Detection of Ischemic ST-Segment Changes Using a Novel Handheld ECG Device in a Porcine Model.

Background: Portable, smartphone-sized electrocardiography (ECG) has the potential to reduce time to treatment for patients suffering acute cardiac ischemia, thereby lowering the morbidity and mortality. In the UMC Utrecht, a portable, smartphone-sized, multi-lead precordial ECG recording device (miniECG 1.0, UMC Utrecht) was developed.

Lack of Prognostic Value of T-Wave Alternans for Implantable Cardioverter-Defibrillator Benefit in Primary Prevention.

Background: New methods to identify patients who benefit from a primary prophylactic implantable cardioverter-defibrillator (ICD) are needed. T-wave alternans (TWA) has been shown to associate with arrhythmogenesis of the heart and sudden cardiac death. We hypothesized that TWA might be associated with benefit from ICD implantation in primary prevention.

High-rate pacing suppresses Torsade de Pointes arrhythmias and reduces spatial dispersion of repolarization in the chronic AV-block dog model.

An electrical storm of Torsade de Pointes arrhythmias (TdP) can be reproducibly induced in the anesthetized chronic AV-block (CAVB) dog by infusion of the I-blocker dofetilide. Earlier studies showed that these arrhythmias 1) arise from locations with high spatial dispersion in repolarization (SDR) and 2) can be suppressed by high-rate pacing. We examined whether suppression of TdP by high-rate pacing is established through a decrease in SDR in the CAVB dog.

Automatic measurement of short-term variability of repolarization to indicate ventricular arrhythmias in a porcine model of cardiac ischaemia.

Aims: An automated method for determination of short-term variability (STV) of repolarization on intracardiac electrograms (STV-ARIauto) has previously been developed for arrhythmic risk monitoring by cardiac implantable devices, and has proved effective in predicting ventricular arrhythmias (VA) and guiding preventive high-rate pacing (HRP) in a canine model. Current study aimed to assess (i) STV-ARIauto in relation to VA occurrence and secondarily (ii-a) to confirm the predictive capacity of STV from the QT interval and (ii-b) explore the effect of HRP on arrhythmic outcomes in a porcine model of acute myocardial infarction (MI).

Methods And Results: Myocardial infarction was induced in 15 pigs.

QRS complex and T wave planarity for the efficacy prediction of automatic implantable defibrillators.

Objective: To test the hypothesis that in recipients of primary prophylactic implantable cardioverter-defibrillators (ICDs), the non-planarity of ECG vector loops predicts (a) deaths despite ICD protection and (b) appropriate ICD shocks.

Methods: Digital pre-implant ECGs were collected in 1948 ICD recipients: 21.4% females, median age 65 years, 61.

Directed graph mapping shows rotors maintain non-terminating and focal sources maintain self-terminating Torsade de Pointes in canine model.

Torsade de Pointes is a polymorphic ventricular tachycardia which is as yet incompletely understood. While the onset of a TdP episode is generally accepted to be caused by triggered activity, the mechanisms for the perpetuation is still under debate. In this study, we analysed data from 54 TdP episodes divided over 5 dogs (4 female, 1 male) with chronic atrioventricular block.

I Activator ML277 Mildly Affects Repolarization and Arrhythmic Outcome in the CAVB Dog Model.

Long QT syndrome type 1 with affected I is associated with a high risk for developing Torsade de Pointes (TdP) arrhythmias and eventually sudden cardiac death. Therefore, it is of high interest to explore drugs that target I as antiarrhythmics. We examined the antiarrhythmic effect of I channel activator ML277 in the chronic atrioventricular block (CAVB) dog model.

Pro-Arrhythmic Potential of Accumulated Uremic Toxins Is Mediated via Vulnerability of Action Potential Repolarization.

Chronic kidney disease (CKD) is represented by a diminished filtration capacity of the kidneys. End-stage renal disease patients need dialysis treatment to remove waste and toxins from the circulation. However, endogenously produced uremic toxins (UTs) cannot always be filtered during dialysis.

Remodeling in the AV block dog is essential for tolerating moderate treadmill activity.

