scholarly journals The Link Between Sex Hormones and Susceptibility to Cardiac Arrhythmias: From Molecular Basis to Clinical Implications

2021 ◽  
Vol 8 ◽  
Author(s):  
Sarah Costa ◽  
Ardan M. Saguner ◽  
Alessio Gasperetti ◽  
Deniz Akdis ◽  
Corinna Brunckhorst ◽  
...  
Keyword(s):  
Sex Hormones ◽  
Cardiac Arrhythmias ◽  
Molecular Basis ◽  
Conduction System ◽  
Cardiac Conduction ◽  
Clinical Implications ◽  
Cardiac Ion Channels ◽  
Increased Risk ◽  
Qt Syndrome ◽  
Underlying Mechanisms

It is well-known that gender is an independent risk factor for some types of cardiac arrhythmias. For example, males have a greater prevalence of atrial fibrillation and the Brugada Syndrome. In contrast, females are at increased risk for the Long QT Syndrome. However, the underlying mechanisms of these gender differences have not been fully identified. Recently, there has been accumulating evidence indicating that sex hormones may have a significant impact on the cardiac rhythm. In this review, we describe in-depth the molecular interactions between sex hormones and the cardiac ion channels, as well as the clinical implications of these interactions on the cardiac conduction system, in order to understand the link between these hormones and the susceptibility to arrhythmias.

scholarly journals Progressive cardiac arrhythmias and ECG abnormalities in the Huntington’s disease BACHD mouse model

2019 ◽  
Vol 29 (3) ◽  
pp. 369-381
Author(s):  
Yujie Zhu ◽  
Isaac Shamblin ◽  
Efrain Rodriguez ◽  
Grace E Salzer ◽  
Lita Araysi ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Cardiac Arrhythmias ◽  
Structural Changes ◽  
Artificial Chromosome ◽  
Conduction System ◽  
Cardiac Conduction ◽  
Cardiac Conduction System ◽  
Increased Risk ◽  
Ecg Abnormalities

Abstract Huntington’s disease (HD) is a dominantly inherited neurodegenerative disease. There is accumulating evidence that HD patients have increased prevalence of conduction abnormalities and compromised sinoatrial node function which could lead to increased risk for arrhythmia. We used mutant Huntingtin (mHTT) expressing bacterial artificial chromosome Huntington’s disease mice to determine if they exhibit electrocardiogram (ECG) abnormalities involving cardiac conduction that are known to increase risk of sudden arrhythmic death in humans. We obtained surface ECGs and analyzed arrhythmia susceptibility; we observed prolonged QRS duration, increases in PVCs as well as PACs. Abnormal histological and structural changes that could lead to cardiac conduction system dysfunction were seen. Finally, we observed decreases in desmosomal proteins, plakophilin-2 and desmoglein-2, which have been reported to cause cardiac arrhythmias and reduced conduction. Our study indicates that mHTT could cause progressive cardiac conduction system pathology that could increase the susceptibility to arrhythmias and sudden cardiac death in HD patients.

The cardiac conduction system in Hurler syndrome: pathological features and clinical implications

1992 ◽  
Vol 2 (2) ◽  
pp. 196-199
Author(s):  
Louis Tsun-cheung Chow ◽  
Wing-Hing Chow
Keyword(s):  
Sinus Node ◽  
Fibrous Tissue ◽  
Conduction System ◽  
Cardiac Conduction ◽  
Cardiac Conduction System ◽  
Clinical Implications ◽  
Hurler Syndrome ◽  
Pathological Features ◽  
Hydropic Degeneration ◽  
Dense Fibrous Tissue

SummaryWe studied the cardiac conduction system in a case of Hurler syndrome. There was dense fibrosis of the supporting matrix of the sinus node and accumulation of mucopolysaccharide in the nodal cells. The bundle branches showed prominent hydropic degeneration, being encased and punctuated by dense fibrous tissue. These changes in the conduction system may predispose to the development of arrhythmias, accounting for the sudden deaths in Hurler syndrome.

