Pulsed Field or Conventional Thermal Ablation for Paroxysmal Atrial Fibrillation.

BACKGROUND: Catheter-based pulmonary vein isolation is an effective treatment for paroxysmal atrial fibrillation. Pulsed field ablation, which delivers microsecond high-voltage electrical fields, may limit damage to tissues outside the myocardium. The efficacy and safety of pulsed field ablation as compared with conventional thermal ablation are not known. METHODS: In this randomized, single-blind, noninferiority trial, we assigned patients with drug-refractory paroxysmal atrial fibrillation in a 1:1 ratio to undergo pulsed field ablation or conventional radiofrequency or cryoballoon ablation. The primary efficacy end point was freedom from a composite of initial procedural failure, documented atrial tachyarrhythmia after a 3-month blanking period, antiarrhythmic drug use, cardioversion, or repeat ablation. The primary safety end point included acute and chronic device- and procedure-related serious adverse events. RESULTS: A total of 305 patients were assigned to undergo pulsed field ablation, and 302 were assigned to undergo thermal ablation. At 1 year, the primary efficacy end point was met (i.e., no events occurred) in 204 patients (estimated probability, 73.3%) who underwent pulsed field ablation and 194 patients (estimated probability, 71.3%) who underwent thermal ablation (between-group difference, 2.0 percentage points; 95% Bayesian credible interval, -5.2 to 9.2; posterior probability of noninferiority, >0.999). Primary safety end-point events occurred in 6 patients (estimated incidence, 2.1%) who underwent pulsed field ablation and 4 patients (estimated incidence, 1.5%) who underwent thermal ablation (between-group difference, 0.6 percentage points; 95% Bayesian credible interval, -1.5 to 2.8; posterior probability of noninferiority, >0.999). CONCLUSIONS: Among patients with paroxysmal atrial fibrillation receiving a catheter-based therapy, pulsed field ablation was noninferior to conventional thermal ablation with respect to freedom from a composite of initial procedural failure, documented atrial tachyarrhythmia after a 3-month blanking period, antiarrhythmic drug use, cardioversion, or repeat ablation and with respect to device- and procedure-related serious adverse events at 1 year. (Funded by Farapulse-Boston Scientific; ADVENT ClinicalTrials.gov number, NCT04612244.).

Comparing pulsed field electroporation and radiofrequency ablation for the treatment of paroxysmal atrial fibrillation: design and rationale of the BEAT PAROX-AF randomized clinical trial.

AIMS: Using thermal-based energy sources [radiofrequency (RF) energy/cryo energy] for catheter ablation is considered effective and safe when performing pulmonary vein isolation (PVI) in patients with paroxysmal atrial fibrillation (AF). However, treatment success remains limited and complications can occur due to the propagation of thermal energy into non-target tissues. We aim to compare pulsed field ablation (PFA) with RF ablation in terms of efficacy and safety for patients with drug-resistant paroxysmal AF. METHODS AND RESULTS: The BEAT PAROX-AF trial is a European multicentre, superiority, open-label randomized clinical trial in two parallel groups. A total of 292 participants were recruited in 9 high-volume European clinical centres in 5 countries. Patients with paroxysmal AF were randomized to PFA (FARAPULSE Endocardial Ablation System©, Boston Scientific) or RF using the CLOSE protocol with contact force sensing catheter (SmartTouch© catheter and CARTO© Biosense Webster). The primary endpoint will be the 1-year recurrence of atrial arrhythmia, and the major secondary safety endpoint will be the occurrence of acute (<7 days) procedure-related serious adverse events, or pulmonary vein stenosis, or atrio-oesophageal fistula up to 12 months. Additionally, five sub-studies investigate the effect of PFA on oesophageal safety, cerebral lesions, cardiac autonomic nervous system, durability of PVI as assessed during redo ablation procedures, and atrial and ventricular function. The study began on 27 December 2021 and concluded recruitment on 17 January 2024. Results will be available in mid-2025. CONCLUSION: The BEAT PAROX-AF trial aims to provide critical insights into the optimal treatment approach for patients with paroxysmal AF.

Pulmonary vein narrowing after pulsed field versus thermal ablation.

