Pulsed Field Ablation of Difficult Ventricular Targets — Swine Study (2024)

Authors, Journal, Affiliations, Type, DOI

• Authors: Moritz Nies, Keita Watanabe, Iwanari Kawamura, Carlos G. Santos-Gallego, Vivek Y. Reddy, Jacob S. Koruth
• Journal: Circulation: Arrhythmia and Electrophysiology 2024;17:e012734
• Affiliations: Helmsley Electrophysiology Center and Atherothrombosis Research Unit, Icahn School of Medicine at Mount Sinai, New York; Department of Cardiology, University Medical Center Hamburg-Eppendorf
• Type: Preclinical in vivo study, 14 Yorkshire swine, acute and 7/21-day survival
• DOI: 10.1161/CIRCEP.124.012734

Overview

A systematic preclinical attempt to solve the three ventricular targets that focal PFA has struggled with: mobile intracavitary structures, the epicardium, and midmyocardial septum. Using the 9-mm lattice-tip Sphere-9 catheter, the study shows that papillary muscles and moderator bands can be ablated reliably with repeated 5.5-second monopolar applications (papillary lesions ≈5.8 mm deep, chordae preserved, no mitral regurgitation at 21 days), that epicardial monopolar lesions are large but shallow (≈9 mm, 20% transmural), and that catheter-tip-to-catheter-tip bipolar PFA achieves 87% transmurality at a mean depth of 14.3 mm — the deepest PFA lesion reported to that point, including across a 21.3 mm wall. Two costs are documented rather than glossed over: bipolar septal ablation within 1 cm of the aortic cusp caused transient complete heart block, and contact quality determined whether a papillary lesion was 5.8 mm or 3.9 mm deep. The work is the preclinical basis for the human lattice-tip and bipolar strategies that followed.

Keywords

Catheter ablation; electroporation; heart ventricles; papillary muscles; swine; tachycardia, ventricular

Key Takeaways

Design

• 14 swine (59.6 ± 3.4 kg); survival 2 days (n=10), 7 days (n=2), 21 days (n=2). One 7-day animal died 1 day post-ablation after reintubation with a defective endotracheal tube; its lesions were excluded (13/14 completed).
• Sphere-9 deflectable lattice-tip catheter, Affera mapping system, HexaPulse generator; biphasic monopolar waveform delivered from the entire tip. ACT 300–400 s.
• Repeat dosing: 3–5 applications of 5.5 s for intracavitary structures, 4–5 for epicardial, 4–7 for bipolar, with 7–8 s between applications.
• All 45 delivered applications produced lesions at necropsy (45/45, 100%).

Intracavitary structures — papillary muscles

• 13 papillary muscles (5 anterior LV, 6 posterior LV, 2 RV) targeted in 7 animals.
• Stable contact (9/13): 18.3 ± 2.4 mm long, 15.3 ± 1.5 mm wide, 5.8 ± 1.0 mm deep, lesion confined to the papillary muscle.
• Intermittent contact (4/13): significantly shallower (3.9 ± 1.3 mm; P=0.014), non-significantly longer and wider (18.8 ± 4.7 mm, 12.7 ± 3.9 mm), with extension into adjacent myocardium.
• Chronic (21 days): homogeneous fibrotic lesions, all chordae intact, no mitral regurgitation on ICE.
• ICE showed rapid myocardial activation/contraction during delivery that visibly improved tip–tissue contact, and echogenic change within minutes that became more prominent during the procedure.

Intracavitary structures — moderator band

• Two swine, 3 and 5 applications. Both lesions transmural, with extension to the septal and lateral RV wall at the insertions.
• Dimensions 19.5 and 24.0 mm long, 15.3 and 13.5 mm wide, 5.1 and 6.1 mm deep; the 6.1-mm lesion placed at the lateral insertion also achieved transmural RV wall ablation.
• Notable because the moderator band is narrow, highly mobile and notoriously difficult with conventional catheters.

Epicardial access

• Transatrial CO₂ or saline-assisted access: right atrial appendage punctured with a 1.9 Fr coronary microcatheter and 0.014″ wire, insufflation/injection to separate pericardial layers, then standard subxiphoid puncture. Successful in 7/7 animals despite full therapeutic heparinisation.
• Mild haemorrhagic pericardial staining in 3/7 (43%); at necropsy minimal effusion and minor adhesions in 5/7; the appendage perforation site was identifiable epicardially in 5/7 but never on the trabeculated endocardial surface.

Epicardial monopolar ablation

• 12 lesions (5 anterior LV, 4 lateral LV, 1 apical LV, 1 posterior LV, 1 inferior RV) in 4 swine; 2 aborted after one application (one VF immediately after delivery, one significant sinus bradycardia), no ST changes and the VF resolved with defibrillation.
• 10 completed lesions: 30.4 ± 4.2 mm long, 23.5 ± 4.1 mm wide, 9.1 ± 1.9 mm deep; 2/10 (20%) transmural.
• Two lesions contained grossly visible coronary branches with preserved lumen and ablated media; no ST elevation, no coronary spasm observed.
• Deeper than endocardial monopolar lesions previously reported (≈6–7 mm); attributed to more stable contact in the confined pericardial space and absence of blood-pool current loss.