Abstract MP239: Hippo Signaling Pathway Maintains Homeostasis Of The Cardiac Conduction System

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Mingjie Zheng ◽  
Jun Wang
Keyword(s):  
Signaling Pathway ◽  
Calcium Homeostasis ◽  
Cardiac Arrhythmias ◽  
Critical Role ◽  
Conduction System ◽  
Conditional Knockout ◽  
Cardiac Conduction ◽  
Cardiac Conduction System ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway

The cardiac conduction system (CCS) is required for initiating and maintaining regular rhythmic heartbeats. The fundamental Hippo signaling pathway plays critical roles in the heart, yet its role in the CCS remains largely unknown. Here, we found that conditional knockout (CKO) of Hippo signaling kinases Lats1 and Lats2 in the CCS using Hcn4 CreERT2 , led to cardiac arrhythmias in adult mice. Compared with controls, Lats1/2 CKO mutant mice had disrupted calcium homeostasis, increased fibrosis and more fibroblast proliferation in the sinoatrial node. Deletion of the Hippo signaling effectors Yap and Taz in the CCS rescued phenotypes caused by Lats1/2 deletion, and these mice had rescued sinus rhythm and reduced fibrosis, which indicated that Lats1/2 function through Yap and Taz in CCS. Our Cleavage Under Targets and Tagmentation (CUT&Tag)-sequencing using Yap antibody followed by RNA-Seq revealed that Yap directly regulates calcium homeostasis genes such as Ryr2 and fibrosis induction genes such as TGF-β family. Further, we discovered that miR-17-92 represses Hippo signaling by directly suppressing Lats2 expression. miR-17-92 CKO in the CCS led to increased Hippo signaling activity and cardiac arrhythmias, indicating that a fine-tuned level of Hippo signaling is critical for CCS homeostasis. Together, our findings reveal the critical role of a miR-Hippo-Yap genetic pathway in maintaining CCS homeostasis.

scholarly journals Short QT Syndrome – Review of Diagnosis and Treatment

2014 ◽  
Vol 3 (2) ◽  
pp. 76 ◽  
Author(s):  
Boris Rudic ◽  
Rainer Schimpf ◽  
Martin Borggrefe ◽  
◽  
◽  
...  
Keyword(s):  
Ventricular Arrhythmias ◽  
Genetic Basis ◽  
Current Data ◽  
Short Qt Syndrome ◽  
First Line Therapy ◽  
Cardiac Ion Channels ◽  
Increased Risk ◽  
History Of ◽  
Qt Syndrome ◽  
Electrocardiogram Ecg

Short QT syndrome (SQTS) is an inherited cardiac channelopathy characterised by an abnormally short QT interval and increased risk for atrial and ventricular arrhythmias. Diagnosis is based on the evaluation of symptoms (syncope or cardiac arrest), family history and electrocardiogram (ECG) findings. Mutations of cardiac ion channels responsible for the repolarisation orchestrate electrical heterogeneity during the action potential and provide substrate for triggering and maintaining of tachyarrhythmias. Due to the malignant natural history of SQTS, implantable cardioverter defibrillator (ICD) is the first-line therapy in affected patients. This review summarises current data and addresses the genetic basis and clinical features of SQTS.

Molecular Basis of Arrhythmias Associated with the Cardiac Conduction System

2013 ◽  
pp. 19-34 ◽  
Author(s):  
Sunil Jit R. J. Logantha ◽  
Andrew J. Atkinson ◽  
Mark R. Boyett ◽  
Halina Dobrzynski
Keyword(s):  
Molecular Basis ◽  
Conduction System ◽  
Cardiac Conduction ◽  
Cardiac Conduction System

scholarly journals Arrhythmogenesis by single ectopic beats originating in the Purkinje system

