LBBB while the 4 (7%) CM pts with LBBB had a median QRSd of 132ms.RBBB occurred in 14% of pts, including 20% of those with CHD.

*� p�.01

Among ventricularly paced pts (n�160), median QRSd was 148ms (range84- 208). Paced QRSd was shorter among those � 10 yrs (144�19ms,p�0.01).Conclusions: A minority of pediatric and CHD pts with ventricular dys-function meet traditional criteria for CRT. Epicardial lead placement, eitherbecause of size � 10kg or single ventricle physiology, may be required inmany pts. Particularly among younger pts, conventional pacing is associ-ated with relatively narrow QRSd, possibly limiting that advantage ofCRT.

385

Post-operative treatment costs of atrial fibrillation undermedicare*John Hernandez, PhD, *Elise M. Pelletier, MS, *Mary AnnClark, MS, *Betsy J. Justason, MS and *Fred Morady, MD.Health Economics and Outcomes Research, Boston ScientificCorp, Natick, MA and Univ of Michigan Medical Ctr, AnnArbor, MI.

Purpose: Substantial research has been devoted to the prevention andtreatment of post-operative atrial fibrillation (AF) following open cardiacsurgery. However, treatment costs associated with post-operative AF in theMedicare Program have not been adequately reported.Methods: Patients � 65 years of age with an initial AF diagnosis withintwo quarters after an open cardiac surgical procedure were identified in theMedicare Standard Analytic Files between July and December 1998 andfollowed for 1 year. Total and AF-related resource use and costs, includinghospital inpatient, outpatient, and physician and supplier services, weremeasured from the Medicare payment perspective. Outpatient prescriptiondrug costs were excluded from this study. All data were inflated by a factorof 20 to determine the aggregate burden of disease to the MedicareProgram.Results: The study included 401 Medicare patients with post-operativeAF. The average age was 74 years; 64% of patients were male. About 60%of patients had a hospital admission with a principal or secondary AFdiagnosis, while 96% of patients had at least 1 AF-related physicianencounter. AF-related treatment costs totaled $143 million, with hospitalinpatient costs comprising 98% of these costs. Approximately 80% ofpatients had co-morbid hypertension, while 37% had diagnoses of AF anddiabetes mellitus. Within the first year following the initial AF diagnosis,18% of patients died.

Conclusion: Post-operative AF patients incur significant AF-related treat-ment costs under Medicare, totaling $143 million annually, or almost$18,000 per patient each year. Health resource use due to AF also wassubstantial. Future studies comparing health resource use and treatmentcosts among cardiac surgery patients with and without AF are planned todetermine the incremental impact of AF to surgical patients.

POSTER SESSION IIThursday, May 20, 2004Session Time: 9:00 a.m.–12:00 noonPresenter Available: 10:15 a.m.–11:15 a.m.Location: Exhibit Hall

386

Reduced L-type Ca2� current in human chronic atrialfibrillation is associated with increased PP2A proteinphosphatase activityDobromir Dobrev, MD, PhD, Torsten Christ, MD, StefanWoehrl, Peter Boknik, MD, Erich Wettwer, PhD, Ralph-Frank Bosch, MD, PhD, Wilhelm Schmitz, MD, PhD,Michael Knaut, MD and Ursula Ravens, MD, PhD. DresdenUniv of Technology, Dresden, Germany, Univ of Tuebingen,Tuebingen, Germany, Univ of Munster, Munster, Germany,Dresden Univ of Technology, Tuebingen, Germany, UnivHosp of Munster, Munster, Germany and Heart Centre,Dresden Univ of Technology, Dresden, Germany.

Chronic atrial fibrillation (AF) is accompanied by a 70% reduction ofL-type Ca2� current (ICa,L) density and a 30-50% decrease in the mRNAexpression of the �1C channel subunit. This quantitative difference couldbe due to changes in regulatory mechanisms of channel function. Wehypothesized that chronic AF is associated with alterations in phosphory-lation dependent regulation of the channel. Right atrial appendages wereobtained from patients in sinus rhythm (SR) and chronic AF. ICa,L wasmeasured with the voltage-clamp technique (holding potential�-80 mV;test potential��10 mV for 200 ms). Protein kinases were activated bynorepinephrine (NE). Type-1 and type-2A protein phosphatases (PP1 andPP2A) were blocked with okadaic acid (OA). The expression of severalproteins was detected with Western blot. Basal peak ICa,L at �10 mV was70% smaller in AF than in SR (�2.6�0.3 pA/pF, n�34/11 [myocytes/patients], AF vs �7.7�0.9 pA/pF, n�64/26, SR). The reduced amplitudeof basal ICa,L was not associated with decreased protein levels of the �1C

and �2A channel subunits. NE (0.01-10 �M) increased ICa,L with a similarmaximum effect in both groups (increase at 10 �M NE: �6.8�1.3 pA/pF,n�13/5, AF vs �6.7�0.8 pA/pF, n�46/19, SR) and with comparablepotency (�log EC50: 7.3, AF vs 6.8, SR). These data provide evidence thatNE dependent phosphorylation is not impaired in AF and suggest thatreduced basal ICa,L may be due to enhanced dephosphorylation. The phos-phatase inhibitor OA (1 �M) increased ICa,L to a greater extent in AF thanin SR (OA-sensitive increase of ICa,L in AF: �7.7�1.4, n�8/4, vs SR:–4.2�0.9 pA/pF, n�18/7; P�0.05), hence absolute current densities weresimilar (AF: �11.9�1.6, n�8/4 vs SR:–13.0�2.9 pA/pF, n�18/7). Theprotein levels of the catalytic subunit of PP2A were 60% higher in chronicAF than in SR though no difference was found for PP1. We conclude thatin chronic AF the ratio of protein kinase/phosphatase activity is altered infavour of increased phosphatase activity resulting in lower basal ICa,L

current density. Our results suggest that protein phosphatases may be apotential drug target for treatment of chronic AF.

387

4-Aminopyridine, an Ito blocker, facilitates L-type calciumcurrent in mouse ventricular myocytesYanggan Wang, MD, PhD, Jun Cheng, BS, Minjie Jiang,MD, Diana T. McCloskey, PhD and Joseph Hill, MD, PhD.UT Southwestern Medical Ctr, Dallas, TX.

Background: Electrical remodeling in heart disease often involves alter-ations of both transient outward (Ito) and L-type calcium (ICa) currents,

S123Poster 2

whereas other membrane currents remain intact. Mechanisms underlyingthe functional, disease-related coupling of these currents are unknown butmay contribute to the elevated risk of arrhythmia in these patients. Toexplore this, we investigated the functional effect of an Ito channel blocker,4-aminopyridine (4-AP), on ICa.Methods: ICa was recorded in dissociated mouse ventricular myocytesusing the whole cell patch clamp method (holding potential �50 mV). Cs�

and TEA were substituted for K� and Na�, respectively, in both externaland internal solutions. Currents were recorded at room temperature.Results: 4-AP (2mM) significantly facilitated calcium influx through theL-type channel by increasing ICa density and slowing the time course of ICa

decay. At peak ICa (�10 mV), extracellular 4-AP increased ICa densityfrom 3.8 � 0.4 to 4.3 � 0.5 pA/pF, an increase of 11.7 � 1.3% (n � 9, p �0.001). In addition, 4-AP slowed the slow time constant of ICa decay (�2)without affecting the fast current decay time constant (�1). For example, at�10 mV, 4-AP slowed �2 from 70.9 � 5.9 to 130.7 � 20.2 ms (n � 9, p �0.05), without affecting �1. The effect of 4-AP on both ICa density and ratesof decay were not voltage dependent. However, 100 �M of 4-AP, whichwas demonstrated to fully block IKur without effect on Ito, had no effect onICa density or kinetics of current decay. To determine the underlyingmechanism, we treated cells with 10 �M KN93, a specific CaMKIIblocker. KN93 significantly suppressed ICa density and accelerated currentdecay and abolished the effects of 4-AP on ICa density and kinetics.Conclusion: This is the first report that 4-AP, an Ito blocker, enhancesL-type calcium current in cardiac myocytes. Facilitation of ICa by 4-AP isantagonized by CaMKII suppression, suggesting that phosphorylation ofchannel subunits or other associated proteins may be involved.

388

Enhanced transmural dispersion of repolarization isessential to the genesis of the first initiating beatcapable of triggering Torsade de PointesZhongxiang Yu, MD, PhD, Qinghai Yao, MD, Ying Wu, MD,Thinn Hlaing, MD, Chongzong Cui, MD, Gan-Xin Yan, MD,PhD and Peter R. Kowey, MD. First Affiliated Hosp, Xi AnJiao Tong Univ, Xi An, China and Main Line Health HeartCtr, Wynnewood, PA.

Background: Previous studies have demonstrated that enhanced transmu-ral dispersion of repolarization (TDR) serves as a functional reentrantsubstrate for the maintenance of Torsade de Pointes (TdP). We hypothe-sized that enhanced TDR is also essential to the genesis of the firstinitiating beat for TdP from phase 2 early afterdepolarization (EAD).Methods: Action potentials from epicardium and endocardium were si-multaneously recorded together with the ECG in the isolated rabbit left andright ventricular wedge preparations. Dofetilide was used to induce phase2 EAD and TdP at a basic cycle length of 2000 ms.Results: In the rabbit left ventricular wedge preparations, dofetilide at 0.01�M preferentially prolonged action potential duration (APD) in endocardium,leading to a marked increase in the QT interval and TDR, and the appearanceof phase 2 EAD in all of eight left ventricular wedge preparations. EndocardialAPD90 and TDR increased markedly from 232�6 to 438�37 ms and from41�3 to 110�13 ms, respectively (P�0.01). Markedly enhanced TDR ap-peared to facilitate transmural propagation of phase 2 EAD that manifested asfrequent R-on-T extrasystoles on the ECG. The extrasystoles, in turn, initiatedTdP in 5 of 8 preparations. On the other hand, a higher dose of dofetilide (0.03�M) was required to produce a comparable increase in endocardial APD andinduce EAD in all of the right ventricular wedge preparations. EndocardialAPD90 increased from 194�6 to 434�42 ms (n�8, P�0.01). Interestingly,dofetilide failed to increase TDR in the right ventricle (25�1 vs. 20�6 ms,p�0.05). Although dofetilide at relatively higher doses induced EAD in all ofeight right ventricular wedge preparations, no R-on-T extrasystoles or TdPwere observed (P�0.01 compared with left ventricles).Conclusions: (1). TDR is significantly greater in rabbit left ventricle thanthe right under a normal condition as well as in the presence of APDprolonging agent. (2). Enhanced TDR across the left ventricular wall iscritical to transmural propagation of phase 2 EAD that manifests as anR-on-T extrasystole on the ECG capable of initiating TdP.

389

Autonomic dysfunction in Brugada syndrome: Newevidence for impaired adrenergic stimulation frombiochemical analyses of endomyocardial biopsiesThomas Wichter, MD, Matthias Meyborg, MD, MatthiasPaul, MD, Joachim Neumann, MD, Joachim Neumann, MD,Tayfun Acil, MD, Peter Boknik, MD, Manfred Fobker, MD,Petra Gerdes, RN and Gunter Breithardt, MD. Univ Hosp ofMunster, Munster, Germany and Univ of Munster, Munster,Germany.

Background: Ventricular tachyarrhythmias in pts with Brugada syndromeusually occur during rest or sleep periods, suggesting a potential patho-physiological role of the autonomic nervous system. Recent studies em-ploying radionuclide imaging for the assessment of sympathetic innerva-tion support the hypothesis of impaired adrenergic stimulation of the heart.Methods: The purpose of our investigation was to further elucidate thishypothesis by analysis of sympathoadrenergic signal transduction path-ways from endomyocardial biopsies in patients with Brugada syndrome.Therefore, we measured the concentration of norepinephrine (NE), tyrosinehydroxylase (TH), NE transport carrier (NET) protein, inhibitory G-protein(Gi�1�2), and cAMP in endomyocardial biopsies from 8 pts with Brugadasyndrome. Tissue samples from 5 pts without known heart disease wereused as controls.Results: Compared to control myocardium, tissue concentration of NEwas reduced in pts with Brugada syndrome (774�177 vs. 1377�96 pg/gtissue; p�0.03). This indicates a reduction of presynaptic (vesicular) NEstorage. The expression of NET was not different but TH tended to hightexpression levels in Brugada syndrome (11.7�16.3 vs. 2.1�0.4 x 10 Mill.PI-Units; p�0.065). These findings reflect compensatory mechanims re-sulting from reduced adrenergic activity. Subsequently, Gi�1�2(39.1�5.6 vs. 52.1�7.3 x 10 Mill. PI-Units; p�0.02) and cAMP (393�80vs. 755�96 pmol/l; p�0.02) were significantly reduced (mean�SEM).Conclusion: The results suggest a pivotal reduction of adrenergic stimu-lation of myocytes in pts with Brugada syndrome which may be due toreduced release and/or enhanced re-uptake of norepinephrine at the syn-aptic cleft. These new findings confirm and expand the concept of aninvolvement of the cardiac autonomic nervous system in the pathophysi-ology and arrhythmogenesis of Brugada syndrome with potential futureimpact on risk stratification and patient management.

390

Digoxin use is associated with increased platelet andendothelial cell activation in patients with non-valvularatrial fibrillationJulio A. Chirinos Medina, MD, Aurelio Castrellon, MD, JuanP. Zambrano, MD, Howard Willens, MD, AgustinCastellanos, MD, Robert J. Myerburg, MD and Yeon Ahn,MD. Univ of Miami, Miami, FL and Coulter PlateletResearch Laboratory/Univ of Miami, Miami, FL.

Background: Intracellular calcium is a key regulator of platelet activationand endothelial cell function. Several studies have shown that digitalisactivate platelets and affect endothelial function in vitro. We aimed todetermine whether digoxin use is associated with increased flow cytometricmarkers of endothelial and platelet activation in patients with non-valvularatrial fibrillation (AF).Methods: We studied 30 consecutive patients admitted to our medicalcenter with AF (age� 62.96 � 9.95; ejection fraction [EF]� 46.23�17).We measured the levels of (1) Platelet activation markers (P-selectin,platelet microparticles, platelet leukocyte conjugates); (2) Endothelial mi-croparticles (EMP) positive for CD31 (EMP31) and E-selectin (EMP62E).Results: Patients who were taking digoxin (n�16; serum level �0.93�0.39 ng/dL) did not demonstrate any significant differences in clin-ical and echocardiographic characteristics when compared to patients nottaking digoxin (n�14). Patients taking digoxin had significantly increasedlevels of P selectin (55.1�13.8 vs 40.09�12.7; p�0.01), platelet-leuko-

S124 Heart Rhythm, Vol 1, No 1, May Supplement 2004

cyte conjugates (72.16� 5.1 vs 61.17� 3.6; p�0.006) and dramaticallyincreased markers of endothelial activation: EMP62E (1698�613 vs.239�27.4; p �0.0002) and EMP31 (3518�870 vs 1565� 819; p�0.002).After correcting for potential confounding conditions (including diabetesmellitus, hypertension, heart failure, systolic and diastolic blood pressure,cancer and EF), the differences in endothelial activation markers persisted(p�0.05) and a trend persisted in platelet activation markers (p for Pselectin � 0.08; p for platelet leukocyte conjugates � 0.08).Conclusions: Digoxin use is associated with increased levels of endothe-lial and platelet activation in AF. If digitalis activate endothelial cells andplatelets at pharmacologic doses, the use of digitalis in conditions such asAF might predispose to thrombosis and vascular events.

391

Electrical and mechanical transmural heterogeneity servesto synchronize contraction across the canine leftventricular wall*Jonathan M. Cordeiro, PhD, William S. Gaetano, BS,Lindsey Greene, BS and *Charles Antzelevitch, PhD.Masonic Medical Research Laboratory, Utica, NY.

The synchronization of contraction across the ventricular wall was evalu-ated by examining unloaded cell shortening kinetics and Ca2� transients inmyocytes isolated from the epicardial (Epi) endocardial (Endo) and mid-myocardial (M) regions of the canine left ventricle.Methods: Epi-, Endo- and M cells were isolated and superfused with abuffer containing 2.0 mM Ca2�. Ca2� transients were measured in cellsloaded with 15 �M fluo-3/AM by confocal microscopy. Unloaded cellshortening was measured using a video edge detector. Both voltage andcurrent clamp recordings were made using patch pipettes.Results: Epicardial cells displayed a significantly faster time to peak inboth cell shortening and calcium transient. Endocardial cells exhibited adelay in the onset of contraction as well as a slower rise in cell shorteningand intracellular Ca2�. When ICa,L was measured using square wavevoltage clamp pulses, the I-V and corresponding fluorescence-voltagerelation were similar among the three cell types. T-tubular spacing wassimilar in epicardial and endocardial cells (1.99 �m vs. 2.01 �m) stainedwith the membrane-selective dye, di-8-ANEPPS. ICa,L measured usingaction potential voltage clamp techniques showed that total charge andpeak ICa,L elicited with an epicardial action potential waveform was greater(by 47�10% and 26�12% (p�0.05), respectively) than with an endocar-dial waveform, suggesting that the larger Ito in epicardium contributes to agreater trigger Ca2� and faster Ca2� transient. We next applied bothwaveforms to the same cell and measured unloaded cell shortening. Epi-cardial waveforms resulted in a faster time-to-peak of cell shortening by16.4�4.9 msec compared to the endocardial waveform (p�0.05).Conclusion: Our results suggest that cell shortening kinetics are acceler-ated in epicardium due in part to a prominent phase 1 giving rise to a largertrigger ICa,L. This mechanism coupled with the delayed onset of cellshortening and slower kinetics of cell shortening acts to synchronizecontraction across the ventricular wall when activation is via the normalendocardial to epicardial direction.

392

Duration of atrial fibrillation determines degree ofmyocardial fibrosisFelix Gramley, MD, Johann Lorenzen, MD, Jurgita Plisiene,MD, Rimantas Benetis, MD, Schmid Michael, MD, RudigerAutschbach, MD, Axel Gressner, MD, Karl Mischke, MD andPatrick Schauerte, MD. Univ Hosp Aachen, Aachen,Germany and Univ Hosp Kaunas, Kaunas, Lithuania.

Objective: Atrial fibrillation (AF) is characterized by atrial fibrosis andthus helps to sustain itself. Apart from the angiotensin system the TGF-�pathway and MMP-system are of importance in extracellular remodeling.This study will examine both systems in AF-associated fibrosis.

Methods: Right atrial appendages (n�120) were grouped according to heartrhythm into 5 groups: sinus rhythm (SR, n�80; G1), chronic paroxysmal andchronic persistent AF 60 months (n�11; G5). The degree of fibrosis and signsof cellular hypertrophy were determined morphologically. Using Westernblots TGF-� receptor I/II (T�RI/II) and Smad 4/7 were quantified. MMP-2/-9enzyme activity was determined zymographically (Boeringer Light Units)while the expression of TGF-�1 and tissue inhibitors of metalloproteinases(TIMPs) was measured by RT-PCR (relative units).Results: Atrial fibrosis significantly increased with the duration of AFfrom 14.3�7.7% (G1) to 21.2�9.2% (G3) to 25.3�4.7% (G5). Signs ofcellular hypertrophy increased in parallel (all significantly). While TGF-�1protein content (profibrotic, MMP-activity inhibiting), T�RII, and Smad 4(transduces TGF-� effect) rose with fibrosis and duration of AF, a declineof T�RI and an increase of i-Smad 7 (inhibits TGF-�1) were observed.Furthermore, as MMP-2 (18.54�5.03 to 45.26�9.8) and �9 (4.42�0.82to 12.47�3.02) activity increased a significant decrease of TIMP-1(1.16�0.01 to 1.09�0.01) and TIMP-2 (1.16�0.02 to 1.14�0.03) wasseen. Since T�RI and II can only signal in concert and i-Smad 7 rises, it isconceivable that during the development of AF associated fibrosis theTGF-�1 pathway loses influence while degradation of atrial extracellularmatrix by MMPs seems to be enhanced.Conclusion: The duration of AF is closely associated with atrial fibrogenesiswith significant fibrosis occurring already after 6 months. While the TGF-�1pathway appears to lose its influence as fibrosis progresses the degradation ofatrial extracellular matrix by MMPs seems to be enhanced. The involvementof the TGF-�1 system may open therapeutic opportunities in fighting atrialfibrosis early by vectors that selectively inhibit i-smad 7.

393

Do pulmonary veins play a central role in atrialarrhythmogenesis associated with atrial tachycardiaremodeling?Tae-Joon Cha, MD, Joachim R. Ehrlich, MD, Denis Chartier,MS, Liming Zhang, MD and Stanley Nattel, MD. MontrealHeart Inst, Montreal, Quebec, Canada.

The pulmonary veins (PVs) are known to play an important role in clinicalAF. The present study was designed to assess the relative cellular changesin PV and left atrium (LA) with atrial tachycardia (AT) remodeling andtheir relationship to atrial arrhythmogenesis.Methods: Dogs were subjected to 7-day AT at 400 bpm, then LA preparationswere coronary-perfused and either studied intact in vitro or subjected tocardiomyocyte isolation. Ion currents were studied with patch clamp.Results: PV and LA cardiomyocytes showed qualitatively similar changesin response to AT (Table). The degree of APD shortening was relativelylarger in LA, so that LA-PV APD differences tended to decrease after AT.In control preparations, atrial premature stimulation produced a maximumof a few (�3) non-stimulated beats; however, atrial tachyarrhythmias couldbe easily induced in AT-remodeled preparations, with a mean duration in7 preparations of 3607�2124 ms (M�SE on a per-heart basis) and cyclelength (CL) of 117�6 ms. To assess the role of PVs in atrial tachyarrhyth-mia, all visible PVs were surgically removed from the atria by incisingproximal to the PV ostia. After PV resection, atrial tachyarrhythmias werejust as easily inducible and persistent (mean duration 3468�2379 ms, CL120�8 ms) as with the PVs intact.Conclusions: AT-induced ionic remodeling is qualitatively similar in LAand PVs. AT-remodeled LA preparations have easily-inducible, persistentatrial tachyarrhythmias in vitro, and PVs do not appear essential for ATpromotion of arrhythmogenesis in this isolated LA preparation.

S125Poster 2

394

Divergent effect of esmolol on action potentials in wildtype and deltaKPQ-SCN5A miceLarissa Fabritz, MD, Paulus Kirchhof, MD, MarkusEmmerich, Burkhard Riemann, Michael Schafers, Michael R.Franz, MD, PhD, Wilhelm Schmitz, MD, PhD, GunterBreithardt, MD, Edward Carmeliet and Peter Carmeliet.Univ Hosp of Munster, Munster, Germany, Georgetown Univand VA Hosp, Washington, DC, Univ of Munster, Munster,Germany and Ctr of Transgene Technology, KU Leuven,Leuven, Belgium.

In patients with long QT syndrome 3, sudden death occurs predominantlyduring bradycardia. Use of �-adrenergic receptor (ar) blockers in thesepatients has therefore been questioned. We studied the effect of �-arblockade and stimulation on monophasic action potentials in hearts ofheterozygeous mice with the knock-in deletion KPQ-SCN5A(SCN5A-TG vs. wild type, WT, n�12 per group) by infusion of esmolol(1.6x10-6M), orciprenaline (1.7x10-6M), or both drugs during AV nodalblock. Intrinsic ventricular bradycardia triggered arrhythmias in 50% ofSCN5A-TG and bradycardia was further aggravated by esmolol. Duringpacing, orciprenaline shortened action potential duration (APD) in bothWT (up to 30%) and SCN5A-TG (up to 50% at long cycle lenghts, CL).With esmolol and orciprenaline infusion, APD increased back to 9% abovebaseline in WT, but prolonged to 30% above baseline in SCN5A-TG(p�0.05 for drug vs. baseline and TG vs. WT, see graphs for values).Maximum �- and �-1-ar densities determined in vitro using autoradiogra-phy of ventricular membrane preparations (n�6 per group) were notdifferent between WT and SCN5A-TG hearts, max(�1)29�2 vs. 30�2fmol/mg protein, max(�1�2)37�1 vs. 41�2 fmol/mg protein, p�ns.Myocardial presynaptic catecholamine recycling was measured in vivo(n�7 per group) using a small animal positron emission tomograph(quadHIDAC-PET, Oxford Positrons Ltd., UK) and the radioactively la-belled catecholamine analogue C-11-hydroxyephedrine (HED). The wash-out of catecholamines was not altered in SCN5A-TG as compared to WT(21.1%/h vs. 22.8%/h, p�ns).

Conclusion: �-ar blocking agents may aggravate the KPQ-SCN5A phe-notype by aggravation of both action potential prolongation and bradycar-dia. Increased sensitivity to esmolol was neither caused by altered presyn-aptic sympathetic function nor by changes in �-ar density.

395

Atrioventricular nodal reentrant tachycardia is induciblein mice expressing the human PRKAG2 geneTapan G. Rami, MD, Yadavendra S. Rajawat, MD, JasvinderSidhu, MD, Robert Roberts, MD and Dirar S. Khoury, PhD.Baylor College of Medicine, Houston, TX.

Previous electrophysiology studies (EPS) have demonstrated presence ofdual AV nodal physiology in 40% of mice. However, AV nodal reentranttachycardia or echo beats have not been induced. We investigated theprevalence of dual AV nodal physiology and inducibility of AV nodalreentrant arrhythmias in transgenic mice (TGM) generated by cardiacspecific overexpression of the human PRKAG2 gene. ECG recordings andintracardiac electrophysiology studies were performed on 11 TGM (age,52�5 wk). Atrial programmed extrastimulation (APES) was applied, anda “jump” in the AV nodal response was defined as an increase in the A2H2or A2V2 interval of greater than or equal to 10 ms with a decrement in theS1S2 interval by 5-10 ms. AV nodal response was described by the AHinterval in 8/11 TGM and by the AV interval in 3/11 TGM. Baseline AHand AV intervals were 22�2 ms and 33�4 ms, respectively. 5/11 TGM

demonstrated dual AV nodal physiology with a “jump” of 14�4 ms. 2/5TGM with a “jump” reproducibly developed either AV nodal reentranttachycardia (1) or echo beats (1) during APES. Surface ECG duringreentrant tachycardia or echo beats exhibited QRS morphology similar tobaseline rhythm and a superior P wave axis consistent with retrograde VAconduction. In conclusion, dual AV nodal physiology was identified in45% of mice expressing the human PRKAG2 gene. First provocation oftypical atrioventricular nodal reentrant tachycardia or echo beats wasdemonstrated in a subset of mice with dual AV nodal physiology (40%).These observations may imply a role for PRKAG2 gene in AV nodaldevelopment.

396

Changes of intra-atrial conduction and expression ofConnexin 43 with age in TGF-� transgenic miceToshiaki Sato, MD, Sander Verheule, PhD, Thomas H.Everett, IV, PhD, Emily E. Wilson, BS, Hidehiro Nakajima,MD, PhD, Hisako O. Nakajima, MD, Loren J. Field, PhDand Jeffrey E. Olgin, MD. UCSF, San Francisco, CA,Maastricht Univ, Maastricht, Netherlands, Univ ofCalifornia-San Francisco, San Francisco, CA and IndianaUniv, Herman B. Wells Center for Pediatric Research,Indianapolis, IN.

Atrial fibrosis has been implicated in arrhythmogenesis of atrial fibrillation(AF). We have previously shown that in a transgenic mouse that overexpressesTGF-�1(Tx), selective and progressive atrial fibrosis provides a substrate forAF. Although exogenous TGF-� has been shown to increase the expression ofCx 43 in cultured myocytes, effects of endogenous TGF-� are not known inin vivo. Therefore, we have studied effects of overexpression of TGF-�1 on theexpression of Cx 43 and electrophysiology on the atrium and compared thembetween the adult and old mice.Methods: Twenty Tx mice and 21 wild-type littermate controls (Wt) weredivided into adult (98-173 days) and old (�366 days) groups. In closed-chestmice, P-wave duration was measured and inducibility of AF was assessed bytransesophageal atrial pacing. Six Langendorff perfused hearts from eachgroup were created to measure Atrial ERP and intra-atrial conduction velocity(CV) at multiple CLs in both atria. CV was calculated from conduction vectorsfrom 4x4 unipolar potentials recorded over an area of 1.2x1.2 mm each on theright and left atrial appendage (RA, LA). The expression of Connexin 43 wasassessed by immuno-staining from each 4 heart.Results: In the old mice, P-wave duration of Tx was shorter than that of Wt(18ms vs.24ms, p�0.05) while there was no significant difference in Txcompared to Wt in the adult group. AF inducibility was less in the old Txthan in adult Tx (20% vs.78%, p�0.05). In the Wt groups, AF was inducedin only 1 old mouse. Neither LA or RA ERP of Tx differed from that of Wtin either age. CV of old Tx was significantly faster than that of adult Tx inboth atria (RA:35 vs.25 cm/s, LA:39 vs.28 cm/s). In the old mice, CV inLA of Tx was significantly faster than that of Wt (39 vs.30 cm/s). The arearatio of Cx43 to myocyte in LA of old Tx (24�2%) was significantly(p�0.05) larger than both that of the adult Tx (15�4%) and old Wt(14�3%).Conclusion: Overexpression of TGF-�1 results in an increased expressionof connexin 43 and an increase in CV in older mice. This appears toprevent the induction of AF even in fibrotic atrium of old Tx.