AIMS: When it occurs, pulmonary vein (PV) stenosis after atrial fibrillation (AF) ablation is associated with significant morbidity. Even mild-to-moderate PV narrowing may have long-term implications. Unlike thermal ablation energies, such as radiofrequency (RF) or cryothermy, pulsed field ablation (PFA) is a non-thermal modality associated with less fibrotic proliferation. Herein, we compared the effects of PFA vs. thermal ablation on PV narrowing after AF ablation. METHODS AND RESULTS: ADVENT was a multi-centre, randomized, single-blind study comparing PFA (pentaspline catheter) with thermal ablation-force-sensing RF or cryoballoon (CB)-to treat drug-refractory paroxysmal AF. Pulmonary vein diameter and aggregate cross-sectional area were obtained by baseline and 3-month imaging. The pre-specified, formally tested, secondary safety endpoint compared a measure of PV narrowing between PFA vs. thermal groups, with superiority defined by posterior probability > 0.975. Among subjects randomized to PFA (n = 305) or thermal ablation (n = 302), 259 PFA and 255 thermal ablation (137 RF and 118 CB) subjects had complete baseline and 3-month PV imaging. No subject had significant (≥70%) PV stenosis. Change in aggregate PV cross-sectional area was less with PFA (-0.9%) than thermal ablation (-12%, posterior probability > 0.999)-primarily driven by the RF sub-cohort (-19.5%) vs. CB sub-cohort (-3.3%). Almost half of all PFA PV diameters did not decrease, but the majority (80%) of RF PVs decreased, regardless of PV anatomic location. CONCLUSION: In this first randomized comparison of PFA vs. thermal ablation, PFA resulted in less PV narrowing-thereby underscoring the qualitatively differential and favourable impact of PFA on PV tissue.

EUropean real-world outcomes with Pulsed field ablatiOn in patients with symptomatic atRIAl fibrillation: lessons from the multi-centre EU-PORIA registry.

AIMS: Pulsed field ablation (PFA) is a new, non-thermal ablation modality for pulmonary vein (PV) isolation in patients with atrial fibrillation (AF). The multi-centre EUropean Real World Outcomes with Pulsed Field AblatiOn in Patients with Symptomatic AtRIAl Fibrillation (EU-PORIA) registry sought to determine the safety, efficacy, and learning curve characteristics for the pentaspline, multi-electrode PFA catheter. METHODS AND RESULTS: All-comer AF patients from seven high-volume centres were consecutively enrolled. Procedural and follow-up data were collected. Learning curve effects were analysed by operator ablation experience and primary ablation modality. In total, 1233 patients (61% male, mean age 66 ± 11years, 60% paroxysmal AF) were treated by 42 operators. In 169 patients (14%), additional lesions outside the PVs were performed, most commonly at the posterior wall (n = 127). Median procedure and fluoroscopy times were 58 (interquartile range: 40-87) and 14 (9-21) min, respectively, with no differences due to operator experience. Major complications occurred in 21/1233 procedures (1.7%) including pericardial tamponade (14; 1.1%) and transient ischaemic attack or stroke (n = 7; 0.6%), of which one was fatal. Prior cryoballoon users had less complication. At a median follow-up of 365 (323-386) days, the Kaplan-Meier estimate of arrhythmia-free survival was 74% (80% for paroxysmal and 66% for persistent AF). Freedom from arrhythmia was not influenced by operator experience. In 149 (12%) patients, a repeat procedure was performed due to AF recurrence and 418/584 (72%) PVs were durably isolated. CONCLUSION: The EU-PORIA registry demonstrates a high single-procedure success rate with an excellent safety profile and short procedure times in a real-world, all-comer AF patient population.

The Use of Next-Generation Sequencing in Pharmacogenomics.

