Racial and Ethnic Disparities in the Use and Outcomes With WATCHMAN FLX: A SURPASS Analysis of the NCDR Left Atrial Appendage Occlusion Registry.

Background: Left atrial appendage occlusion (LAAO) is increasingly used as an alternative to oral anticoagulation for stroke prevention in select patients with atrial fibrillation. Data on outcomes in racial and ethnic minority individuals are limited. This analysis assessed differences in the use and outcomes of LAAO by race and ethnicity in a large national registry.

CONNECT: Coordinating Options for Neurovascular Patients Needing Electrophysiology Consults and Treatments.

Background And Purpose: Though Event Monitors (EM) and Implantable Loop Recorders (ILR) are prevalent in stroke workups, complex processes to obtain placement of these device might result in delays. Our aim was to determine if the CONNECT (Coordinating Options for Neurovascular patients Needing Electrophysiology Consults and Treatments) pathway could improve Stroke-to-Electrophysiology (EP) communications, increase EM and ILR device placements prior to discharge, shorten placement time, and preserve satisfaction.

Methods: We assessed device placements when an EP consult was obtained [Pre-CONNECT (5/1/21-4/30/22), CONNECT (5/1/22-4/30/23)] for patients with stroke.

Catheter ablation vs advanced therapy for patients with severe heart failure and ventricular electrical storm.

Background: Current data on outcomes of an initial strategy of catheter ablation vs advanced therapy in patients with severe heart failure (HF) and electric storm (ES) are limited.

Objective: The purpose of this study was to evaluate the outcomes of ventricular tachycardia (VT) ablation vs left ventricular assist device (LVAD) or heart transplantation (HT) in patients with severe HF and ventricular ES.

Methods: Patients with severe HF and ES who underwent VT ablation, LVAD, or HT between 2012 and 2022 at our medical center were reviewed.

Anticoagulation Alone vs Anticoagulation Plus Aspirin or DAPT Following Left Atrial Appendage Occlusion.

Background: The prevalence of and outcomes associated with different antithrombotic strategies after left atrial appendage occlusion (LAAO) are not well described.

Objectives: This study sought to evaluate patterns of antithrombotic medication strategies at discharge following LAAO with the Watchman FLX device in real-world practice and to compare the risk of adverse events among the different antithrombotic regimens.

Methods: The authors evaluated patients in the NCDR (National Cardiovascular Data Registry) LAAO Registry who underwent LAAO with the second-generation LAA closure device between 2020 and 2022.

Patient-specific vascularized tumor model: Blocking monocyte recruitment with multispecific antibodies targeting CCR2 and CSF-1R.

Tumor-associated inflammation drives cancer progression and therapy resistance, often linked to the infiltration of monocyte-derived tumor-associated macrophages (TAMs), which are associated with poor prognosis in various cancers. To advance immunotherapies, testing on immunocompetent pre-clinical models of human tissue is crucial. We have developed an in vitro model of microvascular networks with tumor spheroids or patient tissues to assess monocyte trafficking into tumors and evaluate immunotherapies targeting the human tumor microenvironment.

Outcomes With the WATCHMAN FLX in Everyday Clinical Practice From the NCDR Left Atrial Appendage Occlusion Registry.

Background: PINNACLE FLX (Protection Against Embolism for Nonvalvular AF Patients: Investigational Device Evaluation of the WATCHMAN FLX LAA Closure Technology) demonstrated improved outcomes and low incidence of adverse events with the WATCHMAN FLX device in a controlled setting. The National Cardiovascular Disease Registry's Left Atrial Appendage Occlusion Registry was utilized to assess the safety and effectiveness of WATCHMAN FLX in contemporary clinical practice in the United States.

Methods: The WATCHMAN FLX Device Surveillance Post Approval Analysis Plan used data from the Left Atrial Appendage Occlusion registry to identify patients undergoing WATCHMAN FLX implantation between August 2020 and September 2022.

Enhancing patient acceptance of ICD implantation through structured shared decision making: conversation is key.

Background: Implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy defibrillators (CRT-D) are lifesaving treatments for patients at risk for sudden cardiac death. Effective physician-patient communication during the shared decision-making process is essential. Electrophysiologist-patient conversations were targeted to obtain objective data on the interaction, understand the conversation framework, and uncover opportunities for improved communication.

Infra-Hisian Conduction Disturbance and Alternating Left Anterior/Posterior Fascicular Block.

We present an unusual case of alternating left anterior and left posterior fascicular block. Given the known risk for progression to complete atrioventricular block with alternating right bundle and left bundle branch block, we performed an electrophysiological study. Findings were consistent with infra-Hisian disease, and the patient underwent pacemaker implantation.

CRISPR PERSIST-On enables heritable and fine-tunable human gene activation.

Current technologies for upregulation of endogenous genes use targeted artificial transcriptional activators but stable gene activation requires persistent expression of these synthetic factors. Although general "hit-and-run" strategies exist for inducing long-term silencing of endogenous genes using targeted artificial transcriptional repressors, to our knowledge no equivalent approach for gene activation has been described to date. Here we show stable gene activation can be achieved by harnessing endogenous transcription factors ( s) that are normally expressed in human cells.

MOSAIC enables saturation mutagenesis of genes and CRISPR prime editing guide RNA optimization in human cells.

