BOOK
Cardiac Sodium Channel Disorders, An Issue of Cardiac Electrophysiology Clinics, E-Book
(2015)
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Book Details
Abstract
The sodium channel, a ubiquitous member of the cardiac, neural, and muscular conduction systems, has been implicated in the pathogenesis of an array of human diseases. Mutations associated with the cardiac sodium channel are responsible for a wide spectrum of disorders. The cardiac sodium channel and associated disorders are comprehensively examined in this issues of the Cardiac Electrophysiology Clinics.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | Cover | ||
| Cardiac Sodium Channel Disorders\r | i | ||
| Copyright\r | ii | ||
| Contributors | iii | ||
| Contents | vii | ||
| Cardiac Electrophysiology Clinics\r | xii | ||
| Foreword\r | xiii | ||
| Preface\r | xv | ||
| Role of the Cardiac Sodium Current in Excitability and Conduction | 657 | ||
| Key points | 657 | ||
| History of sodium current measurements in the heart | 657 | ||
| Na+ inward current and the action potential upstroke in heart | 658 | ||
| Na+ inward current and the safety factor of propagation | 658 | ||
| Na+ inward current, propagation slowing, and propagation block | 658 | ||
| Discontinuous propagation depends on interaction between depolarizing current flow (INa, ICa,L), tissue structure, and cell ... | 660 | ||
| Cell-to-cell propagation across gap junctions versus ephaptic impulse transmission: the role of the Na+ inward current | 661 | ||
| Summary | 663 | ||
| References | 663 | ||
| Role of Rare and Common Genetic Variation in SCN5A in Cardiac Electrical Function and Arrhythmia | 665 | ||
| Key points | 665 | ||
| Introduction | 665 | ||
| Rare SCN5A coding-region variants underlying the inherited cardiac diseases | 665 | ||
| Long QT Syndrome | 665 | ||
| Conduction Disease | 666 | ||
| Brugada Syndrome | 666 | ||
| Sick Sinus Syndrome | 666 | ||
| Sudden Infant Death Syndrome | 666 | ||
| Atrial Fibrillation | 668 | ||
| Dilated Cardiomyopathy | 668 | ||
| Multifocal Ectopic Purkinje-related Premature Contractions | 668 | ||
| Overlap Syndromes | 669 | ||
| Challenges in interpretation of SCN5A genetic test results | 669 | ||
| Reduced penetrance and variable disease expression | 669 | ||
| Common variants in the SCN5A coding region | 669 | ||
| Common variants in the SCN5A noncoding region | 670 | ||
| Summary | 672 | ||
| References | 672 | ||
| NaV1.5 and Regulatory β Subunits in Cardiac Sodium Channelopathies | 679 | ||
| Key points | 679 | ||
| Topology of voltage-gated sodium channel α and β subunits | 679 | ||
| Localization of voltage-gated sodium channel α and β subunits in the heart | 680 | ||
| Tissue Distribution | 680 | ||
| Subcellular Localization | 680 | ||
| Voltage-gated sodium channels exist as macromolecular complexes in heart | 680 | ||
| How are cardiac voltage-gated sodium channels modulated in vitro? | 681 | ||
| Mutations in genes encoding voltage-gated sodium channel β subunits are linked to cardiac disease | 682 | ||
| SCN1B | 682 | ||
| Ventricular arrhythmias and cardiac conduction system defects | 682 | ||
| Atrial arrhythmias | 684 | ||
| Animal models of SCN1B mutations | 684 | ||
| SCN2B | 684 | ||
| SCN3B | 685 | ||
| Ventricular arrhythmia | 685 | ||
| Atrial arrhythmias | 685 | ||
| Animal models of SCN3B | 685 | ||
| SCN4B | 686 | ||
| Summary | 686 | ||
| β Subunits as accomplices of aberrant NaV1.5 | 686 | ||
| Additional arrhythmogenic roles of β subunit gene mutations | 687 | ||
| Voltage-gated Sodium Channel α Subunits Other than Nav1.5 Are Modulated by β Subunits in Heart | 687 | ||
| Voltage-gated Sodium Channel β Subunits Modulate K+ Channels | 688 | ||
| Roles of β subunits in cardiovascular pharmacology and treatment | 688 | ||
| Future directions | 688 | ||
| References | 688 | ||
| Pharmacology and Toxicology of Nav1.5-Class 1 Antiarrhythmic Drugs | 695 | ||
| Key points | 695 | ||
| Learning from history | 695 | ||
| The Arrival of Better Tolerated Drugs | 696 | ||
| The Cardiac Arrhythmia Suppression Trial | 696 | ||
| In vitro mechanisms of sodium channel blocking drug action | 697 | ||
| Subclassifying Drugs | 697 | ||
| Where Is the Receptor? | 698 | ||
| Mutant Channels May Display Altered Drug Sensitivity | 698 | ||
