing a signi cant role by shortening APD and thereby promoting AF maintenance. Here, we e amined the molecular mechanisms underlying I AChc upregulation by ATR. Methods: Cultured dog atrial cardiomyocytes in vitro tachypaced at 3 Hz (P3) for 24 hours were compared to parallel nonpaced controls (P0). I AChc single channel activity was assessed in cell attached patches in P0 and P3 cells, as well as in cell attached and cell free (I ) patches of cells from in vivo ATR dogs (paced at 400 bpm 1 week). Protein e pression was measured by Western blot. Results: In vitro tachypacing for 24 hours activated I AChc (Fig A), mimicking the effect of in vivo ATR (Fig B), whereas 2 hours tachypacing had no signi cant effect. Tachypacing caused a [Ca2 i increase at 2 hours, with subsequent return to baseline (Fig C). Decreasing [Ca2 i during tachypacing with BAPTA AM (1 μM), a cell permeable Ca2 chelator, prevented P3 enhancement of I AChc at 24 hours (Po, channel open probability 0.35±0.03 , vs 1.55±0.18 without BAPTA, P 0.001). I AChc is regulated by protein kinase C (P C). posure of ATR cells to P C inhibitors (BIM I, chelerythrine) suppressed I AChc channel activity. The Ca2 dependent P C isoform P C inhibited, whereas P C enhanced, I AChc, when applied to the intracellular side of I patches. P C e pression was downregulated (by 37 P 0.01) in ATR. Conclusions: ATR induced increases in I AChc result from rate related [Ca2 i loading, likely via downregulation of the Ca2 regulated inhibitory P C isoform P C .

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30 increase in PLB phosphorylation at Thr 17). In addition, there was a 32 decrease in total RyR2 (p 0.05), and a 120 and a 27 increase in RyR P at 2815 (CaM II) 280 (P A CaM II) sites (normalized to total RyR2; P 0.01), respectively. Conclusions: We have developed a large animal model of nonischemic HF that e hibits spontaneous arrhythmias and contractile dysfunction, and which is associated with altered Ca handling (including CaM II activation) similar to human HF. This novel irreversible arrhythmogenic canine HF model will assist in understanding the comple mechanisms in nonischemic HF, and facilitate assessment of new therapies including human scale interventions such as ablation, implantable devices, and cell therapy.

PO3-92 REDUCTION OF VOLTAGE-GATED K+ CHANNELS CURRENTS BY ADIPOCYTOKINES ORIGINATED FROM PERICARDIAL FAT Kun-Tai Lee, MD, I-Hsin Liu, MS, Wei-Chung Tsai, MD, Paul Wei Hua Tang, MD and Wen-Ter Lai, MD. Kaohsiung Medical College Hospital, Kaohsiung, Taiwan

PO3-91 A NOVEL IRREVERSIBLE ARRHYTHMOGENIC CANINE MODEL OF NONISCHEMIC HEART FAILURE EXHIBITING ALTERED CA HANDLING PROTEINS AND ENHANCED CAMKII ACTIVATION Xun Ai, MD, Cheryl Killingsworth, PhD, Gregory Walcott, MD and Steven M. Pogwizd, MD. University of Alabama at Birmingham, Birmingham, AL Introduction: Heart failure (HF) is associated with high mortality from sudden arrhythmic death and pump failure. Future developments in pharmacologic as well as device based therapeutic approaches will require large animal models that not only resemble human HF (in contractile dysfunction, arrhythmogenicity) but which also are large enough for device implantation and which allow for long term studies (irreversible). The goals of our studies were to develop a large animal model of nonischemic HF (based on our HF rabbit model), and to characterize arrhythmogenesis and Ca handling (including CaM II activation). Methods: HF was induced in adult dogs by aortic insuf ciency followed by aortic constriction (3 weeks later). chocardiographic and holter monitoring were performed, as was Western blotting of LV tissue for protein e pression. Results: HF dogs had reduced LV fractional shortening (2 ± 3 vs. 40 ± 2 baseline, N 5, 5, p 0.001), spontaneous PVC’s and non sustained VT, and increased norepinephrine induced VT. Isolated HF LV myocytes had increased length (146 ± 5 μm vs. 124 ± 2 μm of age matched controls; n 65, 27 cells; p 0.05) and reduced shortening (2.6 vs. 4.8 ; p 0.001). HF LV e hibited a 30 downregulation of S RCA2 (vs. age matched controls; n 3, 3; p 0.001). HF LV also showed an increase in CaM II e pression (54 ; p 0.05) and activation (evident by a

Introduction: Amount of pericardial fat tissue are associated with occurrence of cardiac arrhythmias. picardial adipose tissue is a source of several adipocytokines. ffects of adipocytokines from epicardial adipose tissue on ion channels are unknown. Methods: picardial adipose tissues (0.5 to 1.0 g) were taken near the pro imal right coronary artery of rat. The samples were cut into small pieces and transferred into a 12 well plate. Serum free DM M (2 mL/g) was added to the well and incubated at 37°C in a C 2 incubator for 3 hours. The conditioned media were collected and centrifuged at 4°C for 10 minutes. The supernatants contained adipocytokines were corrected. The voltage gated outward current (I v) was measured using whole cell patch clamp method in H c2 cell. The H c2 cells were treated with supernatants (25ug/cc) for 18 hours as a study group. The I v were analyzed and compared between control and study groups. Results: In control and study groups, I v were activated by a series of depolarizing pulse from a holding potential of 70 to 50 mV applied in 10 mV increments. As comparing with control group, the I v were signi cantly decreased in study group at holding potentials 10 (0.82±0.5 vs. ±0.8 pA/pF, P 0.01), 0 (2.0±0. vs. 7.5±1.5 pA/pF, P 0.01), 10 (3.4±1.4 vs. 13.1±3.4, pA/pF, P 0.01), 20 (4.8±2.2 vs. 18.4±5.2, pA/pF, P 0.01), 30 (6.3±2. vs 24.4±6.6 pA/pF, P 0.01) 40 (7.8±3.6 vs 2 .1±7.4 pA/ pF, P 0.01), and 50 mV ( .5±4.1 vs. 34.6± .1, pA/pF, P 0.01), respectively. Conclusions: Adipocytokines delivered from pericardial fat tissue could signi cantly decrease I v. These results could contribute to relationship of pericardial fat and cardiac arrhythmias.

S252 PO3-93 TRANSIENT OUTWARD CURRENT RESPONDS DIFFERENTLY TO EXTERNAL AND INTERNAL PROTONS IN VENTRICULAR MYOCYTES Noriko Saegusa, PhD, Vivek Garg, PhD and Kenneth W. Spitzer, PhD. Nora Eccles Harrison CVRTI,University of Utah, Salt Lake City, UT Introduction: Changes in e tra and intracellular pH (pHo and pHi) accompany myocardial ischemia and protons have ma or effects on cardiac ion currents. However, the separate actions of low pHo and low pHi on transient outward current (Ito), a ma or contributor to early action potential (AP) repolarization, are unresolved and the focus of this pro ect. Methods: Myocytes were enzymatically isolated from subepicardial layers of the left ventricules of adult rabbits. H cells were transfected with h v4.3 or h v1.4. Whole cell Ito (voltage clamp: square pulses and AP clamps) and action potentials were recorded with suction pipettes and pHi was measured with SNARF 1. Starting from control conditions (pHo 7.4, pHi 7.2) each type of acidosis was applied for 1 2 min: low pHo (pHo 6.5, pHi 7.1) and low pHi (pHo 7.4, pHi 6.7) induced by superfusion with Na acetate. Results: Ito from 40 to 60 mV in myocytes was not signi cantly affected by low pHo (n 5). In contrast, low pHi reduced Ito at nearly all voltages (e.g., at 60 mV, control 11.8 ± 1.0 pA/pF, low pHi 5.3 ± 0.3 pA/pF, n , p 0.01, paired, 55 decline) in a pHi dependent manner (p i 6. 1). Low pHo in myocytes induced a right shift in V0.5 of the steady state inactivation curve from 43.5 ± 0.4 mV to 2 .2 ± 1.4 mV (n 5, p 0.01, paired). In contrast, low pHi caused no signi cant voltage dependent shifts in steady state inactivation (n 5) or activation (n ). Phase 1 AP repolarization in myocytes was markedly slowed by low pHi but largely unaffected by low pHo. During AP clamps peak Ito was reduced from 8.4 ± 0.7 to 4.5 ± 0.3 pA/pF (n 7; p 0.05, paired) by low pHi using control and low pHi AP templates. v4.3 current was not signi cantly changed by low pHo (n 3) but was reduced by 34.8 ± 7. (n 4, p 0.05, paired) during low pHi . In contrast, v1.4 current was not signi cantly changed by low pHi (n 4). Conclusions: Selective reductions in pHo and pHi reveal a high sensitivity of ventricular Ito to internal protons that may account, in part, for the slowing of phase 1 repolarization by low pHi. pHi induced changes in v4.3 current appear to contribute to this effect. The absence of shifts in V0.5 during low pHi suggests that surface charge effects are not involved and protons may directly reduce channel permeability.

