An Expandable Lattice Electrode Ablation Catheter: A Novel Radiofrequency Platform Allowing High Current at Low Density for Rapid, Titratable and Durable Lesions

Abstract

Background:

High-current short-duration radiofrequency (RF) energy delivery has potential advantages for cardiac ablation. However, this strategy is limited by high-current density and narrow safety-to-efficacy window. The objective of this study was to examine a novel strategy for radiofrequency energy delivery using a new electrode design capable of delivering high power at a low current density in order to increase the therapeutic range of radiofrequency ablation.

Methods:

The Sphere9 is an expandable spheroid-shaped lattice electrode design with an effective surface area 10-fold larger than standard irrigated electrodes (“lattice catheter”). It incorporates 9 surface temperature sensors with ablation performed in a temperature-controlled mode. Phase I: in 6 thigh muscle preparations, 2 energy settings for atrial ablation were compared between the lattice and irrigated-tip catheters (low-energy: T_max75°C/5sec vs 25W/20sec; high-energy: T_max75°C/7sec vs 30W/20sec). Phase II: in 8 swine, right atrial lines were created in the posterior and lateral walls using low and high energy settings, respectively. Phase III: the safety, efficacy and durability at 30-days were evaluated by electroanatomical mapping and histopathological analysis.

Results:

In the thigh model, the lattice catheter resulted in wider lesions at both low and high energy settings (18.7±3.3 vs. 12.2±1.7mm, p<0.0001; 19.4±2.4 vs. 12.3±1.7mm, p<0.0001). Atrial lines created with the lattice were wider (posterior: 14.7±3.4 vs 9.2±4.0mm, p<0.0001; lateral: 15.8±4.2 vs 5.7±4.2mm, p<0.0001) and required 85% shorter ablation time (12.4sec/cm-line vs 79.8 sec/cm-line). While current-squared (I²) was higher with Sphere9 (7.0±0.04 vs 0.2±0.002A², p<0.0001), the current density was lower (9.6±0.9 vs 16.9±0.09mA/mm², p<0.0001). At 30-days, 100% of ablation lines created with the lattice catheter remained contiguous compared to only 14.3% lines created with a standard irrigated catheter. This was achieved without steam pops or collateral tissue damage.

Conclusion:

In this preclinical model, a novel high-current low-density radiofrequency ablation strategy created contiguous and durable ablation lines in significantly less ablation time and a comparable safety profile.

Introduction

Radiofrequency (RF) is the most common energy used for catheter ablation of arrhythmias. Ablation is performed by applying alternating current from the tip electrode of an ablation catheter through a resistive volume (myocardial tissue and blood) to a patch located on the body surface.¹ The current that passes through the resistive tissue generates heat that raises the tissue temperature. Once this temperature exceeds ~55°C, the cells undergo irreversible thermal-induced necrosis.² There is a positive relationship between current and temperature, such that increased current results in increased tissue heating, leading to larger ablation lesions.³ However, lesion size is limited by the maximal current that can safely be delivered without tissue overheating and steam-pop formation. This current threshold is dependent on the current density defined as the ratio of total current to the effective surface area and is expressed as current density measured in amperes per squared millimeter (A/mm²). The local current density at different regions of the tip electrode varies as a function of ablation tip electrode geometry, tip edge to insulating shaft boundary and the conductivity of surrounding blood, saline and tissue. Average current density is used to provide a descriptive comparison between current densities at the tip.

Standard ablation catheters have a 3.5–4mm tip electrode from which current is delivered. The surface area of these electrodes ranges between 27 – 31mm² (Figure 1, upper panel). As power equals current-squared multiplied by the resistance (P = I²⋅R), ablation at a power of 40W (and average impedance of 110ohms) with standard catheters results in the current output of 600mA and a current density of ≅ 20 mA/mm² (Figure 1, middle panel). Increasing the power from 40 to 50W results in a small increase in current output from 600 to 670mA and a simultaneous increase in the current density from 20 to ~24.0mA/mm². At this current density level, the risk for tissue overheating and steam-pop formation is significantly higher.

Figure 1:

The relationship between surface area and current density. The maximal current that can safely be delivered without overheating the tissue is determined by the average current density. The surface area of standard catheters is 27–31mm² (upper panel). Ablation at a power of 40W results in current density of 20mA/mm² (middle panel). A lattice electrode design has a ~10-fold larger conductive surface area that can deliver higher currents at a lower density (lower panel).

