Procedural and Intermediate-term Results of the Electroanatomical-guided Cardioneuroablation for the Treatment of Supra-Hisian Second- or Advanced-degree Atrioventricular Block: the PIRECNA multicentre registry.

AIMS: Prior case series showed promising results for cardioneuroablation in patients with vagally induced atrioventricular blocks (VAVBs). We aimed to examine the acute procedural characteristics and intermediate-term outcomes of electroanatomical-guided cardioneuroablation (EACNA) in patients with VAVB. METHODS AND RESULTS: This international multicentre retrospective registry included data collected from 20 centres. Patients presenting with symptomatic paroxysmal or persistent VAVB were included in the study. All patients underwent EACNA. Procedural success was defined by the acute reversal of atrioventricular blocks (AVBs) and complete abolition of atropine response. The primary outcome was occurrence of syncope and daytime second- or advanced-degree AVB on serial prolonged electrocardiogram monitoring during follow-up. A total of 130 patients underwent EACNA. Acute procedural success was achieved in 96.2% of the cases. During a median follow-up of 300 days (150, 496), the primary outcome occurred in 17/125 (14%) cases with acute procedural success (recurrence of AVB in 9 and new syncope in 8 cases). Operator experience and use of extracardiac vagal stimulation were similar for patients with and without primary outcomes. A history of atrial fibrillation, hypertension, and coronary artery disease was associated with a higher primary outcome occurrence. Only four patients with primary outcome required pacemaker placement during follow-up. CONCLUSION: This is the largest multicentre study demonstrating the feasibility of EACNA with encouraging intermediate-term outcomes in selected patients with VAVB. Studies investigating the effect on burden of daytime symptoms caused by the AVB are required to confirm these findings.

Cardioneuroablation for the management of patients with recurrent vasovagal syncope and symptomatic bradyarrhythmias: the CNA-FWRD Registry.

BACKGROUND: Cardioneuroablation has been emerging as a potential treatment alternative in appropriately selected patients with cardioinhibitory vasovagal syncope (VVS) and functional AV block (AVB). However the majority of available evidence has been derived from retrospective cohort studies performed by experienced operators. METHODS: The Cardioneuroablation for the Management of Patients with Recurrent Vasovagal Syncope and Symptomatic Bradyarrhythmias (CNA-FWRD) Registry is a multicenter prospective registry with cross-over design evaluating acute and long-term outcomes of VVS and AVB patients treated by conservative therapy and CNA. RESULTS: The study is a prospective observational registry with cross-over design for analysis of outcomes between a control group (i.e., behavioral and medical therapy only) and intervention group (Cardioneuroablation). Primary and secondary outcomes will only be assessed after enrollment in the registry. The follow-up period will be 3 years after enrollment. CONCLUSIONS: There remains a lack of prospective multicentered data for long-term outcomes comparing conservative therapy to radiofrequency CNA procedures particularly for key outcomes including recurrence of syncope, AV block, durable impact of disruption of the autonomic nervous system, and long-term complications after CNA. The CNA-FWRD registry has the potential to help fill this information gap.

Strong, highly porous and sustainable nanocellulose foam made using bioderived hyperbranched crosslinker for thermal insulation and sound absorption.

This paper reports an environment-friendly biobased foam made with cellulose nanofiber (CNF) and a biobased hyperbranched crosslinker, glycerol succinic anhydride (GSA). As a biobased hyperbranched crosslinker, carboxyl-terminated GSA is synthesized through a straightforward esterification process involving glycerol and succinic anhydride. The GSA-crosslinked CNF (GSA/CNF) foam is prepared using a facile, sustainable, cost-effective, and efficient solvent-exchange method. The resulting foam exhibits notable characteristics, including improved dimensional stability, remarkably low density (13.41 mg/cm3) with high porosity (>99 %), and exceptional compressive strength (494 kPa) and modulus (452 kPa). Further, the foam offers outstanding sound absorption capabilities with a coefficient of 0.986 at 2 kHz and remarkably low thermal conductivity (30.18 mW/mK), significantly lower than commonly used and reported porous materials, indicating its potential as an efficient, environmentally friendly sound absorption and thermal insulation material.