PO3-94 CPVT ASSOCIATED RYR2-G230C MUTANT CHANNELS EXHIBIT DECREASED BINDING OF THE STABILIZING SUBUNIT CALSTABIN2 AND ARE LEAKY DURING STRESS Marwan Refaat, MD, Albano C. Meli, PhD, Miroslav Dura, PhD, Steven Reiken, PhD, Anetta Wronska, MS, Julianne Wojciak, MS, Joan Carroll, MA, Andrew R. Marks, MD and Melvin M. Scheinman, MD. University of California San Francisco Medical Center, San Francisco, CA, Columbia University / Department of Physiology and Cellular Biophysics, New York, NY, Georg August University Medical Center (UMG)/Department of Cardiology, Goettingen, Germany Introduction: A 50 year old Caucasian male with a 20 year history of e ertional syncope and cardiac arrest had an ICD, with an appropriate shock.His brother and son had sudden cardiac death after e ercise. He had a RYR2 ly230Cys mutation. The functional effects of this mutation are not known.

Heart Rhythm, Vol 8, No. 5, May Supplement 2011 Methods: Functional characterization of human RyR2 230C channels was performed and compared to wild type (WT) channels blinded to genotype under conditions mimicking stress. Results: At low cytosolic calcium concentration ([Ca2 cyt 150 nM, comparable to diastolic conditions), RyR2 WT and RyR2 230C channel activities were similar [mean opening probability (Po) 0.0076 0.0045 for RyR2 WT vs. 0.00 2 0.0041 RyR2 230C; p NS, n 5 and 5 channels, respectively, Fig. 1A 1C). Protein inase A (P A) treated RyR2 230C channels e hibited a shift to the left in Ca2 dependent activation with a signi cant higher Po at low activating [Ca2 cyt 150 nM (mean Po of 0.0682 0.0202 for RyR2 WT vs. 0.181 0.0380 for RyR2 230C; p 0.05, n 5 and 7 channels, respectively, Fig. 1B 1C). Both WT and RyR2 230C channels e hibited a similar level of P A phosphorylation (Fig. 1D 1 ). The P A treated RyR2 230C channels had a signi cant lower amount of calstabin2 in the channel comple by immunoprecipitation/ immunoblotting (Fig. 1D 1F) compared to WT. Conclusions: RyR2 230C, a novel mutation close to the amino terminus with similar biophysical defects to other mutations near the middle of the RyR2 channel, is associated with decreased binding of the stabilizing subunit calstabin2 . This mutation is unique in that it e erts allosteric effects on RyR2 producing stress induced diastolic Ca2 leakage.

PO3-95 TWO PATHWAYS TO SINOATRIAL NODE DYSFUNCTION IN HEART FAILURE Joseph F. Yanni, MBChB, PhD, Xue Cai, PhD, Tomoko T. Yamanushi, PhD, James O. Tellez, PhD, Tony Corno, PhD, MRCP, Rob Hutcheon, BSc, Oliver Monfredi, MRCP, Guoliang Hao, BSc, Urszula Mackiewicz, MBChB, PhD, Michal Maczewski, MBChB, PhD, Andrzej Beresewicz, MBCHB, FHRS, Halina Dobrzynski, PhD, George Hart, MD, PHD, FHRS and Mark R. Boyett, PhD. University of Manchester, Manchester, United Kingdom, University of Liverpool, Liverpool, United Kingdom, Kagawa Prefectural College of Health Sciences, Takamatsu City, Japan, NHS UK, Manchester, United Kingdom, Medical Center of Postgraduate Education, Warsaw, Poland Introduction: In heart failure (HF), dysfunction of the sinoatrial node (SAN) occurs and bradyarrhythmias are responsible for a substantial proportion of deaths. We investigated whether there are changes in ion channels in the SAN in HF. Methods: Three models were studied: (i) rabbit model of volume and pressure overload (caused by destruction of aortic valve and banding of aorta); (ii) rat model of pulmonary hypertension (PHT; caused by subcutaneous in ection of monocrotaline); and

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(iii) rat model of myocardial infarction (MI; caused by ligation of pro imal left coronary artery). All studies were conducted in accordance with the uide for the Care and Use of Laboratory Animals (US NIH Publication No. 85 23, revised 1 85). In the rabbit model and rat MI model, echocardiography demonstrated severe impairment of left ventricular systolic function. In the two rat models, there was a decrease in the intrinsic heart rate (evidence of SAN dysfunction; measured in Langendorff heart e periments). Tissue was sampled from the right atrium and SAN and e pression of 33~80 ion channel mRNAs was measured using quantitative PCR. Results: During HF, a relatively small number of signi cant changes in e pression were observed in atrial muscle (6, 27 and 7 in rabbit, rat PHT and rat MI models), but a larger number was observed in the SAN (48, 58 and 40 ). In the rabbit and rat PHT models, the bradycardia can be e plained by a downregulation of HCN4 ( 87 and 41 ), Cav1.2 ( 51 and 38 ) and NCX1 ( 46 and 38 ), all of which carry inward current. However, in the rat MI model, there was an upregulation of HCN4 ( 63 ), Cav1.2 ( 55 ) and NCX1 ( 37 ), and instead the bradycardia can be e plained by an upregulation of channels carrying outward current, including R ( 100 ), vLQT1 ( 50 ), ir2.4 ( 267 ) and TWI 2 ( 73 ). Interestingly, there was a downregulation of e pression of R ( 50 and 70 ) and vLQT1 ( 57 and 33 ) in the rabbit and rat PHT models. Conclusions: These results show (i) the dynamic nature of ion channel e pression in the SAN and (ii) there are two pathways to SAN dysfunction in HF, one involving a downregulation of inward current carrying channels and one involving an upregulation of outward current carrying channels.

Candidate genes were evaluated by resequencing and linkage mapping of transcript levels. Results: Heritability of HR in this population was 51 , suggesting a large genetic contribution. Linkage mapping identi ed a region on rat chromosome 13 controlling HR, with peak L D score 6.7. This QTL has not previously been identi ed in human, rat or mouse. Mean nocturnal HR in strains carrying the SHR allele was 388, compared with 357 in BN like strains; an allelic effect of 31bpm (8.7 , p .00005) that is equivalent to 5 bpm in humans, corresponding to a decreased risk of cardiovascular death of 10 2 . Two approaches con rmed that this effect was independent of physiological covariates, suggesting it is intrinsic to the heart. We produced the rst genomewide transcript e pression pro le of the SN. Three genes at the new HR locus were enriched in the SN (FDR .05). ne candidate gene was under genetic control, and potentially causative sequence variants have been identi ed. We translated these ndings to humans using data from a genome wide association study population. Conclusions: We have identi ed a new genetic locus for HR, which does not contain genes in pathways already known to determine HR. We have prioritised three candidate genes at the locus, which may be targets for therapeutic modulation of HR in patients with heart disease.