In order to increase power delivery but maintain a low risk for tissue overheating, current may be delivered over a larger surface area, keeping the current density low. In this study, we describe a novel ablation electrode (“lattice”) designed to allow higher energy delivery at a lower current density. The current is delivered through an expandable lattice electrode with a 10-fold larger effective surface area (275 mm²). While the lattice structure of the lattice is mostly vacant in the expanded state, it behaves as a continuous conductive surface such that the entire structure takes on the same voltage potential. Since the ablation return patches are distant, the vacant region between the lattice struts has approximately the same voltage potential as that immediately next to the struts. As a result, current flows away from the lattice struts rather than between them making the lattice structure behave as a uniform electrode at a small distance from the tip. As a consequence of this behavior and direction of current flow away from the lattice structure, it is the effective area taken by the expanded lattice that affects nearby current density, rather than the surface area of the conductive structure itself. In comparison to standard catheters with which current output of 600mA results in a current density of ~20mA/mm², the lattice can deliver 3600mA at a lower current density of ≅13.0mA/mm² (Figure 1, lower panel). This electrode design can potentially increase the safety-to-efficacy therapeutic window of radiofrequency ablation technology, allowing creation of larger lesions with an improved safety profile.

This study aimed to describe a new radiofrequency ablation electrode design and to examine its safety and efficacy profile in an in-vivo swine model of a thigh muscle preparation and the beating heart.

Methods

Data and methods used in the analysis and materials used to conduct the research will not be available for access.

Experimental design

The experimental design of this study included 3 steps: 1) Thigh muscle preparation: the purpose of this step was to provide a controlled experimental setting allowing accurate measurement of tissue contact force and direct visualization of the catheter and tissue during energy delivery for assessment of tissue injury, formation of coagulum or char; 2) Acute atrial lines in the beating heart: acute safety and efficacy of the investigational system for creation of continuous lines; 3) Long-term evaluation of the atrial lines: a 30-day post ablation evaluation of the safety and efficacy of the investigational system for creating durable atrial lines, including histopathological analysis of the ablation lines and the surrounding structures.

Animals and Protocol

This prospective study included a total of 11 Yorkshire swine (70 to 90 kg) studied under general anesthesia with isoflurane inhalation and mechanical ventilation. The research protocol was approved by the Institutional Animal Care and Use Committee and conformed to the Position of the American Heart Association on Research Animal Use. The study was performed at the Beth Israel Deaconess Medical Center Experimental Electrophysiology Laboratory in Boston, MA.

Radiofrequency Ablation System

This proprietary technology (Affera Inc.) includes an ablation catheter (Sphere9™, “lattice”), a high-energy radiofrequency generator (Hexa-3™) with a peristaltic pump as well as an electroanatomical mapping system. At the core of this technology is the lattice catheter, an 8Fr bidirectional deflectable catheter with an expandable conductive nitinol mesh. The lattice has a spheroid shape with a diameter of 9mm (Figure 2). The lattice contains 9 temperature sensors that are uniformly distributed on its spheroid-shaped surface. The center of the lattice contains a protected irrigation nozzle with micropores that provide efficient and homogeneous cooling unaffected by the pressure applied on the catheter or tissue engagement. The proprietary high-power generator operates in a temperature-controlled mode. Temperature sensor(s) on the catheter that are in contact with the tissue record temperature rise during energy delivery. The small mass of the temperature sensors allows them to quickly respond to temperature changes. Temperature readings collected by the generator allow fast dynamic modulation of current to optimally titrate energy delivery. The lattice also contains 9 independent microelectrodes (0.7mm diameter) incorporated with the surface temperature sensors, as well as an additional electrode within its center that can be used as a local indifferent electrode embedded in blood. Two ring electrodes located on the catheter’s shaft providing proximal bipolar readings. Bipolar electrograms can be configured between any of these electrodes. In particular, bipolar electrograms between each microelectrode and the center electrode can be used to assess the local response to ablation without contamination of far-field activity. These electrograms have a low noise of 3μV peak-to-peak measured in-vivo. The electroanatomical mapping system uses a magnetic sensor placed in the lattice catheter for tracking and building of a 3-dimensional map of the chamber. Anatomy acquisition is performed at a pre-defined respiratory phase (respiratory gating) for accuracy. The system also provides an indication of contact between the catheter and the tissue by continuously evaluating impedance between each of the microelectrodes and the center electrode.

Figure 2:

The Novel Radiofrequency Ablation System. The left panel shows the Sphere9 catheter design. A 7.5Fr bidirectional deflectable catheter with an expandable conductive nitinol mesh (“lattice”). The system includes a proprietary high-power radiofrequency generator. Continuous feedback between the surface temperature sensors and the generator is designed to allow optimal energy delivery without tissue overheating. The graph shows actual data from a 5sec application with a surface temperature limit of 75°C. Note that once the maximal pre-set surface temperature is reached, the generator reduces the current output.

