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JACC. Clinical Electrophysiology Jan 2023
Topics: Humans; Child; Cardiomyopathies; Heart Atria; Heart Block
PubMed: 36697202
DOI: 10.1016/j.jacep.2022.11.025 -
JACC. Clinical Electrophysiology Jan 2023Atrial standstill (AS) is a rare condition characterized by absence of electrical activity within the atria. Studies to date have been limited.
BACKGROUND
Atrial standstill (AS) is a rare condition characterized by absence of electrical activity within the atria. Studies to date have been limited.
OBJECTIVES
The authors sought to describe the clinical characteristics, genetics, and outcomes of patients with AS.
METHODS
This was a retrospective multicenter study of patients <18 years at AS diagnosis, defined as absence of atrial activity documented during an electrophysiology study, device placement, or noninvasive rhythm tracings and confirmed by echocardiogram. Patients with acquired disorders were excluded. Clinical details and genetic variants were recorded and analyzed.
RESULTS
Twenty patients were diagnosed at a median age of 6.6 years (IQR: 2.9-10.8 years). Arrhythmias included 16 (80%) with atrial/supraventricular arrhythmias and 8 (40%) with ventricular tachycardia, including 4 with cardiac arrests. A type 1 Brugada pattern was documented in 4. Pacemakers were implanted in 18 (90%). Although atrial leads were attempted in 15, only 4 achieved pacing at implantation. During a median follow-up of 6.9 years (IQR: 1.2-13.3 years), 7 (35%) had thromboembolic events. Of these, none had atrial pacing, 6 were not on anticoagulation, and 1 was on aspirin. Genetic testing identified SCN5A variants in 13 patients (65%). Analyses suggest SCN5A loss-of-function may be one mechanism driving AS. Ventricular arrhythmias and cardiac arrest were more commonly seen in patients with biallelic SCN5A variants.
CONCLUSIONS
AS may be associated with loss-of-function SCN5A variants. Patients demonstrate atrial and ventricular arrhythmias, and may present challenges during device placement. Patients without the capacity for atrial pacing are at risk for thromboembolic events and warrant anticoagulation.
Topics: Humans; Child; Child, Preschool; Atrial Fibrillation; Heart Atria; Heart Block; Heart Arrest; Anticoagulants
PubMed: 36435694
DOI: 10.1016/j.jacep.2022.08.022 -
Journal of Veterinary Cardiology : the... Apr 2019Pacemaker implantation is considered as a standard procedure for treatment of symptomatic bradycardia in both dogs and cats. Advanced second-degree and third-degree... (Review)
Review
Pacemaker implantation is considered as a standard procedure for treatment of symptomatic bradycardia in both dogs and cats. Advanced second-degree and third-degree atrioventricular blocks, sick sinus syndrome, persistent atrial standstill, and vasovagal syncope are the most common rhythm disturbances that require pacing to either alleviate clinical signs or prolong survival. Most pacemakers are implanted transvenously, using endocardial leads, but rarely epicardial leads may be necessary. To decide whether a patient is a candidate for pacing, as well as which pacing modality should be used, the clinician must have a clear understanding of the etiology, the pathophysiology, and the natural history of the most common bradyarrhythmias, as well as what result can be achieved by pacing patients with different rhythm disturbances. The goal of this review was, therefore, to describe the indications for pacing by evaluating the available evidence in both human and veterinary medicine. We described the etiology of bradyarrhythmias, clinical signs and electrocardiographic abnormalities, and the choice of pacing modality, taking into account how different choices may have different physiological consequences to selected patients. It is expected that this review will assist veterinarians in recognizing arrhythmias that may require permanent pacing and the risk-benefit of each pacing modality and its impact on outcome.
Topics: Animals; Bradycardia; Cardiac Pacing, Artificial; Cat Diseases; Cats; Dog Diseases; Dogs; Pacemaker, Artificial
PubMed: 30709617
DOI: 10.1016/j.jvc.2018.12.003 -
European Heart Journal. Case Reports Jun 2023Juvenile onset of extensive atrial electromechanical failure, including atrial standstill, is a rare disease entity that may precede ventricular cardiomyopathy. Genetic...
Juvenile-onset multifocal atrial arrhythmias, atrial standstill and compound heterozygosity of genetic variants in : sentinel event for evolving dilated cardiomyopathy-a case report.
BACKGROUND
Juvenile onset of extensive atrial electromechanical failure, including atrial standstill, is a rare disease entity that may precede ventricular cardiomyopathy. Genetic variants associated with early-onset atrioventricular (AV) cardiomyopathy are increasingly recognized.
