ARIs in the subendocardium. As these moderate differences diminishunder in vivo conditions, the experimental setting rather than the method-ology seems to account for respective differences in refractory patterns.

Endo Subendo Mid 1 Mid 2 Mid 3 Subepi Epi

ARI In vitro

(ms)

264 � 19 270 � 18* 268 � 23 261 � 23 259 � 19 251 � 15 254 � 14

ERP In vitro

(MS)

276 � 24 277 � 22 275 � 17 271 � 12 271 � 17 268 � 18 265 � 19

AB40-3

ELECTRICAL REMODELING PREDISPOSES THE CANINE HEARTTO DRUG-INDUCED TORSADES DE POINTES, WHICH ISASSOCIATED WITH INCREASED BEAT-TO-BEAT VARIABILITYOF REPOLARIZATIONMorten B. Thomsen, PhD, Avram Oros, MD, MariekeSchoenmakers, MD, PhD, Jurren M. Van Opstal, MD, PhD,Jet D. M. Beekman and Marc A. Vos, PhD. Heart LungCentre Utrecht, Utrecht, The Netherlands and CardiovascularResearch Institute Maastricht, Maastricht, The Netherlands.

Acquired long-QT syndrome in combination with increased beat-to-beatvariability of repolarization duration (BVR) is associated with lethal tor-sades de pointes arrhythmias (TdP) in dogs with chronic-AV block(CAVB). We evaluated the relative contributions of bradycardia and/orventricular remodeling to proarrhythmic BVR with and without IKr block.Methods: Retrospectively, 3 groups of dogs were selected: Sinus-rhythmdogs (SR, n�12); dogs with acute-AV block (AAVB, n�8); and dogs with�3 weeks CAVB (n�27). Under anesthesia, ECG and left ventricularmonophasic action potential duration (LV MAPD90) was measured. LocalBVR was assessed from 30 consecutive LV MAPD90 as previously de-scribed (&n-arysum;ni-ni�1/[30*�2]). All dogs received 25 �g/kgdofetilide IV.Results: The decreased ventricular rate acutely after AV block did notaffect QTc or BVR, whereas weeks of ventricular remodeling increasedboth (Table; *P�0.05 vs. other groups). Neither SR nor AAVB showedany proarrhythmia, whereas dofetilide induced TdP in 20 CAVB dogs(74%). Dofetilide increased the QTc interval in all groups (Table; †P�0.05vs. baseline), whereas BVR was only elevated in the CAVB dogs. Asubanalysis of susceptible vs. resistant CAVB dogs showed dofetilide-induced QTc prolongation in both groups (386�45 to 488�58 ms vs.349�40 to 406�51 ms, respectively; both P�0.05), whereas BVR wasonly increased in susceptible dogs (2.5�0.4 to 5.0�0.8 ms, P�0.05; vs.1.7�0.4 to 1.9�0.4 ms, P�NS).Conclusions: Under drug-free circumstances, an elevated BVR is remod-eling dependent rather than determined by the slower ventricular rate afterAV block. Dofetilide only elevates BVR in proarrhythmic dogs. Thus,BVR may aid the identification of the TdP-susceptible patient.

SR AAVB CAVB

RR baseline, ms 524 � 83* 1111 � 281 1245 � 179QTc baseline, ms 288 � 18 293 � 38 376 � 46*BVR baseline, ms 0.7 � 0.1 0.7 � 0.1 2.3 � 0.6*QTc dofetilide, ms 354 � 41† 348 � 71† 467 � 66†BVR dofetilide, ms 0.7 � 0.1 1.0 � 0.2 4.2 � 1.5†

AB40-4

INCREASED GLOBAL DISPERSION OF VENTRICULARREPOLARIZATION DURING LEFT VENTRICULAR EPICARDIALPACING: IN VIVO EVALUATION BY MONOPHASIC ACTIONPOTENTIAL MAPPING IN SWINEYunlong Xia, MD, Ole Kongstad, MD, PhD, Pyotr Platonov,MD, PhD, Magnus Holm, PhD, Bertil Olsson, MD, PhD and

Shiwen Yuan, MD, PhD. University Hospital, Lund, Swedenand Biosense Webster/Johnson & Johnson, Inc., Waterloo,Belgium.