PO3-96

Hector Barajas Martinez, PhD, Dan Hu, MD, PhD, Denis Avdic, BS, Gabriel Caceres, BS, Ryan Pfeiffer, BS, Elena Burashnikov, BS, Barbara Deal, MD and Charles Antzelevitch, PhD, FHRS. Molecular Genetics Laboratory, Masonic Medical Research Laboratory, Utica, NY, Children’s Memorial Hospital, School of Medicine Northwestern University, Chicago, IL

INTEGRATIVE GENOMIC APPROACHES IDENTIFY NEW GENES CONTROLLING HEART RATE James S. Ware, MRCP, Halina Dobrzynski, PhD, Michal Pravenec, DSc, PhD, Samuel L. Wilkinson, BSc, Phill J. Muckett, BSc, Yalda Jamshidi, PhD, MRCP, Tim J. Aitman, FMedSci, PhD, Nicholas S. Peters, FRCP, MD, FHRS and Stuart A. Cook, PhD, MRCP. MRC Clinical Sciences Centre, and National Heart & Lung Institute, Imperial College London, London, United Kingdom, School of Medicine, University of Manchester, Manchester, United Kingdom, Institute of Physiology, Czech Academy of Science, Prague, Czech Republic, MRC Clinical Sciences Centre, Imperial College London, London, United Kingdom, Division of Clinical Developmental Sciences, St George’s Hospital Medical School, London, United Kingdom, National Heart & Lung Institute, Imperial College London, London, United Kingdom Introduction: Heart rate (HR) is a fundamental measure of cardiac function, and is of prognostic and therapeutic signi cance. We applied genetic and genomic approaches to identify new genes controlling HR in a rat model that has previously been used to nd human cardiovascular disease genes. Methods: Telemetric aortic pressure transducers were implanted into 226 animals from 31 rat strains: the Brown Norway, the Spontaneously Hypertensive Rat, and 2 strains from a recombinant inbred panel derived from these parental strains. HR was measured over several weeks, and each strain genotyped. Statistical analyses were carried out using the R package, and quantitative trait loci (QTL) identi ed by linkage mapping using QTL Reaper. The sinus node (SN) and right atria (RA) of 20 rats were microdissected. ene e pression data were generated with the Affymetri Rat ene 1.0 ST microarray and analysed using Bioconductor.

PO3-97 NOVEL MUTATION IN CACNB1 AS A NEW BRUGADA SYNDROME SUSCEPTIBILITY GENE SECONDARY TO LOSS-OF-FUNCTION IN CARDIAC L-TYPE CALCIUM CHANNEL

Introduction: Cardiac L type voltage dependent calcium channels play a key role in the electrical and mechanical function of the heart. They are composed of a central pore forming CaV1.2 subunit ( 1) and a set of ancillary subunits ( 2, , and 2). Mutations in CACNA1C (Cav1.2), CACNA2D1 ( 2 ), and CACNB2 ( 2) genes have recently been associated by our group with the Brugada (BrS) and early repolarization ( RS) syndromes. Recent studies have identi ed CACNB1 ( 1) in the human heart. The ob ect of this study was to determine whether mutations in the CACNB1 gene are associated with the wave syndromes. Methods: All e ons and intron borders of CACNB1 and 8 Brugada susceptibility genes were screened by direct DNA sequencing from 205 probands diagnosed with wave syndromes. Calcium currents (ICa) were recorded using whole cell patch clamp techniques. Results: A novel mutation in CACNB1 was detected in a BrS proband manifesting a briefer than normal QT interval. The proband is a 20 yr old male with a strong family history of sudden death. His father and uncle died at 37 and 42 years of age, respectively. enetic screening revealed a novel heterozygous mutation in CACNB1 gene (c.7 1A> ) predicting substitution of arginine for histidine at position 264 (p.His264Arg; H264R). Alignment of the amino acid sequence of 1 proteins revealed that histidine at position 264 is highly conserved among species. This mutation was not found in 406 reference alleles from healthy controls. Mutagenesis was performed and the mutated clone was co e pressed with CACNA1C WT, CACNB2 WT, CACNA2D1 WT in TSA201 cells. Patch clamp recordings demonstrated that the mutant signi cantly reduced calcium

S254 channel current (ICa). Homozygous e pression of CACNB1 H264R reduced peak ICa by 5 , whereas heterozygous e pression reduced current by 55 . Conclusions: ur results are the rst to identify CACNB1 as a new BrS susceptibility gene. The CACNB1 H264R mutation is associated with classical phenotypic features of BrS and abbreviated QT interval, consistent with an ICa loss of function. ur results suggest that genetic screening of wave syndromes include CACNB1. Additional studies of the role of the 1 subunit are needed it to gain a better appreciation of the development of an approach to therapy.

PO3-98 A HETEROZYGOUS MUTATION (R231C) LOCATED IN S4 VOLTAGE SENSOR DOMAIN OF THE KCNNQ1 CHANNEL LEADS TO ATRIAL FIBRILLATION, SINUS BRADYCARDIA AND LONG QT SYNDROME Sven Zumhagen, MD, Ulrike Henrion, No Degree, Katja Steinke, MSc, Nathalie Strutz-Seebohm, PhD, Florian Lang, MD, Eric Schulze-Bahr, MD and Guiscard Seebohm, PhD. Institute for Genetics of Heart Diseases (IfGH), University Hospital Münster, Muenster, Germany, Biochemistry I - Cation Channel Group, Bochum, Germany, Department of Physiology I, University of Tübingen, Tuebingen, Germany Introduction: The CNQ1 gene encodes for the slow potassium channel I s, which has a leading part in the cardiac action potential repolarization. However, I s channels are heteromeric channels and composed of CNQ1 and CN subunits. Mutations in CNQ1 can lead to atrial brillations (AF) due to gain of function, where as a loss of function results in the long QT syndrome (LQTS). Methods: N/A Results: In two families (n 25), a CNQ1 (R231C) mutation with an autosomal dominant inheritance was identi ed in 8 (female (f): n 5, age: 25 ± 23) together with 3 additional facultative mutation carriers. Most of them were asymptomatic, whereas SCD occurred in 2, with evidence of underlying LQTS. However, LQTS was diagnosed in 5 pts. (f: n 4; QTc 487 ms). In 2 cases (f: n 1) the leading clinical presentation was AF, of which one had additional LQTS. Further 4 pts. (f: n 2) suffered from sinus bradycardia (SB). Interestingly, two males had SB since day of birth with a heart rate of 57 bpm (normal age dependent HR: >110 bpm). To study the functional characteristics of the CNQ1 mutation, electrophysiological studies were performed by e pressing and functionally analyzing the respective channels in Xenopus laevis oocytes. As a result, the mutation reduced voltage sensitivity of channels, possibly as a result of neutralization of the positive charge. Modeling suggested that the charge carrying side chain of R231 is positioned suitable to transfer transmembrane voltages into conformational energy. Further, the mutation altered the functional interactions with CN subunits. The mutation acted in a subunit dependent manner suggesting altered I s function by the presence of different CN subunits in atria and ventricles as the molecular basis of both, familiar AF and LQTS in mutation carriers. Conclusions: In these cases a mutation in the CNQ1 predisposed not only for LQTS but also to AF and SB. perimentally, the neutralization of the positive charge carried by R231 leads to largely reduced voltage dependence of CNQ1 channels and altered functional CN sensitivity, which cause diverse functional effects depending on the speci c CN subunit. These effects may be causative for the clinical manifestation reported here, whereas the reason for SB is not fully understood yet.