397

Effects of gonadectomy on gender differences in thevulnerability to arrhythmias induced by E4031 in isolatedrabbit heartsTong Liu, MD, PhD, Erdal Gursoy, MD, PhD, Bum-RakChoi, PhD, Barry London, MD, PhD and Guy Salama, PhD.Univ of Pittsburgh, Pittsburgh, PA and Univ of PittsburghSchool of Medicine, Pittsburgh, PA.

Women with acquired long QT have a higher incidence of Torsade depointes (TdP) than men. This gender differences may be related to the

S126 Heart Rhythm, Vol 1, No 1, May Supplement 2004

modulation of cardiac repolarization by sex hormones. Gonadectomy(GDX) was used to test the effects of circulating sex hormones on thesusceptibility to long QT-related arrhythmias.Methods and Results: Optical action potentials (APs) were mapped fromLangendorff perfused rabbit hearts from aged-matched (3 months) adult male(AM) and female (AF) or 14 days after orchiectomy (ORX) and ovariectomy(OVX). The IKr blocker (E4031 0.5 �M) was used to induce LQT and to testfor differences in the vulnerability to arrhythmias. Hearts from GDX rabbits(ORX�6 and OVX�5) had shorter AP durations (APD) than controls. AtCL�500 ms, AM vs. ORX: APD�272�20 (n�5) vs. 222�20 ms, (n�6;p�0.02) and AF vs. OVX: APD�273�29 (n�4) vs. 225�33 (n�4); p�0.08.E4031 increased APD more at the apex than base, reversed the direction ofrepolarization, increased the dispersion of repolarization and elicited sponta-neous early afterdepolarizations (EADs), which progressed to TdP in 2/4 AFbut only 1/5 AM. After GDX, E4031 elicited salvos of EADs in 4/6 ORX,which progressed to arrhythmias in 3/6 ORX hearts whereas E4031 failed toinduce EADs or arrhythmias in all 4 OVX hearts. Western blots analysis fromthe middle of the left ventricle indicated that MinK was significantly moreelevated in OVX (n�3) than ORX (n�4) whereas rabbit erg was moreelevated in ORX than OVX.Conclusions: In adult rabbit hearts, females were highly vulnerable toE4031-induced EADs and TdP whereas males were protected. After GDX,the lack of sexual hormones is associated with a reversal of arrhythmiavulnerability. The data also suggests that gonadal steroids influence ionchannel expression where ORX results in an elevation of IKr and a reduc-tion of IKs compared to OVX, which may account for the enhancedvulnerability to arrhythmias.

398

T wave memory mechanisms involve electricalsynchronization of different regions of the ventricularmyocardiumKaterina Hnatkova, PhD, Alexei N. Plotnikov, MD, Irina N.Shlapakova, MD, Michael R. Rosen, MD and Marek Malik,MD, PhD. St. George’s Hosp Medical School, London,United Kingdom and Columbia Univ, New York, NY.

The term Cardiac Memory (CM) refers to transient changes in T wavemorphology that appear after cessation of ventricular pacing (VP). It is notknown whether in intact hearts in situ, different layers and regions of theventricular myocardium react differently during CM. We therefore inves-tigated the development of T wave morphology during CM.Methods: We studied chronically instrumented, acutely anesthetized dogs.CM was induced by VP at 400 bpm for 120 min, followed by 20 min recoveryof atrial pacing (AP) at 500 ms cycle length. Altogether, 11 experiments wereavailable from 6 animals. Digital ECGs with limb leads I and II � 7 transmuralneedles were recorded at 120 min of VP, after cessation of VP, and at 5, 10 ,and 20 min of recovery. CM was measured as distance between the peaks ofthe AP T wave vector at baseline and during CM on frontal plane anddecreased significantly during recovery (from 0.227�0.046 (SEM) to0.102�0.028, p � 0.05) confirming the presence of CM mechanisms. Multi-lead T wave morphology was assessed by the so-called T wave morphologydispersion (TMD) that expresses the differences in T wave shapes recorded indifferent leads. Low values of TMD indicate spatial synchronisation of dif-ferent parts of ventricular myocardium.Results: The figure shows the development of TMD during CM. Thechanges during recovery were very highly significant compared to baseline(p � NS, 0.007, 0.001, 0.0009, and 0.002, at VP and 0, 5, 10, and 20 minof recovery, respectively).

Conclusion: This data analysis suggests that mechanisms of CM involvesynchronisation of different regions of ventricular myocardium turning thephysiologically elliptic 3D T wave loop into a spherical pattern thuscausing suppression of physiologic repolarisation gradients.

399

Combination of �-adrenoceptor blockade and A1

adenosine receptor activation: Potential therapy for ratecontrol in atrial fibrillation*Arvinder K. Dhalla, PhD, *Dmitry O. Kozhevnikov, *Wei-Qun Wang and *Luiz Belardinelli, MD. CV Therapeutics,Inc, Palo Alto, CA.

Atrial fibrillation (AF) is the most common arrhythmia encountered inclinical practice. Recently, reduction of ventricular rate has been shown tobe as effective as rhythm control (PIAF, STAF, AFFIRM & RACE trials)in patients with AF. �1-adrenoceptor blockade and activation of A1 aden-osine receptors (A1R) have negative chronotropic effects in the heart byinhibiting sympathetic activity and by directly depressing AV nodal andpacemaker function. Thus, we tested the hypothesis that metoprolol(MET), a �-blocker, and tecadenoson (TEC), a novel and selective A1Ragonist, would act synergistically to decrease heart rate. Freely movingmale Sprague Dawley rats (n�50) implanted with telemetry transmitterswere used to study the effects of TEC and MET alone and in combination.Animals were randomly given various doses of TEC and MET alone andin combination in a crossover design. Both TEC (1-30 �g/kg, ip) and MET(0.1-10 mg/kg, ip) decreased heart rate in a dose-dependent manner. Syn-ergistic bradycardia was observed when the two agents were given incombination in that the slowing of heart rate caused by the combinationwas greater than the algebraic sum of bradycardia caused by TEC and METalone (figure). The potencies (ED50 values) of TEC and MET for slowingthe heart rate were 19 �g/kg and 1.3 mg/kg when given alone, and 3.5�g/kg and 0.3 mg/kg when given in combination, respectively. In addition,the duration of bradycardia caused by the combination was significantlyincreased (2-6 fold) when compared to TEC alone. Plasma levels of TEC,determined after a single dose of TEC (20 �g/kg) in the absence andpresence of MET (1 mg/kg) were found to be the same in both groups. Inconclusion, the present study provides the rationale for the evaluation ofcombination therapy of an A1R agonist and a �-blocker for the control ofventricular rate during AF.

400

Adenylyl cyclase VI overexpression improvesatrioventricular conduction in miceAshwani Sastry, BA, Elizabeth Arnold, BA, Hunaid Gurji, BS,Atsushi Iwasa, MD, Alborz Hassankhani, MD, PhD, N. ChinLai, BA, H. Kirk Hammond, MD, David M. Roth, MD andSanjiv M. Narayan, MD. UCSD School of Medicine, SanDiego, CA and UCSD School of Medicine and VA MedicalCtr, San Diego, CA.

Introduction: Overexpression of adenylyl cyclase VI, unlike other sym-pathomimetic interventions, may reduce mortality in heart failure. Werecently showed that cardiac-directed expression of adenylyl cyclase VI(ACVI) reduces early mortality after myocardial infarction in mice. Themechanism for this effect is unknown. We hypothesized that the survivalbenefit of ACVI may relate to improved sinus and atrioventricular (AV)nodal conduction.

S127Poster 2

Methods and Results: First, we studied arrhythmias in mice expressingthe transgene (ACVI �) versus controls (ACVI �). We implanted wirelessextraperitoneal telemetry transmitters in n�6 ACVI � and n�6 ACVI �mice. Following recovery, all mice underwent ligation of the proximal leftanterior descending coronary artery. Seven-day mortality was greater inACVI � than ACVI � mice, and each death was preceded by high gradeAV block and sinus bradycardia (Figure, top), without evidence of pre-ceding heart failure or recurrent ischemia. Second, we performed invasiveelectrophysiological (EP) studies to measure sinus and AV nodal conduc-tion by inserting a 1.7 F octapolar catheter via the right jugular vein to theAV junction in n�11 ACVI � and n�14 ACVI � mice. During pro-grammed stimulation, ACVI � mice had shorter AV Wenckebach cyclelengths (131 ms vs 114 ms; p�0.05) and VA effective refractory periods(127 ms vs 97 ms; p�0.05) than ACVI � mice. Trends for shorter AV 2:1block cycle length (113 ms vs 96 ms; p�0.07) and VA nodal Wenckebachcycle length (166 ms vs 136 ms; p�0.07) were observed in ACVI � versusACVI � mice. No group differences in baseline heart rate or sinus noderecovery times were present, and ventricular arrhythmias could not beinduced.Conclusion: Our data indicate that increased AV nodal conduction mayunderlie improved survival in mice expressing ACVI, suggesting a potentialrole for gene transfer of ACVI for diseases of AV conduction.

401

Unexplained myocardial fibrosis is common in basicmilitary trainees with idiopathic sudden deathRobert E. Eckart, Eric A. Shry, Stephen S. Reich, Richard A.Krasuski and Charles L. Campbell. Brooke Army MedicalCtr, San Antonio, TX.

Background: Sudden cardiac death (SCD) is a rare, but devastating eventthat can occur during basic military training. Many of these deaths areunexplained even after detailed evaluation including autopsy. We sought todetermine pathologic changes that were associated with idiopathic SCD inan autopsy series of military basic trainees.Methods: This study reviewed the autopsy data of non-traumatic suddendeaths during United States Armed Forces enlisted basic training from1977 through 2001. Of the 126 non-traumatic SCD’s, 43 (34%) wereidiopathic. The control population was made up of 50 basic trainees thathad traumatic sudden death and underwent autopsy.Results: Subjects that had idiopathic SCD compared to controls had nosignificant difference in gender (male 84% vs. 96%, p�0.07), age at death(21�5 vs. 20�3 years, p�0.10), nor BMI (22.8�2.9 vs. 23.3�3.5 kg/m2,p�0.50). In subjects with idiopathic SCD, 19 (44%) had documented faileddefibrillation for ventricular tachydysrhythmias prior to death, compared to1 (2%) of the traumatic subjects (p�0.001). The mean cardiac mass ofpatients with idiopathic sudden death was slightly higher than the controlgroup (365�79gm vs. 331�52gm, p�0.02); however, the wall thicknesswas similar (15�3mm vs. 14�3mm, respectively p�0.40). Myocardialfibrosis was significantly more frequent in subjects with idiopathic suddendeath than in those suffering traumatic deaths (12 [34%] v. 0 [0%],p�0.001). Active myocardial necrosis was rare in both groups (6% and 2%respectively, p�0.76).Conclusion: Even after detailed evaluation of basic trainee’s deaths,including autopsy, more than one-third are unexplained. Ventricular tachy-dysrhythmia appears to be the mechanism of death in those patients withSCD who undergo electrocardiography during their event. A significantproportion of subjects suffering idiopathic sudden cardiac death had myo-

cardial fibrosis. Future studies should investigate the causes of myocardialfibrosis in young SCD victims and their links to genetic or other conditionsthat may predispose to premature sudden death.

402

T-wave alternans as a precursor of ventriculartachyarrhythmiasVladimir Shusterman, MD, PhD and Anna Goldberg, BS.Univ of Pittsburgh, Pittsburgh, PA.

An increase in T-wave alternans (TWA) often heralds the onset of ven-tricular tachyarrhythmias (VTA) in experimental studies. In humans, how-ever, only short data segments were available for analysis of TWA prior tothe onset of VTA. Thus, it remained unclear whether the increase in TWAwas a specific precursor of the arrhythmia or a random fluctuation about themean level unrelated to the onset of VTA. To analyze the relationshipbetween TWA and the time of arrhythmia, we examined continuous repo-larization dynamics during 6hrs before the onset of spontaneous sustained(� 30s long) monomorphic ventricular tachycardia in 36 Holter ECGs.Methods: Baseline wander was removed and the fiducial points (Qonset,Tonset, Tpeak, and Tend) were determined in each beat using previouslyvalidated software and verified by an experienced technician. Beat-to-beatchanges in TWA were examined in time domain using the averageddifferences between consecutive T-waves. In addition, the E-TWA (fromTonset to Tpeak) and the L-TWA (from Tpeak to Tend) were identified.The trends in the time series of each variable were examined usingnonparametric Friedman ANOVA.Results: RR intervals shortened during 60min before the onset of VTA(RR:814�224 to 761�199ms, p�.026). TWA increased before the event(p�.025), and 30min before the onset of VTA, exceeded the 3�-level forthe preceding 5hrs (Figure). The TWA peaked at 15min before the onset(131% relative to the 5hr-mean). Both the E-TWA and the L-TWA weresignificantly higher before the onset compared to the 5hr-mean (138% and125%, respectively, p�.02). QT interval, T-wave length (from Tonset toTend), and the peak T-wave amplitude did not change significantly.Conclusions: TWA increased 30min before the onset of VTA and ex-ceeded the 3�-level for the preceding 5hrs. This suggests that the increasein TWA is a non-random phenomenon associated with the onset of ven-tricular tachyarrhythmias.

403

T-wave alternans during cardiac resynchronization therapyis greater in the presence of elevated levels of B-typeNatriuretic PeptideUma Srivatsa, MD, Atsushi Iwasa, MD, Brett J. Berman,MD, Bobbi L. Hoppe, MD, Theodore Oliver and Sanjiv M.Narayan, MD, PhD. UCSD School of Medicine, San Diego, CA,Univ of California-San Diego, San Diego, CA and UCSDSchool of Medicine and VA Medical Ctr, San Diego, CA.

Background: Ventricular stretch, reflected by elevated levels of B-typeNatriuretic Peptide (BNP), may exacerbate ventricular arrhythmias. How-ever, in patients undergoing cardiac resynchronization therapy (CRT) it isunclear whether those who experience ventricular arrhythmias are thosewithout reverse ventricular remodeling and, therefore, higher levels ofBNP. We hypothesized that dispersion of ventricular repolarization duringCRT, measured using T-wave alternans (TWA), would be exacerbated inthe presence of elevated BNP.

S128 Heart Rhythm, Vol 1, No 1, May Supplement 2004

Methods and Results: We studied 57 patients (mean age 69.1�12.3 years)with mean left ventricular ejection fraction 29.4�11.7 % who underwentprogrammed right ventricular (RV) stimulation (PVS). TWA was mea-sured at PVS by pacing from 100 to 120 then 100 bpm (HeartWave,Cambridge Heart). TWA was later measured as an outpatient during RV orbiventricular (BV) pacing in patients who received devices using the sameprotocol. Plasma BNP was measured at each TWA recording. The preva-lence of non-negative TWA was similar during RV or BV pacing (42/56,75 % vs 12/17, 70.6%). However, when BNP was elevated (� 100 pg/ml),TWA during BV pacing was non-negative in 92.3% (12/13) of cases. TWAduring CRT was thus significantly more likely to be non-negative whenBNP was elevated than when it was not (p�0.001; �2). Conversely, TWAduring RV pacing was similar whether BNP was elevated or not, duringPVS (p�0.10) and device pacing (p�0.10). The concordance betweenTWA during BV versus RV device pacing was low in patients whoreceived CRT even though both were measured within 20 minutes of eachother. On prospective follow up (for 326�220 days) there were 5 episodesof sustained ventricular arrhythmias and one death. All events occurred inpatients with elevated BNP and non-negative TWA tests during CRT.Conclusions: Dispersion of repolarization during CRT is exaggeratedwhen BNP is elevated, and may predict spontaneous ventricular arrhyth-mias. Thus, TWA measured during CRT may accurately reflect the ar-rhythmic propensity of decompensated heart failure, and may be morepredictive than TWA during RV pacing.

404

Resonant pacing improves T-wave alternans testing inpatients with dilated cardiomyopathyJohn R. Bullinga, MD, Bryan Piedad, MD, DavidFeigenblum, MD, PhD, *Douglas Holmes, MD, *NeilBernstein, MD, David Sandler, MD and *Larry Chinitz, MD.New York Univ Medical Ctr, New York, NY.

Background: T-wave alternans (TWA) is an important clinical tool forventricular arrhythmia risk stratification. However, the current method ofTWA testing is often non-diagnostic due to a low signal-to-noise ratio(SNR) and perturbations by premature beats. We designed a novel pacingpattern (“resonant pacing”) to improve the SNR and decrease the impact ofpremature beats. Resonant pacing (RP) tests the heart’s response to smallperiodic CL changes that resonate with TWA. We hypothesize that RPimproves signal characteristics for testing alternans physiology comparedto pacing at a constant CL in patients with dilated cardiomyopathy.Methods: We prospectively evaluated 18 patients (16 CAD, EF 25 � 9 %,age 70 � 14 yr) referred for EPS. Simultaneous atrial and ventricularpacing was performed with constant pacing (CP) at a CL of 550 ms and RP(repeated 4-beat pattern of CLs 535, 555, 555, 555 ms). TWA with CP wasclassified using HearTwave (Cambridge Heart). Patients with determinatetests were further analyzed in response to CP and RP using customsoftware. The lead with maximal TWA was analyzed for signal strength(mean VAlt), signal stability (mean VAlt/st dev VAlt), SNR (mean VAlt/mean voltage magnitude of noise bandwidth), premature beats and alter-nans phase inversions with CP and RP.Results: There were 9 TWA positive, 3 TWA negative and 6 indeterminatepatients with CP. In those patients with determinate tests, VAlt with RPcorrelated to VAlt with CP (R � 0.71, p � 0.012). RP increased signalstrength (20 � 8 �V vs. 4 � 2.5 �V, p � 0.00001), signal stability (14.4 �9.5 �V/�V vs. 2.3 � 0.8 �V/�V, p � 0.0012), and the SNR (19 � 13�V/�V vs. 2.4 � 1.6 �V/�V, p � 0.0016) compared to CP. The numberof premature beats was similar with RP compared to CP (1.3 � 2.2 vs.2.1 � 2.6, p � 0.15), however premature beat induced sustained alternansphase inversions was prevented with RP (0.8 � 0.8 vs. 0, p � 0.011).Conclusion: Resonant pacing improves signal strength, signal stability, andthe SNR for TWA testing when compared to constant pacing. The en-hanced signal characteristics that result from resonant pacing may differ-entiate indeterminate test results by more clearly identifying alternansphysiology.

405

Results of microvolt T wave alternans testing areconsistent between atrial pacing and atrial-ventricularpacingSusan R. Neal, RN, Dionyssios A. Robotis, MD, RaminDavouidi, MD, Clifford Browning, MD, Edward Healy, MD,Marylee Mattei, RN, CNP and Lawrence S. Rosenthal, MD,PhD. UMass Memorial Medical Ctr, Worcester, MA.

Background: Microvolt T-wave Alternans (TWA) has shown promise asa means of risk stratification in a variety of patient populations. TWA canbe accurately measured during stress testing or via atrial pacing (AP)provided that there is consistent 1:1 AV conduction at a cycle length of550ms and a regular R-to-R interval. In patients with heart disease, thesecriteria are not always met in part due to poor AV conduction and/orfrequent ectopy. Atrioventricular pacing (AVP) circumvents constraintsimposed by the need for consistent AV conduction. However, there islimited data regarding the accuracy of TWA measured during AVP. Wesought to compare the results of TWA testing via AP to those measured viaAVP.Methods: TWA testing was performed on 32 consecutive patients whopresented in sinus rhythm for either dual chamber ICD implantation orElectrophysiology Study. The HearTwave system (Cambridge Heart inc.)was used for all tests. Tests were performed via AP at 550ms for at least5 min and then Atrial-Right Ventricular Apex pacing (AVP) w/an AVdelay of � 30 ms for at least 5 min. An investigator who was blinded tothe results from the other pacing site interpreted the test results that wereequivocal.Results: Of the 32 patients enrolled 9 had either poor AV conductionand/or frequent ectopy resulting in inclusive test results w/AP. Of the 23patients who successfully completed both pacing protocols (age 62 � 13yrs; 75% male; LVEF 42 � 14; 75%(18) with CAD; and 71%(17) withprior MI), TWA testing was positive with AP in 48% (11) and in 43% (10)with AVP. Overall, there was a 96% (22/23) concordance rate between theresults of AP versus AVP (p��0.0001). Concordance occurred slightlymore frequently for negative studies (100%, 12/12) than for positivestudies (90%, 10/11). Irregular R-to-R intervals were more frequent withAP (52%, 11) than with AVP (22%, 5), p�0.15.Conclusions: In this small sample, there was a highly significant concor-dance of TWA results between AP and AVP (96%). As expected, R-to-Rintervals were more regular with AVP. Although further investigation isneeded, we conclude that it is reasonable to measure TWA with AVP whenadequate AP cannot be achieved.

406

Heart rate and blood pressure variability before, duringand after space flightFrank Beckers, PhD, Bart Verheyden and Andre E. Aubert,PhD. Laboratory of Experimental Cardiology, Leuven,Belgium.

Introduction: Space flight induces cardiovascular deconditioning. Thiscontributes to the occurrence of orthostatic intolerance after return to Earth.The aim of this study was to determine alterations of autonomic modula-tion due to space flight. Heart rate (HRV) and blood pressure variability(BPV) provide a noninvasive means to study the autonomic modulation ofthe cardiovascular system. Low frequency (LF) oscillations in heart rate(HR) provide information about sympathetic modulation and baroreflex,high frequency (HF) modulation of HR is an index of vagal heart ratemodulation. LF blood pressure (BP) fluctuations provide information aboutsympathetic vasomotor tone.Methods: Measurements were performed in 3 astronauts. ECG and con-tinuous BP (finger cuff method) were measured for 10 minutes in supine,sitting and standing position 45 days before launch and at 1, 2, 4, 9, 15, 19and 25 days after return to Earth. In space, ECG was measured at day 5 andday 8. HRV and BPV indices were calculated in time and frequencydomain.

S129Poster 2

Results: Measurements in standing position showed the highest differ-ences after space flight. During spaceflight HR was significantly lowercompared to the pre- and post-flight measurements in standing position(space: 59 bpm; preflight: 72 bpm; postflight: 102 bpm; all p�0.05). Thiswas accompanied by a significant increase in the proportion of HF powerduring spaceflight (5.7% to 11.1%) and a decrease in LF power (3297 ms2

to 1251 ms2). Immediately after spaceflight both LF and HF modulation ofHR were extremely depressed compared to the pre-flight conditions (LF:3297 ms2 to 546 ms2; HF: 303 ms2 to 38 ms2: all p�0.005). A gradualrecovery towards baseline conditions of both indices was observed up to 25days after return from space. In space BPV tended to be lower. BPV wasalready at preflight levels starting from the first day after return to Earth.Conclusion: During spaceflight autonomic modulation of HR is charac-terised by a vagal predominance, while after return to earth overall auto-nomic modulation is extremely depressed. Recovery of autonomic modu-lation is slow. Even after 25 days values are not yet at preflight levels. BPmodulation seems to be less affected.

407

Heart rate, heart rate variability and incidentalarrhythmias in 24-hour Holter recordings predict all-causemortality in healthy middle-aged menCees A. Swenne, PhD, Willem Agema, MD, Annemarie E. DeKoning, BSc, Hedde Van de Vooren, BSc, Arie C. Maan,PhD, Volkert Manger Cats, MD, Ernst E. Van der Wall, MD,MPH and Martin J. Schalij, MD. Leiden Univ Medical Ctr,Leiden, Netherlands and Leiden Foundation for ECGAnalysis (SEAL), Leiden, Netherlands.

Background: Ambulatory ECG recordings contain unique informationabout heart rate dynamics and arrhythmias. Little is known about thelong-term prognostic value in healthy persons. Here we present results ofa 23-year follow-up study.Methods: We studied 157 healthy men, age at inclusion 52�6 [40-60] years,with a normal physical examination, a normal 12-lead ECG according tostandard Minnesota coding criteria, no history of cardiovascular disease, andusing no medication. In the Holter ECGs we measured arrhythmias, minimal,averaged and maximal heart rate (HRmin, HRav, HRmax), averaged standarddeviation (SD) of normal-to-normal beat intervals (SDNN), SD of the normal-to-normal beat interval averages (SDANN), % successive normal-to-normalbeat interval differences exceeding 50 ms (pNN50), and low-frequency heartrate variability in normalized units (LFnu). All cause mortality risk factorswere computed by a Cox proportional hazards model with stepwise removaland reintroduction of variables, for the heart rate (variability) parametersseparately, for the arrhythmias separately, and for all parameters combined.Continuous variables were dichotomized with respect to the mean groupvalues, and relative risks computed.Results: During follow-up 25 persons died. Heart rate (variability) pa-rameters predicting death were elevated HRmin (P�0.009, relative risk(RR) � 3.4, 95% confidence interval (CI) � 1.4-8.6) and SDANN(P�0.002, RR�4.6, CI�1.7-12.3). Parameters from the arrhythmia grouppredicting death were ventricular bigeminy (P�0.049, RR�3.4, CI�1.01-11.4) and presence of one or more paroxysms of atrial fibrillation(P�0.000, RR�89.7, CI�8.1-995). Parameters from both groups predict-ing death were elevated HRmin (P�0.024, RR�3.0, CI�1.2-7.8), SDANN(P�0.007, RR�4.1, CI�1.5-11.1) and paroxysms of atrial fibrillation(P�0.01, RR�26.8, CI�2.2-323).Conclusions: 24h ECG recordings made in apparently healthy middle-agedmen have a strong long-term predictive value for all cause mortality. High riskwas especially associated with elevated HRmin, SDANN and atrial fibrillation.

408

Heart rate turbulence at electrophysiology study predictsinduced ventricular arrhythmias in patients with ischemicleft ventricular dysfunctionAtsushi Iwasa, MD, Michael Hwa, BA, Alborz Hassankhani,MD, PhD, Bobbi L. Hoppe, MD, Michael R. Franz, MD,

PhD and Sanjiv M. Narayan, MD, PhD. UCSD School ofMedicine, San Diego, CA and UCSD School of Medicine andVA Medical Ctr, San Diego, CA.

Background: Heart rate turbulence (HRT) measures heart rate fluctuationsfollowing premature ventricular contractions (PVCs), and predicts total andheart failure mortality post-myocardial infarction. However, it is unclearwhether HRT reflects the substrates for ventricular arrhythmias. We hy-pothesized that HRT measured at the time of programmed ventricularstimulation (PVS) may predict induced ventricular tachycardia (VT) inpatients with ischemic left ventricular dysfunction.Methods: We studied 21 patients with coronary disease, non-sustained VTand LV ejection fraction 27.0�8.7% at PVS. Turbulence onset (TO) wascalculated as the % difference in cycle length of 2 beats pre versus posteach PVC. Turbulence slope (TS) was calculated as the greatest regressionslope (for 5 beats) for 20 beats following a PVC. TO and TS werecalculated at PVS after 51 spontaneous PVCs and 64 PVCs delivered at theright ventricular apex, as well as during preceding Holter monitoring afterspontaneous PVCs (331.5�275.8 per patient).Results: At EPS, 7 patients were induced into sustained monomorphic VTwith 1-3 ventricular extrastimuli; 14 were non-inducible. Abnormal TO(�0%) predicted VT (p�0.01) after spontaneous as well as deliveredPVCs. HRT was concordant for spontaneous versus induced PVCs for TO(0.3�6.7% vs 1.1�7.9%; p�0.6) and TS (9.2�12.7 ms/RR vs 10.9�14.9mm/RR; p�0.5). Using cutpoints of TO � 0% and TS � 2.5 ms/RR, HRTwas also concordant for induced and spontaneous PVCs for TO (p�0.029,�2) as well as TS (p�0.043, �2). There was no relation between TO, TSand PVC coupling interval. Notably, HRT following spontaneous PVCs atHolter recordings (48.5�71.4 days earlier) did not predict inducible VTand differed from HRT following spontaneous PVCs at EPS (TS2.85�2.31 ms/RR vs 10.9�14.9 ms/RR at EPS; p�0.05).Conclusions: In patients with ischemic LV dysfunction at risk for suddendeath, abnormal HRT predicts inducible VT at the time of EPS. Furtherstudies should explore whether HRT predicts spontaneous arrhythmias inthis patient population.

409

Altered epidemiological pattern of sudden cardiac deathamong acute myocardial infarction survivors withoptimized medical and revascularization therapyTimo H. Makikallio, MD, PhD, Petra Barthel, MD, RaphaelSchneider, Axel Bauer, MD, Jari Tapanainen, MD, JuhaPerkiomaki, MD, PhD, *Georg Schmidt, MD, PhD andHeikki V. Huikuri, MD, PhD. Univ of Oulu, Oulu, Finlandand Medizinische Klinik der Technischen UniversitatMunchen, Munich, Germany.

Background: Optimal revascularization and medical therapy may alter theepidemiological pattern of sudden cardiac death (SCD). We tested thehypothesis that optimized therapy is associated with reduced SCD rate inthe current treatment era of acute myocardial infarction (AMI).Methods and Results: A total number of 2130 consecutive pts (meanage 60�10 years) with an AMI from two European centers (Germanyand Finland) was included in the study. In this population, 1004 pts(47%) were treated according to current practice guidelines, i.e. revas-cularization 70%, beta-blockers 94%, ASA 94%, statins 69% andACE-inhibitors 74%, while 1126 pts (53%) received non-optimizedtreatment, defined as lack of any of the treatment mentioned above.During the mean follow-up of 2.9�1.3 years, the incidence of SCD wassignificantly lower among those with optimized treatment (1.2%; an-nual incidence 0.4%) than among those without (3.6%; annual inci-dence 1.4%, p�0.01). In the multivariate analysis after adjusting forage and ejection fraction, the difference between the SCD rate remainedsignificant between the groups (p�0.05). The treatment strategy thathad the most significant impact on differences in the SCD rate wasrevascularization therapy, the hazard ratio of SCD being 2.1 (95% CI,1.2-3.7, p�0.01) for SCD among non-revascularized pts.

