Preclinical assessment of the feasibility, safety and lesion durability of a novel ‘single-shot’ pulsed field ablation catheter for pulmonary vein isolation

Abstract

Aims

Single-shot pulmonary vein isolation can improve procedural efficiency. To assess the capability of a novel, expandable lattice-shaped catheter to rapidly isolate thoracic veins using pulsed field ablation (PFA) in healthy swine.

Methods and results

The study catheter (SpherePVI; Affera Inc) was used to isolate thoracic veins in two cohorts of swine survived for 1 and 5 weeks. In Experiment 1, an initial dose (PULSE2) was used to isolate the superior vena cava (SVC) and the right superior pulmonary vein (RSPV) in six swine and the SVC only in two swine. In Experiment 2, a final dose (PULSE3) was used for SVC, RSPV, and left superior pulmonary vein (LSPV) in five swine. Baseline and follow-up maps, ostial diameters, and phrenic nerve were assessed. Pulsed field ablation was delivered atop the oesophagus in three swine. All tissues were submitted for pathology. In Experiment 1, all 14/14 veins were isolated acutely with durable isolation demonstrated in 6/6 RSPVs and 6/8 SVC. Both reconnections occurred when only one application/vein was used. Fifty-two and 32 sections from the RSPVs and SVC revealed transmural lesions in 100% with a mean depth of 4.0 ± 2.0 mm. In Experiment 2, 15/15 veins were isolated acutely with 14/15 veins (5/5 SVC, 5/5 RSPV, and 4/5 LSPV) durably isolated. Right superior pulmonary vein (31) and SVC (34) sections had 100% transmural, circumferential ablation with minimal inflammation. Viable vessels and nerves were noted without evidence of venous stenosis, phrenic palsy, or oesophageal injury.

Conclusion

This novel expandable lattice PFA catheter can achieve durable isolation with transmurality and safety.

Graphical Abstract

Graphical Abstract.

What’s new?

• This preclinical study using a swine model demonstrates successful ablation of thoracic veins to achieve durable isolation with 10 s/vein without any adverse events.

• We use a novel, one shot multielectrode catheter that can be visualized with its own mapping system.

• Its segments are further colour coded to allow for visualization of rotation and positioning. It can be delivered via a standard transeptal sheath and has an over-the-wire design allowing for simple manipulation.

• Furthermore, it has as a nitinol, pliable expandable (34 mm) design with six mini electrodes allowing for facile fit within different pulmonary vein antral anatomies.

• Histological examination of 31 and 34 sections from the RSPV and the SVC revealed transmural ablation with features typical of pulsed field ablation.

Introduction

Several pulsed field ablation (PFA) technologies are currently being evaluated for atrial fibrillation (AF) ablation given their potential for improved procedural efficiency as well as safety.^1–8 Among AF ablation approaches, ‘single-shot’ circumferential pulmonary vein (PV) ablation approaches are particularly attractive when compared with the point-by-point approach as it simplifies workflow.^9–13 Thus, single-shot catheters capable of PF delivery can realize such advantages simultaneously making this an attractive approach. We describe, in this preclinical report, an efficacy and safety evaluation of an over-the-wire, expandable lattice-shaped catheter that can achieve rapid, durable thoracic vein isolation with a simple workflow.

Methods

Data and methods used in the analysis and materials used to conduct the research will not be available for access. All preclinical experiments were approved by the Institutional Animal Care and Use Committee at CBSET, Inc., Lexington, MA (IACUC protocol number I00294) and at Mount Sinai Hospital, New York, NY. A total of 13 female Yorkshire swine were included in this evaluation.

