- Email: [email protected]
Impedance monitoring during catheter ablation of atrial fibrillation
Impedance monitoring during catheter ablation of atrial fibrillation Marmar Vaseghi, MD, David A. Cesario, MD, PhD, Miguel Valderrabano, MD, Noel G. Boyle, MD, PhD, Osman Ratib, MD, PhD, J. Paul Finn, MD, PhD, Isaac Wiener, MD, Kalyanam Shivkumar, MD, PhD From UCLA Cardiac Arrhythmia Center, Division of Cardiology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California. BACKGROUND Delivery of radiofrequency energy in proximity of a pulmonary vein can cause vein stenosis. A sudden decrease in impedance as the catheter is moved from the vein into the left atrium (LA) has been used to define the pulmonary vein-LA transition during ablation procedures. OBJECTIVES The purpose of this study was to define the variables affecting impedance measurement. METHODS In vitro analysis of impedance was performed in a saline bath using sheaths and a plastic stereolithographic model of the LA. Impedance was continuously monitored during a calibrated pullback from the pulmonary vein into the LA in 37 veins of 10 patients referred for catheter ablation. Location of the catheter was confirmed by the following imaging modalities: intracardiac echocardiography, contrast venography, electroanatomic mapping, and computed tomography/magnetic resonance imaging (offline) in all patients. RESULTS Larger cross-sectional areas containing the catheter correlated with lower impedance in an exponential manner both with respect to sheath size (R2 ⫽ 0.99) and in the stereolithographic model (R2 ⫽ 0.91). In vivo, the impedance in the pulmonary veins decreased in an exponential manner as the catheter was pulled back into the LA. However, impedance at the vein orifice was not significantly higher than the LA. A defined cutoff value for defining the pulmonary vein-LA transition could not be identified. CONCLUSION The primary determinant of impedance is the cross-sectional area of the space containing the catheter. Impedance monitoring alone does not guarantee a catheter tip position outside the pulmonary vein. Intraprocedural imaging confirmation should be considered to avoid radiofrequency application within pulmonary veins. KEYWORDS Impedance; Pulmonary vein stenosis; Catheter ablation (Heart Rhythm 2005;2:914 –920) © 2005 Heart Rhythm Society. All rights reserved.
Introduction Pulmonary vein (PV) stenosis is a well-known complication of catheter ablation of atrial fibrillation that occurs regardDr. Shivkumar is supported by the Doris Duke Charitable Foundation, New York, and the American Heart Association. Dr. Vaseghi is supported by the American Heart Association. Dr. Cesario is supported by a Pfizer Fellowship Grant. Presented at the 2003 Annual Scientific Sessions of the American Heart Association. Address reprint requests and correspondence: Dr. Kalyanam Shivkumar, UCLA Cardiac Arrhythmia Center, Division of Cardiology, Department of Medicine, 47-123 CHS, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, California 90095-1679. E-mail address: [email protected]. (Received April 13, 2005; accepted June 11, 2005.)
less of the type of ablation (targeted focal “sites,” circumferential or segmental isolation at the venoatrial junction, or electrical isolation of PVs).1–12 Furthermore, with the dramatically increasing rise in atrial fibrillation ablations performed worldwide, the incidence of this complication likely will increase.2 The rate of asymptomatic PV stenosis following catheter ablation procedures has been reported to be as high as 16% to 24%.13,14 The rate of symptomatic stenosis, usually caused by the involvement of more than one PV with ⬎70% stenosis, has been reported in 1% to 10% of patients.1–7,13–16 The site of stenosis typically is within 1 cm of the pulmonary ostia, although it can range between 0.4 and 3.5 cm.1,14 Moreover, ablation in and around the PVs induces changes in morphology and mechanical function that extend beyond the ablation zone, and inadvertent ra-
1547-5271/$ -see front matter © 2005 Heart Rhythm Society. All rights reserved.
doi:10.1016/j.hrthm.2005.06.007
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Impedance Monitoring During Catheter Ablation of AF
diofrequency energy application within the PV can lead to stenosis.17 Continuous measurement of impedance via a roving catheter has demonstrated higher values in the PVs than in the left atrium (LA). It has been suggested that impedance monitoring during radiofrequency catheter ablation, especially when an abrupt increase of ⬎4 ⍀ is noted, can detect catheter movement into a PV.18 The purpose of this study was to assess the impact of the cross-sectional area of the vessel/chamber containing the catheter on impedance and to determine the accuracy and limitations of impedance monitoring in identifying catheter tip location during ablation of atrial fibrillation.
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Methods
tion and no arrhythmias. CT scans were used to provide high resolution (1 mm rendered digital imaging communications in medicine [DICOM] images that can be used to create stereolithography files for generation of the threedimensional model). Impedance was measured as a function of cross-sectional area of the PV and distance of the catheter tip from the LA. This model was primarily used because of the uniformly high resistance of plastic, allowing for the evaluation of impedance as a function of distance and area without introducing factors caused by variance in tissue composition and resistance. After submerging the LA model in a saline bath, impedance was measured via an ablation catheter in the LA, the left inferior pulmonary vein (LIPV) os, and then 1, 2, and 3 cm into the LIPV. The cross-sectional area at each location was calculated based on the measured diameters of the model. An impedance curve as a function of area was obtained.
Patient characteristics
MRI and CT
Between June 2002 and June 2004, 110 patients underwent LA catheter ablation procedures for atrial fibrillation at UCLA Medical Center, Los Angeles, California (USA). Of these 110 patients, 10 (9 men and 1 woman; mean age 57 ⫾ 12 years) underwent extensive characterization of LA anatomy correlated with detailed impedance recordings. The average atrial size in our patients was 33 ⫾ 12 mm based on transthoracic echocardiography. Mean ejection fraction (EF) was 0.51 ⫾ 0.1. Four patients had paroxysmal atrial fibrillation. Six patients had persistent atrial fibrillation. All of these patients underwent cardiac magnetic resonance imaging (MRI) or computed tomography (CT) prior to ablation. This study was approved by the UCLA institutional review board.
