Calcium handling abnormalities increase arrhythmia susceptibility in DMSXL myotonic dystrophy type 1 mice.

Background: Myotonic dystrophy type 1 (DM1) is a multiorgan disorder with significant cardiac involvement. ECG abnormalities, including arrhythmias, occur in 80 % of DM1 patients and are the second-most common cause of death after respiratory complications; however, the mechanisms underlying the arrhythmogenesis remain unclear. The objective of this study was to investigate the basis of the electrophysiological abnormalities in DM1 using the DMSXL mouse model.

Elevated Interleukin-6 Levels Are Associated With an Increased Risk of QTc Interval Prolongation in a Large Cohort of US Veterans.

Background: Although accumulating data indicate that IL-6 (interleukin-6) can promote heart rate-corrected QT interval (QTc) prolongation via direct and indirect effects on cardiac electrophysiology, current evidence comes from basic investigations and small clinical studies only. Therefore, IL-6 is still largely ignored in the clinical management of long-QT syndrome and related arrhythmias. The aim of this study was to estimate the risk of QTc prolongation associated with elevated IL-6 levels in a large population of unselected subjects.

Electrophysiological basis of cardiac arrhythmia in a mouse model of myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1) is a multisystemic genetic disorder caused by the increased number of CTG repeats in 3' UTR of gene. DM1 patients experience conduction abnormalities as well as atrial and ventricular arrhythmias with increased susceptibility to sudden cardiac death. The ionic basis of these electrical abnormalities is poorly understood.

Contribution of cytokine-mediated prolongation of QTc interval to the multi-hit theory of Torsade de Pointes.

Background: Torsade de pointes is a potentially lethal polymorphic ventricular tachyarrhythmia that can occur in the setting of long QT syndrome (LQTS). LQTS is multi-hit in nature and multiple factors combine their effects leading to increased arrhythmic risk. While hypokalemia and multiple medications are accounted for in LQTS, the arrhythmogenic role of systemic inflammation is increasingly recognized but often overlooked.

Unravelling Atrioventricular Block Risk in Inflammatory Diseases: Systemic Inflammation Acutely Delays Atrioventricular Conduction via a Cytokine-Mediated Inhibition of Connexin43 Expression.

Background Recent data suggest that systemic inflammation can negatively affect atrioventricular conduction, regardless of acute cardiac injury. Indeed, gap-junctions containing connexin43 coupling cardiomyocytes and inflammation-related cells (macrophages) are increasingly recognized as important factors regulating the conduction in the atrioventricular node. The aim of this study was to evaluate the acute impact of systemic inflammatory activation on atrioventricular conduction, and elucidate underlying mechanisms.

Obstructive Sleep Apnea and Cardiovascular Disease: A Scientific Statement From the American Heart Association.

Obstructive sleep apnea (OSA) is characterized by recurrent complete and partial upper airway obstructive events, resulting in intermittent hypoxemia, autonomic fluctuation, and sleep fragmentation. Approximately 34% and 17% of middle-aged men and women, respectively, meet the diagnostic criteria for OSA. Sleep disturbances are common and underdiagnosed among middle-aged and older adults, and the prevalence varies by race/ethnicity, sex, and obesity status.

Proton Pump Inhibitors Directly Block hERG-Potassium Channel and Independently Increase the Risk of QTc Prolongation in a Large Cohort of US Veterans.

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Voltage/Calcium Uncoupling Underlies Sustained Torsade de Pointes Ventricular Tachyarrhythmia in an Experimental Model of Long QT Syndrome.

Background: Clinical experience showed that the majority of Torsade de Pointes (TdP) ventricular tachyarrhythmia (VT) in patients with long QT syndrome (LQTS) are self-terminating (ST), but the few that are non-self-terminating (NST) are potentially fatal. A paramount issue in clinical arrhythmology is to understand the electrophysiological mechanism of ST vs. NST TdP VT.

Risk of QTc Interval Prolongation Associated With Circulating Anti-Ro/SSA Antibodies Among US Veterans: An Observational Cohort Study.

