Real-world assessment of multipolar and point-by-point mapping for premature ventricular contraction ablation.

AIMS: We aimed to assess the acute and midterm efficacy of premature ventricular contraction (PVC) ablation guided by multielectrode and point-by-point (PbP) mapping. METHODS AND RESULTS: This is a retrospective, international multicentre study of consecutive patients referred for PVC ablation in 10 hospital centres from January 2017 to December 2021. Based on the mapping approach, two cohorts were identified: the 'Multipolar group', where a dedicated high-density mapping catheter was employed, and the 'PbP group', where mapping was performed with the ablation catheter. Procedural endpoints, safety, and acute (procedural) and midterm efficacies were assessed. Of the 698 patients included in this study, 592 received activation mapping [46% males, median age of 55 (41-65) years]-248 patients in the Multipolar group and 344 patients in the PbP group. A higher number of activation points [432 (217-843) vs. 95 (42-185), P < 0.001], reduced mapping time (40 ± 38 vs. 61 ± 50 min, P < 0.001), and shorter procedure time (124 ± 60 vs. 143 ± 63 min, P < 0.001) were reported in the Multipolar group. Both groups had high acute success rates (84.7% with Multipolar mapping vs. 81.3% with PbP mapping, P = 0.63), as well as midterm efficacy (83.4% vs. 77.4%, P = 0.08), with no significant differences in the risk of adverse events (6.0% vs. 3.5%, P = 0.24). However, for left-sided PVC ablation specifically, there was a higher midterm efficacy in the Multipolar group (80.7% vs. 69.5%, P = 0.04), with multipolar mapping being an independent predictor of success [adjusted OR = 2.231 (95% CI, 1.476-5.108), P = 0.02]. CONCLUSION: The acute and midterm efficacies of PVC ablation are high with both multipolar and PbP mapping, although the former allows for quicker procedures and may potentially improve the outcomes of left-sided PVC ablation.

Exploring Molecular Heteroencoders with Latent Space Arithmetic: Atomic Descriptors and Molecular Operators.

A variational heteroencoder based on recurrent neural networks, trained with SMILES linear notations of molecular structures, was used to derive the following atomic descriptors: delta latent space vectors (DLSVs) obtained from the original SMILES of the whole molecule and the SMILES of the same molecule with the target atom replaced. Different replacements were explored, namely, changing the atomic element, replacement with a character of the model vocabulary not used in the training set, or the removal of the target atom from the SMILES. Unsupervised mapping of the DLSV descriptors with t-distributed stochastic neighbor embedding (t-SNE) revealed a remarkable clustering according to the atomic element, hybridization, atomic type, and aromaticity. Atomic DLSV descriptors were used to train machine learning (ML) models to predict 19F NMR chemical shifts. An R2 of up to 0.89 and mean absolute errors of up to 5.5 ppm were obtained for an independent test set of 1046 molecules with random forests or a gradient-boosting regressor. Intermediate representations from a Transformer model yielded comparable results. Furthermore, DLSVs were applied as molecular operators in the latent space: the DLSV of a halogenation (H→F substitution) was summed to the LSVs of 4135 new molecules with no fluorine atom and decoded into SMILES, yielding 99% of valid SMILES, with 75% of the SMILES incorporating fluorine and 56% of the structures incorporating fluorine with no other structural change.

Does Timing of Ventricular Tachycardia Ablation Affect Prognosis in Patients With an Implantable Cardioverter Defibrillator? Results From the Multicenter Randomized PARTITA Trial.