MRI is a valuable tool in evaluating the number, size, and shape of PVs and has been used to estimate the crosssectional area of PVs during the cardiac cycle.19,20 Furthermore, the PV ostial dimensions obtained by intracardiac echocardiography, CT, and venography are all significantly correlated.21 Therefore, in this study, all 10 patients underwent cardiac imaging within 4 weeks prior to the ablation procedure to evaluate the geometry of the LA and PVs. Nine patients underwent MRI prior to ablation. MRI was performed using a 1.5-T Siemens SONATA scanner (Siemens Corp. New York, NY). Axial and coronal, 6-mm halfFourier acquisition single-shot turbo spin-echo (HASTE), images were acquired. This was followed by cine images acquired in multiple oblique planes across the heart and cardiac cavities. Three dimensional magnetic resonance angiography images of the heart and thoracic vessels then were acquired in contiguous coronal planes after uneventful intravenous injection of 40 ml gadolinium. Images were transferred to the image processing laboratory for threedimensional rendering and quantitative evaluation. Cardiac CT scan was performed prior to ablation in one patient secondary to previous pacemaker placement. CT angiography was performed on a Siemens Sensation 16 ultra-fast multislice spiral CT scanner. An initial noncontrast gated scan was performed with continuous 3-mm thick sections. Thereafter, a gated contrast angiogram sequence was performed during uneventful intravenous injection of 125 ml Omnipaque 350, followed by 35 ml saline in a single breath-hold. Slices (1 mm) timed to coincide with the transit of the contrast in the LA were acquired. From the axial images, additional three-dimensional volume rendering and image reformatting were performed in the UCLA Radiology Image Processing Laboratory. The MRI and CT images were also used postprocedure to correlate the impedances measured at 1, 2, 4, and 5 cm with the cross-sectional area of each PV based on the axial images acquired at each site. The diameter was measured
Effect of cross-sectional area on impedance We tested the hypothesis that the major determinant of impedance was the cross sectional area of the space (vessel/ chamber) surrounding the catheter tip. We mimicked transit in and out of PVs by determining the impedance changes when an ablation catheter was placed inside various sheaths (7Fr, 8Fr, 9Fr, 10.5Fr, 12.5Fr) in a saline bath. Impedance was measured using a Stockert Generator (Biosense-Webster, Diamond Bar, CA, USA) with a 4-mm-tip ablation catheter. Impedance was recorded at 2-mm intervals starting with a catheter location 2 mm within each sheath. The catheter subsequently was advanced 10 mm from the sheath opening. Each measurement was repeated three times. Impedance curves for each sheath size were obtained.
Stereolithographic study A stereolithographic plastic model of the LA was constructed with all four PVs attached based on a three-dimensional LA CT image of a patient with normal cardiac func-
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using the Vitrea imaging program. Each area was estimated to be a circle, and the area was obtained using diameter measurements.
Electrophysiologic procedure Informed consent was obtained from all patients. All procedures were performed with the patient under conscious sedation or under general anesthesia. Following a standard transseptal puncture, the intraprocedural activated clotting time was maintained between 250 and 350 seconds using intravenous heparin. All patients underwent an LA catheter ablation procedure that involved placement of ablation lines encircling the PVs and a line connecting the LIPV and the mitral annulus, under intracardiac echocardiography and electroanatomic mapping guidance. Angiograms of the PVs were obtained in all cases. An initial LA angiogram was obtained using a Berman angiographic catheter (USCI), Arrow International, Reading, PA and individual veins were imaged after engagement by the transseptal sheath. Veins were imaged in the anteroposterior/lateral and right/left anterior oblique views.
Identification of PVs and impedance measurement Reconstruction of the LA shell with three-dimensional electroanatomic mapping system (CARTO) was performed in all cases. Cannulation of PVs with a mapping catheter was performed under fluoroscopic and intracardiac echocardiographic guidance (AcuNav, Siemens, Sunnyvale, CA, USA). Electroanatomic tags of the veins were made in all cases. The PV ostia were tagged on the electroanatomic mapping system as reference points and their location confirmed based on intracardiac echocardiographic imaging.
Impedance monitoring Real-time impedance measurements were obtained using a Navi-Star (Biosense-Webster, Diamond Bar, CA) catheter that was linked to a Stockert (Biosense-Webster) radiofrequency generator. Each vein was accessed twice to ensure accurate measurements. The radiofrequency generator/ablation system provided real-time impedance measurement by applying a constant source of current. A grounding pad was placed over the thigh or the liver. Movement of the catheter into a wedge position within a vein and withdrawal of the catheter into the transseptal sheath were associated with the highest impedance values.
Figure 1 Impedance as a function of distance of the catheter from the sheath opening. Top: Increasing sheath size is associated with lower impedance regardless of distance from the sheath, especially up to 4 mm. Bottom: Impedance as a function of the area of the sheaths (in millimeters) for the various distances of the catheter from the opening of the sheath. As the cross-sectional area of the sheath containing the catheter increases, the impedance curves decrease.
used to evaluate trends and regression lines. The exponential data were analyzed using exponential regression analysis.
Results In vitro assessment of cross-sectional area on impedance
Statistical analysis Comparison of impedance measurements were performed with the paired t-test or analysis of variance (ANOVA) with repeated measures. Continuous variables are expressed as mean ⫾ 1 SD and compared by Student’s t-test. P ⬍ .05 was considered significant. The correlation coefficient was
Baseline impedance in the saline bath was 96 ⫾ 2 ⍀. Impedance as a function of sheath size and area and distance of catheter tip from the sheath opening is shown in Figure 1. This impedance decreased in an exponential manner as the catheter was advanced out of the sheath (R2 ⫽ 0.99). Impedance was higher in the smaller sheaths regardless of
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Impedance Monitoring During Catheter Ablation of AF
Figure 2 Impedance as a function of pulmonary vein area in the stereolithographic left atrial model. Note the exponential decrease in impedance as the cross-sectional area of the pulmonary vein increases. The red line indicates the first-order exponential fitted curve. Inset shows a picture of the stereolithographic model.
distance from the sheath (P ⬍ .02), especially within 4 mm of the sheath opening (P ⬍ .001). These data suggest that a major determinant of impedance was the cross-sectional area of the space surrounding the catheter tip. This finding can explain the increase in impedance as a catheter is progressively moved into a wedge position within a PV.