BACKGROUND: Next-generation sequencing (NGS) methods have become more commonly performed in clinical and research laboratories. METHODS: This review summarizes the current laboratory NGS-based diagnostic approaches in pharmacogenomics including targeted multi-gene panel sequencing, whole-exome sequencing (WES), and whole-genome sequencing (WGS). RESULTS: Clinical laboratories perform multiple non-uniform types of pharmacogenetic panels, which can reduce the overall number of single-gene tests to be more cost-efficient. Compared to the targeted multi-gene panels, which are not typically designed to detect novel variants, WES and WGS have a greater potential to identify secondary pharmacogenomic findings, which might be predictive for the pharmacotherapy outcome of different patient settings. WGS overcomes the limitations of WES enabling a more accurate exome-sequencing at appropriate coverage and the sequencing of non-coding regions. Different NGS-based study designs with different test strategies and study populations, varying sample sizes, and distinct analytical and interpretation procedures lead to different identification results of pharmacogenomic variants. CONCLUSIONS: The rapid progress in gene sequencing technologies will overcome the clinical and laboratory challenges of WES and WGS. Further high throughput NGS-based pharmacogenomics studies in different populations and patient settings are necessary to expand knowledge about rare functional variants and to enhance translation in clinical practice.

Preoperative Computed Tomography Angiography for ALT Flaps Optimizes Design and Reduces Operative Time.

BACKGROUND: Computed tomography angiography (CTA) has been widely used for perforator mapping in abdominal-based reconstruction, but it is less widespread in the anterolateral thigh (ALT) flap. However, CTA may be quite useful for ALT planning, as this flap has demonstrated substantial variability in intrapatient bilateral vascular anatomy. This study investigated whether standard use of preoperative CTA resulted in selection of the donor extremity with preferential perforator anatomy, and whether this affected operative time and postoperative outcomes. METHODS: A retrospective review of 105 patients who underwent proposed ALT flap reconstruction was performed. Seventy-nine patients received bilateral lower extremity CTAs, which were evaluated for dominant perforator anatomy (septocutaneous, musculoseptocutaneous, or musculocutaneous). Donor extremity selection was noted, and predicted perforator anatomy was compared with that encountered intraoperatively. RESULTS: Among the 73 patients who received bilateral imaging and ultimately received an ALT, congruent findings between imaging and surgical exploration were observed in 51 (69.8%) patients. Thirty (37.9%) patients had asymmetric perforator anatomy between their bilateral extremities on imaging. Among these, the leg with optimal perforator anatomy was selected in 70% of cases. There were no significant reductions among postoperative complication rates, but selection of the donor site with preferential anatomy was associated with a decrease in operative time (p = 0.049) among patients undergoing extremity reconstruction. CONCLUSION: CTA is a useful tool for optimizing donor site selection for ALT flaps and reducing operative time. We believe that standard use of preoperative CTA in ALTs warrants further consideration.

Pulsed field ablation selectively spares the oesophagus during pulmonary vein isolation for atrial fibrillation.

AIMS: Extra-atrial injury can cause complications after catheter ablation for atrial fibrillation (AF). Pulsed field ablation (PFA) has generated preclinical data suggesting that it selectively targets the myocardium. We sought to characterize extra-atrial injuries after pulmonary vein isolation (PVI) between PFA and thermal ablation methods. METHODS AND RESULTS: Cardiac magnetic resonance (CMR) imaging was performed before, acutely (<3 h) and 3 months post-ablation in 41 paroxysmal AF patients undergoing PVI with PFA (N = 18, Farapulse) or thermal methods (N = 23, 16 radiofrequency, 7 cryoballoon). Oesophageal and aortic injuries were assessed by using late gadolinium-enhanced (LGE) imaging. Phrenic nerve injuries were assessed from diaphragmatic motion on intra-procedural fluoroscopy. Baseline CMR showed no abnormality on the oesophagus or aorta. During ablation procedures, no patient showed phrenic palsy. Acutely, thermal methods induced high rates of oesophageal lesions (43%), all observed in patients showing direct contact between the oesophagus and the ablation sites. In contrast, oesophageal lesions were observed in no patient ablated with PFA (0%, P < 0.001 vs. thermal methods), despite similar rates of direct contact between the oesophagus and the ablation sites (P = 0.41). Acute lesions were detected on CMR on the descending aorta in 10/23 (43%) after thermal ablation, and in 6/18 (33%) after PFA (P = 0.52). CMR at 3 months showed a complete resolution of oesophageal and aortic LGE in all patients. No patient showed clinical complications. CONCLUSION: PFA does not induce any signs of oesophageal injury on CMR after PVI. Due to its tissue selectivity, PFA may improve safety for catheter ablation of AF.