BACKGROUND: Optimal timing for catheter ablation of ventricular tachycardia is an important unresolved issue. There are no randomized trials evaluating the benefit of ablation after the first implantable cardioverter defibrillator (ICD) shock. METHODS: We conducted a 2-phase, prospective, multicenter, randomized clinical trial. Patients with ischemic or nonischemic dilated cardiomyopathy and primary or secondary prevention indication for ICD were enrolled in an initial observational phase until first appropriate shock (phase A). After reconsenting, patients were randomly assigned 1:1 in phase B to immediate ablation (within 2 months from shock delivery) or continuation of standard therapy. The primary end point was a composite of death from any cause or hospitalization for worsening heart failure. Amiodarone intake was not allowed except for documented atrial tachyarrhythmias. On July 23, 2021, phase B of the trial was interrupted as a result of the first interim analysis on the basis of the Bayesian adaptive design. RESULTS: Of the 517 patients enrolled in phase A, 154 (30%) had ventricular tachycardia, 56 (11%) received an appropriate shock over a median follow-up of 2.4 years (interquartile range, 1.4-4.4), and 47 of 56 (84%) agreed to participate in phase B. After 24.2 (8.5-24.4) months, the primary end point occurred in 1 of 23 (4%) patients in the ablation group and 10 of 24 (42%) patients in the control group (hazard ratio, 0.11 [95% CI, 0.01-0.85]; P=0.034). The results met the prespecified termination criterion of >99% Bayesian posterior probability of superiority of treatment over standard therapy. No deaths were observed in the ablation group versus 8 deaths (33%) in the control group (P=0.004); there was 1 worsening heart failure hospitalization in the ablation group (4%) versus 4 in the control group (17%; P=0.159). ICD shocks were less frequent in the ablation group (9%) than in the control group (42%; P=0.039). CONCLUSIONS: Ventricular tachycardia ablation after first appropriate shock was associated with a reduced risk of the combined death or worsening heart failure hospitalization end point, lower mortality, and fewer ICD shocks. These findings provide support for considering ventricular tachycardia ablation after the first ICD shock. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01547208.

Impact of different activation wavefronts on ischemic myocardial scar electrophysiological properties during high-density ventricular tachycardia mapping and ablation.

INTRODUCTION: Scar-related ventricular tachycardia (VT) usually results from an underlying reentrant circuit facilitated by anatomical and functional barriers. The later are sensitive to the direction of ventricular activation wavefronts. We aim to evaluate the impact of different ventricular activation wavefronts on the functional electrophysiological properties of myocardial tissue. METHODS: Patients with ischemic heart disease referred for VT ablation underwent high-density mapping using Carto®3 (Biosense Webster). Maps were generated during sinus rhythm, right and left ventricular pacing, and analyzed using a new late potential map software, which allows to assess local conduction velocities and facilitates the delineation of intra-scar conduction corridors (ISCC); and for all stable VTs. RESULTS: In 16 patients, 31 high-resolution substrate maps from different ventricular activation wavefronts and 7 VT activation maps were obtained. Local abnormal ventricular activities (LAVAs) were found in VT isthmus, but also in noncritical areas. The VT isthmus was localized in areas of LAVAs overlapping surface between the different activation wavefronts. The deceleration zone location differed depending on activation wavefronts. Sixty-six percent of ISCCs were similarly identified in all activating wavefronts, but the one acting as VT isthmus was simultaneously identified in all activation wavefronts in all cases. CONCLUSION: Functional based substrate mapping may improve the specificity to localize the most arrhythmogenic regions within the scar, making the use of different activation wavefronts unnecessary in most cases.

Vitreous humor proteome: unraveling the molecular mechanisms underlying proliferative and neovascular vitreoretinal diseases.

Proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), and neovascular age-related macular degeneration (nAMD) are among the leading causes of blindness. Due to the multifactorial nature of these vitreoretinal diseases, omics approaches are essential for a deeper understanding of the pathophysiologic processes underlying the evolution to a proliferative or neovascular etiology, in which patients suffer from an abrupt loss of vision. For many years, it was thought that the function of the vitreous was merely structural, supporting and protecting the surrounding ocular tissues. Proteomics studies proved that vitreous is more complex and biologically active than initially thought, and its changes reflect the physiological and pathological state of the eye. The vitreous is the scenario of a complex interplay between inflammation, fibrosis, oxidative stress, neurodegeneration, and extracellular matrix remodeling. Vitreous proteome not only reflects the pathological events that occur in the retina, but the changes in the vitreous itself play a central role in the onset and progression of vitreoretinal diseases. Therefore, this review offers an overview of the studies on the vitreous proteome that could help to elucidate some of the pathological mechanisms underlying proliferative and/or neovascular vitreoretinal diseases and to find new potential pharmaceutical targets.