| In vivo mechanisms of sodium channel blocking drug action | 699 | ||
| Proarrhythmia in the Structurally Normal Heart | 699 | ||
| Most Sodium Channel Blockers Exert Other Pharmacologic Effects | 700 | ||
| The Late Sodium Current | 700 | ||
| Summary | 701 | ||
| References | 701 | ||
| Congenital Long QT Syndrome Type 3 | 705 | ||
| Key points | 705 | ||
| Introduction | 705 | ||
| Molecular genetics | 705 | ||
| Clinical presentation | 706 | ||
| Life-threatening Cardiac Events and Genotype-specific Triggers in Long QT Syndrome Type 3 | 706 | ||
| Features of Electrocardiogram | 707 | ||
| Diagnosis | 707 | ||
| Management of long QT syndrome type 3 | 708 | ||
| Lifestyle Modifications | 708 | ||
| Beta-blockers | 708 | ||
| Gene-specific Therapy | 709 | ||
| Mutation-specific Therapy | 710 | ||
| Pitfalls for Gene-specific Therapy in LQT3 | 710 | ||
| Implantable Cardioverter-Defibrillator and Left Cardiac Sympathetic Denervation | 711 | ||
| Summary | 711 | ||
| References | 711 | ||
| Brugada Syndrome and Nav1.5 | 715 | ||
| Key points | 715 | ||
| Introduction | 715 | ||
| Clinical and physiopathologic characteristics of the Brugada syndrome | 716 | ||
| Genetic basis of Brugada syndrome | 716 | ||
| Role of SCN5A mutation in Brugada syndrome | 717 | ||
| Clinical characteristics of patients with Brugada syndrome carrying an SCN5A mutation | 718 | ||
| Genetic counseling in patients with Brugada syndrome | 718 | ||
| Summary | 719 | ||
| References | 719 | ||
| Conduction Disorders and Nav1.5 | 723 | ||
| Key points | 723 | ||
| Introduction | 723 | ||
| AV conduction | 723 | ||
| Anatomy | 723 | ||
| Characteristics of Conduction Tissue | 723 | ||
| Role of Nav1.5 in Atrioventricular Conduction | 724 | ||
| Clinical Manifestations: Degrees of Atrioventricular Block | 725 | ||
| History of familial conduction disease | 726 | ||
| Lev/Lenègre Disease | 726 | ||
| Role of SCN5A in Familial Atrioventricular Block | 726 | ||
| Nav1.5 mutations and conduction disease | 728 | ||
| Clinical Features | 728 | ||
| Overlap Syndromes | 729 | ||
| Treatment and Prognosis | 729 | ||
| Future directions | 729 | ||
| Summary | 730 | ||
| References | 730 | ||
| Dilated Cardiomyopathy and Nav1.5 | 733 | ||
| Key points | 733 | ||
| Introduction | 733 | ||
| Dilated Cardiomyopathy: Definition, Epidemiology, Genetic Heterogeneity, Natural History, and Treatment Options | 733 | ||
| Role of Nav1.5 in the Heart in Health and Disease | 734 | ||
| Genetic variants in the SCN5A gene associated with dilated cardiomyopathy: causal or casual link? | 734 | ||
| Clinical manifestations of dilated cardiomyopathy 1E and treatment options | 737 | ||
| Summary | 738 | ||
| References | 739 | ||
| Atrial Fibrillation and SCN5A Variants | 741 | ||
| Key points | 741 | ||
| Definition and epidemiology of atrial fibrillation | 741 | ||
| Genetics of atrial fibrillation | 742 | ||
| Normal atrial electrophysiology and role of SCN5A/NaV1.5 | 742 | ||
| Role of cardiac potassium and sodium channel mutations in increased susceptibility to atrial fibrillation | 744 | ||
| Role of SCN5A mutations in mixed inherited arrhythmia syndromes | 744 | ||
| SCN5A mutations and atrial fibrillation | 745 | ||
| Challenges associated with linking SCN5A variants with increased susceptibility to atrial fibrillation | 746 | ||
| References | 746 | ||
| The Role of the Cardiac Sodium Channel in Perinatal Early Infant Mortality | 749 | ||
| Key points | 749 | ||
| Introduction | 749 | ||
| The cardiac sodium channel | 750 | ||
| Role of SCN5A in neonatal sudden unexpected deaths | 750 | ||
| Role of SCN5A in intrauterine unexplained fetal death | 751 | ||
| Role of SCN5A in documented life-threatening arrhythmias in the perinatal period | 754 | ||
| Differences among the SCN5A mutations identified in sudden infant death syndrome, intrauterine unexplained fetal death, and ... | 755 | ||
| Clinical implications | 756 | ||
| Acknowledgments | 757 | ||
| References | 757 | ||
| Cardiac Sodium Channel Overlap Syndrome | 761 | ||
| Key points | 761 | ||
| Introduction | 761 | ||
| Cardiac sodium channel structure, function, distribution, and regulation | 762 | ||
| Clinical disorders associated with SCN5A mutations | 763 | ||
| Long QT Syndrome Type 3 | 763 | ||
| Brugada Syndrome | 763 | ||
| Progressive Cardiac Conduction Defect and Sick Sinus Syndrome | 763 | ||
