Journal of Cardiovascular ElectrophysiologyVolume 34, Issue 11 p. i-i COVER IMAGEFree Access Cover Image, Volume 34, Issue 11 Arash Aryana MD, PhD, Corresponding Author Arash Aryana MD, PhD [email protected] orcid.org/0000-0003-0932-8400 Cardiac Arrhythmia Service, Mercy General Hospital and Dignity Health Heart and Vascular Institute, Sacramento, California, USA Correspondence Arash Aryana, MD, PhD, Cardiac Arrhythmia Service, Mercy General Hospital and Dignity Health Heart and Vascular Institute, 3941 J St, Suite #350, Sacramento, CA 95819, USA. Email: [email protected]Search for more papers by this authorSang Yong Ji MD, Sang Yong Ji MD COR Healthcare, Torrance, California, USASearch for more papers by this authorCary Hata BS, Cary Hata BS CRC EP, Inc., Tustin, California, USASearch for more papers by this authorAlan de la Rama BS, Alan de la Rama BS CRC EP, Inc., Tustin, California, USASearch for more papers by this authorKen Nguyen BS, Ken Nguyen BS CRC EP, Inc., Tustin, California, USASearch for more papers by this authorDorin Panescu PhD, Dorin Panescu PhD CRC EP, Inc., Tustin, California, USASearch for more papers by this author Arash Aryana MD, PhD, Corresponding Author Arash Aryana MD, PhD [email protected] orcid.org/0000-0003-0932-8400 Cardiac Arrhythmia Service, Mercy General Hospital and Dignity Health Heart and Vascular Institute, Sacramento, California, USA Correspondence Arash Aryana, MD, PhD, Cardiac Arrhythmia Service, Mercy General Hospital and Dignity Health Heart and Vascular Institute, 3941 J St, Suite #350, Sacramento, CA 95819, USA. Email: [email protected]Search for more papers by this authorSang Yong Ji MD, Sang Yong Ji MD COR Healthcare, Torrance, California, USASearch for more papers by this authorCary Hata BS, Cary Hata BS CRC EP, Inc., Tustin, California, USASearch for more papers by this authorAlan de la Rama BS, Alan de la Rama BS CRC EP, Inc., Tustin, California, USASearch for more papers by this authorKen Nguyen BS, Ken Nguyen BS CRC EP, Inc., Tustin, California, USASearch for more papers by this authorDorin Panescu PhD, Dorin Panescu PhD CRC EP, Inc., Tustin, California, USASearch for more papers by this author First published: 17 November 2023 https://doi.org/10.1111/jce.16138AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Graphical Abstract The cover image is based on the Original Article Preclinical evaluation of a novel single-shot pulsed field ablation system for pulmonary vein and atrial ablation by Arash Aryana et al., https://doi.org/10.1111/jce.16010 Volume34, Issue11November 2023Pages i-i RelatedInformation

Pulsed field ablation (PFA) is a non-thermal ablative strategy that achieves cell death via electroporation. We investigated the durability of PFA lesions using 2 novel PFA/mapping catheters (CRC EP Inc, San Jose, CA) at repeat EP studies performed 3 months post-ablation. In total, 16 pulsed field applications were delivered using the PFA catheters in 3 swine under general anesthesia in the absence of paralytic agents, including: 1 application to the left atrial appendage, 9 applications to the right pulmonary veins (PVs), 3 applications to the inferior common PV and 3 applications to the right ventricle (RV). The design of the PFA catheters consists of an 8-Fr, 16-electrode, bidirectional, 25-mm or 30-mm spiral, the latter bearing 2 distal pairs of mapping electrodes active even during PFA delivery. The catheters were inserted through a commercially available 8.5-Fr steerable introducer (Agilis, Abbott, Chicago, IL). Bipolar PFA (>2 kV) was performed using single-shot, QRS-gated applications under 3D mapping and intracardiac echocardiographic guidance. Skeletal muscle activation intensity was quantified using an accelerometer (Phyphox, Aachen, Germany). Lesions were assessed by pre- versus post-EGM analysis, pacing threshold, 3D voltage mapping (EnSite, Abbott), necropsy, and histology. All applications were single-shot (34 ± 12 s) without repositioning the catheter. Minimal microbubbling was observed with mild to no skeletal muscle stimulation (acceleration <4 m/s2). No tachyarrhythmias were induced during PFA. Immediately post-ablation, bilateral PV isolation was confirmed with partial ablation of posterior wall and the coronary sinus (CS). Repeat 3D mapping at 3 months validated complete lesion durability at the PFA locations, once again illustrating bilateral PV isolation. However, there was conduction recovery at the adjacent, non-ablated/non-targeted sites (e.g., the posterior wall and CS). Accordingly, there was significant reduction in 3-month post- versus pre-PFA EGMs at the atrial PFA sites (1.38 ± 0.70 mV vs. 0.04 ± 0.03 mV, P<0.0001) and at the RV ablation sites (1.6 ± 1.3 mV vs. 0.2 ± 0.1 mV, P<0.05) with marked increase in the pacing thresholds (>20 mA vs. <10 mA, P<0.001). Lesions were contiguous measuring 26 ± 8 x 18 ± 6 mm and transmural in the atria and 38 ± 14 mm x 28 ± 9 mm and 5 ± 2 mm deep in the RV. A novel PFA catheter system can create large, single-shot atrial and ventricular lesions in vivo that are completely durable at 3 months.

