Usefulness of epicardial impedance evaluation for epicardial mapping and determination of epicardial ablation site for ventricular tachycardia: A pilot study. Short title: Impedance evaluation of epicardial VT ablation
Takeshi Kitamura, MD*; Seiji Fukamizu, MD, PhD*; Satoshi Miyazawa, MD*; Iwanari Kawamura, MD*; Rintaro Hojo, MD*; Yuya Aoyama, MD, PhD*; Mitsuhiro Nishizaki, MD, PhD†; Harumizu Sakurada, MD, PhD‡; Masayasu Hiraoka, MD, PhD, FHRS§ * Department of Cardiology, Tokyo Metropolitan Hiroo Hospital, Tokyo, Japan †Department of Cardiology, Yokohama Minami Kyosai Hospital, Yokohama, Japan ‡Tokyo Metropolitan Health and Medical Treatment Corporation Ohkubo Hospital, Tokyo, Japan §Toride Kitasoma Medical Center Hospital, Ibaraki, Japan
Address for correspondence: Takeshi Kitamura, MD Department of Cardiology, Tokyo Metropolitan Hiroo Hospital, 2 – 34 – 10 Ebisu, Shibuya-ku, Tokyo, Japan
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/jce.13361.
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Tel: 81+3-3444-1181, Fax: 81+3-3444-3196 E-mail: [email protected]
Disclosures: None
Abstract Background: During epicardial mapping, determination of appropriate ablation sites in low voltage areas (LVA) is challenging because of large epicardial areas covered by adipose tissue. Objective: To evaluate the impedance difference between epicardial fat and the epicardial LVA using multiple detector computed tomography (MDCT). Methods: We enrolled patients who underwent ventricular tachycardia (VT) ablation via the epicardial approach after endocardial ablation failure. After the procedure, MDCT-derived images of epicardial fat were loaded to the mapping system. Then, all points acquired during sinus rhythm were retrospectively superimposed and analyzed. Results: This study included data from 7 patients (62.5 ± 3.9 years old) who underwent 8 epicardial VT ablation procedures. After the procedure, MDCT-derived images of epicardial fat were registered in 8 procedures. Retrospective analysis of 1595 mapping and 236 ablation points was performed. Of the 1595 mapping points on the merged electroanatomical and epicardial fat maps, normal voltage area (NVA) and low voltage area (LVA) without fat had
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lower impedance than those with fat (NVA without fat 182 ± 46 Ω vs. NVA with fat 321 ± 164.0 Ω, P = 0.001, LVA without fat 164 ± 69 Ω vs. LVA with fat 248 ± 89 Ω, P = 0.002). Of the 236 ablation points, initial impedance before ablation was higher on epicardial fat than on epicardial LVA without fat (134 ± 16 Ω vs. 156 ± 28 Ω, P = 0.01). Conclusions: Real time epicardial impedance evaluation may be useful to determine effective epicardial ablation sites and avoid adipose tissue. However, the number of patients in the present study is limited. Further investigation with a large number of patients is needed to confirm our result.
Keywords: epicardial approach, ventricular tachycardia, radiofrequency catheter ablation, impedance, epicardial fat Introduction During epicardial mapping, determination of appropriate ablation sites in low voltage areas is challenging because of large epicardial areas covered by adipose tissue1-3. Human epicardial fat has been reported to have higher tissue impedance than normal muscle on the epicardial surface4. Moreover, the feasibility and accuracy of integration of computed tomography (CT)-derived epicardial fat and magnetic resonance imaging (MRI)-derived fat with electroanatomical maps5-8 have reported. However, CT or MRI imaging often cannot be performed for patients with severe chronic kidney disease or an implantable cardioverter defibrillator (ICD), which are common in patients who undergo epicardial VT ablation.
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This study aimed to evaluate the impedance difference between epicardial fat and the epicardial low voltage area (LVA) or scar using multiple detector CT (MDCT). In addition, we evaluated the magnitude of reduction of local bipolar amplitude after radiofrequency (RF) application and the characteristics of the local bipolar electrogram (EGM) 9, on higher impedance sites and lower impedance sites. According to previous studies10,11, local bipolar epicardial EGM characteristics differ between EGM with fat versus without fat.
Methods Study population In a consecutive series at the Tokyo Metropolitan Hiroo Hospital between June 2012 to May 2014, 15 patients with structural heart disease (mean age, 63.6±6.5 years) underwent 18 procedures for VT recurrence requiring an epicardial approach after prior endocardial VT ablation. The patient characteristics were shown in Table 1. Antiarrhythmic medications were discontinued >5 half-lives prior to ablation with the exception of amiodarone. Full written informed was provided by all patients. The Institution’s Research Ethics Board approved this study.
Ablation procedure
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All studies were performed under continuous propofol infusion after pre-procedural transthoracic echocardiography to exclude intracardiac thrombus. Endocardial vascular access was obtained via the femoral veins or arteries. In all patients, programmed ventricular stimulation at two right ventricular sites was performed using up to 3 extra stimuli before and after the ablation procedure to assess for inducible VTs. Subxiphoid epicardial access was established before heparin administration. A 9-French non-steerable sheath was inserted into the pericardial space.
Ablation methods 3D mapping and substrate ablation An 8-French quadripolar irrigated catheter (Thermocool Navistar, Biosense Webster, Diamond Bar, CA, USA) or an 8.5-French force-sensing irrigated catheter (Thermocool SmartTouch, Biosense Webster, Diamond Bar, CA, USA) and the CARTO electroanatomic mapping system (Biosense Webster, Diamond Bar, CA, USA) was used for mapping and ablation within the pericardial space. Epicardial voltage mapping was performed with irrigation at 2 ml/min, recording at least 150 points. Intracardiac and epicardial EGMs and the surface electrocardiograms were displayed at a speed of 150mm/s. All EGMs were filtered at a bandpass setting of 50 to 500 Hz. Voltage and impedance were collected during sinus rhythm (SR) and were displayed as 3-dimensional maps.
