Change in the local impedance and electrograms recorded by a micro‐electrode tip catheter during initial atrial fibrillation ablation

Abstract Background A novel measurement of the local impedance (LI) and electrograms recorded from micro‐electrodes on catheter tip has been developed. However, the data during pulmonary vein (PV) ablation is not sufficient. We aimed to investigate the utility of this measurement during initial atrial fibrillation (AF) ablation. Methods We investigated 111 representative radiofrequency applications in 7 AF patients without a history of prior ablation (6 males, age 68 [65‐72] years, 2 persistent AF). The ablation strategy was PV isolation for paroxysmal AF and single ring box isolation for persistent AF, using MiFi catheter. The correlation of the generator impedance (GI) drop and LI drop after radiofrequency applications and the predictive value of the initial LI elevation before radiofrequency applications for LI drop were analyzed. Also, the LI and GI drop were investigated according to the location of RF applications. Results The LI drop was higher than GI drop (23.7 [16.4‐35.7] and 9.0 [6.0‐12.0]; P < .01). There were correlations between the initial LI elevation and LI drop (R 2 = 0.466, P < .01) and between the LI and GI drop (R 2 = 0.263, P < .01). The LI drops significantly differed according to the different anatomical localizations by the Kruskal–Wallis test, although the GI drops did not differ (P < .01 and P = .49, respectively) Conclusion LI drop was associated with initial LI elevation and was larger than GI drop. LI drop was different according to locations, although GI drop was not. These findings might indicate that LI drop would be a more sensitive marker for lesion formation than GI drop.


| INTRODUC TI ON
An electrical pulmonary vein (PV) isolation by catheter ablation has been established as a curative treatment for paroxysmal atrial fibrillation (AF). 1 Since most paroxysmal AF patients are able to be cured by PV isolation and recovery of PV conduction is one of the most frequent causes of AF recurrence, the durability of the PV isolation is essential. 2,3 Successful radiofrequency (RF) catheter ablation is dependent on the ability to deliver an effective lesion with good and stable tissue contact. Contact force (CF) between the catheter tip and myocardium has been identified as one of the most important determinants influencing the RF lesion size as well as the RF power and duration. [4][5][6] Other than the CF, the Force-Time Integral and Ablation Index have been shown to have a positive correlation with better patient outcomes. 4,7 However, such parameters represented factors on the side of delivering RF energy and did not imply the state of the tissue. On the other hand, the generator impedance (GI) between the catheter tip and cutaneous patch is widely known as an electrical index of lesion formation. 8 The previous study suggested that increased tissue contact was associated with a larger GI drop during RF applications. 9 However, the starting GI was not shown to be associated with the CF or lesion creation, and information on GI decreases is available only after starting an RF application.
In addition, GI measurements can be affected not only by the degree of contact with the myocardium but also by other thoracic structures.
Recently, a novel ablation catheter (Intellanav MiFi OI catheter, Boston Scientific) has been developed, which consists of 3 equally spaced 1-mm diameter micro-electrode incorporated into the tip. This novel catheter provides ultra-high-density mapping by micro-electrode bipolar recordings and incorporates a "DirectSense" algorithm to measure the local tissue impedance (LI) from the distal micro-electrodes. 10 The resistive load on the distal electrode of an ablation catheter is influenced by the percentage of surface area covered by myocardium. LI is highly sensitive to objects with dissimilar resistivity. LI is able to distinguish the degree of catheter-tissue contact, because healthy myocardium displays a larger resistivity compared with blood pool. The past studies reported that this catheter provided a high electrogram spatial resolution, which may aid in identifying critical isthmuses and gaps on a line of block, and that the LI drop measurements during RF applications give an indication of the tissue contact and subsequent effective lesions. [11][12][13][14] However, the data on this novel catheter during the initial AF ablation procedure, such as a PV isolation and single ring box isolation, have scarcely been reported. Therefore, the present report investigated the efficacy of the measurement of the local electrogram and LI with a novel MiFi catheter during the initial AF ablation procedure.

| Study population
The RF applications from 7 patients undergoing an initial catheter ablation of paroxysmal or persistent AF at Keio University Hospital were retrospectively analyzed. PV isolations were performed in 5 patients and single ring box isolation in 2. The study protocol was approved by the institutional review board committee at the hospital. All participants provided written informed consent for the procedures.

| Catheter ablation procedure
The ablation procedure was performed under deep sedation with propofol and monitored with a Bispectral Index monitor (Aspect Medical Systems), maintaining the value within the range of 40-60.
An oral airway and facial mask for auto servo-ventilation (ResMed) were provided to stabilize the respirations. Unfractionated heparin was administered before the transseptal punctures to maintain an activated clotting time of 300-400 seconds for the duration of the procedure.
A multielectrode catheter was introduced from the femoral vein and placed in the right ventricle, recording the His bundle electrogram with the proximal electrodes. Another multielectrode catheter was introduced from the right jugular vein and placed in the coronary sinus, to record the right atrial and superior vena cava electrograms with the proximal electrodes, which also could be The target LI drop for a single RF application was ≧20, and the RF application was forcibly stopped when the duration reached 30 seconds, LI drop reached 50 Ω, or esophageal temperature reached 39 degrees. The procedural endpoint was a bidirectional conduction block into and out of the PVs or box area. The surface and endocardial electrograms were continuously monitored and recorded for offline analysis (Bard Electrophysiology, Boston Scientific). The intracardiac electrogram was filtered from 30 to 250 Hz and then measured at a sweep speed of 100 mm/s.