Ablation system

The study catheter used in this report has a large expandable tip (SpherePVI; Affera Inc, Watertown, MA, USA; Figure 1). This catheter has a 7.5 Fr shaft and the tip has a nitinol-based lattice framework, which can expand up to 34 mm in diameter. This expandable tip consists of six sections that can be independently and sequentially energized for ablation. The catheter can be delivered through a standard 8.5-Fr steerable sheath (e.g. Agilis) over a standard 0.032 J-tipped wire. This catheter can be used within an electroanatomical mapping system (Prism-1, Affera Inc., Newton, MA, USA) that has been described previously with the Sphere-9 ‘focal’ catheter.^2,8 Six distally placed microelectrodes are available for recording bipolar or unipolar electrograms and the catheter is not irrigated. Pulsed field ablation is delivered via the same PFA generator that powers the Sphere-9 catheter (HexaPULSE, Affera, Inc.).

Figure 1.

Study catheter and electroanatomic visualization. (A) Expandable nitinol-based lattice frame tip (expandable up to 34 mm in diameter) with a 7.5 Fr shaft. (B) The catheter can be visualized within an anatomical map of the left atrium (within the RSPV). (C) RA anatomical shell collected with the study catheter visualized within the chamber. (D) The catheter visualized within a bipolar voltage electroanatomical map. RA, right atrium; RSPV, right superior pulmonary vein. LAA, left atrial appendage; RAA, right atrial appendage; LSPV, left superior pulmonary vein; ICPV, inferior common pulmonary vein; RL, right lateral; PA, postero-anterior.

To achieve PVI, the wire-tip is positioned within a distal PV branch, and the catheter-tip is advanced into the PV while collapsed. The catheter-tip is then expanded gradually using the actuator in the handle under fluoroscopic or intracardiac echocardiographic guidance. The expanded lattice is positioned to optimize antral and circumferential contact (Figure 2). Tissue contact is facilitated by the deformable lattice framework in its expanded state. The application consisted of a train of microsecond-scale pulses, with 1–2 applications targeted for each PV. These pulses are delivered without the need for synchronization to either atrial or ventricular depolarization.

Figure 2.

Fluoroscopic views. (A–C) Expanded catheter-tip positioned in SVC, RSPV, LSPV over the wire. Note slight deformation of the catheter as it makes the turn from the transeptal to the RSPV in (B). Coronary sinus catheter is present in all panels. LSPV, left superior pulmonary vein; RSPV, right superior pulmonary vein; SVC, superior vena cava.

Preclinical protocols

After an overnight fast, all swine were induced and then mechanically ventilated with isoflurane (1–3%). Neuromuscular paralytics were not used. Femoral venous access (percutaneous and/or via surgical cutdown) was obtained, and after systemic heparin administration, a single transeptal puncture was performed for left atrial access. An 8.5 Fr deflectable sheath was used for mapping and ablation, along with intracardiac echocardiography (ICE; Acunav, Siemens Inc) and fluoroscopic guidance in all swine. Baseline and post-ablation high-density voltage maps (including the assessment of vein potentials) were performed using the Sphere-9 catheter. The Sphere-9 catheter was also used to assess venous isolation in addition to the recording microelectrodes (Figure 3) of the study catheter.

Figure 3.

Representative electroanatomic maps and electrograms. (A) Baseline, immediate post ablation, and follow-up bipolar voltage maps (0.1–1 mV) of LA demonstrating durably isolated RSPV. (B) Baseline, immediate post ablation and follow-up voltage maps of RA demonstrating durably isolated SVC. (C) Voltage map of LA demonstrating durable isolation of RSPV and LSPV. (D) Changes in electrograms obtained from the study catheter before and immediately after PFA. LA, left atria; LSPV, left superior pulmonary vein; LL, left lateral; PA, posterior anterior; RA, right atria; RSPV, right superior pulmonary vein; SVC, superior vena cava.