Background: Recent studies have highlighted the benefits of biventricularpacing therapy for patients with congestive heart failure, but latest in vitrostudies suggested that epicardial pacing might lead to a prominent increasein transmural dispersion, which may be linked to the reported malignantventricular arrhythmias in patients with biventricular pacing. However, thedispersion of global repolarization under epicardial pacing has never beenin vivo evaluated.Methods: Using the CARTO mapping system, global monophasic actionpotential (MAP) mapping of the left and right ventricular endocardium intotal 120�24 sites were performed during RA pacing, RV apical endocar-dial (RVEndo) pacing and LV lateral epicardial (LVEpi) pacing in 10 healthypigs. Local activation time (AT), MAP duration and end-of-repolarization(EOR) time were measured and 3-dimensional maps of the AT and EORwere constructed. Global dispersion of AT and EOR were calculated as themaximal differences of these 2 parameters in each map. ECG was simul-taneously recorded during MAP mapping, from which QT, QT dispersionand Tpeak-Tend intervals were acquired.Results: 1). The global dispersion of AT increased from 52 � 10 msduring RA pacing to 65 � 18 ms during RVEndo pacing, and to 78 � 12 msduring LVEpi pacing. 2). The global dispersion of EOR times during LVEpi

pacing (93 � 18 ms) is significantly greater than those during RA (59 �11 ms, p�0.05) and RVEndo pacing (68 � 16 ms, p�0.05), whereas nosignificant difference was found between those during RA and RVEndo

pacing. (p�0.05) 3). QT intervals, QT dispersion and Tpeak-Tend intervalsduring LVEpi pacing were all significantly greater than those during RAand RVEndo pacing (p�0.05).Conclusion: Compared to RA and RVEndo pacing, LVEpi pacing increases QTinterval, QT dispersion, Tpeak-Tend interval and the global dispersion of ventricu-lar repolarization. These findings provide in vivo evidence supporting the involve-ment of increased dispersion of ventricular repolarization in the incidence ofmalignant ventricular arrhythmias in patients with biventricular pacing.

AB40-5

ENDURANCE TRAINING AGGRAVATES ARRHYTHMOGENICRIGHT VENTRICULAR CARDIOMYOPATHY IN HETEROZYGOUSPLAKOGLOBIN-DEFICIENT MICE - EVIDENCE FORFUNCTIONAL CONDUCTION SLOWING IN MICE AND MENPaulus Kirchhof, MD, PhD, Larissa Fabritz, MD, MelanieZwiener, MD, Henning Witt, PhD, Michael Schafers, MD,Stephan Zellerhoff, MD, Timur Athai, BS, Karl-Heinz Hiller,MD, Hideo Baba, MD, Gunter Breithardt, MD, PhD, PatriciaRuiz, PhD, Thomas Wichter, MD and Bodo Levkau, MD.University Hospital Muenster, Muenster, Germany, ChariteUniversity Medicine Berlin, Berlin, Germany, University ofWurzburg, Wurzburg, Germany and University of Essen,Essen, Germany.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inheritedcardiomyopathy affecting the right ventricle. ARVC is an important causeof sudden death in the young. Mutations in desmosomal proteins (plako-philin, desmoplakin, or plakoglobin) have been associated with ARVC.Whether reduced desmosomal protein function causes ARVC is notknown. Ten months old, but not three or six months old, plakoglobin-deficient mice (plako -/�) developed increased right ventricular volumes,reduced right ventricular function, and spontaneous ventricular ectopy (allp�0.05 vs. wild type littermates (WT)). Endurance training (8 weeks dailyswimming from the 4th month of life) resulted in the full phenotype ofARVC (right ventricular enlargement and arrhythmias) in 6 months oldplako -/� mice (p�0.05 vs. WT and vs. untrained plako -/� mice).Ventricular tachycardias with right ventricular origin occurred spontane-ously in isolated, Langendorff-perfused plako -/� hearts from trained 6months old mice. Furthermore, right ventricular activation times, but notleft ventricular activation times, were prolonged in trained plako -/�hearts. Action potential durations were not prolonged in either trained or 10