Learning From Alarms: A Robust Learning Approach for Accurate Photoplethysmography-Based Atrial Fibrillation Detection Using Eight Million Samples Labeled With Imprecise Arrhythmia Alarms.

Atrial fibrillation (AF) is a common cardiac arrhythmia with serious health consequences if not detected and treated early. Detecting AF using wearable devices with photoplethysmography (PPG) sensors and deep neural networks has demonstrated some success using proprietary algorithms in commercial solutions. However, to improve continuous AF detection in ambulatory settings towards a population-wide screening use case, we face several challenges, one of which is the lack of large-scale labeled training data. To address this challenge, we propose to leverage AF alarms from bedside patient monitors to label concurrent PPG signals, resulting in the largest PPG-AF dataset so far (8.5 M 30-second records from 24,100 patients) and demonstrating a practical approach to build large labeled PPG datasets. Furthermore, we recognize that the AF labels thus obtained contain errors because of false AF alarms generated from imperfect built-in algorithms from bedside monitors. Dealing with label noise with unknown distribution characteristics in this case requires advanced algorithms. We, therefore, introduce and open-source a novel loss design, the cluster membership consistency (CMC) loss, to mitigate label errors. By comparing CMC with state-of-the-art methods selected from a noisy label competition, we demonstrate its superiority in handling label noise in PPG data, resilience to poor-quality signals, and computational efficiency.

The seroprevalence of toxocariasis and related risk factors in children in Ho Chi Minh City, Vietnam: results from a school-based cross-sectional study.

BACKGROUND: Children are especially vulnerable to Toxocara infection and its severe complications; however, there have not been any published data on the disease prevalence and treatment effectiveness in the population of Vietnamese children. This study was conducted to determine the prevalence of toxocariasis and explore factors associated with Toxocara infection in children aged 3-15 y in Ho Chi Minh City, Vietnam. METHODS: We conducted a cross-sectional study using a multistage cluster sampling approach in public schools. Blood samples were collected, and toxocariasis cases were confirmed, based on a history of contact with dogs/cats and positive anti-Toxocara antibody detection via ELISA. We calculated the percentage of seropositive children across gender, grade levels, districts and caregiver education. Multiple regression models were employed to identify potential risk factors. RESULTS: Anti-Toxocara antibodies were found in 14.2% of the 986 children studied. Significant variations in seropositivity were observed across grade levels, districts and caregiver education levels. Multivariable analysis identified caregiver education, contact with dogs/cats and improper handling of pet feces as seropositivity risk factors. CONCLUSION: This was the first community-based prevalence study of toxocariasis in a pediatric population in Vietnam. Implementation of preventive measures such as public education, routine fecal examinations and chemotherapeutic treatment of animals is highly recommended.

Biobased, cellulose long filament-reinforced vanillin-derived epoxy composite for high-performance and flame-retardant applications.

The development of high-strength and intrinsic flame-retardant natural fiber-reinforced green composite (NFRGC) is a landmark for high-performance structural applications. This paper reports a biobased, high-performance, flame-retardant composite material based on diverse bio-resources. Tough and strong cellulose long filaments (CLFs) are combined with vanillin-derived epoxy (VDE) resin to achieve high strength and flame-retardant NFRGC. The green composite was fabricated using a simple hand lay-up and compression molding technique. The green composite showed a noteworthy increment of 100.9 % flexural strength and 346 % flexural modulus compared to the neat VDE resin. Interestingly, despite the highly flammable nature of CLF, the green composite passes a V-0 rating under the UL-94 test, indicating excellent flame-retardant characteristics. Additionally, the green composite demonstrated outstanding hydrophobicity with a water contact angle of 104.2° and good chemical stability in various acidic and organic solvents. The green composite's excellent mechanical and physical properties show its potential for high-strength and flame-retardant structural applications.