Pulsed field ablation prevents chronic atrial fibrotic changes and restrictive mechanics after catheter ablation for atrial fibrillation.

AIMS: Pulsed field ablation (PFA), a non-thermal ablative modality, may show different effects on the myocardial tissue compared to thermal ablation. Thus, this study aimed to compare the left atrial (LA) structural and mechanical characteristics after PFA vs. thermal ablation. METHODS AND RESULTS: Cardiac magnetic resonance was performed pre-ablation, acutely (<3 h), and 3 months post-ablation in 41 patients with paroxysmal atrial fibrillation (AF) undergoing pulmonary vein (PV) isolation with PFA (n = 18) or thermal ablation (n = 23, 16 radiofrequency ablations, 7 cryoablations). Late gadolinium enhancement (LGE), T2-weighted, and cine images were analysed. In the acute stage, LGE volume was 60% larger after PFA vs. thermal ablation (P < 0.001), and oedema on T2 imaging was 20% smaller (P = 0.002). Tissue changes were more homogeneous after PFA than after thermal ablation, with no sign of microvascular damage or intramural haemorrhage. In the chronic stage, the majority of acute LGE had disappeared after PFA, whereas most LGE persisted after thermal ablation. The maximum strain on PV antra, the LA expansion index, and LA active emptying fraction declined acutely after both PFA and thermal ablation but recovered at the chronic stage only with PFA. CONCLUSION: Pulsed field ablation induces large acute LGE without microvascular damage or intramural haemorrhage. Most LGE lesions disappear in the chronic stage, suggesting a specific reparative process involving less chronic fibrosis. This process may contribute to a preserved tissue compliance and LA reservoir and booster pump functions.

Riboswitching with ciprofloxacin-development and characterization of a novel RNA regulator.

RNA molecules play important and diverse regulatory roles in the cell. Inspired by this natural versatility, RNA devices are increasingly important for many synthetic biology applications, e.g. optimizing engineered metabolic pathways, gene therapeutics or building up complex logical units. A major advantage of RNA is the possibility of de novo design of RNA-based sensing domains via an in vitro selection process (SELEX). Here, we describe development of a novel ciprofloxacin-responsive riboswitch by in vitro selection and next-generation sequencing-guided cellular screening. The riboswitch recognizes the small molecule drug ciprofloxacin with a KD in the low nanomolar range and adopts a pseudoknot fold stabilized by ligand binding. It efficiently interferes with gene expression both in lower and higher eukaryotes. By controlling an auxotrophy marker and a resistance gene, respectively, we demonstrate efficient, scalable and programmable control of cellular survival in yeast. The applied strategy for the development of the ciprofloxacin riboswitch is easily transferrable to any small molecule target of choice and will thus broaden the spectrum of RNA regulators considerably.

Diversification of shrub frogs (Rhacophoridae, Pseudophilautus) in Sri Lanka - Timing and geographic context.

Pseudophilautus comprises an endemic diversification predominantly associated with the wet tropical regions of Sri Lanka that provides an opportunity to examine the effects of geography and historical climate change on diversification. Using a time-calibrated multi-gene phylogeny, we analyze the tempo of diversification in the context of past climate and geography to identify historical drivers of current patterns of diversity and distribution. Molecular dating suggests that the diversification was seeded by migration across a land-bridge connection from India during a period of climatic cooling and drying, the Oi-1 glacial maximum around the Eocene-Oligocene boundary. Lineage-through-time plots suggest a gradual and constant rate of diversification, beginning in the Oligocene and extending through the late Miocene and early Pliocene with a slight burst in the Pleistocene. There is no indication of an early-burst phase of diversification characteristic of many adaptive radiations, nor were there bursts of diversification associated with favorable climate shifts such as the intensification of monsoons. However, a late Miocene (8.8 MYA) back-migration to India occurred following the establishment of the monsoon. The back migration did not trigger a diversification in India similar to that manifest in Sri Lanka, likely due to occupation of available habitat, and consequent lack of ecological opportunity, by the earlier radiation of a sister lineage of frogs (Raorchestes) with similar ecology. Phylogenetic area reconstructions show a pattern of sister species distributed across adjacent mountain ranges or from different parts of large montane regions, highlighting the importance of isolation and allopatric speciation. Hence, local species communities are composed of species from disparate clades that, in most cases, have been assembled through migration rather than in situ speciation. Lowland lineages are derived from montane lineages. Thus, the hills of Sri Lanka acted as species pumps as well as refuges throughout the 31 million years of evolution, highlighting the importance of tropical montane regions for both the generation and maintenance of biodiversity.