Rational Engineering of (S)-Norcoclaurine Synthase for Efficient Benzylisoquinoline Alkaloids Biosynthesis.

(S)-Norcoclaurine is synthesized in vivo through a metabolic pathway that ends with (S)-norcoclaurine synthase (NCS). The former constitutes the scaffold for the biosynthesis of all benzylisoquinoline alkaloids (BIAs), including many drugs such as the opiates morphine and codeine and the semi-synthetic opioids oxycodone, hydrocodone, and hydromorphone. Unfortunately, the only source of complex BIAs is the opium poppy, leaving the drug supply dependent on poppy crops. Therefore, the bioproduction of (S)-norcoclaurine in heterologous hosts, such as bacteria or yeast, is an intense area of research nowadays. The efficiency of (S)-norcoclaurine biosynthesis is strongly dependent on the catalytic efficiency of NCS. Therefore, we identified vital NCS rate-enhancing mutations through the rational transition-state macrodipole stabilization method at the Quantum Mechanics/Molecular Mechanics (QM/MM) level. The results are a step forward for obtaining NCS variants able to biosynthesize (S)-norcoclaurine on a large scale.

Nursing Interventions for Patients With Neurogenic Bowel Dysfunction Arising From Complete Spinal Cord Injury: A Scoping Review.

PURPOSE: We mapped key concepts and identified 4 fundamental nursing interventions for patients with neurogenic bowel dysfunction due to complete spinal cord injury (SCI). METHODS: A scoping review was conducted according to the recommendations of the Joanna Briggs Institute. SEARCH STRATEGY: Searches were performed in PubMed, LILACS, CINAHL, COCHRANE, and SCOPUS electronic databases. We use searched the gray literature using the Google Scholar search engine. We formulated a question to guide the search, based on the participants, concept, and context format: "What are the key manual nursing interventions performed in patients with neurogenic bowel dysfunction resulting from complete spinal cord injury?" We included nursing intervention strategies that may be performed by health professionals, patients, or caregivers. Two reviewers independently participated in the selection; disagreements were resolved by a third reviewer and 5 experts. FINDINGS: Thirteen studies conducted between 1998 and 2019 were selected; 5 were randomized clinical trials. Four main interventions were identified for conservative management of neurogenic bowel dysfunction in patients with complete SCI. They were digital-anal stimulation, manual extraction of feces, abdominal massage, and strategies used to stimulate the gastrocolic reflex. CONCLUSIONS: Research suggests that each of these interventions, administered alone or in combination, supports bowel evacuation in patients with a complete SCI. Each of these interventions may be performed by a nurse, and taught to the patient and/or lay caregiver. IMPLICATIONS FOR PRACTICE: An individualized bowel management program for patients with neurogenic bowel dysfunction due to SCI is necessary to ensure regular bowel evacuation, preserve fecal continence, and support dignity and health-related quality of life. The conservative interventions identified in this scoping review should be incorporated in protocols or guidelines for management of neurogenic bowel dysfunction in this vulnerable population.

An Overview of Robotic Colorectal Surgery Adoption and Training in Brazil.

