Comparative evaluation of 2 pulsed field ablation systems for atrial fibrillation: insights from real-world clinical implementation and short-term outcomes.

Background: Pulsed field ablation (PFA) is a safe and effective technology for catheter ablation of atrial fibrillation (AF). Multiple PFA-platforms for AF ablation have been developed. However, evidence comparing the real-world implementation and performance of different PFA systems is still limited.

GPD1L-A306del modifies sodium current in a family carrying the dysfunctional SCN5A-G1661R mutation associated with Brugada syndrome.

Loss-of-function variants of SCN5A, encoding the sodium channel alpha subunit Nav1.5 are associated with high phenotypic variability and multiple cardiac presentations, while underlying mechanisms are incompletely understood. Here we investigated a family with individuals affected by Brugada Syndrome (BrS) of different severity and aimed to unravel the underlying genetic and electrophysiological basis.

Virus-induced inhibition of cardiac pacemaker channel HCN4 triggers bradycardia in human-induced stem cell system.

The enterovirus Coxsackievirus B3 (CVB3) is known to be a major source for the development of cardiac dysfunctions like viral myocarditis (VMC) and dilatative cardiomyopathy (DCM), but also results in bradycardia and fatal cardiac arrest. Besides clinical reports on bradycardia and sudden cardiac death, very little is known about the influence of CVB3 on the activity of human cardiac pacemaker cells. Here, we address this issue using the first human induced pluripotent stem cell (hiPSC)-derived pacemaker-like cells, in which the expression of a transgenic non-infectious variant of CVB3 can be controlled dose- and time-dependently.

Improved Generation of Human Induced Pluripotent Stem Cell-Derived Cardiac Pacemaker Cells Using Novel Differentiation Protocols.

Current protocols for the differentiation of human-induced pluripotent stem cells (hiPSC) into cardiomyocytes only generate a small amount of cardiac pacemaker cells. In previous work, we reported the generation of high amounts of cardiac pacemaker cells by co-culturing hiPSC with mouse visceral endoderm-like (END2) cells. However, potential medical applications of cardiac pacemaker cells generated according to this protocol, comprise an incalculable xenogeneic risk.

Comparative Genomic Reveals Clonal Heterogeneity in Persistent Infection.

Persistent infections caused by remain a clinical challenge. Adaptational mechanisms of the pathogen influencing infection persistence, treatment success, and clinical outcome in these types of infections by have not been fully elucidated so far. We applied a whole-genome sequencing approach on fifteen isolates retrieved from a persistent infection to determine their genetic relatedness, virulome, and resistome.

Atrial fibrillation before heart transplantation is a risk factor for post-transplant atrial fibrillation and mortality.

Aims: Atrial fibrillation (AF) after heart transplantation (HTX) is associated with worse clinical outcomes. The current study aimed to analyse the association between AF before HTX and AF within 30 days after HTX.

Methods And Results: This study included 639 adults who received HTX at Heidelberg Heart Center.

Histone deacetylase 2-dependent ventricular electrical remodeling in a porcine model of early heart failure.

Aims: Heart failure (HF) is linked to electrical remodeling that promotes ventricular arrhythmias. Underlying molecular signaling is insufficiently understood, in particular concerning patients with early disease stages. Previous observations suggest a key role for epigenetic mechanisms in cardiac remodeling processes.

Epigenetic regulation of cardiac electrophysiology in atrial fibrillation: HDAC2 determines action potential duration and suppresses NRSF in cardiomyocytes.

Atrial fibrillation (AF) is associated with electrical remodeling, leading to cellular electrophysiological dysfunction and arrhythmia perpetuation. Emerging evidence suggests a key role for epigenetic mechanisms in the regulation of ion channel expression. Histone deacetylases (HDACs) control gene expression through deacetylation of histone proteins.

cardiac pacemaker function of differentiated human mesenchymal stem cells from adipose tissue transplanted into porcine hearts.

Background: Mesenchymal stem cells (MSC) modified by gene transfer to express cardiac pacemaker channels such as HCN2 or HCN4 were shown to elicit pacemaker function after intracardiac transplantation in experimental animal models. Human MSC derived from adipose tissue (haMSC) differentiate into cells with pacemaker properties , but little is known about their behavior after intracardiac transplantation.

Aim: To investigate whether haMSC elicit biological pacemaker function after transplantation into pig hearts.

Cryoballoon pulmonary vein isolation-mediated rise of sinus rate in patients with paroxysmal atrial fibrillation.

Background: Modulation of the cardiac autonomic nervous system by pulmonary vein isolation (PVI) influences the sinoatrial nodal rate. Little is known about the causes, maintenance and prognostic value of this phenomenon. We set out to explore the effects of cryoballoon PVI (cryo-PVI) on sinus rate and its significance for clinical outcome.

Quantitative Efficacy and Fate of Mesenchymal Stromal Cells Targeted to Cardiac Sites by Radiofrequency Catheter Ablation.

Engraftment and functional integration of stem cells or stem cell-derived cells within cardiac tissue is an important prerequisite for cell replacement therapy aiming at the treatment of heart disease. Recently, a novel intravenous approach for application of mesenchymal stromal cells (MSCs) to cardiac sites has been established using radiofrequency catheter ablation (RFCA)-guided targeting, bypassing the need for open chest surgery or direct myocardial cell injection. However, little is known about the quantitative efficacy and longevity of this strategy.