CASE SUMMARY
A 16-year-old patient presented with atrial brady- and tachyarrhythmias and concomitant impaired atrial electromechanical function (atrial standstill). The atrial phenotype preceded the development of a predominantly right-sided AV dilated cardiomyopathy with pronounced myocardial fibrosis. A His-bundle pacemaker was installed for high-degree AV conduction block and sinus arrest. Using familial-based whole-exome sequencing, a missense mutation and a copy number variant deletion (compound heterozygosity) of the gene (involved in ribosomal RNA synthesis) were identified.
DISCUSSION
Juvenile onset of severe atrial electromechanical failure with atrial arrhythmias should prompt deep pheno- and genotyping and calls for vigilance for downstream cardiomyopathic deterioration.
PubMed: 37501913
DOI: 10.1093/ehjcr/ytad255 -
PloS One 2022The mouse is a useful preclinical species for evaluating disease etiology due to the availability of a wide variety of genetically modified strains and the ability to...
The mouse is a useful preclinical species for evaluating disease etiology due to the availability of a wide variety of genetically modified strains and the ability to perform disease-modifying manipulations. In order to establish an atrial filtration (AF) model in our laboratory, we profiled several commonly used murine AF models. We initially evaluated a pharmacological model of acute carbachol (CCh) treatment plus atrial burst pacing in C57BL/6 mice. In an effort to observe micro-reentrant circuits indicative of authentic AF, we employed optical mapping imaging in isolated mouse hearts. While CCh reduced atrial refractoriness and increased atrial tachyarrhythmia vulnerability, the left atrial (LA) excitation patterns were rather regular without reentrant circuits or wavelets. Therefore, the atrial tachyarrhythmia resembled high frequency atrial flutter, not typical AF per se. We next examined both a chronic angiotensin II (Ang II) infusion model and the surgical model of transverse aortic constriction (TAC), which have both been reported to induce atrial and ventricular structural changes that serve as a substrates for micro-reentrant AF. Although we observed some extent of atrial remodeling such as fibrosis or enlarged LA diameter, burst pacing-induced atrial tachyarrhythmia vulnerability did not differ from control mice in either model. This again suggested that an AF-like pathophysiology is difficult to demonstrate in the mouse. To continue searching for a valid murine AF model, we studied mice with a cardiac-specific deficiency (KO) in liver kinase B1 (Cardiac-LKB1), which has been reported to exhibit spontaneous AF. Indeed, the electrocardiograms (ECG) of conscious Cardiac-LKB1 KO mice exhibited no P waves and had irregular RR intervals, which are characteristics of AF. Histological evaluation of Cardiac-LKB1 KO mice revealed dilated and fibrotic atria, again consistent with AF. However, atrial electrograms and optical mapping revealed that electrical activity was limited to the sino-atrial node area with no electrical conduction into the atrial myocardium beyond. Thus, Cardiac-LKB1 KO mice have severe atrial myopathy or atrial standstill, but not AF. In summary, the atrial tachyarrhythmias we observed in the four murine models were distinct from typical human AF, which often exhibits micro- or macro-reentrant atrial circuits. Our results suggest that the four murine AF models we examined may not reflect human AF well, and raise a cautionary note for use of those murine models to study AF.