S130 Heart Rhythm, Vol 1, No 1, May Supplement 2004

Conclusions: Incidence of SCD is low in the modern treatment era ofpatients after an AMI. Coronary revascularization seems to have a largeimpact on altered epidemiological pattern of SCD.

410

LV function is preserved after AV node ablation andpacing after five year follow-upJames P. Barry, MRCP, Tim R. Cripps, MD, FRCP andAngus K. Nightingale, MD. Bristol Royal Infirmary, Bristol,United Kingdom.

Introduction: AV node ablation and pacemaker implantation is estab-lished as an effective therapy for atrial arrhythmias resistant to standardmedical therapy. Previous studies have revealed a symptomatic benefit attwelve months. There is little data with regard to the long-term effects ofRV apical pacing upon LV function and symptoms. Patients with a historyof AV node ablation and pacemaker with a contemperaneous echocardio-gram performed at our institution were identified. A repeat echocardiogramand MLHF questionnaire were performed at 5 �/�2 years follow up.Results: Between 1995 and 2000 fifty-nine patients were identified.(Meanlength of follow up 5.4 �/� 2.2 years, 33 (59.6%) VVIR, 7 VDD (8.8%)and 19(31.6%) DDD, the mean LV EDD pre implant was 49.3 mm(�/�8.8). Seventeen patients had died by the time of follow up.(Meanlength of follow up 3.6�/�2.5 years, 10 (64.7%) VVIR, 3 (17.6%) VDD,3 (17.6%) DDD, mean LV EDD pre implant 48.6 �/�8.2)Pre ablationassessment showed 1 mildly, 1 moderately and 4 severely impaired and 10normal LV’s.The cause of death was cardiovascular in 9, malignancy in 3and unknown in 5 Of the 43 surviving patients (Mean length of follow up49.5 (�/�8.8) years, 23(57.5%) VVIR, 4 (5%) VDD, 16 (37.5%) DDD,mean LV EDD pre implant 49.5mm (�/�8.8). Pre ablation assessmentshowed 2 mildly, 5 moderately and 4 severely impaired and 32 normalLV’s.Five had their first echo following AV node ablation (mean 11.8 �/�10.03 months). Of the remaining 38 the average time interval between echoand ablation was 16.78 months (�/�23.57),70% had an echo within oneyear of ablation. The repeat echo was performed � 4 yrs after ablation in91 %. The mean EDD at follow up was 53.5(�/�8.0)mm. The meanchange in EDD was 4mm(�/�10.2). The average MHLF score was 23.6(�/121.4).Conclusion: Long term follow up of after of AV node ablation and pacingreveals that LV diameters are preserved despite obligatory RV apicalactivation. Despite concerns over the deleterious effects of RV apex pac-ing, AV node ablation still has a role in patients with atrial arrhythmiasresistant to specific ablation and medical therapies

411

Fast Fourier transformation of the impedance cardiogramrecorded through two defibrillator pads may be a usefulhemodynamic sensor of cardiac arrestNicholas A. Cromie, MRCP, J. Desmond Allen, *Jim Allen,*Allister McIntyre, *John Anderson and A. A. JenniferAdgey, MD. Regional Medical Cardiology Ctr, Royal Groupof Hosps, Belfast, United Kingdom, Queens Univ Belfast,Belfast, United Kingdom and Heartsine Technologies, Belfast,United Kingdom.

Objective: With public access defibrillators the risk of inappropriatemanagement is high. A hemodynamic sensor has the potential to enhanceefficacy of therapy delivered. Accurate detection of cardiac output couldprevent inappropriate shocks and increase the specificity of treatmentalgorithms in cardiac arrest. Does the impedance cardiogram detect loss ofcardiac output?Methods: Episodes of ventricular fibrillation (VF), pulseless electricalactivity (PEA) and asystole were induced in 10 pigs, anesthetized withpentobarbitone and ventilated on room air. The impedance cardiogram(ICG) was determined by passing a low amplitude sinusoidal current

(30 kHz; 0.05 mA) between 2 defibrillator pads (R parasternal and L apicalpositions). The ICG was recorded (with EKG and arterial BP) and the firstorder derivative determined (dZ/dt; BioBench, National Instruments). Foreach episode of VF four 5 second recordings were taken, one prior toinduction (sinus rhythm, SR), 2 during VF and another after successfuldefibrillation (sinus rhythm, SRr). Two 5 second recordings after inductionof PEA (10-15 and 60-65 sec) and similarly for asystole (30-35 and 40-45sec) were made (induced by pentobarbitone iv). Fast Fourier Transforma-tion (FFT) of dZ/dt for each 5 second recording was performed and thepeak value noted between 1.5 and 4.5Hz.Results: Baseline characteristics showed a mean cardiac output of 6.0 (SD1.12) L/min systolic blood pressure of 122 (SD 24.8) mm/Hg and diastolicblood pressure of 87 (SD 25) mm/Hg. FFT amplitude was significantlyhigher for SR (7.6 dBohmsrms: SD 2.27) than for VF (�0.18: SD 4.05;p�0.001), PEA (�3.78: SD 5.16; p�0.001) and asystole (�9.55: SD 4.75;p�0.001). FFT amplitude was also significantly higher for SRr (10.15: SD3.6) than for VF (�0.18: SD 4.05; p�0.001), PEA (�3.78: SD 5.16;p�0.001) and asystole (�9.55: SD 4.75; p�0.001).Conclusion: FFT of the dZ/dt recorded through defibrillation/ECG padshas the potential to be a hemodynamic sensor for cardiac arrest.

412

Electrocardiographic findings in families with hypertrophiccardiomyopathy: A genotype-phenotype correlation studyChristina Pellnitz, MD, Wilhelm Haverkamp, MD, ChristianGeier, MD, Andreas Perrot, PhD, Rainer Dietz, MD and Karl J.Osterziel, MD. Medical Clinic for Cardiology, Campus VirchowClinic and Campus Buch, Charite-Universityhospital Berlin,Berlin, Germany and Campus Virchow Clinic and CampusBuch, Charite-Univ Hosp Berlin, Berlin, Germany.

Objectives: Hypertrophic Cardiomyopathy (HCM) is a common cardiacmuscle disease with high genetical and pathophysiological heterogeneitywhich is associated with sudden death. The aim of the study was to identifygenetically affected probands in families with HCM based on electrocar-diographic findings.Method: We studied 35 probands out of 6 HCM-families with mutationsin the beta-myosin heavy chain (MHC, 4 families) or in the regulatory lightchain (RLC, 2 families). Twenty-two carriers and 13 unaffected familymembers were evaluated with regard to electrocardiographic abnormalitiescompatible with HCM. Abnormal ECG criteria were especially left ven-tricular hypertrophy (fulfilment of Sokolow criteria) and alteration in theP-wave morphology (abnormal P-wave duration). In addition, all probandswere categorized based on echocardiographic maximum septal thickness.Results: We observed low sensitivity of each diagnostic criterium tested(left ventricular hypertrophy 23%, abnormal P-wave 55%), specificity washigh (100% and 92%, respectively). Sensitivity increased to 73% when thetwo criteria were combined. In comparison, abnormal septal wall thickness(�13 mm) had a lower sensitivity (59%), although it was a rather specificfinding (100%). Overall, almost one-half of the affected probands withnormal echocardiogram had ECG abnormalities.Conclusion: In families with mutations in the beta-myosin heavy chain orin the regulatory light chain gene detection of abnormal ECG findings canimprove the identification of genetically affected probands even when theechocardiogram is normal. Thus, the ECG may help to distinguish muta-tion carriers from unaffected probands in familial HCM.

413

High prevalence of echocardiographic markers ofasynchrony in normal volunteersThomas M. Meyer, MD, *Angel R. Leon, MD, DeanNotabartolo, MD, John D. Merlino, MD and *Andrew L.Smith, MD. Emory Crawford Long Hosp, Atlanta, GA.

Background/Objectives: Several studies have found echocardiographicmarkers (including M-mode, tissue Doppler (TDI) and standard Doppler)of asynchrony to be predictive of response to cardiac resynchronization

S131Poster 2

(CRT) with biventricular pacing. The parameters and their cut-off valuesfor response to CRT include:1) Septal-posterior wall motion delay by M-mode (SPWMD) �� 130 ms.2) Interventricular mechanical delay (IVMD) �� 40 ms3) Difference in time to peak systolic velocity between the septal and

lateral walls by TDI (Ts(lateral-septal)) �� 60 ms4) Standard deviation of time to peak systolic velocity among 12 basal

and mid wall segments by TDI (Ts-SD) �� 32.6 ms5) Percentage of LV base wall segments with Delayed Longitudinal Con-

tractions (DLC). Cut-off value ��33% The objective of this study wasto evaluate the prevalence of these markers of asynchrony amongnormal volunteers.

Methods: Volunteers without a history of cardiovascular disease under-went EKG and a full 2-D Echocardiogram (GE, Vivid 7) along with TDI.Using the quantitative analysis software (EchoPac), various markers ofasynchrony as defined above were measure off-line.Results: Echocardiography with TDI was performed in 13 volunteerswithout a history of cardiovascular disease and normal EKG and 2D Echo.There was 10 males and three females with an average age of 34.2 years(�/� 5.2 years). The average QRS duration was 88 ms (�/� 8 ms) andaverage ejection fraction (EF) was 62% (�/� 5.6%). The prevalence of thevarious parameters of asynchrony among the normal volunteers were asfollowed: 69% had TsSD �32.6 ms, 23% had Ts(lateral-septal) �� 60 msand 23% had DLC�33% of basal walls. No volunteer had SPWMD�130ms or IVMD �40 ms.Conclusions: Echocardiographic markers of asynchrony that have beenused to predict response to CRT are common among normal volunteers.

414

Effect of on-road particle exposure on heart rate andheart rate variability in unrestrained ratsJean-Philippe Y. Couderc, PhD, Alison Elder, PhD, Jean Xia,ScD, Sherley Eberly, PhD, Wojciech Zareba, MD, PhD,Christopher Cox, PhD, David Kittelson, PhD, Mark Utell,PhD, Mark Frampton, PhD, Robert Gelein, PhD and GunterObersorster, PhD. Univ of Rochester Medical Ctr, Rochester,NY and Univ of Rochester, Rochester, NY.

Background: Particulate air pollution has been related to increased respi-ratory and cardiovascular morbidity and mortality in humans. In our study,we investigated the effects of on-road exposure to highway aerosols onheart rate (HR) and HR variability (HRV) when computed from the bloodpressure signal in rats using continuous telemetric recordings during 5 daysincluding 4-day post-exposure period.Method: A crossover study was conducted in 16 rats exposed to filtered airand on-road particles. Rats were exposed to freshly-generated highwayaerosols for 6 hrs while housed in compartmentalized chambers in anair-conditioned truck cab. Blood pressure was monitored over the four daysof the post-exposure period. We studied the variation of time and frequencydomain parameters over time using mixed model analysis of variance toevidence any effect of on-road particles.Results: The highway aerosol particle number concentration was 196,000-542,000/cm3; the filtered air particle concentration was 700-6000/cm3. Theparticle size range was 18-28 nm. A significant decreased of HR and HRVin animal exposed to on-road particle was associated with significantchanges (p�0.001) in vagosympathetic balance predominately drawn byan increased in parasympathetic tone (see figure).Conclusion: The study suggests that on-road particle exposures may havean impact on the autonomic nervous system emphasizing the existence ofa link between cardiovascular mortality and particulate air pollution.

415

An optimized protocol for cardiac gated computedtomography of the coronary veins for pretreatmentplanning*Frandics P. Chan, MD, PhD, *Allessandro Napoli, MD,Girish Narayan, MD, *Angela Tsiperfal, RN and *SungChun, MD. Stanford Univ, Stanford, CA, Stanford Univ Hosp,Stanford, CA and Stanford Univ Medical Ctr, Stanford, CA.

Background: Non-invasive CT imaging of the coronary veins may facil-itate the placement of biventricular pacemaker. The presence of left ven-tricular heart failure may degrade contrast opacification and visualizationof the coronary veins. We evaluated the optimal contrast-enhanced CTprotocol in patients with heart failure.Methods: Twelve patients with left heart failure, age range 39-85 year old,underwent CT imaging of their coronary venous system before biventricu-lar pacemaker placement. Their average LV ejection fraction (EF) was22% (range 5-34%). The scans were performed on a 16-slice multi-detectorrow CT (GE LightSpeed Ultra) using 1.25 mm detector width, 0.5 secgantry rotation, and retrospectively ECG-gated reconstruction at 0 to 90%of the cardiac cycle in 10% increments. The heart was scanned from thebottom to the top. A fixed dose of 135 cc of intravenous contrast at300mg/mL of iodine concentration was infused over 45 sec. Images wereobtained at baseline before contrast infusion, and at 50 sec, 90 sec, and 120sec after the start of injection. Contrast densities in Hounsfield units (HU)were measured in the right atrium (RA) and ventricle (RV), the left atrium(LA) and ventricle (LV), and the great cardiac vein (GCV). Results werecorrelated with EF.Results: The GCV achieved an average contrast density of 39.4�12.8HU,184.4�75.8HU, 177.6�46.5HU, and 154.5�26.5HU at baseline, 50 sec,90 sec, and 120 sec, respectively. At 50 sec, average contrast densities inall four cardiac chambers, including the coronary arteries, were higher thanthat in the GCV. At 120 sec, average contrast density in all four cardiacchambers and the GCV were similar. Contrast density in the GCV at 50 secmoderately correlated with EF (r�0.51). The decline of contrast densityfrom 50 to 90 sec also moderately correlated with EF (r�0.62).Conclusion: A simple, standardized cardiac gated CT protocol can imagethe coronary venous system using a fixed dose of contrast agent and animaging delay at 50 sec, which allows visualization of the coronary arteriesas well. A lower EF reduces contrast density and delays peak contrastenhancement in the coronary veins.

416

Normal morphological variants of right ventricle onmagnetic resonance imagingChandra Bomma, MD, Jan Fritz, Darshan Dalal, MBBS,Harikrishna Tandri, MD, Khurram Nasir, MD, Hugh Calkins,MD and David A. Bluemke, MD, PhD. Johns Hopkins UnivSchool of Medicine, Baltimore, MD and Johns Hopkins HospUniv School of Medicine, Baltimore, MD.

Background: Arrhythmogenic right ventricular dysplasia/cardiomyopathy(ARVD/C) is a genetic cardiomyopathy with structural and electricalabnormality mainly affecting the right ventricle (RV). Mangentic Reso-nance (MR) imaging has evolved as one of the leading non invasiveimaging modality to evaluate structural and functional abnormalities of theheart. There is wide variation in reporting about normal shape of the RV.To date normal morphology of the RV has not been described. The aim ofthis study is to describe normal shape of RV in MR imaging.Methods and Results: Study population included 31 (18males, 28�6years) healthy volunteers who has under gone electrocardiographically(ECG) triggered MR imaging on a 1.5T scanner (CV/i, General ElectricMedical Systems, Waukesha, WI) and included both blood suppressed(double inversion recovery) Fast Spin Echo (FSE) and Gradient Echo (GE)sequences. Slice thickness was 8 mm with a slice gap of 2 mm. The matrixand field of view were 256x256 and 24 cm respectively. RV morphologyin four chamber view was assessed by 2 experienced reviewers. Twenty

S132 Heart Rhythm, Vol 1, No 1, May Supplement 2004

(65%) had a wedge shaped and/or triagle shaped RV. Seven (23%) hadbox/trapezium shaped RV and 2(6%) had eliptical/round shaped RV. Twopatients had indeterminate RV shape between triangular and eliptical.Biplane measurements of RV confirmed the above findings with short axesdimension ratio being 65:1 in Triangular shaped RV and 78:1 in boxshaped RV.Conclusion: This results of this study caution physicians interpreting RVshape during ARVD/C evaluation, to consider that triangle/wedge, box/trepizium, round/elliptical shaped RV do exist and could be normal vari-ants. This would decrease the false positive interpretation of MR images indiagnosis of ARVD/C.

417

Prevalence of sleep apnea in a population of DDD and CRTpatients*Pascal Defaye, MD, *Stephane Garrigue, MD, *Jean-LouisPepin, MD, *Yann Poezevara, MS, *Gaelle David, MS,*Francis Murgatroyd, MD and *Philippe Mabo, MD. UnivHosp, Grenoble, France, Hopital Cardiologique du Haut-Leveque, Bordeaux, France, Papworth Hosp, PapworthEverard, United Kingdom and Univ Hosp, Rennes, France.

Sleep Disordered-Breathing (SDB) prevalence has been rated at 30% inpacemaker patients (pts). We sought to determine the prevalence of sleepapnea and its associated symptoms in paced pts according to the pacingindication.Methods: We evaluated by polysomnography (PSG) 88 paced pts notknown for sleep apnea. Pacing indications were: dilated cardiomyopathy(DCM) in 21 pts (24%, age 62�6 y., body mass index (BMI): 26�6),high-degree atrioventricular (AV) block in 36 pts (46%, age 68�10 y.,BMI: 26�4) and sinus node disease (SND) in 31 pts (35%, age 67�6 y.,BMI: 27�4). DCM pts underwent a CRT pacemaker implantation, theother pts being fitted by a DDD device (Talent DR/MSP, ELA Medical,France). All devices were set at 50 bpm basic rate. SDB was confirmed ifthe Apnea-hypopnea index (AHI) recorded by PSG was � 10. The specificEpworth scale assessed patients’ daytime sleep propensity related to thepresence of SDB.Results: A total of 50 pts (57%) presented a SDB: 50% of DCM pts, 63%of AV block pts and 58% of SND pts. The following table summarises themain variables:

*p�0.01.

Only 5% of DCM pts presented a severe SDB pathology (AHI�30)compared to 27% of AV block or SND pts (p�0.01), which is surprisingeven though DCM pts are slightly younger. The majority of events wereobstructive hypopneas (73% in CMD pts, 78% in AV Block pts and 79%in SND pts). The Epworth score was not correlated to AHI (regression line:r�0.08, p�NS), age (r�0.04,p�NS) nor BMI (r�0.01, p�NS). MeanEpworth score was normal (low number of pts with score �10), despite ahigh arousal index for AV Block and SND pts.Conclusions: 1] In paced pts, we observed a non-expected high prevalenceof SDB (57% of pts), mainly obstructive; 2] The severity of the pathologydoes not appear to be correlated with excessive daytime sleepiness; 3] Inpacemaker pts, SDB should be systematically detected due to the high riskof cardiovascular complications.

418

Intra atrial dyssynchrony in patients with congestiveheart failure. A colour tissue doppler imaging studyKatarina Van Beeumen, MD, Mattias Duytschaever, MD,PhD, Nico Van de Veire, MD, Rene Tavernier, MD, PhD,

Thierry Gillebert, MD, PhD and Johan De Sutter, MD, PhD.Univ Hosp Ghent, Ghent, Belgium.

Background: Congestive heart failure (CHF) creates a substrate foratrial fibrillation (AF) by atrial fibrosis and heterogeneity of intraatrial conduction. In the present study we evaluated intra atrial dyssyn-chrony in patients with CHF, using atrial colour tissue doppler imaging(TDI).Methods: We studied 12 healthy controls (age 70 � 6 yrs, group 1), 11patients with coronary artery disease (CAD) without CHF (age 70 � 3 yrs,group 2) and 12 patients with CAD and CHF (age 71 � 8 yrs, group 3).NT-pro Brain Natriuretic Peptide (NT-proBNP) and radionuclide left ven-tricular ejection fraction (LVEF) were measured. Transthoracic echocar-diography (GE, VIVID 7) was used to perform colour TDI of the atriaduring sinus rhythm. Measurements below tricuspid and mitral annuluswere selected on the right atrial free wall (RA), inter atrial septum (IAS)and left atrial free wall (LA). The time difference between the onset of theA wave at RA, IAS and LA were measured.Results: Mean NT-proBNP and mean EF were: group 1 (NT-proBNP109 � 55 pg/ml, EF 61 � 11%), group 2 (NT-proBNP 411 � 228pg/ml, EF 61 � 11%) and group 3 (NT-proBNP 865 � 715 pg/ml, EF33 � 11%), p � 0.05 between groups in ANOVA. The time differencebetween RA and IAS was significantly longer in patients with CHF(23 � 17 ms, p � 0.04) compared with group 1 (5 � 18 ms) and group2 (13 � 13 ms). The time difference between IAS and LA was notdifferent (p � 0.49) between the 3 groups. The time difference betweenRA and IAS correlated weakly but significantly with NT-proBNP (r �0.35, p � 0.04).Conclusions: In patients with CHF, significant intra atrial dyssynchronybetween RA and IAS was observed using non invasive colour TDI. Intraatrial dyssynchrony is related to NT-proBNP levels, a marker of severity ofCHF.

419

Effect of beta blocker therapy on exercise-inducedmicrovolt T-wave alternansPawel Ptaszynski, MD, *Thomas Klingenheben, MD and*Stefan H. Hohnloser, MD. J. W. Goethe Univ, Frankfurt,Germany.

Background: Microvolt level T-wave alternans (MTWA) is increasinglyused for arrhythmia risk stratification in pts with structural heart disease.MTWA determination requires a heart rate (HR) increase to � 105 bpm(assessment during bicycle or treadmill exercise). The influence of betablocker (BB) therapy with respect to reliability of noninvasive MTWAassessment has not been studied prospectively.Method: In consecutive pts scheduled for elective ICD implantation orreplacement, MTWA (spectral method; CH2000; Cambridge Heart Inc.,Bedford, MA) was measured twice, during and after withholding BBtherapy (at least 5 half-times) in random order.Results: Fifty-six consecutive pts in sinus rhythm were included in thestudy. In 14/56 pts (25%) MTWA was positive during BB therapy, whereasafter withholding BB the test was positive in 25/56 pts (45%; p�0.03). Theprevalence of indeterminate MTWA tests decreased from 41% on BB to21% off BB (p�0.03).

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Conclusion: The results of this prospective study suggest that noninvasiveMTWA assessment should be reassessed after withholding BB therapy inpts who previously tested negative or indeterminate while on BB.

420

New quantitative analysis of the time-domain signal-averaged electrocardiogram in patients with bundlebranch block: Evaluation in idiopathic dilatedcardiomyopathyAkiko Harada, Katsuya Kajimoto, MD, Kanki Inoue, MorioShoda, MD, Nobuhisa Hagiwara, MD and Hiroshi Kasanuki,MD. Tokyo Women’s Medical Univ, Tokyo, Japan.

Background: To differentiate between sustained VT (S-VT) and non-sus-tained VT (NS-VT) in patients (pts) with idiopathic dilated cardiomyopathy(I-DCM) by time-domain signal-averaged electrocardiogram (SAECG), de-spite the presence of bundle branch block (BBB), we evaluated three SAECGparameters quantitatively: root mean square voltage of the last 40ms (RMS40),low amplitude signal duration �40�113�V (LAS40), and LAS40 to the totalfiltered QRS duration ratio (LAS40/fQRS ratio).Methods: We examined 107 I-DCM pts by SAECG. In 38 pts with S-VT(20 pts without BBB and 18 pts with BBB) and 69 pts with NS-VT (42 ptswithout BBB and 27 pts with BBB), we quantitatively evaluated theusefulness of the new parameter, LAS40/fQRS ratio, as compared to theRMS40 and LAS40, and retrospectively investigated the efficacy of a newcombination criteria (RMS40�20�V and LAS40/fQRS ratio�0.34) to dif-ferentiate between I-DCM pts with S-VT and NS-VT despite BBB.Results: In the S-VT pts, the RMS40 and LAS40 differed between thosewith and without BBB (21.8�29.1 vs.10.2�6.8�V; p�0.10 and48.4�19.2 vs. 59.7�14.2 msec; P�0.05, respectively). However, for theLAS40/fQRS ratio, no difference was observed between those with andwithout BBB (0.37�0.11 vs. 0.39�0.07; P�0.33). In NS-VT pts, theRMS40 and LAS40 differed between those with and without BBB(44.7�46.8 vs. 22.1�15.8�V; P�0.05 and 34.9�11.7 vs. 42.8�24.1ms;P�0.07, respectively). However, no difference in the LAS/fQRS ratio wasobserved between the two groups, as well as for S-VT (0.29�0.08 vs.0.27�0.14; p�0.43). There was a significant difference in the LAS/fQRSratio between S-VT and NS-VT pts despite BBB (0.38�0.09 vs.0.28�0.10; P�0.0001). Furthermore, in all 107 pts despite BBB, a newcombination criteria of RMS40�20�V and LAS40/fQRS ratio�0.34 dis-tinguished the S-VT pts with a sensitivity of 68%, specificity of 75%,positive predictive value (PV) of 60% and negative PV of 81%.Conclusion: This new combined RMS40�20�V and LAS40/fQRS ra-tio�0.34 criteria is effective in identifying S-VT pts among I-DCM ptsdespite the presence of BBB.

421

The vulnerability of pulmonary veins in patients withatrial fibrillation is predicted by their electrophysiologicalpropertiesMassimo Tritto, MD, Roberto De Ponti, MD, GiammarioSpadacini, MD, Paolo Moretti, MD, Raffaella Marazzi, MD,Marcelo E. Lanzotti, MD and Jorge A. Salerno-Uriarte, MD.

Univ of Insubria-Varese; “Mater Domini” Hosp, Castellanza,Italy and Univ of Insubria-Varese; Ospedale di Circolo andFondazione Macchi, Varese, Italy.

The pulmonary veins (PVs) represent the major target for atrial fibrillation(AF) ablation, but their electrophysiological properties are scarcely known.We prospectively evaluated the PV vulnerability in 32 consecutive pts (31m; mean age: 54�10 yrs) with drug-refractory paroxysmal AF submittedto PV electrical isolation by ostial radiofrequency applications at theatrio-venous conduction breakthroughs.Methods and Results: Programmed electrical stimulation (S1-S2; 400ms basic drive cycle length; pacing output at twice the pacing threshold)was performed by quadripolar catheters placed in the high right atrium(RA) and coronary sinus (CS), and from a couple of distal electrodes ofa basket catheter inserted within the PVs (pacing electrodes at � 1.5 cmfrom the PV ostium). Overall, 94 PVs were tested and spontaneous AFonset was observed from 20 PVs (ArrPVs). The following parameterswere evaluated: 1. RA, CS, and PV effective refractory periods (ERPs);2. the difference between maximum and baseline PV-to-left atrium(LA) conduction time evaluated on the basket recordings during extra-stimulation and basic drive, respectively (PV-LAmax/PV-LAb); 3. AFinduction by premature stimulation. PV ERP did not differ among PVsbut was significantly shorter than RA and CS ERPs, respectively(126�50 ms vs 205�25 ms and 232�30 ms; p �0.001). AF was morefrequently induced during PV pacing than RA and CS stimulation (44%vs 21%; p �0.05), and in ArrPVs as compared to non ArrPVs (70% vs35%; p �0.01). Vulnerable PVs had significantly shorter ERP (96�35vs 150�48 ms; p �0.001), and more decremental LA-PV conduction(PV-LAmax/PV-LAb: 138�44 vs 104�39 ms; p �0.01) as comparedto non-vulnerable PVs.Conclusions: PVs are markedly vulnerable during programmed electricalstimulation in pts with AF. Vulnerable PVs have distinctive electrophysi-ological properties (ultra-short ERP and slower conduction). These find-ings have potential implications for the selection of target PV duringcatheter ablation procedures which should be assessed by further prospec-tive studies.

422

Recurrence of atrial fibrillation after cardioversionincreases risk of deathAhmad A. Elesber, MD, A. Gabriela Rosales, Win K. Shen,MD, Joseph Maalouf, MD, Nasser Ammash, MD, David O.Hodge, MS, Bernard J. Gersh, MD, Stephen C. Hammill, MDand Paul A. Friedman, MD. Mayo Clinic, Rochester, MN.

Background: Atrial fibrillation has been associated with increasedmortality. We sought to determine whether the recurrence of atrialarrhythmia post electrical cardioversion (DCCV) has an influence onsurvival.Methods: A cohort of 323 patients (pts) with documented atrial fibrillationor flutter (171 with a new onset episode) was followed after DCCV forrecurrence and all-cause mortality. Post-surgical pts with atrial fibrillationwere excluded. Cox proportional hazards models were used to constructunivariate and multivariate models. Recurrence was analyzed as a timedependent covariate in the models.Results: The mean age was 71.1�12.4 years with 69% being males,30% had coronary artery disease, 19% had congestive heart failure and68% had hypertension. The mean follow up was 2.0�0.6 years. Theresults of the univariate analysis are reported in the table. In a multi-variate model, age (HR�1.08, 95% CI (1.04,1.11), p�0.0001), historyof coronary artery disease (HR�2.20, 95% CI (1.19, 4.05), p�0.0117),diuretic use (HR�4.62, 95% CI (2.29, 9.31), p�0.0001) and recurrenceof atrial arrhythmia after DCCV (HR�3.15, 95% CI (1.60, 6.19),p�0.0009) were associated with increased mortality.

S134 Heart Rhythm, Vol 1, No 1, May Supplement 2004

Conclusion: Patients with recurrence of atrial fibrillation or flutterfollowing DCCV have a higher mortality than those without recurrence.

