QRS prolongation after premature stimulation is associated with polymorphic ventricular tachycardia in nonischemic cardiomyopathy: Results from the Leiden Nonischemic Cardiomyopathy Study.

Background: Progressive activation delay after premature stimulation has been associated with ventricular fibrillation in nonischemic cardiomyopathy (NICM).

Objectives: The objectives of this study were (1) to investigate prolongation of the paced QRS duration (QRSd) after premature stimulation as a marker of activation delay in NICM, (2) to assess its relation to induced ventricular arrhythmias, and (3) to analyze its underlying substrate by late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMR) and endomyocardial biopsy.

Methods: Patients with NICM were prospectively enrolled in the Leiden Nonischemic Cardiomyopathy Study and underwent a comprehensive evaluation including LGE-CMR, electrophysiology study, and endomyocardial biopsy.

Constitutively Active Acetylcholine-Dependent Potassium Current Increases Atrial Defibrillation Threshold by Favoring Post-Shock Re-Initiation.

Electrical cardioversion (ECV), a mainstay in atrial fibrillation (AF) treatment, is unsuccessful in up to 10-20% of patients. An important aspect of the remodeling process caused by AF is the constitutive activition of the atrium-specific acetylcholine-dependent potassium current (IK,ACh → IK,ACh-c), which is associated with ECV failure. This study investigated the role of IK,ACh-c in ECV failure and setting the atrial defibrillation threshold (aDFT) in optically mapped neonatal rat cardiomyocyte monolayers.

Forced fusion of human ventricular scar cells with cardiomyocytes suppresses arrhythmogenicity in a co-culture model.

Aims: Fibrosis increases arrhythmogenicity in myocardial tissue by causing structural and functional disruptions in the cardiac syncytium. Forced fusion of fibroblastic cells with adjacent cardiomyocytes may theoretically resolve these disruptions. Therefore, the electrophysiological effects of such electrical and structural integration of fibroblastic cells into a cardiac syncytium were studied.

Light-induced termination of spiral wave arrhythmias by optogenetic engineering of atrial cardiomyocytes.

Aims: Atrial fibrillation (AF) is the most common cardiac arrhythmia and often involves reentrant electrical activation (e.g. spiral waves).

Atrium-specific Kir3.x determines inducibility, dynamics, and termination of fibrillation by regulating restitution-driven alternans.

Background: Atrial fibrillation is the most common cardiac arrhythmia. Ventricular proarrhythmia hinders pharmacological atrial fibrillation treatment. Modulation of atrium-specific Kir3.

Engraftment patterns of human adult mesenchymal stem cells expose electrotonic and paracrine proarrhythmic mechanisms in myocardial cell cultures.

Background: After intramyocardial injection, mesenchymal stem cells (MSCs) may engraft and influence host myocardium. However, engraftment rate and pattern of distribution are difficult to control in vivo, hampering assessment of potential adverse effects. In this study, the role of the engraftment patterns of MSCs on arrhythmicity in controllable in vitro models is investigated.

Prolongation of minimal action potential duration in sustained fibrillation decreases complexity by transient destabilization.

Aims: Sustained ventricular fibrillation (VF) is maintained by multiple stable rotors. Destabilization of sustained VF could be beneficial by affecting VF complexity (defined by the number of rotors). However, underlying mechanisms affecting VF stability are poorly understood.

Similar arrhythmicity in hypertrophic and fibrotic cardiac cultures caused by distinct substrate-specific mechanisms.

Aims: Cardiac hypertrophy and fibrosis are associated with potentially lethal arrhythmias. As these substrates often occur simultaneously in one patient, distinguishing between pro-arrhythmic mechanisms is difficult. This hampers understanding of underlying pro-arrhythmic mechanisms and optimal treatment.

Human embryonic and fetal mesenchymal stem cells differentiate toward three different cardiac lineages in contrast to their adult counterparts.

Mesenchymal stem cells (MSCs) show unexplained differences in differentiation potential. In this study, differentiation of human (h) MSCs derived from embryonic, fetal and adult sources toward cardiomyocytes, endothelial and smooth muscle cells was investigated. Labeled hMSCs derived from embryonic stem cells (hESC-MSCs), fetal umbilical cord, bone marrow, amniotic membrane and adult bone marrow and adipose tissue were co-cultured with neonatal rat cardiomyocytes (nrCMCs) or cardiac fibroblasts (nrCFBs) for 10 days, and also cultured under angiogenic conditions.

Antiproliferative treatment of myofibroblasts prevents arrhythmias in vitro by limiting myofibroblast-induced depolarization.

Aims: Cardiac fibrosis is associated with increased incidence of cardiac arrhythmias, but the underlying proarrhythmic mechanisms remain incompletely understood and antiarrhythmic therapies are still suboptimal. This study tests the hypothesis that myofibroblast (MFB) proliferation leads to tachyarrhythmias by altering the excitability of cardiomyocytes (CMCs) and that inhibition of MFB proliferation would thus lower the incidence of such arrhythmias.

Methods And Results: Endogenous MFBs in neonatal rat CMC cultures proliferated freely or under control of different dosages of antiproliferative agents (mitomycin-C and paclitaxel).

Electrical activation of sinus venosus myocardium and expression patterns of RhoA and Isl-1 in the chick embryo.

Unlabelled: Electrical Activity and RhoA in the Embryo.

Introduction: Myocardium at the venous pole (sinus venosus) of the heart has gained clinical interest as arrhythmias can be initiated from this area. During development, sinus venosus myocardium is incorporated to the primary heart tube and expresses different markers than primary myocardium.