Background and Objectives: Robotic surgical systems have rapidly become integrated into colorectal surgery practice in recent years, particularly for rectal resections, where the advantages of robotic platforms over conventional laparoscopy are more pronounced. However, as with any technological advancement, the initial high costs can be a limiting factor, leading to unequal health service access, especially in middle- and lower-income countries. Materials and Method: A narrative review was conducted with the objective of providing an overview of the escalating adoption, current training programmes, and certification process of robotic colorectal surgery in Brazil. Results: Brazil has witnessed a rapid increase in robotic platforms in recent years. Currently, there are 106 robotic systems installed nationwide. However, approximately 60% of the medical facilities which adopted robotic platforms are in the Southeast region, which is both the most populous and economically prosperous in the country. The Brazilian Society of Coloproctology recently established clear rules for the training programme and certification of colorectal surgeons in robotic surgery. The key components of the training encompass theoretical content, virtual robotic simulation, observation, assistance, and supervised procedures in colorectal surgery. Although the training parameters are well established, no colorectal surgery residency programme in Brazil has yet integrated the teaching and training of robotic surgery into its curriculum. Thus far, the training process has been led by private institutions and the industry. Conclusion: Despite the fast spread of robotic platforms across Brazil, several challenges still need to be addressed to democratise training and promote the widespread use of these platforms. It is crucial to tackle these obstacles to achieve greater integration of robotic technology in colorectal surgery throughout the country.

Novel "late potential map" algorithm: Abnormal potentials and scar channels detection for ventricular tachycardia ablation.

BACKGROUND: Automated systems for substrate mapping in the context of ventricular tachycardia (VT) ablation may annotate far-field rather than near-field signals, rendering the resulting maps hard to interpret. Additionally, quantitative assessment of local conduction velocity (LCV) remains an unmet need in clinical practice. We evaluate whether a new late potential map (LPM) algorithm can provide an automatic and reliable annotation and localized bipolar voltage measurement of ventricular electrograms (EGMs) and if LCV analysis allows recognizing intrascar conduction corridors acting as VT isthmuses. METHODS: In 16 patients referred for scar-related VT ablation, 8 VT activation maps and 29 high-resolution substrate maps from different activation wavefronts were obtained. In offline analysis, the LPM algorithm was compared to manually annotated substrate maps. Locations of the VT isthmuses were compared with the corresponding substrate maps in regard to LCV. RESULTS: The LPM algorithm had an overall/local abnormal ventricular activity (LAVA) annotation accuracy of 94.5%/81.1%, which compares to 83.7%/23.9% for the previous wavefront algorithm. The resultant maps presented a spatial concordance of 88.1% in delineating regions displaying LAVA. LAVA median localized bipolar voltage was 0.22 mV, but voltage amplitude assessment had modest accuracy in distinguishing LAVA from other abnormal EGMs (area under the curve: 0.676; p < .001). LCV analysis in high-density substrate maps identified a median of two intrascar conduction corridors per patient (interquartile range: 2-3), including the one acting as VT isthmus in all cases. CONCLUSION: The new LPM algorithm and LCV analysis may enhance substrate characterization in scar-related VT.

Prediction of the Phase Composition Profile of Three-Compound Mixtures in Liquid-Liquid Equilibrium: A Chemoinformatics Approach.

Machine-learning models were developed to predict the composition profile of a three-compound mixture in liquid-liquid equilibrium (LLE), given the global composition at certain temperature and pressure. A chemoinformatics approach was explored, based on the MOLMAP technology to encode molecules and mixtures. The chemical systems involved an ionic liquid (IL) and two organic molecules. Two complementary models have been optimized for the IL-rich and IL-poor phases. The two global optimized models are highly accurate, and were validated with independent test sets, where combinations of molecule1+molecule2+IL are different from those in the training set. These results highlight the MOLMAP encoding scheme, based on atomic properties to train models that learn relationships between features of complex multi-component chemical systems and their profile of phase compositions.

Impact of lockdown during COVID-19 pandemic on physical activity and arrhythmia burden in heart failure patients.

