Superiority of the Combination of Input and Output Parameters to the Single Parameter for Lesion Size Estimation

Abstract

Background: For lesion size prediction, each input parameter, including ablation energy (AE), and output parameter, such as impedance, is individually used. We hypothesize that using both parameters simultaneously may be more optimal.

Methods and Results: Radiofrequency applications at a range of power (30–50 W), contact force (10 g and 20 g), duration (10–60 s), and catheter orientation with normal saline (NS)- or half-normal saline (HNS)-irrigation were performed in excised porcine hearts. The correlations, with lesion size of AE, absolute impedance drop (∆Imp-drop), relative impedance drop (%Imp-drop), and AE*%Imp-drop were examined. Lesion size was analyzed in 283 of 288 lesions (NS-irrigation, n=142; HNS-irrigation, n=141) without steam pops. AE*%Imp-drop consistently showed the strongest correlations with lesion maximum depth (NS-irrigation, ρ=0.91; HNS-irrigation, ρ=0.94), surface area (NS-irrigation, ρ=0.87; HNS-irrigation, ρ=0.86), and volume (NS-irrigation, ρ=0.94; HNS-irrigation, ρ=0.94) compared with the other parameters. Moreover, compared with AE alone, AE*%Imp-drop significantly improved the strength of correlation with lesion maximum depth (AE vs. AE*%Imp-drop, ρ=0.83 vs. 0.91, P<0.01), surface area (ρ=0.73 vs. 0.87, P<0.01), and volume (ρ=0.84 vs. 0.94, P<0.01) with NS-irrigation. This tendency was also observed with HNS-irrigation. Parallel catheter orientation showed a better correlation with lesion depth and volume using ∆Imp-drop, %Imp-drop, and AE*%Imp-drop than perpendicular orientation.

Conclusions: The combination of input and output parameters is more optimal than each single parameter for lesion prediction.

Radiofrequency (RF) catheter ablation is the standard treatment for cardiac arrhythmias,^1,2 but despite efforts at refining ablation technology, including the development of irrigated-tip and contact force (CF)-sensing ablation catheters, success rates of catheter ablation procedures for atrial and ventricular arrhythmias are suboptimal.³ To prevent arrhythmia recurrence, creating a durable lesion of optimal size is one of the most important factors,⁴ and several studies have reported that input factors such as RF power and duration show a positive correlation with lesion size.^5–7 On the other hand, impedance has been used as an output parameter to predict lesion formation because it provides information regarding the tissue reaction during RF ablation.^7–11

Because each input and output parameter is individually used to estimate RF lesion size in the clinical setting, little is known about the usefulness of combining these parameters for predicting lesion size. We recently reported that local impedance (LI), an output parameter, significantly improved lesion size estimation when combined with ablation energy (AE).¹² However, it remains unclear whether the combination of AE and conventional generator impedance improves lesion size prediction compared with their sole use. Therefore, in this study we investigated the utility of a combined parameter to predict lesion size.

Methods

Ex-Vivo Model

A section of the porcine left ventricular myocardium (n=30) excised within 24 h and preserved in a fresh state was placed on a rubber plate and sunk to the bottom of a circulating saline bath at 37℃ (Figure 1A). To simulate the clinical setting, salinity was controlled to maintain the impedance level of 100±5 ohm, measured by the catheter above the myocardial slab, based on the value in the clinical setting. The TactiFlex^TM SE ablation catheter (Abbott, St. Paul, MN, USA) installed with a 4-mm flexible 8Fr tip and a CF-sensor was used in this study. This catheter has a single thermocouple embedded within the tip (0.3 mm from the tip) for temperature monitoring and laser-cut kerfs to distribute irrigant more evenly around the ablation tip. This catheter was positioned perpendicular and parallel to the myocardium through a long sheath (Figure 1B).

Figure 1.