Bipolar PFA

• 18 deliveries in 8 swine: 11 across the interventricular septum (RV to LV), 7 across the LV free wall (endocardium to epicardium), with a second lattice-tip catheter as the return electrode.
• 3 aborted: atrioventricular block at basal septal sites (1 swine) and VF (2 swine). 15 completed, median 6 (4–7) applications.
• 12 lesions analysed (excluding 3 at 21 days with scar contraction): 29.6 ± 5.5 mm long, 21.0 ± 7.3 mm wide, 14.3 ± 4.7 mm deep — significantly deeper than epicardial monopolar (P=0.001) with no difference in length or width.
• Transmurality 13/15 (87%) vs 2/10 (20%) for epicardial monopolar (P=0.002); deepest transmural lesion 21.3 mm; one lesion was transmural across an 11.1 mm septum after a single application.
• Shape depended on separation: cylindrical with tips directly opposed at ~10–15 mm, semicircular as separation increased.
• Chronic (21 days): transmural fibrotic lesions with 27–40% wall thinning but no aneurysm, tissue disruption or liquefactive necrosis — reassuring given the ventricular septal defect risk of bipolar RF.
• Safety: two septal ablations within 1 cm of the aortic cusp produced complete heart block after the last application — one resolved rapidly, one required transient ventricular pacing plus dopamine for 34 minutes. Prominent central haemorrhage and one microvascular obstruction on MRI were seen with bipolar delivery, attributed to concentrated field intensity; temperature was not measured, so a thermal contribution cannot be excluded.

MRI correlation

• All 11 lesions in the 2 imaged swine were visible, with intense late gadolinium enhancement; dark-blood sequences delineated endocardial border and lesion boundary; one septal lesion showed microvascular obstruction.
• Median depth MRI 8.4 mm (4.3–22.2) vs necropsy 9.0 mm (5.3–21.3); r=0.88.

Cautions raised by the authors

• Oedema occurs in the ventricle as it does in the atrium; large lesions plus oedema can cause wall-motion abnormality and haemodynamic compromise, particularly at low ejection fraction or when healthy myocardium is targeted.
• Minimum repeat applications and the tip separation at which transmurality is lost are unknown.
• How far from the conduction system PFA can be delivered safely is undefined.

Limitations of the document

• Healthy swine, not scarred human myocardium. Extrapolation to infarct scar, fat and thinned wall is not direct, though prior work from the group suggests scar does not impair PFA penetration.
• Small, exploratory sample sizes per target (2 moderator bands, 10 epicardial lesions, 15 bipolar lesions), and only 2 animals survived beyond 48 hours — chronic healing is inferred from very few specimens.
• Manufacturer funding and conflicts. Funded by Affera/Medtronic; Koruth and Reddy are consultants with grant support and equity.
• No assessment of coronary spasm at or remote from bipolar or epicardial application sites; a recognised clinical risk of ventricular PFA was outside the study design.
• Temperature not measured during bipolar delivery, so the "non-thermal" characterisation of the deepest lesions is an assumption.
• Healthy-animal VF proclivity is acknowledged by the authors as a species effect that limits inference about clinical arrhythmogenicity and the need for QRS gating.

Key Concepts Mentioned

• concepts/Ventricular-PFA — biophysics and lesion characteristics
• concepts/Ventricular-PFA — the clinical programme this underpins
• concepts/Epicardial-VT-Ablation — epicardial access and lesion creation
• concepts/PVC-Mapping-Ablation — papillary muscle and moderator band targets
• concepts/VT-Ablation-Nonischemic-Cardiomyopathy — midmyocardial septal substrate
• concepts/Late-Gadolinium-Enhancement — MRI lesion visualisation

Key Entities Mentioned

• Sphere-9 lattice-tip catheter, Affera mapping system, HexaPulse generator (Medtronic/Affera)
• Agilis steerable sheath (Abbott); Caravel microcatheter (Asahi Intecc); Hi-Torque Whisper ES wire (Abbott); JCL3.0 guide (Medtronic)
• Mount Sinai Fuster Heart Hospital, New York

Wiki Pages Updated

• Created: wiki/sources/lattice-tip-preclinical-circep-2024.md
• Updated: wiki/concepts/Ventricular-PFA.md
• Updated: wiki/concepts/Pulsed-Field-Ablation.md, wiki/concepts/Epicardial-VT-Ablation.md, wiki/concepts/PVC-Mapping-Ablation.md
• Updated: wiki/sourceindex.md, wiki/wikiindex.md, log.md