Local impedance guides catheter ablation in patients with ventricular tachycardia

Catheter contact and local tissue characteristics are relevant information for successful radiofrequency current (RFC)‐ablation. Local impedance (LI) has been shown to reflect tissue characteristics and lesion formation during RFC‐ablation. Using a novel ablation catheter incorporating three mini‐electrodes, we investigated LI in relation to generator impedance (GI) in patients with ventricular tachycardia (VT) and its applicability as an indicator of effective RFC‐ablation.


| INTRODUCTION
Myocardial electrical impedance has been employed to guide radiofrequency current (RFC)-ablation procedures for the treatment of cardiac arrhythmias for decades. 1,2 Impedance is well-known to reflect tissue characteristics with scarred tissue exhibiting lower impedance. [3][4][5] The impedance of the myocardial tissue during ablation is considered a sensible surrogate of lesion formation. 6 Conventionally, a resistive load of the tissue is measured by the transthoracic impedance from the tip of the catheter to an indifferent electrode on the skin.
Sufficiently high resistive load at the catheter-tissue interface reflects adequate catheter-tissue contact, 7 but thoracic anatomical structures vary between individuals and influence generator impedance (GI). An early clinical study elegantly adopted a model measuring impedance using two body surface electrodes and successfully distinguished between contact and noncontact of catheter and tissue. 8 However, impedance measurements in this model are influenced by the proximity of the body surface electrodes, limiting inter-individual comparability.
Recently, a novel ablation catheter incorporating three minielectrodes in its tip measuring local impedance (LI) at the distal electrode of the catheter has been developed 9 and introduced to clinical practice. 10,11 Herein, we studied LI in comparison to GI during catheter ablation of ventricular tachycardia (VT) to assess its applicability as a feed-back-parameter of RFC-ablation. Our findings suggest that LI can be applied as a sensitive parameter to guide RFC-ablation.

| Study design
Consecutive patients with recurrent VT presenting for catheter ablation in our tertiary center were enrolled in this single-center study. LI and GI were analyzed for baseline impedance, Δimpedance, and drop rate (Δimpedance/time). The study was conducted in accordance with the provisions of the Declaration of Helsinki and its amendments and was approved by the institutional review board of the University Heart Center Hamburg. Written informed consent was obtained from all patients.

| Ablation procedures
In all cases, a steerable 6F decapolar diagnostic catheter (Inquiry, 5  Potential field distortions are divided by the injected current. Impedance is measured from the minielectrodes with a sampling rate of 20 Hz. The catheter has been described in detail previously. 10,11 RFC-ablation in a point-by-point method was analyzed for the complete duration of the RFC-application. Ablation points with instable catheter contact were excluded from the analysis. Dragged RFC-applications were analyzed until the catheter was moved from the initial position on the myocardium. Patients with inducible VT and successful termination by ablation were included in a subgroup analysis comparing impedance drops of RFC-applications terminating the VT to impedance drops for nonterminating RFC-applications. Only specific VT termination was included in the analysis, there was no VT termination by ventricular premature beats. Non-terminating RFC-ablations within a maximum distance of 20 mm from the terminating lesion were included in the subgroup analysis to avoid inclusion of RFC-ablation at sites irrelevant for VT mechanism or RFC-ablation at sites with various tissue characteristics (please see results of the subgroup analysis in paragraph 3.5 of the results section).
ΔLI< 16 Ω was defined as a "low drop" and ΔLI≥ 16 Ω was defined as a "high drop", as a ≥16 Ω drop was shown to be necessary to achieve a loss of capture in the ventricle. 10 The impedance at the start of ablation was considered baseline impedance. 10,11 The difference of baseline impedance and the minimum impedance during RFC-application was defined as ΔLI and ΔGI (Ω), respectively.
Relative ΔLI and relative ΔGI (%) were calculated as proportional impedance drop in relation to baseline impedance. 10

| Voltage measurement
Voltage measurements were acquired during mapping using the 64electrode basket-catheter. Local bipolar voltage ≤0.1 mV was defined as scar and local bipolar voltage ≥1.0 mV as healthy myocardium, according to a previous study by Sacher et al. 13 Local bipolar voltage ≥0.1 mV was defined as nonscarred myocardium. Bipolar voltage recorded from the mini-electrodes of the ablation catheter was analyzed as an additional parameter for substrate characterization with the same cut-off values as for the basket-catheter. Bipolar electrograms were filtered at 30 and 300 Hz. A notch filter was set at 50 Hz.