Ex-vivo experimental model. (A) Ex-vivo experimental model. (B) Left panel shows a perpendicular ablation catheter orientation and right panel shows a parallel orientation to the myocardium. (C) Scheme of lesion measurements. (D) Representative cases of lesion volume and ablation parameters. Note that AE*%Imp-drop is better correlated to the lesion volume compared to AE alone or %Imp-drop alone.

Lesion Creation

RF energies of 30, 40, and 50 W were applied to the left ventricular myocardium by the ablation catheter at 2 CFs (10 g and 20 g), 4 ranges of duration (10, 20, 30, and 60 s), and 2 orientations (perpendicular and parallel to the tissue). The ablation catheter was irrigated with either normal saline (NS, 0.9%) or half-normal saline (HNS, 0.45%) at 13 mL/min (Cool Point^TM, Abbott) during RF application, and a power-controlled ablation mode with a temperature cutoff of 43℃ was used. Lesions in which steam pops (defined as audible pops) occurred were excluded from this study.

Lesion Size Measurements

The lesion border was defined as the location of a change in tissue color. The myocardium was cross-sectioned along the surface length at the level of each lesion. Each lesion was measured with a digital caliper with a resolution of 0.1 mm by the same observer who was blinded to the lesion protocol. The maximum length (a), maximum depth (b), depth to the maximum length (c), surface maximum length (d), and surface width (e) of the created lesion were measured as shown in Figure 1C. Lesion surface area and lesion volume were calculated from the following formulas: lesion volume = (1/6)*π*(a²*b + c*d²/2); lesion surface area = π*d/2*e/2.^12–14

Measured Indices

Time-dependent parameter changes of RF power, duration, CF, temperature, and impedance were automatically collected in the generator (Ampere^TM RF Generator, Abbott). AE (defined as RF power multiplied by duration) represents an input parameter. Wedefined as output parameters as absolute impedance drops during RF application (∆Imp-drop) and relative impedance drops (%Imp-drop, defined as ∆Imp-drop divided by the maximum impedance). The impedance variations were calculated based on the maximum and minimum impedances recorded in the generator during RF applications. AE multiplied by %Imp-drop (AE*%Imp-drop) was calculated to assess the effect of combined input and output parameters. Correlations between these parameters and lesion maximum depth, surface area, and volume were assessed (Figure 1D). Moreover, the effect of catheter orientation during RF on lesion size estimation was also assessed.

Statistical Analysis

Continuous variables are expressed as mean±standard deviation or median and 25–75th percentile. Spearman’s rank correlation analysis was used to assess the correlation between variables.¹⁵ Fisher’s Z transformation was performed to compare the strength of correlation. Statistical significance was defined as P value <0.05. Statistical analyses were performed using StatFlex software version 7.1 (Artech, Osaka, Japan).

Results

Correlation of Ablation Parameters and Lesion Size

Lesion size was analyzed in 283 of 288 lesions (98.3%; NS-irrigation, n=142; HNS-irrigation, n=141) without steam pops. Steam pops occurred in 2 lesions in the NS group and in 3 lesions in the HNS group, all at ablation power of 50 W and RF duration >40 s. Median lesion maximum depth, surface area, and volume with NS- and HNS-irrigation were 3.7 (2.4–4.9) mm and 4.0 (3.0–5.2) mm, 36.7 (29.0–45.8) mm² and 41.2 (32.4–52.9) mm², and 166.8 (83.1–328.1) mm³ and 212.0 (111.2–354.8) mm³, respectively.

Figure 2 shows the correlations between AE, ∆Imp-drop, %Imp-drop, and lesion size with NS-irrigation during RF application. Each of AE, ∆Imp-drop, and %Imp-drop significantly correlated with maximum depth (AE, ρ=0.83; ∆Imp-drop, ρ=0.73; %Imp-drop, ρ=0.75), surface area (AE, ρ=0.73; ∆Imp-drop, ρ=0.78; %Imp-drop, ρ=0.80), and volume (AE, ρ=0.84; ∆Imp-drop, ρ=0.79; %Imp-drop, ρ=0.81).