Impedance in the stereolithographic atrial model
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Figure 3 Impedance as a function of distance from the pulmonary ostia in the atrial model. Note the linear rise in impedance as the catheter is progressively moved into a more wedged position in the stereolithographic model.
the PV ostium as the catheter was advanced further into the PV. The change in impedance compared to the venoatrial junction for the LSPV at different locations as confirmed by fluoroscopy and intracardiac echocardiography is shown in Figure 5. The average change in impedance as a function of the distance from the LA observed in all four PVs is shown in Figure 6. There was no significant difference between impedance measured at the PV ostia compared to the LA (mean change 0.13 ⫾ 1.7 ⍀, P ⫽ .32). Analysis of the
Impedance as function of area and distance within the LIPV of an atrial model submerged in a saline bath is shown in Figures 2 and 3. Impedance uniformly increased in a linear fashion as the catheter was advanced into the PV (R ⫽ 0.99, P ⬍ .001). The area at each location was assumed to be a circle and estimated based on the measured coronal diameter. The impedance as a function of area (Figure 2) shows an exponential decrease as the area increases (R2 ⫽ 0.91, P ⫽ .027).
Impedance as function of distance in vivo Impedance measurements in the LA of 10 patients and from 10 right inferior pulmonary veins (RIPVs), 10 right superior pulmonary veins (RSPVs), 7 LIPVs, and 10 left superior pulmonary veins (LSPVs) were obtained. Measurements were taken in the PVs at the PV ostium, 1, 2, 4, and 5 cm within each PV. Veins that could not be cannulated repeatedly because of steep angulation were excluded. Furthermore, a right middle PV was encountered in two patients in this study, and the impedance was uniformly high within those veins, precluding a detailed analysis. The values obtained for the LSPV and the RSPV of one patient superimposed on the patient’s MRI are shown in Figure 4. The average change in impedance increased with distance from
Figure 4 Impedance map of the left superior pulmonary vein (LSPV) and right superior pulmonary vein (RSPV) obtained during ablation superimposed on the magnetic resonance images obtained before ablation in one patient. Note that the values demonstrated are the actual impedances measured in vivo. The impedances measured in the left atrium are lower than in the pulmonary veins. However, the difference in impedance between the left atrium and the pulmonary vein ostia is unremarkable. LIPV ⫽ left inferior pulmonary vein; RIPV ⫽ right inferior pulmonary vein.
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Figure 5 Fluoroscopy and corresponding intracardiac echocardiographic images confirming catheter location and impedance values measured at various points along the pullback from the vein. The change in the measured impedance (red diamonds) on the graph as a function of distance is superimposed on the axial magnetic resonance images of the pulmonary vein (red triangles). Note that the further the catheter location from the left atrium, the higher the impedance measured. However, impedance measured at the venoatrial junction and 1 cm within the vein are not significantly different secondary to the nature of the curve.
impedance at 1 cm of all 37 PVs showed a significant average increase of 4.2 ⫾ 5.4 ⍀ (P ⬍ .01) compared with the LA. However, the increase in average impedance was not uniform among the four PVs. The change in impedance at 1 cm compared with the LA was 6.8 ⫾ 6.2 ⍀ (P ⬍ .01) for the LSPV, 3.3 ⫾ 2.1 W (P ⬍ .01) for LIPV, and 7.7 ⫾ 7.4 ⍀ (P ⬍ .01) for the RIPV. The change in impedance for the RSPV was 5.3 ⫾ 6.6 ⍀, but this change was not significant (P ⫽ .2). Impedance was measured with respect to the PV area in all 37 veins and plotted as a function of distance at 1, 2, 3, 4, and 5 cm into the PVs using MR and CT images. The cross-sectional area at each point then was calculated using PV diameter as measured by MRI and CT. An inverse relationship between PV diameter and impedance was noted (R ⫽ 0.91, P ⬍ .01). The average impedance increased exponentially as the cross-sectional area decreased (R2 ⫽ 0.93, P ⬍ .01). Qualitatively similar results were obtained in an additional 12 patients with ventricular dysfunction (data not shown). PV angiography was not performed in these cases to reduce radiocontrast use.
Discussion PV stenosis is a well-established complication of atrial fibrillation ablation.1–13 Given the increasing worldwide
prevalence of ablation procedures performed (18 patients underwent procedures in 1995 vs 5,050 patients in 2002),2 the incidence of PV stenosis likely will increase. Of the total
Figure 6 Average change in impedance in the pulmonary veins as a function of distance from the pulmonary vein ostium. The exponential fitted curves are shown. Note the exponential decline in impedance as the catheter is pulled back into the venoatrial junction. This holds true for all four pulmonary veins. Note that the average change in impedance between the venoatrial junction and 1 cm into the pulmonary vein is very small, especially compared with other locations within the pulmonary vein. LIPV ⫽ left inferior pulmonary vein; LSPV ⫽ left superior pulmonary vein; RIPV ⫽ right inferior pulmonary vein; RSPV ⫽ right superior pulmonary vein.
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Impedance Monitoring During Catheter Ablation of AF
of 8,745 patients in one study, 6,000 underwent a procedure to electrically isolate the PVs.2 To decrease the incidence of this complication, impedance monitoring to detect inadvertent catheter movement into the PV has been suggested as a method for preventing radiofrequency energy application into the PV.18 The goal of this study was to gain a better understanding of the factors that affect impedance in the electrophysiology laboratory and to assess the value of impedance monitoring during ablation procedures. In this study, in vitro analysis demonstrated that a decrease in sheath size (a surrogate for vein size) can cause a rise in impedance. Furthermore, a stereolithographic model with uniformly high impedance can demonstrate that the diameter of the cavity containing the catheter can be the sole determinant of impedance, with larger cavities of greater cross-sectional area having lower impedances. In vivo, there was an exponential rise in impedance as the catheter was advanced into the PV, confirming the in vitro data. The impedance was found to be significantly lower in the proximal than in the distal PV. Although prior studies have suggested that factors such as the amount of interposed lung tissue and the architecture of myocardial fibrils account for the impedance rise inside PVs,18,22 our data suggest that the decreased cross-sectional area of the veins is the major factor. A rise in impedance with distance was demonstrated in vitro, where tissue composition and anatomy are not a factor. Furthermore, with respect to cross-sectional area, this rise was exponential. The same exponential rise in impedance with decreasing cross-sectional area was also observed in vivo. This study shows that the true determinant of impedance is the cross-sectional area, both in vitro and in vivo, not tissue anatomy or histology, significantly improving our understanding of impedance. This physiology has been applied to measure arterial lumen area with an impedance catheter.23 Radiofrequency application even in the proximity of the PVs or at the ostia can cause stenosis.1,14,17 PV stenosis occurs regardless of the type of atrial fibrillation procedure performed, even when radiofrequency energy has been delivered outside the PV ostia.1 As the majority of the PV stenosis occurs within 1.2 cm of the pulmonary ostia,1,14 this area was of most interest in this study. In vivo and in vitro, the change in impedance from the LA to the PV ostia was not significant for any of the PVs studied. Contrary to the findings of previous studies,18 the changes in impedance between PV ostia and 1 cm into the PV were not uniform, and a cutoff value for reliable identification of catheter location could not be defined. Indeed, very small changes in impedance could signify movement into the proximal vein. The average change in impedance at 1 cm for the LIPV could be as little as 3.3 ⍀. For the RSPV vein, the change in impedance was not significant compared with the LA, an observation that has been made by others.18 Thus, impedance monitoring cannot detect catheter movement into the proximal PV.