Total Synthesis of (±)-Phomoidride†D.

Described herein is a synthetic strategy for the total synthesis of (±)-phomoidride D. This highly efficient and stereoselective approach provides rapid assembly of the carbocyclic core by way of a tandem phenolic oxidation/intramolecular Diels-Alder cycloaddition. A subsequent SmI2 -mediated cyclization cascade delivers an isotwistane intermediate poised for a Wharton fragmentation that unveils the requisite bicyclo[4.3.1]decene skeleton and sets the stage for synthesis completion.

Identification of RNA aptamers with riboswitching properties.

During the past years customized gene network design has become of tremendous interest among various disciplines in life science. The identification of artificial genetic elements sensitive to internal or external stimuli constitutes the foundation for the design and realization of conditional gene expression systems. Typically, strategies involving selection or screening steps are employed alongside approaches focusing on rational design to select for the desired functionality of a given element. Here we present a fluorescence-based in vivo screening approach that combines an initial in vitro selection with subsequent extensive screening steps and a final rational design to identify RNA based regulators in baker's yeast. These artificial RNA regulators, termed synthetic riboswitches, are derived from RNA aptamers. Our method allows for the separation of aptamers featuring the potential to be transformed into a riboswitch from those inherently unable to confer control over gene expression. The system may be applied to virtually all existing aptamer-ligand pairs and as such presents a powerful means to enhance the setup of switchable genetic circuits.

The genome of the green anole lizard and a comparative analysis with birds and mammals.

The evolution of the amniotic egg was one of the great evolutionary innovations in the history of life, freeing vertebrates from an obligatory connection to water and thus permitting the conquest of terrestrial environments. Among amniotes, genome sequences are available for mammals and birds, but not for non-avian reptiles. Here we report the genome sequence of the North American green anole lizard, Anolis carolinensis. We find that A. carolinensis microchromosomes are highly syntenic with chicken microchromosomes, yet do not exhibit the high GC and low repeat content that are characteristic of avian microchromosomes. Also, A. carolinensis mobile elements are very young and diverse-more so than in any other sequenced amniote genome. The GC content of this lizard genome is also unusual in its homogeneity, unlike the regionally variable GC content found in mammals and birds. We describe and assign sequence to the previously unknown A. carolinensis X chromosome. Comparative gene analysis shows that amniote egg proteins have evolved significantly more rapidly than other proteins. An anole phylogeny resolves basal branches to illuminate the history of their repeated adaptive radiations.

Stereocontrolled Total Synthesis of Muraymycin D1 Having a Dual Mode of Action against Mycobacterium tuberculosis.

A stereocontrolled first total synthesis of muraymycin D1 (1) has been achieved. The synthetic route is highly stereoselective, featuring (1) selective ß-ribosylation of the C2-methylated amino ribose, (2) selective Strecker reaction, and (3) ring-opening reaction of a diastereomeric mixture of a diaminolactone to synthesize muraymycidine (epi-capreomycidine). The acid-cleavable protecting groups for secondary alcohol and uridine ureido nitrogen are applied for simultaneous deprotections with the Boc and tBu groups. Muraymycin D1 (1) and its amide derivatives (2 and 3) exhibited growth inhibitory activity against Mycobacterium tuberculosis (MIC50 = 1.56-6.25 µg/mL) and strong enzyme inhibitory activities against the bacterial phosphotransferases (MurX and WecA) (IC50 = 0.096-0.69 µM).

Noble-Metal-Free Photocatalytic H2 Generation: Active and Inactive 'Black' TiO2 Nanotubes and Synergistic Effects.