Heart Rhythm, Vol 8, No. 5, May Supplement 2011 PO3-99 MULTIPLE ARRHYTHMIC SYNDROMES IN A NEWBORN DUE TO A NOVEL MUTATION IN SCN5A Jonathan M. Cordeiro, PhD, Kirstine Calloe, PhD, Nicole Schmitt, PhD, Ryan Pfeiffer, BS, Ronald Kanter, MD and Charles Antzelevitch, PhD, FHRS. Masonic Medical Research Laboratory, Utica, NY, University of Copenhagen, Copenhagen, Denmark, Duke University Medical Center, Durham, NC Introduction: Mutations in SCN5A have been linked to Brugada syndrome (BrS), progressive conduction disease and Long QT syndrome (LQT3), as well as to pre and neonatal ventricular arrhythmias. Here we describe a novel mutation in NaV1.5 in a newborn giving rise to atrial brillation, slowed conduction, and a slightly prolonged QT interval. Methods: enomic DNA was isolated and all e ons and intron borders of 15 ion channel genes were ampli ed and sequenced. Site directed mutagenesis was performed and CH cells were co transfected with wild type (WT) or mutant NaV1.5 in the absence or presence of NaV1.5 1 subunit. Whole cell patch clamp studies were performed 48 72 hours after transfection. Results: The proband displayed chaotic atrial tachycardia in utero, 2:1 AV block, atrial utter and ventricular brillation in the rst minutes of life. enetic analysis uncovered a missense mutation in SCN5A (Q270 ) encoding NaV1.5. Patch clamp analysis showed about a 40 reduction in peak current density for Q270 compared to WT. However, both fast and slow decays of INa were signi cantly slower in mutant channels both in absence and presence of NaV 1 subunit. Steady state activation and inactivation of Q270 channels were shifted to positive potentials and window current was increased. The tetrodoto in sensitive late INa was increased almost 3 fold compared to WT channels. Action potential voltage clamp e periments revealed that the Q270 mutation increased late INa during the plateau phase of the cardiac action potential in congruence with a LQT3 phenotype. Ranolazine reduced late INa in Q270 channels compared to WT, while e erting minimal effects on peak INa. Conclusions: ur ndings suggest that the Q270 mutation in SCN5A, by reducing peak INa and augmenting late INa, may underlie the life threatening arrhythmias in this neonate characterized by an overlap syndrome consisting of a slightly prolonged QT interval, conduction disease and atrial brillation.

PO3-100 TRPC3 CHANNELS REGULATE CARDIAC FIBROBLAST PROLIFERATION BY CONTROLLING CALCIUM ENTRY Masahide Harada, MD, PhD, Jonathan Ledoux, PhD, Xiao Yan Qi, PhD, Ange Maguy, PhD, Balazs Ordog, PhD, Toyoaki Murohara, MD, PhD, Kaichiro Kamiya, MD, PhD, Itsuo Kodama, MD, Ulrich Schotten, MD, PhD, David Van Wagoner, PhD, Dobromir Dobrev, MD, PhD and Stanley Nattel, MD. Montreal Heart Institute/Université de Montréal, Montreal, QC, Canada, RIEM Nagoya University, Showa-Ku, Nagoya, Japan, University of Maastricht, Maastricht, Netherlands, Cleveland Clinic, Cleveland, OH, University of Heidelberg, Mannheim, Germany Introduction: Cardiac broblast (FB) proliferation and differentiation produce arrhythmogenic substrates. We have reported that a selective transient receptor potential canonical 3 (TRPC3) channel blocker, pyrazole3 (Pyr3), decreases cultured rat FB proliferation and that TRPC3 e pression is upregulated in AF (HRS 2010). However, the cellular/molecular mechanisms remain unclear and were the ob ect of the present study. Methods: Nonselective cation current (INSC) was measured with patch clamp, Ca2 entry with uorescent Ca2 imaging

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(Fluo 4 AM), FB proliferation with ow cytometry and protein e pression by immunoblot. Results: Isolated rat cardiac FBs had signi cant 3 μM Pyr3 sensitive INSC (2.1±0.2 pA/pF at 100 mV). Pyr3 blocked Ca2 in u induced by A or angiotensin II (Fig). FBs were cultured in three conditioned media: (1) normal medium (2.4 mM Ca2 , CTL), (2) low Ca2 medium (0.4 mM) and (3) normal medium with Pyr3 (3 μM). FB number decreased in low Ca2 and Pyr3 vs. CTL (by 32 * and 32 * respectively, n 6, *p 0.05). 2/M cell content, an inde of cell division, also decreased (by 12 * and 20 *), suggesting decreased proliferation. In addition, speci c TRPC3 knockdown with shRNA reduced proliferation by 35 *.The ratio of phosphorylated e tracellular signal regulated kinase ( R 1/2), which is Ca2 sensitive and enhances proliferation, to total R 1/2, decreased in low Ca2 or Pyr3 vs. control (by 68 * and 62 * respectively, n 6). Conclusions: TRPC3 channels control rat cardiac FB proliferation, likely by acting as a Ca2 entry pathway that induces R 1/2 phosphorylation. TRPC3 signalling could provide new targets to prevent arrhythmogenic remodeling.

distribution are e pressed by cardiac myocytes. A highly sensitive microimmunoassay was used to measure the levels of cytokines in the serum of 18 ARVC patients and 35 healthy controls. Results: Increased immunoreactive signal for IL 17, TNF and IL 4 was seen in ventricular tissues in / , 8/ and 7/ cases of ARVC, respectively. Signal was distributed diffusely within cardiac myocytes and occurred in regions devoid of in ammatory in ltrates. ARVC patients had signi cantly increased circulating levels of selected pro in ammatory cytokines including IL 6 receptor, IL 8, macrophage in ammatory protein 1b and monocyte chemoattractant protein1. Levels of TNF receptor types 1 and 2, known to track with adverse outcomes in heart failure, were also elevated. Levels of the anti in ammatory cytokine IL 1 receptor type 2 were signi cantly depressed in ARVC patients compared to controls. Conclusions: We have discovered local myocardial production of cytokines and alterations in the balance between circulating pro in ammatory and anti in ammatory cytokines in patients with ARVC. These observations provide a foundation for future studies in which analysis of serum in ammatory biomarkers can be assessed in risk strati cation and correlated with arrhythmias or other manifestations of disease. These observations also raise the possibility of anti in ammatory therapy in ARVC.

PO3-102 MICRORNA 29B - A MECHANISTIC CONTRIBUTOR AND BIOMARKER IN ATRIAL FIBRILLATION Reza Wakili, MD, Kristin Dawson, BSc, Balazs Ordog, PhD, Sebastian Clauss, MD, Xiao Yan Qi, PhD, Sophie Cardin, PhD, Moritz Sinner, MD, Stefan Kääb, MD, PhD and Stanley Nattel, MD. Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada, Klinikum Grosshadern Munich, University of Munich, Munich, Germany

PO3-101 MYOCARDIAL EXPRESSION AND ELEVATED CIRCULATING LEVELS OF INFLAMMATORY CYTOKINES IN ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY Angeliki Asimaki, MD, PhD, Harikrishna Tandri, MD, Elisabeth R. Duffy, MSc, William J. McKenna, MD, Hugh Calkins, MD, Shiva Gautam, PhD, Daniel G. Remick, MD and Jeffrey E. SafÀtz, MD, PhD. Beth Israel Deaconess Medical Center, Boston, MA, Johns Hopkins, Baltimore, MD, Boston University School of Medicine, Boston, MA, The Heart Hospital, London, United Kingdom Introduction: Immunoreactive signal for the desmosomal protein plakoglobin is reduced at cardiac intercalated disks in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). We recently reported a similar change in plakoglobin signal in two forms of granulomatous myocardial in ammation, sarcoidosis and giant cell myocarditis, but not in lymphocytic (non granulomatous) myocarditis. We also showed that e posure of cultured cardiac myocytes to cytokines associated with granulomatous in ammation (IL 17 and TNF ) causes translocation of plakoglobin from cell cell unctions to intracellular sites, thus implicating cytokines in the pathogenesis of ARVC. Methods: Ventricular myocardium from ARVC patients was analyzed by immunohistochemistry to determine whether selected cytokines that might mediate changes in plakoglobin

Introduction: MicroRNAs (miRs) are involved in cardiac remodeling, and miRs released into the blood have potential value as biomarkers. This study assessed the role of miR2 b, predicted to target collagen (C L) e pression, in an e perimental AF substrate associated with heart failure (HF) and its interest as an AF biomarker. Methods: Dogs sub ected to ventricular tachypacing (VTP, 240 bpm) for 24 h, 1 wk, 2 wk were compared to nonpaced controls (CTLs) (n 8/group). pression of miR2 b and its putative target C L1A1 was assessed in left atrial (LA) tissue and LA broblasts (AFBs) by qPCR. MiR plasma levels were determined in blood from AF , HF , and CTL patients (n 33, 32, 30/group). Results: perimental data: After 1 wk, VTP dogs showed increased AF duration (17 fold***, p 0.001) and LA brosis (4 fold***), which persisted at 2 wk VTP (22 ***, 6 fold*** respectively). MiR2 b e pression fell after 24 h VTP ( 0 ***) and remained reduced at 1 wk ( 75 ,** p 0.01) and 2 wk VTP ( 61 ,* p 0.05). C L1A1 e pression also increased after 1 and 2 wk VTP (10 *, 16 fold***). To further evaluate the role of miR2 b, we produced lentiviral mediated miR2 b knockdown ( D) and overe pression ( ) in AFBs. Mir2 b D increased C L1A1 e pression ( 124 ***), while decreased C L1A1 e pression by 40 *. Clinical data: Plasma miR2 b levels decreased in AF and HF (Fig. A), with enhanced changes in patients with both (Fig. B), while levels of a comparator miR (miR15) not believed to be affected by HF, and unaltered in HF induced canine AF atria, were unchanged (Fig. C, D). Conclusions: MiR2 contributes to atrial pro brillatory structural remodeling and has potential value as a clinical AF biomarker.