S83Session 40

months old plako -/� hearts compared to WT. Histology and electronmicroscopy did not identify right ventricular abnormalities. In 10 patientswith ARVC and ventricular arrhythmias undergoing invasive electrophys-iological study, right ventricular monophasic action potentials were notdifferent from controls (n�6), but QRS durations were prolonged duringfix-frequent right ventricular stimulation compared to controls (n�6) or tolong QT syndrome patients (n�9, both p�0.05).Conclusions: Endurance training accelerates development of ARVC inheterozygous plakoglobin-deficient mice. Right ventricular conductionslowing is the most prominent electrophysiological abnormality both inplako -/� mice and in patients with ARVC, which occurs in conjunctionwith right ventricular dysfunction, but without fibrosis or myocardial fat.

ABSTRACT SESSION 41: CATHETER ABLATION VII: Catheter Ablation of AFFriday, May 19, 20061:30 p.m.–3:00 p.m.

AB41-1

STRETCH INDUCED PULMONARY VEIN ELECTRICALREMODELING IN HUMANSPrashanthan Sanders, MBBS, PhD, Frederic Sacher, MD,Pierre Jaıs, MD, PhD, Li-Fern Hsu, MD, MBBS, Glenn D.Young, MBBS, Meleze Hocini, MD, Martin K. Stiles, MD,Bobby John, MD, Thomas Rostock, MD, Martin Rotter, MD,Yoshihide Takahashi, MD, Mark D. O’Neill, MBBS, PhD,Anders Jonsson, MD, Jacques Clementy, MD and MichelHaıssaguerre, MD. Royal Adelaide Hospital, University ofAdelaide, Adelaide, Australia and Hopital Cardiologique duHaut-Leveque, Bordeaux-Pessac, France.

Introduction: Atrial stretch is common to many clinical conditions thatpredispose to the development of atrial fibrillation (AF). The effects ofatrial stretch on the triggers and perpetuators of AF, in particular thepulmonary veins (PV), are unknown.Methods: 12 patients (5M, 35�10 yrs) undergoing ablation of left sidedaccessory pathways were studied. Atrial stretch was achieved by volumeloading (0.9% saline) to increase left atrial (LA) pressure �2 fold. Tocontrol for procedural variables, 12 further patients underwent the sameprotocol without the induction of stretch. Electrophysiological evalua-tion of the PVs was performed before and after volume loading bysequentially positioning a 10-pole Lasso catheter at the ostium and a4-pole map catheter distally. The following variables were evaluated:PV refractoriness (ERP); PV conduction time (CT); PV-LA functionalrefractoriness (FRP); PV-LA CT; and LA ERP.Results: See Table. Stretch was associated with an increase in LA pressurefrom 6�2 to 15�2 mmHg (�0.0001) This resulted in an increase in theERP of the PV, PV-LA junction, and LA by 7�8%, 5�19% and 7�6%respectively. In addition, it prolonged CT at the PV and PV-LA junction toa greater extent by 28�19% and 23�27% and was associated with pro-longed and more complex PV potentials at the ostia. There was no signif-icant change in any of these variables in controls.Conclusion: Stretch of the PV by volume loading results in an increase inERP and slowing of conduction at the PV and PV-LA junction. The effecton stretch was greater on conduction and was associated with prolongedand more complex potentials at the PV-LA junction.

Pre stretch Post stretch P-value

LSPV ERP (ms) 287 � 32 305 � 31 0.0009RSPV ERP (ms) 291 � 22 305 � 31 0.09LIPV ERP (ms) 277 � 25 313 � 46 0.01RIPV ERP (ms) 289 � 20 300 � 21 0.03PV CT at CL 600 ms (ms) 36 � 9 45 � 11 �0.0001PV-LA FRP (ms) 315 � 35 331 � 67 0.001PVP Duration at CL 600 ms (ms) 40 � 8 48 � 9 �0.0001PV-LA CT at CL 600 ms (ms) 64 � 17 77 � 17 �0.0001LA ERP (ms) 265 � 33 285 � 42 0.004