| Catheter ablation
The irrigated radiofrequency current was delivered in temperaturecontrolled mode with a temperature limit of 43°C as previously described in detail. 12 Initial energy was set to 30 W and titrated to a maximum of 40 W depending on the ablation site and expected myocardial thickness. For inducible and mappable VT, the critical isthmus of the VT was targeted. During the mapping of ongoing VT, we aimed at a maximum point density at the suspected critical site.
Critical isthmus sites were defined a the part of the VT circuit which is delimited by conduction barriers showing the smallest activation region. 14 Length of the isthmus was defined as the distance from the inward wavefront curvature to the outward wavefront curvature. 15 Local signal characteristics were used as an additional parameter.
Entrainment mapping was performed when appropriate. In the case of inducible but hemodynamically instable VT, areas with late potentials and local abnormal ventricular activity (LAVA) were targeted. 12 19 To test homoscedasticity of non-normally distributed data, the Fligner-Killeen-test was used. For a comparison between more than two groups, Kruskall-Wallis-test was used given the non-normality of data distribution.

| RESULTS
Twenty-eight consecutive patients undergoing catheter ablation for recurrent VT were included. Patient characteristics are presented in Table 1. In eight patients (28.6%), substrate mapping and modification only were performed. In 10 patients (35.7%), activation mapping and specific termination of 11 VT during ablation with additional substratebased ablation was performed. In the other 10 patients (35.7%), VT was inducible, but was self-terminating, mechanically terminated or had to be terminated by rapid ventricular pacing or external electrical cardioversion due to hemodynamic compromise ( Table 2).  Figure 1A).  Figure 1B).

| LI but not GI discriminates between scarred and healthy tissue
Baseline LI is lower in scarred tissue even when comparing to healthy tissue in conjunction with borderzone ( Figure S1). Exemplary voltage maps with corresponding LI are shown in Figure 2A,

| Higher ΔLI in RFC-ablation with VT termination
In a subgroup analysis including patient data with VT termination

| High LI drop rate is associated with high ΔLI
Baseline LI for ΔLI≥ 16Ω (high drop) was higher than baseline LI for   Figure S4B). Steam pop did not occur during any RFC-ablation.  Figure S5).

| DISCUSSION
In this study, LI, measured from the tip of a novel ablation catheter with three mini-electrodes, was investigated in relation to the established GI during the ablation of VT. These are our major findings: (1) ΔLI comprises a wider range and has a higher variance compared with ΔGI.
(2  4.2 | LI is more sensitive to impedance reduction than GI as indicated by higher ΔLI drop and higher variance of ΔLI Albeit baseline LI is in general lower than baseline GI, impedance drop during RFC-application is higher for LI than for GI. This finding is in line with initial experimental studies 9 and early clinical data. 10 We showed a correlation of ΔLI with baseline LI, albeit with a low correlation coefficient, which is most likely attributable to heterogenities of ventricular myocardial tissue. We showed higher correlation coefficients for atrial myocardium, 11 a divergence that has been shown previously. 10 Presumably, higher ΔLI can be more easily assessed compared to the smaller and less sensitive ΔGI. Moreover, ΔLI comprised a wider range of values compared to ΔGI. This suggests that LI reflects more subtle changes of tissue characteristics which in turn might remain undetectable by GI. Abbreviations: GI, generator impedance; LI, local impedance; RFC, radiofrequency current; VT, ventricular tachycardia to consider the etiology of the underlying cardiomyopathy when adopting LI for the guidance of catheter ablation in patients with VT.