Figure 2.

Correlations between ablation parameters and lesion characteristics with normal saline irrigation. Correlations of ablation energy, absolute impedance drops from baseline (∆Imp-drop), relative impedance drops (%Imp-drop), AE*%Imp-drop and lesion maximum depth (A), surface area (B), and volume (C), respectively. Blue, green, and red dots represent 30 W, 40 W, and 50 W radiofrequency application, respectively. Circles and triangles represent lesions created with perpendicular and parallel catheter orientations.

Figure 3 shows the correlations between AE, ∆Imp-drop, %Imp-drop, and lesion size with HNS-irrigation. Each of the parameters also correlated with surface area (AE, ρ=0.76; ∆Imp-drop, ρ=0.78; %Imp-drop, ρ=0.81), maximum depth (AE, ρ=0.94; ∆Imp-drop, ρ=0.70; %Imp-drop, ρ=0.74), and volume (AE, ρ=0.90; ∆Imp-drop, ρ=0.74; %Imp-drop, ρ=0.78).

Figure 3.

Correlations between ablation parameters and lesion characteristics with half-normal saline irrigation. Correlations of ablation energy, absolute impedance drops from baseline (∆Imp-drop), relative impedance drops (%Imp-drop), AE*%Imp-drop and lesion maximum depth (A), surface area (B), and volume (C), respectively. Blue, green, and red dots represent 30 W, 40 W, and 50 W radiofrequency application, respectively. Circles and triangles represent lesions created with perpendicular and parallel catheter orientations.

Because %Imp-drop increased the strength of correlation with the lesion maximum depth, surface area, and volume than did ∆Imp-drop regardless of NS- or HNS-irrigation (P<0.05), we defined %Imp-drop as a representative output factor. Additionally, combination indices of AE (representative input parameter) and %Imp-drop (representative output parameter) consistently showed the strongest correlations with lesion size regardless of NS-irrigation (maximum depth, ρ=0.91; surface area, ρ=0.87; volume, ρ=0.94) or HNS-irrigation (maximum depth, ρ=0.94; surface area, ρ=0.86; volume, ρ=0.94) as shown in Figure 2 and Figure 3. Compared with AE alone, AE*%Imp-drop significantly increased the strength of correlation in lesion maximum depth (ρ=0.83 vs. 0.91, P<0.01), surface area (ρ=0.73 vs. 0.87, P<0.01), and volume (ρ=0.84 vs. 0.94, P<0.01) with NS-irrigation. On the other hand, with HNS-irrigation, AE*%Imp-drop improved the strength of correlation in lesion surface area (ρ=0.76 vs. 0.86, P<0.01) and volume (ρ=0.90 vs. 0.94, P<0.01), but there was no difference in correlation coefficients with maximum depth between AE and AE*%Imp-drop (ρ=0.94 vs. 0.94, P=1.00). The relationships between AE*%Imp-drop variation and lesion depth are specifically displayed in Figure 4, which can be used as a reference in creating lesions with NS- and HNS-irrigation.

Figure 4.

Relationships between lesion depth vs. ablation energy multiplied by relative impedance drop (AE*%Imp-drop) variation with normal saline (NS) (A) and half-normal saline (HNS) (B) irrigation. Note that lesion depths <0.5 mm (NS, n=10; HNS, n=7) or >7.5 mm (NS, n=2; HNS, n=4) were excluded from this analysis.

Moreover, we compared correlation coefficients between NS- and HNS-irrigations. As shown in Table 1, AE showed a better correlation with lesion maximum depth (NS vs. HNS, ρ=0.83 vs. 0.94, P<0.01) and volume (NS vs. HNS, ρ=0.84 vs. 0.90, P<0.05) for HNS-irrigation, although there was no significant difference in the strength of correlation with surface area between the NS and HNS groups (NS vs. HNS, ρ=0.73 vs. 0.76, P=0.57). On the other hand, none of ∆Imp-drop, %Imp-drop, and AE*%Imp-drop showed significant differences in the strength of correlation with lesion surface area, maximum depth, and lesion volume between the NS and HNS groups.

