Local impedance measurements during contact force‐guided cavotricuspid isthmus ablation for predicting an effective radiofrequency ablation

Abstract Background An ablation catheter capable of contact force (CF) and local impedance (LI) monitoring (IntellaNav StablePoint, Boston Scientific) has been recently launched. We evaluated the relationship between the CF and LI values during radiofrequency catheter ablation (RFCA) along the cavotricuspid isthmus (CTI). Methods Fifty consecutive subjects who underwent a CTI‐RFCA using IntellaNav StablePoint catheters were retrospectively studied. The initial CF and LI at the start of the RF applications and mean CF and minimum LI during the RF applications were measured. The absolute and percentage LI drops were calculated as the difference between the initial and minimum LIs and 100 × absolute LI drop/initial LI, respectively. Results We analyzed 602 first‐pass RF applications. A weak correlation was observed between the initial CF and LI (r = 0.13) and between the mean CF and LI drops (r = 0.22). The initial LI and absolute and percentage LI drops were greater at effective ablation sites than ineffective ablation sites (median, 151 vs. 138 Ω, 22 vs. 14 Ω, and 14.4% vs. 9.9%; p < .001), but the initial and mean CF did not differ. At optimal cutoffs of 21 Ω and 10.8% for the absolute and percentage LI drops according to the receiver‐operating characteristic analysis, the sensitivity, and specificity for predicting an effective ablation were 57.4% and 88.9% and 80.0%, and 61.1%, respectively. Conclusions The effective sites during the CF‐guided CTI‐RFCA had greater initial LI and LI drops than the ineffective sites. Absolute and percentage LI drops of 21 Ω and 10.8% may be appropriate targets for an effective ablation.


| INTRODUC TI ON
Radiofrequency catheter ablation (RFCA) along the cavotricuspid isthmus (CTI) is a commonly utilized procedure for treating CTIdependent atrial flutters. 1,2 The goal of a CTI-RFCA is to complete bidirectional conduction block along the CTI. 3 Several indices for contributing to successful completion of the CTI bidirectional conduction block have been reported: the contact force (CF), 4 forcetime integral (FTI), 5 ablation index (AI) incorporating the CF, RF application duration, and power in a weighted formula, 6,7 and electroanatomic coupling index. 8 Local impedance (LI) monitoring during RFCA has been reported to be useful for predicting an effective ablation, 9,10 and greater LI drops are associated with an effective lesion formation. [11][12][13] In those previous studies with LI monitoring during RFCA, the LI values were measured using a 4-electrode method with micro-electrodes on the 4.5-mm tip of the ablation catheter (IntellaNav MiFi OI, Boston Scientific). On the other hand, a newer ablation catheter capable of LI monitoring (IntellaNav StablePoint; Boston Scientific), which has been recently introduced to clinical practice, uses a 3-electrode method without micro-electrodes to measure the LI values and has a 4-mm catheter tip. 14 In addition, the newer LI-monitoring ablation catheter is also capable of CF monitoring. As a result of the difference in the LI measurement methods, size of the catheter tip, and presence or absence of CF monitoring, the LI values, and drops during a CTI-RFCA are likely to differ between those two types of LI-monitoring ablation catheters. So far there have been no published clinical studies on CTI-RFCA using an ablation catheter capable of simultaneous CF and LI monitoring. Thus, we sought to investigate the relationship between the CF and LI values during a CTI-RFCA using the newer LI-monitoring ablation catheter and compared those values between the effective and ineffective ablation sites.

| Study population
Fifty consecutive subjects who underwent a first CTI-RFCA and

RFCA of atrial fibrillation (AF) at Gunma Prefectural Cardiovascular
Center from December 2020 to July 2021 were included in this retrospective observational study. All RFCA procedures were performed using the IntellaNav StablePoint ablation catheter with the Rhythmia mapping system (Boston Scientific). Eleven subjects (22.0%) had CTI-dependent atrial flutters before the RFCA procedure.
Oral anticoagulation was started more than 1 month prior to the procedure and was continued throughout the periprocedural period.
All class I antiarrhythmic drugs were stopped pre-procedurally for ≥5 half-lives, while bepridil was continued during the periprocedural period. All subjects gave written informed consent, and the study protocol was approved by the local ethics committee and adhered to the Declaration of Helsinki.