Thigh muscle preparation

In 3 swine, 6 thigh muscle preparations were performed. We have previously reported our thigh muscle preparation technique in swine.⁴ In brief, an incision was made over the thigh muscle, and the skin and connective tissue were elevated to create a cradle overlying the thigh muscle. Venous blood (~400ml) was extracted from the jugular vein and mixed with unfractionated heparin to maintain an activated clotting time of 300–400 seconds. The blood was then circulated at a rate of 200 mL/min and a temperature of 37°C within the thigh muscle cradle using a peristaltic pump and a warming bath. The lattice catheter was positioned perpendicular to the tissue at a constant pressure of 10 grams against the muscle. After each ablation application, the cradle was evacuated of blood, and the underlying tissue and catheter were carefully examined for the presence of char, coagulum or tissue rupture indicative of tissue boiling. The catheter was then positioned at a new location, allowing adequate separation between ablation lesions.

Based on previous ex-vivo and in-vivo studies, we examined 2 energy settings that produced ablation lesions in a depth range of 2–6mm that may be optimal for atrial tissue: a shorter application time for thin tissue (2–4mm): T_max75°C/5sec and a longer application time for thicker tissue (4–6mm): T_max75°C/7sec. In order to evaluate ablation lesions created with lattice compared to standard irrigated catheters, ablation was also performed using a 3.5mm irrigated catheter (“standard”; Blazer™, Boston Scientific, Marlborough, MA) at two commonly used energy settings for atrial tissue: a lower energy setting for thin tissue, 25W/20sec and a higher energy setting for thicker tissue, 30W/20sec. Ablation with both catheters was performed in each thigh muscle preparation to avoid potential differences related to individual muscle preparations. The catheter tip was attached to a suspension arm and positioned perpendicular to the endocardial surface. It was balanced horizontally with the counterweight of a 10-gram ballast to produce 10 grams of contact force. The irrigation solution was normal saline, and the irrigation rate during energy delivery was 15mL/min with both ablation catheters. Upon completion of the study, the animals were euthanized, and the thigh muscles were harvested, labelled and fixated in 10% formalin for ≥ 7 days. Subsequently, ablation lesions were identified and correlated to the lesion index map created at the time of ablation. All ablation lesions were scanned in high-resolution (Epson GT-1500; 1200-dpi) and measured using electronic calipers. Surface maximal and minimal dimensions, depth, and maximal cross-sectional width were measured for each lesion by two independent investigators. In the case of discrepancy ≥10% in either dimension, the lesion was re-measured by three investigators in attempt to reach a consensus or exclude the sample.

Acute atrial lines in the beating heart

In this step, 8 swine were utilized for creation of right atrial lines. The lattice catheter was first used to create a 3-diamensional voltage map of the right atrium (RA) during sinus rhythm. In each animal, two parallel ablation lines between the superior and inferior vena cava were created. One line was positioned lateral to the crista terminalis and a second line posterior to the crista terminalis. This experimental design was intended to evaluate the safety and efficacy of ablation in both the lateral thicker and trabeculated tissue and in the posterior and thinner tissue. In each animal, we performed one line with the lattice catheter and a second line with the standard catheter, such that 4 lines of similar length at each position were compared between the catheters. Ablation at the lateral wall was performed using higher energy setting with both catheters (T_max75°C/7sec; 30W/20sec) while ablation at the posterior wall was performed at the lower energy setting with both catheters (T_max75°C/5sec; 25W/20sec). Ablation was performed in a point-by-point fashion. Based on our results in the thigh muscle, ablation applications made with the lattice catheter were placed at 6–8mm intervals, and ablation applications made with the standard catheter were placed at the conventional 2–4mm intervals. Additional lesions were delivered when electrogram attenuation was deemed inadequate. Figure 3 shows an illustration of the RA ablation design. The following biophysical data was recorded during radiofrequency applications: mean current-squared, temperature (maximal and mean), impedance and impedance drop. Current density was calculated by dividing mean current by total surface area of catheter. The mapping system provides indication for tissue contract when used with the lattice catheter but not with the standard catheter. In order to reduce this potential bias: 1) ablation lesions made with both catheters were positioned on the RA anatomical shell created with the lattice that provided indication for contact; 2) electrogram attenuation was confirmed during each application; 3) changes in impedance were evaluated for each application; 4) intracardiac echocardiography (Acuson™, Malvern, PA) and fluoroscopy were utilized in attempt to verify tissue contact, and 5) A steerable sheath (Agilis, Abbott, IL) was used to enhance contact stability.