Cryothermal energy demonstrates shorter ablation time and lower complication rates compared with radiofrequency in surgical hybrid ablation for recurrent ventricular tachycardia.

BACKGROUND: Recurrent ventricular tachycardia (VT) after prior endocardial catheter ablation(s) presents challenges in the setting of prior cardiac surgery where percutaneous epicardial access may not be feasible. OBJECTIVE: The purpose of this study was to compare the outcomes of cryothermal vs radiofrequency ablation in direct surgical epicardial access procedures. METHODS: We performed a retrospective study of consecutive surgical epicardial VT ablation cases. Surgical cases using cryothermal vs radiofrequency ablation were analyzed and outcomes were compared. RESULTS: Between 2009 and 2022, 43 patients underwent either a cryothermal (n = 17) or a radiofrequency (n = 26) hybrid epicardial ablation procedure with direct surgical access. Both groups were similarly matched for age, sex, etiology of VT, and comorbidities with a high burden of refractory VT despite previous endocardial and/or percutaneous epicardial ablation procedures. The surgical access site was lateral thoracotomy (76.5%) in the cryothermal ablation group compared with lateral thoracotomy (42.3%) and subxiphoid approach (38.5%) in the radiofrequency group, with the remainder in both groups performed via median sternotomy. The ablation time was significantly shorter in those undergoing cryothermal ablation vs radiofrequency ablation (11.54 ± 15.5 minutes vs 48.48 ± 23.6 minutes; P < .001). There were no complications in the cryothermal ablation group compared with 6 patients with complications in the radiofrequency group. Recurrent VT episodes and all-cause mortality were similar in both groups. CONCLUSION: Hybrid surgical VT ablation with cryothermal or radiofrequency energy demonstrated similar efficacy outcomes. Cryothermal ablation was more efficient and safer than radiofrequency in a surgical setting and should be considered when surgical access is required.

Pharmacological inhibition of TBK1/IKKε blunts immunopathology in a murine model of SARS-CoV-2 infection.

TANK-binding kinase 1 (TBK1) is a key signalling component in the production of type-I interferons, which have essential antiviral activities, including against SARS-CoV-2. TBK1, and its homologue IκB kinase-ε (IKKε), can also induce pro-inflammatory responses that contribute to pathogen clearance. While initially protective, sustained engagement of type-I interferons is associated with damaging hyper-inflammation found in severe COVID-19 patients. The contribution of TBK1/IKKε signalling to these responses is unknown. Here we find that the small molecule idronoxil inhibits TBK1/IKKε signalling through destabilisation of TBK1/IKKε protein complexes. Treatment with idronoxil, or the small molecule inhibitor MRT67307, suppresses TBK1/IKKε signalling and attenuates cellular and molecular lung inflammation in SARS-CoV-2-challenged mice. Our findings additionally demonstrate that engagement of STING is not the major driver of these inflammatory responses and establish a critical role for TBK1/IKKε signalling in SARS-CoV-2 hyper-inflammation.

Understanding Cardiac Anatomy and Imaging to Improve Safety of Procedures: The Right Ventricle.

Right ventricular perforation is a catastrophic complication of catheter-based intracardiac interventions. In this context, appreciation of 5 attachments of the right ventricle to the aortoventricular unit is essential to recognize extent of right ventricular free wall. We herein present progressive dissection and virtual and photographic endoscopic images of the hearts without distortion. Real dissection images show us how and where to avoid this complication by indicating the true muscular component of the ventricular septum. Both virtual and photographic endoscopic images, when combined with transillumination, beautifully shows the thin wall regions and trabeculations with unprecedented clarity. We believe recognition of these anatomical nuances can reduce the likelihood of right ventricular perforation.

Transcatheter Aortic Valve Replacement Guided by Preprocedural Simulation of Fluoroscopic Location of the Membranous Septum.