This evaluation was performed in two phases: an initial exploratory study using a dosing strategy (‘PULSE2’, Experiment 1) that was performed to understand feasibility, dosing, and short-term safety in eight swine; and a subsequent higher PF dose (‘PULSE3’, Experiment 2) study that was designed to be a more comprehensive evaluation of durability as well as safety. Pre, post, and follow-up right phrenic nerve pacing was performed for all swine in both experiments. Baseline and follow-up contrast angiography of thoracic veins was performed for all swine in Experiment 2 (Figure 4). All swine in both groups were then survived, remapped to assess isolation durability and phrenic nerve function, and then humanely sacrificed at the end of their pre-determined survival periods.

Figure 4.

Fluoroscopic views and intracardiac echocardiographic views. (A and B) Baseline and 5-week follow-up venous angiograms of the superior vena cava after durable isolation demonstrating no venous stenosis. (C–E) Baseline view of the SVC, catheter-tip positioned in the SVC and the SVC immediately post ablation. Note the slight reduction in the lumen between (C) and (E) (double arrows) post ablation. SVC, superior vena cava.

Experiment 1: A total of eight swine underwent an ablation procedure followed by 1 week survival. Of these, six swine underwent isolation of both the superior vena cava (SVC) and the right superior PV (RSPV), and two animals underwent only isolation of the SVC. Each PFA application (‘PULSE2’) was delivered over 12.5 s, with 1–2 applications targeted for each PV. These animals were survived for 1 week, remapped to assess isolation durability and phrenic nerve function, and humanely sacrificed. Hearts were submitted for pathological assessment.

Experiment 2: A total of five swine underwent an ablation procedure followed by 5-week survival. The SVC, RSPV, and left superior PVs (LSPV) were isolated as part of the evaluation. In addition, PFA was delivered using the study catheter while deployed in the inferior vena cava with the oesophagus forcefully approximated using a previously described technique in three consecutive swine.¹⁴ Each PFA application (‘PULSE3’) was delivered over 5 s, with two applications targeted for each PV. After completion of the survival period, all swine were remapped to assess isolation durability and phrenic function and humanely sacrificed. After a complete gross evaluation of all swine, eight veins [RSPV (n = 4), and SVC (n = 4)] were randomly chosen from four swine for detailed histological assessment.

All explanted hearts and neighbouring organs were carefully examined and photographed and fixed in formalin. Ablated thoracic veins were identified, cut open, and then trimmed to get evenly spaced circumferential sections along the long axis of the vein (4–8 sections/PV). Samples were processed for paraffin embedding, cut to slide, and stained with Masson trichrome (MT) and haematoxylin–eosin (H&E) staining. All three targeted oesophagi were closely examined for evidence of serosal injury and then cut open to inspect the luminal surface. These surfaces were then photographed. One oesophagus was selected and trimmed to produce equally spaced sections along the area of interest for detailed histological evaluation. These sections were similarly processed and stained with H&E. Slides were reviewed by a veterinary pathologist who was blinded to electroanatomic data and outcomes.

Statistical analysis

Continuous variables are expressed as mean ± standard deviation or median with interquartile range, and categorical variables are given as count and percentage. To compare paired data (such as vein diameters pre and post PFA), paired t-test was performed. A P-value <0.05 was considered significant. Statistical analyses were performed with SPSS 24.0 software (SPSS Inc., Chicago, IL, USA).

Results

Procedural workflow

The catheter-tip was easily delivered to all targeted PVs, and the expanded tip was successfully placed. The tip was easily visualized on ICE and fluoroscopic imaging, and the splines were symmetrically positioned in the SVC and LSPV. Positioning within the RSPV resulted in asymmetric splaying of the splines given the sharp turn between transeptal puncture and RSPV ostium in swine. While this did not result in inability to deliver PF, the catheter-tip was repositioned in some instances to ensure proper lesion placement (Figure 2). Pulsed field applications were not associated with skeletal muscular activation and electrogram recordings were obscured during PFA but immediately resolved with termination of PF delivery. Phrenic nerve activation was seen during pulse delivery (more prominent for SVC applications compared with RSPV). Sparse microbubbles were seen on ICE during delivery of PFA and were not accompanied by haemodynamic or EKG changes. Post-ablation, local electrograms were significantly reduced/eliminated in all swine. No atrial or ventricular arrhythmias were seen acutely or after PFA. There were no instances of thrombus adherent to the catheter-tip. Pulsed field ablation was associated with an expected local tissue response noted on ICE imaging (Figure 4).

