BOOK
Cardiac Electrophysiology: From Cell to Bedside E-Book
Douglas P. Zipes | Jose Jalife | William Gregory Stevenson
(2017)
Additional Information
Book Details
Abstract
Rapid advancements in cardiac electrophysiology require today’s health care scientists and practitioners to stay up to date with new information both at the bench and at the bedside. The fully revised 7th Edition of Cardiac Electrophysiology: From Cell to Bedside, by Drs. Douglas Zipes, Jose Jalife, and William Stevenson, provides the comprehensive, multidisciplinary coverage you need, including the underlying basic science and the latest clinical advances in the field.
An attractive full-color design features color photos, tables, flow charts, ECGs, and more.
- All chapters have been significantly revised and updated by global leaders in the field, including 19 new chapters covering both basic and clinical topics.
- New topics include advances in basic science as well as recent clinical technology, such as leadless pacemakers; catheter ablation as a new class I recommendation for atrial fibrillation after failed medical therapy; current cardiac drugs and techniques; and a new video library covering topics that range from basic mapping (for the researcher) to clinical use (implantations).
- Each chapter is packed with the latest information necessary for optimal basic research as well as patient care, and additional figures, tables, and videos are readily available online.
- New editor William G. Stevenson, highly regarded in the EP community, brings a fresh perspective to this award-winning text.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | Cover | ||
| IFC\r | ES1 | ||
| CardiacElectrophysiology: From Cell to Bedside | i | ||
| Copyright | ii | ||
| CONTRIBUTORS | iii | ||
| PREFACE | xix | ||
| VIDEO CONTENTS | xxxi | ||
| I -\rStructural and Molecular Basesof Ion Channel Function | 1 | ||
| 1 -\rVoltage-Gated Sodium Channels and Electrical Excitability of the Heart | 1 | ||
| Subunit Structure of Sodium Channels | 1 | ||
| Three-Dimensional Structure of Sodium Channels | 1 | ||
| Sodium Channel Structure and Function | 3 | ||
| Outer Pore and Selectivity Filter | 3 | ||
| Voltage-Dependent Activation | 5 | ||
| Pore Opening | 5 | ||
| Fast Inactivation | 6 | ||
| Coupling of Activation to Fast Inactivation | 7 | ||
| Slow Inactivation | 7 | ||
| Sodium Channel Genes | 9 | ||
| REFERENCES | 10 | ||
| 2 -\rVoltage-Gated Calcium Channels | 12 | ||
| Molecular Composition of Voltage-Gated Ca2+ Channels | 12 | ||
| L-Type Ca2+ Channels | 15 | ||
| Electrophysiological Properties of L-Type Ca2+ Channels | 15 | ||
| Pharmacology of L-Type Ca2+ Channels | 15 | ||
| Role of L-Type Ca2+ Channels in the Heart | 15 | ||
| T-Type Ca2+ Channels | 17 | ||
| Expression and Molecular Composition of T-Type Ca2+ Channels | 17 | ||
| Electrophysiology | 17 | ||
| Pharmacology | 17 | ||
| Role of T-Type Ca2+ Channels in the Heart | 19 | ||
| Posttranslational Regulation of T-Type Ca2+ Channels | 19 | ||
| Transient Receptor Potential Channels | 19 | ||
| Expression and Molecular Composition of TRP Channels | 19 | ||
| Electrophysiology | 19 | ||
| Pharmacology | 19 | ||
| TRP Channels in Cardiac Development | 20 | ||
| TRP Channels and Cardiac Conduction | 20 | ||
| TRP Channels in Cardiac Fibroblasts | 20 | ||
| TRP Channels and Cardiac Hypertrophy | 20 | ||
| Acknowledgments | 21 | ||
| REFERENCES | 21 | ||
| 3 -\rVoltage-Gated Potassium Channels | 25 | ||
| General Molecular Properties ofVoltage-Gated K+ Channels | 25 | ||
| Alpha Pore-Forming Subunits | 25 | ||
| Accessory (Auxiliary) Subunits | 25 | ||
| General Biophysical Properties of Kv Channels | 27 | ||