Table 1.

Correlations Between Ablation Parameters and Lesion Characteristics With NS and HNS Irrigations

	Correlation coefficient (ρ)		P value
	NS (n=142)	HNS (n=141)
Maximum depth, mm
AE, J	0.83	0.94	<0.01*
ΔImp-drop, Ω	0.73	0.70	0.61
%Imp-drop, %	0.75	0.74	0.85
AE*%Imp-drop, J*%	0.91	0.94	0.080
Surface area, mm2
AE, J	0.73	0.76	0.57
ΔImp-drop, Ω	0.78	0.78	1.00
%Imp-drop, %	0.80	0.81	0.81
AE*%Imp-drop, J*%	0.87	0.86	0.74
Volume, mm3
AE, J	0.84	0.90	<0.05*
ΔImp-drop, Ω	0.79	0.74	0.31
%Imp-drop, %	0.81	0.78	0.50
%AE*%Imp-drop, J*%	0.94	0.94	1.00

AE, ablation energy; Imp, impedance; HNS, half-normal saline; NS, normal saline.

Effect of Catheter Orientation on Lesion Size Estimation

Of the 283 lesions irrigated by either NS or HNS, the difference in the strength of correlation was evaluated between perpendicular and parallel catheter orientation to the tissue during RF application. As shown in Table 2, with a parallel catheter tip orientation, ∆Imp-drop, %Imp-drop, and AE*%Imp-drop showed significantly stronger correlations with lesion maximum depth (perpendicular vs. parallel, ∆Imp-drop, ρ=0.65 vs. 0.84, P<0.01; %Imp-drop, ρ=0.68 vs. 0.85, P<0.05; AE*%Imp-drop, ρ=0.88 vs. 0.95, P<0.01) and volume (perpendicular vs. parallel, ∆Imp-drop, ρ=0.73 vs. 0.86, P<0.05; %Imp-drop, ρ=0.75 vs. 0.87, P<0.05; AE*%Imp-drop, ρ=0.92 vs. 0.96, P<0.05) than with a perpendicular orientation, although there were no significant differences in the correlation of ∆Imp-drop, %Imp-drop, and AE*%Imp-drop with lesion surface area between perpendicular and parallel catheter orientation (∆Imp-drop, ρ=0.73 vs. 0.75, P=0.71; %Imp-drop, ρ=0.75 vs. 0.79, P=0.41; AE*%Imp-drop, ρ=0.86 vs. 0.85, P=0.76). On the other hand, correlations between AE and the 3 types of lesion parameters were not affected by catheter orientation. These trends were similar in both the NS and HNS setting (Supplementary Tables 1,2).

Table 2.

Correlation Between Lesion Characteristics Varying Ablation Parameters and Catheter Orientation

	Correlation coefficient (ρ)		P value
	Perpendicular (n=141)	Parallel (n=142)
Maximum depth, mm
AE, J	0.88	0.89	0.70
ΔImp-drop, Ω	0.64	0.82	<0.01*
%Imp-drop, %	0.67	0.85	<0.01*
AE*%Imp-drop, J*%	0.89	0.95	<0.01*
Surface area, mm2
AE, J	0.77	0.77	1.00
ΔImp-drop, Ω	0.73	0.75	0.71
%Imp-drop, %	0.75	0.79	0.41
AE*%Imp-drop, J*%	0.86	0.85	0.76
Volume, mm3
AE, J	0.88	0.88	1.00
ΔImp-drop, Ω	0.69	0.83	<0.01*
%Imp-drop, %	0.72	0.86	<0.01*
AE*%Imp-drop, J*%	0.92	0.95	<0.05*

AE, ablation energy; Imp, impedance.

Discussion

Major Findings

This study demonstrated the following.