We investigated the preclinical safety and efficacy of ventricular pulsed field ablation (PFA) using a family of novel, 6-/8-Fr, linear, and spiral PFA/mapping catheters (CRC EP, Inc). QRS-gated, bipolar PFA (>2.0 kV) was performed in 10 healthy swine. Altogether, 20 endocardial and epicardial right and left ventricular applications were delivered. The catheters were inserted through an 8.5-Fr steerable introducer. The intensity of skeletal muscle activation was quantified using an accelerometer. Lesions were assessed by pre- versus post-PFA electrogram analysis, pacing threshold, 3D voltage mapping, necropsy, and histology. The swine rete mirabile, liver and kidneys were examined for embolic events. All applications were single-shot (56 ± 18 s) without catheter repositioning. Minimal microbubbling was observed without significant skeletal muscle stimulation (mean acceleration 0.05 m/s2) or ventricular tachyarrhythmias. There was significant reduction in post- versus pre-PFA electrogram amplitude (0.5 ± 0.2 mV versus 3.2 ± 0.9 mV, P < 0.001) with a marked increase in pacing threshold (>20 mA versus 7.5 ± 2.9 mA, P < 0.001). All lesions were large and durable up to 28 days, measuring 32 ± 5 mm (length), 27 ± 8 mm (width), and 8 ± 3 mm (depth) using the spiral catheters and 43 ± 1 mm (length), 7 ± 1 mm (width), and 8 ± 1 mm (depth) using the linear catheters. Despite higher waveform voltages and prolonged applications, no thermal effects were detected at necropsy/histology. Moreover, gross and microscopic examinations revealed no evidence of thromboembolism, vascular or collateral injury. A novel, QRS-gated PFA system using linear and spiral PFA catheters is capable of creating large and durable ventricular lesions in vivo without significant microbubbling, ventricular arrhythmias or thromboembolism.

Background: Pulsed field ablation (PFA) is a non-thermal ablative strategy that achieves cell death via electroporation. Objective: We investigated the preclinical safety and efficacy of PFA using two novel 8-French, 16-electrode spiral PFA/mapping catheters (CRC EP, Inc). Methods: Bipolar PFA (>1.8 kV) was performed using 30 sec, single-shot, QRS-gated applications. Ninety-four atrial structures were ablated in 23 swine, 1 canine, and 1 ovine, including right and left atria and atrial appendages, pulmonary veins, and superior and inferior (IVC) vena cavae. We also examined the impact of PFA on phrenic nerve (14 swine) and on a deviated esophagus after PFA from the IVC (5 swine). Results: All applications were single-shot without catheter repositioning. Minimal microbubbling was observed without significant skeletal muscle twitching/activation (mean acceleration: 0.05 m/s2). There was marked reduction in post- versus pre-PFA atrial electrogram amplitude (0.17{plus minus}0.21 mV vs. 1.18{plus minus}1.08 mV; P<0.0001). Durable conduction block was demonstrated up to 3 months in all targeted tissues. Lesions were contiguous and transmural, measuring 25{plus minus}9 mm x 21{plus minus}7 mm without any thermal effects. Magnetic resonance, gross, and histologic examinations of the brain, rete mirabile and kidneys revealed no thromboembolism. No acute/long-term phrenic nerve dysfunction was encountered. Though within 2 hours of ablation, histologic examinations of the esophagus revealed acute PFA-related changes in the muscular layer, these completely resolved by 21{plus minus}5 days. Conclusion: A novel, single-shot, spiral PFA system is capable of safely creating large, durable atrial lesions without significant adverse effects on the phrenic nerve or the esophagus.