Experiment 1: This cohort included eight swine (weight 62.0 ± 5.1 kg). Pulsed field ablation was successfully delivered to all 14/14 targeted veins (6RSPV, 8 SVC), and all 14 (100%) veins were immediately isolated (Figure 3). There were no acute reconnections noted or recovery of electrograms noted, and no complications occurred. All swine completed their 1-week survival period without issues and then underwent the remapping procedure.

A mean of 1.6 ± 0.6 PULSE2 applications were delivered in each targeted vein. The first three swine in this cohort were isolated with only a single PULSE2 application to the SVC and RSPV. The remaining five swine received two applications per vein except for one RSPV treated with three applications due to suboptimal initial catheter positioning. Durable isolation was observed in 6/6 (100%) RSPVs and 6/8 (75%) SVCs. Both the SVC reconnections occurred in the swine that received one application—i.e. 66% (4/6 veins) durability was seen with one application and 100% (8/8 veins) durability with two or more applications. No phrenic nerve paralysis was observed either acutely or at remapping based on direct pacing. All swine were then humanely sacrificed. Hearts were perfused with triphenyl tetrazolium chloride stain.

Cardiac evaluation

Detailed gross pathological examination of the mediastinal structures was unremarkable; specifically, there was no evidence of injury to the pericardium or to the lung parenchyma. Macroscopic examination of all veins revealed the presence of readily visible areas of circumferential discoloration of the adventitial and endothelial surfaces indicative of transmural and circumferential ablation of the vascular wall. No areas of endocardial thickening, haemorrhage, or thrombus were noted. In the initial cohort (Experiment 1), areas of segmental ablation corresponding to the device footprint could be occasionally visualized towards the antral portions of the ablation zone (only in SVC, Figure 5).

Figure 5.

Gross pathology prior to fixation. ( A and B) The external anterior and lateral view of an ablated SVC. The lesion is outlined with the white dotted line. (C) Internal view of an opened left atrium, demonstrating a circumferential lesion (outlined with the white dotted line) around the RSPV and LSPV. LSPV, left superior pulmonary vein; RSPV, right superior pulmonary vein; - SVC, superior vena cava.

A total of 32 and 52 sections from the SVC and RSPVs respectively were submitted for histology (84 sections in total). Superior vena cava and RSPV ablations lesions were readily identified, and transmural extension was present in all 84/84 (100%) sections (Figure 6A and B). Although such transmural lesions were noted universally, sections were limited to four or eight per vein and therefore do not always comprehensively sample the entire circumference of the vein but are nonetheless representative of cirumferentiality. The maximum depth of lesion in the myocardium was measured for 77 of 84 sections revealing a mean depth of 4.0 ± 2.03 mm. Lesions were noted to extend into connective tissue including adipose tissue and adjacent atria. Several sections demonstrated the presence of viable blood vessels and nerves within the zone of ablation treatment suggesting selective sparing. Endothelial/endocardial surfaces were segmentally ablated in certain regions with evidence of oedema with universal preservation of venous architecture. In areas adjacent to ablation, reactive fibroblasts and mixed inflammatory cells were seen. There was no evidence of neointima/neo-endocardium (endothelial hypertrophy) in any of the examined sections. Among the three swine that received one application per vein, non-circumferential ablation was grossly identified in 2/3 swine in the SVC (Figure 7A). Histology in this group (low dose) revealed focal areas of myocardial sparing (Figure 7C) within the ablation zone in many sections of the SVC. This pattern was not seen in the remaining swine that received two applications/vein or PFA with PULSE3.

