Global Health Inequities in Electrophysiology Care: A State-of-the-Art Review.

This state-of-the-art review examines disparities in the diagnosis, management, and outcomes of cardiac arrhythmias globally. These arrhythmias include atrial fibrillation, ventricular tachyarrhythmias underlying sudden cardiac death, and bradyarrhythmias associated with sinus node and atrioventricular node disease. Arrhythmias in low- and middle-income countries often result in higher mortality rates due to complex and poorly documented risk factors, lack of clinical expertise among health care personnel, lack of sufficient infrastructure, and challenges in access to care.

An improved reporter identifies ruxolitinib as a potent and cardioprotective CaMKII inhibitor.

Ca/calmodulin-dependent protein kinase II (CaMKII) hyperactivity causes cardiac arrhythmias, a major source of morbidity and mortality worldwide. Despite proven benefits of CaMKII inhibition in numerous preclinical models of heart disease, translation of CaMKII antagonists into humans has been stymied by low potency, toxicity, and an enduring concern for adverse effects on cognition due to an established role of CaMKII in learning and memory. To address these challenges, we asked whether any clinically approved drugs, developed for other purposes, were potent CaMKII inhibitors.

CaMKII as a Therapeutic Target in Cardiovascular Disease.

CaMKII (the multifunctional Ca and calmodulin-dependent protein kinase II) is a highly validated signal for promoting a variety of common diseases, particularly in the cardiovascular system. Despite substantial amounts of convincing preclinical data, CaMKII inhibitors have yet to emerge in clinical practice. Therapeutic inhibition is challenged by the diversity of CaMKII isoforms and splice variants and by physiological CaMKII activity that contributes to learning and memory.

The response to cardiac resynchronization therapy in LMNA cardiomyopathy.

Aims: Cardiac implantable electronic device (CIED) therapy is fundamental to the management of LMNA cardiomyopathy due to the high frequency of atrioventricular block and ventricular tachyarrhythmias. We aimed to define the role of cardiac resynchronization therapy (CRT) in impacting heart failure in LMNA cardiomyopathy.

Methods And Results: From nine referral centres, LMNA cardiomyopathy patients who underwent CRT with available pre- and post-echocardiograms were identified retrospectively.

Metabolic heterogeneous zone assessed by FDG-PET is predictive of postablation mortality in patients with ventricular tachycardia.

Purpose: We sought to study the predictive value of the metabolic heterogeneous zone (HZ) as determined by Fluorodeoxyglucose ( FDG) positron emission tomography (PET) viability studies in ventricular tachycardia (VT) patients.

Methods: PET studies utilizing Rubidium ( Rb) tracer for perfusion and FDG tracer for viability were analyzed using PMOD (PMOD Technologies) and further analyzed using 684-segment plots. FDG uptake was normalized to the area with maximal perfusion on the rest Rb study.

Excessive -GlcNAcylation Causes Heart Failure and Sudden Death.

Background: Heart failure is a leading cause of death worldwide and is associated with the rising prevalence of obesity, hypertension, and diabetes. -GlcNAcylation (the attachment of -linked β-N-acetylglucosamine [-GlcNAc] moieties to cytoplasmic, nuclear, and mitochondrial proteins) is a posttranslational modification of intracellular proteins and serves as a metabolic rheostat for cellular stress. Total levels of -GlcNAcylation are determined by nutrient and metabolic flux, in addition to the net activity of 2 enzymes: -GlcNAc transferase (OGT) and -GlcNAcase (OGA).

Oxidized CaMKII and O-GlcNAcylation cause increased atrial fibrillation in diabetic mice by distinct mechanisms.

Diabetes mellitus (DM) and atrial fibrillation (AF) are major unsolved public health problems, and diabetes is an independent risk factor for AF. However, the mechanism(s) underlying this clinical association is unknown. ROS and protein O-GlcNAcylation (OGN) are increased in diabetic hearts, and calmodulin kinase II (CaMKII) is a proarrhythmic signal that may be activated by ROS (oxidized CaMKII, ox-CaMKII) and OGN (OGN-CaMKII).

Location, variations, and predictors of epicardial fat mapping using multidetector computed tomography to assist epicardial ventricular tachycardia ablation.

Background: A significant number of ventricular tachycardia circuits are located close to the epicardial surface and are amendable to epicardial ablation. Epicardial fat often interferes with substrate mapping and ablation, though little is known regarding the distribution of fat and its fluctuation with the cardiac cycle.