Pulsed field ablation (PFA) is a non-thermal ablative strategy that achieves cell death via electroporation. We investigated the preclinical safety and efficacy of PFA using 3 novel PFA/mapping catheters (CRC EP Inc, San Jose, CA). In total, 14 pulsed field applications were delivered in 5 swine under general anesthesia without paralytic agents, including: 7 lesions in the RV and 7 in the LV. The PFA catheter designs consisted of an 8-Fr, 16-electrode, bidirectional, 25-, 30- or 35-mm spiral. The 2 larger catheters had 2 distal mapping electrode pairs. The catheters were inserted through 8.5-Fr steerable introducers. Bipolar PFA (2.5-4.0 kV) was performed using single-shot, QRS-gated applications under intracardiac echocardiographic guidance. The intensity of skeletal muscle activation was quantified using an accelerometer (Phyphox, Aachen, Germany). Lesions were assessed by pre- versus post-EGM analysis, pacing threshold, 3D voltage mapping (EnSite, Abbott, Chicago, IL), necropsy, and histology. The swine rete mirabile and the kidneys were examined to investigate for embolic events related to PFA. All applications were single-shot (56 ± 18 s) without repositioning the catheter. Minimal microbubbling was observed with no skeletal muscle stimulation - acceleration <0.5 m/s2 (noise level). No tachyarrhythmias were induced during PFA. There was marked reduction in post- versus pre-PFA EGMs (0.5 ± 0.2 mV versus 2.0 ± 0.9 mV, P<0.001) and increase in pacing threshold (>20 mA versus 7.5 ± 2.9 mA, P<0.001). All lesions were large and durable up to 28 days of follow-up. The lesions measured: 32.1 ± 4.7 mm (length), 26.6 ± 7.8 mm (width), 8.4 ± 3.1 mm (depth), 62.9 ± 2.1 mm (circumference) and 10.5 ± 3.7 cm3 (volume). Despite the higher waveform voltage and prolonged applications used, no significant thermal effects were detected at necropsy or histology. Moreover, gross and microscopic examinations of the rete mirabile and the kidneys revealed no evidence of thromboembolism in any of the animals. A novel PFA catheter system can create large and durable ventricular lesions using single-shot, 56-sec applications in vivo. Despite the presence of minimal microbubbles, examination of the rete mirabile and the kidneys revealed no thromboembolic events in any of the animals.

Pulsed field ablation (PFA) results in myocardial cell death by electroporation and has been proposed to be a safer ablative strategy than thermal ablation apropos to the esophagus (ESO). We investigated the risk of ESO collateral injury using a novel single-shot PFA system (CRC EP, Inc.) and associated 8-Fr, 14-electrode, spiral PFA catheters (Figure 1A) in a porcine model. In each swine, femoral venous access was obtained under general anesthesia. Their ESO was intentionally deviated toward the inferior vena cava (IVC) using an ESO retractor device (DV8; Manual Surgical Sciences). Single-shot bipolar PFA (1.8-2.5 kV) was performed in the IVC through a deflectable introducer at areas contacting the deviated ESO (Figure 1B). The IVC and the ESO were examined post-sacrifice on gross necropsy and histologically. In 4 swine (55 ± 2 kg), 12 PFA applications were delivered in the IVC toward the deviated ESO. The animals completed the follow-up period without clinical sequelae (their weight increased by: 17 ± 3%). Pathological examination revealed acute PFA-related changes in the ESO muscular layer within 2 h of PFA (Figure 1C). But these changes completely resolved by 18 ± 3 days of follow-up. All IVC treatments were transmural, measuring 14.8 ± 4.9 mm x 5.5 ± 1.1 mm. No other acute or chronic lesions or abnormalities were detected in the ESO mucosa or submucosa in any of the 4 animals (Figure 1D). Intentional PFA of the deviated ESO toward the path of ablation using a novel single-shot PFA system in a porcine model was associated with acute mild changes in the ESO muscular layer which completely resolved during follow-up, without any clinical complications.