BACKGROUND: Restricted outdoor activity during COVID-19 related lockdown may accelerate heart failure (HF) progression and thereby increase cardiac arrhythmias. We analyzed the impact of March/April 2020 lockdown on physical activity and arrhythmia burden in HF patients treated with cardiac resynchronization therapy (CRT) devices with daily, automatic remote monitoring (RM) function. METHODS: The study cohort included 405 HF patients enrolled in Observation of Clinical Routine Care for Heart Failure Patients Implanted with BIOTRONIK CRT Devices (BIO|STREAM.HF) registry in 16 countries, who had left ventricular ejection fraction (LVEF) ≤40% (mean 28.2 ± 6.6%) and NYHA class II/III/IV (47.9%/49.6%/2.5%) before CRT pacemaker/defibrillator implantation. The analyzed RM data comprised physical activity detected by accelerometer, mean heart rate and nocturnal rate, PP variability, percentage of biventricular pacing, atrial high rate episode (AHRE) burden, ventricular extrasystoles and tachyarrhythmias, defibrillator shocks, and number of implant interrogations (i.e., follow-ups). Intraindividual differences in RM parameters before (4-week period) versus during (4-week period) lockdown were tested for statistical significance and independent predictors were identified. RESULTS: There was a significant relative change in activity (mean -6.5%, p < .001), AHRE burden (+17%, p = .013), and follow-up rate (-75%, p < .001) during lockdown, with no significant changes in other RM parameters. Activity decreased by ≥8 min/day in 46.5% of patients; predictors were higher LVEF, lower NYHA class, no defibrillator indication, and more activity before lockdown. AHRE burden increased by ≥17 min/day in 4.7% of patients; predictors were history of atrial fibrillation, higher LVEF, higher body mass index, and activity decrease during lockdown. CONCLUSION: Unfavorable changes in physical activity, AHRE burden, and follow-up rate were observed during lockdown, but not in ventricular arrhythmia.

Mononitrate Isosorbide as an Adjunctive Therapy in Schizophrenia: A Randomized Controlled Crossover Trial.

BACKGROUND: Schizophrenia is a complex disabling mental disorder, and many patients present poor response to available treatments. Accumulating evidence about the role of the glutamate/nitric oxide pathway in mediating the positive and negative symptoms of schizophrenia suggests potential benefits of drugs that modulate this system. The aim of this study was to test the efficacy of isosorbide mononitrate (ISMN) as an adjunctive therapy for symptomatic outpatients with schizophrenia. METHODS: This was a 2-month randomized, double-blind, placebo-controlled trial with 24 schizophrenia patients. Participants were treated with ISMN 50 mg for 1 month and placebo for another month in a crossover design. The Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale, Global Assessment of Functioning, and MATRICS Cognitive Consensual Battery were used for symptom assessment and arterial spin labeling was used to assess brain activation patterns. RESULTS: We found significant differences in the total, general, and positive subscales of the PANSS, Global Assessment of Functioning scores, and Clinical Global Impression scores during treatment with ISMN relative to placebo. No treatment effects were found comparing scores in the MATRICS Cognitive Consensual Battery and the negative subscale of the PANSS between the active and placebo conditions. A post hoc analysis of neuroimaging data showed reduced activity in the thalamus in subgroup of patients with severe psychopathology. CONCLUSIONS: Schizophrenia patients with persistent symptoms showed significant improvement after 4 weeks of treatment with ISMN 50 mg/d compared with placebo. Isosorbide mononitrate added beneficial effects to antipsychotic treatment in terms of positive symptoms and functioning.

Retrospective multicenter study on endoscopic treatment of upper GI postsurgical leaks.