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When RF energy was delivered to the epicardial surface, this was preceded by coronary angiography to ensure that energy was delivered at a minimum distance of 0.5 cm from a major epicardial coronary artery. The impedance at ablation points was measured immediately before RF application with irrigation flow at 2 ml/min, as during mapping. In addition, in the lateral pericardial space, high-output pacing (20 mA/2ms) from the ablation catheter also preceded ablation in order to identify the left phrenic nerve. An RF delivery was first attempted at a power of up to 30 W for 30 seconds. Maximum temperature limit was 43˚C, and irrigation flow was titrated at 17 ml/min. Areas with impedance greater than 200 Ω were not considered to be eligible ablation sites. When a force-sensing ablation catheter was used, force vector orientation (FVO) was used so that the catheter force was directed towards the cardiac surface, at least parallel to the cardiac surface. The irrigant was aspirated at the beginning of mapping and ablation, then at regular intervals (10-20 min) during procedure via the pericardial 9-French sheath side port. Epicardial ablation target sites were identified on the basis of an activation map and an entrainment map for stable VT, and a substrate and a pace map for unstable VT. If the RF energy was delivered during VT, additional substrate ablations during SR were performed in all patients. We retrospectively analyzed the pre- and post-ablation parameters of each ablation point during SR. Ablation points during VT or ablation points guided by VT activation/entrainment map during SR were excluded. Then, mapping points during SR and ablation points during SR were analyzed.
Postoperative processing of CT imaging
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The postoperative offline imaging analysis is briefly shown in Figure 1. We processed the CT images retrospectively. Six patients underwent an electrocardiogram-gated cardiac CT on a 64-slice scanner (TOSHIBA CT Aquilion one 64, Tokyo, Japan) with intravenous iodinated contrast agent. Axial images were reconstructed with a 1.0 mm-thickness slice at 1.0 mm intervals. Epicardial adipose tissue was defined as the adipose tissue between the surface of the heart and the visceral layer of the pericardium13. The epicardial adipose tissue area was determined as the adipose tissue with a density between -195 and -45Hounsfield units, using a standalone workstation (Ziostation2, Ziosoft Inc., Tokyo, Japan)13. Then, the reconstructed three-dimensional (3-D) epicardial fat tissue shell was integrated into the CARTO system, and subsequently merged with the epicardial 3-D anatomical map created during the procedure. Visual alignment was performed using the ventricular apex and aortic cusps as a landmark. Then, surface registration was refined using automatic surface registration with a mean registration error of 2.8±1.5 mm. After processing, all superimposed mapping points and ablation points were analyzed.
Local bipolar electrograms All bipolar pre- and post-ablation EGMs during SR were analyzed. On the voltage map, LVA was defined as less than 1.5 mV6). The catheter contact to cardiac surface was verified by use of a force sensing catheter in two patients, and by using fluoroscopy and local pacing in other patients. Bipolar EGM characteristics, such as EGM duration, number of deflections, or EGM amplitude were evaluated at each point pre-ablation, with particular attention to abnormal
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EGMs frequently observed in scar even under epicardial fat (> 4 spikes, subdivided into double potentials, continuously fragmented potentials, late potentials, other abnormal morphologies).5, 21
The magnitude of reduction of the local EGM amplitude (ΔEGM) of each ablation point after
RF application was also evaluated. ΔEGM≥50% was defined as indicating of successful lesion formation14.
Statistics Continuous variables are presented as mean ± standard deviation. Comparison of continuous variables was performed using the Student t-test for normally distributed variables. Dichotomous variables were compared between cases and controls using the chi-square contingency test and Fisher’s exact probability test. Kruskal-Wallis test was used for non-parametric comparisons when there are more than and equal to three groups to be compared. Steel Dwass test was used for post-hoc analysis after Kruskal-Wallis test. All reported P-values are two-sided, with a P-value of 0.5 mV) and with LVA (1.5 mV, the impedance was greater in mapping points with CF ≥20 g. There was, however, no significant association for other areas. The impedance in LVA among mapping points and ablation points with contact force towards the parietal pericardium with ≥10 g were higher than those with CF 5-9 g. Regarding FVO, among ablation points with CF ≥10 g, the impedance with ablation points pointing toward pericardium was higher than those with pointing toward cardiac surface with CF ≥10 g (p = 0.023).
Electrogram characteristics of pre-ablation sites.
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Almost all ablation points EGM (98.7%) revealed abnormal EGM specific to scar, even under fat5): 94.6% (double potentials: 7.4%, continuously fragmented potentials 41.9%, late potentials: 30.1%, other abnormal morphologies: 15.2%) or duration >50 ms (95.7%). There was no statistical difference between areas without vs. with fat in the amplitude of pre-ablation bipolar voltage (without fat: 0.80±0.64 mV vs. with fat: 1.14±0.68 mV; P = 0.222). Pre-ablation bipolar EGM duration without fat was longer than that with fat (without fat: 86.4±27.1 ms vs. with fat: 73.1±21.1 ms; P = 0.01). There was a significant difference in EGM duration between mapping points in LVA without fat and NVA without fat (LVA without fat 75.5 ± 25 ms vs. NVA without fat 48.2 ± 18 ms, P < 0.001).
Comparison of ablation efficacy One hundred sixty four of 236(69.4%) ablation sites had a >50% ΔEGM, which we had defined as indicating lesion creation. The ablation points with ΔEGM more than 50% were more frequently observed on the area without fat than on those with fat (75/94: 79.7%, vs. 89/142: 62.7%, P = 0.002) (Table 3). Regarding impedance, number of ablation points with Δ impedance >10 Ω in ablation points without fat was not statistically different from that with fat (P = 0.48).
Discussion Epicardial impedance evaluation to determine appropriate ablation sites during VT ablation This article is protected by copyright. All rights reserved.