423

Atrial arrhythmias post surgical MAZE: Findings duringcatheter ablationOussama M. Wazni, MD, Nassir F. Marrouche, MD, SoufianAlmahameed, MD, MBBS, David O. Martin, MD, MPH, WalidI. Saliba, MD, Robert A. Schweikert, MD and Andrea Natale,MD. The Cleveland Clinic Foundation, Cleveland, OH.

Background: The “cut and saw” MAZE procedure is being considered fortreatment of atrial fibrillation (AF). We describe our findings in patientsundergoing ablation of atrial arrhythmias after surgical MAZE.Methods and results: Twenty-three patients (15 men) with a mean age of64�12 years presented with arrhythmias refractory to antiarrhythmic drugs(AADs) after 14� 14 months post Maze surgery for treatment of AF. Eightpatients underwent “cut and saw” MAZE for lone AF with no othersurgical indication. Fifteen patients underwent MAZE in addition to an-other surgical procedure: mitral valve surgery (11 patients) and CABG (4patients). Eight patients (35%) had recurrent AF secondary to recoveredpulmonary vein ostial conduction. Five patients were documented to havefocal atrial tachycardia (AT), which was mapped to the coronary sinus in3 patients, to the posterolateral right atrium (RA) in 1 patient and to the leftatrial (LA) septum in 1 patient. Four patients had RA incisional atrial flutter(AFL) and 6 had LA incisional AFL. In the latter group the AFL circuitwas mapped around the right pulmonary veins in two patients and aroundthe mitral valve annulus in 4 patients. Twenty-two out of the 23 patientswere treated successfully with radiofrequency ablation (RFA). RFA wasunsuccessful in one patient with multiple right atrial arrhythmias in thesetting of severe mitral regurgitation and severe biatrial enlargement. Atone-year followup 20 patients were arrhythmia free on no AADs. Onepatient with mitral valve annulus AFL had recurrence of AFL and oneother patient had recurrence of AF.Conclusion: After surgical MAZE approximately a third of patients expe-riencing atrial arrhythmias have AF secondary to PV-LA conduction re-covery. Moreover, incisional AFL seems to be a common finding in thisgroup of patients. Catheter based mapping and ablation of these arrhyth-mias seems to be feasible and effective.

424

Does alcoholic intoxication really promote atrialfibrillation? Experimental evidence against theproarrhythmic effects of ethanolGuilherme Fenelon, MD, Carlos E. Balbao, MD, RinaldoFernandes, MD, Otavio Ayres, MD, Priscila Landim, MDand Angelo De Paola, MD. Paulista School of Medicine-Federal Univ of Sao Paulo, Sao Paulo, Brazil.

Background: Alcohol has long been related to atrial fibrillation (holidayheart syndrome), but its electrophysiologic actions remain unclear.Methods: We evaluated the effects of alcohol in 23 chloralose-anesthe-tized dogs (10-27 kg) at baseline and after 2 cumulative intravenous dosesof ethanol: first dose 1.5 ml/kg (plasma level 191 mg/dL); second dose 1.0

ml/kg (267 mg/dL). In 13 closed-chest dogs (5 with intact autonomicnervous system, 5 under complete autonomic blockade and 3 sham con-trols), electrophysiologic evaluation and monophasic action potential(MAP) recordings were undertaken in the right atrium and ventricle. 2Decho and ultrastructural analysis were performed in 5 additional dogs. Inthe remaining 5 dogs, open-chest biatrial epicardial mapping with 8 bipoleson the bundle of Bachmann was undertaken.Results: In closed-chest dogs with intact autonomic nervous system,ethanol did not change mean arterial pressure. Also, no effects were notedon surface ECG variables: sinus cycle length; P wave duration; PR interval;QRS duration; and QTc. No changes were observed on PA, AH and HVintervals, corrected sinus node recovery time and Wenckebach point. At acycle length of 300 ms, no significant effects were noted on atrial (98 vs 98vs 98 ms) and ventricular (150 vs 160 vs 150 ms) ERP and on right atrialMAP90 (97 vs 92 vs 96 ms). These results were not altered by autonomicblockade. No changes occurred in sham controls. In open-chest dogs, atrapid rates (200 ms), ethanol did not affect inter-atrial conduction time (62vs 63 vs 63 ms), conduction velocity (125 vs 125 vs 124 cm/s) andwavelength (12.4 vs 12.2 vs 12.6 cm). Further, ethanol did not alter leftatrial ERP (100 vs 98 vs 102 ms). Atrial arrhythmias were not induced inany dog, either at baseline or after ethanol. Histological and ultrastructuralfindings were normal but LV ejection fraction decreased in treated dogs (77vs 73 vs 64%; p�0.04).Conclusion: Ethanol at medium and high doses depresses LV systolicfunction but has no effects on atrial electrophysiological parameters. Thesefindings suggest that acute alcoholic intoxication does not promote atrialarrhythmias.

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Late atrial reentry tachycardias depend on the type ofsurgical approach to the mitral valvePeter Lukac, Anders K. Pedersen, MD, Peter T. Mortensen,MD, Henrik K. Jensen and Peter S. Hansen, MD. AarhusUniversity Hosp at Skejby, Aarhus, Denmark.

Background: The knowledge of the impact of surgical approach to themitral valve on late atrial reentry tachycardia may be relevant for thechoice of the procedure and ablation of these arrhythmias.Methods and results: Twenty-two consecutive patients(pts) (16 males,age 62�11 years) underwent catheter ablation of atrial tachycardias guidedby electroanatomic mapping. Pts were 5�8 years after mitral valve sur-gery. Eight pts had been operated using the superior transseptal approach,9 pts using the left atrial approach and 5 pts had had a radiofrequencyMAZE procedure additional to mitral valve operation performed. Theincisions could be identified in most pts as lines of double potentials, oftenwith adjacent areas of dense scar or low voltage areas. In 10 pts, the leftatrium was mapped. While 5 of these pts had also dense scar areas notcorresponding to incisions in the left atrium, such an area was found onlyin 1 pt in the whole group in the right atrium. Twenty-eight tachycardiacircuits were documented (Table).

Left atrial reentry tachycardias were not further classified because only halfof them were mapped. Typical atrial flutter and left atrial reentry tachy-cardia were frequent with both approaches. However, half of the ptsoperated with the superior transseptal approach had right atrial incisionaltachycardia, where the central obstacle was formed by the right atrial partof the incision.Conclusion: The superior transseptal approach was associated with fre-quent occurrence of right atrial incisional tachycardia. Furthermore, it mayparticularly predispose to typical atrial flutter by creating a long posterior

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line of block. Further studies are needed to investigate, if these findingstranslate into a higher incidence of late atrial reentry tachycardia after thisapproach.

426

The “rS” pattern in lead III: A novel ECG finding inpatients with Mahaim fibers (right-sided accessorypathways with anterograde slow conduction anddecremental properties)Eduardo B. Sternick, MD, Carl Timmermans, MD, PhD,Eduardo A. Sosa, MD, PhD, Fernando E. S. Cruz, MD,Maurıcio I. Scanavacca, MD, PhD, Luz-Maria Rodriguez,MD, PhD, Marcio L. A. Fagundes, MD, Luiz M. Gerken,MD and Hein J. J. Wellens, MD, PhD. Biocor Instituto,Belo Horizonte, Brazil, Univ Hosp Maastricht, Maastricht,Netherlands, Inst do Coracao, Sao Paulo, Brazil, Inst deCardiologia Laranjeiras-Ministerio da Saude, Rio deJaneiro, Brazil, Academic Hosp Maastricht, Maastricht,Netherlands and Inst Nacional de Cardiologia Laranjeiras,Rio de Janeiro, Brazil.

Background: Previous reports did not describe specific ECG findings inpatients with “Mahaim physiology” during sinus rhythm. The12-lead ECGis interpreted as normal in the majority of patients.Methods: We retrospectively analysed the ECG of 40 patients (pts)with right-sided atriofascicular or atrioventricular accessory pathways(AP) with anterograde slow and decremental conduction who under-went radiofrequency catheter ablation guided by discrete proximal APpotentials (n�32), distal AP potentials (n�6) or surgical ablation(n�2). 33 patients had LBBB-like antidromic tachycardia, 2 pts hadAVNRT with a bystander Mahaim conduction, 2 pts had non-sustainedrepetitive automatic tachycardia arising in the Mahaim fiber, 1 hadpreexcited atrial fibrillation and 1 pt presented with antidromic tachy-cardia due to an associated AP. 1 pt was non-inducible. Twenty-four ptswere females and 16 males. Mean age at ablation was 24�12 (range 8to 80) years. Five pts had associated manifest AP (WPW), and 3 had aconcealed AP. Eight pts (20%) had Ebstein’s disease. Location of theMahaim fiber was right lateral in 32 pts, right anterior in 3 pts and rightposterior in 3 pts, right posteroseptal in 1 pt and midseptal in 1 pt. Wealso analysed the 12-lead ECG of 25 pts with a right free wall manifestAP as a control group.Results: In the 30 minimally preexcited pts (75%) we found three QRSpatterns in lead III: rS in 25 pts with a r/S ratio � 1/4, rsR’ in 2 pts andrsr’s’ in 1 pt. This pattern was not constantly observed in leads II and avF.In the control group “rS” pattern was present in 5 patients (20%)(p�0.01),but always associated with a wide QRS (�0.14 sec) and a r/S ratio � 1/4.After ablation of the Mahaim pathway different QRS patterns emerged: themost common beeing qR or QR in 18 pts.Conclusion: A rS pattern in lead III during sinus rhythm associated witha narrow QRS complex is the most common ECG abnormality in ptswith a Mahaim fiber. This QRS pattern which was present in 62% of thepts with Mahaim fibers when associated with a narrow QRS and a r/Sratio � 0,25 was highly specific for Mahaim, and not seen with rightfree wall WPW.

427

Usefulness of hand-grip manoeuvre to inducesupraventricular tachycardias during electrophysiologicevaluationRoberto De Ponti, MD, Massimo Tritto, MD, Raffaella Marazzi,MD, Giammario Spadacini, MD, Fabrizio Caravati, MD, PaoloMoretti, MD, Marcelo E. Lanzotti, MD and Jorge A. Salerno-Uriarte, MD. Univ of Insubria-Varese; Ospedale di Circolo andFondazione Macchi, Varese, Italy, Univ of Insubria-Varese;

“Mater Domini” Hosp, Castellanza, Italy and Univ of Insubria,H di Circolo & Macchi Foundation, Varese, Italy.

Aim: To evaluate the usefulness of hand-grip manoeuvre to induce su-praventricular tachycardia at EP testing in non inducible pts.Methods: 38 pts (27 M; mean age 33�10 yrs) undergoing EP evalua-tion for documented narrow QRS tachycardias (16 pts; 42%) or nondocumented self-terminating effort palpitations (22 pts; 58%) wereconsidered. No pt had history of syncope. In all of them, during EPstudy even aggressive atrial and ventricular stimulation protocols alsoduring isoprenalin infusion up to 5 �g/Kg/min induced no arrhythmia,nor evidenced an arrhythmogenic substrate. In all this cases, while onisoprenalin infusion, programmed atrial stimulation with multiple ex-trastimuli was repeated during hand-grip manoeuvre prolonged for3 min.Results: During hand-grip manoeuvre an atrioventricular nodal reen-trant tachycardia was reproducibly induced in 24 pts, a focal atrialtachycardia in 5 pts, whereas 9 pts remained still non inducible. Symp-toms during the induced tachycardia were recognized by all patients asthe spontaneous palpitations. In pts with an inducible atrioventricularnodal reentrant tachycardia, shortening of both the fast and slow path-way refractoriness was observed during hand-grip and tachycardia wasinduced by S2S3 stimulation upon antegrade block of the fast pathway.In all pts, ablation of the slow atrioventricular nodal pathway or of theatrial focus was successfully accomplished. One pt had recurrenceduring follow-up and was successfully retreated.Conclusions: Hand-grip manoeuvre allows induction and, hence, treat-ment of the clinical arrhythmia in 76% of pts with supraventri-cular tachycardias, who are non inducible by aggressive EP testing.The majority of this subset of pts has effort palpitations. Hand-grip manoeuvre seems to magnify the effect of pharmacologic beta-adrenergic stimulation on both fast and slow atrioventricular nodalpahways.

428

Electrophysiologic characteristics of the connectionbetween the coronary sinus and the left atrium in humans*Stephen W. Lord, MRCP, Weiwei Zhang, MD, Suhua Yan,MD, Bruce Q. Wilson, FRACP and Mark A. McGuire,FRACP. Royal Prince Alfred Hosp, Sydney, Australia.

Background: Recordings from the coronary sinus (CS) are sometimes usedas a means of recording left atrial (LA) activity during electrophysiologic(EP) studies. However, the CS has a muscle coat that can generate elec-trical potentials. A catheter in the CS may record both CS and far-field LApotentials. Failure to recognize the origin of components of the CS elec-trogram is a potential source of error in accessory pathway location. Theaim of this study was to elucidate the origin of components of the CSelectrogram.Subjects: Eleven patients undergoing ablation of left sided accessorypathways.Methods: During EP study parallel decapolar catheters were placed in theCS and LA. Simultaneous CS and LA recordings were made during sinusrhythm, supraventricular tachycardia (SVT) and pacing. The source of CSelectrogram components was identified and the activation of the LA andCS compared.Results: During sinus rhythm, CS and LA components occurred simul-taneously making identification difficult. Temporal separation of the com-ponents was observed with premature atrial stimuli, SVT or ventricularpacing in 9 of 11 subjects. The amplitude and frequency of the CS and LAsignals were similar meaning that they could not be differentiated usingmorphological criteria. Connections between the CS and LA at a siteclearly different from the accessory pathway were identified in five ofeleven subjects. LA activation was clearly different from CS activationduring SVT in these subjects. In one subject far field LA activation was

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absent in the CS recording leading to potential error in localization of thepathway.

Figure shows different activation of CS and LA during SVT (left panel)and catheter position (LAO above RAO).Conclusions: Failure to identify the origin of components of the CSelectrogram may lead to incorrect localization of the accessory pathway.

429

Efficacy of implantable cardioverter-defibrillators for theprimary and secondary prevention of juvenile suddendeath in patients with catecholaminergic polymorphicventricular tachyarrhythmiasFernando E. S. Cruz, MD, Cinzia Moncalvo, MD, Marcio L. A.Fagundes, MD, Raffaella Bloise, MD, Carlo Napolitano, MD,Bernardo R. Tura, MD, Lania R. Xavier, MD, Roberto M. S. Sa,MD, Angelo A. V. De Paola, MD, Lutgarde M. S. Vanheusdenand Silvia G. Priori, MD, PhD. Inst de CardiologiaLaranjeiras-Ministerio da Saude, Rio de Janeiro, Brazil, Inst deCardiologia Moleculare, Pavia, Italy and IRCCS Fondazione S.Maugeri, Univ of Pavia, Pavia, Italy.

Background: Catecholaminergic Polymorphic Ventricular Tachyarrhyth-mia (CPVT) with a normal heart is a highly lethal genetic devastatingdisease. Many authors have emphasized the risk of juvenile sudden deathwith reported mortality as high as 20 to 30 percent.Methods: We conducted a retrospective multicenter study to determine theefficacy of Implantable Cardioverter-Defibrillators (ICD) for primary andsecondary prevention of sudden death in 12 patients with inherited CPVToccurring in the structurally normal heart. Data on stored electrograms ofappropriate and inappropriate discharges were analyzed to identify malig-nant tachyarrhythmias related to the triggering event.Results: The age of 12 patients, at the time of ICD implantation were 14to 43 years old (mean age, 25 � 9); 6 patients were less than 22 years old.ICD were discharged appropriately in 6 patients (50%) in restoring sinusrhythm. The time interval between implantation and first appropriate shockvaried from 1 to 58 months (mean, 18 � 19). A total of 6 patientsexperimented inappropriate discharges. The average rate of appropriatedefibrillator discharges were 1.6 � 3.5, 0.4 � 0.7 and 0.2 � 0.6 for thefirst, second and third year respectively. All patients were in use ofBeta-blocker agents (Nadolol-10 pts, Metroprolol and Atenolol-1 pt each).The average Follow-Up period was 46 � 22 months. All patients survivedto the end of the study.Conclusions: 1-This multicenter study established a crucial role of im-plantable Cardioverter-Defibrillator therapy for primary and secondaryprevention of sudden death in patients with inherited CPVT. 2-Isolatedtherapy with Beta Blocker agents does not prevent malignant events inCPVT patients.

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Frequency of concealed gene defects in unexplainedsudden deathSumeet S. Chugh, MD, Olga Senashova, Allison Watts,Zhengfeng Zhou, Qiuming Gong, Jack L. Titus, MD, PhDand Susan J. Hayflick. Oregon Health & Science Univ,

Portland, OR and JE Edwards Registry of CardiovascularDisease, St. Paul, MN.

Background: Patients with sudden cardiac death (SCD) and apparentlynormal heart may constitute up to 5% of overall SCD cases. In suchpatients, systematic post-mortem genetic analysis of archived tissue usinga candidate gene approach, may identify etiologies of SCD.Methods: We performed analysis of KCNQ1, KCNH2, SCN5A, KCNE1and KCNE2 defects in a subgroup of 12 adult subjects with unexplainedsudden death, from a 13-year, 270-patient autopsy series of SCD. Ar-chived, paraffin-embedded myocardial tissue blocks obtained at the origi-nal post-mortem examination were the source of DNA for genetic analysis.Results: Two patients were found to have the same HERG defect, amissense mutation in exon 7 (nucleotide change G1681A, coding effectA561T). The mutation was heterozygous in patient 1, but patient 2 ap-peared to be homozygous for the defect. Patch-clamp recordings showedthat the A561T mutant channel expressed in HEK cells failed to generateHERG current. Western blot analysis implicated a trafficking defect in theprotein, resulting in loss of post-translational processing from the immatureto the mature form of HERG. No mutations were detected among theremaining 4 candidate genes.Conclusions: In this autopsy series, two of 12 patients (17%) withunexplained sudden death were observed to have a defect in HERG among5 candidate genes tested. There is significant potential for expansion of thecandidate gene pool for sudden arrhythmic death syndromes.

431

Use of irbesartan to maintain sinus rhythm in lone atrialfibrillation patients. A prospective and randomized studyAntonio H. Madrid, MD, Irene Marin, MD, Carlos Escobar,MD, Manolo Gomez Bueno, MD, Enrique Bernal, MD,Sebastian Nannini, MD, Liliana Limon, MD and ConcepcionMoro, MD. Hosp Ramon y Cajal, Madrid, Spain.

The inhibition of the renin-angiotensin system is beneficial in the manage-ment of cardiovascular diseases. Major clinical trials have shown thatangiotensin II type-1 receptor blockers and/or angiotensin-converting en-zyme inhibitors are helpful to prevent atrial fibrillation. The present studyhas evaluated the effect of treatment with the angiotensin II type 1 receptorblocker irbesartan on maintaining sinus rhythm after conversion from apersistent episode in lone atrial fibrillation patients.To be included in the present study, patients must have had an episode ofpersistent atrial fibrillation for � 7 days, in the absence of cardiac orextracardiac causes and with normal blood pressure values (“lone atrialfibrillation”) Patients were then randomized and scheduled for electricalcardioversion. Three groups of patients were compared: Group I wastreated with amiodarone, group II was treated with amiodarone plus irbe-sartan 150-mg daily and group III with amiodarone plus irbesartan 300-mgdaily. The primary end point was the length of time to a first recurrence ofatrial fibrillation. From a total of 456 patients assessed in the study, 79 wereincluded and analyzed with the use of intention-to-treat analysis. Twenty-five patients were randomly allocated to group I, 28 to group II and 26 togroup III. The patients were cardioverted and followed. During the fol-low-up period (median time, 210 days ırange, 60 to 900y 6 of the patientsin the 300-mg group (23 %) and 10 of the patients in the 150-mg group (35%) reached the primary end-point, as compared with 12 (48 %) in theamiodarone alone group. The Kaplan-Meier analysis of time to first recur-rence during the follow-up period showed that patients treated with irbe-sartan 300 mg had a greater probability of remaining free of atrial fibril-lation (85% versus 42,8% for amiodarone and 59,7% foramiodarone�irbesartan 150-mg), hazard ratio for a recurrence in group III:0,17 (95% CI 0,05-0,618; p� 0,0075). Patients with lone atrial fibrillationtreated with amiodarone plus irbesartan 300-mg had a significantly lowerrate of recurrence of atrial fibrillation than did patients treated with ami-odarone alone.

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432

Effects of a Na� channel blocker on electrophysiologicalproperties of the pulmonary veins in patients with atrialfibrillationKoichiro Kumagai, MD, PhD, Masahiro Ogawa, MD, HirooNoguchi, MD, Tomoo Yasuda, MD and Keijiro Saku, MD,PhD. Univ Hosp of Fukuoka, Fukuoka, Japan.

Na� channel blockers are used for the treatment of atrial fibrillation (AF).However, the effects of Na� channel blockers on the electrophysiologicalproperties of the pulmonary veins (PVs) have not been well characterized.Therefore, we assessed the effects of pilsicainide, a pure Na� channelblocker (class 1c drug), on the electrophysiological characteristics withinthe PV and at the PV-left atrial (LA) junction using multielectrode basketcatheter mapping.Methods and Results: PV mapping using a basket catheter was performedin 22 patients with paroxysmal AF. Thirty-two bipolar electrograms wererecorded simultaneously from a basket catheter. Twenty-two PVs, includ-ing 17 left superior and 5 right superior PVs, were studied at 92 pacingsites. The proximal electrode of the basket catheter was located at thePV-LA junction. The programmed stimulation was performed in the distalPV and PV-LA junction before and after infusion of pilsicainide (1 mg/kg).Pilsicainide significantly prolonged the effective refractory period (ERP) ofthe distal PV (from 183�35 to 228�46 ms, P�0.01) and ERP of thePV-LA junction (from 242�48 to 262�48 ms, P�0.05). The degree ofERP prolongation by pilsicainide in the distal PV was significantly higherthan that in the PV-LA junction (21�12 versus 6�6 %, P�0.05). Pilsic-ainide significantly prolonged the conduction time (S1-A1) from the distalPV to PV-LA junction (from 44�16 to 59�17 ms, P�0.01), however, itdid not change the conduction time at the shortest coupled extrastimulus(S2-A2, from 153�30 to 138�46 ms, NS) or the maximum conductiondelay (S2-A2–S1-A1, from 104�32 to 78�42 ms, NS). In a patient withinduced sustained AF, pilsicainide blocked the conduction from the LA toPV at the PV-LA junction, and then terminated AF.Conclusions: In patients with AF, pilsicainide has antiarrhythmic effectson the PV and PV-LA junction by modifying the ERP heterogeneity andthe conduction properties. Therefore, if the PV and PV-LA junction mightplay an important role as a substrate for the maintenance of AF, pilsicainidemay terminate AF by pharmacological PV isolation.

433

Pacemapping of Koch’s triangle avoids AV block duringablation of atrio-ventricular nodal re-entrant tachycardiaNadir Sitta, MD, Pietro Delise, MD, Leonardo Coro, MD,Mauro Fantinel, MD, Aldo Bonso, MD, Roberto Mantovan,MD, Roberto Verlato, MD, Franco Zoppo, MD, Daniele D’Este,MD, Elena Marras, MD and Luigi Sciarra, MD. ConeglianoHosp, Conegliano (TV), Italy, Feltre Hosp, Feltre (TV), Italy,Umberto I Hosp Mestre, Mestre (VE), Italy, Treviso Hosp,Treviso, Italy, Camposampiero Hosp, Camposampiero (PD),Italy and Mirano Hosp, Mirano (VE), Italy.

Introduction: Slow pathway (SP) ablation for atrio-ventricular nodal re-entrant tachycardia (AVNRT) can be complicated by a second and/or athird degree AV block. We assessed the usefulness of pace-mapping ofKoch’s triangle (PMKT) in preventing this complication.Methods: 909 patients (pts) with AVNRT underwent an ablative treatmentin 6 Centers and were analized. 487 pts (Group 1) had a conventional SPablation; 422 pts (Group 2) had an ablation guided by PMKT, whichlocalized the anterograde fast pathway (AFP) on the basis of the shorteststimulus-His interval obtained stimulating the anteroseptal, midseptal andposterosepatal area of the Koch’s triangle.Results: In Group 2, AFP was anteroseptal in 384 pts (91%), midseptal in33 pts (7.8%), posteroseptal or absent in 5 pts (1.2%). In 33/34 pts withmidseptal AFP, SP ablation was strictly performed in the posteroseptalarea. In 4/5 patients with posteroseptal/no AFP, retrograde FP was ablated.Two patients refused ablation. Transient or permanent AV block occurred

in 12/487 pts (2.4%) of Group 1 and in 1/422 pts (0.2%) of Group 2(p�0.014); in particular permanent second-third degree AV block wascreated in 7/487 (1.4%) of Group 1 vs 0/422 of Group 2 (p�0.038).Ablation was successful in all cases.Conclusions: PMKT identifies patients with AFP abnormally close to the SPor without AFP. In these cases, guiding ablation, it allows to avoid AV block.

434

Differential pacing with recording from proximal coronarysinusPawel Derejko, MD, Massimo Tritto, MD, DariuszKozlowski, MD, PhD, Lukasz J. Szumowski, MD, PhD,Franciszek Walczak, MD, PhD, Ewa Szufladowicz, MD, PhD,Piotr Urbanek, MD, Roman Kepski, PhD, Roberto De Ponti,MD and Jorge A. Salerno, MD, PhD. Inst of Cardiology,Warsaw, Poland, Univ of Insubria-Varese; “Mater Domini”Hosp, Castellanza, Italy and Medical Univ of Gdansk,Gdansk, Poland.

To test the hypothesis whether differential pacing from low lateral (LLRA)and mid lateral (MRA) right atrium and recording from CS is a reliablemethod to discriminate between very slow conduction versus block incavo-tricuspid isthmus (CTI) in pts treated with RF ablation for typicalAFL.Methods: 43 pts were included into the study. 55 assessments were per-formed: 43 after block and 12 before the block in the CTI was completed(pseudoblock). Methods Lateral right atrial wall was sequentially pacedfrom LLRA and MRA after creating an ablation line in CTI and conductiontimes to proximal CS were measured (LRA-CS and MRA-CS). Moreoverablation line was mapped during CS pacing in order to record corridor ofdouble potentials (DP). The difference between LRA-CS and MRA-CStime intervals (LRA-MRAdiff) was calculated and it was compared be-tween pts with complete and incomplete block, as well as the presence ofcontinuos line of widely spaced DP (WSDP).Results: In 10 out of 12 cases evaluated before achieving complete blockLRA-MRAdiff was above 0 (suggesting complete block). 2 cases with theLRA-MRAdiff below 0 were excluded from further analysis. The LRA-MRAdiff was 15,1�9,1 vs 23,2�10,9 ms (p�0,03) in pts with incompleteand complete block, respectively. However, the considerable overlap be-tween two groups was observed. In 30 out of 43 pts with block WSDP wererecorded. In none of the pts with gap in the line the continuous corridor ofWSDP was observed. However, in 13 out of 43 pts with block patterndifferent from WSDP (with triple potentials or terminal potential only butwithout single or fragmented potentials) was observed. Calculated sesitiv-ity (sens), specifity (spec), positive and negative predictive values (ppv)and (npv) of WSDP are as follows: sens-0,69; spec-1; ppv-1; npv-0,48.Conclusion:1. DPc with recording from CS may be misleading in discriminating

between complete block versus slow conduction in CTI.2. Presence of continuous corridor of WSDP allows to exclude gap in the

line due to its high spec and ppv.3. More than one method of ablation line assessment should be used.

435

Three-dimensional voltage mapping to identify theprotected isthmus in atypical right atrial flutterYenn-Jiang Lin, MD, Ching-Tai Tai, MD, Chao-Hon Lai,MD, Yoga Yuniadi, MD, Yu-An Ding, MD and Shih-AnnChen, MD. Taipei Veterans General Hosp, Taipei, TaiwanRepublic of China.

Background: Voltage mapping is useful in detecting critical isthmus andguiding radiofrequency ablation for scar related tachycardia. The purposeof this study was to assess voltage mapping for characterization of the rightatrial (RA) substrate without atriotomy, and to guide catheter abaltion foratypical right atrial flutter (AFL).

S138 Heart Rhythm, Vol 1, No 1, May Supplement 2004

Material and Methods: The study population consisted of 7 patients (age66.5 � 15.2 years) with atypical AFL. Isopotential mapping during sinus rhythm,atrial pacing, and tachycardia were visualized using a noncontact mapping system(Ensite 3000). Votage mapping was analyzed offline using automated computerprogram. The low voltage zone (LVZ) was characterized by a threshold value ofless than 30 % of the maximum peak negative voltage (PNV).Results: The area of LVZ was 59.4 %, 47.7%, and 47.9% of RA surfacearea during sinus rhythm, atrial pacing, and atypical AFL, respectively.During atrial pacing, all patients had a protected isthmus between the LVZsin the crista terminalis (CT). Activation wavefronts of atypical AFL prop-agated through the isthmus with slow conduction in all patients. Linearablation on the protected isthmus effectively eliminated the atypical AFLin 7 patients without complications. After a follow-up of 11 � 2 months(range 7-14), all patients had no recurrence of atypical AFL.Conclusion: The present study demonstrated that voltage mapping duringatrial pacing was useful in detecting the protected isthmus of atypical RA AFL.This isthmus was located in the CT and bordered by LVZs. Radiofrequencyablation of this isthmus was effective in eliminating atypical AFL.