Figure 3:

Ablation line design in the right atrium. In each swine, two right atrial lines were created. One line was positioned posterior to the crista terminalis (Crista t.) in the smooth and thin tissue, and a second line was positioned lateral to the crista terminalis in the thick and trabeculated tissue. The ablation settings for each line and for the specific catheter are shown in the yellow rectangles.

After completion of the ablation lines, the RA was re-mapped during sinus rhythm using the lattice catheter with particular attention to the ablation lines. These were mapped at a fill threshold of 2mm, limiting point-to-point interpolation to ≤2mm. Line continuity was evaluated by the presence of a continuous line of reduced low bipolar voltage. Since a specific cutoff for the lattice catheter has not been yet determined, we have adjusted the voltage scale similarly for both lines to identify the area of ablation. The voltage amplitude was ultimately compared to the pathological findings.

Chronic atrial lines in the beating heart

Following completion of the acute study, the animals were extubated, recovered and survived for a period of 30-days before the chronic mapping study. A voltage map of the RA was created using the lattice catheter during sinus rhythm. The operators were blinded to the ablation strategy of each animal such that the lines were mapped at a similar density with a fill threshold of ≤2mm.

Pathological analysis

After completion of the chronic mapping phase, Triphenyl Tetrazolium Chloride (TTC) was infused 15 minutes before euthanasia to allow differentiation between metabolically active and inactive tissue.⁵ Following euthanasia, the heart-lung complex was excised for pathological analysis. The lungs and mediastinal structures were carefully examined for signs of collateral damage. The epicardial aspect of the RA was examined, and it was subsequently dissected medially to the RA appendage to expose the ablation lines. Line dimensions were measured on the endocardial surface. The width of each line was measured along the longitudinal axis at 5mm increments. Following a gross pathological examination, the heart was fixed in 10% formalin solution for ≥7 days and embedded in paraffin. The fixed tissue was then inserted into a large cassette (4×2cm) able to accommodate the full width of each line. The tissue was sectioned longitudinally at 500µm intervals for staining with H&E and Masson’s trichrome (for evaluation of collagen). The lines were analyzed for linear continuity and transmurality by a pathologist blinded to the ablation strategy.

Safety assessment

Safety measurements included evaluation for: 1) steam pop formation during ablation. This was evaluated by presence of an audible pop or sudden rise in impedance with or without a temperature drop. In the beating heart lines experiment, an intra-cardiac echocardiography (ACUSON AcuNav™, Siemens) was also utilized for evaluation of steam pops; 2) presence of char or coagulum on the catheter was evaluated after completion of each ablation application in the thigh muscle preparation model and after each line in the RA; 3) phrenic nerve injury was evaluated with cine loops during the terminal study, and 4) lung injury was evaluated by gross pathological examination of the right lung. Pathological analysis of the epicardium and pericardium were also performed.

Statistical Analysis

Descriptive statistics are reported as mean ± SD for continuous variables and as absolute frequencies and percentages for categorical variables. Comparison between the lattice and standard catheters was performed using the two sample t-test with unequal variance and the Wilcoxon rank-sum test, as appropriate. Ablation with both catheters and at all experimental settings was evenly distributed between all animals to avoid potential differences related to individual muscle preparations. A p < 0.05 was considered statistically significant. Statistical analyses were performed with Stata/MP version 14 (StataCorp, College Station, TX).

Results

Thigh muscle ablation model

In the swine thigh muscle preparation, radiofrequency ablation was performed at two energy settings designed for thin and thick atrial tissue based on earlier benchtop experiments. At low energy settings, ablation with the lattice catheter was performed at T_max75°C/5sec (n=20) and ablation using the standard catheter was performed at 25W/20sec (n=19). Ablation with the lattice catheter resulted in significantly wider lesions (18.7±3.3mm vs. 12.2±1.7mm; p<0.0001) that were slightly shallower (4.7±0.8mm vs. 5.4±1.2mm; p=0.04). At higher energy settings designed for the thick lateral wall, ablation with the lattice catheter was performed at T_max75°C/7sec (n=21) and ablation using the standard catheter was performed at 30W/20sec (n=18). Ablation with the lattice catheter created significantly wider lesions (19.4±2.4mm vs. 12.2±1.7mm, p<0.0001) of similar depth (5.8±0.5mm vs. 5.6±0.8mm, p=0.35). Figure 4 shows a representative pathological specimen comparing lesion dimensions and shape between the two catheters at different energy settings.