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Our results demonstrate that the impedance value during epicardial mapping and ablation were lower in area without CT derived epicardial fat than those with epicardial fat in cases with a subcutaneous epicardial approach. As previously reported, cardiac MDCT or enhanced MRI are the gold standard for visualization of epicardial fat, particularly with real-time image integration5-9. However, among the patient population requiring epicardial VT ablation and severe renal dysfunction or ICD implantation, which are contraindications for MRI, are common. Moreover, real-time image integration may have problems with merging or shift. Even in the presence of severe renal dysfunction or an ICD the impedance value of ablation catheters can be continuously monitored in real time. Adipose tissue is known to have a higher impedance than normal myocardium4, 14. Higher impedance in regions with fat was observed compared to normal muscle in the setting of open heart surgery by direct measurement via placement of a non-irrigated ablation catheter onto the epicardial surface4. Similarly, our study showed that the epicardial impedance of epicardial fat detected by CT was higher than in regions without fat among NVA and LVA. In addition, even among a smaller number of ablation sites, ablation site with fat had higher impedance, and lower ablation efficacy was observed at the ablation sites. Therefore, impedance measurement can be a useful tool to detect appropriate ablation sites without fat. However, when comparing the previous publication, there was a difference in the impedance value between Jacobson’s study4 and the present study. There are several possible reasons for this difference. First, during mapping, the irrigant was continuously flowing at a low flow rate.
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Hence, there was a constant, certain amount of pericardial fluid in the closed space, which might have led the impedance to be lower. On the contrary, Jacobson’s study may not have included epicardial fluid between the ablation catheter tip and the epicardial surface. Second, we used an irrigated catheter in all cases. In contrast, the previous study used a non-irrigated catheter. With an irrigated catheter, a certain amount of saline constantly existed between the cardiac surface and the catheter tip, which was presumably acting as a conductor. Hence, impedance might be lower in our study. Third, impedance in contact with myocardium was reported to be higher than that not in contact, 15,16. In the present study, a certain amount of points might not be in substantial contact with myocardium, which might have lowered impedance. Fourth, in the open space, the catheter distal tip is not completely in contact with fluid, myocardium or other conductor but air. On the other hand, the catheter distal tip in pericardial space by using a subcutaneous approach is in contact with conductors (at least more conductive than air) at all aspects. This environment may possibly affect impedance. Therefore, a definite value to detect epicardial fat appears to depend upon the clinical situation and ablation setting. We also first performed two comparisons between mapping points in LVA without fat and with fat, and between ablation points in LVA without fat and with fat. In both situations, impedance was lower without fat. On the contrary, in Jacobson’s study, there was no comparison in LVA. In clinical practice, RF delivery at NVA is not common during SR. Therefore, our study is more practical in terms of the clinical ablation setting. Interestingly, the difference between without fat and with fat was still observed in the lower impedance and the smaller impedance ranges in ablation points, which might offer more practical implication to determine eligible
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ablation sites during epicardial ablation. Meanwhile, the lack of a large difference in impedance between without fat vs. with fat among ablation points may possibly result from a relatively thin layer of fat6), and selection bias of ablation points less than 200 Ω.
Comparison of Ablation efficacy The local voltage amplitude reduction magnitude between pre- and post-RF delivery was greater at low voltage ablation points without epicardial fat. Moreover, a higher prevalence of ablation points with local voltage amplitude reduction magnitude more than 50% was observed at ablation points without CT derived epicardial fat. These results indicate that during epicardial ablation, efficacy was limited when adipose tissue was present between the ablation catheter tip and epicardial myocardium17. Further, we also evaluated impedance drop after RF application. According to the results, the impedance drop was statistically higher at the ablation site without fat. On the contrary, there was no statistical difference in the percentage of ablation points with an impedance drop by 10 Ω18) between two groups. Thus, we can’t conclude whether impedance drop potentially is a helpful indicator of lesion formation through the fat. Further investigation by using an experimental model with direct lesion measurement is needed to verify that the impedance drop can be an indicator of substantial ablation lesion in comparison between ablation sites with fat and without fat. Finally, our observation may indicate that higher power should be required to deliver a sufficient ablation lesion when there is fat over the target area; this would require verification by an experimental study.
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Other factors influencing impedance during epicardial mapping and ablation Impedance is commonly affected by many factors between a measuring catheter tip and an indifferent patch or electrode. Many factors may have affected impedance. First, impedance in LVA was lower than in NVA in the present study. Previous studies have identified lower impedance in scar tissue compared to healthy tissue19,20). Although our study did not include imaging evaluation to detect scar and included damaged but still surviving myocardium in LVA, the findings in the present study do not contradict those results. Second, although it was challenging to measure the amount of fluid during epicardial mapping and ablation, we considered that during ablation there may have been a larger amount of fluid because of the high flow rate of the irrigant than during mapping. Therefore, a slightly larger amount of fluids might lead to lower impedance as fluids can behave as a conductor. Third, we analyzed the effects of CF and FVO. Regarding CF, higher CF were observed with higher impedance in several settings although there was no consistent trend with a statistical difference. In terms of FVO, among ablation points vector toward parietal pericardium with more than 10 g force had significantly higher impedance than that in ablation points with a vector toward cardiac surface with more than 10g. No consistent trend was, however, observed with regard to the effect of FVO. Further investigation with more points may clarify the association between CF/FVO and impedance.
Study limitations This article is protected by copyright. All rights reserved.
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This study was a single-center, retrospective analysis with a small sample size. Our study did not evaluate the thickness of adipose tissue at each ablation point. The measured tissue impedance is dependent on the type and size of the tip electrode. We performed impedance measurement only by a 3.5 mm tip open irrigated ablation catheter. Therefore, our results are only applicable to that ablation catheter. When we speculated the amount of pericardial fluid during comparison between mapping points in LVA and ablation points in the same area, it is impossible to know for certain the amount of pericardial fluid. LVA was defined by only voltage map created by 3.5 mm tip mapping catheter, with wide interelectrode spacing. Thus, a more closely spaced catheter with high density mapping may provide different results. In addition, during mapping, a certain amount of points might have been not in sufficient contact with cardiac surface, which may have attenuated voltage amplitude. Finally, we did not verify scar by using imaging, which may mean that LVA included NVA covered by thick fat in the analysis. However, with regard to ablation points, almost all ablation points had specific EGM characteristics for scar, even under fat tissue5), and we confirmed ablation targets for induced and clinical VTs by using entrainment/activation map or pace map at all points. Therefore, we believe the ablation points were within scar tissue with or without fat.
