Pathophysiology Of Arrhythmias Research Articles

Pathophysiology and treatment of adults with arrhythmias in the emergency department, part 1: Atrial arrhythmias.

This article, the first in a 2-part review, aims to reinforce current literature on the pathophysiology of cardiac arrhythmias and various evidence-based treatment approaches and clinical considerations in the acute care setting. Part 1 of this series focuses on atrial arrhythmias. Arrhythmias are prevalent throughout the world and a common presenting condition in the emergency department (ED) setting. Atrial fibrillation (AF) is the most common arrhythmia worldwide and expected to increase in prevalence. Treatment approaches have evolved over time with advances in catheter-directed ablation. Based on historic trials, heart rate control has been the long-standing accepted outpatient treatment modality for AF, but the use of antiarrhythmics is often still indicated for AF in the acute setting, and ED pharmacists should be prepared and poised to help in AF management. Other atrial arrhythmias include atrial flutter (AFL), atrioventricular nodal reentry tachycardia (AVNRT), and atrioventricular reentrant tachycardia (AVRT), which warrant distinction due to their unique pathophysiology and because each requires a different approach to utilization of antiarrhythmics. Atrial arrhythmias are typically associated with greater hemodynamic stability than ventricular arrhythmias but still require nuanced management according to patient subset and risk factors. Since antiarrhythmics can also be proarrhythmic, they may destabilize the patient due to adverse effects, many of which are the focus of black-box label warnings that can be overreaching and limit treatment options. Electrical cardioversion for atrial arrhythmias is generally successful and, depending on the setting and/or hemodynamics, often indicated. Atrial arrhythmias arise from a variety of mechanisms, and appropriate treatment depends on various factors. A firm understanding of physiological and pharmacological concepts serves as a foundation for exploring evidence supporting agents, indications, and adverse effects in order to provide appropriate care for patients.

The intercalated disc: a unique organelle for electromechanical synchrony in cardiomyocytes.

The intercalated disc (ID) is a highly specialized structure that connects cardiomyocytes via mechanical and electrical junctions. Although described in some detail by light microscopy in the 19th century, it was in 1966 that electron microscopy images showed that the ID represented apposing cell borders and provided detailed insight into the complex ID nanostructure. Since then, much has been learned about the ID and its molecular composition, and it has become evident that a large number of proteins, not all of them involved in direct cell-to-cell coupling via mechanical or gap junctions, reside at the ID. Furthermore, an increasing number of functional interactions between ID components are emerging, leading to the concept that the ID is not the sum of isolated molecular silos but an interacting molecular complex, an "organelle" where components work in concert to bring about electrical and mechanical synchrony. The aim of the present review is to give a short historical account of the ID's discovery and an updated overview of its composition and organization, followed by a discussion of the physiological implications of the ID architecture and the local intermolecular interactions. The latter will focus on both the importance of normal conduction of cardiac action potentials as well as the impact on the pathophysiology of arrhythmias.

Патогенетические механизмы развития фибрилляции предсердий, ассоциированной с новой коронавирусной инфекцией (обзор литературы)

The lack of research and formed ideas on the pathogenetic nature of arrhythmia associated with COVID-19 makes it difficult to assess and predict its development, as well as the choice of a strategy to prevent its formation. COVID-19 has a direct impact on the cardiovascular system, and in severe cases, it entails adverse consequences for the patient. The links of pathogenesis that form various disorders in the cardiovascular system are unclear and remain unexplored. The purpose of the study: based on the studied literature, to present and systematize possible pathophysiological mechanisms that can potentiate the development of various arrhythmias, including atrial fibrillation in patients who had a coronavirus infection. Materials and Methods. A literature review of scientific papers over the past 3 years was carried out in the search engines PubMed and eLIBRARY using keywords. For this meta-analysis, we used articles containing the evidence and experimental base on the most recent issues related to the epidemiology and pathophysiology of arrhythmias in patients who underwent a new coronavirus infection SARS-CoV-2 – atrial fibrillation. For the systematization of facts and a detailed study of literary sources in scientific work, general theoretical research methods were used: methods of analysis and synthesis. Results and Discussion: we present data of epidemiology, pathophysiology of the most frequent arrhythmias in patients who had a new coronavirus infection SARS-CoV-2 – atrial fibrillation. Conclusion. Transferred COVID-19 infection has a direct impact on the possibility of developing rhythm disturbances, which pose a significant danger to the life quality in patients with a new coronavirus infection.