436

Improvement in left ventricular function followingradiofrequency catheter ablation of atrial fibrillation inpatients with congestive heart failureYong-Mei Cha, MD, Samuel J. Asirvatham, MD, Paul A.Friedman, MD, Thomas M. Munger, MD, Janis M.Haroldson, RN, Christine M. Bluhm, RN and Dougles L.Packer, MD. Mayo Clinic, Rochester, MN.

Background: Progressive left ventricular (LV) dysfunction is associatedwith an increased risk of atrial fibrillation (AF). AF may also precipitate orexacerbate LV dysfunction due to loss of atrial transport function and rapidventricular response rates. It remains unclear, however, whether ablation inthis group of assumed substrate-mediated arrhythmia is effective for elim-inating AF and improving quality of life.Methods: The study cohort consisted of 19 patients (pts) who had AF withLVEF �40% among 420 pts who underwent AF ablation at the MayoClinic from 7/1999 to 8/2003. These pts had AF of 6.9 � 4.8 years (12paroxysmal, 7 persistent/chronic) and failed 2.5 � 1.4 antiarrhythmic drugs(AADs). Twelve pts had class II and 7 had Class III heart failure. The meanleft atrial (LA) size was 51.4 � 3.7mm.Results: In this cohort, 15 pts underwent pulmonary vein (PV) isolationalone while 4 underwent wide area circumferential ablation with adjunctivelinear lesions. Fifty-two pulmonary veins (14 LS, 10 LI, 16 RS and 12 RI)were ablated. Four had linear ablation of the lateral LA isthmus and 1underwent right atrial linear ablation. Acutely, AF was eliminated in 18 pts.Over long-term follow-up of 18 � 13 months, 13 out of 19 pts were freeof AF (68%), although 6 required AADs. Three out of four pts with widearea circumferential ablation were AF free off AADs. LVEF was increasedfrom 34 � 6% to 51 � 7% (p�0.003) and quality of life was substantiallyimproved (NYHA function class from 2.3 � 0.5 to 1.5 � 0.7, p�0.002).Conclusion: Aggressive intervention in pts with LV dysfunction can behighly successful despite underlying LV and LA pathology. These pts,when so treated, similarly show a significant improvement in quality of lifeand some reversal of cardiomyopathy.

437

Predictive value of early atrial fibrillation recurrence aftercircumferential pulmonary vein ablation*Emanuele Bertaglia, MD, Giuseppe Stabile, MD, GaetanoSenatore, MD, Franco Zoppo, MD, Pietro Turco, MD,Claudia Abbagnale, MD, Antonio De Simone, MD, MasimoFazzari, MD and *Pietro Pascotto, MD. Ospedale Civile,Mirano, Italy, Casa di Cura, Maddaloni, Italy, OspedaleCivile, Cirie, Italy and Villa Maria Cecilia, Cotignola, Italy.

Aim: The large amount of radiofrequency energy applications requiredduring circumferential pulmonary vein ablation (CPVA) to treat paroxys-

mal or persistent atrial fibrillation (AF) creates an irritative trigger whichcould favor the occurrence of early AF relapses. Aim of this study was toevaluate whether the occurrence of early AF relapse could correlate withthe long term outcome of CPVA.Methods: We studied 143 consecutive patients (pts) who underwentCPVA between March 2001 and March 2003. After CPVA cardiac rhythmwas continuously monitored during the first 48 h. Outpatient visits and 24-hECG Holter monitoring were scheduled at 1 month, 3 month, and aftereach 3 months. Patients were also advised to perform an additional ECG inthe event of palpitations. Pts who did not present symptomatic or asymp-tomatic AF lasting � 30 sec after the first 3 months of follow up weredefined responders.Results: AF relapsed during the first 48 h in 33/143 pts (23%), betweenthe first 48 h and the 1st month in 28/143 pts (20%), and during the 2nd and3rd months in 5/143 pts (3%). After a mean follow up of 15.7�7.2 months(range 6-33), 103/143 pts (72%) resulted responders. Pts who did notrelapse during the 1st month resulted more frequently responders than ptswho relapsed during the 1st month (95% vs 48%, p�0.0001), Pts whorelapsed during the first 48 h and pts who relapsed between 48 h and the1st month had the same probability of long term clinical success (48% and42% respectively, p�0,62).Conclusion: After CPVA, absence of relapse during the 1st month predicts avery good long term outcome (95% of success). However, AF relapse withinthe first month after CPVA does not predict a bad long term outcome, becausealmost 50% of pts who relapsed within the first month resulted responders toCPVA.

438

Reverse left atrial remodeling and improved systolicfunction after pulmonary vein antrum isolation for atrialfibrillationGeorge K. Joseph, MD, Kenneth C. Civello, Jr., MD, MPH,J. David Burkhardt, MD, Yaariv Khaykin, MD, Atul Verma,MD, Mandeep Bhargava, MD, Jennifer E. Cummings, MD,Ahmad A. Karim, MD, Patrick J. Tchou, MD, David O.Martin, MD, MPH and Andrea Natale, MD. The ClevelandClinic Foundation, Cleveland, OH.

Background: Pulmonary vein antrum isolation (PVAI) for atrial fibrillation(AF) can result in restoration of sinus rhythm. The impact of this procedureon mechanical left atrial (LA) function and remodeling remains unknown.Methods: 53 patients (40 male and 13 female) who underwent successfulRF ablation for atrial fibrillation and stayed in sinus rhythm post PVAIwere studied using a number of echocardiographic variables. These in-cluded left atrial (LA) size and LA systolic area (LASA) on an average of4 months prior to PVAI and 9 months post ablation. 44 patients hadparoxysmal AF and 9 had persistent AF. All patients included were in sinusrhythm at the time of the pre-procedure and post-procedure echocardio-grams.Results: At follow up the LASA and LA size was significantly reduced onthe post-PVAI echocardiograms. (See Table)

Conclusion: In most patients, pulmonary vein antrum isolation with RFablation with restoration of sinus rhythm results in reverse remodeling ofLA and improvement of atrial contraction. These findings may be alsoresponsible improvement in symptoms post PVAI.

439

Incidence of assymptomatic pulmonary vein stenosis inpatients submitted to segmental disconnection ofpulmonary veinsSantiago Nava, MD, Lluis Mont, MD, Teresa M. de Caralt,MD, Andrea Scalise, MD, Eduardo Bartholomay, MD,Antonio Berruezo, MD and Josep Brugada, MD, PhD.

S139Poster 2

Cardiovascular Inst, Hosp Clinic, Univ of Barcelona,Barcelona, Spain and Univ of Barcelona, Barcelona, Spain.

Pulmonary vein radiofrequency ablation is a new curative procedure forpatients with atrial fibrillation. Pulmonary vein (PV) stenosis has beenrecognized as one potential complication, which may be underestimated ifthe patient is assymptomatic.Methods and Results: We prospectively studied a series of 57 consecutivepatients, treated with radiofrequency ablation for refractory atrial fibrilla-tion. Contrast enhanced Magnetic Resonance Angiography (MRA) of pul-monary veins was performed three months after the procedure.Mean age was 50 � 10 years, 81% were men. In 37 patients the procedureconsisted in a segmental ablation of the ostium of the pulmonary vein,mapping with a LASSO catheter and ablation with a 4 mm tip ablationcatheter. In 21 patients an electroanatolmical encircling of the 4 pulmonaryveins was performed with a CARTO 8mm tip ablation catheter. Twenty-four patients in the LASSO group and 13 patients in the CARTO grouphave been studied with MRA after completing a 3 month follow-up. In theCARTO group no stenosis has been found. In the LASSO group 4 (16%)patients had one PV stenosis, three of the left superior vein and one of theleft inferior. We analyzed the number of pulmonary veins treated in thisgroup and found a total of 42 pulmonary veins treated and 4 (9%) stenosisdetected. All patients were asymptomatic. There were no differences intemperature, power, impendance, number of applications and total time ofradiofrequency application in patients with stenosis and those without. Theprobability of stenosis for vein treated, is 9% for one vein treated, 18% for2 veins, 25% for 3 and 32% for 4 veins treated.Conclusion: There is a significant incidence of assimptomatic pulmonaryvein stenosis in patients with segmental ablation. Magnetic ResonanceAngiography is useful for the detection of this complication.

440

Effect of biatrial subthreshold stimulation on atrialeffective refractory periodJoseph Y. Chan, MRCP, Jeffery W. Fung, MRCP, Hamish C.Chan, MRCP, Winnie W. Chan, MRCP, Cheuk M. Yu, MD,FRCP and John E. Sanderson, MD, FRCP. Prince of WalesHosp, Chinese Univ of Hong Kong, Hong Kong, China.

Background: Timely atrial extrastimuli (AE) given in the refractory period(subthreshold) can prevent the induction of atrial fibrillation (AF) byanother AE delivered in the vulnerable period. Theoretically, because theAE was subthreshold, no atrial activation and hence propagation will beelicited and its effect should be confined to the pacing site. This study aimsto investigate the effect of SS on a distant site atrial effective refractoryperiod (AERP).Methods: 27 consecutive patients were included in the study, 5 patientswere excluded from analysis because of induction of sustained AF duringthe study. AERP of right atrial septum was determined after 5 minutes ofpacing with 4 different protocols and 3 sets of cycle length (CL) com-menced in random order with 10 minutes of washout time between eachprotocol. Protocols were as shown in table below, pacing at high rightatrium (HRA) and bi-atrial (HRA � coronary sinus) was at twice diastolicthreshold. SS was commenced by introduction of an electrical impulse of2.0msec in duration and 20mA in amplitude at 50msec after the precedingcaptured pacing impulse. The mean of 3 AERP measurements was re-corded.Results: Analysis showed that the pacing protocol but not the CL hadsignificant effect on the AERP. Multiple comparisons showed that theBi-atrial � SS group had significant longer AERP than groups without SS(protocol 4 versus protocol 1, p� 0.001; versus protocol 2, p�0.289;versus protocol 3, p� 0.007).

Conclusion: Bi-atrial SS significantly prolongs AERP. The effect of SS isnot confined to its application sites and when large enough area of atrialtissue received SS, its effect can spread to more distant sites. The studyresult suggests that biatrial SS may be an effective pacing therapy forprevention of AF.

441

Mechanisms of recurrent atrial fibrillation after pulmonaryvein isolation by segmental ostial ablationKristina Lemola, MD, Aman Chugh, MD, Burr Hall, MD,Peter Cheung, MD, Eric Good, DO, Jihn Han, MD, KamalaTamirisa, MD, Frank Bogun, MD, Frank Pelosi, Jr., MD,*Fred Morady, MD and *Hakan Oral, MD. Univ ofMichigan Health System, Ann Arbor, MI.

Background: Recovery of conduction into a previously isolated pulmonaryvein (PV) is a common observation when there is recurrent atrial fibrilla-tion (AF) soon after segmental ostial ablation (SOA). However, the mech-anisms of recurrent AF have been unclear.Methods and Results: A repeat ablation procedure was performed in 40patients who had recurrent paroxysmal AF at a mean of 7 � 6 months afterSOA to isolate the PVs. During the repeat procedure, a ring catheter wasinserted into each PV during sinus rhythm and AF to determine whether theveins were still isolated, and if not, whether there were PV tachycardiaswith a cycle length shorter than in the adjacent left atrium during AF. Therewas recovery of conduction over a previously ablated muscle fascicle in�1 PV in 39 patients (98%). There were 10�2 episodes of PV tachycardiaper minute in 27 (59%) of the 40 patients. Repeat ablation was performedby SOA (17 patients) or by left atrial ablation to encircle the left andright-sided PVs 1-2 cms away from the ostia, with additional ablation linesin the posterior left atrium and mitral isthmus (23 patients). At 6 months offollow-up, among 17 patients who underwent repeat ablation by SOA, AFrecurred in 2 of the 12 patients (17%) who had PV tachycardias, and in 3of the 5 patients who did not (60%, p�0.07). Among the 23 patients whounderwent left atrial ablation, AF recurred in 3 of the 12 patients (25%)who had PV tachycardias, and in 2 of the 11 patients (18%) who did not(p�0.7).Conclusions: Recovery of conduction in previously ablated muscle fasci-cles is a common finding in patients with recurrent AF after SOA. Theefficacy of repeat SOA tends to depend on the presence of PV tachycardias,whereas the efficacy of left atrial ablation is independent of whether or notPV tachycardias are present during AF.

442

Electrical isolation of the pulmonary veins in patientswith atrial fibrillation induces acute changes in thecardiac autonomic balanceGiammario Spadacini, MD, Massimo Tritto, MD, Roberto DePonti, MD, Paolo Moretti, MD, Raffaella Marazzi, MD,Marcelo E. Lanzotti, MD, Luciano Bernardi, MD and JorgeA. Salerno-Uriarte, MD. Univ of Insubria-Varese; “MaterDomini” Hosp, Castellanza, Italy, Univ of Insubria-Varese;Ospedale di Circolo and Fondazione Macchi, Varese, Italy,Univ of Pavia, Pavia, Italy and Univ of Insubria-Varese;Fondazione Macchi, Varese, Italy.

Electrical isolation (EI) of pulmonary veins (PVs) by radiofrequency (RF)applications may cure atrial fibrillation (AF). Anatomical studies demos-trated that autonomic fibers run close to the epicardial layers of PV ostia.We prospectively evaluated the changes of sympathovagal balance aftereach PV EI by analysing time and frequency domain RR interval variabil-ity in 15 consecutive pts (13 m, mean age 52�10 yrs) with drug-refractoryparoxysmal AF.Methods and Results: A total of 52 PVs were successfully isolated byostial RF applications at the conduction breakthroughs evidenced by abasket catheter. For each PV, the temporal sequences of RR interval, ofrespiratory signal and of arterial blood pressure were acquired for a 5 min

S140 Heart Rhythm, Vol 1, No 1, May Supplement 2004

period during controlled respiration at 15 cycles/min (COLIN, CBM 7000)before and 10 min after EI (randomly performed). Heart rate (HR) high-and low-frequency components (normalized HF and LF units) were eval-uated by autoregressive spectral analysis of RR intervals. Data regardinglateral (L) PVs (#27) and medial (M) PVs (#25) were compared. Total RFdelivery to achieve PV EI did not differ between LPV and MPV (22�13vs 29�18 min; p ns). After LPV EI, a HR slowing as compared to baselinewas observed (RR: 954�137 vs 827�43 ms; p �0.0001), not associatedwith any significant change in RR variability (460�631 vs 462�962 ms;p ns) and normalized LF and HF units. Instead, after MPV EI, a HRincrease (781�116 vs 946�135 ms; p �0.01) associated with a trendtowards a reduction of time domain HR variability (124�63 vs 519�577ms; p ns) was found. The latter modification was mostly due to a reducedvagal output, as shown by the decrease of the normalized HF units(16.5�22.3% vs 40.9�30.3%; p �0.01).Conclusions: In the short-term, RF delivery close to PV ostia affectautonomic drive and, particularly, the parasympathetic efferences. Auto-nomic response patterns significantly differ according to the area where RFis applied suggesting a asymmetric distribution of sympathetic and vagalefferences. Further studies are warranted to evaluate the long-term evolu-tion of such changes, and their influence on clinical outcome.

443

Residual atrial septal defects after pulmonary veinisolation proceduresOwen A. Obel, MD, Moussa Mansour, Michael Picard, MD,Jeremy N. Ruskin, MD and David Keane. MassachusettsGeneral Hosp, Boston, MA.

Introduction: Catheter ablation for atrial fibrillation (AF) by performinga pulmonary vein isolation (PVI) procedure has gained wide acceptance.Most centers employ an approach to the left atrium (LA) involving doubletranseptal punctures.Object: Although previous studies have examined the risk of ASD aftersingle transeptal puncture for ablation, it is not known whether the doubletranseptal puncture performed during a PVI results in residual atrial septaldefects (ASD), a possible risk factor for stroke.Methods: 30 patients undergoing repeat PVI procedures were examined. Thepresence of an ASD was examined for by transesophageal echocardiography(TEE) before each PVI procedure using color flow Doppler. Following TEE,two separate transeptal punctures were made on each occasion with a Brock-enbrough needle through a 9 Fr SL1 sheath and dilator.Results: 30 patients had a total of 66 PVI procedures with TEE performedbeforehand. The mean time between procedures was 218 days (49–752). 3patients had a pre-existing patent foramen ovale. Of the remaining patients,2 had evidence of a residual ASD. The interval between procedures was 33days in one patient and 100 days in the other.Conclusions: PVI is a commonly performed procedure. Patients whoundergo PVI are at risk of stroke during and after the procedure. RecurrentAF occuring after a PVI is similarly a risk factor for stroke. Even whensmall, ASDs comprise a risk factor for stroke. We have shown that thestandard technique employed during PVI procedures involving doubletranseptal punctures is associated with a small incidence of ASD. Althoughit is possible that the ASD seen 33 days after the first PVI may have healed,it is unlikely that the ASD seen 100 days following the procedure wouldhave resolved.

444

Minimizing cardiac perforation during linear ablation foratrial fibrillationLi-Fern Hsu, MBBS, Pierre Jaıs, MD, Meleze Hocini, MD,Prashanthan Sanders, MD, PhD, Martin Rotter, MD,Yoshihide Takahashi, MD, Christophe Scavee, MD, FredericSacher, MD, Jean-Luc Pasquie, MD, PhD, Jacques Clementy,MD and Michel Haıssaguerre, MD. Hopital Cardiologiquedu Haut-Leveque, Bordeaux-Pessac, France.

Background: Cardiac tamponade complicating radiofrequency (RF) catheterablation of atrial fibrillation (AF) has a reported incidence of approximately1% for pulmonary vein isolation (PVI) procedures, and up to 6% for left atrial(LA) linear lesions. We evaluated patients with periprocedural cardiac tam-ponade over a 1-year period to identify risk factors. After implementingcorrective measures, we reviewed the incidence over the subsequent year.Methods: During the initial year, 348 AF ablation procedures wereperformed, comprising PVI in all, with additional linear lesions at themitral isthmus in 73% and cavotricuspid isthmus (CTI) in 76%. An irri-gated-tip ablation catheter was used, with power limited to 25-35W for PVIand 45-60W for linear lesions. Heparin (50 IU/kg) was administered aftertransseptal puncture. Variables selected for analysis as potential risk factorsincluded clinical, echocardiographic and ablation parameters.Results: In the first year, 9 cases (2.6%; 6 male) of tamponade requiringdrainage were observed. Two were mechanical perforations from inadver-tent catheter movement into the LA appendage while the other 7 resultedfrom “popping” during linear ablation: 5 during mitral isthmus, and 2during CTI ablation. Peak RF power was significantly higher in patientswith tamponade compared to those without (53�4W vs 49�7W, p�0.02),and was �48W in all 7 cases. Temperature remained �50°C in all, and nodifferences in RF duration, clinical or echocardiographic data were ob-served. Subsequently, RF power for linear ablation was limited to �45W.Over the following year, among 398 AF ablation procedures, tamponadeoccurred in 3 (0.8%, p�0.05 compared to first year), 2 as a result of“popping” (at peak RF power of 42W and 40W respectively) and the otherby mechanical trauma. There was no diminution of procedural success ratewith reduction of RF power.Conclusion: The risk of cardiac perforation complicating AF ablationremains highest during linear ablation, mainly associated with use of highenergy and “popping”. Reducing delivered energy limits this complication,but further measures or technologies to prevent “popping” are required.

445

Feasibility of tandem use of coronary sinus shock andtransvenous left ventricular pace leads*David Schwartzman, MD. Univ of Pittsburgh, Pittsburgh, PA.

Background: Atrial fibrillation and heart failure frequently coexist. Im-plantable device-based therapies for each of these entities has been shownto be effective. Their coexistence has not been evaluated thus far. Oneaspect of this is the potential for hardware conflicts.Methods: We report our experience with 10 pts with atrial fibrillation andheart failure who had initially undergone implantation of an atrial arrhyth-mia management device (Medtronic 7276). In each pt, a coronary sinusshock lead (CS, Medtronic 6937A) was implanted to optimize atrial defi-brillation energy. These pts subsequently developed an indication forcardiac resynchronization therapy. To achieve resynchronization, eachpatient underwent implantation of a lead via the coronary sinus into alateral left ventricular vein (LV, Medtronic 4193) while leaving the CS leadin situ. The LV lead was married to the right ventricular lead (Medtronic6947) using an adaptor.Results: 1. Intraoperative: the presence of the CS lead did not significantlyimpede implantation of the LV lead nor compromise its stability. The atrialdefibrillation threshold was unchanged by the LV lead. LV lead functionwas unaltered by atrial defibrillation shocks; 2. Followup (mean 9�6months): among the 10 pts, 8 have elicited one or more ambulatory atrialdefibrillation shocks. There has been no LV lead dislodgement, dysfunc-tion, nor significant changes in pace/sense function. Atrial defibrillationsuccess rates have been unchanged.Conclusion: Based on our experience in this small cohort, tandem use ofCS and LV leads appears feasible.

446

Targeted linear and focal left atrial ablation guided by aregistered 3DCT*Mitchell N. Faddis, MD, PhD, *Walter Blume, MS,*Jennifer Finney, BS, Scott Greenberg, MD, *Andrew Hall,

S141Poster 2

PhD, *Jessica Schafersman, BS, *Michael Talcott, DVM,*Raju Viswanathan, PhD and *Bruce Lindsay, MD.Washington Univ, St. Louis, MO and Washington UnivSchool of Medicine, St. Louis, MO.

Catheter ablation of atrial fibrillation requires accurate catheter positioning.This study tested the accuracy and utility of a magnetic ablation catheter(MC) that is remotely controlled to perform left atrial focal and linearablation guided by a three-dimensional navigation interface (3D-Nav).Methods: The magnetic guidance system (MGS) and catheter advancersystem (CAS) remotely control a 7 Fr MC. The MC is manipulated by anexternal magnetic field applied by the MGS and axial translation by theCAS. The 3D-Nav uses a 3D-CT blood pool image for catheter navigation.A computer algorithm registered the 3D-CT to the real-time cardiac posi-tion by extraction of 3D coordinates of 3-5 pulmonary vein (PV) positionson othogonal fluoroscopic views. PV positions were visualized by placingthe MC in the PV or by contrast angiography. Each identified PV wasmatched with its image in the 3D-CT for registration. 3 canines werestudied (25-30 kg). Transeptal access to the left atrium was placed trans-venously. Three anatomically distinct focal ablation targets were markedon the registered 3D-CT. The real-time catheter position was projected onthe 3D-CT to guide MC navigation. Radiofrequency (RF) energy rangedfrom 20-50 watts for 60 seconds to achieve a �5 ohms decrease inimpedance. Linear ablation between the right and left superior PV ostiawas guided by the 3D-Nav. The accuracy of ablation targeting was mea-sured acutely by the linear displacement of the ablation lesion from theintended target.Results: Remote control of the MC with a 3D-Nav was successful forguiding the catheter to PV in all three animals. Six focal ablation targetswere identified acutely with a displacement from the intended target of 0-1cm. The linear ablation was successful with displacement of one end of theablation line observed in 2 animals (5mm, 10 mm).Conclusion: Focal and linear left atrial ablation is possible by remotecontrol with the MGS guided by a 3D-Nav. Refinements in the registrationof the 3D-CT should improve the accuracy of the 3D-Nav. This cathetersystem may facilitate ablation of atrial fibrillation and avoid radiationexposure to the operator.

447

Fibrillatory cycle length for monitoring substratemodification during catheter ablation of atrial fibrillation*Michel Haıssaguerre, MD, Li-Fern Hsu, MBBS,Prashanthan Sanders, MD, PhD, *Pierre Jaıs, MD, MelezeHocini, MD, Jean-Luc Pasquie, MD, PhD, YoshihideTakahashi, MD, Martin Rotter, MD, Frederic Sacher, MD,Christophe Scavee, MD, Dipen C. Shah, MD, StephaneGarrigue, MD and Jacques Clementy, MD. HopitalCardiologique du Haut-Leveque, Bordeaux-Pessac, France.

Prolongation of atrial fibrillation cycle length (AFCL) has been consis-tently observed during pharmacologic cardioversion in experimental stud-ies as a reflection of substrate modification. This parameter was evaluatedduring catheter ablation of AF.Methods: 81 patients underwent ablation during ongoing AF using pul-monary vein isolation (PVI, n�56) or linear ablation following PVI ateither the mitral isthmus (n�15) or roof (connecting superior PV, n�10).Mean AFCL was determined at a distance from the ablated area before andduring PVI, before and after linear ablation, by averaging sequences of 30consecutive cycles. Inducibility of AF was performed by 20mA left/rightatrial burst pacing at shortest captured cycle lengths.Results: PVI terminated AF in 42 patients (75%), with the number of PVrequiring isolation to terminate AF increasing with prior AF duration(p�0.02). PVI resulted in progressive or abrupt prolongation of AFCL tovarying degrees depending on the targeted PV, with some PV ablation notchanging AFCL while others producing a significant jump in AFCL. Thecumulative prolongation of AFCL was greater in patients with AF termi-

nation (30�17 vs 14�11ms, p�0.001) and was not linked to total RFdelivery. In patients with persistent AF after PVI, mitral isthmus and roofline interrupted AF in 11/15 and 4/10 patients respectively, associated witha greater prolongation of AFCL (isthmus:44�13ms; roof: 22�5ms) thanthose without AF termination. Sustained AF was non-inducible in 57%after PVI, 77% after mitral isthmus line and 50% after roof line. Non-inducibility of AF after ablation correlated with the degree of cumulativeincrease in AFCL (p�0.05).Conclusion: An increase in AFCL is observed both during PVI and addi-tional linear ablation to a varying extent depending on the target and theindividual. The magnitude in decline in fibrillatory rate correlated with AFtermination and subsequent non-inducibility. Fibrillatory cycle length canbe used for individualized monitoring during AF ablation.

448

High-resolution dominant frequency mapping revealsdifferent spatial distributions of activation rate inpatients with paroxysmal versus chronic atrial fibrillationOmer Berenfeld, PhD, Prashanthan Sanders, MD, PhD, RaviVaidyanathan, BS, Pierre Jaıs, MD, Meleze Hocini, MD,Michel Haıssaguerre, MD and Jose Jalife, MD. Inst forCardiovascular Research, SUNY Upstate Medical Univ,Syracuse, NY and Hopital Cardiologique du Haut-Leveque,Bordeaux, France.

Background: Animal studies demonstrated that local excitation duringacute atrial fibrillation (AF) is distributed in well demarcated dominantfrequency (DF) domains, with maximum DFs being higher in the pulmo-nary vein (PV) region and the posterior left atrium (LA) than in the rightatrium (RA). Whether similar distribution of DFs exists in humans with AFis not known. We hypothesized that in humans the predominance of DFvalues in the LA and the PV regions will be different in patients withparoxysmal (PAF) versus chronic (CAF) AF.Methods: Twelve pts (55�7 yrs) with PAF (n�7) or CAF (n�5) withspontaneous or inducible sustained AF (�10 min) were studied. TheCARTO mapping system was utilized to acquire local and surface signalsover 5 sec during AF while creating a 3D geometry. Points were acquireduniformly throughout the atria and coronary sinus (CS). Point-by-pointanalysis of DFs and regularity of the activity was carried out based on thehighest spectral peak and the relative power of the DF, respectively, andthen colour-coded on the geometry map to characterize their spatial dis-tribution. Signals showing low regularity were excluded.Results: During AF, DFs are distributed non-uniformly through the twoatria and the CS with varying number of sites showing maxima in DFvalues. Overall, DFs in 103�25 points/pt range between 3.66 and 13.18 Hzaveraging 6.07�0.52 Hz. Two-way ANOVA revealed that DFs in the atriaare organized with similar hierarchy in both PAF and CAF pts; maximumDFs in both LA and PVs (10.16�1.72 Hz) are higher than in RA(8.57�1.17 Hz) and CS (7.52�2.29 Hz, p � 0.001). The highest DFs inPAF pts are primarily located at the PVs region (4/7), never in the RA. Inthe CAF pts, the highest DFs are distributed uniformly in both atria and CS,not in the PVs region.Conclusion: PAF in humans shows a hierarchical distribution of DFs,whereby LA and PVs activate at higher rates than RA. In CAF pts, a moreuniform distribution of the DFs is observed, with the highest DF beingpredominantly outside the PV region. These results may have implicationsfor better localization of AF termination targets in patients.

449

Comparison of lesion volumes after radio-frequencyablation with platinum-iridium and gold electrode in theporcine heartAlexander Bitzen, Alexander Yang, Jan Schrickel, Jorg O.Schwab, MD, Helga Bielik, *Karsten Schlodder, *RobertBlum, *Sabine Wurtz, Berndt Luderitz and Thorsten Lewalter,

S142 Heart Rhythm, Vol 1, No 1, May Supplement 2004

MD. Univ of Bonn, Bonn, Germany and Biotronik, Berlin,Germany.