| Selectivity Filter and Permeation Pore | 27 | ||
| Activation Gating Mechanisms | 27 | ||
| Inactivation Gating Mechanisms | 30 | ||
| N-Type Inactivation | 30 | ||
| C/P-Type Inactivation (Molecular Transitions in the Selectivity Region) | 30 | ||
| AG-Type Inactivation (Molecular Transitions Involving the Recoil of the Activation Gate [S6]) | 31 | ||
| U-Type Inactivation Properties | 32 | ||
| Specific Cardiac Kv Currents | 32 | ||
| Transient Outward Currents (Ito1) | 32 | ||
| Molecular Basis and Biophysical Properties of Ito1 | 32 | ||
| Regulation of Ito1 | 32 | ||
| Physiological Role of Ito1 | 33 | ||
| Voltage-Gated Delayed Rectifiers Channels (IK) | 33 | ||
| Molecular and Biophysical Properties of IK | 33 | ||
| Regulation of IK | 34 | ||
| Physiological Role of IK | 34 | ||
| Myocardial Ca2+-Activated K+ Channels | 35 | ||
| General Molecular and Biophysical Properties | 35 | ||
| Small Conductance (SK) Ca2+-Activated K+ Channels | 35 | ||
| Molecular and Biophysical Properties of SK Channels | 35 | ||
| Regulatory Properties of SK Channels | 35 | ||
| Physiological Role of SK Channels | 35 | ||
| Acknowledgments | 35 | ||
| REFERENCES | 35 | ||
| 4 - Structural and Molecular Bases of\rCardiac Inward Rectifier Potassium Channel Function | 38 | ||
| Background | 38 | ||
| A Family of Genes Encodes Inward Rectifier Potassium Channels | 38 | ||
| Classical Cardiac Inward Rectifier Potassium Channels | 38 | ||
| Kir2 Subfamily Underlies Cardiac IK1 | 38 | ||
| Crystal Structure of Kir2 Channels | 38 | ||
| Mechanism of Polyamine-Induced Rectification | 40 | ||
| Rectification Properties Are Related to Electrostatic Interactions in the Cytoplasmic Pore of a Kir Channel | 40 | ||
| Differential Properties of Kir2.x Subfamily | 41 | ||
| Cellular and Membrane Localization | 41 | ||
| Pharmacology and Regulation | 41 | ||
| Channelopathies | 42 | ||
| Acetylcholine-Activated Potassium Channels | 43 | ||
| Structure and Function | 43 | ||
| Cellular and Membrane Localization | 44 | ||
| Pharmacology and Regulation | 45 | ||
| Channelopathies | 45 | ||
| ATP-Sensitive Potassium Channels | 45 | ||
| Structure and Function | 45 | ||
| Cellular and Membrane Localization | 46 | ||
| Pharmacology and Regulation | 47 | ||
| Channelopathies | 47 | ||
| Conclusion | 47 | ||
| REFERENCES | 47 | ||
| 5 -\rMammalian Calcium Pumps in Health and Disease | 49 | ||
| Sarco/Endoplasmic Reticulum Ca2+ ATPase | 49 | ||
| Secretory Pathway Ca2+ ATPase | 52 | ||
| Plasma Membrane Ca2+ ATPase | 53 | ||
| Ca2+ Pumps in the Disease Process | 55 | ||
| Sarco/Endoplasmic Reticulum Ca2+ Pump | 56 | ||
| Secretory Pathway Ca2+ Pump | 56 | ||
| Plasma Membrane Ca2+ ATPase Pump | 57 | ||
| Final Comments | 57 | ||
| Acknowledgment | 57 | ||
| REFERENCES | 58 | ||
| 6 -\rStructural and Molecular Bases of Sarcoplasmic Reticulum Ion Channel Function | 60 | ||
| The Sarcoplasmic Reticulum | 60 | ||
| Structural Arrangement of the Sarcoplasmic Reticulum | 60 | ||
| Molecular Players of Excitation–Contraction Coupling | 60 | ||
| Molecular Structure of the Cardiac\rRyanodine Receptor | 60 | ||
| Accessory Proteins of the RyR2 Channel | 62 | ||
| Ca2+ Regulation of RyR2 Channels | 62 | ||
| Modulation of RyR2 Channel Function | 62 | ||
| Phosphorylation | 62 | ||
| Oxidation and Nitrosylation | 63 | ||
| Cytosolic Modulators | 63 | ||
| RyR2 Channels in Disease | 63 | ||
| Catecholaminergic PolymorphicVentricular Tachycardia | 63 | ||
| Role of RyR2 Channels in Heart Failure | 64 | ||
| Acknowledgment | 64 | ||
| REFERENCES | 64 | ||
| 7 -\rOrganellar Ion Channels and Transporters | 66 | ||
| Introduction | 66 | ||