CRISPR prime editing offers unprecedented versatility and precision for the installation of genetic edits . Here we describe the development and characterization of the Multiplexing Of Site-specific Alterations for Characterization ( ) method, which leverages a non-viral PCR-based prime editing method to enable rapid installation of thousands of defined edits in pooled fashion. We show that MOSAIC can be applied to perform saturation mutagenesis screens of: (1) the fusion gene, successfully identifying known and potentially new imatinib drug-resistance variants; and (2) the untranslated region (UTR), re-confirming non-coding regulatory elements involved in transcriptional initiation.

Characterizing cardiac contractile motion for noninvasive radioablation of ventricular tachycardia.

Background: Respiratory motion management strategies are used to minimize the effects of breathing on the precision of stereotactic ablative radiotherapy for ventricular tachycardia, but the extent of cardiac contractile motion of the human heart has not been systematically explored.

Objective: We aim to assess the magnitude of cardiac contractile motion between different directions and locations in the heart.

Methods: Patients with intracardiac leads or valves who underwent 4-dimensional cardiac computed tomography (CT) prior to a catheter ablation procedure for atrial or ventricular arrhythmias at 2 medical centers were studied retrospectively.

Impact of artificial intelligence arrhythmia mapping on time to first ablation, procedure duration, and fluoroscopy use.

Introduction: Artificial intelligence (AI) ECG arrhythmia mapping provides arrhythmia source localization using 12-lead ECG data; whether this information impacts procedural efficiency is unknown. We performed a retrospective, case-control study to evaluate the hypothesis that AI ECG mapping may reduce time to ablation, procedural duration, and fluoroscopy.

Materials And Methods: Cases in which system output was used were retrospectively enrolled according to IRB-approved protocols at each site.

Pulsed Field Ablation Index-Guided Ablation for Lesion Formation: Impact of Contact Force and Number of Applications in the Ventricular Model.

Background: The effect of contact force (CF) on lesion formation is not clear during pulsed field ablation (PFA). The aim of this study was to evaluate the impact of CF, PFA, and their interplay through the PFA index (PF index) formula on the ventricular lesion size in swine.

Methods: PFA was delivered through the CF-sensing OMNYPULSE catheter.

Radiotherapy for hyoid bone metastasis from lung adenocarcinoma: A case report.

Background: Metastasis to the hyoid bone is an exceptionally rare occurrence, with documented cases limited to breast, liver, colon, skin, lung, and prostate cancers. This report highlights an unusual case involving the metastasis of lung adenocarcinoma to the hyoid bone, accompanied by a distinctive headache. Previous documentation involved surgical resection of the hyoid mass.

Stroke Prevention in Atrial Fibrillation: Our Current Failures and Required Research.

Nonvalvular atrial fibrillation is a common rhythm disorder of middle-aged to older adults that can cause ischemic strokes and systemic embolism. Lifelong use of oral anticoagulants reduces the risk of these ischemic events but increases the risk of major and clinically relevant hemorrhages. These medications also require strict compliance for efficacy, and they have nontrivial failure rates in higher-risk patients.

Patient-Specific Vascularized Tumor Model: Blocking TAM Recruitment with Multispecific Antibodies Targeting CCR2 and CSF-1R.

Tumor-associated inflammation drives cancer progression and therapy resistance, with the infiltration of monocyte-derived tumor-associated macrophages (TAMs) associated with poor prognosis in diverse cancers. Targeting TAMs holds potential against solid tumors, but effective immunotherapies require testing on immunocompetent human models prior to clinical trials. Here, we develop an in vitro model of microvascular networks that incorporates tumor spheroids or patient tissues.

Innate TCRβ-chain engagement drives human T cells toward distinct memory-like effector phenotypes with immunotherapeutic potentials.

Clonotypic αβ T cell responses to cargoes presented by major histocompatibility complex (MHC), MR1, or CD1 proteins underpin adaptive immunity. Those responses are mostly mediated by complementarity-determining region 3 motifs created by quasi-random T cell receptor (TCR) gene rearrangements, with diversity being highest for TCRγδ. Nonetheless, TCRγδ also displays nonclonotypic innate responsiveness following engagement of germline-encoded Vγ-specific residues by butyrophilin (BTN) or BTN-like (BTNL) proteins that uniquely mediate γδ T cell subset selection.

A T cell receptor β chain-directed antibody fusion molecule activates and expands subsets of T cells to promote antitumor activity.

Despite the success of programmed cell death-1 (PD-1) and PD-1 ligand (PD-L1) inhibitors in treating solid tumors, only a proportion of patients respond. Here, we describe a first-in-class bifunctional therapeutic molecule, STAR0602, that comprises an antibody targeting germline Vβ6 and Vβ10 T cell receptors (TCRs) fused to human interleukin-2 (IL-2) and simultaneously engages a nonclonal mode of TCR activation with costimulation to promote activation and expansion of αβ T cell subsets expressing distinct variable β (Vβ) TCR chains. In solution, STAR0602 binds IL-2 receptors in cis with Vβ6/Vβ10 TCRs on the same T cell, promoting expansion of human Vβ6 and Vβ10 CD4 and CD8 T cells that acquire an atypical central memory phenotype.