Background: A preclinical model standardized at different remodeling stages after AV block induction in awake state is suitable for the evaluation of improved cardiac devices. We studied exercise-induced cardiorespiratory parameters at three different timepoints after inducing AV block in dogs.

Methods: Mongrel dogs (n = 12) were placed on a treadmill with a 10% incline and performed a moderate exercise protocol (10-minute run at 6 km/h).

Chronically altered ventricular activation causes pro-arrhythmic cardiac electrical remodelling in the chronic AV block dog model.

Aims: Altered ventricular activation (AVA) causes intraventricular mechanical dyssynchrony (MD) and impedes contraction, promoting pro-arrhythmic electrical remodelling in the chronic atrioventricular block (CAVB) dog. We aimed to study arrhythmogenic and electromechanical outcomes of different degrees of AVA.

Methods And Results: Following atrioventricular block, AVA was established through idioventricular rhythm (IVR; n = 29), right ventricular apex (RVA; n = 12) pacing or biventricular pacing [cardiac resynchronization therapy (CRT); n = 10].

I inhibitor JNJ303 prolongs the QT interval and perpetuates arrhythmia when combined with enhanced inotropy in the CAVB dog.

Introduction: Impaired I induced by drugs or due to a KCNQ1 mutation, diagnosed as long QT syndrome type 1 (LQT1) prolongs the QT interval and predisposes the heart to Torsade de Pointes (TdP) arrhythmias. The anesthetized chronic AV block (CAVB) dog is inducible for TdP after remodeling and I inhibitor dofetilide. We tested the proarrhythmic effect of I inhibition in the CAVB dog, and the proarrhythmic role of increased contractility herein.

QRS micro-fragmentation as a mortality predictor.

Aims: Fragmented QRS complex with visible notching on standard 12-lead electrocardiogram (ECG) is understood to represent depolarization abnormalities and to signify risk of cardiac events. Depolarization abnormalities with similar prognostic implications likely exist beyond visual recognition but no technology is presently suitable for quantification of such invisible ECG abnormalities. We present such a technology.

Exploring the Correlation Between Fibrosis Biomarkers and Clinical Disease Severity in PLN p.Arg14del Patients.

Pathogenic variants in (, like p. Arg14del), are found in patients diagnosed with arrhythmogenic (ACM) and dilated cardiomyopathy (DCM). Fibrosis formation in the heart is one of the hallmarks in p.

Buccal Mucosa Cells as a Potential Diagnostic Tool to Study Onset and Progression of Arrhythmogenic Cardiomyopathy.

In arrhythmogenic cardiomyopathy (ACM) pathogenic variants are found in genes encoding desmosomal proteins and in non-desmosomal genes, such as (, p.Arg14del variant). Previous research showed that plakoglobin protein levels and localization in the cardiac tissue of ACM patients, and p.

Aetiology of Heart Failure, Rather than Sex, Determines Reverse LV Remodelling Response to CRT.

Introduction: Cardiac resynchronization therapy (CRT) is an established therapy for patients with heart failure with reduced ejection fraction (HFrEF). Women appear to respond differently to CRT, yet it remains unclear whether this is inherent to the female sex itself, or due to other patient characteristics. In this study, we aimed to investigate sex differences in response to CRT.

Does mechanical dyssynchrony in addition to QRS area ensure sustained response to cardiac resynchronization therapy?

Aims: Judicious patient selection for cardiac resynchronization therapy (CRT) may further enhance treatment response. Progress has been made by using improved markers of electrical dyssynchrony and mechanical discoordination, using QRSAREA, and systolic rebound stretch of the septum (SRSsept) or systolic stretch index (SSI), respectively. To date, the relation between these measurements has not yet been investigated.

Q waves are the strongest electrocardiographic variable associated with primary prophylactic implantable cardioverter-defibrillator benefit: a prospective multicentre study.

Aim: The association of standard 12-lead electrocardiogram (ECG) markers with benefits of the primary prophylactic implantable cardioverter-defibrillator (ICD) has not been determined in the contemporary era. We analysed traditional and novel ECG variables in a large prospective, controlled primary prophylactic ICD population to assess the predictive value of ECG in terms of ICD benefit.