Topics: AMP-Activated Protein Kinases; Animals; Atrial Fibrillation; Atrial Flutter; Atrial Function, Left; Atrial Remodeling; Carbachol; Cardiac Pacing, Artificial; Disease Models, Animal; Electrocardiography; Mice; Mice, Inbred C57BL; Myocardium; Myocytes, Cardiac; Tachycardia, Ventricular
PubMed: 34995278
DOI: 10.1371/journal.pone.0256512 -
Biology Mar 2022Cardiolaminopathies are a heterogeneous group of disorders which are due to mutations in the genes encoding for nuclear lamins or their binding proteins. The whole... (Review)
Review
Cardiolaminopathies are a heterogeneous group of disorders which are due to mutations in the genes encoding for nuclear lamins or their binding proteins. The whole spectrum of cardiac manifestations encompasses atrial arrhythmias, conduction disturbances, progressive systolic dysfunction, and malignant ventricular arrhythmias. Despite the prognostic significance of cardiac involvement in this setting, the current recommendations lack strong evidence. The aim of our work was to systematically review the current data on the main cardiovascular outcomes in cardiolaminopathies. We searched PubMed/Embase for studies focusing on cardiovascular outcomes in mutation carriers (atrial arrhythmias, ventricular arrhythmias, sudden cardiac death, conduction disturbances, thromboembolic events, systolic dysfunction, heart transplantation, and all-cause and cardiovascular mortality). In total, 11 studies were included (1070 patients, mean age between 26-45 years, with follow-up periods ranging from 2.5 years up to 45 ± 12). When available, data on the -mutated population were separately reported (40 patients). The incidence rates (IR) were individually assessed for the outcomes of interest. The IR for atrial fibrillation/atrial flutter/atrial tachycardia ranged between 6.1 and 13.9 events/100 pts-year. The IR of atrial standstill ranged between 0 and 2 events/100 pts-year. The IR for malignant ventricular arrhythmias reached 10.2 events/100 pts-year and 15.6 events/100 pts-year for appropriate implantable cardioverter-defibrillator (ICD) interventions. The IR for advanced conduction disturbances ranged between 3.2 and 7.7 events/100 pts-year. The IR of thromboembolic events reached up to 8.9 events/100 pts-year. Our results strengthen the need for periodic cardiological evaluation focusing on the early recognition of atrial arrhythmias, and possibly for the choice of preventive strategies for thromboembolic events. The frequent need for cardiac pacing due to advanced conduction disturbances should be counterbalanced with the high risk of malignant ventricular arrhythmias that would justify ICD over pacemaker implantation.
PubMed: 35453731
DOI: 10.3390/biology11040530 -
Biochimica Et Biophysica Acta Jul 2016The SCN5A gene encodes the alpha-subunit of the Nav1.5 ion channel protein, which is responsible for the sodium inward current (INa). Since 1995 several hundred... (Review)
Review
The SCN5A gene encodes the alpha-subunit of the Nav1.5 ion channel protein, which is responsible for the sodium inward current (INa). Since 1995 several hundred mutations in this gene have been found to be causative for inherited arrhythmias including Long QT syndrome, Brugada syndrome, cardiac conduction disease, sudden infant death syndrome, etc. As expected these syndromes are primarily electrical heart diseases leading to life-threatening arrhythmias with an "apparently normal heart". In 2003 a new form of dilated cardiomyopathy was identified associated with mutations in the SCN5A gene. Recently mutations have been also found in patients with arrhythmogenic right ventricular cardiomyopathy and atrial standstill. The purpose of this review is to outline and analyze the following four topics: 1) SCN5A genetic variants linked to different cardiomyopathies; 2) clinical manifestations of the known mutations; 3) possible molecular mechanisms of myocardial remodeling; and 4) the potential implications of gene-specific treatment for those disorders. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.
Topics: Action Potentials; Animals; Cardiomyopathies; Genetic Markers; Genetic Predisposition to Disease; Genetic Therapy; Heart Rate; Humans; Mutation; Myocytes, Cardiac; NAV1.5 Voltage-Gated Sodium Channel; Phenotype; Risk Factors; Ventricular Remodeling
PubMed: 26916278
DOI: 10.1016/j.bbamcr.2016.02.014 -
Circulation Journal : Official Journal... Jul 2016Atrial standstill is one of the important clinical consequences on the heart in severe hyperkalemia, but it occurs even at modest potassium ion elevation. The extent to... (Clinical Trial)
Clinical Trial
BACKGROUND
Atrial standstill is one of the important clinical consequences on the heart in severe hyperkalemia, but it occurs even at modest potassium ion elevation. The extent to which other factors might potentiate the electrocardiographic changes induced by hyperkalemia remains unclear.
METHODS AND RESULTS
This was a retrospective review of the data on 12,639 hospital admissions over a 15-year period. A total of 778 patients with hyperkalemia were identified, 28 of whom had atrial standstill, and had several parameters measured prior to any treatment of hyperkalemia. Patients with atrial standstill were older (P=0.036), had lower diastolic blood pressure (DBP; P<0.0001) and serum sodium concentration (P<0.0001), higher serum potassium (P<0.0001), and high prevalence of angiotensin converting-enzyme inhibitor (ACEI; P=0.009) or mineral corticoid receptor (MR)-blocker (P=0.006), compared with those without atrial standstill. On multivariate logistic regression, DBP <67 mmHg (P=0.006), serum sodium ion <135 mmol/L (P=0.006) and serum potassium ion >6.1 mmol/L (P=0.018) were identified as independent indicators of atrial standstill, after adjusting for sex, age, chronic maintenance hemodialysis, diuretics use or ACEI/angiotensin receptor blocker and MR blocker.