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Conclusions Real-time epicardial impedance evaluation may be useful to determine effective epicardial ablation sites without adipose tissue. Higher impedance may indicate epicardial myocardium covered with adipose tissue. It may mainly guide ablation in the difficult situation where real-time imaging integration is not available or may be a supplementary tool with real-time imaging integration. However, the number of patients in the present study is limited. Further investigation with a larger number of patients is needed to verify our result.
Acknowledgements We would like to thank Dr. Ruairidh Martin from Newcastle University, Newcastle-upon-Tyne, UK, for English editing.
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Table 1. Patient characteristics. Variables
n=7
Age (years)
62.5 ± 3.9
Male/female sex, n/n
7/0
ICD implantation, n (%)
7/7(100)
Antiarrhythmic medication therapy, n (%) 6/7(85.7) Mexiletine, n (%)
1/7(14.2%)
Carvedirol, n (%)
5/7(71.4%)
Amiodarone, n (%)
3/7(42.9)
Sotalol, n (%)
1/7(14.2%)
Serum creatinine (mg/mL)
0.9±0.2
Brain natriuretic peptide (pg/mL)
312±168
ECG findings Atrial fibrillation, n (%)
0(0%)
Biventricular pacing, n (%)
0/7(0%)
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QRS duration during sinus rhythm (ms)
122±27
UCG parameters Left ventricular ejection fraction (%)
31.4±9.5
Procedure results (8 sessions) Irrigation catheter
8/8 100%
Number of induced VT
12, (1.5 VT/session), median 265 ms
Entrainment mapping
6/12 (50%)
Activation mapping
3/12 (25%)
Pace mapping
12/12 (100%)
Non-inducibility
6/8 (75%)
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Table 2, Comparisons of impedance at epicardial mapping sites during sinus rhythm between areas with CT-derived fat and without CT-derived fat, and mapping details. Total mapping points during sinus rhythm
Total n=1595
n=1595
Without
With fat
fat
n=717
p-value
n=878
Mean amplitude of bipolar
2.58±
EGM (mV)
1.44
Mean impedance (Ω)
2.79±1.67
2.48±1.88
0.18
226±103
182±76
289±97
0.002
Impedance range
89-698
89-284
149-698
Mean mapping time (min)
26.7± 10.2
Mean total amount of irrigant
53.4±
during mapping (ml)
20.4
Number of mapping
957
511
446
243±103
182±46
321±164
124-698
124-284
221-698
points>0.5mV (n) Mean impedance in the area>0.5mV (Ω) Impedance range in the
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0.001
25
area>0.5mV (Ω) Number of mapping points in
638
367
271
218±99
164±69
248±89
89-322
89-221
149-322
LVA (n) Mean impedance in LVA (Ω)
0.002
Impedance range in LVA (Ω)
Table 3. Comparison of epicardial ablation sites during sinus rhythm between areas without CT-derived fat and with CT-derived fat.
Total epicardial ablation points
Without fat
With fat
during sinus rhythm
n=94
n=142
0.80±0.64
1.14±0.68
0.222
86.4±27.1
73.1±21.1
0.01
p-value
n=236 Pre-ablation mean amplitude of bipolar EGM (mV) Pre-ablation mean duration of bipolar EGM (ms)
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Pre-ablation mean number of
5.8±4.0
4.2±3.0
0.10
deflection of bipolar EGM (n) Pre-ablation mean impedance (Ω)
134±16
156±28
0.02
Post-ablation mean amplitude of
0.43±0.22
0.65±0.50
0.002
55.2±18
46.6±14
0.030
bipolar EGM (mV) Δ bipolar EGM between pre- and post-ablation (%) Number of ablation points with
75/94(79.7%) 89/142(62.7%)
0.01
Δbipolar EGM>50% (n) Δimpedance between pre- and
17±8.4
12.6±6.3
0.004
83/94(88.2)
130/142(91.5)
0.48
post-ablation (Ω) Number of ablation points withΔ impedance>10 Ω, n(%)
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Figure legends Figure 1: Processing of off-line analysis in the present study. This is an example of a patient with remote anteroseptal myocardial infarct with epicardial ventricular tachycardia ablation. A: Three-dimensional epicardial fat meshes were created from the short-axis or longitudinal-axis contrast-enhanced computed tomography imaging slices. B: The computed tomography was segmented and imported into the mapping system. C: The epicardial voltage map and impedance map, merging enhanced computed tomography images acquired before the ablation session. D: The epicardial voltage map and impedance map, merging computed tomography images of the epicardium acquired after off-line processing.
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Figure 2: Box plots demonstrating comparison of impedance between without fat and with fat among mapping points in different group. LVA = low voltage area.
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Figure 3: Box plots demonstrating comparison of impedance between without fat and with fat among ablation points. Ab = ablation.
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Takeshi Kitamura, MD*; Seiji Fukamizu, MD, PhD*; Satoshi Miyazawa, MD*; Iwanari Kawamura, MD*; Rintaro Hojo, MD*; Yuya Aoyama, MD, PhD*; Mitsuhiro Nishizaki, MD, PhD†; Harumizu Sakurada, MD, PhD‡; Masayasu Hiraoka, MD, PhD, FHRS§ * Department of Cardiology, Tokyo Metropolitan Hiroo Hospital, Tokyo, Japan †Department of Cardiology, Yokohama Minami Kyosai Hospital, Yokohama, Japan ‡Tokyo Metropolitan Health and Medical Treatment Corporation Ohkubo Hospital, Tokyo, Japan §Toride Kitasoma Medical Center Hospital, Ibaraki, Japan
Address for correspondence: Takeshi Kitamura, MD Department of Cardiology, Tokyo Metropolitan Hiroo Hospital, 2 – 34 – 10 Ebisu, Shibuya-ku, Tokyo, Japan
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/jce.13361.
