14

Anatomic Location of Pulmonary Vein Electrical Disconnectionwith Balloon-Based Catheter Ablation

KAREN P. PHILLIPS, M.B.B.S.,∗ ROBERT A. SCHWEIKERT, M.D.,∗ WALID I. SALIBA, M.D.,∗

SAKIS THEMISTOCLAKIS, M.D.,† ANTONIO RAVIELE, M.D.,† ALDO BONSO, M.D.,†ANTONIO ROSSILLO, M.D.,† J. DAVID BURKHARDT, M.D.,∗ JENNIFER CUMMINGS, M.D.,∗

and ANDREA NATALE, M.D.∗

From the ∗Section of Pacing and Electrophysiology, Cleveland Clinic, Cleveland, Ohio, USA;and †Department of Cardiology, Umberto I Hospital, Mestre-Venice, Italy

Location of Electrical Isolation with Balloon Catheters. Introduction: Balloon-based cathetersare an emerging technology in catheter ablation for atrial fibrillation, which aim to achieve consistent andrapid ablation encirclement of pulmonary veins (PVs). Recent emphasis has been placed on achieving moreproximal electrical isolation within the PV–left atrial (LA) junction. We sought to evaluate the preciseanatomic level of PV electrical disconnection with current design balloon-based catheters.

Methods and Results: Thirteen patients with drug-refractory paroxysmal atrial fibrillation undergoingballoon catheter ablation with the endoscopic laser system (CardioFocus) or the high frequency-focused ul-trasound system (ProRhythm) underwent electroanatomic mapping (EAM) of the left atrium. Intracardiacechocardiographic (ICE) imaging was used for visualization of the position of the balloon catheter duringenergy delivery. Detailed point analysis of the location of electrical disconnection was then documented onEAM and with ICE.

Successful electrical isolation was achieved in all 52 PVs. Despite ICE imaging confirming balloon catheterposition at the antrum of the PVs, the location of electrical disconnection was demonstrated to be at or nearthe tubular ostium of the PVs on EAM and on ICE in all patients.

Conclusion: Current generation balloon-based catheter ablation achieves electrical isolation distal inthe LA–PV junction. This may limit the results of such systems in treating nonparoxysmal forms of atrialfibrillation. (J Cardiovasc Electrophysiol, Vol. 19, pp. 14-18, January 2008.)

atrial fibrillation, catheter ablation, balloon catheter, laser, focused ultrasound

Introduction

Catheter ablation for atrial fibrillation has become an ac-cepted, efficacious therapy1 for a condition affecting around6% of people over the age of 65 years.2 The importance ofelectrical isolation of the pulmonary veins (PVs) from thebody of the left atrium as a central strategy of catheter ablationis supported by an expanding body of literature.3-6 However,procedural outcomes and efficacy using point-by-point lesioncreation with a conventional ablation catheter are operator-dependent and time-consuming. Emerging technologies suchas balloon-based ablation catheters7,8 are attempting to pro-vide tools to achieve more consistent and rapid encirclementof the PVs.

Drs. Themistoclakis, Bonso, and Raviele received a research grant for workrelated to this study.

Dr. Schweikert received honoraria from St. Jude Medical, Biosense-Webster,and Johnson & Johnson.

Address for correspondence: Robert A. Schweikert, M.D., Section of Pacingand Electrophysiology, Department of Cardiovascular Medicine, ClevelandClinic, 9500 Euclid Avenue, Cleveland OH, 44195. Fax: 216-445-3595;E-mail: schweir@ccf.org

Manuscript received 8 May 2007; Revised manuscript received 20 July 2007;Accepted for publication 24 July 2007.

doi: 10.1111/j.1540-8167.2007.00964.x

The importance of arrhythmogenic triggers and substrateat the junction of the left atrium and PVs has recently been em-phasized,9-11 especially in nonparoxysmal patterns of atrialfibrillation,12 and the potential advantage of more proximallevels of isolation has been suggested.9-11 Additionally, theincidence of complications attributable to more distal sitesof ablation within the PVs, such as PV stenosis,13,14 has alsostrongly supported this strategy. In keeping with this, thecurrent generation of balloon catheters has been modified indesign to achieve positioning and targeted ablation proximalto the tubular ostium of the PV.15

We sought to evaluate the anatomic level of PV electricaldisconnection with regards to the PV–left atrial (LA) junctionin patients undergoing catheter ablation for atrial fibrillationwith two novel balloon catheter-based ablation systems—theendoscopic–laser balloon (EAS, CardioFocus, Norton, MA,USA) and high frequency-focused ultrasound balloon (HIFU,ProRhythm, Ronkonkoma, NY, USA) catheter systems.