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Several differences between the in vitro and in vivo studies are noteworthy. Impedances measured in vivo were lower in absolute value compared to the in vitro studies. This could be in part due to the composition of the vein wall compared with the stereolithographic model and sheaths. Also, in the in vitro sheath model, differences in impedance even 2 mm outside of the sheath were noted. Similar results were demonstrated in the stereolithographic plastic model. In contrast, the impedance measurements near the ostia in vivo show much smaller changes as the catheter is moved in and out of the vein ostia. Because the confounding effects of cardiac motion are not a factor in vitro, submillimeter accuracy in catheter location can be achieved. Finally, at 2 mm outside of the sheaths, a large difference was noted between various sheath sizes. The most likely reason for this change is that a higher effective area of the electrode tip is in contact with electrolytes with larger compared with smaller sheaths. Our study did confirm that a very acute rise in impedance (⬎250 ⍀) likely is secondary to movement of catheter deep (⬎2 cm) into the PV and/or back inside the sheath. This held true for both the in vivo and the in vitro experiments. The acute rise as the catheter is advanced into smaller cross-sectional areas of the PV in vivo may be explained by the insulating effect of air in the lungs. Clearly, radiofrequency application (or any other energy deliver) should not be allowed at sites showing high impedance values.
Study limitations Although catheter position was confirmed with contrast venography, fluoroscopy, and intracardiac echocardiography during the procedure, simultaneous cardiac MR images could not be obtained during the procedure (i.e., using open magnet MR). Impedance measurements then had to be superimposed on cardiac MR images postprocedure. Although this could serve as a source of error, given the accuracy of MRI in determining volume, cross-sectional area, and distance, it likely did not play a major role in the results. Dynamic changes of vein orifice are an unlikely source of major error. Sheaths have a small taper at their tip, which varies slightly among the different sheath types and sizes; therefore, we could not account for the effect of this difference in cross-sectional area on our impedance curves. Thirty-seven PVs from 10 patients were studied, a rather small number. However, despite the small number of PVs, the in vivo and in vitro studies of the effect of area on impedance correlated extremely well, with correlation coefficients ⬎0.9 and P ⬍ .01. Therefore, we do not believe the small number of patients had a great impact on the results and the understanding of the factors that affect impedance. Data using three imaging modalities (intracardiac echocardiography, electroanatomic mapping, and MRI) in an additional 12 patients showed identical results.
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Conclusion In this study, the major determinant of impedance, both in vitro and in vivo, was the cross-sectional area of the cavity containing the ablation catheter. An exponential decline in impedance was demonstrated as the catheter was pulled back from the PV into the LA. During LA catheter ablation in live patients, no significant difference in impedance at the LA compared with the PV ostia was observed. Although there was a rise in impedance in three of four PVs at 1 cm compared with the LA, this rise was nonuniform. This is the first study to analyze factors affecting impedance in vivo and in vitro in a systematic fashion. The results give physicians a better understanding of a parameter routinely measured during ablation procedures, its values and its limitations.
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References 15. 1. Packer DL, Keelan P, Munger TM, Breen JF, Asirvatham S, Peterson LA, Monahan KH, Hauser MF, Chandrasekaran K, Sinak LJ, Holmes DR Jr. Clinical presentation, investigation, and management of pulmonary vein stenosis complicating ablation for atrial fibrillation. Circulation 2005;111:546 –554. 2. Cappato R, Calkins H, Chen S, Davies W, Iesaka Y, Kalman J, Kim Y, 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. 3. Haissaguerre M, Jais P, Shah DC, Garrigue S, Takahashi A, Lavergne T, Hocini M, Peng JT, Toudaut R, Clementy J. Electrophysiological end point for catheter ablation of atrial fibrillation initiated from multiple pulmonary vein foci. Circulation 2000;101:1409 –1417. 4. Chen SA, Hseih MH, Tai CT, Tsai CF, Prakash Vs, Yu WC, Hsu TL, Ding YA, Chang MS. Initiation of atrial fibrillation by ectopic beats originating from the pulmonary veins: electrophysiologic characteristics, pharmacological responses, and effects of radiofrequency ablation. Circulation 1999;100:1879 –1886. 5. Packer DL, Asirvatham S, Monahan KH, Shen WK, Rea RF, Hammill SC. Progression of pulmonary vein stenosis in patients following focal atrial fibrillation ablation (abstr). Circulation 2001;104(Suppl II):II-461. 6. Gerstenfeld EP, Guerra P, Sparks PB, Hattori K, Lesh MD. Clinical outcome after radiofrequency catheter ablation of focal atrial fibrillation triggers. J Cardiovasc Electrophysiol 2001;12:900 –908. 7. Leite L, Asirvatham S, Hammill SC, Friedman PA, Munger TM, Shen WK, Packer DL. Clinical and electrophysiological predictors of pulmonary vein stenosis following radiofrequency catheter ablation for atrial fibrillation (abstr). Pacing Clin Electrophysiol 2002;25:559. 8. Kanagaratnam L, Tomassoni G, Schweikert R, Pavia S, Bash D, Beheiry S, Lesh M, Niebauer M, Saliba W, Chung M, Tchou P, Natale A. Empirical pulmonary vein isolation in patient with chronic atrial fibrillation using a three-dimensional non fluoroscopic mapping system: long term follow-up. Pacing Clin Electrophysiol 2001;24:1749 – 1774. 9. Marrouche NF, Dresing T, Cole C, Bash D, Saad E, Balaban K, Pavia SV, Schweikert R, Saliba W, Abdul-Karim A, Pisano E, Fanelli R, Tchou P, Natale A. Circular mapping and ablation of the pulmonary