| Atrial Fibrillation | 764 | ||
| Dilated Cardiomyopathy | 764 | ||
| Cardiac sodium channel overlap syndrome: clinical and genetic perspective | 765 | ||
| Cardiac sodium channel overlap syndrome: biophysical perspective | 766 | ||
| Mutation-specific versus individual-specific disease expressivity and severity | 767 | ||
| Clinical and environmental factors influencing disease expressivity and severity | 768 | ||
| Genetic modifiers of disease expressivity and severity | 768 | ||
| Are most SCN5A mutations potential overlap syndrome–causing mutations? | 770 | ||
| Sodium channel complexity: novel insights | 770 | ||
| Summary | 772 | ||
| References | 772 | ||
| Cardiac Sodium Channel Nav1.5 and Drug-Induced Long QT Syndrome | 777 | ||
| Key points | 777 | ||
| Introduction | 777 | ||
| Origin of cardiac current alterations leading to action potential and QT interval prolongation | 777 | ||
| Drug-induced long QT syndrome | 780 | ||
| Cardiac repolarization reserve | 780 | ||
| Role of the late sodium in drug-induced long QT syndrome | 780 | ||
| Role of genetic variants in SCN5A in drug-induced long QT syndrome | 781 | ||
| Summary | 782 | ||
| Acknowledgments | 782 | ||
| References | 782 | ||
| Disease Caused by Mutations in NaV-β Subunit Genes | 785 | ||
| Key points | 785 | ||
| Introduction | 785 | ||
| Cardiac diseases and NaV-β subunits | 786 | ||
| Long QT Syndrome | 786 | ||
| Brugada Syndrome | 787 | ||
| Idiopathic Ventricular Fibrillation | 789 | ||
| Cardiac Conduction Disorders | 790 | ||
| Atrial Fibrillation | 791 | ||
| Neurologic diseases and NaV-β subunits | 791 | ||
| Epilepsy, Febrile Seizures, and Dravet Syndrome | 791 | ||
| Pain Sensation | 791 | ||
| Neurodegenerative Disease | 791 | ||
| Sudden Unexplained Death in Epilepsy | 791 | ||
| Sudden infant death syndrome and NaV-β subunits | 792 | ||
| Cancer and NaV-β subunits | 792 | ||
| Summary | 792 | ||
| References | 792 | ||
| Diseases Caused by Mutations in Nav1.5 Interacting Proteins | 797 | ||
| Key points | 797 | ||
| Clinical importance | 797 | ||
| Definition of sodium channel interacting proteins and the sodium channel complex | 797 | ||
| Mutations, disease, and causality | 800 | ||
| Scope of this review | 800 | ||
| SNTA1 and long QT syndrome/sudden infant death syndrome | 800 | ||
| Caveolin-3 and Long QT Syndrome/Sudden Infant Death Syndrome | 802 | ||
| Glycerol phosphate dehydrogenase 1 like and brugada syndrome | 803 | ||
| MOG1 and Brugada Syndrome/Atrial Fibrillation | 804 | ||
| Plakophilin-2 and brugada syndrome and cardiomyopathy | 804 | ||
| Sarcolemma membrane-associated protein and brugada syndrome | 805 | ||
| Z-band alternatively spliced PDZ motif protein and dilated cardiomyopathy/left ventricular noncompaction syndrome | 805 | ||
| Summary | 805 | ||
| Acknowledgments | 806 | ||
| References | 806 | ||
| Use of Drugs in Long QT Syndrome Type 3 and Brugada Syndrome | 811 | ||
| Key points | 811 | ||
| Introduction | 811 | ||
| Long QT type 3 | 812 | ||
| Brugada syndrome | 813 | ||
| Overlap syndromes | 813 | ||
| Mechanisms of drug interaction | 813 | ||
| Drug lists online | 814 | ||
| Sensible treatment based on the cardiac phenotype | 815 | ||
| Summary | 815 | ||
| References | 815 | ||
| Sodium Current Disorders | 819 | ||
| Key points | 819 | ||
| Introduction | 819 | ||
| Sodium current disorders: missing link from bench to bedside | 820 | ||
| Brugada syndrome | 820 | ||
| Long QT syndrome | 821 | ||
| Sick sinus syndrome/cardiac conduction disease | 821 | ||
| Atrial fibrillation | 821 | ||
| Dilated cardiomyopathy | 821 | ||
| Summary | 822 | ||
| References | 822 | ||
| Sodium Current Disorders | 825 | ||
| Key points | 825 | ||
| Introduction | 825 | ||
| Phenotypes associated with SCN5A and related genes | 825 | ||
| Long QT Syndrome Type 3 | 826 | ||
| Brugada Syndrome | 826 | ||
| Progressive Cardiac Conduction Defect | 827 | ||
| Sick Sinus Syndrome | 828 | ||
| Dilated Cardiomyopathy | 828 | ||
| Atrial Fibrillation | 828 | ||
| The complexity of SCN5A phenotypes: implications for genetic testing | 829 | ||
| Genetic Testing in Mendelian Traits Associated with Cardiac Sodium Channel | 829 | ||
| The Role of Common Genetic Variations and Their Modulatory Role | 831 | ||
| Summary | 831 | ||
| References | 831 | ||
| Index | 835 |