Cryocure-VT: the safety and effectiveness of ultra-low-temperature cryoablation of monomorphic ventricular tachycardia in patients with ischaemic and non-ischaemic cardiomyopathies.

AIMS: The ultra-low-temperature cryoablation (ULTC) ablation system using -196°C N2 cryogen has been reported to create lesions with freeze duration-dependent depth titratable to over 10 mm with minimum attenuation by scar. Cryocure-VT (NCT04893317) was a first-in-human clinical trial evaluating the safety and efficacy of a novel, purpose-built ULTC catheter in endocardial ablation of scar-dependent ventricular tachycardias (VTs). METHODS AND RESULTS: This prospective, multi-centre study enrolled patients referred for de novo or second ablations of recurrent monomorphic VT of both ischaemic and non-ischaemic aetiologies. Primary safety and efficacy endpoints of the study were freedom from device- or procedure-related major adverse events (MAEs) up to 30 days post-ablation, acute non-inducibility of clinical VTs at the end of the procedure, and freedom from sustained VT or implantable defibrillator intervention at 6 months. Ultra-low-temperature cryoablation was performed in 64 patients (age 67 ± 11 years, 78% ischaemic, ejection fraction = 35 ± 10%) at 9 centres. The primary acute effectiveness endpoint was achieved in 94% (51/54) of patients in whom post-ablation induction was attempted. There were no protocol-defined MAEs; four procedure-related serious adverse events resolved without clinical sequelae. At 6-month follow-up, 38 patients (60.3%) remained VT-free, and freedom from defibrillator shock was 81.0%, with no significant difference between ischaemic and non-ischaemic cohorts. In 47 patients with defibrillator for at least 6 months prior to the ablation, the VT burden was reduced from median of 4, inter-quartile range (IQR, 1-9) to 0, IQR (0-2). CONCLUSION: In this first-in-human multi-centre experience, endocardial ULTC ablation of monomorphic VT appears safe and effective in patients with both ischaemic-cardiomyopathy and non-ischaemic-cardiomyopathy. CLINICAL TRIAL REGISTRATION: NCT04893317.

Ultra-Low-Temperature Cryoablation for Ventricular Tachycardia: An Early Single-Centre Report of Acute Results.

Background: Endocardial catheter ablation for ventricular tachycardia (VT) may fail because of the inability to deliver transmural lesions. Ultra-low-temperature cryoablation (ULTC) uses near-critical nitrogen and can generate temperatures as low as -196 °C. We report a series of 18 patients who underwent ULTC at the McGill University Health Centre (MUHC), representing the largest single-centre experience to date. Methods: Eighteen patients with monomorphic drug-refractory VT underwent VT ablation with ULTC at our institution as part of the first-in-human CryoCure-VT trial (NCT04893317). After voltage map, the mapping catheter was replaced with the ULTC catheter, and lesions were applied over a fixed duration of time (60-180 seconds), followed by a 60-second thaw and another application at the original duration (freeze-thaw-freeze). Duration of ablation time was selected depending on the wall thickness of the left ventricle monitored with intracardiac echo to achieve tissue depths of 4.5 to 7.5 mm. Results: Baseline left ventricular ejection fraction was 32%, mean age 71 years, 94% were male. A total of 32 sustained VTs were induced in 16 of 18 patients. A total of 177 cryoablation lesions were delivered (9.8 lesions per patient). Of the 16 patients with inducible VT, 15 (94%) were rendered noninducible postablation, and 1 was inducible only for a nonclinical VT. Complications included 1 pericardial effusion that required drainage. From 18 patients, 16 (89%) were discharged within the first 24 hours postablation. Conclusions: ULTC is feasible and permits acute control of monomorphic VT during VT ablation procedures in drug-refractory patients.