Introduction: The application of radio-frequency alternating current is thestandard method for catheter ablation to treat congenital cardiac tachyar-rhythmias. Platinum-iridium tip electrodes with an approximate length of4-10 mm are currently used for energy transmission. The primary successof an ablation procedure is related to the induction of sufficient lesionvolumes, especially in case of right-atrial flutter, ostial pulmonary veindisconnection and left-ventricular tachycardia. We compared lesion vol-umes achieved by a new gold alloy with those of Platinum-iridium elec-trodes.Methods: The ablations were performed in a porcine heart using a specialexamination chamber filled with a sodium chloride solution (38 °C) andsimulating physiological cardiac flow-through conditions (1.5 l/min). Con-stant orthogonal pressure was applied on the myocardium by the unad-justed electrode. We used 10 different myocardium samples to perform anablation with both a 4 mm platinum-iridium and gold alloy (duration 60sec, catheter tip temp. 60 °C, max. power 30 W). The samples were cutapart vertical to their necrosis, and the sections magnified by microscopeand digitalized. Afterwards the lesions were measured on a personal com-puter.Results: Using the platinum-iridium electrode the mean width was 5,16 �1,54 mm and the mean depth 2,96 � 0,81 mm, whereas the gold electrodecaused lesions with a mean width of 8,67 � 1,84 mm and a mean depth of4,85 � 1,01 mm. Presuming an ellipsoid necrosis form the calculated meanlesion volume was 109,90 � 100,9 mm3 for platinum-iridium and466,28 � 262,48 mm3 for gold (p � 0,05).Conclusion: The new gold alloy achieves higher lesion volumes than theconventional platinum-iridium alloy under identical circumstances. There-fore the gold electrode might be advantageous for catheter ablations inareas of higher myocardial thickness.

450

Safety and efficacy of epicardial cryoablation*Daniel L. Lustgarten, MD, PhD, Stephen Bell, BSc,Nicholas Hardin, MD, James Calame, RN and *PeterSpector, MD. Univ of Vermont FAHC, Burlington, VT.

Background: Percutaneous pericardial access allows epicardial ablation tobe performed using standard intravenous catheters. We studied safety andefficacy of epicardial cryoablation in a canine model.Methods: Epicardial access was obtained using a subxiphoid 8 Fr sheath.Cryoablation was delivered to atrial and ventricular sites. In the ventricleablation was delivered over a major epicardial coronary artery (-90°Ctarget temperature for 4 minutes using either a linear or a 6mm tipcatheter). Angiography was used to identify vessel targets and was repeatedafter catheter thaw. Continuous 12-lead ECG monitoring and intracardiacultrasound were performed. Angiography was repeated at 4-6 weeks (n�5)[Group 1] or at 6 months (n�5) [Group 2] followed by pathologic exam-ination. Tetrazolium chloride stained lesions were analyzed grossly andhistologically.Results: Cryoablation was delivered to 19 atrial and 26 ventricular targets.Nine of 45 lesions were associated with superficial injury to adjacent lungtissue. Acute angiographic stenosis was seen in 4/12 arterial targets(Group1) and 6/14 arterial targets (Group 2). No wall motion abnormalitieswere found by ultrasound and all ECG changes normalized post thaw. Nostenoses were seen at follow up angiography. Neointimal proliferation wasseen at histological evaluation in 7/12 arterial targets from Group 1 and11/14 from Group 2. Occlusive injury was seen in one small branch vessel.The average depth of atrial lesions was 1.2 � 1.5 mm, (n�19; 11/19transmural). The average depth of ventricular lesions was 2.1 � 1.4 mm(n�26; 0/26 transmural).Conclusions: Epicardial cryothermy delivered using standard catheterscaused little damage in adjacent non cardiac tissue but significant vasculardamage when applied directly above epicardial arteries. Angiography wasmisleading as most lesions were ablumenal and therefore not appreciatedangiographically. Ventricular lesions were superficial. Posterior left atrial

lesions were transmural suggesting epicardial cryoablation may be usefulin pulmonary vein encirclement procedures. This warrants further investi-gation.

451

EASYTRAK® 3 a spiral fixation coronary venous lead:Factors that predict implant success*Claudio Schuger, MD, *Gregory Botteron, MD, *Valerie A.Smith, PhD, *Jill E. Schafer, MS and *Ronald D. Berger,MD, PhD. Henry Ford Hosp, Detroit, MI, St. Anthony’sMedical Ctr, Kirkwood, MO, Guidant Corp, St. Paul, MNand Johns Hopkins Hosp, Baltimore, MD.

Introduction: Large branch vessels present challenges in implantingcoronary venous (CV) leads for cardiac resynchronization therapy (CRT).A new lead design (EASYTRAK-3) is secured with a spiral fixationmechanism to provide stability in large branch vessels. This lead design iscomplementary to existing leads (EASYTRAK) that use a tined fixationmechanism. It is unknown pre-operatively which patients (pts) are suitablefor each type of lead. Baseline demographics were examined retrospec-tively to predict implant success for this new lead.Methods: The EASYTRAK-3 clinical trial enrolled 115 pts (88 male, 27female). Physician investigators were encouraged but not required to at-tempt placement of the spiral-fixation lead. Success rate was measuredbased on all pts in whom a CV lead implant was attempted. Baselinedemographics were analyzed using a multivariate logistic regression withstepwise variable selection.Results: Of the 115 pts enrolled, 101 (88%) were successfully implantedwith a tined-fix (27 pts) or spiral-fix lead (74 pts). Consistent with previousstudies, body surface area (BSA) was the only independent predictor ofoverall CV lead implant success (P�0.02). In the 100 pts in whom a spiralfixation lead was attempted, a success rate of 74% was observed. In the 26cases in which the spiral-fix lead was attempted but failed, all but 3 patientsreceived the tined fix lead. The tined fix lead was attempted in an additional5 pts and successful in 4, giving an overall implant success rate of 96%(101/105) in those pts in which either lead was attempted. The onlyindependent predictor of spiral-fix implant success vs. tined-fix was gen-der, with males being 2.7 times more likely to have a successful EA-SYTRAK-3 implant (P�0.04). Of the 75 males successfully implanted, 59(79%) received a spiral fixation lead while of the 26 females implanted,only 15 (58%) received a spiral fixation lead.Conclusion: Gender is the only independent non-invasive predictor ofspiral-fix vs. tined-fix CV lead implant success. Adding EASYTRAK-3 tothe EASYTRAK family of leads may improve the overall implant successrate in situations where the venous anatomy can be accessed.

452

Introduction of permanent cardiacstimulation/defibrillation leads via the retro-pectoralveinsJean Pierre Camous, Sr., MD, Florence Raybaud, MD,Philippe Benoit, MD, Ingrid Lesto, MD and Marcel Baudouy,MD. Nice, France.

To introduce permanent cardiac stimulation/defibrillation leads, the ce-phalic vein is most often used. Direct puncture of the subclavian vein canbe done first or as an alternative. However, this latter route has recognizedcomplications. Because of this, we explored the possibility of using theretro-pectoral veins when the cephalic vein is not suitable.The retro-pectoral veins are located by the same cutdown approach used tofind the cephalic vein. Above the cla-vicular portion of the pectoralis majormuscle one generally finds one or more small and distensible vein that willac-cept the leads.From July 1992 to June 2002 the same operator performed 719 implanta-tions of cardiac pacemakers/defibrillators. In the vast majority (82 % ofcases) 2 or 3 leads were placed . The cephalic vein could be used in 539patients. Retro-pectoral veins were looked for in 159 cases and found and

S143Poster 2

used in 147 (95.5 %) ; there were no complications related to this route ofcannulation, but the operation time was slightly longer.In conclusion, retro-pectoral veins can be frequently used to introducepermanent cardiac stimulation/defibrillation leads. Currently, even if thevein is small, using a guidewire and a split introducer, we can alwaysaccess the cephalic or retro-pectoral veins.

453

CRT: Correlation between electrophysiological parameterat implant and clinical outcomeEzio Soldati, MD, Maria Grazia Bongiorni, MD, GiuseppeArena, MD, Gabriele Giannola, MD, Federico Baldi, MDand Mario Mariani, MD. Pisa, Italy.

Cardiac Resynchronization Therapy (CRT) is critically dependent on boththe anatomy of the coronary sinus (CS) which can be only known duringthe implant. The availability of Electrophysiological (EP) parameters atimplant predicting the clinical outcome would be very useful, particularlyin pts with adverse CS anatomy. Aim of this study was to evaluate all theEP parameters at the implant of CRT devices in order to find thosepredicting a favourable clinical outcome.Materials and Methods: we evaluated 34 consecutive pts (27 men, meanage 67 years) submitted to CRT. Before the implant all the pts weresubmitted to clinical evaluation (NYHA class, hospitalization during theprevious 6 months), Echo determination of EF, LVEDV and MI, 6 minuteswalking test and Minnesota QOL questionnaire. At the implant QRS width,intervals between RV and LV electrograms, RV, LV and biventricularpaced QRS width were recorded. During the follow-up the pts weresubmitted to the same tests performed before the implant. According to theevaluation the pts were divided into: group I (not responders), group II(mildly responders, improvement in some but not all tests), group III(clearly responders, improvement in all the tests).Results: CRT devices (20 PM, 14 ICD) were implanted in all pts. Accord-ing with the follow-up evaluation (mean 10.3 months, range 6-21) the ptswere divided in group I (4), group II (11) and group III (19). The EPparameters predicting the clinical outcome were found to be the ratiobetween biventricular paced and RV paced QRS width and biventricularpaced and mean RV and LV paced QRS width. Particularly biventricularpaced QRS duration in any patient of group III was �80% of RV pacedand mean paced QRS width.Conclusions: the ratio between biventricular paced and RV paced QRSwidth and biventricular paced and mean RV and LV paced QRS width canpredict the clinical outcome in patients submitted to CRT. This parametercan be easily detected during the implant and can be particularly useful toposition the LVPL in presence of adverse CS anatomy.

454

Emerging problems: Transvenous extraction of leads fromcardiac veinsGabriele Giannola, MD, Maria Grazia Bongiorni, MD, EzioSoldati, MD, Giuseppe Arena, MD, Chiara Bartoli, MD,Federica Lapira, MD, Giulio Zucchelli, MD and MarioMariani, MD. Pisa, Italy.

Although cardiac resynchronization therapy (CRT) is a very effectivetherapy of heart failure, some complications may occur. From 2 to 10% ofimplanted devices may fail or become infected. Sepsis of any intravascularpart of the pacing system is the main cause of lead extraction. The number ofpatients with a CRT device are increasing so it will increase the number ofleads that become infected or malfunctioning with need to extraction. Patients:since 1998 we managed 17 patients (15M, mean age 66.87 years) with a leadin coronary sinus (CS) or in cardiac veins and an indication for lead extraction(6�sepsis, 8�local infection, 3�malfunction). Leads characteristics: 14 leads(Medtronic�8, Pacesetter�3, Guidant�2, Biotronik�1) were placed in theCS tributaries veins for left ventricular pacing, 1 in CS main for left atriumpacing and 2 in the middle cardiac vein (inadvertently placed for right ven-tricular pacing) The mean pacing period was 31.06 months (range 3-156).

Methods: for transvenous extraction we used mechanical tools (CookVascular Inc.) with superior and inferior approach.Results: We removed all the leads: 8 (47%) leads with manual tractionwithout dilation, while for the remaining it was necessary mechanicaldilation, in 2 cases it was necessary a transfemoral approach and in 1 casea hybrid approach with open heart surgery because of large vegetations(area 900 mm2). Adherences were located in subclavian vein (1), anoni-mous vein (3), right atrium (3), coronary sinus ostium (1), coronary sinus(2). Dilation of CS adherences was performed by transfemoral approachusing 7F XL polypropylene sheaths. Manual traction was effective forleads with shorter pacing period.Conclusions: procedures for leads with a short pacing period are easier.Adherences are mainly present in the venous system. Older leads extractionis more difficult, tools for dilation into the CS from inferior approach maybe very useful and should be implemented.

455

Impact of implant duration and indication for removal onthe need for laser-assist during lead extractionSydney L. Gaynor, MD, Jennifer S. Lawton, MD, MaryeGleva, MD, Ralph J. Damiano, Jr., MD and Marc R. Moon,MD. Washington Univ School of Medicine, St. Louis, MO.

Objective: Laser-assist greatly facilitates extraction of chronically im-planted pacing and defibrillator leads, but it is available only in selectedcenters and is not necessary in all cases. The purpose of this study was todevelop an algorithm to predict which patients require laser-assist andwould benefit from transfer to a tertiary center with lead extraction capa-bilities.Methods: Between 1998 and 2003, 500 pacing (302) and defibrillator (198)leads were extracted from 283 patients in the operating room 61 � 48(mean � SD) months after implantation. Leads were explanted for sepsis(111, 22%), pocket infection (184, 37%), and non-infected indications(205, 41%). Lead position included right atrium (172, 34%) ventricle (303,61%), and superior vena cava (25, 5%).Results: Multivariate analysis identified three factors that predicted theneed for laser-assist during lead extraction: 1.) implant duration, 2.) indi-cation for removal, and 3.) lead position (p�0.001 for all). Septic leadsrarely required laser-assist, but non-infected leads required laser-assist inmost cases (Figure). For non-septic leads, laser-assist was necessary for64 � 3% (� 70% confidence limit) ventricular, 48 � 5% atrial, and 12 �7% caval leads (p�0.005).Conclusions: Septic leads can most often be removed without laser-assist.However, patients with non-infected leads in place greater than 12 months,and patients with a pocket infection 24 to 36 months after lead implanta-tion, would likely benefit from transfer to a tertiary center with laserextraction capabilities, especially for removal of ventricular leads.

456

Far-field R-wave sensing at non-traditional atrial pacingsites*Michael D. Gammage, MD, *Cesar Khazen, MD, *AntonisS. Manolis, MD, *Inge Sieben, *Bart Gerritse, PhD and*Luigi Padeletti, MD. Univ Hosp, Birmingham, UnitedKingdom, AKH Wien, Vienna, Austria, Univ Hosp Patras,Patras, Greece, Medtronic, Maastricht, Netherlands, Bakken

S144 Heart Rhythm, Vol 1, No 1, May Supplement 2004

Research Ctr, Maastricht, Netherlands and Careggi UnivHosp, Florence, Italy.

The use of atrial pacing sites other than the right atrial appendage may offerimproved arrhythmia control, shorter atrial depolarisation times and morephysiological atrio-ventricular timing. These potential benefits may, how-ever, be diminished by unfavourable Far-Field (FF) R-wave sensing. Aspart of a prospective study of a new, catheter-delivered, 4.1 French,bipolar, active fixation lead (SelectSecure, Medtronic), we analysed the FFsensing performance of 115 leads randomly assigned to either Inter-AtrialSeptum ( [IAS], n�55) or low atrial septum (Coronary Sinus Os [CSO],n�60) positions. Data were recorded at pre-discharge, 2 weeks, 1 and 3months post implant. Data are mean � standard deviation, analysed by arepeated analysis of variance model.

When the FF R-wave amplitudes are compared over time the FF R-waveis significantly higher for CSO (p � 0.007)

There were no significant changes in FF R-wave amplitude ratio over time(p�0.20) FF R-wave sensing values are statistically greater at the CSOthan IAS, but the similar ratio of P to R-wave at both sites suggest that thisdifference is unlikely to be clinically significant; the ratio is large enoughto allow effective device programming to ensure correct sensing perfor-mance. These data suggest that this new catheter/lead system can be usedto safely position leads in atrial septal sites that may enable more beneficialatrial pacing effects.

457

No benefit from single capacitance auxiliary coronaryvenous defibrillation*John R. Paisey, MRCP, *Arthur M. Yue, MRCP, *FrederickBessoule, BSc, *Paul R. Roberts, MD and *John M. Morgan,MD. Southampton Univ Hosps, Southampton, UnitedKingdom and Ela Medical SA, Paris, France.

Background: Defibrillation of left ventricle via the coronary venous (CV)system has been demonstrated to be efficacious and safe in man. Theincreasing use of cardiac resynchronisation therapy (CRT) in implantablecardioverter defibrillators (ICDs) creates a cohort in whom CV defibrilla-tion may become an acceptable technique. The only CV configurations inhumans to show a reduction in defibrillation threshold (DFT) measured byenergy have required separate CV and right ventricular (RV) capacitors.We examined the feasibility of single capacitance auxiliary CV defibrilla-tion using an electrode designed for investigational CV defibrillation.Methods: 4 patients, all male, aged 64�/�10 years meeting standardindications for ICD were implanted with a left sub pectoral ICD (Ela Alto2) and dual coil RV/superior vena cava (SVC) defibrillation lead(Medtronic 6947). Coronary sinus was cannulated using standard CRTintroducing catheters and a custom designed over the wire CV defibrilla-tion electrode (Ela Medical) advance into lateral cardiac vein (LCV).Defibrillation threshold (DFT) was assessed by a binary search for theconfigurations RV to SVC � can and RV � LCV to SVC � can.Inductions (30 Hz AC) and therapies were delivered from the implanteddevices.

Results: The mean DFT were RV, 10�/�3 and RV�LCV, 16�/�10Joules. Two patients had lower DFT with RV and 2 lower with RV�LCVanodes.Conclusion: There is no benefit from single capacitance auxiliary LCVdefibrillation using this technology in man. Limiting proportion of currentdirected though LCV by measures such as connecting resistors in series orparallel capacitors (as previously demonstrated) may be required to opti-mise biventricular defibrillation circuits.

458

Chronic lead performance of two aging bipolar ventricularpacing leadsW. Ben Johnson, MD, Loline Voegtlin, RN, BSN, CindyStanton, RN, BSN, *Rick D. McVenes, BS, *Alan R. Braly,BS, *Nancy Germanson, MS and *Kenneth E. Cobian, BS.Iowa Heart Ctr, P.C., Des Moines, IA and Medtronic, Inc,Minneapolis, MN.

We report the first year results of a single center prospective studycomparing the long term (LT) performance of 2 bipolar (BP) pacingleads (LDs) of similar construction, with the exception of their insula-tion, Models 4024 (inner/outer [I/O] insulations of 55D polyurethane)and 5024 (I/O MDX silicone). This retrospective study was initatedafter noting gradual drops in bipolar impedance beginning at approxi-mately 7 years post-implantation (PI) for the Model 4024 LD. Althoughthe Medtronic chronic lead study reports survival probabilities of99.8 � 0.3% and 99.2 � 0.5%, respectively, for the 4024 and 5024 LDsafter 10 years, there is concern that subclinical performance changesmay be evolving in aging 4024 LDs.Methods: To date, 120 and 89 patients were enrolled with 4024 and 5024LDs, respectively, with greater than 6 years PI. BP and unipolar (UP)impedance (Z), sensing and stimulation thresholds (ST) were taken in-office at 4 and 2 month intervals for non-pacemaker dependent and pace-maker dependent pts, respectively, and compared with “baseline values” at6-8 weeks and chronic values taken at approximately 6 years PI. Analysisof LD performance was conducted using Z criteria of �200�, �300�,�30% decrease from baseline, UP-BP Z �50� and sensing and STcriteria.Results: Two 4024 LDs that fell below 200� demonstrated rising STs. No4024 LDs with BP Z below 300�, but �200�, exhibited ST rises �0.15ms at 2.5V. There were statistically significant differences between the4024 and 5024 LDs for lead age at last FU (p�0.003), BP Z at 6 years(p�0.007) and at last FU (p�0.000002), and 2.5V ST at 6 years(p�0.0003). There were no other significant differences between the pop-ulations.Conclusions: (1) These results confirm the 4024 BP Z decrease observedin the previous retrospective study. (2) Leads with �200 ohms Z and risingST may require clinical action. (3) Prospect LT comparisons of these LDscontinue.

S145Poster 2

459

Low incidence of venous thrombosis after ICD orbiventricular implants in the modern eraJean Champagne, MD, FRCP, Francois Philippon, MD,Gilles O’hara, MD, Franck Molin, MD, Line Dufort, RN,Louis Blier, MD and Marcel Gilbert, MD. Quebec Heart Inst,Quebec City, Quebec, Canada.

The incidence of venous thrombosis (VeT) after transvenous pacing or ICDlead implantation has been demonstrated historically in up to 20-30% ofcases long term, and tends to occur early after lead insertion. VeT rate withcurrent ICD or biventricular (Biv) technology (various lead size, multipleleads) is not well established.Methods: A total of 120 pts (84% male, mean age of 64 � 11 y) whounderwent ICD or Biv implantation were prospectively studied with ve-nous duplex ultrasonography performed 1 to 6 months (median: 42 days)after implantation.Results: Dual chamber ICD was implanted in 58% (70 pts), single cham-ber ICD in 23% (28 pts) and Biv device in 18% (22 pts). The mean EF was33 � 12% (median: 31). Warfarin was reintroduced after implantation in40 pts (33%) according to previous medical indications. Ultrasonographywas performed 46 � 28 days (CI: 41-52, median:42) after implantation.VeT (complete occlusion) occurred in only 3 pts (2.5%), all with dualchamber ICD and without warfarin and all were asymptomatic. The VeTincidence in the population without warfarin was 3.8%. Numbers of leads,Biv or EF were not independent VeT predictors.Conclusions: Biv device, larger size or multiple leads were not associated inour series with an increase in the short term VeT rate. Long term assessmentof the VeT incidence in that population need to be reassessed. Warfarin use forother clinical indications added a protective effect on the VeT rate.

460

Impact of coronary revascularization on long-termcardiovascular outcomes of VF out-of-hospital cardiacarrest survivors resuscitated by early defibrillationThomas J. Bunch, MD, Roger D. White, MD, Douglas L.Packer, MD, David O. Hodge, MS and Bernard J. Gersh,MD. Mayo Clinic, Rochester, MN.

Background: Previous studies reported that the major benefit of revascu-larization in patients with underlying severe CAD was in primary preven-tion of sudden death. However the impact of revascularization in OHCAsurvivors for secondary prevention of sudden death is unclear.Methods: Patients with an OHCA between 1990-2000 who received earlydefibrillation for VF in Olmsted County Minnesota (MN) were included.Those OHCA survivors with an acute MI or CAD without a MI werefurther studied. Survival and the cumulative probability of appropriate ICDdeployment were estimated using the Kaplan-Meier method.Results: Two hundred patients presented in VF OHCA; of these 138 (69%)survived to hospital admission (7 died in the emergency department prior toadmission) and 79 (40%) were discharged. The average length of follow-up was4.8 � 3.0 years. Thirty-seven (47%) of the OHCA hospital-discharge survivorspresented with an acute MI. Nineteen acute MI patients underwent revasculariza-tion (4 CABG, 15 PTCA), and 7 received an ICD and 9 Amiodarone. Theobserved survival was 17 out of 19 (89%) in those undergoing revascularizationversus 9 out of 18 (50%) in the nonrevascularized group (p�0.01). There was nodifference in ICD shocks between groups (p�0.19). Twenty-five (32%) hospitaldischarge survivors presented with CAD without an acute MI. Fifteen underwentrevascularization (10 CABG, 5 PTCA), and 12 received an ICD and 3 Amioda-rone. There was no significant difference in survival between the groups [13 out of15 (87%) revascularization, 6 out of 10 (60%) no revascularization, p�0.17] norICD shocks (p�0.09).Conclusion: Revascularization after acute MI in VF OHCA survivorsimproves long-term survival in addition to initial device or drug antiar-rhythmic management. This benefit is less prominent in patients presentingwith underlying CAD without a MI in this study.

461

Arrhythmia recurrences and hospitalizations after hybridtherapy for rhythm control in drug-refractory persistentand permanent atrial fibrillationHygriv B. Rao, MD, *Sanjeev Saksena, MD and Sina Zaim,MD. RWJ Medical School and Passaic General Hosp,Warren, NJ and UMDNJ Medical School and PassaicGeneral Hosp, Warren, NJ.

Background: Rhythm control(RC) strategies using antiarrhythmic drugs(AAD) have not improved clinical outcomes in patients with atrial fibril-lation (AF) & repeated hospitalizations and cardioversion(CV) are com-mon in this population.Objectives: We hypothesised that effective RC could be achieved “hy-brid” therapies (Rx) and could reduce AF recurrences, need for CV& AFhospitalizations.Methods: 47 pts with persistent or permanent AF, mean age 66�8 yrs,with cardiac disease in 38 pts, refractory to mean of 2.3 AAD underwentRA ablation and implantation of a DDDR pacemaker (PM, n�27) orcombination atrial & ventricular defibrillator (AV ICD, n�20). 35 pts weretreated with overdrive dual site RA pacing ( PM�20, AV ICD � 15) and12 pts with overdrive high RA pacing ( PM � 7, AV ICD �5). They werefollowed for 1-71 (mean 24�15) mos. 44 pts underwent RA maze proce-dures, 2 pts had isthmus ablation, &1 pt had focal AF ablation. Previouslyineffective AAD were continued. Endpoints were freedom from permanentAF (RC), hospitalizations for AF recurrences (AF hosp) and CV(CV hosp)& need for CV after Rx.Results: All pts had persistent or permanent AF before Rx with a range of1-25 CV attempts (mean 3.1/pt) before abandoning CV therapy. After Rx,RC was achieved in 41 pts (87%). 33 pts (70%) became asymptomatic,infrequent persistent AF recurred in 2 pts, & paroxysmal AF in 6 pts. 23 pts(46%) had symptomatic AF recurrences (range 1-4, mean 1.7 events/pt).AF Hosp (Figure) declined from an average of 2.55/pt to 0.81/pt after Rx(p�.05 ). CV Hosp (Figure) declined from an average of 1.12/pt to 0.38/pt( p�.05 ). After Rx, the need for CV declined from an average of 3.1/pt to0.55/pt (p �0.01).Conclusions: “Hybrid” therapy achieves effective RC & reduces AFrelated hospitalizations. This may potentially be a clinically and cost-effective strategy.

462

The National Registry to Advance Heart Health: Primaryand secondary prevention of sudden cardiac death*Charles A. Athill, MD and *Dennis Haack, PhD. San DiegoCardiac Ctr, San Diego, CA and REGISTRAT, Lexington, KY.

Objective: ADVANCENT, The National Registry to Advance HeartHealth, is a long-term, observational, longitudinal registry that will studythe management of 100,000 patients with left ventricular dysfunction andejection fraction (EF) � 40%. By September 30, 2003, 49 centers hadenrolled 4176 patients in ADVANCENT. In the present analysis, wesought to assess utilization of implantable cardioverter defibrillator (ICD)in primary and secondary prevention of sudden cardiac death.Results: Of the 4176 patients in the ADVANCENT registry, 598 (14.3%)reported a VT/VF episode. Of the 598 VT/VF patients, 471 (78.8%) had an

S146 Heart Rhythm, Vol 1, No 1, May Supplement 2004

ICD device implanted subsequent to the VT/VF episode. Ischemic patientswere more likely to have an ICD device implanted (79.8% and 72.5% forischemic and non-ischemic patients, respectively, p�.08). Among femalespatients, 75 of 104 (72.1%) had an ICD device implanted subsequent to theVT/VF episode while 396 of 494 men (80.2%) had an ICD device im-planted (p�.13). Among the 502 white patients reporting a VT/VF episode,397 (79.1%) had an ICD device implanted while 88 of 110 (80.0%)patients of other races had an ICD implanted (p�.97). Of the 4176 patients,998 (23.9%) had history of prior myocardial infarct (MI) and EF � 30%.Of these 998 patients, 87.2 % of patients who had a VT/VF episodereceived an ICD. However, of MI patients with EF � 30% who did nothave a prior VT/VF (MADIT II criteria), only 42.8% received an ICD.Conclusion: Men are more likely than women to have an ICD deviceimplanted subsequent to a VT/VF episode. Patients with ischemic cardio-myopathy were more likely to receive an ICD compared to non-ischemicsubsequent to VT/VF episode. Despite the proven benefit of ICDs inpatients with prior VT/VF episode and MI patients with EF � 30%, thislife-saving therapy remains underutilized.

463

The impact of AV optimized RV pacing in patients withimplanted cardioverter-defibrillators and reduced leftventricular functionPeter Lercher, MD, Manfred Wonisch, MD, AstridFahrleitner, MD, Daniel Scherr, MD, Brigitte Rotman, MDand Werner Klein, MD. Graz, Austria and Internal Medicine,Graz, Austria.

Background: The implantable cardioverter-defibrillator (ICD) improvessurvival in patients with life-threatening ventricular arrhythmias. Recentclinical trials have shown that patients with impaired left ventricularejection fraction (LVEF) and dual chamber ICD devices have higherhospitalization rates due to new or worsened heart failure (HF). This studywas designed to evaluate the influence of right ventricular (RV) pacing onhospitalization rate, quality of life (QoL), arrhythmic events, neurohumoralparameters for HF and cardio-respiratory exercise parameters in patientswith reduced LVEF and a dual chamber ICD.Methods: This study was a monocentric, randomized, single-blindedcross-over trial comparing a three-month period of either AV optimizedRV pacing or DDI programming, which guarantees permanent intrinsic AVconduction. Patients with reduced LVEF (� 40%), stable medication, noindication for antibradycardia pacemaker therapy, permanent sinus rhythmand implanted dual chamber ICD were included. At baseline, after 3 and 6months QoL was assessed by questionnaires, echocardiography, cardiopul-monary exercise tests were performed, patients underwent ICD interroga-tion and blood samples were taken after 30 minutes of supine rest.Results: A total of 25 patients (age 62 � 10 years) were included. One patientdied during follow-up due to cardiogenic shock and one withdrew from thestudy. During optimized RV pacing NT-pro-BNP levels were significantlyhigher (837 � 540 vs. 692 � 578 fmol/ml; p � 0.03), maximal oxygen uptakesignificantly reduced (20.9 � 5.2 ml/kg/min vs. 22.5 � 6.4 ml/kg/min vs.; p �0.03). QoL, arrhythmic events and big endothelin levels did not differ signif-icantly. Hospitalization rate for heart failure was significantly higher during theRV pacing period (6 pts vs. 2 pts)Conclusion: Our data indicate that AV optimized RV pacing worsens heartfailure and exercise capacity in patients with reduced LVEF and an im-planted dual chamber ICD. These results imply that even AV optimizedpacing should be avoided in this selected group of patients without indi-cation for antibradycardia pacing.