Academic cardiac electrophysiologists' perspectives on sleep apnea care.

Obstructive sleep apnea syndrome (OSAS) is an important, modifiable risk factor in the pathophysiology of arrhythmias including atrial fibrillation (AF). The purpose of the study was to evaluate cardiac electrophysiologists' (EPs) perception of OSAS. We designed a 27-item online Likert scale-based survey instrument entailing several domains: (1) relevance of OSAS in EP practice, (2) OSAS screening and diagnosis, (3) perception on treatments for OSAS, (4) opinion on the OSAS care model. The survey was distributed to 89 academic EP programs in the USA and Canada. While the survey instrument questions refer to the term sleep apnea (SA), our discussion of the diagnosis, management, and research on the sleep disorder is more accurately described with the term OSAS. A total of 105 cardiac electrophysiologists from 49 institutions responded over a 9-month period. The majority of respondents agreed that sleep apnea (SA) is a major concern in their practice (94%). However, 42% reported insufficient education on SA during training. Many (58%) agreed that they would be comfortable managing SA themselves with proper training and education and 66% agreed cardiac electrophysiologists should become more involved in management. Half of EPs (53%) were not satisfied with the sleep specialist referral process. Additionally, a majority (86%) agreed that trained advanced practice providers should be able to assess and manage SA. Time constraints, lack of knowledge, and the referral process are identified as major barriers to EPs becoming more involved in SA care. We found that OSAS is widely recognized as a major concern for EP. However, incorporation of OSAS care in training and routine practice lags. Barriers to increased involvement include time constraints and education. This study can serve as an impetus for innovation in the cardiology OSAS care model.

The role of inflammation in the pathogenesis and treatment of arrhythmias.

The pathogenesis of arrhythmias is complex and multifactorial. The role of inflammation in the pathogenesis of both atrial and ventricular arrhythmias (VA) has been explored. However, developing successful pharmacotherapy regimens based on those pathways has proven more of a challenge. This narrative review provides an overview of five common arrhythmias impacted by inflammation, including atrial fibrillation (AF), myocardial infarction, arrhythmogenic cardiomyopathy, cardiac sarcoidosis, and QT prolongation, and the potential role for anti-inflammatory therapy in their management. We identified arrhythmias and arrhythmogenic disease states with the most evidence linking pathogenesis to inflammation and conducted comprehensive searches of United States National Library of Medicine MEDLINE® and PubMed databases. Although a variety of agents have been studied for the management of AF, primarily in an effort to reduce postoperative AF following cardiac surgery, no standard anti-inflammatory agents are used in clinical practice at this time. Although inflammation following myocardial infarction may contribute to the development of VA, there is no clear benefit with the use of anti-inflammatory agents at this time. Similarly, although inflammation is clearly linked to the development of arrhythmias in arrhythmogenic cardiomyopathy, data demonstrating a benefit with anti-inflammatory agents are limited. Cardiac sarcoidosis, an infiltrative disease eliciting an immune response, is primarily treated by immunosuppressive therapy and steroids, despite a lack of primary literature to support such regimens. In this case, anti-inflammatory agents are frequently used in clinical practice. The pathophysiology of arrhythmias is complex, and inflammation likely plays a role in both onset and duration, however, for most arrhythmias the role of pharmacotherapy targeting inflammation remains unclear.

Stem cells and cardiac arrhythmias.