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vein for treatment of atrial fibrillation: impact of different catheter technologies. J Am Coll Cardiol 2004;40:464 – 474. Taylor GW, Kay GN, Zheng X, Bishop S, Ideker RE. Pathological effects of extensive radiofrequency energy applications in the pulmonary veins in dogs. Circulation 2000;101:1736 –1742. Robbins IM, Colvin EV, Doyle TP, Kemp WE, Loyd JE, McMahon WS, Kay GN. Pulmonary vein stenosis after catheter ablation of atrial fibrillation. Circulation 1998;98:1769 –1775. Yu WC, Hsu TL, Tai CT, Tsai CF, Hsieh MH, Lin WS, Lin YK, Tsao HM, Ding YA, Chang MS, Chen SA. Acquired pulmonary vein stenosis after radiofrequency catheter ablation of focal atrial fibrillation. J Cardiovasc Electrophysiol 2000;11:677– 681. Saad EB, Rossilo 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, Themistoclakis S, Brachmann J, Saliba WI, Schweikert RA, Natale A. Pulmonary vein stenosis after radiofrequency ablation of atrial fibrillation: functional characterization, evolution, and influence of the ablation strategy. Circulation 2003;108:3102–3107. Jin Y, Ross DL, Thomas SP. Pulmonary vein stenosis and remodeling after electrical isolation for treatment of atrial fibrillation: short- and medium-term follow-up. Pacing Clin Electrophysiol 2004;27:1362– 1370. Purerfellner H, Aichinger J, Martinek M, Nesser HJ, Cihal R, Gschwendtner M, Dierneder J. Incidence, management, and outcome in significant pulmonary vein stenosis complicating ablation for atrial fibrillation. Am J Cardiol 2004;93:1428 –1431, A10. Arentz T, Jander N, von Rosenthal J, Blum T, Furmaier R, Gornandt L, Josef Neumann F, Kalusche D. Incidence of pulmonary vein stenosis 2 years after radiofrequency catheter ablation of refractory atrial fibrillation. Eur Heart J 2004;24:963–969. Schwartzman D, Kanzaki H, Bazaz R, Gorscan J 3rd. Impact of catheter ablation on pulmonary vein morphology and mechanical function. J Cardiovasc Electrophysiol 2004;15:161–167. Cheung P, Hall B, Chugh A, Good E, Lemola K, Han J, Tamirisa K, Pelosi F Jr, Morady F, Oral H. Detection of inadvertent catheter movement into a pulmonary vein during radiofrequency catheter ablation by real-time impedance monitoring. J Cardiovac Electrophysiol 2004;15:674 – 678. Kato R, Lickfett L, Meininger G, Dickfeld T, Wu R, Juang G, Angkeow P, LaCorte J, Bluemke D, Berger R, Halperin HR, Calkins H. Pulmonary vein anatomy in patients undergoing catheter ablation of atrial fibrillation: lessons learned by use of magnetic resonance imaging. Circulation 2003;107:2004 –2010. Bowman AW, Kovacs SJ. Prediction and assessment of time-varying pulmonary vein area via MRI and Doppler echocardiography. Am J Physiol Heart Circ Physiol 2005;288:H280 –H286. Wood MA, Wittkamp M, Henry D, Martin R, Nixon JV, Shepard RK, Ellenbogen KA. A comparison of pulmonary vein ostial anatomy by computerized tomography, echocardiography, and venography in patients with atrial fibrillation having radiofrequency catheter ablation. Am J Cardiol 2004;93:49 –53. Hocini M, Ho SY, Kawara T, Linnenbank AC, Potse M, Shah D, Jais P, Janse MJ, Haissaguerre M, De Bakker JM. Electrical conduction in canine pulmonary veins: electrophysiological and anatomic correlation. Circulation 2002;105:2442–2448. Kassab GS, Lontis ER, Horlyck A, Gregersen H. Novel method for measurement of medium size arterial lumen area with an impedance catheter: in vivo validation. Am J Physiol Heart Circ Physiol 2005; 288:H2014 –H2020.
Introduction Pulmonary vein (PV) stenosis is a well-known complication of catheter ablation of atrial fibrillation that occurs regardDr. Shivkumar is supported by the Doris Duke Charitable Foundation, New York, and the American Heart Association. Dr. Vaseghi is supported by the American Heart Association. Dr. Cesario is supported by a Pfizer Fellowship Grant. Presented at the 2003 Annual Scientific Sessions of the American Heart Association. Address reprint requests and correspondence: Dr. Kalyanam Shivkumar, UCLA Cardiac Arrhythmia Center, Division of Cardiology, Department of Medicine, 47-123 CHS, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, California 90095-1679. E-mail address: [email protected]. (Received April 13, 2005; accepted June 11, 2005.)
less of the type of ablation (targeted focal “sites,” circumferential or segmental isolation at the venoatrial junction, or electrical isolation of PVs).1–12 Furthermore, with the dramatically increasing rise in atrial fibrillation ablations performed worldwide, the incidence of this complication likely will increase.2 The rate of asymptomatic PV stenosis following catheter ablation procedures has been reported to be as high as 16% to 24%.13,14 The rate of symptomatic stenosis, usually caused by the involvement of more than one PV with ⬎70% stenosis, has been reported in 1% to 10% of patients.1–7,13–16 The site of stenosis typically is within 1 cm of the pulmonary ostia, although it can range between 0.4 and 3.5 cm.1,14 Moreover, ablation in and around the PVs induces changes in morphology and mechanical function that extend beyond the ablation zone, and inadvertent ra-
1547-5271/$ -see front matter © 2005 Heart Rhythm Society. All rights reserved.
doi:10.1016/j.hrthm.2005.06.007
Vaseghi et al
Impedance Monitoring During Catheter Ablation of AF
diofrequency energy application within the PV can lead to stenosis.17 Continuous measurement of impedance via a roving catheter has demonstrated higher values in the PVs than in the left atrium (LA). It has been suggested that impedance monitoring during radiofrequency catheter ablation, especially when an abrupt increase of ⬎4 ⍀ is noted, can detect catheter movement into a PV.18 The purpose of this study was to assess the impact of the cross-sectional area of the vessel/chamber containing the catheter on impedance and to determine the accuracy and limitations of impedance monitoring in identifying catheter tip location during ablation of atrial fibrillation.