Methods

A cohort of 13 patients undergoing balloon catheter-basedablation for paroxysmal atrial fibrillation was prospectivelystudied with intracardiac echocardiography (ICE) and Cartoelectroanatomic mapping (Biosense Webster, Diamond Bar,CA, USA) or Ensite NavX intracardiac mapping (St JudeMedical, Minneapolis, MN, USA) for the respective loca-tions of balloon position at the time of energy delivery and ofsubsequent electrical disconnection of the PV. These patients

Phillips et al. Location of Electrical Isolation with Balloon Catheters 15

represent a cohort from larger series of 30 and 10 patients,respectively, undergoing laser balloon catheter-based abla-tion therapy and high frequency-focused ultrasound ballooncatheter-based therapy for atrial fibrillation. Informed con-sent was obtained from all patients and the study was per-formed in accordance with the Institutional Research guide-lines at Cleveland Clinic and Umberto I Hospital. Inclusioncriteria from the broader patient series required patients tohave a paroxysmal pattern of atrial fibrillation and to havefailed treatment with at least one antiarrhythmic drug. Pa-tients with significant structural heart disease were excluded,as were patients with a LA diameter greater than 5 cm.

Procedure

Within 24 hours of the planned ablation procedure, allpatients underwent contrast-enhanced multislice computed-tomography (CT) cardiac imaging. Proprietary software wasused to preload the 3D reconstructive images of the left atriumonto the cardiac mapping system (Carto, Biosense Websterand Ensite NavX, St Jude Medical). Patients with PV ostialarger than 2.4 cm in diameter were deemed unsuitable forballoon-based catheter ablation and were not included.

Under conscious intravenous sedation, internal jugularand femoral venous access were obtained. A duodecapolarcatheter was placed in the coronary sinus from a superior ap-proach, with the proximal 10 electrodes floating in the rightatrium. An ICE probe (AcuNav Catheter, Siemens Acuson,Mountain View, CA, USA) was positioned in the mid-rightatrium. Dual transseptal punctures were performed under ICEand fluoroscopic visualization to obtain LA access. Systemicanticoagulation with intravenous heparin was commencedprior to the first transseptal puncture with a target ACT of 400seconds.16 A 4-mm roving catheter was employed pre- andpost-ablation for creation of detailed electroanatomic mapsof the left atrium and PVs with either Ensite NavX (St JudeMedical) or Carto (Biosense Webster), in which case coregis-tration with the preacquired CT image was performed. Cartoimage integration was performed using landmark registra-tion of the posterior aspect of all four PVs during evaluationwith ICE and angiography as previously described.17 Taggedostial points for each PV were also attached to each NavXelectroanatomic map, as identified by angiography and ICEimaging. A circular decapolar mapping catheter was posi-tioned distal to the ostium of each PV to document baselineLA–PV electrical connections.

Figure 1. Fluoroscopic images during endo-scopic laser balloon catheter ablation demon-strating the inflated balloon catheter and cir-cular mapping catheter within the left atrium,and the intracardiac echocardiography probein the right atrium at the level of the intera-trial septum. Panel A, in LAO 30◦ projection,shows the balloon catheter positioned at theostium of the left superior PV. Panel B, in APprojection, shows the balloon catheter nearthe ostium of the right superior PV .

Balloon Catheter Ablation

Either of two-balloon catheter ablation systems wereutilized—an endoscopic laser balloon ablation system (EAS,CardioFocus) or high intensity focused ultrasound balloonablation system (HIFU, ProRhythm).