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Heart Rhythm, Vol 8, No. 5, May Supplement 2011 PO3-104 NOVEL INSIGHT IN PROTECTIVE EFFECTS OF HSPB AGAINST CONTRACTILE DYSFUNCTION AND STRUCTURAL CHANGES USING A DROSOPHILA MELANOGASTER MODEL FOR ATRIAL FIBRILLATION Deli Zhang, MSc, Lei Ke, MD, Katkarina Mackovicova, MSc, Johan Van Der Want, PhD, Ody Sibon, PhD, Robert Henning, MD, PhD, Harm Kampinga, PhD and Bianca Brundel, PhD. University of Groningen, Groningen, Netherlands

PO3-103 CONNEXIN43 INHIBITION BY PROINFLAMMATORY CYTOKINES IS BLOCKED BY DOCOSAHEXAENOIC ACID: A POTENTIAL MECHANISM FOR THE ANTIARRHYTHMIC EFFECTS OF OMEGA 3 FATTY ACIDS Jennifer Baum, BS, Elena Dolmatova, MD and Heather S. Duffy, PhD. BIDMC/Harvard Medical School, Boston, MA Inroductions: The proin ammatory cytokine Interleukin 1beta (IL 1b) increases in the heart post myocardial infarction (MI) causing the proarrhythmic loss of the gap unction protein, Conne in43 (C 43). mega 3 Fatty acids, particularly docosahe aenoic acid (DHA), e hibit antiarrhythmic/anti in ammatory properties. Therefore we hypothesize that mega 3 fatty acids positively regulate C 43 to increase coupling post MI. Methods: Cultured cells were treated with IL 1b either with or without preincubation of 30uM DHA. Western blot of cell fractions was done to e amine C 43 levels. Immunostaining was used to e amine C 43 and NFkB, the downstream mediator of IL 1b signaling. C 43 channel function was assessed using a dye spread assay. Results: Western blot showed that IL 1b caused a downregulation of C 43 (0.1uM IL 1b) in both the soluble and insoluble cellular fractions (43 / 6 and 74 / 6 respectively). Interestingly DHA pretreatment caused signi cant upregulation in both fractions of IL 1b treated cells (1 8 / 28 soluble and 224 / 26 insoluble) (p 0.05 n 3). Dye spread assays showed IL 1b signi cantly inhibits C 43 function (200. / 17.7 um [Control vs. 112.8 / 14. um [0.1uM IL 1b , p 0.05) but DHA treated cells remained highly coupled in the presence of IL 1b [167. / 21. um [DHA vs. 164.4 / 22.3 um [DHA 0.1uM IL 1b , p 0.05, n 4). amination of downstream effectors of IL 1b signaling showed no change in N or p38 activation with DHA treatment. IL 1b stimulated translocation of NFkB to the nucleus, with an increase in uorescence intensity up 341 / 28 (p 0.05 n 3) relative to control, however this effect was almost completely abolished with DHA treatment, up only / 64 compared to control suggesting that mega 3 Fatty acid inhibits the canonical IL 1b signal transduction pathway. Conclusions: mega 3 Fatty acid treatment inhibited IL 1b stimulated loss of membrane bound C 43 as well as increased cytoplasmic C 43. DHA, therefore, alters the e pression of C 43 in the presence of proin ammatory cytokines by blocking signaling through NFkB suggesting a novel cardio protective mechanism by which mega 3 Fatty acids may prevent proarrhythmic loss of C 43 post MI.

Introduction: The most common clinical tachycardia, Atrial Fibrillation (AF), is a progressive disease, caused by cardiomyocyte remodeling, which nally result in contractile dysfunction and AF persistence. Recently, we observed a protective role of heat shock proteins (HSPs), especially the small HSPB1 member, in AF. ur understanding of tachycardia remodeling is currently hampered by the lack of suitable (genetic) manipulatable in vivo models for rapid screening of key targets in remodeling. We hypothesized that Drosophila melanogaster can be e ploited to study tachycardia remodeling and the protective effect of HSPs by HSP inducing drug treatments or by utilizing genetically manipulated small HSP overe pressing strains. Methods: arly pupae from Drosophila were tachypaced for 20min at 5Hz and reduction in heart rate and arrhythmicity were assessed. HSP e pression was induced by a Heat shock (HS, 1h, 370C), A (1mM), or B P 15 (1mM) pretreatment. To assess the effect of individual small HSPs, transgenic strains were created, with overe pression of DMHSP23, DmHSP27, DmC 4461, DmC 740 and DmC 14207. Results: Tachypacing of Drosophila resulted in gradual and signi cant cardiomyocyte remodeling, such as reduced contraction rate, increase in arrhythmic episodes and reduction in heart wall shortening, compared to normal pacing. HS, A, or B P 15 pretreatment resulted in a signi cant induction of HSP e pression and protection against tachycardia remodeling. Furthermore, only DmHSP23 overe pressing strains were protected against tachycardia remodeling. (Ultra)structural evaluation of the tachypaced heart wall revealed loss of sarcomeres and mitochondrial damage which were absent in tachypaced DmHSP23 overe pressing Drosophila. Conclusions: Tachypacing of Drosophila resulted in cardiomyocyte remodeling, which was prevented by general HSP inducing treatments and the overe pression of a single small HSP, DmHSP23. The ndings are comparable to in vitro and in vivo models for AF and therefore tachypaced Drosophila melanogaster can be used as an in vivo model system for a rapid identi cation of novel targets for remodeling and intervention.

PO3-105 MULTISCALE MODELING OF CA CYCLING IN CARDIAC VENTRICULAR MYOCYTE: MACROSCOPIC CONSEQUENCES OF MICROSCOPIC DYADIC FUNCTION Namit Gaur, MS and Yoram Rudy, PhD. Washington University, Saint Louis, MO Introduction: Structural defects in t tubules during heart failure can lead to reduced density of L type Ca channels (LCCs) and/ or coupling between dyads. enetic mutations in calsequestrin (CSQN) can result in altered SR Ca buffering ability or impaired regulation of ryanodine receptor (RyR2) gating. These alterations occur at the level of the dyad and can affect whole cell behavior in comple ways. In this study, using a physiologically detailed multiscale model of Ca cycling, we e plore effects of such changes in dyadic function on whole cell behavior in a paced

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ventricular myocyte. Methods: A mutiscale mathematical model of Ca cycling in a cardiac ventricular myocyte containing 10,000 diffusively coupled stochastically functioning dyads was developed and used for the study. A model of CSQN modulation of RyR2 gating (luminal Ca sensor) was developed and included in the model. Results: Reduction in number of LCCs from 15 to 4 and RyR2s from 100 to 25 in the dyad results in asynchronous activation of dyads, smaller (peak 0.6 ± 0.06 M vs 0.84 ± 0.04 M) and slower (time to peak (TTP) 5 ± 4 ms vs 31 ± 2 ms), Ca transient (CaT). Impaired inter dyad coupling results in asynchronous activation of dyads, smaller (peak 0.54 ± 0.06 M vs 0.84 ± 0.04 μM) and slower (TTP 58 ± 3 ms vs 31 ± 2 ms) CaT. ffect of impaired inter dyad coupling on synchrony of activation of dyads was negligible when the number of LCCs in the dyad was increased to 25 or the volume of dyadic space reduced by 50 . Impaired luminal Ca sensor function increased the frequency of diastolic Ca sparks (380 ± 10 s 1 vs 40 ± 4 s 1). It also induced Ca waves (10 ± 2 s 1) and long lasting Ca release events (11 ± 1 s 1). Increased frequency of Ca waves and long lasting Ca release events occurred only in the presence of inter dyad coupling. Conclusions: Dyadic structural changes associated with heart failure can result in smaller CaT and slower CaT kinetics. These effects are due to asynchronous activation of dyads. Impaired luminal Ca sensor increases the frequency of Ca sparks, waves and long lasting Ca release events. These effects are modulated by inter dyad coupling and buffering capacity of CSQN.