Background Anti-Sjögren's syndrome-related antigen A-antibodies (anti-Ro/SSA-antibodies) are responsible for a novel form of acquired long-QT syndrome, owing to autoimmune-mediated inhibition of cardiac human ether-a-go-go-related gene-potassium channels. However, current evidence derives only from basic mechanistic studies and relatively small sample-size clinical investigations. Hence, the aim of our study is to estimate the risk of QTc prolongation associated with the presence of anti-Ro/SSA-antibodies in a large population of unselected subjects.

Androgen Deprivation Therapy for Prostatic Cancer in Patients With Torsades de Pointes.

Background: Men normally have shorter heart rate-corrected QT interval (QTc) than women, at least in part due to accelerating effects of testosterone on ventricular repolarization. Accumulating data suggest that androgen-deprivation therapy (ADT) used for the treatment of prostatic cancer, may increase Torsades de Pointes (TdP) risk by prolonging QTc. However, the evidence for such an association is currently limited to few case reports, in most cases deriving from the analysis of uncontrolled sources such as pharmacovigilance databases.

Autoimmune Calcium Channelopathies and Cardiac Electrical Abnormalities.

Patients with autoimmune diseases are at increased risk for developing cardiovascular diseases, and abnormal electrocardiographic findings are common. Voltage-gated calcium channels play a major role in the cardiovascular system and regulate cardiac excitability and contractility. Particularly, by virtue of their localization and expression in the heart, calcium channels modulate pace making at the sinus node, conduction at the atrioventricular node and cardiac repolarization in the working myocardium.

Acquired Long QT Syndrome and Electrophysiology of Torsade de Pointes.

Congenital long QT syndrome (LQTS) has been the most investigated cardiac ion channelopathy. Although congenital LQTS remains the domain of cardiologists, cardiac electrophysiologists and specialised centres, the much more frequently acquired LQTS is the domain of physicians and other members of healthcare teams required to make therapeutic decisions. This paper reviews the electrophysiological mechanisms of acquired LQTS, its ECG characteristics, clinical presentation, and management.

Role of spatial dispersion of repolarization in reentry around a functional core versus reentry around a fixed anatomical core.

Introduction: Successful initiation of spiral wave reentry in the neonatal rat ventricular myocyte (NRVM) monolayer implicitly assumes the presence of spatial dispersion of repolarization (DR), which is difficult to quantify. We recently introduced a NRVM monolayer that utilizes anthopleurin-A to impart a prolonged plateau to the NRVM action potential. This was associated with a significant degree of spatial DR that lends itself to accurate quantification.

Autoimmune and inflammatory K channelopathies in cardiac arrhythmias: Clinical evidence and molecular mechanisms.

Cardiac K channelopathies account for a significant proportion of arrhythmias and sudden cardiac death (SCD) in subjects without structural heart disease. It is well recognized that genetic defects are key factors in many cases, and in practice, the term cardiac channelopathies currently coincides with inherited cardiac channelopathies. However, mounting evidence demonstrate that not only genetic alterations but also autoimmune and inflammatory factors can cause cardiac K-channel dysfunction and arrhythmias in the setting of a structurally normal heart.

Cryoballoon Ablation for the Treatment of Atrial Fibrillation: A Meta-analysis.

Background: Ablation therapy is the treatment of choice in antiarrhythmic drugrefractory atrial fibrillation (AF). It is performed by either cryoballoon ablation (CBA) or radiofrequency ablation. CBA is gaining popularity due to simplicity with similar efficacy and complication rate compared with RFA.

Interleukin-6 inhibition of hERG underlies risk for acquired long QT in cardiac and systemic inflammation.

Increased proinflammatory interleukin-6 (IL-6) levels are associated with acquired long QT-syndrome (LQTS) in patients with systemic inflammation, leading to higher risks for life-threatening polymorphic ventricular tachycardia such as Torsades de Pointes. However, the functional and molecular mechanisms of this association are not known. In most cases of acquired LQTS, the target ion channel is the human ether-á-go-go-related gene (hERG) encoding the rapid component of the delayed rectifier K current, IKr, which plays a critical role in cardiac repolarization.