Contexte: L'ablation endocardique par cathéter pour traiter la tachycardie ventriculaire (TV) peut être un échec, en raison de l'incapacité à créer des lésions transmurales. La cryoablation à ultra-basse température (ULTC, pour ultra-low-temperature cryoablation) réalisée au moyen d'azote près de son point critique liquide-vapeur peut produire des températures aussi basses que ­196 °C. Nous faisons état d'une série de 18 patients ayant subi une ULTC au Centre universitaire de santé McGill (CUSM), ce qui représente la plus importante expérience menée dans un seul établissement jusqu'à ce jour. Méthodologie: Au total, 18 patients atteints de TV monomorphe pharmacorésistante ont subi une ablation de la TV par ULTC à notre établissement, dans le cadre du premier essai mené chez l'humain sur la guérison par cryothérapie de la TV (NCT04893317). Après l'obtention de la carte électrophysiologique, le cathéter de cartographie a été remplacé par le cathéter d'ULTC, qui a permis de créer des lésions par l'application de froid pendant une durée fixe (de 60 à 180 secondes), suivie d'une période de dégel de 60 secondes, puis d'une autre application de froid pendant la même durée que la première application (cycle gel-dégel-gel). La durée de l'ablation a été déterminée en fonction de l'épaisseur de la paroi du ventricule gauche surveillée par échocardiographie endocavitaire afin d'obtenir des profondeurs tissulaires de 4,5 à 7,5 mm. Résultats: La fraction d'éjection du ventricule gauche initiale était de 32 %, l'âge moyen des sujets était de 71 ans et 94 % d'entre eux étaient de sexe masculin. Au total, 32 TV soutenues ont été induites chez 16 patients sur 18. Dans l'ensemble, 177 lésions de cryoablation ont été créées (soit 9,8 lésions par patient). Après l'ablation, nous avons été incapables d'induire une TV chez 15 (94 %) des 16 patients chez qui nous en avions induit avant l'intervention et, chez le patient restant, nous avons pu induire une TV non clinique seulement. Les complications comprenaient un cas d'épanchement péricardique ayant nécessité un drainage. Au total, 16 (89 %) des 18 patients ont reçu leur congé de l'hôpital dans les 24 heures suivant l'ablation. Conclusions: L'ULTC est réalisable et permet une maîtrise rigoureuse de la TV monomorphe lors des interventions d'ablation de la TV chez les patients dont la TV est pharmacorésistante.

2024 European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society expert consensus statement on catheter and surgical ablation of atrial fibrillation.

In the last three decades, ablation of atrial fibrillation (AF) has become an evidence-based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for regularly updated versions of this partnership which were issued in 2012 and 2017. Seven years after the last consensus, an updated document was considered necessary to define a contemporary framework for selection and management of patients considered for or undergoing catheter or surgical AF ablation. This consensus is a joint effort from collaborating cardiac electrophysiology societies, namely the European Heart Rhythm Association, the Heart Rhythm Society (HRS), the Asia Pacific HRS, and the Latin American HRS.

Predictors of Success for Pulmonary Vein Isolation With Pulsed-Field Ablation Using a Variable-Loop Catheter With 3D Mapping Integration: Complete 12-Month Outcomes From inspIRE.

BACKGROUND: We previously presented the safety and early efficacy of inspIRE study (Pulsed-Field Ablation (PFA) System for the Treatment of Paroxysmal Atrial Fibrillation by Irreversible Electroporation). With the study's conclusion, we report the outcomes of the full pivotal study cohort, with an additional analysis of predictors of success. METHODS: InspIRE was a prospective, multicenter, single-arm clinical trial of drug-refractory paroxysmal atrial fibrillation. Pulmonary vein isolation was performed with a variable-loop circular catheter integrated with a 3-dimensional mapping system. Follow-up with 24-hour Holter was at 3, 6, and 12 months, as well as remote rhythm monitoring: weekly from 3 to 5 months, monthly from 6 to 12 months, and for symptoms. The primary effectiveness end point (PEE) was acute pulmonary vein isolation plus freedom from any atrial arrhythmia at 12 months. Additional subanalyses report predictors of PEE success. RESULTS: The patient cohort included 186 patients: aged 59±10 years, female 30%, and CHA2DS2-VASc 1.3±1.2. The previously reported primary adverse event rate was 0%. One serious procedure-related adverse event, urinary retention, was reported. The PEE was achieved in 75.6% (95% CI, 69.5%-81.8%). The clinical success of freedom from symptomatic recurrence was 81.7% (95% CI, 76.1%-87.2%). Simulating a monitoring method used in standard real-world practice (without protocol-driven remote rhythm monitoring), this translates to a freedom from all and symptomatic recurrence of 85.8% (95% CI, 80.8%-90.9%) or 94.0% (95% CI, 90.6%-97.5%), respectively. Multivariate analyses revealed that left ventricular ejection fraction ≥60% (adjusted odds ratio, 0.30) and patients receiving ≥48 PFA applications (adjusted odds ratio, 0.28) were independent predictors of PEE success. Moreover, PEE success was 79.2% in patients who received ≥12 PFA applications/vein compared with 57.1% in patients receiving fewer PFA applications. CONCLUSIONS: The inspIRE study confirms the safety and effectiveness of pulmonary vein isolation using the novel 3-dimensional mapping integrated circular loop catheter. An optimal number of PFA applications (≥48 total or ≥12 per vein) resulted in an improved 1-year success rate of ≈80%. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04524364.