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Tel: 81+3-3444-1181, Fax: 81+3-3444-3196 E-mail: [email protected]
Disclosures: None
Abstract Background: During epicardial mapping, determination of appropriate ablation sites in low voltage areas (LVA) is challenging because of large epicardial areas covered by adipose tissue. Objective: To evaluate the impedance difference between epicardial fat and the epicardial LVA using multiple detector computed tomography (MDCT). Methods: We enrolled patients who underwent ventricular tachycardia (VT) ablation via the epicardial approach after endocardial ablation failure. After the procedure, MDCT-derived images of epicardial fat were loaded to the mapping system. Then, all points acquired during sinus rhythm were retrospectively superimposed and analyzed. Results: This study included data from 7 patients (62.5 ± 3.9 years old) who underwent 8 epicardial VT ablation procedures. After the procedure, MDCT-derived images of epicardial fat were registered in 8 procedures. Retrospective analysis of 1595 mapping and 236 ablation points was performed. Of the 1595 mapping points on the merged electroanatomical and epicardial fat maps, normal voltage area (NVA) and low voltage area (LVA) without fat had
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lower impedance than those with fat (NVA without fat 182 ± 46 Ω vs. NVA with fat 321 ± 164.0 Ω, P = 0.001, LVA without fat 164 ± 69 Ω vs. LVA with fat 248 ± 89 Ω, P = 0.002). Of the 236 ablation points, initial impedance before ablation was higher on epicardial fat than on epicardial LVA without fat (134 ± 16 Ω vs. 156 ± 28 Ω, P = 0.01). Conclusions: Real time epicardial impedance evaluation may be useful to determine effective epicardial ablation sites and avoid adipose tissue. However, the number of patients in the present study is limited. Further investigation with a large number of patients is needed to confirm our result.
Keywords: epicardial approach, ventricular tachycardia, radiofrequency catheter ablation, impedance, epicardial fat Introduction During epicardial mapping, determination of appropriate ablation sites in low voltage areas is challenging because of large epicardial areas covered by adipose tissue1-3. Human epicardial fat has been reported to have higher tissue impedance than normal muscle on the epicardial surface4. Moreover, the feasibility and accuracy of integration of computed tomography (CT)-derived epicardial fat and magnetic resonance imaging (MRI)-derived fat with electroanatomical maps5-8 have reported. However, CT or MRI imaging often cannot be performed for patients with severe chronic kidney disease or an implantable cardioverter defibrillator (ICD), which are common in patients who undergo epicardial VT ablation.
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This study aimed to evaluate the impedance difference between epicardial fat and the epicardial low voltage area (LVA) or scar using multiple detector CT (MDCT). In addition, we evaluated the magnitude of reduction of local bipolar amplitude after radiofrequency (RF) application and the characteristics of the local bipolar electrogram (EGM) 9, on higher impedance sites and lower impedance sites. According to previous studies10,11, local bipolar epicardial EGM characteristics differ between EGM with fat versus without fat.
Methods Study population In a consecutive series at the Tokyo Metropolitan Hiroo Hospital between June 2012 to May 2014, 15 patients with structural heart disease (mean age, 63.6±6.5 years) underwent 18 procedures for VT recurrence requiring an epicardial approach after prior endocardial VT ablation. The patient characteristics were shown in Table 1. Antiarrhythmic medications were discontinued >5 half-lives prior to ablation with the exception of amiodarone. Full written informed was provided by all patients. The Institution’s Research Ethics Board approved this study.
Ablation procedure
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All studies were performed under continuous propofol infusion after pre-procedural transthoracic echocardiography to exclude intracardiac thrombus. Endocardial vascular access was obtained via the femoral veins or arteries. In all patients, programmed ventricular stimulation at two right ventricular sites was performed using up to 3 extra stimuli before and after the ablation procedure to assess for inducible VTs. Subxiphoid epicardial access was established before heparin administration. A 9-French non-steerable sheath was inserted into the pericardial space.
Ablation methods 3D mapping and substrate ablation An 8-French quadripolar irrigated catheter (Thermocool Navistar, Biosense Webster, Diamond Bar, CA, USA) or an 8.5-French force-sensing irrigated catheter (Thermocool SmartTouch, Biosense Webster, Diamond Bar, CA, USA) and the CARTO electroanatomic mapping system (Biosense Webster, Diamond Bar, CA, USA) was used for mapping and ablation within the pericardial space. Epicardial voltage mapping was performed with irrigation at 2 ml/min, recording at least 150 points. Intracardiac and epicardial EGMs and the surface electrocardiograms were displayed at a speed of 150mm/s. All EGMs were filtered at a bandpass setting of 50 to 500 Hz. Voltage and impedance were collected during sinus rhythm (SR) and were displayed as 3-dimensional maps.
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When RF energy was delivered to the epicardial surface, this was preceded by coronary angiography to ensure that energy was delivered at a minimum distance of 0.5 cm from a major epicardial coronary artery. The impedance at ablation points was measured immediately before RF application with irrigation flow at 2 ml/min, as during mapping. In addition, in the lateral pericardial space, high-output pacing (20 mA/2ms) from the ablation catheter also preceded ablation in order to identify the left phrenic nerve. An RF delivery was first attempted at a power of up to 30 W for 30 seconds. Maximum temperature limit was 43˚C, and irrigation flow was titrated at 17 ml/min. Areas with impedance greater than 200 Ω were not considered to be eligible ablation sites. When a force-sensing ablation catheter was used, force vector orientation (FVO) was used so that the catheter force was directed towards the cardiac surface, at least parallel to the cardiac surface. The irrigant was aspirated at the beginning of mapping and ablation, then at regular intervals (10-20 min) during procedure via the pericardial 9-French sheath side port. Epicardial ablation target sites were identified on the basis of an activation map and an entrainment map for stable VT, and a substrate and a pace map for unstable VT. If the RF energy was delivered during VT, additional substrate ablations during SR were performed in all patients. We retrospectively analyzed the pre- and post-ablation parameters of each ablation point during SR. Ablation points during VT or ablation points guided by VT activation/entrainment map during SR were excluded. Then, mapping points during SR and ablation points during SR were analyzed.