Recent discoveries in the physiology and pathology of myocardial progenitor cells have allowed researchers to better understand a variety of cardiac pathologies and look at the pathophysiology of arrhythmias from a different perspective. Since the myocardium is composed of a syncytium of electrically interconnected cells, the process of incorporation of newly formed or imported cells into its structure is particularly important. Progenitor cells are stimulated by spontaneous electrical activity, a lengthy action potential, and easily induced triggering activity. All these can lead to arrhythmias development via the three classical mechanisms (reentrancy, automatism, or triggering activity). Transplanted stem cells can influence the electrophysiological properties of cardiomyocytes, thus creating a proarrhythmic substrate. The islets of unbound cells can form an anatomical block, causing unidirectional blockages and recurrent arrhythmias. Similarly, stem cells are capable of establishing heterotopic excitation foci with cardiac stimulatory activity. Finally, the paracrine factors produced by stem cells can also cause proarrhythmic effects. The review examines the factors that influence the proarrhythmic properties of administered stem cells and the mechanisms of arrhythmia development. The results indicate that further research should be carried out to establish the possible impact of stem cells on the development of arrhythmias.

The role of epicardial adipose tissue and autonomic nervous system in pathophysiology of cardiac arrhythmias

<p>The role of epicardial adipose tissue (EAT) in the pathogenesis and prognosis of cardiovascular diseases has been actively discussed. This review provides information regarding the main mechanisms by which EAT influences the pathophysiology of rhythm disturbances, such as atrial fibrillation and ventricular arrhythmias, as well as their relationship with chronic heart failure. The pathogenesis of cardiac arrhythmias is exceedingly complex. As such, the mechanism by which EAT influences arrhythmias and heart failure can vary according to the anatomy and type of arrhythmia, one of which involves the autonomic nervous system (ANS). Some studies have shown a good treatment effects by targeting EAT in atrial fibrillation, whereas others have found that EAT volume can be used to predict the efficacy of radiofrequency ablation, a method for treating atrial fibrillation and ventricular arrhythmias. However, no standards have yet been established for the use of EAT visualisation. Fundamental, translational and clinical research are needed to study the role of EAT and ANS in the pathogenesis of cardiovascular diseases.</p><p>Received 15 March 2021. Revised 25 April 2021. Accepted 26 April 2021.</p><p><strong>Funding:</strong> The work is supported by a grant of the Russian Science Foundation (project No. 17-75-20118).</p><p><strong>Conflict of interest:</strong> The authors declare no conflicts of interests.</p><p><strong>Contribution of the authors</strong><br />Conception and study design: D.V. Losik, N.A. Nikitin, S.M. Minin, A.B. Romanov, A.M. Chernyavskiy<br />Drafting the article: D.V. Losik, I.L. Mikheenko, E.V. Fisher, N.A. Nikitin<br />Critical revision of the article: D.V. Losik, I.L. Mikheenko, E.V. Fisher, N.A. Nikitin<br />Final approval of the version to be published: D.V. Losik, N.A. Nikitin, S.M. Minin, E.V. Fisher, I.L. Mikheenko, A.M. Chernyavskiy, A.B. Romanov</p>

Proton Quantum Tunneling: Influence and Relevance to Acidosis-Induced Cardiac Arrhythmias/Cardiac Arrest.

Acidosis and its associated pathologies predispose patients to develop cardiac arrhythmias and even cardiac arrest. These arrhythmias are assumed to be the result of membrane depolarization, however, the exact mechanism of depolarization during acidosis is not well defined. In our study, the model of quantum tunneling of protons is used to explain the membrane depolarization that occurs during acidosis. It is found that protons can tunnel through closed activation and inactivation gates of voltage-gated sodium channels Nav1.5 that are present in the membrane of cardiac cells. The quantum tunneling of protons results in quantum conductance, which is evaluated to assess its effect on membrane potential. The quantum conductance of extracellular protons is higher than that of intracellular protons. This predicts an inward quantum current of protons through the closed sodium channels. Additionally, the values of quantum conductance are influential and can depolarize the membrane potential according to the quantum version of the GHK equation. The quantum mechanism of depolarization is distinct from other mechanisms because the quantum model suggests that protons can directly depolarize the membrane potential, and not only through indirect effects as proposed by other mechanisms in the literature. Understanding the pathophysiology of arrhythmias mediated by depolarization during acidosis is crucial to treat and control them and to improve the overall clinical outcomes of patients.