| RFCA
We previously published the RFCA procedures and periprocedural anticoagulation protocol. 13,15 During the procedure, propofol or dexmedetomidine, and pentazocine were administered intravenously to maintain deep conscious sedation. The activated clotting time was maintained between 300 and 400 s by an intravenous continuous and bolus infusion of heparin throughout the procedure. A multielectrode catheter was positioned in the coronary sinus (CS) via the right femoral vein and served as the positional reference for mapping using the Rhythmia system. A steerable sheath (Agilis NxT; Abbott) was advanced into the right atrium (RA), and the ablation catheter was introduced through the sheath. The CTI linear ablation was performed with a point-by-point ablation from the tricuspid annulus to the inferior vena cava during CTI-dependent atrial flutters or pacing from the proximal CS. Continuous RF lesions were created along the CTI with an inter-lesion distance of 4-5 mm between two neighboring lesions. Each application of RF energy was delivered with a target CF of 5-20 g, power output of 25-40 W, RF duration of 20-40 s, and maximum temperature of 40°C at an irrigation flow rate of heparinized saline of 8 or 15 ml/min. The RF energy deliveries were started when the ablation catheter tip was positioned on the target ablation site and the CF values reached ≥5 g and were stopped when the LI values reached the plateau of the impedance curve, decreased to >50 Ω from that when starting the RF applications, or increased steadily during ongoing ablation. 14 If the ablation catheter tip was displaced during the ongoing ablation, the RF energy deliveries were immediately stopped and applied again at the same site after repositioning the ablation catheter tip. When the LI values did not sufficiently drop during the ongoing ablation, the RF power output was increased up to 40 W or the catheter orientation relative to the ablation site (parallel, oblique, or perpendicular) was changed at the operators' discretion. When the LI values rapidly dropped, the RF power output was decreased.
First-pass conduction block was defined as the completion of bidirectional conduction block by the first linear ablation from the tricuspid valve annulus to the inferior vena cava without any additional RF applications. When the first-pass block was not achieved or the recovery of conduction occurred during the waiting period, the conduction gaps were mapped using the ablation catheter or a 64-electrode minibasket catheter (IntellaMap Orion, Boston Scientific), and additional RF ablation was applied to eliminate the gaps. During the additional RF applications at sites with gaps, the catheter orientation relative to those sites was changed from that during the initial RF applications, so that the LI values would further drop. The completion of bidirectional conduction block along the CTI was verified by standard electrophysiological methods, including differential pacing maneuvers and recording widely spread double potentials along the CTI ablation line. 16,17

| Procedural parameters
Effective ablation sites were defined as those sites without conduction gaps during the first-pass CTI-RFCA, while ineffective ablation sites were defined as those with conduction gaps. The following procedural parameters during the first-pass CTI-RFCA were evaluated: the CF, RF power output, RF application duration, RF energy delivery, FTI, and LI. The initial and mean CF were defined as the CF values measured at the start of the RF applications and the average value of the CF during the RF applications, respectively. The FTI was calculated by multiplying the mean CF by the RF application duration. The LI was measured using a 3-electrode method, by driving a non-stimulatory alternating current (5.0 μA at 14.5 kHz) between the tip electrode and proximal ring to create a local potential field. 14 The initial and minimum LIs were defined as the LI value measured at the start of the RF applications and minimum value during the RF applications, respectively ( Figure 1). Further, the absolute and percentage LI drops were obtained as the difference between the initial and minimum LIs and 100 × absolute LI drop/initial LI, respectively.

| Statistical analysis
Normally distributed continuous variables were expressed as the mean ± standard deviation (SD), non-normally distributed continuous variables were as the median and interquartile range (IQR, 25th-75th percentile), and categorical variables were as the number and percentage of subjects. A Mann-Whitney's U-test was used for a comparative analysis between the effective and ineffective ablation sites during the first-pass CTI-RFCA. The relationship between the CF values and LI drops was evaluated using Pearson's correlation coefficient. To compare the strength of the association of the parameters for predicting an effective RF ablation, the area under the receiver operating characteristics (ROC) curve for each parameter was estimated. The statistical significance for all tests was accepted at a p-value of <0.05. The statistical analyses were performed using JMP 11.2 software (SAS Institute Inc.,).