2024 European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society expert consensus statement on catheter and surgical ablation of atrial fibrillation.

In the last three decades, ablation of atrial fibrillation (AF) has become an evidence-based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for regularly updated versions of this partnership which were issued in 2012 and 2017. Seven years after the last consensus, an updated document was considered necessary to define a contemporary framework for selection and management of patients considered for or undergoing catheter or surgical AF ablation. This consensus is a joint effort from collaborating cardiac electrophysiology societies, namely the European Heart Rhythm Association, the Heart Rhythm Society, the Asia Pacific Heart Rhythm Society, and the Latin American Heart Rhythm Society .

Recent developments in piezo-photocatalytic CO2 reduction: concepts, mechanism, and advances.

Out of the high number of photocatalytic applications, CO2 reduction has proved to be quite a boon for the present world. Increasing CO2 emissions owing to fossil fuel usage has been a menace to our society. To date, many methods have been developed to redress the situation. One of them is photocatalysis, which has been a well-known branch of energy and environmental applications since 1972. This is due to its low energy consumption and green nature. In recent years, a new phenomenon has come into existence wherein a combination of mechanical energy and photocatalysis can increase the efficiency of any catalytic process. In this regard, this frontier article will discuss the recent developments in piezo-photocatalysis for CO2 reduction. The main focus will be understanding the underlying mechanisms of efficiency enhancements in photocatalytic systems. Initially, the mechanism of CO2 reduction and its current needs will be discussed in the introduction. Further, a collection of recent reports from the literature and various material systems will be discussed to gain insights into the latest developments in the area. Then, literature and references that are purely mechanism-based with deeper analysis will be discussed, along with crucial characterization techniques for piezo-photocatalysts. Many factors need to be factored in for a better understanding of piezo-photocatalysis, e.g., factors such as piezo energy source, material design, and CO2 adsorption, require more attention to increase the CO2 reduction capability of photocatalysts. Based on the discussions in this article, researchers will gain new perceptions on the combination of vibrational energy and light energy to enhance CO2 reduction yields. Moreover, this article can advance understanding of techniques such as Kelvin probe microscopy, the requirement of simulation studies, and CO2 reduction mechanisms to better understand the piezo behavior of materials and ways to improve them for maximum product yield.

Cardiac Pulsed Field Ablation Lesion Durability Assessed by Polarization-Sensitive Optical Coherence Reflectometry.