2010 ◽  
Vol 299 (4) ◽  
pp. H1002-H1011 ◽  
Author(s):  
Makarand Deo ◽  
Patrick M. Boyle ◽  
Albert M. Kim ◽  
Edward J. Vigmond
Keyword(s):  
Ventricular Myocytes ◽  
Conduction System ◽  
Cardiac Conduction ◽  
Ectopic Beat ◽  
Tissue Conductivity ◽  
Purkinje System ◽  
Ectopic Beats ◽  
Reentrant Arrhythmia ◽  
Underlying Mechanisms

Cells in the Purkinje system (PS) are known to be more vulnerable than ventricular myocytes to secondary excitations during the action potential (AP) plateau or repolarization phases, known as early afterdepolarizations (EADs). Since myocytes have a lower intrinsic AP duration than the PS cells to which they are coupled, EADs occurring in distal branches of the PS are more likely to result in propagating ectopic beats. In this study, we use a computer model of the rabbit ventricles and PS to investigate the consequences of EADs occurring at different times and places in the cardiac conduction system. We quantify the role of tissue conductivity and excitability, as well as interaction with sinus excitation, in determining whether an EAD-induced ectopic beat will establish reentrant activity. We demonstrate how a single ectopic beat arising from an EAD in the distal PS can give rise to reentrant arrhythmia; in contrast, EADs in the proximal PS were unable to initiate reentry. Clinical studies have established the PS as a potential substrate for reentry, but the underlying mechanisms of these types of disorder are not well understood, nor are conditions leading to their development clearly defined; this work provides new insights into the role of the PS in such circumstances. Our findings indicate that simulated EADs in the distal PS can induce premature beats, which can lead to the tachycardias involving the conduction system due to interactions with sinus activity or impaired myocardial conduction velocity.

scholarly journals Arrhythmic risk during pregnancy and postpartum in patients with long QT syndrome

2021 ◽  
Author(s):  
Babken Asatryan ◽  
Marina Rieder ◽  
Alessandro Castiglione ◽  
Katja E. Odening
Keyword(s):  
Sex Hormones ◽  
Long Qt Syndrome ◽  
Cardiac Arrhythmias ◽  
Postpartum Period ◽  
Genetic Disorder ◽  
Adult Women ◽  
Primary Role ◽  
Long Qt ◽  
Pregnancy And Postpartum ◽  
Qt Syndrome

AbstractCongenital long QT syndrome (LQTS) is a genetic disorder characterized by a prolonged QT interval in the surface electrocardiogram (ECG) that predisposes affected individuals to arrhythmic syncope, ventricular torsades-de-pointes, and sudden cardiac death at a young age. Investigations of large patient cohorts revealed sex-related differences in the LQTS phenotype. Adult women with LQTS are at higher risk for cardiac arrhythmias than are adult men with LQTS. Sex hormones are thought to play the primary role for these gender differences. Clinical experience and translational studies indicated that females with LQTS have a lower risk for cardiac arrhythmias during pregnancy and elevated risk in the postpartum period due to contrasting effects of estradiol and progesterone, as well as postpartum hormones on the action potential and arrhythmia substrate. However, this pro- or anti-arrhythmic potential of hormones varies depending on the underlying genotype, partly since sex hormones have distinct effects on different (affected) cardiac ion channels. Thus, a comprehensive evaluation of women with LQTS prior to and during pregnancy, during labor, and in the postpartum period with consideration of the patient’s disease- and gene-specific risk factors is essential to providing precision management in this patient group. This review discusses the current understanding of hormonal influences in LQTS and provides practical guidance for the optimal management of LQTS patients during pregnancy, delivery, and the postpartum period.

scholarly journals Screening for circulating miR-208a and -b in different cardiac arrhythmias of dogs

2018 ◽  
Vol 62 (3) ◽  
pp. 359-363 ◽  
Author(s):  
Agnieszka Noszczyk-Nowak ◽  
Maciej Zacharski ◽  
Marcin Michałek
Keyword(s):  
Cardiac Arrhythmias ◽  
High Sensitivity ◽  
Tissue Expression ◽  
Heart Tissue ◽  
Treatment Monitoring ◽  
Conduction System ◽  
Cardiac Conduction ◽  
Canine Heart ◽  
Serum Samples ◽  
Novel Mirna