Pulsed field ablation (PFA) is a non-thermal ablative strategy that achieves cell death via electroporation. We investigated the safety and efficacy of PFA using 2 novel 8-Fr, 14-electrode spiral PFA/mapping catheters (CRC EP, Inc; Figure 1). In total, 26 structures were ablated in 9 swine and 1 sheep, including: right and left PVs, right (RAA) and left (LAA) atrial appendages, SVC, posterior LA, and RV. In 4 swine, PFA was also performed in the IVC to assess injury to the esophagus (ESO) deviated using a retractor device (DV8). Bipolar PFA (1.8-2.5 kV) was performed using 90 sec, single-shot, QRS-gated applications. Pre- and post-EGMs, pacing threshold, and conduction block were assessed. Lesions were analyzed by 3D voltage mapping, necropsy and histology. The impact of PFA on phrenic nerve (PN) was specifically examined in 7 and the ESO in 4 animals. All applications were single-shot without repositioning the catheter. There was marked reduction in post- vs. pre-PFA EGMs in the atria (0.1 ± 0.2 mV vs. 1.5 ± 1.1 mV; P<0.0001) and ventricles (0.6 ± 0.4 mV vs. 2.4 ± 2.5 mV; P=0.005). Complete, durable conduction block was demonstrated 3 weeks post-PFA in all targeted PVs, RAA and LAA (Figure 2). No cases of diminished PN function occurred despite low-output pacing capture using the PFA catheter in the SVC, RAA and LAA. Lesions were contiguous and transmural (Figure 3) in the atria (25 ± 9 mm x 19 ± 7 mm) and 8 ± 1 mm deep and measuring 27 ± 3 mm x 15 ± 2 mm in the RV. No PN or ESO abnormalities were detected at 3 weeks post-PFA. A novel, single-shot, spiral PFA system is capable of producing large, durable atrial and ventricular lesions without adverse effects on the PN or ESO.

Objectives The primary objective was to test in vivo for the first time the general operation of a new multifunctional intracardiac echocardiography (ICE) catheter constructed with a microlinear capacitive micromachined ultrasound transducer (ML‐CMUT) imaging array. Secondarily, we examined the compatibility of this catheter with electroanatomic mapping (EAM) guidance and also as a radiofrequency ablation (RFA) catheter. Preliminary thermal strain imaging (TSI)‐derived temperature data were obtained from within the endocardium simultaneously during RFA to show the feasibility of direct ablation guidance procedures. Methods The new 9F forward‐looking ICE catheter was constructed with 3 complementary technologies: a CMUT imaging array with a custom electronic array buffer, catheter surface electrodes for EAM guidance, and a special ablation tip, that permits simultaneous TSI and RFA. In vivo imaging studies of 5 anesthetized porcine models with 5 CMUT catheters were performed. Results The ML‐CMUT ICE catheter provided high‐resolution real‐time wideband 2‐dimensional (2D) images at greater than 8 MHz and is capable of both RFA and EAM guidance. Although the 24‐element array aperture dimension is only 1.5 mm, the imaging depth of penetration is greater than 30 mm. The specially designed ultrasound‐compatible metalized plastic tip allowed simultaneous imaging during ablation and direct acquisition of TSI data for tissue ablation temperatures. Postprocessing analysis showed a first‐order correlation between TSI and temperature, permitting early development temperature‐time relationships at specific myocardial ablation sites. Conclusions Multifunctional forward‐looking ML‐CMUT ICE catheters, with simultaneous intracardiac guidance, ultrasound imaging, and RFA, may offer a new means to improve interventional ablation procedures.

Background: The standard approach for the catheter ablation of arrhythmias and the accompanying guidance of intracardiac echocardiography (ICE) is performed from the endocardial aspect of the heart. This approach may now also include percutaneous epicardial mapping which has been developed and utilized in several electrophysiology (EP) laboratories. Previous research using percutaneous pericardial procedures has been safely and effectively applied to a range of supraventricular arrhythmia substrates. Methods: Our family of ICE devices now includes a new 9F forward-looking catheter which is constructed with a silicon based capacitive micromachined ultrasonic transducer (CMUT) technology. Several CMUT ML catheters have been tested in 3 porcine experiments. The percutaneous epicardial approach was tested with successful imaging of heart chambers from the oblique sinus of the pericardial space. Results: This micro-linear (ML) catheter provides high-resolution, real-time, 2D ultrasound images at 14 MHz, and is capable of both electrical mapping and electroanatomical guidance. Although the 24 element array aperture is small (1.6 mm), the imaging depth of penetration is considerable (> 3 cm). A thin metalized cap can be placed over the array for performing radiofrequency ablation without distorting imaging. Conclusions: This silicon based technology has the unique prospect of enhancing both miniaturization and multiple modalities of operation.