CONCLUSIONS
Hyponatremia and decline in DBP are associated with atrial standstill in patients with hyperkalemia. (Circ J 2016; 80: 1781-1786).
Topics: Aged; Aged, 80 and over; Arrhythmias, Cardiac; Blood Pressure; Female; Humans; Hyperkalemia; Hyponatremia; Male; Middle Aged; Retrospective Studies
PubMed: 27301330
DOI: 10.1253/circj.CJ-16-0283 -
International Heart Journal Jan 2019Emery-Dreifuss muscular dystrophy (EDMD) is a group of hereditary muscular dystrophy syndrome caused by deficiency of genes encoding nuclear envelope proteins. Patients... (Review)
Review
Emery-Dreifuss muscular dystrophy (EDMD) is a group of hereditary muscular dystrophy syndrome caused by deficiency of genes encoding nuclear envelope proteins. Patients having EDMD show the triad of muscle dystrophy, joint contracture, and cardiac disease. In almost all patients, cardiac involvement is prevalent and is the most severe aspect of EDMD. Cardiac disease is predominantly shown by conduction defects, atrial fibrillation/flutter, and atrial standstill. Sudden death and heart failure because of left ventricular dysfunction are important causes of mortality, particularly in those patients that have the LMNA mutation. Medical treatment of EDMD is limited to addressing symptoms and ambulation support; moreover, pacemaker implantation is necessary when there are severe conduction defects and bradycardia occurs. Note that automated defibrillation devices may be considered for those patients who have a high risk of sudden death, rate, or rhythm control. Also, anticoagulation should be initiated in those patients who have atrial fibrillation/flutter. Thus, for optimal management, a multidisciplinary approach is required.
Topics: Abnormalities, Multiple; Anticoagulants; Atrial Fibrillation; Cardiomyopathies; Cleft Palate; Contracture; Death, Sudden; Female; Genetic Diseases, Inborn; Heart Atria; Heart Block; Heart Diseases; Humans; Hydrocephalus; Interdisciplinary Communication; Limb Deformities, Congenital; Male; Muscular Dystrophies; Muscular Dystrophy, Emery-Dreifuss; Pacemaker, Artificial; Ventricular Dysfunction, Left
PubMed: 30518714
DOI: 10.1536/ihj.17-604 -
Progress in Biophysics and Molecular... 2008Both gain- and loss-of-function mutations in the SCN5A gene, which encodes the alpha-subunit of the cardiac voltage-gated Na+ channel Na(v)1.5, are well established to... (Review)
Review
Both gain- and loss-of-function mutations in the SCN5A gene, which encodes the alpha-subunit of the cardiac voltage-gated Na+ channel Na(v)1.5, are well established to underlie hereditary arrhythmic syndromes (cardiac channelopathies) such as the type 3 long QT syndrome, cardiac conduction diseases, Brugada syndrome, sick sinus syndrome, atrial standstill and numerous overlap syndromes. Although patch-clamp studies in heterologous expression systems have provided important information to understand the genotype-phenotype relationships of these diseases, they could not clarify how mutations can be responsible for such a large spectrum of diseases, the late age of onset or the progressiveness of some of them, and for the overlapping syndromes. Genetically modified mice rapidly appeared as promising tools for understanding the pathophysiological sequence of cardiac SCN5A-related channelopathies and several mouse models have been established. Here, we review the results obtained on these models that, for most of them, convincingly recapitulate the clinical phenotypes of the patients but that also have their own limitations. Mouse models turn out to be powerful tools to elucidate the pathophysiological mechanisms of SCN5A-related diseases and offer the opportunity to investigate the cellular consequences of SCN5A mutations such as the remodelling of other gene expression that might participate in the overall phenotype and explain some of the differences among patients. Finally, they also constitute useful tools for future studies addressing as yet unanswered questions, such as the role of genetic and environmental modifiers on cardiac conduction and repolarisation.
Topics: Animals; Arrhythmias, Cardiac; Brugada Syndrome; Disease Models, Animal; Humans; Long QT Syndrome; Mice; Mice, Knockout; Mice, Mutant Strains; Mice, Transgenic; Muscle Proteins; Mutation; NAV1.5 Voltage-Gated Sodium Channel; Sodium Channels; Voltage-Gated Sodium Channel beta-1 Subunit
PubMed: 19041666
DOI: 10.1016/j.pbiomolbio.2008.10.012