Figure 6.

Gross pathology post formalin fixation. (A) The luminal view of an ablated SVC (opened anteriorly) that was shown to have reconnected at follow-up. The lesion (pale region) is outlined with the white dotted line. The white arrow points to an area within the lesion boundary that is partially spared as evident by its darker appearance. The yellow dotted lines are shown to demonstrate where sections, if taken, could miss a region of non-contiguous lesion. (B and C) The lesion is outlined and can be seen to encompass the entire circumference of the SVC and right superior pulmonary vein. SVC, superior vena cava.

Figure 7.

Histology: Masson’s trichrome (MT) staining—blue, fibrosis; pink, healthy myocardium. Experiment 1: (A and B) Demonstrates transmural lesions in the SVC and RSPV. (C) Section from SVC in animal with one application/vein that was noted to have reconnected: Small islands of spared myocardium can be seen. (D and E) Experiment 2: Higher magnification sample image of the section of RSPV demonstrating transmural ablation with viable blood vessels and nerves (D) and a transmural wide ablation of the antral wall (E). RSPV, right superior pulmonary vein; SVC, superior vena cava.

Experiment 2: This cohort included five swine (weight 57.1 ± 11.5 kg). All 15/15 targeted veins (5 RSPV, 5 SVC, and 5 LSPV) were acutely isolated without any instances of acute reconnections (Figure 3). Two consecutive applications were applied to isolate 14/15 veins with one RSPV treated with three applications to extend antral coverage. 3/5 swine also received 8 linear overlapping PF applications from within the inferior vena cava (IVC) onto the deviated oesophagus after administration of paralytic agents (due to ablation directly adjacent to the diaphragm). All swine were then recovered and completed the 5-week follow-up period. Electroanatomic mapping demonstrated wide area of low-voltage consistent with antral isolation (Figure 3). Right superior PV, SVC angiography revealed no differences from baseline for both cohorts—baseline and follow-up RSPV, and SVC diameters were unchanged at 2.02 vs. 2.06 cm (P = 0.661) and 2.29 vs. 2.31 (P = 0.728) mm, respectively (Figure 4). In total, 14/15 (93.3%) veins were durably isolated with one LSPV (small vessel) that revealed a single late potential suggesting an area of focal reconnection with delay.

Cardiac evaluation

Gross necropsy was limited to mediastinal observations and there was no evidence of injury to the pericardium or lung. There was no evidence of endocardial trauma or thrombus. Confluent, circumferential bands of ablated tissue were visualized both at sacrifice and after formalin fixation (Figures 5 and 6). Histological examination of all sections of RSPV (n = 31) and SVC (n = 34) revealed the presence of circumferential transmural ablation (65/65, 100%) without myocardial sparing. There was minimal inflammation, no evidence of mineralization and there were viable blood vessels and nerves within and around ablated areas (Figure 7D and E). Details of histological findings are summarized in Table 1. Lesions were characterized by the presence of fibrosis involving variably sized segments of the vein and often extended into tissues immediately adjacent to the adventitia. Ablated segments also demonstrated the presence of mild neointimal proliferation.

Table 1.

Histological findings

Animal	Tissue	Transmurality	Inflammation	Neutrophils	Histiocytes	Lymphocytes	Giant cells	Eosinophils	Plasma cells	Mineralization	Preserved vessels/nerves
Swine 1	RSPV	8/8	1	0	0	1	0	0	0	0	Yes
	SVC	9/9	1	0	0	1	0	0	0	0	Yes
Swine 2	RSPV	9/9	1	0	0	1	0	0	0	0	Yes
	SVC	8/8	1	0	0	1	0	0	0	0	Yes
Swine 3	RSPV	6/6	1	0	0	1	0	0	0	0	Yes
	SVC	8/8	1	0	0	1	0	0	0	0	Yes
Swine 4	RSPV	8/8	1	0	0	1	0	0	0	0	Yes
	SVC	9/9	1	0	0	1	0	0	0	0	Yes

Histomorphology changes scoring: 0 = vNo response; 1 = Minimal/focal/barely detectable; 2 = Mild/focal or rare multifocal/slightly detectable; 3 = Moderate/multifocal to confluent/easily detectable; 4 = Marked/diffuse/overwhelming presence.