Postoperative processing of CT imaging
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The postoperative offline imaging analysis is briefly shown in Figure 1. We processed the CT images retrospectively. Six patients underwent an electrocardiogram-gated cardiac CT on a 64-slice scanner (TOSHIBA CT Aquilion one 64, Tokyo, Japan) with intravenous iodinated contrast agent. Axial images were reconstructed with a 1.0 mm-thickness slice at 1.0 mm intervals. Epicardial adipose tissue was defined as the adipose tissue between the surface of the heart and the visceral layer of the pericardium13. The epicardial adipose tissue area was determined as the adipose tissue with a density between -195 and -45Hounsfield units, using a standalone workstation (Ziostation2, Ziosoft Inc., Tokyo, Japan)13. Then, the reconstructed three-dimensional (3-D) epicardial fat tissue shell was integrated into the CARTO system, and subsequently merged with the epicardial 3-D anatomical map created during the procedure. Visual alignment was performed using the ventricular apex and aortic cusps as a landmark. Then, surface registration was refined using automatic surface registration with a mean registration error of 2.8±1.5 mm. After processing, all superimposed mapping points and ablation points were analyzed.
Local bipolar electrograms All bipolar pre- and post-ablation EGMs during SR were analyzed. On the voltage map, LVA was defined as less than 1.5 mV6). The catheter contact to cardiac surface was verified by use of a force sensing catheter in two patients, and by using fluoroscopy and local pacing in other patients. Bipolar EGM characteristics, such as EGM duration, number of deflections, or EGM amplitude were evaluated at each point pre-ablation, with particular attention to abnormal
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EGMs frequently observed in scar even under epicardial fat (> 4 spikes, subdivided into double potentials, continuously fragmented potentials, late potentials, other abnormal morphologies).5, 21
The magnitude of reduction of the local EGM amplitude (ΔEGM) of each ablation point after
RF application was also evaluated. ΔEGM≥50% was defined as indicating of successful lesion formation14.
Statistics Continuous variables are presented as mean ± standard deviation. Comparison of continuous variables was performed using the Student t-test for normally distributed variables. Dichotomous variables were compared between cases and controls using the chi-square contingency test and Fisher’s exact probability test. Kruskal-Wallis test was used for non-parametric comparisons when there are more than and equal to three groups to be compared. Steel Dwass test was used for post-hoc analysis after Kruskal-Wallis test. All reported P-values are two-sided, with a P-value of 0.5 mV) and with LVA (1.5 mV, the impedance was greater in mapping points with CF ≥20 g. There was, however, no significant association for other areas. The impedance in LVA among mapping points and ablation points with contact force towards the parietal pericardium with ≥10 g were higher than those with CF 5-9 g. Regarding FVO, among ablation points with CF ≥10 g, the impedance with ablation points pointing toward pericardium was higher than those with pointing toward cardiac surface with CF ≥10 g (p = 0.023).
Electrogram characteristics of pre-ablation sites.
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Almost all ablation points EGM (98.7%) revealed abnormal EGM specific to scar, even under fat5): 94.6% (double potentials: 7.4%, continuously fragmented potentials 41.9%, late potentials: 30.1%, other abnormal morphologies: 15.2%) or duration >50 ms (95.7%). There was no statistical difference between areas without vs. with fat in the amplitude of pre-ablation bipolar voltage (without fat: 0.80±0.64 mV vs. with fat: 1.14±0.68 mV; P = 0.222). Pre-ablation bipolar EGM duration without fat was longer than that with fat (without fat: 86.4±27.1 ms vs. with fat: 73.1±21.1 ms; P = 0.01). There was a significant difference in EGM duration between mapping points in LVA without fat and NVA without fat (LVA without fat 75.5 ± 25 ms vs. NVA without fat 48.2 ± 18 ms, P < 0.001).
Comparison of ablation efficacy One hundred sixty four of 236(69.4%) ablation sites had a >50% ΔEGM, which we had defined as indicating lesion creation. The ablation points with ΔEGM more than 50% were more frequently observed on the area without fat than on those with fat (75/94: 79.7%, vs. 89/142: 62.7%, P = 0.002) (Table 3). Regarding impedance, number of ablation points with Δ impedance >10 Ω in ablation points without fat was not statistically different from that with fat (P = 0.48).
Discussion Epicardial impedance evaluation to determine appropriate ablation sites during VT ablation This article is protected by copyright. All rights reserved.
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Our results demonstrate that the impedance value during epicardial mapping and ablation were lower in area without CT derived epicardial fat than those with epicardial fat in cases with a subcutaneous epicardial approach. As previously reported, cardiac MDCT or enhanced MRI are the gold standard for visualization of epicardial fat, particularly with real-time image integration5-9. However, among the patient population requiring epicardial VT ablation and severe renal dysfunction or ICD implantation, which are contraindications for MRI, are common. Moreover, real-time image integration may have problems with merging or shift. Even in the presence of severe renal dysfunction or an ICD the impedance value of ablation catheters can be continuously monitored in real time. Adipose tissue is known to have a higher impedance than normal myocardium4, 14. Higher impedance in regions with fat was observed compared to normal muscle in the setting of open heart surgery by direct measurement via placement of a non-irrigated ablation catheter onto the epicardial surface4. Similarly, our study showed that the epicardial impedance of epicardial fat detected by CT was higher than in regions without fat among NVA and LVA. In addition, even among a smaller number of ablation sites, ablation site with fat had higher impedance, and lower ablation efficacy was observed at the ablation sites. Therefore, impedance measurement can be a useful tool to detect appropriate ablation sites without fat. However, when comparing the previous publication, there was a difference in the impedance value between Jacobson’s study4 and the present study. There are several possible reasons for this difference. First, during mapping, the irrigant was continuously flowing at a low flow rate.