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tion and no arrhythmias. CT scans were used to provide high resolution (1 mm rendered digital imaging communications in medicine [DICOM] images that can be used to create stereolithography files for generation of the threedimensional model). Impedance was measured as a function of cross-sectional area of the PV and distance of the catheter tip from the LA. This model was primarily used because of the uniformly high resistance of plastic, allowing for the evaluation of impedance as a function of distance and area without introducing factors caused by variance in tissue composition and resistance. After submerging the LA model in a saline bath, impedance was measured via an ablation catheter in the LA, the left inferior pulmonary vein (LIPV) os, and then 1, 2, and 3 cm into the LIPV. The cross-sectional area at each location was calculated based on the measured diameters of the model. An impedance curve as a function of area was obtained.
Patient characteristics
MRI and CT
Between June 2002 and June 2004, 110 patients underwent LA catheter ablation procedures for atrial fibrillation at UCLA Medical Center, Los Angeles, California (USA). Of these 110 patients, 10 (9 men and 1 woman; mean age 57 ⫾ 12 years) underwent extensive characterization of LA anatomy correlated with detailed impedance recordings. The average atrial size in our patients was 33 ⫾ 12 mm based on transthoracic echocardiography. Mean ejection fraction (EF) was 0.51 ⫾ 0.1. Four patients had paroxysmal atrial fibrillation. Six patients had persistent atrial fibrillation. All of these patients underwent cardiac magnetic resonance imaging (MRI) or computed tomography (CT) prior to ablation. This study was approved by the UCLA institutional review board.
MRI is a valuable tool in evaluating the number, size, and shape of PVs and has been used to estimate the crosssectional area of PVs during the cardiac cycle.19,20 Furthermore, the PV ostial dimensions obtained by intracardiac echocardiography, CT, and venography are all significantly correlated.21 Therefore, in this study, all 10 patients underwent cardiac imaging within 4 weeks prior to the ablation procedure to evaluate the geometry of the LA and PVs. Nine patients underwent MRI prior to ablation. MRI was performed using a 1.5-T Siemens SONATA scanner (Siemens Corp. New York, NY). Axial and coronal, 6-mm halfFourier acquisition single-shot turbo spin-echo (HASTE), images were acquired. This was followed by cine images acquired in multiple oblique planes across the heart and cardiac cavities. Three dimensional magnetic resonance angiography images of the heart and thoracic vessels then were acquired in contiguous coronal planes after uneventful intravenous injection of 40 ml gadolinium. Images were transferred to the image processing laboratory for threedimensional rendering and quantitative evaluation. Cardiac CT scan was performed prior to ablation in one patient secondary to previous pacemaker placement. CT angiography was performed on a Siemens Sensation 16 ultra-fast multislice spiral CT scanner. An initial noncontrast gated scan was performed with continuous 3-mm thick sections. Thereafter, a gated contrast angiogram sequence was performed during uneventful intravenous injection of 125 ml Omnipaque 350, followed by 35 ml saline in a single breath-hold. Slices (1 mm) timed to coincide with the transit of the contrast in the LA were acquired. From the axial images, additional three-dimensional volume rendering and image reformatting were performed in the UCLA Radiology Image Processing Laboratory. The MRI and CT images were also used postprocedure to correlate the impedances measured at 1, 2, 4, and 5 cm with the cross-sectional area of each PV based on the axial images acquired at each site. The diameter was measured
Effect of cross-sectional area on impedance We tested the hypothesis that the major determinant of impedance was the cross sectional area of the space (vessel/ chamber) surrounding the catheter tip. We mimicked transit in and out of PVs by determining the impedance changes when an ablation catheter was placed inside various sheaths (7Fr, 8Fr, 9Fr, 10.5Fr, 12.5Fr) in a saline bath. Impedance was measured using a Stockert Generator (Biosense-Webster, Diamond Bar, CA, USA) with a 4-mm-tip ablation catheter. Impedance was recorded at 2-mm intervals starting with a catheter location 2 mm within each sheath. The catheter subsequently was advanced 10 mm from the sheath opening. Each measurement was repeated three times. Impedance curves for each sheath size were obtained.
Stereolithographic study A stereolithographic plastic model of the LA was constructed with all four PVs attached based on a three-dimensional LA CT image of a patient with normal cardiac func-
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using the Vitrea imaging program. Each area was estimated to be a circle, and the area was obtained using diameter measurements.
Electrophysiologic procedure Informed consent was obtained from all patients. All procedures were performed with the patient under conscious sedation or under general anesthesia. Following a standard transseptal puncture, the intraprocedural activated clotting time was maintained between 250 and 350 seconds using intravenous heparin. All patients underwent an LA catheter ablation procedure that involved placement of ablation lines encircling the PVs and a line connecting the LIPV and the mitral annulus, under intracardiac echocardiography and electroanatomic mapping guidance. Angiograms of the PVs were obtained in all cases. An initial LA angiogram was obtained using a Berman angiographic catheter (USCI), Arrow International, Reading, PA and individual veins were imaged after engagement by the transseptal sheath. Veins were imaged in the anteroposterior/lateral and right/left anterior oblique views.
Identification of PVs and impedance measurement Reconstruction of the LA shell with three-dimensional electroanatomic mapping system (CARTO) was performed in all cases. Cannulation of PVs with a mapping catheter was performed under fluoroscopic and intracardiac echocardiographic guidance (AcuNav, Siemens, Sunnyvale, CA, USA). Electroanatomic tags of the veins were made in all cases. The PV ostia were tagged on the electroanatomic mapping system as reference points and their location confirmed based on intracardiac echocardiographic imaging.