Figure 4:

Lesions dimensions in the thigh muscle ablation model. Cross-section of ablation lesions created with the lattice and standard catheter. Lesions created with the lattice catheter are wider at both low and high energy settings. Increasing the application duration by 2 seconds resulted in a titratable effect with approximately 20% increased depth.

The biophysical parameters of the ablation in the thigh preparation model are summarized in table 1. The mean current-squared was significantly higher with the lattice catheter in both the low and high energy settings (8.9±0.003A² vs. 0.2±0.0007A²; P<0.0001 and 9.0±0.006A² vs. 0.34±0.001A²; P<0.0001, respectively). Yet, the current density was lower with the lattice catheter at both high and low energy settings (11.1±0.2mA/mm² vs. 17.1±0.9 mA/mm²; P<0.0001 and 11.2±0.3 mA/mm² vs. 18.9±1.0 mA/mm²; P<0.0001, respectively). Although the lattice catheter delivered higher current, maximal surface temperature was only 63.7±4.9C° and 65.7±4.2C° at low and high energy settings, respectively. This is likely due to the distribution of current over a large surface area (i.e., lower current density). There were no steam pops, char or coagulation in any of the thigh muscle lesions.

Table 1.

Biophysical data and lesion dimensions in the thigh muscle ablation model

	Lattice catheter Tmax75°C/5sec (n=20)	Standard catheter 25W/20sec (n=19)	p-value	Lattice catheter Tmax75°C/7sec (n=21)	Standard Catheter 30W/20sec (n=18)	p-value
Mean current squared (A2)	8.9±0.4	0.2±0.0007	<0.0001*	9±1.0	0.34±0.001	<0.0001*
Current density (mA/mm2)	11.1±0.2	17.1±0.9	<0.0001†	11.2±0.3	18.9±1.0	<0.0001†
Power density (W/mm2)	1.1±0.07	0.8±0.01	<0.0001*	1.1±0.06	1.0±0.01	<0.0001*
Baseline impedance (Ω)	37.5±1.9	98.7±11.2	<0.0001*	37.4±1.5	96.2±11.2	<0.0001*
Impedance drop (%)	4.42±0.7	11.6±4.1	<0.0001*	4.89±0.7	10.4±3.1	<0.0001*
Max temperature (C°)	63.7±4.9	32.1±1.3	<0.0001*	65.7±4.2	34.2±1.4	<0.0001*
Mean temperature (C°)	51.2±3.4	30.4±1.3	<0.0001*	53.8±2.8	32.1±1.1	<0.0001*
Width (mm)	18.7±3.3	12.2±1.7	<0.0001†	19.4±2.4	12.3±1.7	<0.0001†
Depth (mm)	4.7±0.8	5.4±1.2	0.0364†	5.8±0.5	5.6±0.8	0.2863†

^*Two sample t-test

^†Wilcoxon rank-sum test

Acute atrial lines in the beating heart

In eight swine, 4 lateral and posterior lines of similar length were created with each catheter. Ablation in the lateral wall was performed at high energy settings (T_max75°C/7sec; 30W/20sec) while ablation in the posterior wall was performed at lower energy settings (T_max75°C/5sec; 25W/20sec). The length of the lines was similar between the two catheters (p=0.89). Ablation with the lattice catheter required a fewer number of applications per line. In the posterior position, the number of applications per line was 10.5±2.1 compared to 24.8±3.6 (p=0.0005). In the lateral position, the number of applications was 12.5±3.4 compared to 24.3±4.0 (p=0.004). In addition, the time per application was shorter with the lattice catheter, such that the overall ablation speed was significantly higher (12.4sec/cm-line compared to 79.8sec/cm-line; p<0.0001). Figure 5 shows the electroanatomical map created by this novel mapping system with visualization of the lattice catheter during ablation, and its effect on electrogram amplitude reduction. The supplementary video shows a posterior ablation line created with the lattice and standard catheters.

Figure 5:

Catheter and electrogram display during ablation. A snapshot from a lateral line created with the novel system. The anatomical shell of the right atrium was created with the lattice catheter. The catheter is visualized by the mapping system and tracked using magnetic sensors. Note that ~2 seconds into radiofrequency delivery (arrow), electrograms recorded on mini-electrodes d1–4 have disappeared. These electrodes corresponded to the area of maximal heating.

The biophysical parameters of the ablation in the right atrium are summarized in table 2. The mean current-squared was significantly higher with the lattice catheter in both the posterior and lateral lines (6.6±0.07A² vs. 0.22±0.0007A²; p<0.0001 and 7.4±0.03A² vs. 0.23±0.0004A²; p<0.0001, respectively). However, the current density was lower with the lattice catheter at both the posterior and lateral lines (9.4±1.0mA/mm² vs. 16.7±1.0 mA/mm²; p<0.0001 and 9.9±0.7 mA/mm² vs. 17.1±0.8 mA/mm²; p<0.0001, respectively).