The laser-based balloon catheter (EAS, CardioFocus) isdelivered to the left atrium through a deflectable 15 Fr sheath.A fluid-filled balloon of maximum diameter 20 mm, 25 mm,or 30 mm is then inflated (Fig. 1). The catheter is equippedwith endoscopic capabilities to assist with visualization ofballoon-tissue contact and for final positioning of the ballooncatheter before energy delivery. An optical fiber allows for-ward projection of a 90–150◦ arc of visible light onto the tis-sue interface to visualize the proposed location of energy de-livery. The arc generator may be manipulated independentlyof balloon position to adjust both the circumferential positionand the radial projection for targeted lesion creation. A diodelaser is used to generate a continuous wave of laser energyat 980 nm, transmitted via the optical fiber to the tissue for60 seconds, achieving 6 Watts/cm of arc length. During thisstudy, maximal radial projection was selected for each arclesion to attempt the most proximal level of ablation with theballoon tip positioned at the ostium.

The ultrasound-based balloon (HIFU, ProRhythm) is a de-flectable catheter system delivered to the left atrium througha 14 Fr sheath. A dual-balloon design of either 20 mm, 25mm, or 30 mm maximum diameter incorporates a fluid-filledchamber in front of a carbon dioxide filled balloon to createa required reflective interface for the generation of a focusedultrasound beam. Contact with the endocardial surface is notrequired for successful energy delivery. Once positioned atthe ostium of the PV, ultrasound energy is focused into aconvergent circular beam on the target tissue in front of theballoon for 40 to 60 seconds to create thermal injury. Over-lapping segmental lesion creation is also possible with theHIFU balloon catheter system.

Confirmation of Anatomic Level of PV ElectricalDisconnection

Following balloon catheter ablation, complete electricaldisconnection of each respective PV was confirmed with thecircular mapping catheter, as evidenced by entrance blockand or dissociated firing from within the PV.16 The proximalextent of isolation was defined by the complete abolition of

16 Journal of Cardiovascular Electrophysiology Vol. 19, No. 1, January 2008

TABLE 1

Procedural and Follow-Up Outcomes for the Patient Cohort

Energy Technical Procedural Arrhythmia Follow-UpPatient No. Source Success–PVs Isolated Complications Recurrence Time (months)

1 Laser 4/4 - No 142 Laser 4/4 Cardiac tamponade Yes 133 Laser 4/4 - No 134 Laser 4/4 - No 135 Laser 4/4 - Yes 96 Laser 4/4 - No 97 Laser 4/4 - No 98 Laser 4/4 Right phrenic nerve paralysis Yes 99 Laser 4/4 - No 9

10 HIFU 4/4 - No 911 HIFU 4/4 - No 912 HIFU 4/4 - No 713 HIFU 4/4 - No 8

PV = pulmonary vein.

local electrograms and was identified by careful withdrawalof the circular mapping catheter toward the PV–LA junctionand then documented by electroanatomic mapping with de-tailed point by point analysis. The level of isolation of eachvein was again reviewed with real-time ICE imaging to com-pare the position with the original ostial tag assigned on themapping system. The anatomy of the pulmonary vein–LAjunction was defined as follows: the pulmonary vein ostiumwas defined as the point of reflection of the parietal peri-cardium from the LA body, corresponding with an abruptangle change from the tubular portion of the pulmonary veinthat can be visualized with angiography; the pulmonary veinantrum was defined as the funnel-like or cup-like proximalextension of the pulmonary vein before the junction with themore gradual curvature of the dome of the left atrium as de-tected by CT 3D reconstruction and by ICE; a common ostiumwas defined as coalescence of the superior and inferior veinsprior to the ostial junction with the left atrium.

Results

On preprocedural CT imaging 12 patients had separateidentifiable ostia of the four PVs and one patient had a longdiscrete common ostium for the left PVs. Nine patients un-derwent ablation with the endoscopic laser-based balloon andfour patients with the ultrasound-based balloon. The proce-dural and follow-up outcome data for the cohort are presentedin Table 1.