BACKGROUND: Pulsed field ablation uses electrical fields to cause nonthermal cell death over several hours. Polarization-sensitive optical coherence reflectometry is an optical imaging technique that can detect changes in the tissue ultrastructure in real time, which occurs when muscular tissue is damaged. The objective of this study was to evaluate the ability of a polarization-sensitive optical coherence reflectometry system to predict the development of chronic lesions based on acute changes in tissue birefringence during pulsed field ablation. METHODS: Superior vena cava isolation was performed in 30 swine using a biphasic, bipolar pulsed field ablation system delivered with a nonirrigated focal tip catheter. Acute changes in tissue birefringence and voltage abatement were analyzed for each individual lesion. A high-resolution electroanatomical map was performed at baseline and 4 to 12 weeks after ablation to locate electrical gaps in the ablated area. RESULTS: A total of 141 lesions were delivered and included in the analysis. Acute electrical isolation based on the electroanatomical map was achieved in 96% of the animals, but chronic isolation was only seen in 14 animals (46%). The mean voltage abatement of lesions that showed recovery was 82.8%±14.6% versus 84.4%±17.4% for those that showed fibrosis (P=0.7). The mean acute reduction in tissue birefringence in points demonstrating fibrosis was 63.8%±11.3% versus 9.1%±0.1% in the points that resulted in electrical gaps. A threshold of acute reduction of birefringence of ≥20% could predict chronic lesion formation with a sensitivity of 96% and a specificity of 83%. CONCLUSIONS: Acute tissue birefringence changes assessed with polarization-sensitive optical coherence reflectometry during pulsed field ablation can predict chronic lesion formation and guide the ablation procedure although limited by the tissue thickness.

Cardioneuroablation as a strategy to prevent pacemaker implantation in young patients with vasovagal syncope.

Background: Cardioneuroablation (CNA) is an ablation technique that targets epicardial ganglionic plexi to reduce syncope burden and avoid pacemaker implantation in patients with cardioinhibitory vasovagal syncope (VVS). This study aims to demonstrate feasibility and safety of CNA in high-risk refractory VVS patients using continuous monitoring with an implantable loop recorder (ILR). Methods: Data was collected prospectively for patients undergoing CNA. Patients were required to have recurrent syncope with documented asystole, refractory to conservative measures. Ganglionic plexi (GPs) were identified by fragmented signals and high frequency stimulation (HFS). Ablation was performed until loss of positive response to HFS, Wenckebach cycle shortening was achieved, or an increase in sinus rate of > 20 bpm. Follow-up was performed through remote and clinic follow-up of their ILRs. Results: Between December 2020 and July 2023 six patients (mean age 29 ± 3, 67 % female)underwent CNA. The baseline heart rate and Wenckebach cycle length was 63.2 ± 15 bpm and 582 ms before and 91 ± 5 bpm and 358 ms after ablation respectively. During a median follow-up of 13.4 months, 3/5 patients had no further syncopal episodes, 1 had a recurrence, underwent repeat CNA with no further episodes at 1 year, and 1 had 5 syncopal events, which was a dramatic reduction from nearly daily episodes pre-CNA. There were no procedure related complications. Conclusions: A dramatic reduction in documented pauses and syncope burden was noted post CNA. Appropriate patient selection with rigorous objective follow-up in an experienced center is necessary. Larger studies are required to confirm these findings.

The prospect of CuxO-based catalysts in photocatalysis: From pollutant degradation, CO2 reduction, and H2 production to N2 fixation.

The topic of photocatalysis and CuxO-based materials has been intertwined for quite a long time. Its relatively high abundance in the earth's crust makes it an important target for researchers around the globe. One of the properties exploited by researchers is its ability to exist in different oxidation states (Cu0, Cu+, Cu2+, and Cu3+) and its implications on photocatalytic efficiency improvement. Recently, they have been extensively used as photocatalytic materials for dye and pollutant degradation. However, it has almost reached saturation levels, therefore, currently, they are being mostly utilized for CO2 reduction and H2 evolution. Hence, this review will discuss the evolution (in application) of CuxO-based photocatalysts, relating to their past, present, and future. Moreover, photocatalytic efficiency improvement strategies such as doping, heterojunction formation, and carbonaceous construction with other materials will also be touched upon. Finally, the prospect of Cu2O-based photocatalysts will be discussed in the field of photocatalytic N2 fixation to ammonia. The significance of N2 chemisorption on photocatalysts to maximize ammonia production will also be given importance.

Perspectives on pulsed field ablation: how to judge endpoints.