| Historical Overview of Mitochondrial Ion Channel/Transporter Research | 66 | ||
| Overview of Mitochondrial Bioenergetics and Mitochondrial Membrane Potential | 68 | ||
| Overview of Mitochondrial Reactive Oxygen Species Generation and Mitochondrial Membrane Potential | 68 | ||
| Overview of Mitochondria-Induced Apoptosis | 69 | ||
| Ion Channels/Transporters at the Mitochondrial Inner Membrane | 69 | ||
| Mitochondrial Ca2+ Channels/Transporters Regulating Mitochondrial Ca2+ Influx | 69 | ||
| Mitochondrial Ca2+ Uniporter Protein Complex | 69 | ||
| MCU (CCDC109A). | 69 | ||
| MCUb (CCDC109B). Rizzuto’s group reported a novel protein MCUb, which serves as an endogenous dominant-negative pore forming sub... | 69 | ||
| EMRE. Essential MCU regulator, EMRE (known as C22ORF32) is the first identified auxiliary subunit reported that has a TMD.29 EMR... | 69 | ||
| MICU1, 2, and 3. Historically, MICU1 (encoded by CBARA1/EFHA3) was the first regulatory element for the MCU pore discovered just... | 69 | ||
| Other Proposed Auxiliary Subunits. Mitochondrial calcium uniporter regulator 1 (MCUR1) encoded by CCDC90A was proposed as a poss... | 70 | ||
| Mitochondrial Ryanodine Receptor | 70 | ||
| Letm1 (Ca2+/H+ Antiporter) | 70 | ||
| Mitochondrial Ca2+ Channels/Transporters Regulating Mitochondrial Ca2+ Efflux | 70 | ||
| Mitochondrial Na+/Ca2+ Exchanger (NCLX) | 70 | ||
| Mitochondrial Permeability Transition Pores | 70 | ||
| Mitochondrial K+ Channels | 73 | ||
| Mitochondrial KATP Channel | 73 | ||
| Mitochondrial KCa Channel | 73 | ||
| Proton Fluxes and Uncoupling Proteins | 73 | ||
| Anion Channels and Mitochondrial Volume Control | 73 | ||
| Ion Channels/Transporters at the Mitochondrial Outer Membrane | 73 | ||
| Voltage-Dependent Anion Channel | 73 | ||
| Apoptosis-Induced Channels | 74 | ||
| Mitochondrial Ion Channels/Transporters in Cardiac Function and Dysfunction | 74 | ||
| Overview of Mitochondrial Structure and Function in the Heart | 74 | ||
| Mitochondrial Ion Channels/Transporters in Cardiac Dysfunction: Novel Therapeutic Targets | 77 | ||
| Role of Mitochondrial Ion Channels/Transporters in Cardioprotection Against Ischemia-Reperfusion Injury | 77 | ||
| Role of Mitochondrial Ion Channels/Transporters in Cardiac Arrhythmias | 77 | ||
| Closing Remarks | 78 | ||
| REFERENCES | 78 | ||
| 8 -\rMolecular Organization, Gating, and Function of Connexin-Based Gap Junction Channels and Hemichannels | 80 | ||
| Connexins Expression and Oligomerization | 80 | ||
| De Novo Formation of Gap Junction Channels | 80 | ||
| Voltage and Chemical Gating of Connexin-Based Channels | 81 | ||
| Hemichannels: Function and Physiological Relevance | 82 | ||
| Cell–Cell Coupling and Electrical Anisotropy in the Heart | 84 | ||
| Passive Electrical Properties of the Sinoatrial Node | 85 | ||
| Passive Electrical Properties of the Atrioventricular Node | 85 | ||
| Passive Electrical Properties of Conductive and Working Systems of Ventricles and Signal Transfer in P–M Contacts | 85 | ||
| Alterations of Cell–Cell Coupling in Connexin-Deficient Animals and Disease-Related Mutations | 87 | ||
| Acknowledgments | 88 | ||
| REFERENCES | 88 | ||
| II -\rBiophysics of Cardiac IonChannel Function | 90 | ||
| 9 - Structure–Function Relations of Heterotrimetric Complexes of Sodium Channel α- and β-Subunits | 90 | ||
| Sodium Channel β-Subunits | 92 | ||
| Nav Channel α- and β-Subunit Complex | 93 | ||
| Nav Channel α-α Subunit Interactions and Macromolecular Complex | 93 | ||
| Summary and Future Directions | 94 | ||
| Acknowledgment | 94 | ||
| REFERENCES | 94 | ||
| 10 -\rRegulation of Cardiac Calcium Channels | 96 | ||