With ICE guidance all balloon catheters were confirmedto be positioned proximal to the tubular ostium of eachdiscrete PV or common ostium during energy delivery(Fig. 2). In the case with the left common ostium, the max-imum diameter ultrasound balloon was trialed unsuccess-fully to attempt ablation at the level of the common ostium.The balloon catheter had poor stability and tissue appositionbecause of undersizing relative to the common ostium. Asmaller balloon catheter was ultimately required for individ-ual isolation of the superior and inferior vein ostia.

Successful electrical disconnection was achieved in 52 of52 PVs and confirmed with the circular mapping catheter.Postablation electroanatomic maps demonstrated the levelof electrical isolation of the PV–LA junction to be at thetubular portion of the ostium of each PV (Figs. 3 and 4). In nopatient was a significant portion of the CT-defined antrum of

the PV–LA junction incorporated in the ablation lesions. Nosignificant difference was apparent in the proximal extent ofisolation achieved between the two balloon catheter systems.

Discussion

The significant finding from this study is that the ac-tual level of electrical isolation with current design balloon

Figure 2. Intracardiac echocardiography images of laser balloon catheterpositioning within the PV antrum prior to energy delivery. In panel A theballoon is positioned at the left superior PV ostium. In panel B, completeocclusion of the right superior PV ostium with the balloon catheter is demon-strated with color Doppler imaging.

Phillips et al. Location of Electrical Isolation with Balloon Catheters 17

Figure 3. Cartomerge electroanatomic mapsof the left atrium from a posterior view withthe location of ablation lesions and level ofpulmonary venous electrical disconnectionshown with red dots. Panel A is from a conven-tional catheter ablation showing inclusion ofthe PV antra in the electrically disconnectedPV segments. Panel B is from an endoscopiclaser balloon catheter ablation showing moredistal electrical disconnection at the level ofthe tubular ostium of the PVs.

catheter ablation is relatively distal in the LA–PV junction,more so than was expected from either the design of thecatheter or from the ICE images during energy delivery. Theevolution of balloon catheter design has already seen sig-nificant changes since the first generation, which deliveredenergy in a radial direction from the maximum diameter ofthe inflated balloon and required positioning within the pul-monary vein lumen.18 Newer design balloon catheters haveattempted to address the original shortcomings with balloonsshaped for more proximal seating at the PV antrum and tech-nology that allows energy delivery to be variably projectedforward of the catheter onto target tissue. Despite modifi-cations in design, this study suggests that current genera-tion balloon catheter systems remain unable to address abla-tion of potential arrhythmogenic triggers and substrate fromthe more proximal regions of the PV–LA junction and PVantrum.

Figure 4. Side by side views of NavX bipo-lar voltage map (on right) and preloaded 3Dreconstructive CT imaging (on left) of the leftatrium from a posterior view. Panel A, above,is a baseline bipolar voltage map with normalvoltages (>1.5 mV) shown in purple. Panel B,below is from the same patient following ul-trasound balloon catheter ablation with scaror electrically silent areas shown in gray andnormal voltages (>1.5 mV) shown in purple.

One potential explanation of the apparent discrepancy be-tween the ICE visualized position of the balloon and thedocumented level of isolation from CT coregistered elec-troanatomic maps is the impact of the catheter equipment oncausing distension and deformation of the tissue interface ofthe LA wall and PVs,17 possibly allowing a more distal migra-tion of the balloon catheter into the LA–PV junction duringpositioning and energy delivery. Whether balloon catheterdesign can be further modified to achieve energy deliverywithin the PV antrum and potentially at other sites withinthe left atrium awaits further evaluation. Our increased ap-preciation of the asymmetry, complexity, and variability inthe observed anatomy of the LA–PV junction19,20 creates asignificant challenge for the successful design of a “one-size-fits-all” balloon catheter.

The preliminary reported outcomes from this patient co-hort and from a larger series of patients who have undergone

18 Journal of Cardiovascular Electrophysiology Vol. 19, No. 1, January 2008

current-generation laser balloon-based ablation appear to becomparable to success rates from conventional catheter ab-lation procedures in patients with paroxysmal atrial fibrilla-tion.21 The increased emphasis on targeting the more proxi-mal PV–LA junction9-11 and non-PV left atrial and right atrialsites for ablation in nonparoxysmal patterns of atrial fibril-lation12 may, however, limit the utility of balloon catheter-based therapies in these settings.