Enhancing Team‐based Learning of Pharmacology Using Technology‐assisted Prerequisite Content Preparation

Multiple modalities are encouraged for creating and enhancing active learning in pharmacology pedagogy in pharmacy and medical schools. Team‐based learning engages students in a detailed pedagogy that begins with pre‐class self‐directed preparation, leading up to an in‐class individual Readiness Assurance Test (iRAT), which can be set by the program to mandate a certain level of competency by individual students. Typically, the iRAT is subsequently administered to the entire team as a team Readiness Assurance Test (tRAT). Based on the iRAT performance, a short lecture is delivered, emphasizing possible areas of class deficiency identified by the iRAT. Finally, students are asked to work in teams on application exercises. Although TBL is very effective in encouraging active participation in and out of class, team dynamics and other factors may lead to grade inflation when team scores mask and enhance the performance of borderline students. The California Northstate University College of Pharmacy employs a hybrid‐TBL approach to engage learners in an active learning environment, with multiple didactic courses in the first, second and third professional years (P1, P2, P3) of the Doctor of Pharmacy program. To enhance TBL delivery in our pharmacology courses, we prepared a series of video lectures using online technology to help students prepare for their iRATs and tRATs. These short “Info‐Blast” video lectures were typically 30–40 minutes in length, posted to YouTube, and emphasized the salient learning objectives, goals, terminology, and concepts included in prerequisite content required for upcoming pharmacology course lectures. Lectures included Pharmacogenomics, Biotechnology and An Introduction to Viruses in the Cell and Molecular Biology course (P1), and the pathophysiology of arrhythmia, the pharmacology of antiarrhythmic drugs, dyslipidemia, and dyslipidemia drugs in the Pathophysiology and Pharmacology II, Cardiovascular Sciences course (P2). The YouTube videos were accompanied by documents detailing self‐directed Learning Objectives and a Practice Question Workbook, all of which were posted at least two weeks ahead of the class. Students provided comments and suggestions verbally and via email which were strongly positive. Student iRAT scores and exam performance scores were captured using TurningPoint and ExamSoft and showed a positive correlation with the number of hours spent watching the video lectures. Among the advantages mentioned by students was the ease of access, the ability to repeat the lecture and detailed clarity added to expectations regarding outcomes and performance. One disadvantage mentioned was the extra time needed to prepare using the enhanced content, which we hope to address by using online technology such as InsertLearning to incorporate textual sources with the posted video lectures.Support or Funding InformationThe work was supported by the California Northstate University College of PharmacyThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Neuromodulation Approaches for Cardiac Arrhythmias: Recent Advances.

This review aims to describe the latest advances in autonomic neuromodulation approaches to treating cardiac arrhythmias, with a focus on ventricular arrhythmias. The increasing understanding of neuronal remodeling in cardiac diseases has led to the development and improvement of novel neuromodulation therapies targeting multiple levels of the autonomic nervous system. Thoracic epidural anesthesia, spinal cord stimulation, stellate ganglion modulatory therapies, vagal stimulation, renal denervation, and interventions on the intracardiac nervous system have all been studied in preclinical models, with encouraging preliminary clinical data. The autonomic nervous system regulates all the electrical processes of the heart and plays an important role in the pathophysiology of cardiac arrhythmias. Despite recent advances in the clinical application of cardiac neuromodulation, our comprehension of the anatomy and function of the cardiac autonomic nervous system is still limited. Hopefully in the near future, more preclinical data combined with larger clinical trials will lead to further improvements in neuromodulatory treatment for heart rhythm disorders.

Ventricular arrhythmia in chronic kidney disease patients.