Impedance monitoring Real-time impedance measurements were obtained using a Navi-Star (Biosense-Webster, Diamond Bar, CA) catheter that was linked to a Stockert (Biosense-Webster) radiofrequency generator. Each vein was accessed twice to ensure accurate measurements. The radiofrequency generator/ablation system provided real-time impedance measurement by applying a constant source of current. A grounding pad was placed over the thigh or the liver. Movement of the catheter into a wedge position within a vein and withdrawal of the catheter into the transseptal sheath were associated with the highest impedance values.
Figure 1 Impedance as a function of distance of the catheter from the sheath opening. Top: Increasing sheath size is associated with lower impedance regardless of distance from the sheath, especially up to 4 mm. Bottom: Impedance as a function of the area of the sheaths (in millimeters) for the various distances of the catheter from the opening of the sheath. As the cross-sectional area of the sheath containing the catheter increases, the impedance curves decrease.
used to evaluate trends and regression lines. The exponential data were analyzed using exponential regression analysis.
Results In vitro assessment of cross-sectional area on impedance
Statistical analysis Comparison of impedance measurements were performed with the paired t-test or analysis of variance (ANOVA) with repeated measures. Continuous variables are expressed as mean ⫾ 1 SD and compared by Student’s t-test. P ⬍ .05 was considered significant. The correlation coefficient was
Baseline impedance in the saline bath was 96 ⫾ 2 ⍀. Impedance as a function of sheath size and area and distance of catheter tip from the sheath opening is shown in Figure 1. This impedance decreased in an exponential manner as the catheter was advanced out of the sheath (R2 ⫽ 0.99). Impedance was higher in the smaller sheaths regardless of
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Figure 2 Impedance as a function of pulmonary vein area in the stereolithographic left atrial model. Note the exponential decrease in impedance as the cross-sectional area of the pulmonary vein increases. The red line indicates the first-order exponential fitted curve. Inset shows a picture of the stereolithographic model.
distance from the sheath (P ⬍ .02), especially within 4 mm of the sheath opening (P ⬍ .001). These data suggest that a major determinant of impedance was the cross-sectional area of the space surrounding the catheter tip. This finding can explain the increase in impedance as a catheter is progressively moved into a wedge position within a PV.
Impedance in the stereolithographic atrial model
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Figure 3 Impedance as a function of distance from the pulmonary ostia in the atrial model. Note the linear rise in impedance as the catheter is progressively moved into a more wedged position in the stereolithographic model.
the PV ostium as the catheter was advanced further into the PV. The change in impedance compared to the venoatrial junction for the LSPV at different locations as confirmed by fluoroscopy and intracardiac echocardiography is shown in Figure 5. The average change in impedance as a function of the distance from the LA observed in all four PVs is shown in Figure 6. There was no significant difference between impedance measured at the PV ostia compared to the LA (mean change 0.13 ⫾ 1.7 ⍀, P ⫽ .32). Analysis of the
Impedance as function of area and distance within the LIPV of an atrial model submerged in a saline bath is shown in Figures 2 and 3. Impedance uniformly increased in a linear fashion as the catheter was advanced into the PV (R ⫽ 0.99, P ⬍ .001). The area at each location was assumed to be a circle and estimated based on the measured coronal diameter. The impedance as a function of area (Figure 2) shows an exponential decrease as the area increases (R2 ⫽ 0.91, P ⫽ .027).
Impedance as function of distance in vivo Impedance measurements in the LA of 10 patients and from 10 right inferior pulmonary veins (RIPVs), 10 right superior pulmonary veins (RSPVs), 7 LIPVs, and 10 left superior pulmonary veins (LSPVs) were obtained. Measurements were taken in the PVs at the PV ostium, 1, 2, 4, and 5 cm within each PV. Veins that could not be cannulated repeatedly because of steep angulation were excluded. Furthermore, a right middle PV was encountered in two patients in this study, and the impedance was uniformly high within those veins, precluding a detailed analysis. The values obtained for the LSPV and the RSPV of one patient superimposed on the patient’s MRI are shown in Figure 4. The average change in impedance increased with distance from
Figure 4 Impedance map of the left superior pulmonary vein (LSPV) and right superior pulmonary vein (RSPV) obtained during ablation superimposed on the magnetic resonance images obtained before ablation in one patient. Note that the values demonstrated are the actual impedances measured in vivo. The impedances measured in the left atrium are lower than in the pulmonary veins. However, the difference in impedance between the left atrium and the pulmonary vein ostia is unremarkable. LIPV ⫽ left inferior pulmonary vein; RIPV ⫽ right inferior pulmonary vein.
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Figure 5 Fluoroscopy and corresponding intracardiac echocardiographic images confirming catheter location and impedance values measured at various points along the pullback from the vein. The change in the measured impedance (red diamonds) on the graph as a function of distance is superimposed on the axial magnetic resonance images of the pulmonary vein (red triangles). Note that the further the catheter location from the left atrium, the higher the impedance measured. However, impedance measured at the venoatrial junction and 1 cm within the vein are not significantly different secondary to the nature of the curve.
impedance at 1 cm of all 37 PVs showed a significant average increase of 4.2 ⫾ 5.4 ⍀ (P ⬍ .01) compared with the LA. However, the increase in average impedance was not uniform among the four PVs. The change in impedance at 1 cm compared with the LA was 6.8 ⫾ 6.2 ⍀ (P ⬍ .01) for the LSPV, 3.3 ⫾ 2.1 W (P ⬍ .01) for LIPV, and 7.7 ⫾ 7.4 ⍀ (P ⬍ .01) for the RIPV. The change in impedance for the RSPV was 5.3 ⫾ 6.6 ⍀, but this change was not significant (P ⫽ .2). Impedance was measured with respect to the PV area in all 37 veins and plotted as a function of distance at 1, 2, 3, 4, and 5 cm into the PVs using MR and CT images. The cross-sectional area at each point then was calculated using PV diameter as measured by MRI and CT. An inverse relationship between PV diameter and impedance was noted (R ⫽ 0.91, P ⬍ .01). The average impedance increased exponentially as the cross-sectional area decreased (R2 ⫽ 0.93, P ⬍ .01). Qualitatively similar results were obtained in an additional 12 patients with ventricular dysfunction (data not shown). PV angiography was not performed in these cases to reduce radiocontrast use.