Study Limitations

The technology of CT image integration with real-timeelectroanatomic catheter mapping used at the time of per-forming these studies had several limitations that preventeda quantitative analysis of the level of isolation with respectto the PV-LA junction. The anatomic level of PV isolationwas able to be descriptively judged with a high degree of cer-tainty based on ostial landmark points attached to the elec-troanatomic maps and confirmed by ICE imaging.

The exclusion of patients with significantly dilated leftatria from the current study precludes any assessment of therelative seating of these balloon catheter systems within theLA–PV junction in the setting of distorted anatomy, althoughprior MRI studies have suggested that ostial diameters do notappear to vary significantly between patients with paroxysmaland persistent forms of atrial fibrillation.19 The anatomic levelof isolation in patients with significant LA dilatation will,however, require confirmation in future studies.

Conclusion

Current design balloon catheter ablation systems achieveelectrical disconnection distal in the LA–PV junction, nearor at the tubular ostium of the PVs. This may limit the resultsof such systems in treating nonparoxysmal forms of atrialfibrillation.

References

1. Cappato R, Calkins H, Chen SA, Davies W, Iesaka Y, Kalman J, KimYH, Klein G, Packer D, Skanes A: Worldwide survey on the methods,efficacy and safety of catheter ablation for human atrial fibrillation.Circulation 2005;111:1100-1105.

2. Martin A, Benbow LJ, Butrous GS, Leach C, Camm AJ: Five-yearfollow-up of 101 elderly patients by means of long-term ambulatorycardiac monitoring. Eur Heart J 1984;5:592-596.

3. Marrouche NF, Dresing T, Cole C, Bash D, Saad E, Balaban K, PaviaS, Schweikert R, Saliba W, Abdul-Karim A, Pisano E, Fanelli R, TchouP, Natale A: Circular mapping and ablation of the pulmonary vein fortreatment of atrial fibrillation: Impact of different catheter techniques.J Am Coll Cardiol 2002;40:464-474.

4. Haissaguerre M, Jais P, Shah DC, Garrigue S, Takahashi A, LavergneT, Hocini M, Peng JT, Roudaut R, Clementy J: Electrophysiologicalendpoint for catheter ablation of atrial fibrillation initiated from multiplepulmonary vein foci. Circulation 2000;101:1409-1417.

5. Chen SA, Hsieh MH, Tai CT, Tsai CF, Prakash VS, Yu WC, Hsu TL,Ding YA, Chang MS: Initiation of atrial fibrillation by ectopic beatsoriginating from the pulmonary veins: Electrophysiological characteris-tics, pharmacological responses and effects of radiofrequency ablation.Circulation 1999:100;1879-1886.

6. Oral H, Knight BP, Tada H, Ozayadin M, Chugh A, Hasan S, ScharfC, Lai SWK, Greenstein R, Pelosi F Jr, Strickberger A, Morady F: Pul-monary vein isolation for paroxysmal and persistent atrial fibrillation.Circulation 2002;105:1077-1081.

7. Natale A, Pisano E, Shewchik J, Bash D, Fanelli R, Potenza D,Santarelli P, Schweikert R, White R, Saliba W, Kanagaratnam L,Tchou P, Lesh M: First human experience with pulmonary vein iso-lation using a through-the-balloon circumferential ultrasound abla-tion system for recurrent atrial fibrillation. Circulation 2000;102:1879-1882.

8. Wong T, Markides V, Peters N, Davies DW: Anatomical left atrialcircumferential ablation to electrically isolate pulmonary veins using anovel focused ultrasound balloon catheter. Heart Rhythm 2006;3:370-371.

9. Oral H, Scharf C, Chugh A, Hall B, Cheung P, Good E, VeerareddyS, Pelosi F Jr, Morady F: Catheter ablation for paroxysmal atrial fib-rillation. Segmental pulmonary vein ostial ablation versus left atrialablation. Circulation 2003;108:2355-2360.

10. Ouyang F, Bansch D, Ernst S, Schaumann A, Hachiya H, Chen M,Chun J, Falk P, Khanedani A, Antz M, Kuck KH: Complete isolationof left atrium surrounding the pulmonary veins. New insights fromthe double-lasso technique in paroxysmal atrial fibrillation. Circulation2004;110:2090-2096.