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Hence, there was a constant, certain amount of pericardial fluid in the closed space, which might have led the impedance to be lower. On the contrary, Jacobson’s study may not have included epicardial fluid between the ablation catheter tip and the epicardial surface. Second, we used an irrigated catheter in all cases. In contrast, the previous study used a non-irrigated catheter. With an irrigated catheter, a certain amount of saline constantly existed between the cardiac surface and the catheter tip, which was presumably acting as a conductor. Hence, impedance might be lower in our study. Third, impedance in contact with myocardium was reported to be higher than that not in contact, 15,16. In the present study, a certain amount of points might not be in substantial contact with myocardium, which might have lowered impedance. Fourth, in the open space, the catheter distal tip is not completely in contact with fluid, myocardium or other conductor but air. On the other hand, the catheter distal tip in pericardial space by using a subcutaneous approach is in contact with conductors (at least more conductive than air) at all aspects. This environment may possibly affect impedance. Therefore, a definite value to detect epicardial fat appears to depend upon the clinical situation and ablation setting. We also first performed two comparisons between mapping points in LVA without fat and with fat, and between ablation points in LVA without fat and with fat. In both situations, impedance was lower without fat. On the contrary, in Jacobson’s study, there was no comparison in LVA. In clinical practice, RF delivery at NVA is not common during SR. Therefore, our study is more practical in terms of the clinical ablation setting. Interestingly, the difference between without fat and with fat was still observed in the lower impedance and the smaller impedance ranges in ablation points, which might offer more practical implication to determine eligible
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ablation sites during epicardial ablation. Meanwhile, the lack of a large difference in impedance between without fat vs. with fat among ablation points may possibly result from a relatively thin layer of fat6), and selection bias of ablation points less than 200 Ω.
Comparison of Ablation efficacy The local voltage amplitude reduction magnitude between pre- and post-RF delivery was greater at low voltage ablation points without epicardial fat. Moreover, a higher prevalence of ablation points with local voltage amplitude reduction magnitude more than 50% was observed at ablation points without CT derived epicardial fat. These results indicate that during epicardial ablation, efficacy was limited when adipose tissue was present between the ablation catheter tip and epicardial myocardium17. Further, we also evaluated impedance drop after RF application. According to the results, the impedance drop was statistically higher at the ablation site without fat. On the contrary, there was no statistical difference in the percentage of ablation points with an impedance drop by 10 Ω18) between two groups. Thus, we can’t conclude whether impedance drop potentially is a helpful indicator of lesion formation through the fat. Further investigation by using an experimental model with direct lesion measurement is needed to verify that the impedance drop can be an indicator of substantial ablation lesion in comparison between ablation sites with fat and without fat. Finally, our observation may indicate that higher power should be required to deliver a sufficient ablation lesion when there is fat over the target area; this would require verification by an experimental study.
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Other factors influencing impedance during epicardial mapping and ablation Impedance is commonly affected by many factors between a measuring catheter tip and an indifferent patch or electrode. Many factors may have affected impedance. First, impedance in LVA was lower than in NVA in the present study. Previous studies have identified lower impedance in scar tissue compared to healthy tissue19,20). Although our study did not include imaging evaluation to detect scar and included damaged but still surviving myocardium in LVA, the findings in the present study do not contradict those results. Second, although it was challenging to measure the amount of fluid during epicardial mapping and ablation, we considered that during ablation there may have been a larger amount of fluid because of the high flow rate of the irrigant than during mapping. Therefore, a slightly larger amount of fluids might lead to lower impedance as fluids can behave as a conductor. Third, we analyzed the effects of CF and FVO. Regarding CF, higher CF were observed with higher impedance in several settings although there was no consistent trend with a statistical difference. In terms of FVO, among ablation points vector toward parietal pericardium with more than 10 g force had significantly higher impedance than that in ablation points with a vector toward cardiac surface with more than 10g. No consistent trend was, however, observed with regard to the effect of FVO. Further investigation with more points may clarify the association between CF/FVO and impedance.
Study limitations This article is protected by copyright. All rights reserved.
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This study was a single-center, retrospective analysis with a small sample size. Our study did not evaluate the thickness of adipose tissue at each ablation point. The measured tissue impedance is dependent on the type and size of the tip electrode. We performed impedance measurement only by a 3.5 mm tip open irrigated ablation catheter. Therefore, our results are only applicable to that ablation catheter. When we speculated the amount of pericardial fluid during comparison between mapping points in LVA and ablation points in the same area, it is impossible to know for certain the amount of pericardial fluid. LVA was defined by only voltage map created by 3.5 mm tip mapping catheter, with wide interelectrode spacing. Thus, a more closely spaced catheter with high density mapping may provide different results. In addition, during mapping, a certain amount of points might have been not in sufficient contact with cardiac surface, which may have attenuated voltage amplitude. Finally, we did not verify scar by using imaging, which may mean that LVA included NVA covered by thick fat in the analysis. However, with regard to ablation points, almost all ablation points had specific EGM characteristics for scar, even under fat tissue5), and we confirmed ablation targets for induced and clinical VTs by using entrainment/activation map or pace map at all points. Therefore, we believe the ablation points were within scar tissue with or without fat.
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Conclusions Real-time epicardial impedance evaluation may be useful to determine effective epicardial ablation sites without adipose tissue. Higher impedance may indicate epicardial myocardium covered with adipose tissue. It may mainly guide ablation in the difficult situation where real-time imaging integration is not available or may be a supplementary tool with real-time imaging integration. However, the number of patients in the present study is limited. Further investigation with a larger number of patients is needed to verify our result.
Acknowledgements We would like to thank Dr. Ruairidh Martin from Newcastle University, Newcastle-upon-Tyne, UK, for English editing.