AB41-2

RELATIONSHIP BETWEEN MODE OF ARRHYTHMIARECURRENCE AND THE ACHIEVEMENT OF CHRONIC AFTERMINATION BY ABLATIONMichel Haıssaguerre, MD, Prashanthan Sanders, MBBS,PhD, Yoshihide Takahashi, MD, Meleze Hocini, MD, AndersJonsson, MD, Mark D. O’Neill, MBBS, PhD, Martin Rotter,MD, Thomas Rostock, MD, Frederic Sacher, MD, PierreBordachar, MD, Pierre Jaıs, MD, PhD and JacquesClementy, MD. Hopital Cardiologique du Haut Leveque,Bordeaux-Pessac, France.

Termination of long lasting persistent atrial fibrillation (CAF) can beperformed by catheter ablation targeting thoracic veins and multiple leftatrial sites. This study describes the clinical outcome and subsequentarrhythmia recurrence depending on the achievement of acute AF termi-nation in a cohort of consecutive pts.Methods: 99 pts (53 � 9yrs) underwent ablation of CAF (16 � 25months) involving isolation of pulmonary veins, ablation of coronarysinus and all left atrial areas showing rapid/heterogeneous activity, andlinear lesions at the roof and mitral isthmus. Activation mapping wasperformed after conversion to atrial tachycardias (AT) until restorationof sinus rhythm. At 1, 3, 6 and 12 months after ablation patientsunderwent clinical review and 24-hour ambulatory ECG monitoring toidentify asymptomatic arrhythmia. Repeat mapping and ablation wasperformed in patients experiencing persistent arrhythmia.Results: AF terminated in 83pts (Term, 84%): directly to sinus rhythmin 13 or via ablation of intermediate AT in 70 pts. AF could not beterminated without DC or pharmacological cardioversion in 16 pts(NoTerm,16%). The amount of delivered RF energy did not differbetween groups. Three months after ablation, sustained arrhythmiarecurrence was documented in 46 pts with a similar incidence in Term(37 pts, 46%) and No Term groups (9 pts, 56%). However AT was thedominant mode of recurrence in Term pts (35/37) whereas AF was themost common arrhythmia observed in No Term pts (5/9; p�0.002). Therecurrent arrhythmia was unrelated to whether CAF terminated in AT orsinus rhythm at the index procedure. Repeat ablation was performed in41 pts showing macro-reentry due to gaps in ablation lines and/or focalarrhythmias demonstrating a clustered distribution. Cardioversion wasperformed in 5 pts. At 8�6months of follow-up, 95 pts (96%) were insinus rhythm while 4 had paroxysmal arrhythmia.Conclusions: Catheter ablation of CAF associated with acute AF termina-tion achieves maintenance of sinus rhythm in 96% of pts. However repeatprocedures are commonly required for arrhythmia recurrence which takesthe form of AT in Term pts and of AF in No Term pts.

AB41-3

EFFECTS OF GAP GEOMETRY ON CONDUCTION THROUGHDISCONTINUOUS RADIOFREQUENCY LESIONSFrancisco J. Perez, MD and Mark A. Wood, MD. VirginiaCommonwealth University, Richmond, VA.

Background: Gaps of sufficient width or cross sectional area within linearradiofrequency (RF) lesions may preserve conduction through the lesion.The purpose of this study is to test the hypothesis that the geometry of thegap will also affect conduction through the lesion.Methods: RF lesions were created in isolated perfused rabbit right ven-tricular free wall preparations to produce gaps with 3 different lesiongeometries: straight, bifurcating and angled. Angled preparations contained2 right angles within the conduction path. Optical mapping was used toassess bidirectional conduction through the myocardium before and aftergap formation during pacing at 1000, 400 and 200 ms cycle lengths.Results: After lesion formation, 9 of 10 straight gap preparations and 1 of10 angled gap preparations demonstrated bidirectional conduction (p �0.001) at all cycle lengths. Nine of 10 bifurcated gap preparations demon-strated bidirectional conduction and 1 demonstrated unidirectional conduc-tion at all cycle lengths. Two bifurcated gap preparations showed unidi-

S84 Heart Rhythm, Vol 3, No 5, May Supplement 2006