(1) Correlations with each lesion characteristic (depth, surface area, and volume) were strongest for AE*%Imp-drop and were consistent for both NS- and HNS-irrigation using the TactiFlex^TM catheter.

(2) AE showed stronger correlations with lesion depth and volume with HNS-irrigation that NS-irrigation, although the correlations of impedance drops with lesion characteristics showed no differences between the NS- and HNS-irrigation groups.

(3) Parallel catheter orientation improved lesion depth and volume estimations using ∆Imp-drop, %Imp-drop, and AE*%Imp-drop compared with the perpendicular.

Efficacy of the Combined Parameter

In the present study, we demonstrated that the combination of the well-known input parameter AE and the output parameter ‘relative impedance drop’ was superior to an input or output parameter alone in predicting lesion size. We have previously reported a similar finding using a catheter specifically capable of measuring LI: that the combined index of AE*%LI-drop improved lesion size estimation than AE alone;¹² however, most ablation catheters in the market are not able to measure LI. Our findings suggest that the concept may be similarly shared in any ablation system using a generator impedance.

Multiple factors including RF power, ablation electrode temperature, RF duration, catheter-tissue CF, ablation circuit impedance, electrode diameter, direction of ablation placement, tissue thickness/architecture, and myocardial blood flow have been reported to influence lesion size.⁵ Recently, combined indices of RF power, duration, and CF such as the ablation index (AI) and lesion size index (LSI) have been reported as useful for predicting lesion size,^16,17 and AI- and LSI-guided catheter ablation has been associated with lower recurrence rates in patients with atrial fibrillation.^18,19 However, several studies showed that these index-guided lesion sizes varied widely with different power and CF settings, and also were associated with a tissue condition.^20–22 These findings imply that a combination of input parameters such as power, duration, and CF may be insufficient for predicting lesion size due to the lack of tissue information during RF application. On the other hand, impedance decreases as a result of tissue heating at the electrode-tissue interface, and tissue temperature at the electrode-tissue interface correlates with lesion size.^,23,24 Several studies have reported a correlation between a decrease in impedance and lesion size;^6–8 however, Wright et al showed a poor correlation between impedance drop and lesion depth.²⁵ Moreover, little is known about whether continuously increasing the RF duration will continue to lead to larger impedance drops.

Given that each of the input and output parameters has different advantages and disadvantages, it seems reasonable to combine these independent parameters. Therefore, we assessed the utility of a combination parameter that included both input and output parameters for lesion size estimation, and we demonstrated that AE*%Imp-drop correlated better with lesion size than each factor alone. Most recently, Schillaci et al reported the usefulness of combining CF (input parameter) and LI (output parameter) to treat premature ventricular contractions.²⁶

Effect of the Irrigant

In this study, AE showed stronger correlations with lesion depth and volume using HNS-irrigation compared with NS-irrigation. Nguyen et al reported that RF ablation with HNS-irrigation created larger lesions than with NS-irrigation for the same delivered power in ex-vivo and in-vivo models.²⁷ They speculated that HNS increases the impedance surrounding the ablating electrode and RF energy dissipation into the irrigant decreases, resulting in more effective RF current delivery to myocardial tissue. The amount of the energy set before RF application (input parameter) might be more effectively delivered not to the blood pool but to the tissue during RF application with HNS-irrigation, which may explain the stronger correlations between AE and lesion depth and volume compared with that of NS-irrigation. Steam pops have been reported to occur more frequently during RF application with HNS-irrigation than with NS-irrigation,²⁸ which may lead to difficulty in precise lesion size assessment using HNS-irrigation. Yamaguchi et al reported that the FlexAbility^TM ablation catheter demonstrated a significantly lower frequency of steam pops than the TactiCath^TM ablation catheter, and they speculated that the lower current density, attributed to the larger tip size (4 mm for FlexAbility^TM vs. 3.5 mm for TactiFlex^TM), together with effective cooling at the heated catheter-tissue interface due to the laser-cut kerfs incorporated into the catheter’s tip, mitigated excessive tissue heating.¹⁴ Given that the same tip design as the Flex Ability^TM ablation catheter has been installed in the TactiFlex^TM ablation catheter, the TactiFlex^TM catheter may also have less frequent steam pops despite HNS-irrigation, thus allowing us to evaluate the association between AE and lesion size.