Over the past five years a number of different synthesis approaches has been reported to obtain so-called 'black' titania. One of the outstanding features of the material is that certain synthesis processes lead to the formation of an intrinsic co-catalytic center and thus enable noble-metal free photocatalytic H2 -generation. In the present work, using TiO2 nanotube layers, we compare three common 'blackening' approaches, namely i) the original high-pressure hydrogenation (HPT-H2 ), ii) a classic high temperature reduction in Ar, and iii) an electrochemical (cathodic) reduction. We demonstrate that except for high pressure hydrogenation also cathodic reduction leads to an activation of TiO2 - that is, it exhibits noble-metal-free photocatalytic H2 generation. Moreover, we show that a combination of cathodic reduction/high pressure hydrogenation leads to a synergistic effect, that is, a significant enhancement of the combined co-catalytic activity.

Black TiO2 nanotubes: cocatalyst-free open-circuit hydrogen generation.

Here we report that TiO2 nanotube (NT) arrays, converted by a high pressure H2 treatment to anatase-like "black titania", show a high open-circuit photocatalytic hydrogen production rate without the presence of a cocatalyst. Tubes converted to black titania using classic reduction treatments (e.g., atmospheric pressure H2/Ar annealing) do not show this effect. The main difference caused by the high H2 pressure annealing is the resulting room-temperature stable, isolated Ti(3+) defect-structure created in the anatase nanotubes, as evident from electron spin resonance (ESR) investigations. This feature, absent for conventional reduction, seems thus to be responsible for activating intrinsic, cocatalytic centers that enable the observed high open-circuit hydrogen generation.

Hydrogenated anatase: strong photocatalytic dihydrogen evolution without the use of a co-catalyst.

The high-pressure hydrogenation of commercially available anatase or anatase/rutile TiO2 powder can create a photocatalyst for H2 evolution that is highly effective and stable without the need for any additional co-catalyst. This activation effect cannot be observed for rutile; however, for anatase/rutile mixtures, a strong synergistic effect can be found (similar to results commonly observed for noble-metal-decorated TiO2). EPR and PL measurements indicated the intrinsic co-catalytic activation of anatase TiO2 to be due to specific defect centers formed during hydrogenation. These active centers can be observed specifically for high-pressure hydrogenation; other common reduction treatments do not result in this effect.

Results From Complex Abdominal Reconstruction at Non-Academic Institution can Favorably Compare to Major Academic Centers: An Abdominal Core Health Quality Collaborative Database Review.

BACKGROUND: Many complex abdominal hernias are referred to tertiary academic institutions for evaluation and treatment. The purpose of this study was to compare clinical outcomes from complex abdominal hernia repairs and abdominal wall reconstructions at a community hospital vs high volume academic centers participating in Abdominal Core Health Quality Collaborative (ACHQC). METHODS: Patients undergoing elective complex abdominal hernia repair were identified in our community setting and treated between 2016 and 2019. These results were then compared to Academic centers in the ACHQC database. Complex hernia definition was limited to those who have undergone any myofascial advancement procedure for homogeneity. Informed consent was obtained, and study was IRB approved. All data was de-identified. RESULTS: A total of 180 patients underwent complex abdominal hernia repair at our community hospital. The ACHQC database identified 6299 patients meeting criteria at participating academic centers. Demographics were similar between the two groups including hernia grade, size and wound class. Academic centers tended to have patients with previous component separations (25.7% vs 10.6%) and immunosuppressed (7.2% vs 2.8%), while the community hospital patients included more patients with tobacco use (18.9% vs 12.1%) and hypertension (65% vs 54.9%). Operative times were significantly less at the community hospital, patients requiring >240 minutes of time for repair at academic centers (39.6% vs 5%). Postoperatively length of stay was significantly shorter at the community hospital group averaging 3.7 days vs academic centers of 6 days (P < .05). Although overall complications were less in the community hospital group (26.5% vs 19.4%). Readmission within 30 days was nearly twice as frequent in the community hospital group (14.4% vs 7.7%). CONCLUSION: Community hospitals can provide comparable care and surgical expertise as major academic centers in regard to complex hernias in a large majority of cases. There is a need for dedicated care coordination and continuous review of supporting staff and outcomes is necessary to assure quality care. There is still a need to identify which patients would benefit from treatment at an academic center as opposed to a community hospital in order to maximize patient access and outcomes at both types of hospital setting. Further investigation needs to be performed regarding criteria for which patients should be transferred to academic centers for their complex hernia care. Identifying patients who would benefit from treatment at Academic Centers as opposed to Community hospitals should continue to be investigated.