464

Predictive value of inflammatory status for the occurrenceof malignant ventricular tachycardia: A prospective studyin a large patient population with an implantablecardioverter defibrillatorFlorian Streitner, MD, Juergen Kuschyk, MD, Susanne Spehl,MD, Christian Veltmann, MD, Constanze Echternach, MD,

Frank Fischer, MD, Martina Brueckmann, MD, MartinBorggrefe, MD, PhD and Christian Wolpert, MD. Univ ofMannheim, Mannheim, Germany.

Background: As recently demonstrated cytokine expression predicts aworse outcome in patients with advanced heart failure and is elevated incoronary artery disease (CAD). However, little is known about whethercytokine expression is predictive of ventricular tachyarrhythmia (VT/VF)or sudden cardiac death. The aim of this prospective study was to assess therelationship between cytokine levels and the risk of experiencing a VT/VFin patients with an implantable cardioverter defibrillator (ICD).Patients and Methods: C-reactive protein (CRP) and Interleukin-6 (IL-6)serum levels were prospectively determined in 51 patients (mean age65�10 years, mean left ventricular ejection fraction 44%�17%) in theabsence of an acute infection. In all patients CRP and IL-6 was redeter-mined after 9 months. 47 out of 51 patients (92.2%) suffered from CAD oridiopathic dilated cardiomyopathy. VT/VF-events were analysed by storedelectrograms of the ICD-device. Cytokine serum levels were correlatedwith the probability of a VT/VF prospectively from the first cytokine leveldetermination.Results: The mean serum level of IL-6 at baseline vs. 9 month follow-upwas 6.03�4.94 vs. 4.46�5.77 pg/ml (CRP was 5.09�7.73 vs. 5.63�6.45mg/l). A total of 88 VT/VF-episodes occured 13 out of 51 patients. Patientswith future VT/VF had significantly higher IL-6 levels than patients with-out VT/VF-episodes (8.96�4.98 vs. 5.02�4.17 pg/ml at baseline(p�0.01), 7.8�4.88 vs. 3.31�7.0 pg/ml at follow-up (p�0,04)). CRP didnot differ significantly (p�0.05). There was no statistical difference in IL-6and CRP serum levels found for the comparison of functional status(NYHA-class), underlying heart disease or left ventricular ejection fractionabove or below 40%.Conclusions: 1. Elevated IL-6 levels predict the risk of a future VT/VF incontrast to CRP. 2. Inflammation seems to be one mechanism contributingto the triggering of ventricular tachyarrhythmias in ICD-patients. 3. In-creased expression of IL-6 is found in patients with malignant VT or VFirrespective of the underlying heart disease.

465

Ventricular arrhythmias developed by ischemic and non-ischemic heart failure patients implanted withbiventricular cardioverter-defibrillators for primary orsecondary prevention: The InSync ICD Italian RegistryMaurizio Lunati, MD, Maurizio Gasparini, MD, MarioBocchiardo, MD, Giuseppe Boriani, MD, Antonio Curnis,MD, Antonio Vincenti, MD, Maurizio Landolina, MD,Gabriele Zanotto, MD, *Luca Allaria, MS and *AlessandraDenaro, MS. Ospedale Niguarda Ca’ Granda, Milan, Italy,Istituto Clinico Humanitas, Rozzano, Italy, Civile Hosp, Asti,Italy, S. Orsola Hosp, Bologna, Italy, Spedali Civili, Brescia,Italy, Ospedale S. Gerardo dei Tintori, Monza, Italy, IRCCSPoliclinico S. Matteo, Pavia, Italy, Ospedale Civile, Verona,Italy, Medtronic Italy, Milan, Italy and Medtronic ItaliaS.p.A., Rome, Italy.

Aim: To evaluate the incidence and the characteristics of ventriculararrhythmic events developed by ischemic (ISC) and non-ischemic (N-ISC)heart failure (HF) patients (pts) receiving cardiac resynchronization ther-apy (CRT), combined with ICD for primary (PP) or secondary prevention(SP) of sudden death.Methods: 179 pts (161 male, 65�9 years, NYHA class 2.9�0.6, ejectionfraction 26�7%, QRS width 169�31 ms) received CRT with ICD back-up, and were so distributed: 108 ISC (whose 46 PP pts), 71 N-ISC (whose31 PP pts). They were followed for a mean period of 15�8 months. Alldevice-recorded events were collected and subsequently manually ana-lyzed.Results: Symptomatic improvement was evident at follow up. 15 ISC pts(5 PP, 10 SP) and 17 N-ISC pts (4 PP, 13 SP) developed a total of 159arrhythmic events: 130 Ventricular Tachycardias (VT) and 29 VentricularFibrillations. We observed: 1) More episodes in N-ISC group (87 vs 72

S147Poster 2

events; p�0.05); 2) Higher percentage of self-terminated episodes in N-ISC group (33.3% vs 5.6%; p�0.0001); 3) Higher efficacy of first anti-tachy pacing (ATP) therapy in N-ISC group (91.4% vs 63.5%; p�0.0001);4) Lower number of delivered therapies per patient in N-ISC group(1.1�0.4 vs 1.3�0.6; p�0.005); 5) Higher incidence of events in SP group(71.9% vs 28.1%; p�0.0006); 6) Higher percentage of self-terminatedepisodes in PP group (22.5% vs 11.7%; p�0.06) Shorter VT cycle lengthin PP pts (326�25 ms vs 378�61 ms; p�0.0001).Conclusions: Our data indicate that N-ISC pts tend to have more arrhyth-mic episodes in comparison with ISC pts, but a substantial proportion ofVT terminates spontaneously or is more easily terminated by ATP. More-over, pts implanted for SP present a larger number of episodes requiringICD intervention. Further studies could elucidate the necessity of specificdevices or tailored parameters programming to optimize the treatment indifferent categories of pts candidate to CRT with ICD.

466

Is there an increased acute embolic risk after internaldefibrillation of induced ventricular fibrillation (VF) inthe setting of ICD testing?Torsten Becker, MD, Margit Vater, MD, Klaus Donges, MD,Thomas Kleemann, MD, Monika Rameken, MD, JochenSenges, MD and Karlheinz Seidl, MD. Heart CenterLudwigshafen, Ludwigshafen, Germany.

Background: External electrical cardioversion of atrial fibrillation undereffective anticoagulation is associated with an increased embolic risk of0,6-1 %, which in part is attributable to the creation of a thrombogenicmilieu due to “atrial stunning”. Whether a similar situation occurs in thesetting of internal defibrillation of a ventricular tachycardia or VF in ICDpatients has not been investigated.Methods: We analyzed the data of 842 Pts. with an ICD since 1996regarding the incidence of embolic complications after internal defibrilla-tion of induced VF in the setting of ICD testing.Results: In 5 of 842 Pts. (0,6 %) ischemic stroke occured. All Pts. hadstructural heart disease. The mean time interval from ICD testing to strokewas 20 � 8 (0-45) hours, 5 � 5 shocks (1-13) have been delivered.Regarding embolic risk factors all Pts. had an EF � 40 %, 4/5 Pts. hadatrial fibrillation at the time of testing. 1/5 Pts. had former stroke , 2/5 Pts.had diabetes and 4/5 Pts. had arterial hypertension. 2/5 Pts. were undereffective anticoagulation at the time of testing, 2/5 had ASA therapy. NoPt. died as a result of stroke.Conclusions: Pts. with atrial fibrillation at the time of internal defibrilla-tion in the setting of ICD testing had an increased incidence of stroke.Wether transesophageal echocardiography before ICD testing in Pts. withatrial fibrillation could prevent periprocedural embolic events is unknown.Further studies are needed.

467

Ventricular antitachycardia pacing by implantablecardioverter defibrillators reduces shocks forinappropriately detected supraventricular tachycardia*Mark S. Wathen, MD, *Kent J. Volosin, MD, *Michael O.Sweeney, MD, *Koroush Khalighi, MD, *Robert C. Canby,MD, *Christian Machado, MD, *Wayne O. Adkisson, MD,*Donald S. Rubenstein, MD, *Mary F. Otterness, MS, *AliceJ. Stark, RN, PhD, *Jeffrey M. Gillberg, MS and *Paul J.Degroot, MS. Vanderbilt Univ Medical Ctr, Nashville, TN,Univ of Pennsylvania, Philadelphia, PA, Brigham andWomen’s Hosp, Boston, MA, Easton Hosp, Easton, PA, TexasCardiac Arrhythmia Foundation, Austin, TX, ProvidenceHosp and Medical Ctrs, Southfield, MI, PortsmouthCardiology, Portsmouth, VA, Arrhythmia Consultants,Greenville, SC and Medtronic, Inc, Minneapolis, MN.

Shocks for inappropriate detection of SVT remains a major problem in ICDpatients (pts). In this analysis, we explore the outcome for ventricular ATP

applied to SVT inappropriately detected in the VT or fast VT (FVT) zones.Methods: In the PainFREE Rx II trial, ICDs were programmed with 3zones (VF �240ms; FVT � 240-320ms; VT �320ms) but with either ATPor shock for FVT. FVT detection required 18/24 intervals. If 1 or more ofthe last 8 intervals was �240 ms, the episode was detected as VF and didnot receive ATP. A physician panel reviewed detected episodes with storedEGM to classify them as VT/FVT/VF or SVT: atrial fibrillation/flutter(AF/AFL), sinus or atrial tachycardia (ST/AT), or other SVT. All percent-ages and p-values are adjusted for multiple episodes/pt by GEE methods.Results: In the ATP arm (n�315 pts), out of 859 episodes of device-detected VT or FVT, 236 (27%) were actually inappropriately detectedSVTs. All were treated by ATP. Of these, 168 (61%) were deemed ATPsuccesses by the device and thus did not get shocked. Success was higherin the VT zone (152/188, 70%) than the FVT zone (16/48, 46%) [p�0.03].Among SVT categories, ATP success was highest for the “other SVTs”(67/68, 98%)–which were mostly 1:1 rhythms-followed by ST/AT (74/105,58%) and AF/AFL (27/63, 46%). Of the 168 successes, 83 (43%) were trueterminations of SVT, as opposed to simply being ventricular rate slowingthat satisfied the ICD termination algorithm. SVT recurrence is difficult tomeasure. We found that device “successes” were no more likely to resultin inappropriate redetection within 5 minutes than true terminations [32/85(17%) vs. 15/83 (13%), p�0.93]. Importantly, none of these within-5-minute redetections received shocks.Conclusions: Ventricular ATP greatly reduces shocks for inappropriatelydetected SVT. Shocks are prevented by either terminating the SVT or bydelaying the shock until the SVT self-terminates or slows. Ventricular ATPis particularly effective in terminating 1:1 SVTs, which are among the mostdifficult for ICD detection algorithms to discriminate from true VT.

468

Efficacy of anti-tachycardia pacing in bi-ventricular andright-ventricular pacingJohannes Heintze, MD, *Juergen Vogt, MD, *Bart Gerritse,PhD, *Sandra Jacobs, PhD and *Berthold Stegemann, PhD.Herz-und Diabetes Zentrum Nordrhein Westfalen, BadOeynhausen, Germany and Bakken Research Ctr, Maastricht,Netherlands.

Aim: Cardiac resynchronization therapy (CRT) in combination with animplantable cardioverter defibrillator (ICD) is now widely utilized in pa-tients with left ventricular dyssynchrony and indication for an ICD. Com-bination devices such as the InSync ICD (Medtronic Model 7272) offerindependent programmability of CRT and anti-tachycardia pacing (ATP).As the majority of ventricular tachycardia (VT) originate from the leftventricle and ATP efficacy should be higher for stimuli close to the re-entrycircuit, we hypothesize bi-ventricular (BV) ATP to be more effective thanright-ventricular (RV) ATP and obtain efficacy estimates.Methods: The InSync ICD study enrolled 89 heart failure (HF) pts inNYHA II-IV, LVEF�35% and QRS width �130 msec. We retrospectivelyanalyzed VT episodes collected by the device that fulfilled the followingadditional criteria: 1. true VT with spontaneous onset, 2. delivery of at leastone ATP therapy and 3. known efficacy of ATP. First-therapy ATP effi-cacy was analyzed using a logistic GEE model, controlling for the effect ofVT cycle length, cardiac medication (amiodarone, beta-blocker, digitalis,ACE-I, vasodilators and statins) and heart failure ethiology.Results: Twenty-six (26) pts experienced a total of 610 VT episodes; 569VT in episodes in 23 pts fulfilled all additional criteria above. First ATPtherapy was successful in 494 episodes (86.6%). Of these 23 pts, ATP wasprogrammed to BV in 10 pts and to RV in 16 pts, where 3 pts had bothmodes programmed at different times. Logistic regression GEE modelefficacy estimates of first-therapy efficacy were 88.7% (CI: 80.7-93.6%)for BV ATP and 68.3% (CI: 49.7-82.4%) for RV ATP (p�0.0006). OnlyVT cycle length, presence of ACE-I and statins significantly added to themodel. Controlling for this covariates first-therapy efficacy estimates were91.7%(83.5-96.0%) for BV ATP and 77.5%(55.2-90.6%) for RV ATP(p�0.01).

S148 Heart Rhythm, Vol 1, No 1, May Supplement 2004

Conclusions: ATP is effective in patients with HF. BV ATP has a signif-icantly higher ATP efficacy. Superiority is maintained after correction forVT cycle length and cardiac medication. The clinical benefit of BV ATP inpatients with heart failure needs to be prospectively evaluated.

469

Do pre-hospital discharge pacemaker checks provide anyadditional clinical benefit?*Kevin Wheelan, MD, *Darlene Legge, RN, BSN, *BrentSakowski, MS, *Sue Bruce, RN, *David Roberts, MS, *L.Murphy Johnston, BA, *Thomas P. Beveridge, MD, *PeterWells, MD, Ravi Vallabahn, MD, Michael Donsky, MD and*Jay O. Franklin, MD. Baylor Univ Medical Ctr, Dallas, TX.

Background: A retrospective analysis of 250 consecutive, newly im-planted, pacemaker (IPG) datasets from a single center was performed todetermine the clinical benefit of the pre-hospital discharge (PHD) evalua-tion.Methods: We evaluated 56 single and 194 dual chamber IPGs that wereprogrammed to adequate safety margins at implant. Data was analyzed toevaluate the number of IPGs requiring reprogramming or lead revisionprior to- or during the PHD evaluation. Local IRB approval was obtained.Results: No significant findings were detected at the PHD check in 246 of250 patients, 98.4% (one-sided 95% CI, 96.4%). One of the 246 patientshad an atrial lead dislodgment that was discovered via telemetry and chestx-ray, and repositioned prior to the PHD check. Four of the 250 patientsrequired reprogramming at PHD. In these four patients, the IPG wasappropriately sensing intrinsic events but sensitivity was adjusted, (3 atrialand 1 ventricular), to increase the sensing safety margin. None of these fourpatients required surgical intervention in the six months following implant.The lead dislodgement and IPG reprogrammings involved active fixationleads. There were 193/194 atrial active fixation leads and 168/250 ventric-ular active fixation leads in the study group.Conclusion: Pacemaker checks prior to hospital discharge may not provideincremental clinical benefit. Although this data was evaluated from apopulation of high volume implanting physicians, we believe the resultsmay be applied to all patients. Given the current environment of costcontainment and resource constraints, careful evaluation of post implanttelemetry and patient symptoms may ensure patient safety, and allow thedelay of the pacemaker evaluation until the first follow-up clinic visit.

470

Has CTOPP impacted pacing mode selection*G. Frank O. Tyers, MD, M Gao, MD, PhD, R. I. Hayden,MD, FRCS, R Leather, MD, FRCP and M Kiely, PhD.British Columbia Cardiac Registry, Vancouver, BritishColumbia, Canada.

Objective: CTOPP completed enrolment in Feb 96 and by 2000 haddemonstrated an 18% decrease in atrial fibrillation (p�0.046) but the 9.4%drop in CV death and stroke lacked statistical significance. We examinedCTOPP’s effect on mode selection.Method: The BCCR, a prospectively entered population-based (4 million)regional database (22,446 pacers, 29,898 leads) was examined for implantand mode selection trends for calendar years 1997 to 2002.Results: New pacemaker implant rates per million population (pMP)were: 1997-473; 1998-456; 1999-505; 2000-513; 2001-486; 2002-510.During the same period pacer replacements increased from 130 to 157pMP, giving a 2002 utilization rate of 667 pMP. Over the 6yr period, theuse of AAI�R and VDD�R pacers was low, declining from 42 and 69/yrto 33 and 25/yr respectively. The decline in DDD use from 321 to 306/yrwas more than offset by the increase in DDDR use from 317 to 750/yr. VVIuse declined from 741 to 410/yr, which was only partially offset by the VVIRincrease from 384 in 1997 to 580 in 1999, with no further increase through2002 (583/yr). Use of physiologic pacing increased by 32.3% (12.9/40) from40% (749/1874) in 97 to 52.9% (1114/2107) of implants in 02.

Discussion: Our pacer implant rate pMP was higher than expected fromretrospective world survey reports and within the range of France, Belgiumand Germany. As in Europe, we also noted a wide range in physiologicimplant rates between institutions, initially varying from 3.5% (lowestcommunity hospital) to 69% (children’s hospital). CTOPP was widely andincorrectly quoted as showing no benefit from physiologic pacing and thismay have somewhat affected use in B.C. as our utilization rates have beena little lower than two other western provinces and the U.S. However, ouruse of, and rate of use of, physiologic pacing are progressively increasingin keeping with current standards and patient needs. CTOPP has notdecreased use of physiologic pacing in Canada.

471

Treatment crossovers did not affect randomized treatmentcomparisons in the Mode Selection Trial (MOST)Anne S. Hellkamp, MS, *Kerry L. Lee, PhD, *Michael O.Sweeney, MD, Mark S. Link, MD and *Gervasio A. Lamas,MD. Duke Clinical Research Inst, Durham, NC, Brigham andWomen’s Hosp, Boston, MA, Tufts-New England Medical Ctr,Boston, MA and Mt. Sinai Medical Ctr, Miami, FL.

Background: MOST, a 2010-pt, 6-year trial comparing DDDR to VVIRpacing in sinus node dysfunction, demonstrated no difference in death orstroke between pacing modes, and modest reductions in heart failurehospitalization (HFH) and atrial fibrillation (AF) with DDDR pacing.However, a moderate proportion of VVIR-randomized pts were tempo-rarily or permanently crossed over to DDDR pacing. The effect of thesetreatment crossovers on study results has not been described.Methods: Cox proportional hazards models were used to examine associ-ation of pacing mode with event risk. “As-randomized” analyses comparedtreatment arms according to randomized pacing mode. “As-treated” anal-yses used time-dependent covariates to account for all mode changesduring follow-up. All analyses included covariates pre-specified in thestudy design: age, gender, prior stroke, prior CHF, prior MI, CharlsonIndex, prior SVT, and prior VT/VF.Results: Of 996 VVIR-randomized pts, 375 (38%) were DDDR-paced forat least part of follow-up. Time spent in DDDR mode among these ptsaccounted for 27% of follow-up days among all VVIR-randomized pts. Of1014 DDDR-randomized pts, only 53 (5%) were VVIR-paced at somepoint, accounting for 1.5% of follow-up days among all DDDR-random-ized pts. Although as-treated analyses showed slightly lower hazard ratios(HR) and p-values favoring DDDR vs. VVIR pacing compared to as-randomized models, the interpretation of treatment effects was unchanged(table).

Conclusions: Though treatment crossovers accounted for � 25% fol-low-up time in the VVIR-randomized group, this did not affect studyresults. Endpoint comparisons between randomized modes are accuratereflections of DDDR and VVIR pacing in this study population.

472

Nocturnal overdrive pacing does not reduce sleep apnea inpacemaker patients*Heinz Theres, MD, *Christoph Melzer, MD, *Firat Duru,MD, Kristina Lemola, MD, *Ingo Fietze, MD, *KonradBloch, MD, *Ulla Strobel, *Mark Erickson, BSc, *Yong Cho,PhD and *Toby Markowitz, BSc. I. Medizinische KlinikCharite, Berlin, Germany, Univ of Zurich, Zurich,

S149Poster 2

Switzerland, Medtronic AG, Zurich, Switzerland andMedtronic, Inc, Minneapolis, MN.

Background: Sleep apnea (SA) is a common disorder in 4% of middle-aged women, 9% of middle-aged men and approximately half of heartfailure patients. SA is also associated with an increased cardiovascularmorbidity. In a recent study by Garrigue, et al., 15 subjects, with SA, dualchamber (DC) pacemakers (PM), and without heart failure, had fewercentral and obstructive apneas, total duration of apnea, number of hypop-neas and a 60% reduction in the apnea hypopnea index (AHI) with DDDoverdrive pacing compared to spontaneous heart rate (HR).Methods: We hypothesized that DC or atrial nocturnal overdrive pacing(NOP) may reduce AHI compared to spontaneous rhythm with backuppacing in subjects with SA. This single blind, crossover study usedDDD(R) or AAI(R) modes. The control arm lower rate (LR) was set to 45bpm at night; NOP arm LR was 75 bpm at night. Daytime LR�60 bpm.Day/night LR switched automatically using the PM sleep function. Sub-jects remained in each arm for 1 week. A sleep study was conducted at theend of each week. Subjects without permanent atrial arrhythmia, not usingCPAP, and with atrial or DC PM with the sleep function were recruited.Subjects had prior diagnosis of SA with AHI�15 or high probability of SAbased on questionnaires.Results: Sixteen subjects, 13 male, had a mean age of 70�8 yrs and BMIof 30.7�5.9 kg/m2. Indications for PM were sinus arrest in 6, AV block in8, sinus arrest and AV block in 1, and bradycardic response to atrialfibrillation in 1.

Although some subjects had improved AHI with NOP, there was no overalldifference in AHI, total sleep time, or SaO2min. Mean HR was signifi-cantly higher during NOP by 16 bpm.Conclusion: Individual improvements suggest that patient selection maybe important. However in this study of subjects with SA and PM, NOP didnot reduce the severity of SA as measured by AHI.

473

Impact of left and right bundle branch block onintracoronary blood flow dynamicsHeinrich Wieneke, MD, Wolfram Rechenberg, MD, StefanSack, MD and Raimund Erbel. Univ Essen, Essen, Germany.

Background: The impact of right bundle branch block (RBBB) and leftbundle branch block (LBBB) on myocardial perfusion is not completelyunderstood as data are often blurred by underlying cardiac disease.The aim of the study was to investigate whether conduction delays perse affect coronary perfusion as a measure of myocardial oxygen de-mand.Methods: Intracoronary Doppler was performed in 9 patients with rightbundle branch block (RBBB), 11 patients with left bundle branch block(LBBB) and 12 control subjects. All patients had angiographically normalcoronary arteries and normal global left ventricular function. Baseline(bAPV) and peak average flow velocity after adenosine were measured inthe left anterior descending artery and coronary flow velocity reserve(CFVR) was calculated.Results: There was no significant difference between the groups withrespect to the pressure-rate-product and age as major determinants ofcoronary flow velocity. Patients with LBBB and RBBB had a significanthigher bAPV compared to the control group. CFVR was also reduced inpatients with LBBB.Conclusion: The present data show that particually LBBB is associatedwith a marked increase in coronary resting flow velocity. This suggeststhat bundle branch blocks produce mechanoenergetic disturbances thatlead to an abnormally increased myocardial oxygen demand what may

contribute to the adverse outcome associated with intraventricular con-duction delays.

474

The effects of dual chamber coupled pacing onhemodynamics and myocardial oxygen consumption*David E. Euler, PhD, *Ruth N. Klepfer, PhD, *Vincent E.Splett, MS, *David M. Schneider, *Deborah A. Jaye and *D.Curtis Deno, MD, PhD. Medtronic, Inc, Minneapolis, MN.

Background: Paired electrical stimulation of the ventricular myocardiumhas been reported to evoke sustained postextrasystolic potentiation with aconcomitant increase in myocardial oxygen consumption. The purpose ofthis study was to investigate the hemodynamic and metabolic effects of anew method of inducing postextrasystolic potentiation with dual chambercoupled pacing in the intact canine heart.Methods: Left ventricular (LV) and aortic pressure (micromanometers),and aortic and coronary blood flow (ultrasonic flowprobes) were monitoredin 6 open-chest anesthetized dogs. A coupled premature stimulus wasdelivered each cardiac cycle to the right ventricle 40 ms after the ventric-ular effective refractory period. An atrial stimulus was also delivered 60 msprior to each ventricular stimulus. Dual chamber coupled pacing wasapplied continuously for 30-60 minutes (43 � 12 minutes).Results: Compared to baseline, there was an increase in LV peak �dp/dt(77 � 37%, P�0.01), LV systolic pressure (24 � 4%, P�0.01), LVend-diastolic pressure (17 � 15%, P�0.05), aortic pulse pressure (64 �16%), and stroke volume (53 � 21%, P�0.01). There was also an increasein external cardiac work (81 � 40%, P�0.01) and cardiac power (20 �12%, P�0.01). There was a significant reduction in mechanical heart rate(33 � 8%, P�0.01) and mean aortic pressure (7 � 6%, P�0.05). Theseresponses were sustained throughout the period of dual chamber coupledpacing. There were no significant changes in cardiac output, coronaryblood flow, or myocardial oxygen consumption. In addition, there was nosignificant change in myocardial lactate extraction.Conclusions: Dual chamber coupled pacing evokes sustained postextra-systolic potentiation while reducing mechanical heart rate in the intactcanine heart. The increase in contractile performance occurs in the absenceof significant changes in coronary blood flow, myocardial oxygen con-sumption or myocardial lactate metabolism. This type of pacing might beuseful in treating patients with heart failure.

475

The effect of temporary switching off ventricularresynchronization on selected markers of inflammationand NO productionAndrzej Rubaj, MD, PhD, Piotr Rucinski, MD, AndrzejKutarski, MD, PhD and Krzysztof Oleszczak, MD. MedicalUniv of Lublin, Lublin, Poland.

CHF is associated with endothelial dysfunction and a decrease in endo-thelial derived NO production, which contributes to circulatory decompen-sation. Elevated levels of TNF and IL6 were found to be positively relatedto severity of CHF. These cytokines may cause oxidative stress, endothelialdysfunction, increase expression of adhesion molecules (ICAM-1,VCAM-1) and directly contribute to LV pump dysfunction and remodel-ing. In pts with CRT system implanted the rapid deterioration in CHFsymptoms was observed in cases of loss of resynchronization.The aim of our study was to evaluate the effect of temporary switchingoff CRT on NO production, level of selected cytokines: TNF, Il6,

S150 Heart Rhythm, Vol 1, No 1, May Supplement 2004

ICAM, VCAM and marker of oxidative stress-malondialdehyde(MDA).Methods: The study population consisted of 28 pts with CRT pacingsystem implanted due to generally accepted indications. At least 4 weekstime after implantation, pts underwent evaluation, the pacing mode wasthen changed to RV, and after 2 days the evaluation process was repeated.TNF, ICAM, VCAM, BNP, IL6 were measured with commercially avail-able ELISA tests. Oxidative stress was assessed by measuring plasmaMDA level while NOX using the vanadium-based simple assay for nitriteand nitrate measurement.Results: RV pacing in comparison to BiV pacing was associated withsystolic function deterioration (Ao-VTI 21,4 vs 19,4; p�0,0007), increasein serum levels of TNF (12,3 vs 20,4 pg/ml; p�0,01), Il6 (18,0 vs 25,1pg/ml; p�0,00) and MDA (2,56 vs 2,79 �mol/l; p�0,00) and decreasedNOX level (38,4 vs 26,3 �mol/l; p�0,04). VCAM concentration decreased(1186 vs 1020 ng/ml; p�0,02) and ICAM did not change (506 vs 499ng/ml; p�0,6). BNP level didn’t change significantly.Conclusions: Systolic function worsening in RV pacing mode in com-parison to CRT is associated with increase of inflammatory and oxida-tive stress markers: TNF, Il6, MDA. CRT influence on adhesion mol-ecules expression is incoherent in our study. The results indicate thateven 48 h of loss of resynchronization can augment inflammatory statusand decrease NO production, what may be responsible for pts statusdeterioration.

476

Chronic performance of a subcutaneousphotoplethysmography sensor*Yelena Nabutovsky, MS, *Todd Pavek, DVM, *GregoryWright, BS and *Robert G. Turcott, MD, PhD. St. JudeMedical, Sunnyvale, CA and St. Jude Medical, Sylmar, CA.

Background: A subcutaneous photoplethysmography (sPPG) sensor useslight to detect changes in vascular volume from a location outside thebloodstream. Incorporation into a pacemaker, ICD, or chronically im-planted monitor may facilitate therapy optimization and disease monitoringby providing continuous assessment of hemodynamic function and arterialO2 saturation. We evaluated the performance of chronically implantedsPPG sensors in dogs over several months. Studies are ongoing.Methods: 4 dogs were implanted with 2-4 sPPG sensors in the neck orposterior thorax. Each sensor contained a red and infra-red (IR) LED,photodetector, and supporting electronics encapsulated in epoxy and at-tached to a transcutaneous connector. Data were collected at implant and,after administration of medetomidine for sedation and atropine for regu-larization of cycle length, every 3� 1 days for 4-7 months starting 3 weekspost-implant. Pulse amplitude and DC offset were calculated. At explant,the fibrous encapsulation was histologically analyzed.Results: Cardiac pulses were readily detectable throughout the study andat sensor explant in all dogs. The differences in pulse amplitude and offsetassociated with time since implant, wavelength, and orientation are sum-marized in the table. A minimally to moderately neovascularized encap-sulation formed over all sensors (thickness 2.8 � 2.2 mm), consisting offibrous and granulation tissue, with a grossly avascular layer adjacent toprobe. Overall response was typical for foreign inert material.Conclusion: Despite encapsulation of sPPG sensors, pulse amplitude andDC offset remained relatively constant over time, and cardiac pulses couldbe easily measured throughout the study. These results suggest suitabilityof sPPG technology for chronic cardiac monitoring.