PURPOSE OF REVIEW: This review highlights pulse field ablation's (PFA) significance in treating atrial fibrillation. PFA uses short-pulsed electrical fields, offering safety advantages over thermal methods. Multicenter studies' findings on PFA's safety, efficiency, and efficacy, compared with thermal techniques, are discussed. RECENT FINDINGS: The review encompasses major PFA systems utilized in multicenter studies: penta-spline, circular, and lattice catheters. These studies affirm PFA's safety, with minimal complications like esophageal injury, phrenic nerve complications, and pulmonary vein stenosis. PFA also demonstrates procedural efficiency benefits because of rapid pulse delivery. However, PFA's efficacy appears on par with thermal ablation, showing similar rates of atrial arrhythmia recurrence during follow-up periods. The studies explore diverse postablation monitoring strategies, underscoring the necessity for standardized monitoring or consistent transformation of arrhythmia data. SUMMARY: In conclusion, PFA marks a promising era for atrial fibrillation treatment with improved safety and efficiency. Efficacy is comparable to thermal methods, though technology advancements could alter this. PFA's potential as a safer and faster alternative positions it as a dominant atrial fibrillation ablation technology. Careful analysis and standardized monitoring are vital to assess PFA's potential and clinical implications.

Enabling N2 to Ammonia Conversion in Bi2 WO6 -Based Materials: A New Avenue in Photocatalytic Applications.

The field of photocatalysis has been evolving since 1972 since Honda and Fujishima's initial push for using light as an energy source to accomplish redox reactions. Since then, many photocatalysts have been studied, semiconductors or otherwise. A new photocatalytic application to convert N2 gas to ammonia (N2 fixation or nitrogen reduction reaction; NRR) has emerged. Many researchers have steered their research in this direction due to developments in the ease of ammonia detection through UV-Vis spectroscopy. This concept will specifically discuss Bi2 WO6 -based materials, techniques to enhance their photocatalytic activity (CO2 reduction, H2 production, pollutant removal, etc.), and their current application in photocatalytic NRR. Initially, a brief introduction of Bi2 WO6 along with its VB and CB potentials will be compared to various redox potentials. A final topic of interest would be a brief description of photocatalytic nitrogen fixation with additional consideration to Bi2 WO6 -based materials in N2 fixation. A major problem with photocatalytic NRR is the false ammonia quantification in Bi-based materials, which will be discussed in detail and also ways to minimize them.

Progress in atrial fibrillation ablation during 25 years of Europace journal.

The first edition of Europace journal in 1999 came right around the time of the landmark publication of the electrophysiologists from Bordeaux, establishing how elimination of ectopic activity from the pulmonary veins (PVs) resulted in a marked reduction of atrial fibrillation (AF). The past 25 years have seen an incredible surge in scientific interest to develop new catheters and energy sources to optimize durability and safety of ablation, as well as study the mechanisms for AF and devise ablation strategies. While ablation in the beginning was performed with classic 4 mm tip catheters that emitted radiofrequency (RF) energy to create tissue lesions, this evolved to using irrigation and contact force (CF) measurement while increasing power. Also, so-called single-shot devices were developed with balloons and arrays to create larger contiguous lesions, and energy sources changed from RF current to cryogenic ablation and more recently pulsed field ablation with electrical current. Although PV ablation has remained the basis for every AF ablation, it was soon recognized that this was not enough to cure all patients, especially those with non-paroxysmal AF. Standardized approaches for additional ablation targets have been used but have not been satisfactory in all patients so far. This led to highly technical mapping systems that are meant to unravel the drivers for the maintenance of AF. In the following sections, the development of energies, strategies, and tools is described with a focus on the contribution of Europace to publish the outcomes of studies that were done during the past 25 years.

Wearable Cardiac Rhythm Monitoring Device for Detection of Postoperative Atrial Fibrillation.