We show the virtual simulation of the fluoroscopic location of the membranous septum using preprocedural cardiac computed tomographic data sets. Recognizing the risk distance before the procedure can help individualize implantation strategy to reduce the risk of atrioventricular conduction axis damage during transcatheter aortic valve replacement. (Level of Difficulty: Advanced.).

Ventricular Parasystole in Cardiomyopathy Patients: A Link Between His-Purkinje System Damage and Ventricular Fibrillation.

BACKGROUND: The clinical relevance and prognostic implications of ventricular parasystole are unknown. OBJECTIVES: This study sought to assess the prevalence of ventricular parasystole in patients with implantable cardioverter-defibrillators (ICDs) and ventricular parasystole's association with ventricular arrhythmias and conduction system abnormalities. METHODS: This study retrospectively evaluated patients who underwent ICD interrogation at a single center between June 1, 2019, and August 31, 2020, and reviewed all available ICD and electrocardiogram data. This study identified patients with ventricular parasystole and compared the prevalence of ventricular fibrillation (VF), ventricular tachycardia (VT), and new conduction system abnormalities in those with ≥5 years of intrinsic QRS-complex electrocardiograms to those without parasystole. RESULTS: This study included 374 patients (age 57 ± 21 years, 72% male, 45% nonischemic, 32% ischemic cardiomyopathy), of which, 104 (28%) had VT only, 39 (10%) VF only, and 10 (3%) both VT/VF. Ventricular parasystole was identified in 33 patients (9%); parasystolic foci were predominantly from the His-Purkinje system. Compared with those without parasystole, patients with parasystole had a significantly higher rate of VF (36% vs 11%; P < 0.01), but not VT (42% vs 29%; P = 0.12). Patients with parasystole, compared with those without parasystole, had a higher prevalence of new conduction abnormalities, particularly progressive intraventricular conduction delay (11 of 18 [61%] vs 12 of 83 [14%]; P < 0.01) and new right bundle branch block (4 of 18 [22%] vs 1 of 83 [1%]; P < 0.01). CONCLUSIONS: Ventricular parasystole was strongly associated with new conduction system abnormalities and VF in patients who have cardiomyopathy with ICDs, suggesting a potential link between VF and His-Purkinje damage in this patient population.

Magnetic resonance imaging is safe in patients with left bundle branch pacing.

BACKGROUND: The use of left bundle branch pacing (LBBP) has dramatically increased since it was first described in 2016, but to date there are no published data on the safety of performing magnetic resonance imaging (MRI) in these patients. METHODS: Patients with LBBP who underwent MRI between January 2016 and October 2022 were retrospectively studied in our clinical center, which has a special program for imaging patients with cardiac devices. All patients underwent close cardiac monitoring throughout the MRI scans. Occurrence of arrhythmias or other adverse effects during MRI were assessed. LBBP lead parameters immediately pre- and post-MRI and at an outpatient follow-up were compared. RESULTS: Fifteen patients with LBBP underwent a total of 19 MRI sessions during the study period. Lead parameters did not significantly change after the MRI or on follow-up, which took place at a median of 91 days after the MRI. No patient developed arrhythmias during the MRI sessions, and no adverse effects such as lead dislodgement were reported. CONCLUSION: Although larger studies are necessary to verify our findings, MRI in patients with LBBP appears safe based on this initial case series.

Outcomes in orthotopic heart transplantation following pacemaker implantation.