BACKGROUND AND AIMS: Therapeutic endoscopy plays a critical role in the management of upper GI (UGI) postsurgical leaks. Data are scarce regarding clinical success and safety. Our aim was to evaluate the effectiveness of endoscopic therapy for UGI postsurgical leaks and associated adverse events (AEs) and to identify factors associated with successful endoscopic therapy and AE occurrence. METHODS: This was a retrospective, multicenter, international study of all patients who underwent endoscopic therapy for UGI postsurgical leaks between 2014 and 2019. RESULTS: Two hundred six patients were included. Index surgery most often performed was sleeve gastrectomy (39.3%), followed by gastrectomy (23.8%) and esophagectomy (22.8%). The median time between index surgery and commencement of endoscopic therapy was 16 days. Endoscopic closure was achieved in 80.1% of patients after a median follow-up of 52 days (interquartile range, 33-81.3). Seven hundred seventy-five therapeutic endoscopies were performed. Multimodal therapy was needed in 40.8% of patients. The cumulative success of leak resolution reached a plateau between the third and fourth techniques (approximately 70%-80%); this was achieved after 125 days of endoscopic therapy. Smaller leak initial diameters, hospitalization in a general ward, hemodynamic stability, absence of respiratory failure, previous gastrectomy, fewer numbers of therapeutic endoscopies performed, shorter length of stay, and shorter times to leak closure were associated with better outcomes. Overall, 102 endoscopic therapy-related AEs occurred in 81 patients (39.3%), with most managed conservatively or endoscopically. Leak-related mortality rate was 12.4%. CONCLUSIONS: Multimodal therapeutic endoscopy, despite being time-consuming and requiring multiple procedures, allows leak closure in a significant proportion of patients with a low rate of severe AEs.

Machine Learning Classification of One-Chiral-Center Organic Molecules According to Optical Rotation.

In this study, machine learning algorithms were investigated for the classification of organic molecules with one carbon chiral center according to the sign of optical rotation. Diverse heterogeneous data sets comprising up to 13,080 compounds and their corresponding optical rotation were retrieved from Reaxys and processed independently for three solvents: dichloromethane, chloroform, and methanol. The molecular structures were represented by chiral descriptors based on the physicochemical and topological properties of ligands attached to the chiral center. The sign of optical rotation was predicted by random forests (RF) and artificial neural networks for independent test sets with an accuracy of up to 75% for dichloromethane, 82% for chloroform, and 82% for methanol. RF probabilities and the availability of structures in the training set with the same spheres of atom types around the chiral center defined applicability domains in which the accuracy is higher.

Anticoagulation after typical atrial flutter ablation: Systematic review and meta-analysis.

BACKGROUND: Cavotricuspid isthmus (CTI) ablation in typical atrial flutter (AFL) restores sinus rhythm in 95% of patients, which may lead to the discontinuation of oral anticoagulation during follow-up. Therefore, we aimed to systematically review the clinical impact of oral anticoagulation in the incidence of thromboembolic events (TE) after typical AFL ablation. METHODS: We searched for controlled studies evaluating the impact of anticoagulation in the incidence of TE in patients submitted to AFL ablation in MEDLINE, CENTRAL, PsycINFO database (June/2021). The primary outcome was TE events (ischemic stroke or systemic embolism). A meta-analysis was performed deriving risk ratios (RR) and 95% confidence intervals (CI). Statistical heterogeneity was measured through I2 metric. The confidence in the evidence was appraised with Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. RESULTS: Eight observational studies with 4870 patients were included. TE events were not significantly reduced (RR 1.18, 95% CI 0.59-2.36; n = 4870; GRADE very low). A meta-regression showed that for each 10% increase in the prevalence of previous AF in the studied population, anticoagulation reduced TE risk in 32%. There were no significant differences regarding bleeding events (RR 2.16, 95% CI 0.43-10.97, I2  = 0%; GRADE low), but there was a lower all-cause mortality (RR 0.24, 95% CI 0.17-0.32, GRADE low). CONCLUSION: The best available evidence lacks robustness and the data did not definitely associate anticoagulation after typical AFL ablation with reduced TE.