Methods And Results: Electrocardiograms from 1477 ICD patients and 700 control patients (EU-CERT-ICD; non-randomized, controlled, prospective multicentre study; ClinicalTrials.

Ventricular TLR4 Levels Abrogate TLR2-Mediated Adverse Cardiac Remodeling upon Pressure Overload in Mice.

Involvement of the Toll-like receptor 4 (TLR4) in maladaptive cardiac remodeling and heart failure (HF) upon pressure overload has been studied extensively, but less is known about the role of TLR2. Interplay and redundancy of TLR4 with TLR2 have been reported in other organs but were not investigated during cardiac dysfunction. We explored whether TLR2 deficiency leads to less adverse cardiac remodeling upon chronic pressure overload and whether TLR2 and TLR4 additively contribute to this.

Autonomic modulation of ventricular electrical activity: recent developments and clinical implications.

Purpose: This review aimed to provide a complete overview of the current stance and recent developments in antiarrhythmic neuromodulatory interventions, focusing on lifethreatening vetricular arrhythmias.

Methods: Both preclinical studies and clinical studies were assessed to highlight the gaps in knowledge that remain to be answered and the necessary steps required to properly translate these strategies to the clinical setting.

Results: Cardiac autonomic imbalance, characterized by chronic sympathoexcitation and parasympathetic withdrawal, destabilizes cardiac electrophysiology and promotes ventricular arrhythmogenesis.

Robust neuromorphic coupled oscillators for adaptive pacemakers.

Neural coupled oscillators are a useful building block in numerous models and applications. They were analyzed extensively in theoretical studies and more recently in biologically realistic simulations of spiking neural networks. The advent of mixed-signal analog/digital neuromorphic electronic circuits provides new means for implementing neural coupled oscillators on compact, low-power, spiking neural network hardware platforms.

Severe Bradycardia Increases the Incidence and Severity of Torsade de Pointes Arrhythmias by Augmenting Preexistent Spatial Dispersion of Repolarization in the CAVB Dog Model.

Introduction: Torsade de pointes arrhythmias (TdP) in the chronic atrioventricular block (CAVB) dog model result from proarrhythmic factors, which trigger TdP and/or reinforce the arrhythmic substrate. This study investigated electrophysiological and arrhythmogenic consequences of severe bradycardia for TdP.

Methods: Dofetilide (25 μg/kg per 5 min) was administered to eight anesthetized, idioventricular rhythm (IVR) remodeled CAVB dogs in two serial experiments: once under 60 beats per minute (bpm), right ventricular apex paced (RVA60) conditions, once under more bradycardic IVR conditions.

The canine chronic atrioventricular block model in cardiovascular preclinical drug research.

Ventricular cardiac arrhythmia is a life threating condition arising from abnormal functioning of many factors in concert. Animal models mirroring human electrophysiology are essential to predict and understand the rare pro- and anti-arrhythmic effects of drugs. This is very well accomplished by the canine chronic atrioventricular block (CAVB) model.

Segment length in cine (SLICE) strain analysis: a practical approach to estimate potential benefit from cardiac resynchronization therapy.

Background: Segment length in cine (SLICE) strain analysis on standard cardiovascular magnetic resonance (CMR) cine images was recently validated against gold standard myocardial tagging. The present study aims to explore predictive value of SLICE for cardiac resynchronization therapy (CRT) response.

Methods And Results: Fifty-seven patients with heart failure and left bundle branch block (LBBB) were prospectively enrolled in this multi-center study and underwent CMR examination before CRT implantation.

Short-Term Variability of the QT Interval Can be Used for the Prediction of Imminent Ventricular Arrhythmias in Patients With Primary Prophylactic Implantable Cardioverter Defibrillators.

Background Short-term variability of the QT interval (STV) has been proposed as a novel electrophysiological marker for the prediction of imminent ventricular arrhythmias in animal models. Our aim is to study whether STV can predict imminent ventricular arrhythmias in patients. Methods and Results In 2331 patients with primary prophylactic implantable cardioverter defibrillators, 24-hour ECG Holter recordings were obtained as part of the EU-CERT-ICD (European Comparative Effectiveness Research to Assess the Use of Primary Prophylactic Implantable Cardioverter Defibrillators) study.