Acquired long QT syndrome and torsade de pointes.

Since its initial description by Jervell and Lange-Nielsen in 1957, the congenital long QT syndrome (LQTS) has been the most investigated cardiac ion channelopathy. Although congenital LQTS continues to remain the domain of cardiologists, cardiac electrophysiologists, and specialized centers, the by far more frequent acquired drug-induced LQTS is the domain of all physicians and other members of the health care team who are required to make therapeutic decisions. This report will review the electrophysiological mechanisms of LQTS and torsade de pointes, electrocardiographic characteristics of acquired LQTS, its clinical presentation, management, and future directions in the field.

Sudden Cardiac Death in Ischemic Heart Disease: Pathophysiology and Risk Stratification.

Sudden cardiac death (SCD) accounts for approximately 360,000 deaths annually in the United States. Ischemic heart disease is the major cause of death in the general adult population. SCD can be due to arrhythmic or nonarrhythmic cardiac causes.

Congenital Long QT syndrome and torsade de pointes.

Since its initial description by Jervell and Lange-Nielsen in 1957, the congenital long QT syndrome (LQTS) has been the most investigated cardiac ion channelopathy. A prolonged QT interval in the surface electrocardiogram is the sine qua non of the LQTS and is a surrogate measure of the ventricular action potential duration (APD). Congenital as well as acquired alterations in certain cardiac ion channels can affect their currents in such a way as to increase the APD and hence the QT interval.

2017 ISHNE-HRS expert consensus statement on ambulatory ECG and external cardiac monitoring/telemetry.

Ambulatory ECG (AECG) is very commonly employed in a variety of clinical contexts to detect cardiac arrhythmias and/or arrhythmia patterns which are not readily obtained from the standard ECG. Accurate and timely characterization of arrhythmias is crucial to direct therapies that can have an important impact on diagnosis, prognosis or patient symptom status. The rhythm information derived from the large variety of AECG recording systems can often lead to appropriate and patient-specific medical and interventional management.

Systemic inflammation as a novel QT-prolonging risk factor in patients with torsades de pointes.

Objective: Increasing evidence indicates systemic inflammation as a new potential cause of acquired long QT syndrome (LQTS), via cytokine-mediated changes in cardiomyocyte ion channels. Torsade de pointes (TdP) is a life-threatening polymorphic ventricular tachycardia occurring in patients with LQTS, usually when multiple QT-prolonging factors are simultaneously present. Since classical risk factors cannot fully explain TdP events in a number of patients, we hypothesised that systemic inflammation may represent a currently overlooked risk factor contributing to TdP development in the general population.

2017 ISHNE-HRS expert consensus statement on ambulatory ECG and external cardiac monitoring/telemetry.

Ambulatory ECG (AECG) is very commonly employed in a variety of clinical contexts to detect cardiac arrhythmias and/or arrhythmia patterns which are not readily obtained from the standard ECG. Accurate and timely characterization of arrhythmias is crucial to direct therapies that can have an important impact on diagnosis, prognosis or patient symptom status. The rhythm information derived from the large variety of AECG recording systems can often lead to appropriate and patient-specific medical and interventional management.

Obstructive sleep apnea and arrhythmia: A systemic review.

There is a growing consensus in the scientific community that suggests a strong association between obstructive sleep apnea (OSA) and cardiovascular (CVD) conditions and events, including coronary artery disease, hypertension, arrhythmia, heart failure, and sudden cardiac death. We reviewed evidence on the relationship between OSA and arrhythmia. Our conclusion, based on our review of the literature, is that the evidence supports a strong link between OSA and cardiovascular mortality, which warrants treating OSA.

Cardiac Rhythm Device Threshold Testing Via Pulse Oxymetry.

Threshold testing of cardiac rhythm devices is essential to monitoring the proper functioning of such devices (1). However, the currently method of applying multiple ECG leads to the patient is burdensome and time consuming (2). We are presenting a completely new way to perform cardiac rhythm device threshold testing using pulse oximetry.