3D-targeted, electrocardiographic imaging-aided stereotactic radioablation for ventricular tachycardia storm: a case report.

Background: Stereotactic arrhythmia radioablation (STAR) is a promising non-invasive therapy for patients with ventricular tachycardia (VT). Accurate identification of the arrhythmogenic volume, or clinical target volume (CTV), on the radiotherapy (RT) 4D planning computed tomography (CT) scan is key for STAR efficacy and safety. This case report illustrates our workflow of electro-structural image integration for CTV delineation.

Multi-omic profiling of pathogen-stimulated primary immune cells.

We performed long-read transcriptome and proteome profiling of pathogen-stimulated peripheral blood mononuclear cells (PBMCs) from healthy donors to discover new transcript and protein isoforms expressed during immune responses to diverse pathogens. Long-read transcriptome profiling reveals novel sequences and isoform switching induced upon pathogen stimulation, including transcripts that are difficult to detect using traditional short-read sequencing. Widespread loss of intron retention occurs as a common result of all pathogen stimulations.

Preconception Physical Exercise Is Associated with Phenotype-Specific Cardiovascular Alterations in Women at Risk for Gestational Hypertensive Disorders.

: Gestational hypertensive disorders (GHD) pose significant maternal and fetal health risks during pregnancy. Preconception physical exercise has been associated with a lower incidence of GHD, but insights into the cardiovascular mechanisms remain limited. This study aimed to evaluate the effect of preconception physical exercise on the complete cardiovascular functions of women at risk for GHD in a subsequent pregnancy.

Variant patterns of electrical activation and recovery in normal human hearts revealed by noninvasive electrocardiographic imaging.

Aims: Although electrical activity of the normal human heart is well characterized by the electrocardiogram, detailed insights into within-subject and between-subject variations of ventricular activation and recovery by noninvasive electroanatomic mapping are lacking. We characterized human epicardial activation and recovery within and between normal subjects using non-invasive electrocardiographic imaging (ECGI) as a basis to better understand pathology.

Methods And Results: Epicardial activation and recovery were assessed by ECGI in 22 normal subjects, 4 subjects with bundle branch block (BBB) and 4 with long-QT syndrome (LQTS).

The electromechanical window for arrhythmia-risk assessment.

The electromechanical window (EMW) is calculated by subtracting the repolarization duration from a mechanical reference representing contraction duration in the same heartbeat (eg, aortic valve closure during echocardiography with simultaneous electrocardiography). Here, we review the current knowledge on the role of the EMW as an independent parameter for ventricular arrhythmia-risk stratification. We (1) provide a standardized approach to echocardiographic EMW assessment, (2) define relevant cutoff values for both abnormal EMW negativity and positivity, (3) discuss pathophysiological underpinnings of EMW negativity, and (4) outline the potential future role of cardiac electromechanical relations in patients with proarrhythmic conditions.

The Dutch Idiopathic Ventricular Fibrillation Registry: progress report on the quest to identify the unidentifiable.

Background: Idiopathic ventricular fibrillation (iVF) is a rare cause of sudden cardiac arrest and, by definition, a diagnosis of exclusion. Due to the rarity of the disease, previous and current studies are limited by their retrospective design and small patient numbers. Even though the incidence of iVF has declined owing to the identification of new disease entities, an important subgroup of patients remains.

Comparing adolescent- and adult-onset unexplained cardiac arrest: Results from the Dutch Idiopathic VF Registry.

Background: Current cohorts of patients with idiopathic ventricular fibrillation (IVF) primarily include adult-onset patients. Underlying causes of sudden cardiac arrest vary with age; therefore, underlying causes and disease course may differ for adolescent-onset vs adult-onset patients.

Objective: The purpose of this study was to compare adolescent-onset with adult-onset patients having an initially unexplained cause of VF.

Mitral annular disjunction in idiopathic ventricular fibrillation patients: just a bystander or a potential cause?

Aims: Previously, we demonstrated that inferolateral mitral annular disjunction (MAD) is more prevalent in patients with idiopathic ventricular fibrillation (IVF) than in healthy controls. In the present study, we advanced the insights into the prevalence and ventricular arrhythmogenicity by inferolateral MAD in an even larger IVF cohort.

Methods And Results: This retrospective multi-centre study included 185 IVF patients [median age 39 (27, 52) years, 40% female].

Novel gene fusion discovery in Spitz tumours and its relevance in diagnostics.

In addition to morphologic analysis, molecular diagnostic work up of Spitz tumours is often of great value for their accurate diagnosis/classification. Nowadays, next-generation sequencing (NGS) is the predominant screening method in molecular diagnostics. Up to 80% of these melanocytic neoplasms comprise gene fusions as genetic anomalies for which the driver codes for a protein harbouring a kinase domain.

A Framework for Assessing the Effect of Cardiac and Respiratory Motion for Stereotactic Arrhythmia Radioablation Using a Digital Phantom With a 17-Segment Model: A STOPSTORM.eu Consortium Study.

Purpose: The optimal motion management strategy for patients receiving stereotactic arrhythmia radioablation (STAR) for the treatment of ventricular tachycardia (VT) is not fully known. We developed a framework using a digital phantom to simulate cardiorespiratory motion in combination with different motion management strategies to gain insight into the effect of cardiorespiratory motion on STAR.