Clinical impact of MultiPoint pacing in responders to cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy demonstrated benefits in heart failure. However, only 60-70% are responders and only 22% are super-responders. MultiPoint pacing (MPP) improves structural remodeling, but data in responder patients is scarce. METHODS: A prospective, randomized study of the efficacy of MPP was conducted in patients who were CRT responders after 6 months of bi-ventricular (BiV) therapy. At 6 months, responder patients (LV end-systolic volume [LVESV] reduction ≥15%) were randomized to either continued BiV therapy or to MPP programmed with wide anatomical separation ≥30 mm, and followed until 12 months. Efficacy was determined by 6-12 month changes in LVESV and LV ejection fraction (LVEF). Evaluations of super-responder rate (LVESV reduction ≥30%) and quality of life (NYHA, EQ-5D, MLHFQ) were also performed. RESULTS: From February 2017 to February 2019, 73 CRTs with Quartet LV leads were implanted (42.9% female, 65.7 ± 10.8 years old, 79.5% dilated cardiomyopathy). At 6 months, 74.2% responded to BiV and were randomized to BiV (n = 25) or MPP (n = 24). MPP versus BiV delivered greater LVESV improvement (8.3% decrease in MPP vs. 10.3% increase in BiV patients, p = .047), greater increase in LVEF (7.7% vs. 1.8%, p = .008), and higher 0-12 month super-responder rate (86.4% vs. 56.0%, p = .027). More MPP vs. BiV patients experienced an improvement in NYHA (84.6% vs. 50.0%, p = .047) and EQ-5D (94.4% vs. 54.0%, p = .006). CONCLUSIONS: MPP with wide anatomical spacing in CRT responder patients resulted in improved LV reverse remodeling with higher rates of super-responders, and better quality of life metrics.

When the lead extractor becomes the assistant for new lead implant.

With the increasing number of cardiovascular implantable electronic device upgrade and vein obstruction caused by previous leads, it is important to have alternative techniques to upgrade the device with the maintenance of functioning leads. We report an 83-year old male with 13-year old one-lead dual-chamber pacemaker, ischemic cardiac disease and pre-dialytic chronic kidney disease submitted to an upgrade to cardiac resynchronization therapy. A sub-occlusion in the transition of left brachiocephalic vein and the superior vena cava was documented. Re-permeabilization was only achieved with a TightRail™ rotating dilator sheath over a guidewire with successful left ventricle lead implant.

Modified snare technique improves left ventricular lead implant success for cardiac resynchronization therapy.

BACKGROUND: Left ventricular (LV) lead placement is the most challenging aspect of cardiac resynchronization therapy (CRT) device implantation, with a failure rate of up to 10% due to complex coronary anatomies. We describe a modified snare technique for LV lead placement and evaluate its safety and efficacy in cases when standard methods fail. METHODS AND RESULTS: A prospective study was conducted of patients indicated for a CRT implant. When LV lead delivery to the target vessel failed using standard techniques, a modified snare technique was employed. Patients were evaluated every 6 months. From 2015 to 2019, 566 CRTs were implanted (26.1% female, 72 ± 10.2 years old, follow-up duration 18.9 ± 15.8 months). The standard LV implant technique failed in 94 cases (16.6%), of which the modified snare technique was successful in 92 (97.9%). There were no differences between the modified snare and standard techniques in the rates of 30-day postimplant CRT all-cause mortality (3.2% vs. 1.7%, p = .33), 4-year all-cause mortality (15.9% vs. 15.5%, p = .49), or major acute complications (7.4% vs. 3.8%, p = .12). However, the 4-year procedural reintervention rate was lower with the modified snare technique (3.2% vs. 10.2%, p < .05), specifically LV implant failure or dislodgement rates (0% vs. 5.3%, p < .05), improving the response rate (71.8% vs. 55.1%, p < .05). CONCLUSIONS: For challenging coronary sinus anatomies that preclude LV lead placement by standard methods, this modified snare alternative was safe and effective, with comparable mortality and complications, but significantly lower procedural reintervention and higher response rates.

Paroxysmal and persistent atrial fibrillation ablation outcomes with the pulmonary vein ablation catheter GOLD duty-cycled phased radiofrequency ablation catheter: quality of life and 12-month efficacy results from the GOLD Atrial Fibrillation Registry.