Oesophageal safety evaluation

The oesophageal safety study was completed successfully in all three swine and these swine specifically did not demonstrate any significant in-life observations during the survival period. At the time of necropsy, the adventitial surface was noted to be completely preserved with no evidence of lesion or injury in the targeted regions. Post-formalin fixation, specimens were opened and no luminal lesions were noted. Three small areas of faint brown discoloration were noted on the adventitial surface in one specimen, two of which were far from the region targeted with PFA and therefore unrelated to ablation. A single section was taken from the discoloured area nearest to the targeted area and submitted for histology along with nine other sections from another specimen. All sections from the two animals had no evidence of oesophageal ablation on gross and microscopic analysis. Minimal histological changes that were interpreted to be unrelated to ablation treatment were observed—rare inflammatory cells within the muscularis layer with no evidence of myofibre degeneration and/or fibrosis in a few sections. An oesophageal section revealed the presence of some adventitial extravasated erythrocytes that was also interpreted to be post mortem and not ablation related.

Discussion

We present a preclinical evaluation of a novel, lattice-shaped catheter designed to rapidly isolate PVs. Important features of this catheter and its ablative capacity demonstrated in this report are: (i) over-the-wire delivery through a standard 8.5 Fr deflectable sheath, (ii) the tip can be variably expanded up to 34 mm and has an expandable architecture that optimizes PV fit, (iii) it can visualized (if needed) within a proprietary mapping system, (iv) has embedded microelectrodes that can detect local PV potentials, (v) the catheter can ablate PVs to achieve durable isolation (‘ablate and map’ capability) with very short ablation times of 10 s/vein, and (vi) achieves 100% transmurality on histology and sections demonstrating typical features of pulse field ablation such as sparing of nerves, vessels, and the oesophagus.

Ablation efficacy and safety

The findings of this report indicate that the study catheter and its proprietary waveform was successfully delivered achieving 100% acute isolation of all 29/29 veins. Durable isolation was achieved in all but one vein with the final dose (two PULSE3 applications/vein), however with the lowest dose (one PULSE2 application/vein) durability was only 66%. This excellent durability is supported by the gross and histological assessment that demonstrated circumferential lesions with transmurality rates of 100%. The findings in this report are in-line with other preclinical evaluations of single-shot PFA systems. A recent report described the successful use of a multi-spline expandable catheter (Farawave, Farapulse Inc, CA, USA) to isolate veins in healthy swine; the report demonstrated 100% durable isolation (18/18 thoracic veins) at 10 weeks with a transmurality rate of 90.8% (138/152 sections) seen with their final dose/waveform.¹ Our report describes an earlier durability assessment (5 weeks vs. 10 weeks) but we demonstrate wide antral lesions with mature homogenous fibrosis suggesting that durability rates are unlikely to regress over longer follow-up. Importantly, this report recapitulates all the efficacy and safety features characteristics of PFA, i.e. there was no acute or chronic evidence of phrenic palsy despite phrenic activation and delivery atop the phrenic nerve (SVC isolation), there was no evidence of venous stenosis despite ablation within the vein (distal tip of catheter was placed in all veins), and there was no evidence of oesophageal injury. Additionally, we observed no evidence of haemorrhage or endocardial thrombus on gross examination, whereas histology revealed homogenous fibrosis, discrete margins, absence of coagulation necrosis, and evidence of sparing of nerves and small blood vessels. These are all characteristic of the non-thermal ablation mechanism of PFA.^{1–8,14–18}