PO3-106 LAMINAR MICROSTRUCTURE MEDIATES VIRTUAL ELECTRODE POLARIZATIONS THAT ABOLISH REENTRY. Jesse L. Ashton, MSc, Mark L. Trew, PhD, Darren A. Hooks, MBChB, PhD and Bruce H. Smaill, PhD. Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand Introduction: It is widely argued that shock induced virtual electrode polarizations (V Ps) are key contributors to successful termination of reentry (cardioversion). To date, however, neither e perimental nor modeling studies have been able to con rm the role of V Ps formed by myocardial laminar microstructure in cardioversion. The ob ective of this study was to elucidate the e tent to which laminar discontinuities could contribute to the success or failure of cardioversion using a biophysically based model of myocardial microstructure, suf ciently large enough to support reentry. Methods: Spiral wave reentry was generated in large domain (~15cm²) 2D models derived from high resolution images of midwall porcine left ventricular myocardium. A modi ed LRd cell model incorporating an asymmetric response to electric shock and electroporation was used. lectric shocks of varying duration and waveform with uniform voltage gradients were applied at a range of strengths. Action potentials from regions ad acent to the pre shock wavefront were reconstructed. The de brillation threshold (DFT) for models with representation of discontinuous laminar microstructure was compared to that for models with continuously varying description of myo bre orientation. Results: Virtual electrodes were generated distal to shock electrodes along laminar discontinuities. They mediated cardioversion by eliminating available e citable tissue and e tending the action potential duration (APD) of tissue directly in the path of the pre shock wavefront. Weak shocks and shocks of short duration failed to e tend APD suf ciently, leading to failure of cardioversion by persistence of pre shock reentry or generation of reentry with a different morphology. The

de brillation threshold (DFT) with a monophasic shock 10 ms in duration was substantially lower for the discontinuous model (2.1 V/cm) than the control continuous model (>14 V/cm). Conclusions: The DFT in the discontinuous model is close to the range of shock strengths used clinically. This study shows for the rst time that virtual electrodes generated by laminar discontinuities derived from real myocardium are a key contributor to effective cardioversion.

PO3-107 POSSIBLE TARGET SITE OF THERAPY IN CATECHOLAMINERGIC POLYMORPHIC VENTRICULAR TACHYCARDIA: A THEORETICAL STUDY Yi-Hsin Chan, MD, Chia-Tung Wu, MD, Yung-Hsin Yeh, MD, Lung-Sheng Wu, MD, Chun-Li Wang, MD, Wei-Jan Chen, MD, Tzu-Shiu Hsu, MD and Chi-Tai Kuo, MD. Chang Gung Memorial Hospital, Taoyuan, Taiwan Introduction: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a congenital arrhythmogenic disease with repeated ventricular arrhythmia during high adrenergic tone. It is a serious disease with a high mortality but its management is limited. The aim of this study is to investigate the underlying electrophysiological mechanisms by which the RyR2 mutations result in CPVT through adrenergic stimulation. Also, sites targeted for anti arrhythmic therapy are investigated in order to nd potential managements in CPVT. Methods: The mutant RyR2 with reduced stored overloaded induced Ca2 release (S ICR) threshold is incorporated into the Luo Rudy dynamic (LRd) cell model to elucidate the underlying pathologies of CPVT. A variety of blockade (from 0~ 0 ) in speci c ion channels including the Na /Ca2 e changer (INaCa), fast Na channel (INa), RyR2 receptor (Irel), Ca2 ATPase (S RCA) (Iup) or L type Ca2 channel (ICa(L)) are performed to simulate the speci c drugs in target sites. Results: The simulations reveal that adrenergic stimulation increases Ca2 load in cardiac myocyte, which facilitates spontaneous SR Ca2 leakage, resulting in triggered arrhythmias. The frequency of spontaneous SR Ca2 leakage, intracellular Ca2 oscillation, and DAD episodes increases with gradually reducing the S ICR threshold. f note, sustained DADs mediated triggered activities post pause happened in the simulated mutant cell. Blockade of the INaCa (up to 10 blockade), in contrast to the Iup (up to 30 blockade), ICa(L) and INa, (up to 40 blockade), and followed by Irel (up to 80 blockade), is most effective in suppressing the triggered arrhythmias in CPVT. Speci cally, dual blockade of ICa(L)/ Iup, INa/Irel or ICa(L)/Irel have the synergistic effect in CPVT management. Conclusions: ur simulations reveal that the therapy in targeting at the Na /Ca2 e changer (INaCa) may be potentially useful in suppressing CPVT related arrhythmias. Besides, dual blockade of ICa(L)/Iup, INa/Irel or ICa(L)/Irel have the synergistic effect in CPVT management, if clinically available in the future.

PO3-108 MODELING FORCE AND CARDIAC INOTROPY IN RABBIT VENTRICULAR MYOCYTE Jose L. Puglisi, PhD, Jorge A.. Negroni, PhD and Donald M.. Bers, PhD. University of California Davis, Davis, CA, Favaloro University, Buenos Aires, Argentina Introduction: adrenergic stimulation is an important physiological modulator of cardiac activity. Activation of adrenergic receptors ( AR) increases intracellular levels of cAMP that in turn activates protein kinase A (P A). Several

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proteins involved in e citation contraction coupling ( CC) can be phosphorylated by P A. The multiplicity of targets of sympathetic stimulation and the non linear interplay between the proteins involved in CC, makes it dif cult to predict the consequences of adrenergic induced alterations on action potential (AP), Ca transients and force. Moreover these alterations can be deleterious in either chronic or acute stimulation. To construct a mathematical description that accurately reproduces critical aspects of the AR response it is necessary to include the myo laments not as a simple passive buffer but as an entity capable of feedback to others Ca transport systems. Methods: We incorporated a new model of force generation/ shortening into a comprehensive mathematical description of the rabbit ventricular AP and Ca transient (LabH ART). The computer programs was implemented using LabVI W (National Instruments) on a windows PC. Results: The model was able to reproduce isotonic and isometric contractions and the classical curves of Force vs. Ca and Force vs cell length relationships. Isoproterenol (IS ) application was simulated by altering L type Ca current, the slowly activating delayed recti er current, sarcoplasmic reticulum (SR) Ca pump, SR Ca leak, myo laments Ca sensitivity and cross bridge cycling. The latter modi cation was essential to reproduce the IS induced increase in force generation/shortening e perimentally observed. AP duration (APD) adaptation to pacing frequencies was also e amined. IS shortened APD at all frequencies compared to control and attened the adaptation curve, thus allowing an APD compatible with short cycle lengths (up to 5 Hz). Conclusions: This model provides a useful framework to study cardiac inotropy and constitutes a starting point to investigate electro mechanical feedback in cardiac performance. The new version LabH ART 5.3 is freely available online at ww.labheart. org

Results: Computationally, isoproterenol increased APDR slope by 0 and shortened AL by 25 , which compared well to the 135 and 30 observed in AF patients. Isoproterenol also caused a leftward shift in AL onset by >45 msec, as seen in AF patients. Modeling revealed that alterations to ion currents which shorten AL and shift functional AL onset also increase APDR slope. Speci cally, reducing I r inactivation and shifting INa inactivation to negative potentials produced the greatest increases in APDR slope and decreases/shifts in AL. In AF patients but not controls, isoproterenol promoted AF initiation. Conclusions: Computational modeling and clinical measurements suggest that isoproterenol steepens APDR and shortens AL, primarily by reducing I r inactivation and increasing sodium channel availability. Future work should e amine whether altered potassium and sodium current kinetics also e plain enhanced AF susceptibility from isoproterenol.