On the other hand, the correlations between impedance-based parameters and lesion characteristics showed no differences between the NS- and HNS-irrigation groups, although ablation using HNS could theoretically cause more impedance decreases because of the effective RF current delivery. These results suggest that the type of irrigant has little effect on the proportionality between lesion sizes and the magnitude of impedance drops, although the gradient between them might be larger in the HNS- than in the NS-irrigation group.

Effect of Catheter Orientation

Parallel catheter orientation improved lesion size prediction using impedance-based and combined parameters, especially lesion depth and volume. Moreover, these tendencies were consistent for both NS- and HNS-irrigation. By contrast, a correlation between AE and lesion size did not differ with catheter orientation, suggesting that RF energy was proportionally delivered to the myocardium in both orientations with this catheter. These findings suggest that even with the same AE set before the application as an input, more current flows into the tissue, but not into the blood pool with this catheter because a larger electrode surface is attached to the tissue with parallel catheter placement. The total energy may more effectively flow into the tissue, resulting in a larger impedance drop reflecting the temperature variation with parallel catheter placement, which may partially explain the better correlation between the impedance drops and the lesion sizes with parallel catheter placement.

Clinical Implication and Future Direction for Research

In this study, we clearly demonstrated that AE*%Imp-drop, a combination of input and output parameters, correlated more strongly with lesion size than each parameter alone. Although we have demonstrated a similar finding previously with a specific catheter capable of measuring LI,¹² we have here demonstrated that this theory may also be applicable to general ablation systems where only generator impedance can be measured. Because the lesion’s characteristics are affected by several parameters, machine learning technology could be used to create an ideal formula based on both input and output real-time parameters.

Study Limitations

First, our study was conducted using an ex-vivo model with a porcine heart, although it was preserved in as fresh a state as possible. The results may not be the same as in an in-vivo model and human heart. However, a precisely controlled model was required to achieve the purpose of this study, so the ex-vivo model was more suitable. Second, unlike AI and LSI, we did not include CF in the formula of lesion size estimation, the reason being that the strength of the correlation did not improve at all but was even worse if 2 ranges of CF (10 g and 20 g) were included in the formula (data not shown). Thirdly, the lack of multiple ranges of initial impedances before RF application is a notable limitation of the present study. However, the formula may be useful at least in clinically relevant settings (e.g., power, 30–50 W; CF, 10 g and 20 g; duration, 10–60 s in the saline impedance level of 100±5 ohm). Finally, this study investigated lesion size in the setting of RF duration ≤60 s. Therefore, the formula proposed in this study to predict lesion size may not be adopted in a setting of RF duration >60 s.

Conclusions

Compared with AE alone, AE*%Imp-drop showed a stronger correlation with lesion size. The combination of input and output parameters may be optimal for accurately predicting lesion size.

Acknowledgments

We appreciate the technical support for this experiment from Mr. Takenori Yamada, Mr. Masashi Uemoto, Mr. Hiroki Kitabata, and Ms. Lisa Sakurai from Abbott Medical Japan LLC.

Conflicts of Interest

M.G., M.T., and S.M. received honoraria from Medtronic Japan, Boston Scientific, Japan Lifeline, APEX, and WIN International. C.A.M. has received honoraria from Medtronic, Boston Scientific, Biosense Webster, and Adagio. No other authors have a conflict of interest to declare.

Funding

This work was partially supported by JSPS KAKENHI Grant Number 22K16068.

IRB Information

The ethical committee of Tokyo Medical and Dental University granted an exemption from requiring ethics approval because this research was neither a clinical study nor an animal experiment.