Patients with chronic kidney disease (CKD) are susceptible to the occurrence of ventricular arrhythmias. The leading cause of death in dialysis patients is cardiac arrhythmias. The pathophysiology of arrhythmias in this population is complex and seems to be related to structural cardiac abnormalities caused by CKD, associated with several triggers, such as water and electrolyte disorders, hormonal conditions, arrhythmogenic drugs, and the dialysis procedure itself. Little is known about the clinical outcomes in CKD patients with asymptomatic ventricular arrhythmias. The results of treatments with anti-arrhythmic drugs and invasive devices are controversial in these patients, according to the available literature. The aim of this study was to review this often-neglected topic, which is of special importance in the CKD population.

The role of inflammation in cardiac arrhythmias pathophysiology

The pathophysiology of cardiac arrhythmias is highly complex. Inflammation causes electrophysiological changes that contribute to increased vulnerability of arrhythmias, a process known as electrical remodeling. There have been many biomarkers and proteins associated with pathophysiology of cardiac arrhythmias such as C‑reactive protein, tumor necrosis factor‑α, interleukin-2, interleukin-6, interleukin-8, and monocyte chemoattractant protein-1. At present large attention is paid to the clinical studies on the inflammation in the pathogenesis of the atrial fibrillation (AF), given the limited effectiveness of the current therapeutic approaches. Understanding the main process, molecular mechanism and signaling pathways underlying the pathogenesis of the inflammatory dilated cardiomyopathy (iDCM) will be essential for developing new effective therapeutic strategies.

162 Simultaneous measurement of calcium transients and electrical activity in murine cardiac tissue – a novel system for the study of cardiac arrhythmia

Introduction Cardiac arrhythmia is a major source of morbidity and mortality. More effective diagnosis and treatment requires a deeper understanding of the underlying pathophysiology of arrhythmia. Aberrant calcium handling is implicated in arrhythmogenesis. This study describes the development of a novel system to simultaneously measure calcium and electrophysiology at the tissue level. Existing research primarily employs single cell or whole heart models, but there is a translational gap between these levels of study which this model is intended to bridge. Methods A combined calcium fluorescence and solid-state electrical recording system was set up on an inverted microscope. Samples of murine tissue were loaded with a fluorescent calcium indicator dye (Fluo-4 AM). Intracellular calcium transients (elicited by electrical stimulation via external electrodes) were recorded by a CMOS digital camera, which measured emission light from samples excited with a narrow wavelength LED. The validity of this calcium imaging system was assessed by measuring the effects of decreased cycle length and pharmacological agents on calcium transients. Electrical and fluorescence data were then obtained simultaneously. Electrical data were recorded by contact electrodes in a multi-electrode array. Results Tissue was successfully loaded with fluorescent dye and calcium transients (observed as increases in green fluorescence) elicited by electrical stimulation were recorded. Calcium transient height and duration decreased by 19% (p Conclusion The current study describes the successful development of a calcium fluorescence imaging system and its integration into a multi-electrode array recording system. This experimental paradigm provides a novel multi-parametric tool for the study of arrhythmia in cardiac tissue.

Mitochondrial cardiomyopathy and related arrhythmias.

Mitochondrial dysfunction has been shown to be involved in the pathophysiology of arrhythmia, not only in inherited cardiomyopathy due to specific mutations in the mitochondrial DNA but also in acquired cardiomyopathy such as ischemic or diabetic cardiomyopathy. This article briefly discusses the basics of mitochondrial physiology and details the mechanisms generating arrhythmias due to mitochondrial dysfunction. The clinical spectrum of inherited and acquired cardiomyopathies associated with mitochondrial dysfunction is discussed followed by general aspects of the management of mitochondrial cardiomyopathy and related arrhythmia.

Catheter ablation of lone atrial fibrillation.