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Introduction: Inhibition of glycolysis has been shown in isolated cardiac myocytes to promote action potential duration (APD) and Cai2 transient alternans causing triggered beats. However, the role of glycolytic inhibition ( I) in promoting triggered activity and ventricular brillation (VF) in intact hearts remains unclear. We hypothesized that I promotes early afterdepolarizations ( AD), triggered activity and VF in aged brotic, but not in normal young adult, rat hearts. Methods: Simultaneous dual voltage and Cai2 LV epicardial optical mapping and microelectrode recordings were made from the left ventricular (LV) of isolated perfused aged (~2 years) and adult (~3 months) male rat (Fisher344) hearts in Langendorff setting. I was induced by replacing glucose with 10 mM sodium pyruvate in o ygenated Tyrode’s solution. Results: I promoted spontaneous VF in 2 out 31aged hearts but in none (0 out of 18) of the adult hearts (P 0.001). VF was initiated by AD mediated triggered activity that originated from LV base in18 out of 2 mapped VF episodes in (N 10). I signi cantly (P 0.05) slowed the Cai2 transient decline rate and shortened the APD causing ADs to coincide in time with elevated cytosolic Cai2 levels. While I caused similar degrees of V Cai2 changes in adult hearts, it however failed to promote ADs and VF. libenclamide, a mi ed sarcolemmal and mitochondrial ATP sensitive channel blocker, reversed APD shortening by I and suppressed VF in 5 out of 7 hearts studied (all P 0.05). However, 5 hydro ydecanoate, a selective mitochondrial ATP sensitive channel blocker, failed to prevent I mediated shortening of APD and VF in all 7 hearts studied. The effects of I were reversible. Mean LV brosis averaged 32±8 in the aged and 4±1 adult hearts (P 0.001) Conclusions: The combined I’s slowing of Cai2 reuptake and shortening of the APD via activation of sarcolemmal ATP sensitive channels promote ADs, triggered activity and VF in

ISOPROTERENOL ALTERS POTASSIUM AND SODIUM CURRENT KINETICS TO STEEPEN ACTION POTENTIAL DURATION RESTITUTION AND SHORTEN ACTIVATION LATENCY IN HUMAN ATRIAL FIBRILLATION Jason D. Bayer, MS, David E. Krummen, MD, Sanjiv M. Narayan, MD, PHD, FHRS and Natalia A. Trayanova, PhD, FHRS. Johns Hopkins University, Baltimore, MD, University of California San Diego, La Jolla, CA Introduction: Isoproterenol may steepen atrial action potential duration restitution (APDR) and shorten activation latency (AL) and thus facilitate atrial brillation (AF). However, the mechanisms by which isoproterenol produce these clinical effects are unclear. Using computer modeling, we investigated if ion current densities and kinetics modi ed by isoproterenol e plain altered APDR and AL as observed clinically. Methods: Realistic tissue models of human atria tissue were developed for control and persistent AF. Ion current remodeling in AF was modeled from slot blot and patch clamp data. Isoproterenol concentration of 1 μm was simulated by increasing the current densities of I ur by 50 , I s by 250 , and ICaL Iup simultaneously until the calcium transient doubled. Alterations in ion current kinetics were simulated by factoring the forward and backward rate constants of I r inactivation by 3 and 1/3, respectively, shifting the inactivation and activation curves for ICaL by 2 mV, and the curves of INa by 10 mV and 5 mV, respectively, to depolarized potentials. APDR and AL curves were generated by S1S2 pacing in each model, and were validated with restitution curves from left atrial monophasic action potentials via the same S1S2 pacing protocol in 1 persistent AF and 6 control patients (age 62± y).

PO3-110 SARCOLEMMAL BUT NOT MITOCHONDRIAL ATP CHANNEL BLOCK PREVENTS SPONTANEOUS VENTRICULAR FIBRILLATION INITIATED BY GLYCOLYTIC INHIBITION IN FIBROTIC HEARTS Jong Hwan Lee, MD, PhD, Norishige Morita, MD, Aneesh Bapat, BS, Pargol Samanianpour, MD, Michael C. Fishbein, MD, William J. Mandel, MD, James N. Weiss, MD and Hrayr S. Karagueuzian, PhD. Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of, Translational Arrhythmia Research Unit, Cardiovascular Research Laboratory, David Geffen School of Medicine at UCLA, Los Angeles, CA, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, Southern California Cardiovascular Group, Beverly Hills, CA

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Poster Session III

brotic aged rat hearts. Young adult hearts without brosis are less susceptible, possibly because the source sink mismatch in well coupled tissue suppresses AD formation.

PO3-111 THE LATE SODIUM CURRENT BLOCKER RANOLAZINE SUPPRESSES MULTIFOCAL VENTRICULAR FIBRILLATION Jong Hwan Lee, MD, PhD, Norishige Morita, MD, Pargol Samanianpour, MD, Yuanfang Xie, PhD, Zhilin Qu, PhD, James N. Weiss, MD and Hrayr S. Karagueuzian, PHD, FHRS. Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of, Translational Arrhythmia Research Section, UCLA Cardiovascular Research Laboratory and the Division of Cardiology, Departments of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA Introduction: We previously have shown that o idative stress with hydrogen pero ide (H2 2, 0.1mM) promotes ventricular brillation (VF) in aged rat hearts, which is sustained by multifocal triggered beats initiated by early afterdepolarizations ( ADs). We hypothesized that the late Na current (INa L) blocker ranolazine (R) suppresses multifocal VF by progressively decreasing the number of AD mediated triggered foci. Methods: Aged (~2 years) rat hearts (male Fisher344) were isolated and perfused in Langendorff setting and stained with a voltage sensitive dye to optically map the activation pattern of the left ventricular (LV) epicardial surface. Microelectrode recordings were made from selected LV epicardial sites to de ne the cellular mechanism of focal activity. Results: R (10 M) perfusion, beginning 5 s after the onset of 0.1mM pero ide induced VF, terminated the VF after a mean of 1.3±0.4 min (N 8, 26 episodes). n washout of R and in the continued presence of H2 2, cellular ADs and triggered activity progressively emerged in 7 out of 8 hearts culminating in VF after a mean of 36±10 min of R washout. In 8 additional hearts, R (10 M) was perfused for 30 min before H2 2. VF was prevented in all 8 hearts for up to one hour of e posure to H2 2. n washout of R and in the continued presence of H2 2 VF reemerged in 7 out of 8 hearts after a mean of 25±8 min washout of R. Activation maps showed that the VF was sustained by multiple epicardial foci separated by recovered tissues that appeared at an average of 6.8±3.2 every 100 ms. The number of foci decreased from 6.8±3.2 to 3.5±1.2 foci after a mean of 1.1±04 min eventually leading to only a single focus causing a brief ( 6 s) period of VT before the resumption of sinus rhythm. Simulations in 2D tissue using realistic ventricular cardiac cell model with increased INa L to mimic R effect led to AD mediated multifocal VF. Block of the INa L caused a progressive reduction in the number of foci leading to VF termination. Conclusions: Late Na current blockade with R is effective in suppressing o idative stress mediated ADs and multifocal VF in aged hearts with increased brosis.