PURPOSE: This study evaluated the use of a wearable, patch-based cardiac rhythm monitoring device in detecting postoperative atrial fibrillation (POAF) among cardiac surgical patients within 30 days after hospital discharge. DESCRIPTION: From the SEARCH-AF (The Post-Surgical Enhanced Monitoring for Cardiac Arrhythmias and Atrial Fibrillation) CardioLink-1 trial, this study examined rates of POAF according to surgery type and the incremental value of continuous cardiac rhythm monitoring among patients who underwent valve surgery. The primary outcome was cumulative atrial fibrillation or atrial flutter lasting for ≥6 minutes detected by continuous monitoring or atrial fibrillation or atrial flutter documented by a 12-lead electrocardiogram within 30 days of randomization. EVALUATION: The primary outcome occurred in 8.2%, 13.5%, and 21.2% of patients who underwent isolated coronary artery bypass grafting (CABG), isolated valve surgery, and combined CABG and valve surgery. Relative to patients who underwent isolated CABG, those patients who had valve surgery were more likely to experience POAF. A higher diagnostic yield was obtained when the patch-based cardiac rhythm monitor was applied in patients who underwent valve surgery. CONCLUSIONS: Use of a wearable, patch-based cardiac monitoring device was an effective detection strategy among patients undergoing valve surgery, given their higher risk of developing POAF.

Optimization of Intercalated 2D BiOCl Sheets into Bi2WO6 Flowers for Photocatalytic NH3 Production and Antibiotic Pollutant Degradation.

Photocatalytic N2 fixation is a complex reaction, thereby prompting researchers to design and analyze highly efficient materials. Herein, one-pot hydrothermal Bi2WO6-BiOCl (BW-BiOCl) heterojunctions were synthesized by varying the molar ratio of tungsten: chlorine precursor. Major morphological transformations in BiOCl were observed wherein it turned from thick sheets ∼230 nm in pure BiOCl to ∼30 nm in BW-BiOCl. This was accompanied by extensive growth of {001} facets verified from X-ray diffraction (XRD) and field-emission scanning electron microscopy (FESEM) analyses. A p-n heterojunction was formed between Bi2WO6 and BiOCl evidenced via photoluminescence (PL), time-resolved photoluminescence (TRPL), photocurrent response, and electrochemical impedance spectroscopy (EIS) analyses. The formation of heterojunction between Bi2WO6 and BiOCl led to the reduction of the work function in the BW-BiOCl 0.25 hybrid confirmed via ultraviolet photoelectron spectroscopy (UPS) analysis. BW-BiOCl 0.25 could produce ammonia up to 345.1 µmol·L-1·h-1 owing to the formation of a robust heterojunction with an S-scheme carrier transport mechanism. Recycle tests resulted in no loss in N2 reduction activities with post-catalytic analysis, showcasing the high stability of the synthesized heterojunction. Novel performance was owed to its excellent chemisorption of N2 gas on the heterojunction surface verified by N2-temperature programmed desorption (TPD). BW-BiOCl 0.25 also displayed a superior rate constant of 3.03 × 10-2 min-1 for 90 min CIP degradation time, higher than pristine BiOCl and Bi2WO6. Post-photocatalytic Fourier transform infrared (FTIR) spectroscopy of BW-BiOCl 0.25 revealed the presence of C-H stretching peaks in the range of 2850-2960 cm-1 due to adsorbed CIP and methanol species in CIP degradation and N2 fixation, respectively. This also confirmed the enhanced adsorption of reacting species onto the heterojunction surface.

Thermal Profiles for Focal Pulsed Electric Field Ablation.

BACKGROUND: Pulsed electrical field (PEF) ablation may cause tissue heating. These changes are reportedly small, but each PEF system and waveform will have a different behavior, and data are lacking. OBJECTIVES: This study sought to compare the temperature profile of focal point, monopolar biphasic PEF ablation versus radiofrequency (RF). METHODS: Ablation lesions were performed on perfused thigh muscle of swine. PEF lesions were performed with 3 compatible ablation catheters at the highest (25 amp) energy, and 1 catheter (Tacticath SE) was also used at the 22- and 19-amp levels. Temperature changes in the tissue were measured using fluoroptic temperature probes inserted at the muscle surface, as well as 3 mm and 7 mm below the surface. Temperatures were recorded continuously at baseline, during delivery, and after ablation. Muscle temperatures were compared with those of RF lesions performed with 1 catheter (Tacticath SE) at 30 W for 30 seconds. RESULTS: PEF ablation with 3energy settings produced small temperature changes. Maximum average temperature rise for PEF for the maximum (25-amp) energy setting (32 lesions) was 7.6 °C, 2.8 °C, and 0.9 °C at the surface, 3-mm depth, and 7-mm depth, respectively. The temperature rise was dose dependent, with lower energy settings yielding less temperature rise. RF ablations (10 lesions) produced temperature increases of 16.6 °C, 39.8 °C, and 9.5 °C at the surface, 3-mm depth, and 7-mm depth, respectively. CONCLUSIONS: PEF caused detectable temperature changes in muscle tissue, which never exceeded 2.8 °C at the 3-mm depth versus baseline. By contrast, RF produced substantial temperature rises. These data support that focal monopolar biphasic energy delivered by this PEF technology retains a favorable thermal safety profile.