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12. Cather Ablation of Cardiac Arrhythmias second edition. Wood MA, Huang SK. Elsevier, 2011. 13. Rosito GA, Massaro JM, Hoffmann U, Ruberg FL, Mahabadi AA, Vasan RS, O'Donnell CJ, Fox CS. Pericardial fat, visceral abdominal fat, cardiovascular disease risk factors, and vascular calcification in a community based sample: The Framingham Heart Study. Circulation. 2008;117:605-613. 14. Geddes LA, Baker LE. The specific resistance of biological material - a compendium of data for the biomedical engineer and physiologist. Med Biol Eng. 1967;5:271-293. 15. Foster KR, Schwan HP: Dielectric properties of tissues and biological materials: A critical review. Crit Rev Biomed Eng 1989;17:25-117. 16. Thiagalingam A, D'Avila A, McPherson C, Malchano Z, Ruskin J, Reddy VY. Impedance and Temperature Monitoring Improve the Safety of Closed-Loop Irrigated-Tip Radiofrequency Ablation. J Cardiovasc Electrophysiol. 2007; 18: 318-325 17. d'Avila A1, Houghtaling C, Gutierrez P, Vragovic O, Ruskin JN, Josephson ME, Reddy VY. Catheter ablation of ventricular epicardial tissue: a comparison of standard and cooled-tip radiofrequency energy. Circulation. 2004;109:2363-2369. 18. Bourke T, Buch E, Mathuria N, Michowitz Y, Yu R, Mandapati R, Shivkumar K, Tung R. Biophysical parameters during radiofrequency catheter ablation of scar-mediated ventricular tachycardia: epicardial and endocardial applications via manual and magnetic navigation. J Cardiovasc Electrophysiol. 2014;25:1165-73.
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19. Fallert MA, Mirotznik MS, Downing SW, Savage EB, Foster KR, Josephson ME, Bogen DK: Myocardial electrical impedance map- ping of ischemic sheep hearts and healing aneurysms. Circulation 1993;87:199-207.
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Table 1. Patient characteristics. Variables
n=7
Age (years)
62.5 ± 3.9
Male/female sex, n/n
7/0
ICD implantation, n (%)
7/7(100)
Antiarrhythmic medication therapy, n (%) 6/7(85.7) Mexiletine, n (%)
1/7(14.2%)
Carvedirol, n (%)
5/7(71.4%)
Amiodarone, n (%)
3/7(42.9)
Sotalol, n (%)
1/7(14.2%)
Serum creatinine (mg/mL)
0.9±0.2
Brain natriuretic peptide (pg/mL)
312±168
ECG findings Atrial fibrillation, n (%)
0(0%)
Biventricular pacing, n (%)
0/7(0%)
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QRS duration during sinus rhythm (ms)
122±27
UCG parameters Left ventricular ejection fraction (%)
31.4±9.5
Procedure results (8 sessions) Irrigation catheter
8/8 100%
Number of induced VT
12, (1.5 VT/session), median 265 ms
Entrainment mapping
6/12 (50%)
Activation mapping
3/12 (25%)
Pace mapping
12/12 (100%)
Non-inducibility
6/8 (75%)
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Table 2, Comparisons of impedance at epicardial mapping sites during sinus rhythm between areas with CT-derived fat and without CT-derived fat, and mapping details. Total mapping points during sinus rhythm
Total n=1595
n=1595
Without
With fat
fat
n=717
p-value
n=878
Mean amplitude of bipolar
2.58±
EGM (mV)
1.44
Mean impedance (Ω)
2.79±1.67
2.48±1.88
0.18
226±103
182±76
289±97
0.002
Impedance range
89-698
89-284
149-698
Mean mapping time (min)
26.7± 10.2
Mean total amount of irrigant
53.4±
during mapping (ml)
20.4
Number of mapping
957
511
446
243±103
182±46
321±164
124-698
124-284
221-698
points>0.5mV (n) Mean impedance in the area>0.5mV (Ω) Impedance range in the
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0.001
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area>0.5mV (Ω) Number of mapping points in
638
367
271
218±99
164±69
248±89
89-322
89-221
149-322
LVA (n) Mean impedance in LVA (Ω)
0.002
Impedance range in LVA (Ω)
Table 3. Comparison of epicardial ablation sites during sinus rhythm between areas without CT-derived fat and with CT-derived fat.
Total epicardial ablation points
Without fat
With fat
during sinus rhythm
n=94
n=142
0.80±0.64
1.14±0.68
0.222
86.4±27.1
73.1±21.1
0.01
p-value
n=236 Pre-ablation mean amplitude of bipolar EGM (mV) Pre-ablation mean duration of bipolar EGM (ms)
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Pre-ablation mean number of
5.8±4.0
4.2±3.0
0.10
deflection of bipolar EGM (n) Pre-ablation mean impedance (Ω)
134±16
156±28
0.02
Post-ablation mean amplitude of
0.43±0.22
0.65±0.50
0.002
55.2±18
46.6±14
0.030
bipolar EGM (mV) Δ bipolar EGM between pre- and post-ablation (%) Number of ablation points with
75/94(79.7%) 89/142(62.7%)
0.01
Δbipolar EGM>50% (n) Δimpedance between pre- and
17±8.4
12.6±6.3
0.004
83/94(88.2)
130/142(91.5)
0.48
post-ablation (Ω) Number of ablation points withΔ impedance>10 Ω, n(%)
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Figure legends Figure 1: Processing of off-line analysis in the present study. This is an example of a patient with remote anteroseptal myocardial infarct with epicardial ventricular tachycardia ablation. A: Three-dimensional epicardial fat meshes were created from the short-axis or longitudinal-axis contrast-enhanced computed tomography imaging slices. B: The computed tomography was segmented and imported into the mapping system. C: The epicardial voltage map and impedance map, merging enhanced computed tomography images acquired before the ablation session. D: The epicardial voltage map and impedance map, merging computed tomography images of the epicardium acquired after off-line processing.
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Figure 2: Box plots demonstrating comparison of impedance between without fat and with fat among mapping points in different group. LVA = low voltage area.
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Figure 3: Box plots demonstrating comparison of impedance between without fat and with fat among ablation points. Ab = ablation.
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