Methods: We studied 40 patients who underwent a 64-slice multidetector computed tomography in order to describe patterns of epicardial fat distribution, variation during cardiac cycle, and clinical predictors of epicardial fat.

Atrial remodelling in atrial fibrillation: CaMKII as a nodal proarrhythmic signal.

CaMKII is a serine-threonine protein kinase that is abundant in myocardium. Emergent evidence suggests that CaMKII may play an important role in promoting atrial fibrillation (AF) by targeting a diverse array of proteins involved in membrane excitability, cell survival, calcium homeostasis, matrix remodelling, inflammation, and metabolism. Furthermore, CaMKII inhibition appears to protect against AF in animal models and correct proarrhythmic, defective intracellular Ca(2+) homeostasis in fibrillating human atrial cells.

Meta-Analysis of the Relation of Ventricular Arrhythmias to All-Cause Mortality After Implantation of a Left Ventricular Assist Device.

Ventricular arrhythmias (VAs) are commonly reported after implantation of left ventricular assist devices (LVADs). Their relation to all-cause mortality and potential risk factors remains unclear. We conducted a meta-analysis of observational studies with the primary objective of evaluating the association of post-LVAD VAs with all-cause mortality at 60, 120, and 180 days.

Three-dimensional 123I-meta-iodobenzylguanidine cardiac innervation maps to assess substrate and successful ablation sites for ventricular tachycardia: feasibility study for a novel paradigm of innervation imaging.

Background: Innervation is a critical component of arrhythmogenesis and may present an important trigger/substrate modifier not used in current ventricular tachycardia (VT) ablation strategies.

Methods And Results: Fifteen patients referred for ischemic VT ablation underwent preprocedural cardiac (123)I- meta-iodobenzylguanidine ((123)I-mIBG) imaging, which was used to create 3-dimensional (3D) innervation models and registered to high-density voltage maps. 3D (123)I-mIBG innervation maps demonstrated areas of complete denervation and (123)I-mIBG transition zone in all patients, which corresponded to 0% to 31% and 32% to 52% uptake.

Differences in quantitative assessment of myocardial scar and gray zone by LGE-CMR imaging using established gray zone protocols.

Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) imaging is the gold standard for myocardial scar evaluation. Heterogeneous areas of scar ('gray zone'), may serve as arrhythmogenic substrate. Various gray zone protocols have been correlated to clinical outcomes and ventricular tachycardia channels.

Improved conduction and increased cell retention in healed MI using mesenchymal stem cells suspended in alginate hydrogel.

Introduction: Mesenchymal stem cells (MSCs) have been associated with reduced arrhythmias; however, the mechanism of this action is unknown. In addition, limited retention and survival of MSCs can significantly reduce efficacy. We hypothesized that MSCs can improve impulse conduction and that alginate hydrogel will enhance retention of MSCs in a model of healed myocardial infarction (MI).

Impact of ICD artifact burden on late gadolinium enhancement cardiac MR imaging in patients undergoing ventricular tachycardia ablation.

Background: Cardiac magnetic resonance imaging (CMRI) is the gold standard for myocardial scar evaluation. Although ideal for substrate assessment in ventricular tachycardia (VT), most patients have an implantable cardioverter-defibrillator (ICD) at presentation for ablation. This study evaluates the ICD artifact burden during standard late gadolinium enhancement CMRI (LGE-CMRI) evaluation of myocardial scar in VT patients with ICDs.

Assessment of ventricular tachycardia scar substrate by intracardiac echocardiography.

Background: Intracardiac echocardiography (ICE) is increasingly used to guide complex ablation procedures. This study aimed to assess the scar substrate of ventricular tachycardia (VT) by ICE in patients undergoing VT ablation.

Methods: In 22 patients undergoing VT ablation (10 ischemic, 12 nonischemic), the Biosense CARTOSOUND module (Biosense Webster, Diamond Bar, CA, USA) was used for three-dimensional reconstruction of the ventricles.

Impact of fluoroscopy unit on the accuracy of a magnet-based electroanatomic mapping and navigation system: an in vitro and in vivo validation study.

Introduction: During mapping and ablation procedures, the movement of large ferromagnetic items (i.e., fluoroscopic equipment) introduce heterogeneities in the electromagnetic field, which may affect the accuracy of electromagnet-based navigation.