Self-administered intranasal etripamil using a symptom-prompted, repeat-dose regimen for atrioventricular-nodal-dependent supraventricular tachycardia (RAPID): a multicentre, randomised trial.

BACKGROUND: Etripamil is a fast-acting, intranasally administered calcium-channel blocker in development for on-demand therapy outside a health-care setting for paroxysmal supraventricular tachycardia. We aimed to evaluate the efficacy and safety of etripamil 70 mg nasal spray using a symptom-prompted, repeat-dose regimen for acute conversion of atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia to sinus rhythm within 30 min. METHODS: RAPID was a multicentre, randomised, placebo-controlled, event-driven trial, conducted at 160 sites in North America and Europe as part 2 of the NODE-301 study. Eligible patients were aged at least 18 years and had a history of paroxysmal supraventricular tachycardia with sustained, symptomatic episodes (≥20 min) as documented by electrocardiogram. Patients were administered two test doses of intranasal etripamil (each 70 mg, 10 min apart) during sinus rhythm; those who tolerated the test doses were randomly assigned (1:1) using an interactive response technology system to receive either etripamil or placebo. Prompted by symptoms of paroxysmal supraventricular tachycardia, patients self-administered a first dose of intranasal 70 mg etripamil or placebo and, if symptoms persisted beyond 10 min, a repeat dose. Continuously recorded electrocardiographic data were adjudicated, by individuals masked to patient assignment, for the primary endpoint of time to conversion of paroxysmal supraventricular tachycardia to sinus rhythm for at least 30 s within 30 min after the first dose, which was measured in all patients who administered blinded study drug for a confirmed atrioventricular-nodal-dependent event. Safety outcomes were assessed in all patients who self-administered blinded study drug for an episode of perceived paroxysmal supraventricular tachycardia. This trial is registered at ClinicalTrials.gov, NCT03464019, and is complete. FINDINGS: Between Oct 13, 2020, and July 20, 2022, among 692 patients randomly assigned, 184 (99 from the etripamil group and 85 from the placebo group) self-administered study drug for atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia, with diagnosis and timing confirmed. Kaplan-Meier estimates of conversion rates by 30 min were 64% (63/99) with etripamil and 31% (26/85) with placebo (hazard ratio 2·62; 95% CI 1·66-4·15; p<0·0001). Median time to conversion was 17·2 min (95% CI 13·4-26·5) with the etripamil regimen versus 53·5 min (38·7-87·3) with placebo. Prespecified sensitivity analyses of the primary assessment were conducted to test robustness, yielding supporting results. Treatment-emergent adverse events occurred in 68 (50%) of 99 patients treated with etripamil and 12 (11%) of 85 patients in the placebo group, most of which were located at the administration site and were mild or moderate, and all of which were transient and resolved without intervention. Adverse events occurring in at least 5% of patients treated with etripamil were nasal discomfort (23%), nasal congestion (13%), and rhinorrhea (9%). No serious etripamil-related adverse events or deaths were reported. INTERPRETATION: Using a symptom-prompted, self-administered, initial and optional-repeat-dosing regimen, intranasal etripamil was well tolerated, safe, and superior to placebo for the rapid conversion of atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia to sinus rhythm. This approach could empower patients to treat paroxysmal supraventricular tachycardia themselves outside of a health-care setting, and has the potential to reduce the need for additional medical interventions, such as intravenous medications given in an acute-care setting. FUNDING: Milestone Pharmaceuticals.