Table 2.

Biophysical and mapping parameters in the right atrial ablation line model

		Posterior line			Lateral line
		Lattice catheter Tmax75°C/5sec	Standard catheter 25W/20sec	p-value	Lattice catheter Tmax75°C/7sec	Standard catheter 30W/20sec	p-value
Biophysical ablation parameters	No. of Applications/line	10.5±2.1	24.8±3.6	0.0005†	12.5±3.4	24.3±4.0	0.0043†
	radiofrequency time/line (sec)	52.5±10.4	495±71.9	<0.0001*	87.5±23.9	485±80.6	<0.0001*
	Mean current-squared (A2)	6.6±0.1	0.22±0.0007	<0.0001*	7.4±0.03	0.23±0.0004	<0.0001*
	Current density (mA/mm2)	9.4±1.0	16.7±1.0	<0.0001*	9.9±0.7	17.1±0.8	<0.0001*
	Power density (W/mm2)	1.3±0.2	0.8±0.03	<0.0001*	1.5±0.1	1.0±0.03	<0.0001*
	Baseline impedance (Ω)	51.1±3.0	112.9±11.6	<0.0001*	54.1±6.7	128.3±10.2	<0.0001*
	Impedance drop (%)	14.3±5.9	12.5±3.8	0.0381†	15.5±5.6	15.4±4.3	0.905†
	Max temperature (C°)	74±5.7	33.3±2.2	-	69.2±7.9	32.5±2.5	-
	Mean temperature (C°)	62.2±5.1	31.1±1.8	-	57.1±6.4	30±2.6	-
Acute mapping	Length of low voltage (mm)	73.0±13.7	56.0±18.4	0.188†	72.7±2.4	47.6±32.9	0.179†
	Width of low voltage (mm)	16.1±5.2	9.5±4.8	<0.0001*	14.0±6.8	4.3±5.5	<0.0001*
Chronic mapping (30-day)	Length of low voltage (mm)	77.9±2.6	52.4±29.9	0.216*	65.0±10.8	36.9±11.1	0.034*
	Width of low voltage (mm)	15.0±4.3	6.9±4.7	<0.0001*	10.6±6.2	2.0±2.4	<0.0001*
Pathology	Length (mm)	60.0±5.0	68.5±12.7	0.329†	68.3±7.6	55.0±22.0	0.369†
	Width (mm)	13.1±4.0	6.8±2.4	<0.0001*	13.1±4.5	5.4±2.4	<0.0001*

^*Two sample t-test

^†Wilcoxon rank-sum test

An acute post-ablation voltage map showed that lines created with the lattice catheter were wider in both the posterior (16.1±5.2mm vs. 9.5±4.8mm, p<0.0001) and lateral positions (14.0±6.8mm vs. 4.3±5.5mm, p<0.0001). All posterior lines with both catheters showed a contiguous line of low voltage (Figure 6). In the lateral, thicker and trabeculated position, the lattice catheter produced all contiguous lines (4/4) while ablation with the standard catheter resulted in 0/4 contiguous lines (Figure 7). Table 2 details the voltage measurements and line integrity with both ablation catheters.

Figure 6:

Posterior line: Acute and long-term effect. Posterior lines created with the lattice catheter required a smaller number of applications and a shorter radiofrequency (RF) ablation time. At 30-days, the line created with the lattice catheter remained contiguous and wider in comparison to the line created with the standard catheter. The latter also showed a gap highlighted by the arrow and visualized in the gross pathological specimen. The histological slides show transmural fibrosis with both catheters but wider lesions with the lattice catheter.

Figure 7:

Lateral line: Acute and long-term effect. The difference between the ablation technologies is highlighted in the lateral line of thicker and trabeculated tissue. The line created with the lattice catheter resulted in a wide and contiguous low voltage abnormality while the line formed by a standard catheter was narrow and interrupted by multiple gaps (left panel). At 30-days, lines created with the lattice catheter remained contiguous while the lines created with the standard catheter showed normal voltage amplitude (middle panel). These findings were consistent with the gross pathology. The Mason trichrome staining shows transmural and homogenous collagen deposition in the lesion made by the lattice catheter in contrast to islands of collagen surrounded by cardiomyocytes in the lesion made by the standard catheter.

Assessment of line durability

Seven swine were mapped after a 30-day survival period. One animal died due to anesthesia-related complications before the second mapping procedure. In this swine, necropsy was performed and showed no evidence of cardiac, pericardial or pleural complications.