| Overview | 96 | ||
| Calcium Channel Expression in the Myocardium | 96 | ||
| L-Type Versus T-Type Channel Expression and Gating | 96 | ||
| The Cardiac L-Type Calcium Channel Is a Multiprotein Complex | 97 | ||
| Cav1.2 Structure and Gating | 98 | ||
| Voltage Effects on Activation and Inactivation | 100 | ||
| Activation | 100 | ||
| Inactivation | 100 | ||
| Calcium–Calmodulin Regulates Activation and Inactivation Gating | 100 | ||
| Posttranslational Modifications Effects on Ca2+ Channel Gating | 102 | ||
| β-Adrenergic-Modulated Ca2+ Channel Gating | 102 | ||
| Facilitation | 102 | ||
| Other Protein Interactions Effecting L-Type Ca2+ Channel Gating | 102 | ||
| RGK Proteins | 102 | ||
| Calcineurin | 103 | ||
| Cav1.2 Coupled Gating | 103 | ||
| N-Terminal–C-Terminal Interaction | 104 | ||
| REFERENCES | 104 | ||
| 11 -\rInhibition of Phosphoinositide 3-Kinase and Acquired Long QT Syndrome | 106 | ||
| Acquired Long QT Syndrome and hERG | 106 | ||
| PI3K Signal Transduction | 106 | ||
| Effects of PI3kα Inhibition on CardiacPlateau Currents | 107 | ||
| INaP | 107 | ||
| IKr | 108 | ||
| IKs | 108 | ||
| INa | 109 | ||
| ICaL | 110 | ||
| How Changes in Plateau Currents Caused by PI3K Inhibition Affect the Cardiac Action Potential Duration | 110 | ||
| Incidence of Early Afterdepolarizations | 110 | ||
| Evidence That Some Drugs Block IKr Alone, While Others Inhibit PI3K and Block IKr | 110 | ||
| Diabetes and Acquired Long QT Syndrome | 111 | ||
| Therapeutic Approaches | 111 | ||
| Conclusions | 111 | ||
| Acknowledgment | 111 | ||
| REFERENCES | 112 | ||
| 12 -\rStructural Determinants and Biophysical Properties of hERG1 Channel Gating | 113 | ||
| Physiological Role and Clinical Importance of Cardiac hERG1 Channels | 113 | ||
| hERG1 Channel Currents | 113 | ||
| Ionic Currents | 113 | ||
| Gating Currents | 115 | ||
| Structural Basis of hERG1 Channel Gating and Permeation | 115 | ||
| Selectivity Filter and Ion Permeation | 116 | ||
| Voltage Sensing and Channel Activation | 117 | ||
| Role of Intracellular Domains in Channel Gating | 117 | ||
| Structural Basis of hERG1 Channel Inactivation | 119 | ||
| Pharmacology of Inactivation Gating | 119 | ||
| Markov Models of hERG1 Channel Gating | 119 | ||
| REFERENCES | 121 | ||
| 13 -\rMolecular Regulation of Cardiac Inward Rectifier Potassium Channels by Pharmacological Agents | 122 | ||
| Inward Rectifier Potassium Current | 122 | ||
| Molecular Basis | 122 | ||
| Physiology | 122 | ||
| Pathophysiology | 122 | ||
| III -\rIntermolecular Interactions andCardiomyocyte Electrical Function | 160 | ||
| 17 -\rIon Channel Trafficking in the Heart | 160 | ||
| Overview of Ion Channel Trafficking in the Heart | 160 | ||
| Targeted Delivery | 160 | ||
| Cx43 Trafficking in the Heart | 160 | ||
| Cx43 Forward Trafficking in Normal Heart Physiology | 162 | ||
| Cx43 Forward Trafficking in Heart Pathophysiology | 162 | ||
| Regulation of Cx43 Forward Trafficking by Its Alternatively Translated Isoforms | 162 | ||
| Cx43 Internalization in Healthy Cardiomyocytes | 163 | ||
| Cx43 Internalization in Diseased Cardiomyocytes | 163 | ||
| CaV1.2 Channel Trafficking in the Heart | 163 | ||
| CaV1.2 Internalization | 165 | ||
| Conclusions | 165 | ||
| REFERENCES | 165 | ||
| 18 -\rMicrodomain Interactions of Macromolecular Complexes and Regulation of the Sodium Channel Nav1.5 | 167 | ||
| Nav1.5 and Interacting Proteins | 167 | ||
| Localization of Nav1.5 in Cardiac Cells: Evidence for Distinct Pools | 167 | ||
| Proteins Interacting With Nav1.5 Without Demonstrated Roles in Arrhythmias | 167 | ||
| Ubiquitin-Protein Ligases of the Nedd4/Nedd4-Like Family | 169 | ||