Discussion PV stenosis is a well-established complication of atrial fibrillation ablation.1–13 Given the increasing worldwide
prevalence of ablation procedures performed (18 patients underwent procedures in 1995 vs 5,050 patients in 2002),2 the incidence of PV stenosis likely will increase. Of the total
Figure 6 Average change in impedance in the pulmonary veins as a function of distance from the pulmonary vein ostium. The exponential fitted curves are shown. Note the exponential decline in impedance as the catheter is pulled back into the venoatrial junction. This holds true for all four pulmonary veins. Note that the average change in impedance between the venoatrial junction and 1 cm into the pulmonary vein is very small, especially compared with other locations within the pulmonary vein. LIPV ⫽ left inferior pulmonary vein; LSPV ⫽ left superior pulmonary vein; RIPV ⫽ right inferior pulmonary vein; RSPV ⫽ right superior pulmonary vein.
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of 8,745 patients in one study, 6,000 underwent a procedure to electrically isolate the PVs.2 To decrease the incidence of this complication, impedance monitoring to detect inadvertent catheter movement into the PV has been suggested as a method for preventing radiofrequency energy application into the PV.18 The goal of this study was to gain a better understanding of the factors that affect impedance in the electrophysiology laboratory and to assess the value of impedance monitoring during ablation procedures. In this study, in vitro analysis demonstrated that a decrease in sheath size (a surrogate for vein size) can cause a rise in impedance. Furthermore, a stereolithographic model with uniformly high impedance can demonstrate that the diameter of the cavity containing the catheter can be the sole determinant of impedance, with larger cavities of greater cross-sectional area having lower impedances. In vivo, there was an exponential rise in impedance as the catheter was advanced into the PV, confirming the in vitro data. The impedance was found to be significantly lower in the proximal than in the distal PV. Although prior studies have suggested that factors such as the amount of interposed lung tissue and the architecture of myocardial fibrils account for the impedance rise inside PVs,18,22 our data suggest that the decreased cross-sectional area of the veins is the major factor. A rise in impedance with distance was demonstrated in vitro, where tissue composition and anatomy are not a factor. Furthermore, with respect to cross-sectional area, this rise was exponential. The same exponential rise in impedance with decreasing cross-sectional area was also observed in vivo. This study shows that the true determinant of impedance is the cross-sectional area, both in vitro and in vivo, not tissue anatomy or histology, significantly improving our understanding of impedance. This physiology has been applied to measure arterial lumen area with an impedance catheter.23 Radiofrequency application even in the proximity of the PVs or at the ostia can cause stenosis.1,14,17 PV stenosis occurs regardless of the type of atrial fibrillation procedure performed, even when radiofrequency energy has been delivered outside the PV ostia.1 As the majority of the PV stenosis occurs within 1.2 cm of the pulmonary ostia,1,14 this area was of most interest in this study. In vivo and in vitro, the change in impedance from the LA to the PV ostia was not significant for any of the PVs studied. Contrary to the findings of previous studies,18 the changes in impedance between PV ostia and 1 cm into the PV were not uniform, and a cutoff value for reliable identification of catheter location could not be defined. Indeed, very small changes in impedance could signify movement into the proximal vein. The average change in impedance at 1 cm for the LIPV could be as little as 3.3 ⍀. For the RSPV vein, the change in impedance was not significant compared with the LA, an observation that has been made by others.18 Thus, impedance monitoring cannot detect catheter movement into the proximal PV.
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Several differences between the in vitro and in vivo studies are noteworthy. Impedances measured in vivo were lower in absolute value compared to the in vitro studies. This could be in part due to the composition of the vein wall compared with the stereolithographic model and sheaths. Also, in the in vitro sheath model, differences in impedance even 2 mm outside of the sheath were noted. Similar results were demonstrated in the stereolithographic plastic model. In contrast, the impedance measurements near the ostia in vivo show much smaller changes as the catheter is moved in and out of the vein ostia. Because the confounding effects of cardiac motion are not a factor in vitro, submillimeter accuracy in catheter location can be achieved. Finally, at 2 mm outside of the sheaths, a large difference was noted between various sheath sizes. The most likely reason for this change is that a higher effective area of the electrode tip is in contact with electrolytes with larger compared with smaller sheaths. Our study did confirm that a very acute rise in impedance (⬎250 ⍀) likely is secondary to movement of catheter deep (⬎2 cm) into the PV and/or back inside the sheath. This held true for both the in vivo and the in vitro experiments. The acute rise as the catheter is advanced into smaller cross-sectional areas of the PV in vivo may be explained by the insulating effect of air in the lungs. Clearly, radiofrequency application (or any other energy deliver) should not be allowed at sites showing high impedance values.
Study limitations Although catheter position was confirmed with contrast venography, fluoroscopy, and intracardiac echocardiography during the procedure, simultaneous cardiac MR images could not be obtained during the procedure (i.e., using open magnet MR). Impedance measurements then had to be superimposed on cardiac MR images postprocedure. Although this could serve as a source of error, given the accuracy of MRI in determining volume, cross-sectional area, and distance, it likely did not play a major role in the results. Dynamic changes of vein orifice are an unlikely source of major error. Sheaths have a small taper at their tip, which varies slightly among the different sheath types and sizes; therefore, we could not account for the effect of this difference in cross-sectional area on our impedance curves. Thirty-seven PVs from 10 patients were studied, a rather small number. However, despite the small number of PVs, the in vivo and in vitro studies of the effect of area on impedance correlated extremely well, with correlation coefficients ⬎0.9 and P ⬍ .01. Therefore, we do not believe the small number of patients had a great impact on the results and the understanding of the factors that affect impedance. Data using three imaging modalities (intracardiac echocardiography, electroanatomic mapping, and MRI) in an additional 12 patients showed identical results.
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Conclusion In this study, the major determinant of impedance, both in vitro and in vivo, was the cross-sectional area of the cavity containing the ablation catheter. An exponential decline in impedance was demonstrated as the catheter was pulled back from the PV into the LA. During LA catheter ablation in live patients, no significant difference in impedance at the LA compared with the PV ostia was observed. Although there was a rise in impedance in three of four PVs at 1 cm compared with the LA, this rise was nonuniform. This is the first study to analyze factors affecting impedance in vivo and in vitro in a systematic fashion. The results give physicians a better understanding of a parameter routinely measured during ablation procedures, its values and its limitations.
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