Atrial fibrillation is the most common sustained arrhythmia in clinical practice, associated with increased mortality, risk of stroke and heart failure, as well as the reduction of the quality of life. Atrial fibrillation may be encountered in young otherwise healthy individuals, due to the isolated electrophysiological disorder limited mostly to the pulmonary veins and posterior left atrial wall, or associated with the presence of advanced underlying heart disease and numerous cardiac and non-cardiac comorbidities with significant structural remodeling of the atrial myocardium. Due to limited efficacy and serious side effects of antiarrhythmic drugs, catheter ablation of atrial fibrillation, based on the pulmonary vein isolation for paroxysmal atrial fibrillation and adjunctive substrate modification for persistent atrial fibrillation, has emerged as an attractive and promissing alternative therapeutic option for selected patients with atrial fibrillation. In this review article, we discuss the electrophysiological left atrial abnormalities underlying lone atrial fibrillation and the role of pulmonary veins in pathophysiology of arrhythmia, and we summarize results of the studies on the long term outcome of catheter ablation of atrial fibrillation, as well as the studies on comparison of antiarrhythmic drugs with catheter ablation for treatment of atrial fibrillation. In addition, we present available data that provide better understanding of mechanisms, diagnosis, prevention and treatment of specific procedure-related complications and discuss current periprocedural anticoagulation strategies and their impact on the thromboembolic risk reduction.

Physical lineage tracing of cells contributing to the chicken cardiac conduction system

Purpose: Knowledge about the developmental origin of the cardiac conduction system (CCS) is important to understand the pathophysiology of arrhythmias. During early development, the heart consists of two bilateral plates of splanchnic mesoderm, which fuse to form the primary heart tube (PHT) derived from the first heart field. A large number of cells at the venous pole of the PHT constitute a different cardiac progenitor population, called the second heart field (SHF). This population of cells expresses the LIM-homeodomain transcription factor Islet-1 (Isl-1). The contribution of this SHF population to the developing CCS remains the subject of discussion. We explored the feasibility of in ovo physical lineage tracing in chicken embryos, to perform long-term follow-up of SHF-derived cells contributing to the CCS. Methods and results: Labeling was achieved by injecting a solution of two fluorescent dyes (DiI/5-TAMRA, Invitrogen) at HH stages 14-17, using a programmable microinjector (IM-300 Narishige, Japan). Right-sided labeling of the splanchnic mesoderm and the right cardinal vein was performed. Early embryos were sacrificed and analyzed 1-3 hours after injection (HH stages 14-17), and sectioned serially. Sections were stained for the myocardial marker cTnI, for Nkx2.5 which was expressed in both myocardium and mesenchyme and for Isl-1. Fluorescent labeling was found in the second heart field mesenchyme surrounding the sinus venosus and the right cardinal vein. In older stages of development (up to HH26), labeling of the developing sinus node and venous valves was found. Conclusions: Our results show that it is feasible to label the SHF and elements of the CCS in ovo, which makes it possible to trace the fate of these cells over a longer period of time. Follow-up after HH stage 26 is needed to determine whether the contributions of the SHF are not only found in the sinus node but also in the atrioventricular node, common bundle and bundle branches Future plans include earlier labeling experiments as well as contribution of the left-sided SHF and determination of the differentiation capacities of these SHF derived cells.

Adipocytokines modulate ionic currents – A key to lipotoxicity potentiated cardiac arrhythmia

Obesity with excessive fat was an important risk factor for the occurrence or progression of cardiac arrhythmia. As compared to abdominal fat, the amount of epicardial fat more correlates with the occurrences of atrial fibrillation, which suggests the distinctive arrhythmogenic effects of epicardial fat. Adipose tissue secrets numerous adipocytokines, thus epicardial fat may have more cardiac effects than other body fat [1]. Adipocytokines can enhance local inflammation and generate myocardial remodeling, which play a role in the pathophysiology of arrhythmia. Fatty infiltration or fatty metamorphosis can induce abnormal automaticity from degenerated myocardial cells. Adipose tissues also serve as obstacles for an activation wave front or by producing atrial fibrosis, which may interfere with atrial conduction and enhance the generation of reentry circuits. Lee et al. investigated the effects of adipocytokines from different body fats on delayed rectifier K outward currents (IKr) in cardiomyocytes [2]. In their study, H9c2 cells were treated with adipocytokine-free medium (the Adipo-free group), and with adipocytokines from rat epicardial (central fat group) or limb (peripheral fat group) fat tissues. They found that adipocytokines significantly decreased IKr in H9c2 cells, and IKr was more prominently decreased by adipocytokines from epicardial fat than from limb fat. Although the mechanisms were not fully elucidated, Lee et al. pointed out the direct electrophysiological effects of adipocytokines and also demonstrated stronger ionic effects of epicardial fat than other body fat. Decreased IKr can prolong action