477

Immediate outcomes of cardiac resynchronizationtherapies compared to pacemaker and internal cardiacdefibrillators: Are there differences?Robert Fishel, MD, Allan Anderson, MD, Salvatore Battaglia,BS, Lynn Tarkington, BA, April Simon, RN, MSN, Steve Culler,PhD and Edmund Becker, PhD. JFK Medical Ctr, Atlantis, FL,Medical City Dallas Hosp, Dallas, TX, HCA, Inc., Nashville,TN, Cardiac Data Solutions, Inc., Atlanta, GA and Emory UnivRollins School of Public Health, Atlanta, GA.

Background: For patients with advanced CHF, cardiac resynchronizationtherapy is an alternative intervention. Little empirical evidence is availableon CRT usage and outcomes compared to conventional PPM and ICDtreatment.Method: Using the HCA Casemix database, an administrative database ofall consecutive admissions in any HCA hospital, all patients admittedduring the period October 2002 through March 2003 for CRT, PPM, orICD for were utilized. Patient characteristics, comorbiditites, proceduralvariables, and complications were identified using ICD9 codes. Data on12,776 admissions were analyzed comparing CRT versus PPM and CRT-Dversus ICD.Results: Patients who received CRT-D therapy as opposed to CRT therapyare more likely to be male, S/P CABG surgery, S/P ICD, S/P MI, havecardiogenic shock, and have SVT. Over 84% of all CRT and CRT-Dpatients have CHF but only about a third have a bundle branch block. CRTpatients have significantly less unadjusted mortality, neurologic and car-diac complications, post-op infection, and device related malfunctions thanPPM patients. CRT-D patients have significantly lower unadjusted infec-tion and neurologic complication rates than ICD patients, but CRT-Dpatients had higher unadjusted mortality and shock/hemorrhage rates thanICD patients although these were not statistically significant. After con-trolling for age, gender, and 32 co-morbid and procedural characteristics,CRT patients were significantly more likely to be discharged home andexperience less device related malfunctions than PPM patients. CRT-Dpatients were 4.2 times more likely to experience shock/hemorrhage thanICD patients. Logistic regression results showed no significant differencesin either CRT or CRT-D comparison for the outcomes of mortality, ARF,stroke, cardiac complications or post-op infections.Conclusions: Despite having substantially different demographics andco-morbidities, patients receiving CRT therapy demonstrate no differencesin major complications when compared to patients receiving conventionalpacemaker and ICD therapies.

478

A new registry for tracking outcomes in heart failurepatients treated in the era of expanded device therapiesBruce L. Wilkoff, MD, Shane Bailey, MD, Leslie A. Saxon,MD, Teresa Demarco, MD, James B. Young, MD, RobertBourge, MD, G. Neal Kay, MD and Harold Javitz, PhD. TheCleveland Clinic Foundation, Cleveland, OH, Univ ofSouthern California, Los Angeles, CA, Univ of California,San Francisco, CA and Univ of Alabama at Birmingham,Birmingham, AL.

Background: There is a lack of prospective outcome data obtained inambulatory heart failure patients not enrolled in clinical trials that assessesthe relationship between medical and device therapies. Expanding indica-tions for the implantable defibrillators (ICD), resynchronization devices(CRT, CRT-D), implantable hemodynamic monitors and ventricular assistdevices (VAD) influence medical therapies and impact outcomes.Methods: Demographic and clinical data were collected from a represen-tative cohort of ambulatory patients with left ventricular dysfunction re-ferred to tertiary centers across the U.S. with expertise in heart failure andarrhythmias. Tertiary centers included University of Southern California,University of California, San Francisco, Cleveland Clinic Foundation andUniversity of Alabama, Birmingham. Registry initiation began 4/03. Cur-

S151Poster 2

rent registry enrollment is 77 patients. Over 700 variables are prospectivelycollected and updated every 3 months.Results: The majority of patients seen at the listed tertiary centers wasreferred for heart failure management and had NYHA functional classII-III heart failure symptoms. Almost half of the patients had either isch-emic or idiopathic cardiomyopathy as the etiology of their heart failure.Less than 10% of patients were treated with biventricular pacing. Amajority of the patients were male and transplant status had not beenaddressed in almost half of the patients.

Conclusions: The CHART Registry continues to provide novel and mean-ingful outcome data in a cohort of patients treated in the era of combinedarrhythmia and heart failure management. This data can be utilized toassess the effects of this treatment approach on important clinical andeconomic outcomes.

479

Narrowing of the widest native QRS may predictimprovement in clinical parameters in patients withcardiac resynchronization therapy devicesYaariv Khaykin, MD, J. David Burkhardt, MD, George K.Joseph, MD, Mandeep Bhargava, MD, Jennifer E.Cummings, MD, Atul Verma, MD, Ahmad Abdul-Karim, MD,Kenneth Ng, MD, Navin Kedia, MD, Richard Grimm, MD,Patrick J. Tchou, MD and *Bruce L. Wilkoff, MD. TheCleveland Clinic Foundation, Cleveland, OH.

Few parameters have been shown to predict improvement in patients treatedfor congestive heart failure (CHF) with cardiac resynchronization therapy(CRT). To assess whether narrowing of the native QRS duration after CRTdevice implantation predicts improvement in clinical and echocardiographicparameters, we collected these data for 217 consecutive patients treated withprimary CRT therapy at the Cleveland Clinic Foundation between 09/01/1998and 10/14/2002 (age 66.4�12.2 years, 71% male, 53% ischemic cardiomy-opathy). All patients had pre and post implantation 12-lead ECG and 2D-echocardiograms. Widest QRS in any lead before and after CRT was docu-mented. Functional status was assessed during follow-up at the CHF clinic.While the mean QRS did not significantly narrow with CRT [178 �27 msecpre to 181 �24 msec post, p� 0.28], in patients who experienced QRSnarrowing with CRT, the likelihood of NYHA functional class improvementwas significantly higher versus patients in whom the widest QRS did not

narrow (sensitivity 72%, specificity 50%, OR 2.5 [1.2-5.3]). A similar trendwas seen for improvement in ejection fraction (EF) and mitral regurgitation inthose with narrowed QRS.Conclusion: Narrowing of the widest native QRS complex after CRTdevice implantation predicts improvement in NYHA functional class andmay predict improvement in ejection fraction and mitral regurgitation.

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Long term improvement in coronary venous lead implantprocedures*David Delurgio, MD, *Venkateshwar Gottipaty, MD,*Kyong T. Turk, MD, *Michael C. Giudici, MD, *ImranNiazi, MD, *Jill E. Schafer, MS and *Lisa Ludvig, MS.Emory Univ Hosp, Atlanta, GA, Providence Hosp, Columbia,SC, St. Elizabeth Regional Medical Ctr, Lincoln, NE, GenesisMedical Ctr, Davenport, IA, St. Luke’s Medical Ctr,Milwaukee, WI and Guidant Corp, St. Paul, MN.

Background: Cardiac resynchronization therapy (CRT) device implants areassociated with longer procedures than conventional pacemaker or defibrillatorimplants due to the placement of an additional coronary venous (CV) lead. Itis hypothesized that procedure times have improved as CV lead implants havebecome more prevalent. The purpose of this analysis is to determine if pro-cedure times and implant success rates with current CV leads have improvedwhen compared to those originally introduced four years ago.Methods: Two prospective multi-center CRT trials with CV leads wereanalyzed. Data from the CONTAK® CD study using the EASYTRAK®

lead was compared to the ongoing DECREASE-HF study of the EA-SYTRAK® 2 lead. Outcomes of interest between the two studies includedprocedure time (skin-to-skin), fluoroscopy time, ability to cannulate thecoronary sinus (CS), and implant success rates.Results: Comparisons are tabulated below. Significant improvement wasobserved in all outcomes. Over time, procedure duration was reduced by 28%and fluoroscopic exposure was reduced by 39%. Furthermore, the ability tocannulate the CS and successfully implant the lead has also significantlyimproved. * 4 of the 5 implanted patients in whom the attempt was unsuc-cessful at the first procedure, were successful at a subsequent procedure.

Conclusion: Current experience with implanting CV leads has markedlyimproved since originally introduced. Physicians are achieving greaterimplant success in less time with decreased radiation exposure. Thisachievement may be due to increased physician experience and improvedimplant tools.

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Impact of LV and RV pacing sites on long term clinicaloutcome in heart failure patients treated by cardiacresynchronization therapyChristophe Leclercq, MD, Guillaume Lecoq, MD, ChristopheCrocq, MD, Dominique Pavin, MD, Jean-Claude Daubert,MD and Philippe Mabo, MD. Ctr Cardio-Pneumologique,Rennes, France.

Cardiac Resynchronization Therapy (CRT) is effective to improvefunctional status in patients (pts) with conventional indications as

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described in the 2002 NASPE guidelines. The aim of this study was toevaluate the impact of LV and RV leads locations on functional statusand mortality.Methods: 139 consecutive patients, 68�8 years, were implanted with abiventricular pacemaker for severe heart failure (96 pts in NYHA class III,43 in class IV despite optimized drug therapy) between 1994 and 2000. .The mean LV ejection fraction was 21 � 6 % and the mean QRS duration188 � 28 ms. The target LV lead position was a lateral vein. The RVandLV leads position were optimized in each patient to achieve the shortestbiventricularly paced QRS.The clinical response was assessed at 6-months follow-up by a compositeendpoint. Responder pts (R) had to be alive, without new hospitalizationfor HFand functionally improved with a decrease � 1 NHYA class and/ora � 10% increase in peak VO2.Results: The LV lead was implanted in a lateral or postero-lateral (L)coronary sinus vein in 73% of pts and in a non lateral location in 27% (noL). The RV lead was screwed in the interventricular septum in 72% ofpatients (RVS) and at the apex (RVA) in the others. In the overall popu-lation, 73% was considered as R. No significant difference was observedwhatever the left and right leads positions.Mortality rate was evaluated at 36 months FU according the combinationof the of the LV and RV leads.Conclusions: In this open study, No significant difference was observed inclinical response between different RV and LV lead positions. The mor-tality rate trended to be higher in pts with RV apical lead and no lateral LVlead. Theses results have to be confirmed by further prospective studies.

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Long-term follow-up of cardiac resynchronization therapyDarryl R. Davis, MD, *Andrew D. Krahn, MD, *Anthony S.Tang, MD, Robert Lemery, MD, *Martin Green, MD,*Raymond Yee, MD, *Allan C. Skanes, MD, *George J.Klein, MD and *David Birnie, MD. Univ of Ottawa HeartInst, Ottawa, Ontario, Canada and London Health SciencesCtr, London, Ontario, Canada.

Background: Cardiac resynchronization therapy (CRT) has recently beenshown to be an effective short-term therapy for patients with drug refrac-tory heart failure and intraventricular conduction delay. Little is knownabout the long-term effects of this therapy.Methods: We evaluated all patients with at least two years follow-up whounderwent CRT at two Canadian centers.Results: A total of 85 consecutive patients (66 � 9 years; 90% male)implanted between Dec 1997-Nov 2001 were included in the study. Allpatients fulfilled standard CRT indications with a mean NYHA class of3.1 � 0.4, QRS duration of 168 � 22 ms and MIBI-gated ejection fractionof 21 � 6%. Eighteen of the 85 patients were implanted with a combinationAICD and CRT device. Use of combination device was at the physician’sdiscretion and it should be noted that combination devices were notavailable in Canada until 2000. Mean QRS duration and LV-EF after CRTwere 164 � 33ms and 28 � 12% respectively (P�ns for change in QRS,P�0.01 for change in LV-EF). Within a mean clinical follow-up of 3.0 �1.0 years, 30 of the 85 patients died and 8 patients underwent cardiactransplantation with 4 transplant-related deaths (mean survival time 3.53 �0.26 years). 10 patients died of sudden cardiac death, 8 patients died ofprogressive heart failure and 12 patients died of non-cardiac causes. TheKaplan-Meier graph below illustrates survival from the first of death ortransplantation. None of the baseline factors (age, EF, etiology, QRSduration, ICD) or indices of CRT (change in EF or QRS duration) werepredictive of poor outcome. There was a clear trend for patients withgreater LV-EF gain to have better outcome (p�0.1).Conclusions: This observational data represents one of the longest fol-low-up databases of patients undergoing CRT. The significant morbidity

and mortality found following CRT highlights the severity of the under-lying cardiac pathology and concurrent illnesses.

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Usefulness of conventional echocardiographic parametersfor prediction of the acute hemodynamic improvement bycardiac resynchronisation therapy*Christoph Stellbrink, MD, Nadim Bidaoui, MS, *Ole-Alexander Breithardt, MD, Anil M. Sinha, MD, Hans-Christian Elbracht, MS, *Angelo Auricchio, MD, PhD,*Christian Butter, MD, *Etienne Huvelle, MD and *JulioSpinelli. Univ Hosp RWTH, Aachen, Germany and RWTHAachen, Aachen, Germany.

Cardiac resynchronisation therapy (CRT) improves left ventricular (LV)hemodynamics. Currently, QRS width is being used as the main parameterto identify responders to CRT. In 56 patients (pts.) of the PATH-CHF IIstudy (40 m, 16 w, age 60�8 yrs., 22 ischemic, 34 non-ischemic cardio-myopathy, QRS 156�19 ms), we analyzed whether the addition of simpleechocardiographic (echo) parameters allows better prediction of acutehemodynamic improvement with CRT than QRS width alone. In all pts.2-dimensional and Doppler echo were performed before implantation of aCRT pacemaker. Moreover, an invasive hemodynamic study was per-formed in which different atrioventricular delays and LV pacing sites weretested in a random fashion using a FLEXSTIM™ device. The hemody-namic response was quantified by the increase in the slope of left ventric-ular pressure rise (LV �dP/dt), measured with a micromanometer catheter(Millar™). Pts. with an increase in LV �dP/dt �10% were classified asresponders. Predictive factors were determined by multivariate analysis;sensitivity and specificity, positive and negative predictive values forresponsers to CRT were determined by binary logistic regression.Results: QRS width, early diastolic acceleration time (EAT), fractionalshortening (FS) and aortic velocity time integral (AoVTI) were predictivefor an acute increase in LV �dP/dt. Binary logistic regression revealed aregression coefficient of z�-4,504 � 0,06 x QRS-0,136 x FS-0,051 xAoVTI-0,013 x EAT

Conclusion: Conventional echo parameters improve identification of pts.with acute hemodynamic improvement with CRT compared to QRS widthalone.

484

Transthoracic access for electroanatomic mapping andablation in patients with arrhythmia following FontanpalliationRodrigo Nehgme, MD, Michael Carboni, MD, Jennifer Care,RN and John Murphy, MD. Nemours Cardiac Ctr, A.I.duPont Hosp for Children, Wilmington, DE and A.I. duPontHosp for Children, Wilmington, DE.

Background: The incidence of atrial arrhythmias following Fontan palli-ation is high. In the absence of a fenestration, access to the pulmonaryvenous atrium (PVA) is limited to a retrograde arterial approach or needle

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puncture of the Fontan baffle. We report a novel percutaneous, transtho-racic (TT) technique that provides direct, rapid, and reliable access to thePVA for RF ablation.Patients and Methods: Four patients (Pts) (1.2 to 17 years, 9.2 to 68.4kg) with a lateral tunnel Fontan underwent TT procedures under generalanesthesia. Angiography was performed in the baffle, ventricle, andascending aorta to define cardiac anatomy and course of the internalmammary artery. Under biplane fluoroscopy a 20 G 5 cm or a Chibaneedle was advanced over a rib at the selected intercostal space aimingposteriorly and medial to the baffle. Access to the PVA was confirmedby blood return and contrast injection. A 4F sheath was advanced overa 0.018 floppy wire and up-sized to a 7F sheath. A Navistar Biosense-Webster (CARTO) catheter was advanced to the PVA for mapping,pacing and ablation. Additional catheters were placed in the baffle andesophagus for recording, pacing, and to serve as reference. SVT wasinduced by atrial pacing at baseline or with isoproterenol. Electroana-tomic mapping was used to define activation sequence, areas of ana-tomic block, and location of the His electrogram. Candidate areas weretested with entrainment techniques. RF ablation was performed andsuccess defined as the inability to re-induce sustained SVT.Findings: Intraatrial reentry tachycardia (IART) was seen in 3 andectopic atrial tachycardia in 1 Pt. All arrhythmias were ablated. Proce-dure time ranged from 3.7 to 4.9 hrs and fluoroscopy time from 31 to70 min. Hospital stay was 2 days. One patient had a pneumothorax and1 a hemothorax which were drained. IART recurred in 1 Pt at 3 monthsand 2 Pts are free of SVT at 3 and 12 months. Follow up is not availablein 1 Pt.Summary: Percutaneous TT access provided a direct route to the PVA forsuccessful mapping and RF ablation of SVT in Fontan Pts. It couldrepresent the only access in Pts with external conduit or covered stentFontan completion.

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Proximity of coronary arteries to the atrioventricular valveannulus in young patients: Implications for ablationprocedures*James C. Perry, MD. Children’s Hosp, San Diego, UCSD,San Diego, CA.

Coronary artery injury is a known, rare complication of catheter abla-tion procedures. Ablation lesion depth and resistive heating of thecoronaries likely cause injury. In smaller hearts this is a greater con-cern. There are no data on the distance (D) from the atrioventricularvalve annulus (AVVA) endocardial surface to the coronary arteries.This study was begun to examine differences in D at standard locationsalong the AVVA as a guide to ablation safety and development of newablation systems.Methods: Normal heart specimens were examined from patients (pts)dying from non-cardiac causes. Measurements were made in formalinizedhearts from the endocardial aspect of the mitral and tricuspid AVVA andcoronary sinus os to the adventitia of the adjacent coronary artery at the AVgroove. D was measured at each of 11 accessory pathway locations usingthe nomenclature of the Pediatric Ablation Registry.Results: A total of 8 hearts were studied from pts ranging in age from 1-16years (avg 8 yrs). None had a history of cardiac disease or hypertrophy.Hearts were not enlarged for age. There were differences in D both by ageand AVVA location as shown in the graph. D for right anteroseptallocations was greatest, all � 4 mm. The right anterior location (below theright appendage) was � 5 mm in 7/8 pts. D was � 5 mm for all pts at 1cm within the coronary sinus. Each of the 4 pts � 7 yrs old had a consistentD of � 4 mm for 8/11 locations. None of the 8 pts had a “shepard’s crook”superior bend of a right dominant coronary to the posterior descendingartery.Conclusions: There are significant differences in D from the AVVA tocoronaries based on AVVA location and age. As ablation lesions mayexceed 4 mm or more in depth, the risk of damage to coronaries during

ablation procedures may be related to AVVA location and highest inthose pts � 7 yrs of age. Analyses of D in fixed and living hearts areongoing.

486

Experience with transcatheter cryotherapy for treatmentof supraventricular arrhythmias in young patientsElizabeth V. Saarel, MD, Peter S. Fischbach, MD, FrankPelosi, Jr., MD, *Fred Morady, MD and MacDonald Dick,II, MD. Univ of Michigan Health System, Ann Arbor, MI andUniv of Michigan, Ann Arbor, MI.

Introduction: There are few reports of transcatheter cryotherapy (CRYO)for treatment of supraventricular tachycardia (SVT) in young patients.Purpose: To report the initial experience with CRYO ablation at ourinstitution.Methods and Results: Eleven consecutive subjects (mean age 12.9�/�8.2,range 5.7-28.5, median 17.1 years; 6 female) underwent transcatheter CRYOat the University of Michigan between 8/1/03 and 11/24/03. All patients haddocumented SVT prior to electrophysiologic study (EPS). Seven subjects hadAV nodal re-entry tachycardia (AVNRT), 3 Wolff-Parkinson-White syndrome(WPW) and atrioventricular re-entry tachycardia (AVRT) (each with 2 acces-sory pathways (APs) including 2 right free wall, 2 right anteroseptal, 1 rightposterolateral, and 1 left posteroseptal), and 1 junctional ectopic tachycardia(JET). Three subjects had undergone prior attempts at radiofrequency ablation(RFA) of the SVT substrate (2 AVNRT, 1 WPW). Ten subjects had normalcardiac anatomy, whereas 1 patient with WPW had hypertrophic cardiomy-opathy. CRYO mapping (-30 degrees for 1 min) and attempted CRYO abla-tion (-75 degrees for 4 min) utilizing the CryoCath© 7 FR Freezor© 4 mm tipcatheter was performed in all subjects. Success was defined as loss of pre-excitation (WPW), slow pathway ablation (AVNRT), and non-inducible SVT.

Five minor complications occurred: Transient complete heart block (HB) inboth patients with anteroseptal APs during RFA, transient complete HB in 1patient with an anteroseptal AP during CRYO mapping, transient 2nd degreeHB in the patient with JET during CRYO mapping, and transient 1st degreeHB in a single patient with AVNRT during CRYO mapping. There were nomajor complications.Conclusions: Transcatheter CRYO proved safe for use in young patients.CRYO was more effective for treatment of AVNRT and JET than WPW inthis early experience.

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Outcomes following electroanatomic mapping and ablationfor the treatment of ectopic atrial tachycardia in thepediatric population

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Rose M. Cummings, DO, Melinda Dobbs, RN, BSN, MargaretJ. Strieper, DO, Robert M. Campbell, MD, Lynne Costello,RN, BSN, Virginia Balfour, RN, Amanda Burchfield, RN andPatricio A. Frias, MD. Sibley Heart Ctr, Children’sHealthcare of Atlanta, Emory Univ, Atlanta, GA.

Background: Ectopic atrial tachycardia (EAT) is often resistant to medicaltherapy, with radiofrequency ablation (RFA) being a preferred treatmentoption. Three-dimensional electroanatomic (3-D) mapping was introducedas a tool for improved substrate localization. To date, there are no pub-lished data reporting this technology in pediatric pts with EAT. Theobjective of this study was to examine our experience with 3-D mappingand standard mapping in this population.Methods: Retrospective review of pediatric pts with EAT requiring RFAfrom 1993-present. We analyzed method of ablation, acute success andrecurrence rates, procedure and fluoroscopy times, and cardiac function.Results: Twenty-five pts underwent 31 RFA procedures. All pts have beenfollowed for � 6 mos (6 mos-7 yrs). Standard mapping (Group 1) was usedin 11 pts (5F/6M, 1.4-11.8 yrs) who underwent 13 RFA procedures; 3-Dmapping (Group 2, Oct 2000-present) was used in 16 pts (8F/8M, 2.7-17yrs) who underwent 18 RFA procedures. Left-sided focus was present in6/13 in Group 1 and 7/18 in Group 2 (all transeptal, NS). There was a trendtoward fewer lesions (15�14, median 9.5 in Group 1; 8�6, median 6.5 inGroup 2) with 3-D mapping (NS). There were no differences in acutesuccess rates (10/13 Group 1 vs. 18/18 Group 2, NS). However, recurrenceor persistence of tachycardia at intermediate follow-up (2 wk-1 yr) wasdocumented in 7 of 13 cases in Group 1, compared to only 2 of 18 casesin Group 2 (p�0.01). Six pts underwent repeat RFA: 2 pts using standardmapping (1 failure, 1 success), and 4 pts using 3-D mapping [all acute andlong-term (�1 yr) success]. Procedure (232�84 vs. 268�72 min, skin-to-skin) and fluoroscopy (47�24 vs. 40�20 min) times were similar (NS). Ofthe 25 pts, 17 (7-Group 1, 10-Group 2, NS) presented with cardiomyopathy(EF 38.6�12.1%). Successful RFA resulted in improved EF (61.1�11.6%,p�0.0001) in the 14 pts in whom pre and post RFA echos were available.Conclusion: Compared to standard techniques, 3-D electroanatomic map-ping has resulted in no acute failures, statistically reduced recurrence ratesand improved overall success in the management of EAT.

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Pediatric electrophysiologists can safely performelectrophysiology studies on adults with congenital heartdiseaseChristopher S. Snyder, MD, Richard A. Friedman, MD,Naomi J. Kertesz, MD and Arnold L. Fenrich, MD. YaleUniv School of Medicine, New Haven, CT and BaylorCollege of Medicine, Houston, TX.

Adults with congenital heart disease (CHD) frequently have arrhythmias.In addition, their venous and arterial anatomy may be abnormal or oc-cluded. The purpose of this study was to review the safety and efficacy ofa pediatric electrophysiologist performing electrophysiology studies (EPS)on adults with CHD.Methods: All EPS were performed at Yale and Texas Children’s Hospitalsafter 1995. Patient (pts) records were reviewed for demographics, cardiacdiagnosis, surgery, arrhythmia, vascular access, procedure and complica-tions.Results: 64 pts age � 18 were identified with CHD. CHD pts average;age � 24 years(18-37), weight � 71.7 kg(42-130), height �170 cm(137-201). An EPS was performed on 30 pts with the other 34 having EPS withattempted radiofrequency ablation. Supraventricular tachycardia (SVT)occurred in 33 pts (52%) and ventricular tachycardia (VT) in 31 pts (48%).Vascular access was easily obtained in 97% of pts, with only 3% requiringcatheterization from the neck and/or arm. Access to the ventricle in Fontanpts was arterial. Fluoroscopy time averaged 34.2 minutes (range 0.1-152).In SVT pts the most frequently encountered CHD was tricuspid atresia(26%), ventricular inversion (18%) and d-transposition of great arteries(18%). Ablation was successful in 23/32 (72%), and unsuccessful in 9 (4with intra-atrial reentry, and 2 para-Hissian pathways). In VT pts, most

common CHD included tetralogy of Fallot (24%), d-transposition of greatarteries (21%) and ventricular inversion (17%). VT ablation was attemptedin 2 and successful in 1. Complications occurred in 3 pts (4%) withpermanent (1) or transient (1) atrio-ventricular node injury, or coagulum oncatheter (1). No deaths occurred.Conclusions: (1) Arrhythmias are relatively common in adults with CHD.(2) It is imperative to know the venous anatomy when performing EPS onadult CHD pts. (3) SVT can be successfully ablated in � 70% of these pts.(4) Adults with CHD can undergo safe and effective electrophysiologystudies performed by pediatric electrophysiologists.

POSTER SESSION IIIThursday, May 20, 2004Session Time: 2:00 p.m.–4:00 p.m.Presenter Available: 3:45 p.m.–4:45 p.m.Location: Exhibit Hall

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Tachycardia-induced cellular hypertrophy: An in-vitro pacingmodel to study molecular biology of cardiomyocytesAndreas Goette, MD, Alicja Bukowska, PhD, Cornelia Muller,PhD, Pamela Polczyk, Tager Tager, PhD, Samuel C. Dudley,MD, PhD, Helmut U. Klein, MD and Uwe Lendeckel, PhD.Univ Hosp Magdeburg, Magdeburg, Germany.

Cardiac tachyarrhythmia are known to induce significant electrophysiolog-ical and structural changes in cardiomyocytes. The purpose of the presentstudy was to analyze the molecular mechanism of tachycardia-inducedcellular hypertrophy using an in-vitro pacing model.Methods: Pluripotent P19 cells were differentiated into cardiomyocytesin-vitro. Pacing of cardiomyocytes was performed within a cell cultureincubator up to 24 hours at a rate of 0.5 and 2.0 Hz using a pair ofcustom-built carbon electrodes. RT-PCR and Western Blotting was used todetermine the expression of the angiotensin II converting enzyme (ACE),and mitogen-activated protein kinases (ERK1/2). Protein/DNA ratio andamounts of intracellular thiol-groups were used as a marker for hypertro-phy and oxidative stress, respectively.Results: In-vitro differentiation of P19 cells into cardiomyocytes wasdemonstrated at the molecular level by the expression of GATA-4, �myosin heavy chain (MHC) and �-MHC. Pacing at 2Hz caused a signif-icant increase in protein/DNA ratio (1 � 0.015 vs. 1.1 � 0.041, p � 0.05),whereas pacing at 0.5 Hz did not cause a hypertrophic response. Geneexpression of ACE (175 %; p � 0.01), and ERK1/2 (219 � 79 % vs100 � 10 %; p � 0.05) were up-regulated during 2 Hz pacing comparedto control. The regulatory changes of ACE and ERK1/2 were confirmed atthe protein level. Thiol-groups declined by 25 % during rapid pacing.Interestingly, verapamil treatment inhibited the hypertrophic response andattenuated the loss of intracellular thiol-groups (marker for oxidativestress) during pacing at 2 Hz.Conclusions: An increased intracellular calcium influx during rapid pacingtriggers the activation of hypertrophic pathways and causes oxidativestress. The presented pacing model appears valid to investigate the func-tional role of different signaling pathways in-vitro.

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Electrical propagation in synthetic strands from fetalmurine atrial myocytes lacking Connexin 43Philippe Beauchamp, PhD, Karin De Peyer, Karen G. Green,BA, Jeffrey E. Saffitz, MD, PhD, Etienne Delacretaz, MD, PhDand Andre G. Kleber, MD, PhD. Physiologisches Inst, Bern,Switzerland, Washington Univ School of Medicine, St. Louis,MO and Washington Univ School of Medicine, St Louis, MO.

Connexin (Cx) proteins form electrical connections between myocytes andare important determinants of cardiac electrical impulse propagation. Atrialmurine myocardium contains Cx43 and Cx40. These are two connexinscharacterized by high single channel electrical conductances. To assess the

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