Several other features specific to the study catheter are notable. The delivery of the catheter in and out of the deflectable sheath was easy and there were no instances of entrainment of air into the sheath or air embolism. The lattice was adequately radio-opaque and was easily visualized on ICE imaging. Delivery into the PV was straightforward and circumferential ostial contact was easy to achieve by using the expandable lattice structure of the catheter. The lattice structure was observed to be unevenly distributed due to anatomical constraints when targeting the RPSV (a common occurrence in the swine model) but this did not preclude PF delivery and also did not impact durability of isolation. Catheter deformation can occur clinically, and lack of impaired ablation outcomes despite this occurrence as suggested in this report, is an important advantage, when compared with other bipolar ‘single-shot’ tip designs that require adequate separation of ablative electrodes to ensure successful delivery as well as good outcomes.^1,4,5,19 Pulsed field delivery resulted in muscular and diaphragmatic stimulation (as expected) but this did not result in catheter dislocation. It must be noted that all procedures were performed under general anaesthesia but without any need of paralytic agents. The extent of nerve stimulation was felt to be comparable to other preclinical evaluations performed by the authors with other PFA systems.^1,2

There was no evidence of sinus node dysfunction despite targeting the SVC—this is reassuring in that ablation was confined to myocardium proximate to the catheter and did not result in unintended ablation of non-target nearby structures. There were also no instances of AV block, ST-T wave changes, or atrial or ventricular arrhythmias during or after applications. We observed sparse microbubbles during PF delivery (expected with PFA) but this was not accompanied by ST-T changes. The ICE imaging features of microbubble formation at the time of PFA applications was consistent with other PFA therapies the authors are familiar with.^1,2,5,20 Intracardiac echocardiography imaging demonstrated post-PFA narrowing of venous lumens as a result of thickening of ablated tissue (Figure 4). This is consistent with our prior experience with PFA in the swine model and represents oedema within ablated myocardium and extracellular tissue.² In Experiment 2, angiography was repeated after the survival period and showed complete resolution.

There were no instances of thrombus either on the catheter-tip or on the endocardium at necropsy/histology and importantly there was no evidence of endocardial trauma. We also performed oesophageal safety assessment using a model that mimics a ‘worst-case assessment’ by artificially forcing contact between the thin-walled IVC and the deviated oesophagus. It is important to note that we placed repeated (8) overlapping applications to maximize the chance of observing any evidence of damage. Despite this aggressive approach, we did not observe any evidence of oesophageal serosal/mucosal injury. These data form the basis for further preclinical evaluations of durability and safety and first-in-human evaluation.

Limitations

The safety and durability demonstrated in this series are relatively short-term (up to 5 weeks) and long-term follow-up studies to demonstrate persistence of durability and safety will be reassuring. We did not perform, a dedicated characterization/evaluation of the relevance of the microbubbles seen with this catheter and separate evaluations are needed. The number of longitudinal sections per targeted veins were limited to between four and eight and therefore may have missed segments with either no ablation or non-transmural lesions leading to an overestimation of cirumferentiality and transmurality—in fact, the sections from the three veins that were not durably isolated did not demonstrate lack of transmural lesions. However, the gross observation of wide, distinct lesions encompassing the entire venous wall coupled with durable electrical isolation confirmed with high-density mapping is reassuring. Finally, it should be appreciated that healthy swine atria and collateral organ damage assessment have limited ability to predict clinical findings of both durability and safety. Separate and careful assessments need to be performed during clinical evaluations.

Conclusion

Single-shot PFA can be achieved rapidly and safely using a novel lattice-expandable catheter to isolate thoracic veins. A dose-dependent improvement in lesion durability was demonstrated with excellent transmurality and safety, with evidence of sparing of nerves, vessels, and the oesophagus consistent with the non-thermal nature of pulsed fields.

Supplementary material

Supplementary material is available at Europace online.

Funding

This study was supported by a research grant from Affera Inc.

Data availability

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