PO3-112 IMPAIRING N-CADHERIN-MEDIATED ADHESION INCREASES THE RISK OF INDUCIBLE VENTRICULAR ARRHYTHMIAS IN ISOLATED RAT HEARTS Jiangang Zou, MD, Hongjun Zhu, PhD, hegui wang, PhD and kejiang Cao, MD. Nanjing Medical University, Nanjing, China Introduction: Recent studies suggest that cadherin mediated adherens unctions may be impaired in ventricular arrhythmia related diseases or pathological processes, concomitantly with a decrease in conne in 43 (C 43). In this study, we aimed to

evaluate the acute arrhythmogenic effects of adherens unction impairment in isolated rat hearts Methods: Fifty si isolated adult male rat hearts were perfused with 0.2 mM AHAVD (a synthetic peptide speci cally inhibits N cadherin, n 18), 0.2 mM IPPINL (A nonsense peptidase contains the high conservative sequence in cadherins, n 18) or o ygenated H buffer as control (n 20), respectively. Results: Ventricular tachyarrhythmias tended to be induced in AHAVD perfused hearts ( /18) more than in the IPPINL perfused (4/18) or control (3/20) groups (P 0.05) by programmed e tra stimuli. Conduction velocity of left ventricular myocardium showed an inversed pattern in these three groups (53.5±6.3, 65.2±6.2 and 66.3±8.8cm/s, respectively, P 0.05). Neither effective refractory period nor epicardial action potential duration at 0 repolarization (APD 0) discriminated signi cantly between the groups post 1 hour of perfusion. Redistribution of C 43 and decreasing of PS368 can be observed in the tissue of AHAVD perfused hearts. Conclusions: ur results indicate that reduction of functional gap unction in the intercalated discs of cardiomyocytes may be one of the initial mechanisms by which myocardial conduction is blunted and susceptibility to ventricular tachyarrhythmias increased in rat hearts with impaired adherens unctions.

PO3-113 EFFECT OF VAGOTOMY ON THE ACTIVITY OF CARDIAC AUTONOMIC GANGLIA AND DISTRIBUTION OF DOMINANT FREQUENCY IN THE LEFT ATRIUM Hung-Yu Chang, MD, Li-Wei Lo, MD, Yenn-Jiang Lin, MD and Shih-Ann Chen, MD. Cheng-Hsin General Hospital, Taipei, Taiwan, Veterans General Hospital-Taipei, Taipei, Taiwan Introduction: Both e trinsic (vagosympathetic nerve) and intrinsic (ganglionated ple i, P) cardiac autonomic nervous systems are important for initiation and maintenance of atrial brillation (AF). We aimed to evaluate the effect of vagotomy on the activity of P and the change of dominant frequency (DF) distribution in the left atrium (LA). Methods: Si anesthetized dogs received mid thoracotomy, and the biatria were e posed. Acetylcholine patch was applied on ma or LA Ps, including anterior right P (AR P), inferior right P (IR P), superior left P (SL P), inferior left P (IL P), and also superior vena cava aorta P (SVC Ao P) to induce AF. An nsite Array was deployed in the LA for recording AF before and after vagotomy. Results: The LA global mean DF was higher before vagotomy than that after vagotomy (7.8±1.0 Hz vs. 7.0±1.7 Hz, p 0.004).

S260 The ma imal DF distribution was located at the corresponding (primary) and nearby (secondary) Ps during LA P activation and at the LA septum during SVC Ao P activation before vagotomy ( gure). After vagotomy, the ma imal DF distribution shifted to non P LA sites during 4 LA Ps and SVC Ao P activation. Conclusions: The LA global mean DF during AF was signi cantly lower after vagotomy. The distribution of the ma imal DF was located at the primary and secondary Ps before vagotomy, and it shifted to non P LA sites after vagotomy, suggesting the tonic vagal activity is important for the P activation during cholinergic AF.

Heart Rhythm, Vol 8, No. 5, May Supplement 2011 site selection during CFA ablation in human AF.

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PO3-114 PREVALENCE OF COMPLEX FRACTIONATED ATRIAL ELECTROGRAMS IN HUMAN LONG LASTING PERSISTENT AF. HIGH DENSITY EPICARDIAL MAPPING DEMONSTRATES SIGNIFICANT VARIABILITY ACCORDING TO CFAE DEFINITION Geoff Lee, MBChB, Kurt Roberts-Thomson, MBBS, PhD, Steven J. Spence, No Degree, Teh Andrew, MBBS, Saurabh Kumar, MBBS, Patrick Heck, MBBS, Liang-Han Ling, MBBS, John C. Goldblatt, MBBS and Jonathan M. Kalman, MBBS, PhD. The Royal Melbourne Hospital, Melbourne, Australia, Royal Adelaide Hospital, Melbourne, Australia Introduction: During ablation of persistent AF, comple fractionated atrial electrograms may be de ned either by the presence of: 1) Visual Fractionation (VFrac) comple multi component signals and or continuous electrical activity and or 2) discrete high frequency electrograms with CL 120ms. It remains unclear if the 2 de nitions identify the same atrial substrate. Methods: High density epicardial mapping of the posterior LA was performed in 7 pts with long lasting persistent AF > 1 yr undergoing cardiac surgery (68±16yrs, LA 50±5mm, 6/7 F>50 ). Using a 128 point electrode plaque, 10s segments of simultaneous data were analyzed. Point by point analysis was performed to determine the spatial distribution of CFA using 3 de nitions: 1. VFrac ( >2 de ections greater than 50ms duration and or continuous electrical activity) 2. AFCL 100ms 3. AFCL 120ms. Results: The of sites deemed CFA varied markedly between pts (76 to 13 by AFCL 120 de nition) and was signi cantly different using the 3 de nitions in each pt (Figure 1). There was poor correlation between sites of 1. VFrac and AFCL 100ms (r 0.16, P 0.05) 2. Vfrac and AFCL 120ms, (r 0.18, P 0.05). The of points with CL 120msec that showed VFrac was 33±18 . Conversely, the of points with VFrac which showed CL 120msec was 62±30 . Sens, Spec, PPV and NPV for AFCL 120ms detecting VFrac was 42 , 72 , 32 , 7 respectively (P 0.001). Conclusions: The prevelance of CFA varies markedly between pts and is highly dependent on the de nition of CFA adopted. Correlation between sites showing short CL and those with Visual Fractionation is low. This may have implications for

HIGH-DENSITY EPICARDIAL MAPPING OF HUMAN ATRIAL FIBRILLATION: SPATIAL RELATIONSHIP BETWEEN COMPLEX ELECTROGRAMS AND REGIONS OF HIGH DOMINANT FREQUENCY Geoffrey Lee, MBChB, Kurt Roberts-Thomson, MBBS, PhD, Steven Spence, No Degree, Andrew Teh, MBBS, Saurabh Kumar, MBBS, Patrick Heck, MBBS, Liang-Han Ling, MBBS, John C. Goldblatt, MBBS and Jonathan M. Kalman, MBBS, PhD. The Royal Melbourne Hospital, Melbourne, Australia, The Royal Adelaide Hospital, Melbourne, Australia Introduction: Comple fractionated atrial electrograms (CFA ) and regions of High Dominant Frequency may both identify sites critical to the maintenance of human AF. The anatomic and spatial relationship between these regions is unclear. Methods: 7 patients with long lasting persistent AF underwent high density epicardial mapping of the posterior LA. Using a 128 point electrode mapping plaque, 10 second segments of simultaneous data were analyzed. Simultaneous point by point analysis was performed to determine the spatial relationship between CFA de ned visually by multi component (>2 de ections greater than 50msec duration) and/or continuous signals and High DF sites (local DF 20 greater than the DF of ad acent sites) Results: Visually de ned CFA were present at 25±8 of sites. 17±5 HDF sites were identi ed per patient with a median DF of 8.7 Hz (IQR 7.6 10.4Hz). HDF sites were distributed equally throughout the posterior LA. There was poor point by point correlation between CFA and HDF (r 0.107). nly 35 of points representing HDF also showed comple visual fractionation. Despite this poor point by point correlation, spatial analysis revealed 84 of CFA were found ad acent (less than 2.5mm) to and partially surrounding a HDF site, 12 were 2.5 5mm and 4 5 10mm away from a HDF site.There was a poor correlation between sites of high HDF and regions of AFCL 120ms, r 0.188. Conclusions: Sites of visual CFA and regions of High Dominant Frequency infrequently show anatomic overlap. However, high density spatial analysis reveals that CFA are usually observed ad acent to and surrounding sites of HDF. This is consistent with CFA representing wavebreak around a high frequency focus as previously described in animal studies.