Comparison of cerebral safety after atrial fibrillation using pulsed field and thermal ablation: Results of the neurological assessment subgroup in the ADVENT trial.

BACKGROUND: Atrial fibrillation (AF) ablation carries the risk of silent cerebral event (SCE) and silent cerebral lesion (SCL). Although "silent," these may have long-term clinical implications and are challenging to study as postprocedural magnetic resonance imaging (MRI) is not standard of care. OBJECTIVE: The neurological assessment subgroup (NAS) of ADVENT compared cerebral effects of pulsed field ablation (PFA) with standard-of-care thermal ablation. METHODS: The NAS included consecutive randomized PFA and thermal ablation patients who received postprocedural brain MRI 12-48 hours after ablation. Patients with apparent SCE or SCL findings underwent a modified Rankin scale assessment. MRI images were subsequently reviewed by a blinded brain imaging core laboratory. RESULTS: In total, 77 patients with paroxysmal AF were enrolled at 6 centers; 71 had analyzable scans (34 PFA; 37 thermal ablation). Through individual center review, 6 PFA and 4 thermal scans were identified as SCE/SCL positive, of which 3 PFA and 0 thermal SCE/SCL findings were confirmed by a blinded core laboratory. MRI findings revealed 1 patient with 2- to 4-mm SCEs, 1 patient with a 3-mm SCE, and 1 patient with 2 SCLs (5.5 mm and 11 mm). All modified Rankin scale and National Institutes of Health Stroke Scale scores were 0 before discharge and at 90-day follow-up. There were only 2 neurological safety events (1 transient ischemic attack [PFA] and 1 stroke [thermal ablation]) in the ADVENT study, neither of which was part of the NAS. CONCLUSION: The ADVENT trial provides the first prospective, randomized data on the cerebral impact of PFA and thermal ablation of AF. Incidence of SCE/SCL after ablation in the NAS was low.

Nitroglycerin to Ameliorate Coronary Artery Spasm During Focal Pulsed-Field Ablation for Atrial Fibrillation.

BACKGROUND: In treating atrial fibrillation, pulsed-field ablation (PFA) has comparable efficacy to conventional thermal ablation, but with important safety advantages: no esophageal injury or pulmonary vein stenosis, and rare phrenic nerve injury. However, when PFA is delivered in proximity to coronary arteries using a pentaspline catheter, which generates a broad electrical field, severe vasospasm can be provoked. OBJECTIVES: The authors sought to study the vasospastic potential of a focal PFA catheter with a narrower electrical field and develop a preventive strategy with nitroglycerin. METHODS: During atrial fibrillation ablation, a focal PFA catheter was used for cavotricuspid isthmus ablation. Angiography of the right coronary artery (some with fractional flow reserve measurement) was performed before, during, and after PFA. Beyond no nitroglycerin (n = 5), and a few testing strategies (n = 8), 2 primary nitroglycerin administration strategies were studied: 1) multiple boluses (3-2 mg every 2 min) into the right atrium (n = 10), and 2) a bolus (3 mg) into the right atrium with continuous peripheral intravenous infusion (1 mg/min; n = 10). RESULTS: Without nitroglycerin, cavotricuspid isthmus ablation provoked moderate-severe vasospasm in 4 of 5 (80%) patients (fractional flow reserve 0.71 ± 0.08). With repetitive nitroglycerin boluses, severe spasm did not occur, and mild-moderate vasospasm occurred in only 2 of 10 (20%). Using the bolus + infusion strategy, severe and mild-moderate spasm occurred in 1 and 3 of 10 patients (aggregate 40%). No patient had ST-segment changes. CONCLUSIONS: Ablation of the cavotricuspid isthmus using a focal PFA catheter routinely provokes right coronary vasospasm. Pretreatment with high doses of parenteral nitroglycerin prevents severe spasm.