All 4 posterior lines created with the lattice catheter remained contiguous in the second mapping procedure compared to only 1 of 3 lines applied with the standard catheter (Figure 6). In addition, lines created with the lattice catheter remained wider (15.0±4.3mm vs. 6.9±4.7mm; p<0.0001). In the lateral position, all 3 lines created with the lattice catheter were contiguous compared to 0 of the 4 lines created with the standard catheter, showing multiple gaps as observed immediately after ablation (Figure 7). The lateral lines created with the lattice catheter remained significantly wider (10.6±6.2mm vs. 2.0±2.4mm; p<0.0001). Figures 6 and 7 show voltage maps immediately after ablation and at 30-days for both the posterior and lateral line, respectively.

Histopathological analysis

Gross pathological findings: Posterior lines created with the lattice catheter were all contiguous compared to only 1/3 lines created with the standard catheter. In addition, posterior lines created with the lattice catheter were wider (13.1±4.0mm vs. 6.8±2.4mm; p<0.0001; Figure 6). All lateral lines produced with the lattice catheter were contiguous compared to none of the lines applied with a standard catheter; these showed multiple gaps with punctate lesions buried between bundles of trabeculated tissue. Lines created with the lattice catheter were wider (13.1±4.5mm vs. 5.4±2.4mm, p<0.0001; Figure 7). The histological results were consistent with the gross pathological evaluation. On the posterior wall, both ablation technologies produced transmural fibrosis, although lesions created with the lattice catheter were wider (Figure 6). In the lateral wall, lesions generated with the lattice catheter were of full-thickness and resulted in transmural fibrosis involving the pectinate muscles as well as the crypts between them. In comparison, ablation with the standard catheter resulted in discrete fibrotic lesions with multiple small gaps between them (Figure 7).

Safety assessment

There were no differences in the safety profile between the catheters. Specifically, there were no steam-pops, char or coagulum formation on the catheters. There was no perforation, pericardial effusion or excessive damage to the right pleura or lungs. There was no phrenic nerve paralysis at the terminal study.

Discussion

Radiofrequency catheter ablation is the corner stone of invasive therapies for cardiac arrhythmias. While it is overall useful for the treatment of certain arrhythmias that require focal applications, it is less effective for the treatment of atrial fibrillation where durable, contiguous and transmural lines are the basis of the ablative strategy.^{6, 7} In addition, it has limited efficacy for ablation in the thick ventricle and particularly in the scar. These limitations of current radiofrequency technologies are a common reason for arrhythmia recurrence in many of our patients.

Biophysics of ablation in healthy tissue and particularly in scar is a complex science with multiple variables. The factors that govern radiofrequency-induced thermal injury include variables we have learned to control such as power and duration, but multiple other variables are not incorporated into our current algorithms, including the effective surface area of ablation, catheter stability, regional blood flow and tissue thermodynamics.

Nevertheless, a fundamental limitation of current radiofrequency catheters is the relatively narrow safety-to-efficacy window such that ablation at low power settings results in incomplete effect while ablation at slightly higher power settings results in tissue overheating and steam pop formation. This narrow therapeutic window is largely the result of the high current density in the standard ablation electrode. First, as the surface area of the resistive volume is small, even low currents may result in tissue overheating and steam pop formation. Furthermore, the actual surface area of ablation is unpredictable and is dependent on the angle of the catheter, contact force and tissue characteristics (i.e., smooth tissue vs. trabeculations). As such, ablation is often performed at a relatively low power range and for long durations, which contributes to catheter motion, tissue edema and injury to neighboring structures by passive heating. Second, a point heat source creates small lesions as current density decreases with the inverse square of the distance from the electrode, and furthermore, resistive heating decreases with the inverse fourth power of the distance from the catheter.⁸ Third, lines created by a point heat source often result in a meandring line contour with multiple potential areas for gaps, particularly in the underappreciated three-dimensional structure.

This study examined a conceptually novel strategy for radiofrequency ablation using an electrode design capable of a temperature-controlled high-power ablation. The biophysical properties of this technology were first evaluated in a controlled thigh muscle preparation model and second in the beating heart for creation of ablation lines. We also evaluated the safety and efficacy of this technology in comparison to standard irrigated catheters.

Major Findings:

1. The lattice electrode design allowed delivery of higher power at a lower current density compared to standard irrigated tip catheters.

2. Ablation lesions created with the lattice catheter were wider and the effect on lesion depth was titratable to the physiological range of human atrial thickness.

3. Ablation with the lattice catheter resulted in increased ablation line continuity and long-term durability, particularly in the thicker and trabeculated tissue.