Methods And Materials: The 4-dimensional (4D) extended cardiac-torso (XCAT) phantom was expanded with the 17-segment left ventricular (LV) model, which allowed placement of STAR targets in standardized ventricular regions.

Outcomes in Dutch DPP6 risk haplotype for familial idiopathic ventricular fibrillation: a focused update.

Background: The genetic risk haplotype DPP6 has been linked to familial idiopathic ventricular fibrillation (IVF), but the associated long-term outcomes are unknown.

Methods: DPP6 risk haplotype-positive family members (DPP6 cases) and their risk haplotype-negative relatives (DPP6 controls) were included. Clinical follow-up data were collected through March 2023.

Reliability of panel-based mutational signatures for immune-checkpoint-inhibition efficacy prediction in non-small cell lung cancer.

Objectives: Mutational signatures (MS) are gaining traction for deriving therapeutic insights for immune checkpoint inhibition (ICI). We asked if MS attributions from comprehensive targeted sequencing assays are reliable enough for predicting ICI efficacy in non-small cell lung cancer (NSCLC).

Methods: Somatic mutations of m = 126 patients were assayed using panel-based sequencing of 523 cancer-related genes.

SUsPECT: a pipeline for variant effect prediction based on custom long-read transcriptomes for improved clinical variant annotation.

Our incomplete knowledge of the human transcriptome impairs the detection of disease-causing variants, in particular if they affect transcripts only expressed under certain conditions. These transcripts are often lacking from reference transcript sets, such as Ensembl/GENCODE and RefSeq, and could be relevant for establishing genetic diagnoses. We present SUsPECT (Solving Unsolved Patient Exomes/gEnomes using Custom Transcriptomes), a pipeline based on the Ensembl Variant Effect Predictor (VEP) to predict variant impact on custom transcript sets, such as those generated by long-read RNA-sequencing, for downstream prioritization.

The circle of reentry: Characteristics of trigger-substrate interaction leading to sudden cardiac arrest.

Sudden cardiac death is often caused by ventricular arrhythmias driven by reentry. Comprehensive characterization of the potential triggers and substrate in survivors of sudden cardiac arrest has provided insights into the trigger-substrate interaction leading to reentry. Previously, a "Triangle of Arrhythmogenesis", reflecting interactions between substrate, trigger and modulating factors, has been proposed to reason about arrhythmia initiation.

Understanding repolarization in the intracardiac unipolar electrogram: A long-lasting controversy revisited.

The optimal way to determine repolarization time (RT) from the intracardiac unipolar electrogram (UEG) has been a topic of debate for decades. RT is typically determined by either the Wyatt method or the "alternative method," which both consider UEG T-wave slope, but differently. To determine the optimal method to measure RT on the UEG.

High-resolution structural-functional substrate-trigger characterization: Future roadmap for catheter ablation of ventricular tachycardia.

Introduction: Patients with ventricular tachyarrhythmias (VT) are at high risk of sudden cardiac death. When appropriate, catheter ablation is modestly effective, with relatively high VT recurrence and complication rates. Personalized models that incorporate imaging and computational approaches have advanced VT management.

Importance of Systematic Diagnostic Testing in Idiopathic Ventricular Fibrillation: Results From the Dutch iVF Registry.

Background: Idiopathic ventricular fibrillation (iVF) is a diagnosis of exclusion. Systematic diagnostic testing is important to exclude alternative causes for VF. The early use of "high yield" testing, including cardiac magnetic resonance (CMR), exercise testing, and sodium channel blocker provocation, has been increasingly recognized.

In silico analysis of the dynamic regulation of cardiac electrophysiology by K 11.1 ion-channel trafficking.

Cardiac electrophysiology is regulated by continuous trafficking and internalization of ion channels occurring over minutes to hours. K 11.1 (also known as hERG) underlies the rapidly activating delayed-rectifier K current (I ), which plays a major role in cardiac ventricular repolarization.

Variant Location Is a Novel Risk Factor for Individuals With Arrhythmogenic Cardiomyopathy Due to a Desmoplakin () Truncating Variant.

Background: Truncating variants in desmoplakin (tv) are an important cause of arrhythmogenic cardiomyopathy; however the genetic architecture and genotype-specific risk factors are incompletely understood. We evaluated phenotype, risk factors for ventricular arrhythmias, and underlying genetics of tv cardiomyopathy.

Methods: Individuals with tv and any cardiac phenotype, and their gene-positive family members were included from multiple international centers.

CIRCprimerXL: Convenient and High-Throughput PCR Primer Design for Circular RNA Quantification.

Circular RNA (circRNA) is a class of endogenous non-coding RNA characterized by a back-splice junction (BSJ). In general, large-scale circRNA BSJ detection is performed based on RNA sequencing data, followed by the selection and validation of circRNAs of interest using RT-qPCR with circRNA-specific PCR primers. Such a primer pair is convergent and functional on the circRNA template but divergent and non-functional on the linear host gene.

State-of-the-Art Multimodality Imaging in Sudden Cardiac Arrest with Focus on Idiopathic Ventricular Fibrillation: A Review.

Idiopathic ventricular fibrillation is a rare cause of sudden cardiac arrest and a diagnosis by exclusion. Unraveling the mechanism of ventricular fibrillation is important for targeted management, and potentially for initiating family screening. Sudden cardiac arrest survivors undergo extensive clinical testing, with a growing role for multimodality imaging, before diagnosing "idiopathic" ventricular fibrillation.