Supplementary Files

Please find supplementary file(s);

https://doi.org/10.1253/circj.CJ-23-0574

References

• 1.   Calkins H, Hindricks G, Cappato R, Kim YH, Saad EB, Aguinaga L, et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Europace 2018; 20: e1–e160.
• 2.   Cronin EM, Bogun FM, Maury P, Peichl P, Chen M, Namboodiri N, et al. 2019 HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias. Heart Rhythm 2020; 17: e2–e154.
• 3.   Ptaszek LM, Koruth J, Santangeli P, Piccini JP, Ranjan R, Mahapatra S, et al. Safe and effective delivery of high-power, short-duration radiofrequency ablation lesions with a flexible-tip ablation catheter. Heart Rhythm O2 2022; 4: 42–50.
• 4.   El Haddad M, Taghji P, Phlips T, Wolf M, Demolder A, Choudhury R, et al. Determinants of acute and late pulmonary vein reconnection in contact force-guided pulmonary vein isolation: Identifying the weakest link in the ablation chain. Circ Arrhythm Electrophysiol 2017; 10: e004867.
• 5.   Ariyarathna N, Kumar S, Thomas SP, Stevenson WG, Michaud GF. Role of contact force sensing in catheter ablation of cardiac arrhythmias: Evolution or history repeating itself? JACC Clin Electrophysiol 2018; 4: 707–723.
• 6.   Yamaguchi J, Takigawa M, Goya M, Martin CA, Yamamoto T, Ikenouchi T, et al. Comparison of three different approaches to very high-power short-duration ablation using the QDOT-MICRO catheter. J Cardiovasc Electrophysiol 2023; 34: 888–897.
• 7.   Ikeda A, Nakagawa H, Lambert H, Shah DC, Fonck E, Yulzari A, et al. Relationship between catheter contact force and radiofrequency lesion size and incidence of steam pop in the beating canine heart: Electrogram amplitude, impedance, and electrode temperature are poor predictors of electrode-tissue contact force and lesion size. Circ Arrhythm Electrophysiol 2014; 7: 1174–1180.
• 8.   Avitall B, Mughal K, Hare J, Helms R, Krum D. The effects of electrode-tissue contact on radiofrequency lesion generation. Pacing Clin Electrophysiol 1997; 20: 2899–2910.
• 9.   Harvey M, Kim YN, Sousa J, el-Atassi R, Morady F, Calkins H, et al. Impedance monitoring during radiofrequency catheter ablation in humans. Pacing Clin Electrophysiol 1992; 15: 22–27.
• 10.   Takigawa M, Yamamoto T, Amemiya M, Martin CA, Ikenouchi T, Yamaguchi J, et al. Impact of baseline pool impedance on lesion metrics and steam pops in catheter ablation. J Cardiovasc Electrophysiol 2023; 34: 1671–1680.
• 11.   Amemiya M, Takigawa M, Goya M, Martin CA, Anzai T, Takahashi K, et al. Comparison of two catheters measuring local impedance: Local impedance variation vs. lesion characteristics and steam pops. J Interv Card Electrophysiol 2022; 65: 419–428.
• 12.   Takigawa M, Goya M, Iwakawa H, Martin CA, Anzai T, Takahashi K, et al. Impact of a formula combining local impedance and conventional parameters on lesion size prediction. J Interv Card Electrophysiol 2022; 63: 389–398.
• 13.   Iwakawa H, Takigawa M, Goya M, Iwata T, Martin CA, Anzai T, et al. Clinical implications of local impedance measurement using the IntellaNav MiFi OI ablation catheter: An ex vivo study. J Interv Card Electrophysiol 2022; 63: 185–195.
• 14.   Yamaguchi J, Takigawa M, Goya M, Martin C, Amemiya M, Yamamoto T, et al. Impact of tip design and thermocouple location on the efficacy and safety of radiofrequency application. J Interv Card Electrophysiol 2023; 66: 885–896.