4. Lines created with the lattice catheter required smaller number of applications and shorter radiofrequency ablation time.

This technology integrates an electroanatomical mapping system, a hybrid multielectrode mapping/ablation catheter and a high-power radiofrequency generator. The core of this technology is the lattice catheter, which allows high energy ablation at lower current density. The ability to drive high current into the tissue without overheating resulted in short applications of consistent thermal injury. The 9mm lattice electrode created wide lesions at both 5 and 7 second application duration that led to more continuous and homogenous lines, and at a fraction of the ablation time required by the standard catheter. An additional potential advantage of the lattice electrode is its malleable symmetric and textured design which allows a relatively consistent and stable tissue contact and hence energy delivery. In contrast, standard linear catheters have variable degrees of contact between the tip electrode and the tissue, and may be less stable when engaging tissue, which may result in less predictable current delivery. In these situations, steam pops can occur even with delivery of low currents (i.e., trabeculations).

The concept of high-power and short-duration ablation has gained recent popularity, particularly for pulmonary vein isolation. We have studied and reported on this subject.^{9, 10} While this concept improves lesion consistency and reduce the ablation time, one of the major limitations of this strategy is the limited safety-to-efficacy window such that minimal changes in application duration results on one hand in ineffective lesions and on the other hand in tissue overheating and steam-pop formation. Increasing the surface area of the ablation electrode results in a wider surface of ablation, a more homogenous heat distribution and lower risk of tissue overheating. Delivery of such higher currents requires monitoring of tissue temperature provided by the multiple surface temperature sensors with ablation performed in a temperature-controlled mode.

Ablation energy is reported as current (or current-squared) rather than power. Although, it has become customary to report power in watts in order to describe tissue energy delivery, the relationship between power and tissue temperature is inconsistent and depends on tip to return patch impedance which varies between patients, different anatomical locations in the heart and even as a result of heating during ablation. As such, ablation at similar power values can result in variable tissue heating and lesion dimensions.¹¹ Although this variability is often inconsequential during low energy ablation settings, it has greater significance for ablation at higher energies whereas the range of variability is proportionally increased. We believe that reporting power in these setting can be misleading while reporting a scale of current is a more accurate measure.

In addition, physicians often use the magnitude of impedance decrease during radiofrequency ablation as an indirect marker of catheter contact and lesion formation.¹² While this measure has been evaluated for irrigated catheters used at standard energy settings, it has limited utility as a marker for high energy ablation and particularly when using a different electrode design. In this study, we found poor correlation between current-squared, lesion dimensions and changes in impedance (Tables 1 and 2). These findings are consistent with our recent study which showed weak-to-moderate correlation of impedance drop with lesion dimensions, while current square (I2) and baseline impedance had moderate-to-high correlation with lesion dimensions.¹¹

Study Limitations

The major limitation of this study is related to the challenge of comparing dissimilar technologies. In this case, it was not possible to measure contact force with the standard catheter using this novel mapping system. However, we made significant effort to confirm the presence of tissue contact by using a steerable sheath, monitoring impedance decrease and electrogram attenuation with each application. Safety evaluation included investigation for the presence of char, coagulum or stem pop including any damage to neighboring structures (i.e., pericardium and lungs). However, we did not perform ablation lesions in the left atrium for the purpose of evaluating the potential effect on the esophagus, as the swine has a different anatomical relationship between the atria and the esophagus. In addition, this study compared relatively low ablation energy settings aimed for atrial tissue. These settings may be insufficient for evaluating the safety of ablation at higher power.

Conclusions

This study reports a novel radiofrequency ablation platform for producing fast, titratable and durable lesions. This technology allows delivery of high power at a low current density. It allows producing more contiguous, transmural and durable lines in the atrium compared to standard irrigated catheters and at significantly shorter ablation duration. The benefits of this technology may also be attractive for ablation in the ventricle, where it may allow the delivery of larger and deeper lesions.

What is known?

• High-current short-duration radiofrequency (RF) energy delivery has potential advantages for atrial ablation.

• However, this strategy is limited by a high-current density with a narrow safety-to-efficacy window.

What the study adds?

• A novel 8Fr catheter with an expandable spheroid-shaped radiofrequency electrode design has a ~10-fold larger effective surface area compared to a standard 3.5mm electrode. It can thus deliver significantly higher currents at a lower density.

• It incorporates multiple surface temperature sensors with ablation performed in a temperature-controlled mode that may facilitate high power ablation without tissue overheating.

• In a swine model of chronic atrial ablation lines, this novel catheter creates more contigious lines that are more durable compared to standard irrigated catheters with less ablation time and a comparable safety profile.