BACKGROUND: Bradyarrhythmias including sinus node dysfunction (SND) and atrioventricular block (AVB) can necessitate pacemaker (PPM) implantation in orthotopic heart transplant (OHT) recipients. Prior studies have shown conflicting findings regarding the effect of PPM implantation on survival. We evaluated the effect of PPM indication on long-term re-transplant-free survival in OHT patients. METHODS: We conducted a retrospective cohort study of OHT patients at UCLA Medical Center from 1985 to 2018. Indication for PPM (SND, AVB) was identified. Cox proportional hazards model with pacemaker implantation as a time-varying covariate was used to evaluate its effect on the primary endpoint of retransplant or death. We included 1609 OHTs in 1511 adult patients with median follow-up of 12 years. RESULTS: At transplant, patients were aged 53 ± 13 years and 1125 (74.5%) were male. Pacemakers were implanted in 109 (7.2%) patients; 65 for SND (4.3%) and 43 for AVB (2.8%). Repeat OHT was performed in 103 (6.4%) cases and 798 (52.8%) patients died during the follow-up period. The risk of the primary endpoint was significantly higher in patients requiring PPM for AVB (HR 3.0, 95% CI 2.1-4.2, p < .01) after controlling for age at OHT, gender, hypertension, diabetes, renal disease, history of repeat OHT, acute rejection, transplant coronary vasculopathy, and atrial fibrillation, but not PPM for SND (HR 1.0, 95% CI 0.70-1.4, p = 1.0). CONCLUSIONS: Patients who required PPM for AVB, but not SND, were at significantly higher risk of death or retransplant compared to patients who did not require PPM.

Steering Potential for Printing Highly Aligned Discontinuous Fibre Composite Filament.

DcAFF (discontinuous aligned fibre filament) is a novel material for fused filament fabrication (FFF) 3D printing made of highly aligned discontinuous fibres produced using high performance discontinuous fibre (HiPerDiF) technology. It reinforces a thermoplastic matrix to provide high mechanical performance and formability. Accurate printing of DcAFF poses a challenge, especially for complex geometries, because: (i) there is a discrepancy between the path where the filament experiences the adhering pressure from the filleted nozzle and the nozzle path; and (ii) the rasters display poor adhesion to the build platform immediately after deposition, which causes the filament to be dragged when the printing direction changes. This paper explains the implication of these phenomena on steering capabilities and examines the techniques for improving DcAFF printing accuracy. In the first approach, the machine parameters were adjusted to improve the quality of the sharp turning angle without changing the desired path, but this showed insignificant effects in terms of precision improvements. In the second approach, a printing path modification with a compensation algorithm was introduced. The nature of the inaccuracy of the printing at the turning point was studied with a first-order lag relationship. Then the equation to describe the deposition raster inaccuracy was determined. A proportional-integral (PI) controller was added to the equation to calculate the nozzle movement in order to bring the raster back to the desired path. The applied compensation path is shown to give an accuracy improvement in curvilinear printing paths. This is particularly beneficial when printing larger circular diameter curvilinear printed parts. The developed printing approach can be applied with other fibre reinforced filaments to achieve complex geometries.

Light-Responsive Elastin-Like Peptide-Based Targeted Nanoparticles for Enhanced Spheroid Penetration.

We describe here a near infrared light-responsive elastin-like peptide (ELP)-based targeted nanoparticle (NP) that can rapidly switch its size from 120 to 25 nm upon photo-irradiation. Interestingly, the targeting function, which is crucial for effective cargo delivery, is preserved after transformation. The NPs are assembled from (targeted) diblock ELP micelles encapsulating photosensitizer TT1-monoblock ELP conjugates. Methionine residues in this monoblock are photo-oxidized by singlet oxygen generated from TT1, turning the ELPs hydrophilic and thus trigger NP dissociation. Phenylalanine residues from the diblocks then interact with TT1 via π-π stacking, inducing the re-formation of smaller NPs. Due to their small size and targeting function, the NPs penetrate deeper in spheroids and kill cancer cells more efficiently compared to the larger ones. This work could contribute to the design of "smart" nanomedicines with deeper penetration capacity for effective anticancer therapies.

A Case of Bradycardia With Irregular Rhythm and Varying QRS Morphology.

We describe the case of a 92-year-old male patient presenting with shortness of breath and an electrocardiogram showing bradycardia with irregular rhythm and varying QRS morphology. A differential diagnosis is discussed. (Level of Difficulty: Advanced.).