AIMS: The GOLD AF Registry has been designed to prospectively assess the population, indications, and outcomes using second-generation phased radiofrequency (RF) ablation (pulmonary vein ablation catheter GOLD) in a global examination of standard-of-care use for the treatment of paroxysmal and persistent atrial fibrillation (AF). METHODS AND RESULTS: GOLD AF (NCT02433613) is a prospective, observational, multi-centre registry designed to characterize efficacy and safety of phased RF ablation in patients with AF. The primary endpoint was freedom from AF recurrence at 12-month follow-up after a 90-day blanking period. Ancillary objectives include safety, procedural efficiency, and quality of life (QoL). The QoL assessment using the Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) and the European Heart Rhythm Association (EHRA) Score of AF-related symptoms was collected at baseline and 12 months. In total, 1054 patients were included in this analysis (age 60.6, 67.6% male, 26.5% PersAF). Kaplan-Meier estimate of freedom from AF recurrence was 77.7% at 12 months. Peri-procedural device or procedure-related complications were observed in 26 (2.5%) patients, with a low stroke rate of 0.3%. One-year post-ablation, the EHRA AF Symptom score decreased in 68% of patients. The AFEQT score improvement was observed in 88.4% and 90.4% of patients who completed the questionnaire in-person or interviewed by phone at 12 month follow-up, respectively. CONCLUSION: Phased RF ablation for the treatment of paroxysmal and persistent AF demonstrated a 77.7% freedom from AF recurrence at 12 months in addition to a significant reduction in arrhythmia symptoms and clinically meaningful improved QoL. Low peri-procedural complication rate of <3% was reported.

The Outcomes of Switching from Short- to Long-Term Intravitreal Corticosteroid Implant Therapy in Patients with Diabetic Macular Edema.

BACKGROUND: First-line treatment for diabetic macular edema (DME) is usually with antivascular endothelial growth factor agents, followed by intravitreal corticosteroids as a second-line treatment option. Long-term corticosteroids may offer quality of life and effectiveness benefits over short-term implants. OBJECTIVES: To evaluate outcomes of patients with persistent or recurrent DME who switched from a short-term (dexamethasone) to a long-term (fluocinolone acetonide, FAc) corticosteroid intravitreal implant in a real-world setting. METHODS: This is a retrospective study in 9 Portuguese centers. An FAc intravitreal implant was administered according to product labeling. Effectiveness outcomes were mean change in visual acuity (VA; ETDRS letters), central retinal thickness (CRT; µm), and macular volume (MV; mm3). The safety outcome was mean change in intraocular pressure (IOP; mm Hg). All were analyzed at months 1 and 3, and then quarterly until month 24 after implantation. RESULTS: Forty-four eyes from 36 patients were analyzed. Mean duration of DME was 3.3 ± 1.9 years, and mean follow-up was 8 months. From baseline following FAc implantation, VA increased significantly at months 1 and 6 (mean +6.82 and +13.02 letters, respectively; p = 0.005), and last observation carried forward (LOCF; mean +8.3 letters; p = 0.002). CRT improved significantly at months 1 and 6 (mean -71.81 and -170.77 µm, respectively; p = 0.001), and LOCF (mean -121.46 µm; p = 0.001). MV was consistently, but not significantly, decreased from baseline to LOCF (mean -0.69 mm3; p = 0.062). The mean change in IOP was -0.25 and +0.88 mm Hg at months 1 and 6, respectively (p = 0.268), and +1.86 mm Hg at LOCF (p = 0.036). Increases were controlled with topical medication in most cases. CONCLUSIONS: The FAc intravitreal implant is effective in patients previously treated with short-term corticosteroid implants. Thus, after a suboptimal response to antiangiogenics or a short-term corticosteroid, a single FAc implant may be considered an effective and tolerable treatment that can improve long-term outcomes for patients with sight-threatening DME.