Inherited calcium channelopathies in the pathophysiology of arrhythmias

Regulation of calcium flux in the heart is a key process that affects cardiac excitability and contractility. Degenerative diseases, such as coronary artery disease, have long been recognized to alter the physiology of intracellular calcium regulation, leading to contractile dysfunction or arrhythmias. Since the discovery of the first gene mutation associated with catecholaminergic polymorphic ventricular tachycardia (CPVT) in 2001, a new area of interest in this field has emerged--the genetic abnormalities of key components of the calcium regulatory system. Such anomalies cause a variety of genetic diseases characterized by the development of life-threatening arrhythmias in young individuals. In this Review, we provide an overview of the structural organization and the function of calcium-handling proteins and describe the mechanisms by which mutations determine the clinical phenotype. Firstly, we discuss mutations in the genes encoding the ryanodine receptor 2 (RYR2) and calsequestrin 2 (CASQ2). These proteins are pivotal to the regulation of calcium release from the sarcoplasmic reticulum, and mutations can cause CPVT. Secondly, we review defects in genes encoding proteins that form the voltage-dependent L-type calcium channel, which regulates calcium entry into myocytes. Mutations in these genes cause various phenotypes, including Timothy syndrome, Brugada syndrome, and early repolarization syndrome. The identification of mutations associated with 'calcium-handling diseases' has led to an improved understanding of the role of calcium in cardiac physiology.

The kidneys are a window to the heart

It is expected that an electrophysiologist's attention is singularly focused on the heart. There exists, however, an interplay between the heart and other organ systems that greatly affects not only the pathophysiology of cardiac arrhythmias but also the ability to effectively manage them. Perhaps nowhere is this relationship more profound than in patients with chronic kidney disease (CKD), in whom the elevated risk of sudden cardiac death (SCD) is increasingly apparent yet the approach to prevention muddled in uncertainty. Mild-to-moderate kidney dysfunction and the risk of sudden cardiac death in the setting of acute myocardial infarctionHeart RhythmVol. 9Issue 4PreviewAlthough end-stage renal disease is known to elevate the risk of sudden cardiac death (SCD), the role of less severe renal impairment in SCD is unclear. Full-Text PDF

SCN5A variants in Japanese patients with left ventricular noncompaction and arrhythmia

Left ventricular noncompaction (LVNC) is a genetically heterogenous disorder. Mutations in the human cardiac sodium channel alpha-subunit gene ( SCN5A) are involved in the pathophysiology of cardiac arrhythmias and cardiomyopathies. This study was performed to compare the frequency of SCN5A variants in LVNC patients with or without arrhythmias, and to investigate the relationship between variants and disease severity. DNA was isolated from the peripheral blood of 62 Japanese probands with LVNC, comprising 17 familial cases and 45 sporadic cases. Blood samples were screened for variants in SCN5A using single-strand conformational polymorphism analysis (SSCP) and DNA sequencing. Seven variants, rs6599230:G > A, c.453C > T, c.1141-3C > A, rs1805124:A > G (p.H558R), rs1805125:C > T (p.P1090L), c.3996C > T, and rs1805126:T > C were identified in 7 familial and 12 sporadic cases. The frequency of SCN5A variants was significantly higher in the patients with arrhythmias than those without (50% vs 7%: P = 0.0003), suggesting these variants represent a risk factor for arrhythmia and supporting the hypothesis that genes encoding ion channels are involved in LVNC pathophysiology. The LVNC patients with heart failure also had high occurence of SCN5A variants, suggesting the presence of SCN5A variants and/or arrhythmias increase the severity of LVNC.