Verapamil inhibits Kir2.3 channels by binding to the pore and interfering with PIP binding.

The inwardly rectifying potassium current of the cardiomyocyte (I) is the main determinant of the resting potential. Ion channels Kir2.1, Kir2.

Economic evaluation of remote monitoring of patients with an implantable cardiac defibrillator (REMOTE-CIED study).

Introduction: Remote patient monitoring (RPM) of heart failure patients has the potential to reduce healthcare resource use and costs, but current evidence has been inconclusive. This study aims assess the impact of RPM of heart failure patients with an implantable cardioverter defibrillator on medical resource use, direct medical costs, quality-adjusted life years (QALYs), and travel time of patients, and to estimate its commercial headroom in the Netherlands and Germany.

Methods: Data from the REMOTE-CIED randomized controlled trial were used to calculate differences in length of hospital stay, outpatient clinic visits, telephone consults, emergency room visits, and travel time between patients on in-clinic follow-up and RPM in the Netherlands, Germany, and France.

Clinical valuation of ST changes in a group of patients with ventricular arrhythmias: The inSighT Study.

Background: The inSighT study was designed to determine the prevalence of ischemic changes as recorded by implantable cardioverter-defibrillator (ICD) ST deviations in intracardiac electrocardiograms (EGM) over the 24 h preceding malignant ventricular arrhythmias (VT/VF).

Methods: The study enrolled patients with known coronary artery disease (CAD) or high risk of future development of CAD implanted with an ICD equipped with an ST monitoring feature (Ellipse™/Fortify Assura™, St. Jude Medical).

Identification of p.C335R Variant in a Large Family with Dilated Cardiomyopathy and Conduction Disease.

Introduction: Familial dilated cardiomyopathy (DCM) is clinically variable and has been associated with mutations in more than 50 genes. Rapid improvements in DNA sequencing have led to the identification of diverse rare variants with unknown significance (VUS), which underlines the importance of functional analyses. In this study, by investigating human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), we evaluated the pathogenicity of the p.

Effect of remote monitoring on clinical outcomes in European heart failure patients with an implantable cardioverter-defibrillator: secondary results of the REMOTE-CIED randomized trial.

Aims: Remote patient monitoring (RPM) systems offer a promising alternative to conventional In-Clinic check-ups, hereby reducing unnecessary clinic visits. Especially with the rise of the COVID-19 pandemic, this reduction is of paramount importance. Regarding the association between RPM and clinical outcomes, findings of previous studies have been inconsistent.

Combined amiodarone and digitalis therapy before heart transplantation is associated with increased post-transplant mortality.

Aims: Amiodarone and digitalis are frequently used drugs in patients with heart failure. Both have separately been linked to reduced post-transplant survival, but their combined impact on mortality after HTX remains uncertain. This study investigated the effects of combined amiodarone and digitalis use before HTX on post-transplant outcomes.

Postcardiac injury syndrome after cardiac implantable electronic device implantation.

Background: Postcardiac injury syndrome (PCIS) is an inflammatory complication that derives from injury to the epicardium, myocardium, or endocardium. It occurs after trauma, myocardial infarction, percutaneous coronary intervention, cardiac surgery, intracardiac ablation, and implantation of cardiac implantable electronic device (CIED). In this study we assessed the incidence of PCIS after CIED implantation and its possible risk factors.

Risk factors and survival of patients with permanent pacemaker implantation after heart transplantation.

Background: Permanent pacemaker (PPM) implantation after heart transplantation (HTX) may be required due to severe bradycardia. The aim of this study was to investigate the risk factors, indications, perioperative outcomes and complications of PPM implantation after HTX as well as the underlying effect on post-transplant mortality including causes of death.

Methods: This registry study included 621 patients receiving HTX at Heidelberg Heart Center between 1989 and 2018.

Effect of remote monitoring on patient-reported outcomes in European heart failure patients with an implantable cardioverter-defibrillator: primary results of the REMOTE-CIED randomized trial.

Aims: The European REMOTE-CIED study is the first randomized trial primarily designed to evaluate the effect of remote patient monitoring (RPM) on patient-reported outcomes in the first 2 years after implantation of an implantable cardioverter-defibrillator (ICD).

Methods And Results: The sample consisted of 595 European heart failure patients implanted with an ICD compatible with the Boston Scientific LATITUDE® RPM system. Patients were randomized to RPM plus a yearly in-clinic ICD check-up vs.

Remote monitoring of implantable cardioverter defibrillators: Patient experiences and preferences for follow-up.

Background: Patient satisfaction with remote patient monitoring (RPM) of implantable cardioverter defibrillators (ICDs) seems to be high, yet knowledge on long-term patient experiences is limited. The European REMOTE-CIED study explored patients' experiences with RPM, examined patient's preferences for ICD follow-up, and identified determinants of patient's preferences in the first 2 years postimplantation.

Methods: European heart failure patients (N = 300; median age = 66 years [interquartile range (IQR) = 59-73], and 22% female) with a first-time ICD received a Boston Scientific LATITUDE RPM system (Marlborough, MA, USA) and had scheduled in-clinic follow-ups once a year.

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.

Use of the wearable cardioverter-defibrillator (WCD) and WCD-based remote rhythm monitoring in a real-life patient cohort.

The wearable cardioverter-defibrillator (WCD) was introduced to provide protection from sudden cardiac death (SCD) in patients with transiently elevated risk or during ongoing risk stratification. Benefits and clinical characteristics of routine WCD use remain to be assessed in larger patient populations. This study aims to identify determinants of WCD compliance, therapies, and inappropriate alarms in a real-life cohort.

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.