• 15.   Sheskin DJ. Handbook of parametric and nonparametric statistical procedures. 5th edn. Boca Raton: CRC press, 2011.
• 16.   Nakagawa H, Ikeda A, Govari A, Papaioannou T, Constantine G, Bar-Tal M, et al. Prospective study using a new formula incorporating contact force, radiofrequency power and application time (Force-Power-Time Index) for quantifying lesion formation to guide long continuous atrial lesions in the beating canine heart. Circulation 2013; 128: A12104 (Abstract).
• 17.   Calzolari V, De Mattia L, Indiani S, Crosato M, Furlanetto A, Licciardello C, et al. In vitro validation of the lesion size index to predict lesion width and depth after irrigated radiofrequency ablation in a porcine model. JACC Clin Electrophysiol 2017; 3: 1126–1135.
• 18.   Ioannou A, Papageorgiou N, Lim WY, Wongwarawipat T, Hunter RJ, Dhillon G, et al. Efficacy and safety of ablation index-guided catheter ablation for atrial fibrillation: An updated meta-analysis. Europace 2020; 22: 1659–1671.
• 19.   Mattia L, Crosato M, Indiani S, Causin E, Licciardello C, Maria Squasi PA, et al. Prospective evaluation of lesion index-guided pulmonary vein isolation technique in patients with paroxysmal atrial fibrillation: 1-year follow-up. J Atr Fibrillation 2018; 10: 1858.
• 20.   Lozano Granero C, Franco E, Matía Francés R, Hernández-Madrid A, Sánchez-Pérez I, Zamorano Gómez JL, et al. Impact of power and contact force on index-guided radiofrequency lesions in an ex vivo porcine heart model. J Interv Card Electrophysiol 2022; 63: 687–697.
• 21.   Tofig BJ, Lukac P, Nielsen JM, Hansen ESS, Tougaard RS, Jensen HK, et al. Radiofrequency ablation lesions in low-, intermediate-, and normal-voltage myocardium: An in vivo study in a porcine heart model. Europace 2019; 21: 1919–1927.
• 22.   Barkagan M, Leshem E, Shapira-Daniels A, Sroubek J, Buxton AE, Saffitz JE, et al. Histopathological characterization of radiofrequency ablation in ventricular scar tissue. JACC Clin Electrophysiol 2019; 5: 920–931.
• 23.   Hartung WM, Burton ME, Deam AG, Walter PF, McTeague K, Langberg JJ. Estimation of temperature during radiofrequency catheter ablation using impedance measurements. Pacing Clin Electrophysiol 1995; 18: 2017–2021.
• 24.   Hindricks G, Haverkamp W, Gülker H, Rissel U, Budde T, Richter KD, et al. Radiofrequency coagulation of ventricular myocardium: Improved prediction of lesion size by monitoring catheter tip temperature. Eur Heart J 1989; 10: 972–984.
• 25.   Wright M, Harks E, Deladi S, Suijver F, Barley M, van Dusschoten A, et al. Real-time lesion assessment using a novel combined ultrasound and radiofrequency ablation catheter. Heart Rhythm 2011; 8: 304–312.
• 26.   Schillaci V, Arestia A, Maddaluno F, Shopova G, Agresta A, Salito A, et al. Combining contact force and local impedance to treat idiopathic premature ventricular contractions from the outflow tracts: Impact of ablation strategy on outcomes. J Interv Card Electrophysiol 2023, doi:10.1007/s10840-023-01528-6.
• 27.   Nguyen DT, Gerstenfeld EP, Tzou WS, Jurgens PT, Zheng L, Schuller J, et al. Radiofrequency ablation using an open irrigated electrode cooled with half-normal saline. JACC Clin Electrophysiol 2017; 3: 1103–1110.
• 28.   Tschabrunn CM, Pothineni NVK, Sauer WH, Doynow D, Salas J, Liao TE, et al. Evaluation of radiofrequency ablation irrigation type: In vivo comparison of normal versus half-normal saline lesion characteristics. JACC Clin Electrophysiol 2020; 6: 684–692.