The C-terminal HCN4 variant P883R alters channel properties and acts as genetic modifier of atrial fibrillation and structural heart disease.

Atrial fibrillation (AF) is the most frequent sustained arrhythmia and can lead to structural cardiac changes, known as tachycardia-induced cardiomyopathy (TIC). HCN4 is implicated in spontaneous excitation of the sinoatrial node, while channel dysfunction has been associated with sinus bradycardia, AF and structural heart disease. We here asked whether HCN4 mutations may contribute to the development of TIC, as well.

Augmentation of myocardial I dysregulates calcium homeostasis and causes adverse cardiac remodeling.

HCN channels underlie the depolarizing funny current (I) that contributes importantly to cardiac pacemaking. I is upregulated in failing and infarcted hearts, but its implication in disease mechanisms remained unresolved. We generated transgenic mice (HCN4) to assess functional consequences of HCN4 overexpression-mediated I increase in cardiomyocytes to levels observed in human heart failure.

Pacemaker cell characteristics of differentiated and HCN4-transduced human mesenchymal stem cells.

Aims: Cell-based biological pacemakers aim to overcome limitations and side effects of electronic pacemaker devices. We here developed and tested different approaches to achieve nodal-type differentiation using human adipose- and bone marrow-derived mesenchymal stem cells (haMSC, hbMSC).

Main Methods: haMSC and hbMSC were differentiated using customized protocols.

Cardiac K13.1 (THIK-1) two-pore-domain K channels: Pharmacological regulation and remodeling in atrial fibrillation.

Cardiac two-pore-domain potassium (K) channels have been proposed as novel antiarrhythmic targets. K13.1 (THIK-1) channels are expressed in the human heart, and atrial K13.

ANK2 functionally interacts with KCNH2 aggravating long QT syndrome in a double mutation carrier.

Pathogenic long QT mutations often comprise high phenotypic variability and particularly variants in ANK2 (long QT syndrome 4) frequently lack QT prolongation. We sought to elucidate the genetic and functional background underlying the clinical diversity in a 3-generation family with different cardiac arrhythmias. Next-generation sequencing-based screening of patients with QT prolongation identified the index patient of the family carrying an ANK2-E1813K variant and a previously uncharacterized KCNH2-H562R mutation in a double heterozygous conformation.

Cloning and characterization of zebrafish K13.1 (THIK-1) two-pore-domain K channels.

Two-pore-domain potassium (K) channels conduct background potassium currents in the heart and other tissues. K currents are involved in the repolarization of action potentials and stabilize the resting membrane potential. Human K13.

German Cardiac Society Working Group on Cellular Electrophysiology state-of-the-art paper: impact of molecular mechanisms on clinical arrhythmia management.

Cardiac arrhythmias remain a common challenge and are associated with significant morbidity and mortality. Effective and safe rhythm control strategies are a primary, yet unmet need in everyday clinical practice. Despite significant pharmacological and technological advances, including catheter ablation and device-based therapies, the development of more effective alternatives is of significant interest to increase quality of life and to reduce symptom burden, hospitalizations and mortality.

Novel approach to discriminate left bundle branch block from nonspecific intraventricular conduction delay using pacing-induced functional left bundle branch block.

Purpose: Left bundle branch block (LBBB) has a predictive value for response to cardiac resynchronization therapy as reported by Zareba et al. (Circulation 123(10):1061-1072, 2011). However, based on ECG criteria, the discrimination between complete LBBB and nonspecific intraventricular conduction delay is challenging.

Role of ion channels in heart failure and channelopathies.

Heart failure (HF) is a complication of multiple cardiac diseases and is characterized by impaired contractile and electric function. Patients with HF are not only limited by reduced contractile function but are also prone to life-threatening ventricular arrhythmias. HF itself leads to remodeling of ion channels, gap junctions, and intracellular calcium handling abnormalities that in combination with structural remodeling, e.

Cardiovascular pharmacology of K17.1 (TASK-4, TALK-2) two-pore-domain K channels.

K17.1 (TASK-4, TALK-2) potassium channels are expressed in the heart and represent potential targets for pharmacological management of atrial and ventricular arrhythmias. Reduced K17.

Identification and functional characterization of zebrafish K17.1 (TASK-4, TALK-2) two-pore-domain K channels.

Human K17.1 (TASK-4, TALK-2) two-pore-domain potassium (K) channels have recently been implicated in heart rhythm disorders including atrial fibrillation and conduction disease. The functional in vivo significance of K17.

Subtype-specific differentiation of cardiac pacemaker cell clusters from human induced pluripotent stem cells.

Background: Human induced pluripotent stem cells (hiPSC) harbor the potential to differentiate into diverse cardiac cell types. Previous experimental efforts were primarily directed at the generation of hiPSC-derived cells with ventricular cardiomyocyte characteristics. Aiming at a straightforward approach for pacemaker cell modeling and replacement, we sought to selectively differentiate cells with nodal-type properties.

Fully digital data processing during cardiovascular implantable electronic device follow-up in a high-volume tertiary center.

Background: Increasing numbers of patients with cardiovascular implantable electronic devices (CIEDs) and limited follow-up capacities highlight unmet challenges in clinical electrophysiology. Integrated software (MediConnect) enabling fully digital processing of device interrogation data has been commercially developed to facilitate follow-up visits. We sought to assess feasibility of fully digital data processing (FDDP) during ambulatory device follow-up in a high-volume tertiary hospital to provide guidance for future users of FDDP software.