| Impedance assessment
The GI was measured from Maestro 4000 between the dome electrode and cutaneous patch. At the same time, the LI was measured from the micro-electrodes of the MiFi ablation catheter by injecting a non-stimulatory alternating current (5.0 μA, 14.5 kHz) between the tip electrode and proximal ring to create a local potential field. The amplitude of the potential field distortions, caused by contact with high resistivity myocardium, between each micro-electrode and the distal ring was recorded. The potential measurement was converted into the impedance by dividing it by the injection current. 10 The highest impedance among three impedance measurements by the micro-electrodes was used as the LI. The reference LI was recorded in the blood pool of the left atrium prior to the initial RF application. The initial impedance just before the RF application and impedance drop after the RF application were measured both from the micro-electrodes of the catheter and from the generator. The initial LI elevation was defined as the difference between the initial LI and reference LI.
The impedance drop was defined as an impedance decrease during a RF application. The correlation of the GI and LI drop and predictive value of the initial LI elevation for the LI and GI drop were analyzed.

| Electrogram amplitude assessment
The electrograms were recorded from the standard tip bipolar recordings from the dome to ring and the micro-electrode bipolar recordings, just prior to the RF application and right after the RF application. For the electrogram from the micro-electrode recording, the maximum value from the three micro-electrode pair recordings was used. The electrogram amplitude recorded by the two different methods was compared during sinus rhythm and AF

rhythm.
Also, in order to investigate the effectiveness of the microelectrode bipolar recordings in prior RF applicated regions, we assessed the electrogram amplitudes at the last five RF applications before completion of PV or box isolation in all cases. We compared the electrogram amplitudes using the standard tip bipolar recordings and micro-electrode bipolar recordings in these ablation points before the RF applications started. F I G U R E 1 Radiofrequency applications assessed in the present study. We conducted the radiofrequency applications with an adequate distance from the prior ablation lesions at first, and then we added radiofrequency applications to anatomically fill the gaps. In order to exclude the influence of the adjacent ablation lesions, we only investigated the former radiofrequency applications, shown in this figure. A, For the pulmonary vein (PV) isolation, we investigated the radiofrequency applications on the PV anterior wall, posterior wall, roof portion, and bottom portion of each PV. B, For the box isolation, we investigated the radiofrequency applications on the left PV anterior wall, roof area, bottom area, and right PV anterior wall. LPV, left pulmonary vein; RPV, right pulmonary vein

| Study subject
The baseline characteristics of all 7 patients (6 males and 1 female) are listed in Table 1

| Impedance Assessment
The impedance data and electrogram amplitude data before and after the RF applications are summarized in Table 2 Figure 5B). The representative intracardiac electrogram is shown in Figure 5A. The electrogram amplitudes were higher and sharper in micro-electrode bipolar recordings, comparing to the standard tip bipolar recordings.

| D ISCUSS I ON
This was a retrospective observational study including patients who underwent an initial AF ablation (ipsilateral circumferential PV isolation or single ring box isolation). The major findings were as follows.  Another feature of the MiFi catheter is the electrogram recordings from the micro-electrodes, which provide a higher electrogram spatial resolution and may aid in identifying the critical location

Patients (n = 7)
Local impedance  during the ablation procedure. 11 The present study showed that the electrogram amplitude recorded by the micro-electrodes was larger than that by the standard tip bipolar recording from the dome to ring. By providing a high electrogram spatial resolution, this novel electrogram recording could aid in performing AF ablation, since we often need to conduct a PV isolation during an AF rhythm. In the additional assessment of the last five RF applications before completion of the PV or BOX isolations, the electrogram amplitudes in both standard tip bipolar recordings and micro-electrode bipolar recordings were relatively low. Even in these low voltage regions with prior RF applications, the electrogram amplitudes by micro-electrode bipolar recordings were significantly higher than the standard tip bipolar recordings, which suggested that the micro-electrode bipolar recording could be useful in low voltage region such as diseased atria or atria with prior AF ablations.

| LI M ITATI O N S
The present study had several limitations. First, this was a singlecenter observational study; and therefore, the results were generally affected by multiple confounding factors. The limited sample size also influenced our analysis. Second, since no complications were recorded in the present study, the amount of the LI drop showing excessive contact was unknown. Third, it is quite helpful to represent an impedance curve in this investigation, however, only the initial and final LI values were saved in this version of RHYTHMIA system we used. Therefore, the tilts of LI changes were unknown. As the LI curves of all RF applications are saved in the new version of RHYTHMIA system, the LI curves should be investigated in the future study. Fourth, our study did not provide any information on the quality of the tissue contact and did not investigate the effectiveness of the RF applications, though the change in the amplitudes of the electrograms was assessed. Recently, a new catheter, which is able to measure both contact force and LI drop, began to be used in the clinical setting. The correlation between these two parameters should be investigated in the future study.
Finally, our interpretations are only applicable to the de novo ablation sites, since the local impedance and local electrogram could have been affected by the prior adjacent RF application.

| CON CLUS ION
The LI drop was associated with the initial LI elevation and was larger than the GI drop, and LI drop was different according to different locations although GI drop was not. Our findings indicate that the LI drop would be a more sensitive marker for the lesion formation than the GI drop. The MiFi electrodes could record higher amplitudes of the local electrograms as compared to the conventional electrodes, which would be helpful for PV ablation.

ACK N OWLED G EM ENTS
We thank Mr John Martin for his linguistic advice.

D I S C LO S U R E S TAT E M E N T CO N FLI C T O F I NTE R E S T
Authors declare no conflict of interests for this article.

I R B A PPROVA L N U M B E R
20120275, IRB approval date: 2020/5/29.