AbstractIntroductionIn recent years, the high sensitivity and specificity of novel miRNA biomarkers have been utilised for early diagnosis and treatment monitoring of various diseases. Previous reports showed that abnormal expression of miR-208 in mice resulted in the development of an aberrant cardiac conduction system and consecutive arrhythmias. On the other hand, a study on infarcted human heart tissue showed upregulation of miR-208a in subjects with ventricular tachyarrhythmias compared to healthy controls. We prospectively investigated the expression of miR-208a and -208b in the serum of dogs presenting different cardiac arrhythmias.Material and MethodsA total of 28 dogs with atrial fibrillation (n = 8), ventricular premature contractions (n=6), conduction system disturbances (n = 7), and free of heart conditions (as controls) (n = 7) were enrolled in the study. Total RNA was extracted from serum samples and miR-208a and -b, miR-16 as well as a cel-miR-39-5p spike-in were analysed with qPCR and ddPCR.ResultsmiR-208a and miR-208b were not expressed in any of the samples. The calculated ddPCR miR-16 relative expression (normalised with cel-miR-39 spike-in) showed a good correlation (r = 0.82; P < 0.001) with the qPCR results.ConclusionThis outcome warrants further investigation, possibly focusing on tissue expression of miR-208 in the canine heart.

Hereditary Long QT Syndrome Associated with Cardiac Conduction System Disease

1989 ◽  
Vol 12 (3) ◽  
pp. 479-485 ◽  
Author(s):  
ARNOLD J. GREENSPON ◽  
GREGORY A. KIDWELL ◽  
LINDA D. BARRASSE ◽  
SCOTT E. HESSEN ◽  
MICHAEL GIUDICI
Keyword(s):  
Long Qt Syndrome ◽  
Conduction System ◽  
Cardiac Conduction ◽  
Cardiac Conduction System ◽  
Long Qt ◽  
System Disease ◽  
Conduction System Disease ◽  
Qt Syndrome

Expression and coassociation of ERG1, KCNQ1, and KCNE1 potassium channel proteins in horse heart

2002 ◽  
Vol 283 (1) ◽  
pp. H126-H138 ◽  
Author(s):  
Melissa R. Finley ◽  
Yan Li ◽  
Fei Hua ◽  
James Lillich ◽  
Kathy E. Mitchell ◽  
...  
Keyword(s):  
Cardiac Arrhythmias ◽  
Molecular Basis ◽  
Cardiac Tissue ◽  
Delayed Rectifier ◽  
Related Gene ◽  
Rt Pcr ◽  
Delayed Rectifier Current ◽  
Cardiac Action ◽  
Qt Syndrome ◽  
Α Subunits

In dogs and in humans, potassium channels formed by ether-a-go-go-related gene 1 protein ERG1 (KCNH2) and KCNQ1 α-subunits, in association with KCNE β-subunits, play a role in normal repolarization and may contribute to abnormal repolarization associated with long QT syndrome (LQTS). The molecular basis of repolarization in horse heart is unknown, although horses exhibit common cardiac arrhythmias and may receive drugs that induce LQTS. In horse heart, we have used immunoblotting and immunostaining to demonstrate the expression of ERG1, KCNQ1, KCNE1, and KCNE3 proteins and RT-PCR to detect KCNE2 message. Peptide N-glycosidase F-sensitive forms of horse ERG1 (145 kDa) and KCNQ1 (75 kDa) were detected. Both ERG1 and KCNQ1 coimmunoprecipitated with KCNE1. Cardiac action potential duration was prolonged by antagonists of either ERG1 (MK-499, cisapride) or KCNQ1/KCNE1 (chromanol 293B). Patch-clamp analysis confirmed the presence of a slow delayed rectifier current. These data suggest that repolarizing currents in horses are similar to those of other species, and that horses are therefore at risk for acquired LQTS. The data also provide unique evidence for coassociation between ERG1 and KCNE1 in cardiac tissue.

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