Prevalence and risk markers of early psychological distress after ICD implantation in the European REMOTE-CIED study cohort.

Background: Evidence on psychological distress in patients living with an implantable cardioverter defibrillator (ICD) is inconclusive. The current study is the first to examine the prevalence and risk markers of anxiety and/or depression in a large international cohort of European ICD patients with or without cardiac resynchronization therapy (CRT).

Method: Heart failure patients (N=569) from France, Germany, Spain, Switzerland and the Netherlands participating in the REMOTE-CIED study completed a set of questionnaires 1-2weeks post ICD-implantation, including the 7-item Generalized Anxiety Disorder scale and the 9-item Patient Health Questionnaire to assess anxiety and depressive symptoms, respectively.

Inhibition of inwardly rectifying Kir2.x channels by the novel anti-cancer agent gambogic acid depends on both pore block and PIP interference.

The caged xanthone gambogic acid (GA) is a novel anti-cancer agent which exhibits anti-proliferative, anti-inflammatory and cytotoxic effects in many types of cancer tissues. In a recent phase IIa study, GA exhibits a favourable safety profile. However, limited data are available concerning its interaction with cardiac ion channels.

Role of plasma membrane-associated AKAPs for the regulation of cardiac I current by protein kinase A.

The cardiac I current stabilizes the resting membrane potential of cardiomyocytes. Protein kinase A (PKA) induces an inhibition of I current which strongly promotes focal arrhythmogenesis. The molecular mechanisms underlying this regulation have only partially been elucidated yet.

Dual Mechanism for Inhibition of Inwardly Rectifying Kir2.x Channels by Quinidine Involving Direct Pore Block and PIP-interference.

Class IA antiarrhythmic drug quinidine was one of the first clinically used compounds to terminate atrial fibrillation and acts as multichannel inhibitor with well-documented inhibitory effects on several cardiac potassium channels. In the mammalian heart, heteromeric assembly of Kir2.1-2.

Efficacy, High Procedural Safety And Rapid Optimization Of Cryoballoon Atrial Fibrillation Ablation In The Hands Of A New Operator.

Background: Cryoballoon (CB) ablation is successful in eliminating atrial fibrillation (AF).

Purpose: The purpose of this study was to assess procedural efficacy and safety of CB ablation performed by a newly trained operator.

Methods: Forty patients with documented paroxysmal AF (58 ± 11 years, 26 male) undergoing CB catheter ablation were prospectively enrolled.

miR-19b Regulates Ventricular Action Potential Duration in Zebrafish.

Sudden cardiac death due to ventricular arrhythmias often caused by action potential duration (APD) prolongation is a common mode of death in heart failure (HF). microRNAs, noncoding RNAs that fine tune gene expression, are frequently dysregulated during HF, suggesting a potential involvement in the electrical remodeling process accompanying HF progression. Here, we identified miR-19b as an important regulator of heart function.

Personalized Computer Simulation of Diastolic Function in Heart Failure.

The search for a parameter representing left ventricular relaxation from non-invasive and invasive diagnostic tools has been extensive, since heart failure (HF) with preserved ejection fraction (HF-pEF) is a global health problem. We explore here the feasibility using patient-specific cardiac computer modeling to capture diastolic parameters in patients suffering from different degrees of systolic HF. Fifty eight patients with idiopathic dilated cardiomyopathy have undergone thorough clinical evaluation, including cardiac magnetic resonance imaging (MRI), heart catheterization, echocardiography, and cardiac biomarker assessment.

Inhibition of Cardiac Kir Current (IK1) by Protein Kinase C Critically Depends on PKCβ and Kir2.2.

Background: Cardiac inwardly rectifying Kir current (IK1) mediates terminal repolarisation and is critical for the stabilization of the diastolic membrane potential. Its predominant molecular basis in mammalian ventricle is heterotetrameric assembly of Kir2.1 and Kir2.

Novel Endothelial Cell-Specific AQP1 Knockout Mice Confirm the Crucial Role of Endothelial AQP1 in Ultrafiltration during Peritoneal Dialysis.

The water channel aquaporin-1 (AQP1) mediates about 50% ultrafiltration during a 2-hour hypertonic dwell in global AQP1 knockout (AQP1-/-) mice. Although AQP1 is widely expressed in various cell types including mesothelial cells, the ultrafiltration has been assumed to be mediated via endothelial AQP1 of the peritoneum. The partial embryonic lethality and reduced body weight in AQP1-/- mice may reflect potential confounding phenotypic effects evoked by ubiquitous AQP1 deletion, which may interfere with functional analysis of endothelial AQP1.

Long-term outcome of patients with and without super-response to CRT-D.

Objective: To compare outcome between patients with and without super-response to cardiac resynchronization therapy-defibrillator (CRT-D).

Methods And Results: In this cohort study, 167 consecutive CRT-D candidates were included. Super-response to CRT-D was defined clinically [improvement of ≥1 New York Heart Association (NYHA) class or ≥50 m in six-minute walk distance (6MWD)] and echocardiographically [increase of left ventricular ejection fraction (LVEF) ≥1 category (LVEF <30 to 30-40 % or 30-40 to 41-51 %) or reduction of left ventricular end-diastolic diameter (LVEDD) ≥10 mm].

Towards Personalized Cardiology: Multi-Scale Modeling of the Failing Heart.

Background: Despite modern pharmacotherapy and advanced implantable cardiac devices, overall prognosis and quality of life of HF patients remain poor. This is in part due to insufficient patient stratification and lack of individualized therapy planning, resulting in less effective treatments and a significant number of non-responders.

Methods And Results: State-of-the-art clinical phenotyping was acquired, including magnetic resonance imaging (MRI) and biomarker assessment.