| RE SULTS
Tables 1 and 2 present the baseline and procedure-related characteristics of the study subjects. The mean age was 67 ± 11 years, and 35 subjects (70.0%) were men. Thirty-two subjects (64.0%) had first-pass CTI conduction block, while the remaining 18 (36.0%) had some residual conduction gaps after the first-pass CTI ablation. No recovery of conduction along the CTI occurred during the waiting period in the study subjects. Finally, CTI bidirectional conduction block was completed in all subjects. No procedure-related complications occurred in this series, including an audible steam pop, cardiac tamponade, or stroke. During a median follow-up period of 169 days (IQR, 109-231 days) after the RFCA procedure, none of the subjects had any recurrences of CTI-dependent atrial flutters. were analyzed (  Comparison of the procedure-related parameters between the initial and additional RF applications at the ineffective ablation sites during the first-pass CTI-RFCA. Thus, the use of CF-sensing ablation catheters has been widespread in RFCA procedures and novel markers of the ablation lesion quality such as the AI and lesion size index have been developed. 20,21 On the other hand, the LI also provides information on the cathetertissue coupling, issue characteristics, and tip electrode surface area covered by the myocardium. Previous studies reported that LI drops could predict the lesion formation during RF ablation and were significantly greater at effective ablation sites than ineffective ablation sites. [9][10][11][12][13] However, the CF-related information was not available in those studies because the LI-monitoring ablation catheter

| Relationship between the CF and LI during the CTI-RFCA
The LI depends on not only the catheter-tissue contact but also several factors: the tissue characteristics, catheter orientation relative to the ablation site (parallel, oblique, or perpendicular), and tip electrode surface area covered by the myocardium. 9,11,14,23 This may be why the initial CF hardly correlated with the initial LI in the current study. Further, the mean CF and FTI were comparable between effective and ineffective ablations sites, and the LI drops hardly correlated with the mean CF and FTI. That may be because those factors that can affect the LI values mentioned above have an impact on LI drops during RF ablation. Since the CTI often has a complex anatomy, such as a pouch, not only the magnitude of the CF but also the catheter tip-tissue coupling is important to achieve an effective RF ablation. Therefore, simultaneous CF and LI monitoring appeared to be useful to improve the catheter tip-tissue coupling and consequently the RF lesion formation by directly providing biophysical feedback.

| LI drops for predicting an effective ablation during the CTI-RFCA
The transmurality and continuity of the RF lesions are essential for creating bidirectional conduction block along the CTI. 6

| Study limitations
This study had several limitations. First, this was a retrospective, non-randomized, single-center study that included a limited sample size. A prospective, randomized, multicenter study comparing a CTI-RFCA guided by CF and LI monitoring and that guided by conventional surrogate markers estimating the lesion formation will be needed to further validate the usefulness of simultaneous CF and LI monitoring during a CTI-RFCA. Second, this study focused on the acute success of the CF-and LI-guided CTI-RFCA. The long-term efficacy of the CTI-RFCA procedure remains unknown. That is because 11 subjects had clinically detected CTI-dependent atrial flutters, while the remaining 39 did not have pre-diagnosed CTI-dependent atrial flutters and underwent a CTI-RFCA as part of an AF catheter ablation. Third, the CF and LI values fluctuated with the respiratory movements during the CTI-RFCA. Finally, we did not evaluate the relationship between the LI and anatomical features of the CTI, such as the presence of a pouch, because not all subjects underwent either right atreiography or intracardiac echocardiography.

| CON CLUS IONS
Effective ablation sites during the CF-guided CTI-RFCA had higher initial LI values and greater LI drops than ineffective ablation sites.
An absolute LI drop of 21 Ω and percentage LI drop of 10.8% may be appropriate targets for an effective ablation during a CTI-RFCA using an ablation catheter capable of simultaneous CF and LI monitoring.

ACK N OWLED G M ENT
We would like to thank Mr. John Martin for his help in the preparation of the manuscript.

CO N FLI C T O F I NTE R E S T
The authors declare no conflict of interest for this article. The protocol for this research project has been approved by a suitably consti-