11. Verma A, Marrouche NF, Natale A: Pulmonary vein antrum isolation:Intracardiac echocardiography-guided technique. J Cardiovasc Electro-physiol 2004;15:1335-1340.

12. Haissaguerre M, Sanders P, Hocini M, Takahashi Y, Rotter M, Sacher F,Rostock T, Hsu LF, Bordachar P, Reuter S, Roudaut R, Clementy J, JaisP: Catheter ablation of long-lasting persistent atrial fibrillation: Criticalstructures for termination. J Cardiovasc Electrophysiol 2005;16:1125-1137.

13. Saad EB, Rossillo A, Saad CP, Martin DO, Bhargava M, Erciyes D,Bash D, Williams-Andrews M, Beheiry S, Marrouche NF, Adams J,Pisano E, Fanelli R, Potenza D, Raviele A, Bonso A, ThemistoclakisS, Brachmann J, Saliba WI, Schweikert RA, Natale A: Pulmonary veinstenosis after radiofrequency ablation of atrial fibrillation. Functionalcharacterization, evolution and influence on ablation strategy. Circula-tion 2003;108:3102-3107.

14. Arentz T, Jander N, von Rosenthal J, Blum T, Furmaier R, GornandtL, Josef Neumann F, Kalusche D: Incidence of pulmonary vein steno-sis 2 years after radiofrequency catheter ablation of refractory atrialfibrillation. Eur Heart J 2003;24:963-969.

15. Themistoclakis S, Wazni OM, Saliba W, Schweikert R, Bonso A,Rossillo A, Gordon M, Melsky J, Raviele A, Natale A: Endoscopicfiberoptic assessment of balloon occlusion of the pulmonary vein os-tium in humans: Comparison with phased-array intracardiac echocar-diography. Heart Rhythm 2006;3:44-49.

16. Natale A, Raviele A, Arentz T, Calkins H, Chen SA, Haissaguerre M,Hindricks G, Ho Y, Kuck KH, Marchlinski F, Napolitano C, PackerD, Pappone C, Prystowsky EN, Schilling R, Shah D, ThemistoclakisS, Verma A: Venice chart international consensus document on atrialfibrillation. J Cardiovasc Electrophysiol 2007;18:560-580.

17. Fahmy TS, Mlcochova H, Wazni OM, Patel D, Cihak R, Kanj M, Be-heiry S, Burkhardt JD, Dresing T, Hao S, Tchou P, Kautzner J, Schweik-ert R, Arruda M, Saliba W, Natale A: Intracardiac echo-guided imageintegration: Optimizing strategies for registration. J Cardiovasc Elec-trophysiol 2007;18:276-282.

18. Saliba W, Wilber D, Packer D, Marrouche NF, Schweikert RA, PisanoE, Shewchik J, Bash D, Fanelli R, Potenza D, Santarelli P, Tchou P,Natale A: Circumferential ultrasound ablation for pulmonary vein isola-tion: Analysis of acute and chronic failures. J Cardiovasc Electrophysiol2002;13:957-961.

19. Mansour M, Holmvang G, Sosnovik D, Migrino R, Abbara S, RuskinJ, Keane D: Assessment of pulmonary vein anatomic variability bymagnetic resonance imaging: implications for catheter ablation tech-niques for atrial fibrillation. J Cardiovasc Electrophysiol 2004:15;387-394.

20. Mlcohova H, Tintera J, Porod V, Peichl P, Cihak R, Kautzner J:Magnetic resonance angiography of pulmonary veins: Implicationsfor catheter ablation of atrial fibrillation. Pacing Clin Electrophysiol2005;28:1073-1080.

21. Reddy V, Neuzil P, Themistoclakis S, Bonso A, Rossillo A, RavieleA, Saliba W, Schweikert R, Ernst S, Kuck KH, Ruskin J, Natale A:Long-term single-procedure clinical results with an endoscopic balloonablation catheter for pulmonary vein isolation in patients with atrialfibrillation. Circulation 2006;II:747.