| 14-3-3η (eta) Protein | 170 | ||
| Calmodulin | 171 | ||
| Ca2+/Calmodulin-Dependent Protein Kinase II | 171 | ||
| Protein Tyrosine Phosphatase PTPH1 | 171 | ||
| Telethonin | 171 | ||
| α-Actinin-2 | 171 | ||
| Synapse-Associated Protein 97 | 172 | ||
| Dynactin-2 | 172 | ||
| Coxsackievirus and Adenovirus Receptor | 172 | ||
| Proteins Interacting With Nav1.5 That Are Linked to Cardiac Arrhythmias | 172 | ||
| Caveolin-3 | 172 | ||
| α-1 Syntrophin and the Dystrophin/Utrophin Complex7 | 172 | ||
| Glycerol-3-Phosphate Dehydrogenase–Like Protein | 173 | ||
| MOG1 | 173 | ||
| Plakophilin-2 | 173 | ||
| Desmoglein-2 | 173 | ||
| Ankyrin-G | 173 | ||
| Fibroblast Growth Factor HomologousFactors | 174 | ||
| Z-Band Alternatively Spliced PDZ Motif Protein | 174 | ||
| Conclusions and Perspectives | 174 | ||
| Acknowledgment | 174 | ||
| REFERENCES | 174 | ||
| 19 - Fibroblast Growth Factor\rHomologous Factors Modulate Cardiac Sodium and Calcium Channels | 177 | ||
| The Structure of Fibroblast Growth Factor Homologous Factors | 177 | ||
| Fibroblast Growth Factor Homologous Factors Regulate Voltage-Gated Sodium Channels | 178 | ||
| Arrhythmia Mutations Result From Aberrant Fibroblast Growth Factor Homologous Factor–Voltage-Gated Sodium Channels Interaction | 178 | ||
| Fibroblast Growth Factor Homologous Factors Regulate Voltage-Gated Calcium Channels | 178 | ||
| CHANNELS17919Novel Fibroblast Growth Factor Homologous Factor Roles and Future Directions | 179 | ||
| Acknowledgment | 179 | ||
| REFERENCES | 179 | ||
| 20 -\rMacromolecular Complexes and Cardiac Potassium Channels | 180 | ||
| The Four General Classes of Accessory Subunits | 180 | ||
| Kvβ Family | 180 | ||
| minK and minK-Related Proteins | 181 | ||
| Potassium Channel–Interacting Protein | 182 | ||
| Potassium Channel–Associated Protein | 182 | ||
| The Membrane-Associated Guanylate Kinase Proteins | 182 | ||
| Membrane Lipids and Potassium Channel Complexes | 183 | ||
| Lipids and the Biophysical Properties of Potassium Channels | 183 | ||
| Lipid Rafts and Clustering of Potassium Channels | 184 | ||
| Macromolecular Complex Involved in the Delivery of Potassium Channels | 185 | ||
| Conclusion | 185 | ||
| REFERENCES | 185 | ||
| 21 -\rReciprocity of Cardiac Sodium and Potassium Channels in the Control of Excitability and Arrhythmias | 187 | ||
| Sodium Channels and Cardiac Excitation | 187 | ||
| The Inward Rectifier Potassium Current | 188 | ||
| Intermolecular Interactions Involving PDZ Domains | 188 | ||
| NaV1.5-Interacting Proteins | 189 | ||
| NaV1.5 Interacts With SAP97 | 189 | ||
| NaV1.5 Interacts With Syntrophins | 189 | ||
| Two Pools of NaV1.5 Channels | 190 | ||
| Kir2.1 Interacts With Both SAP97 and α-Syntrophin | 190 | ||
| Reciprocal Regulation of NaV1.5 and Kir2.1 | 190 | ||
| SAP97 and Syntrophin Are Involved in NaV1.5-Kir2.1 Interactions | 190 | ||
| NaV1.5-Kir2.1 Interactions Are Posttranslational and Model-Independent | 191 | ||
| NaV1.5-Kir2.1 Interactions Involve Membrane Trafficking | 193 | ||
| Reciprocal NaV1.5-Kir2.1 Interactions Control Reentry Frequency | 194 | ||
| Concluding Remarks | 195 | ||
| Acknowledgments | 195 | ||
| 22 -\rThe Intercalated Disc: A Molecular Network That Integrates Electrical Coupling, Intercellular Adhesion, and Cell Excitability | 198 | ||
| Introduction and Historical Perspective | 198 | ||
| Intercalated Disc Proteins in Inherited and Acquired Diseases | 198 | ||
| Structural Features of the Intercalated Disc | 199 | ||
| Adherens Junctions | 199 | ||
| Desmosomes | 200 | ||
| The “Area Composita” | 200 | ||
| Transcriptional Regulation by Mechanical Junction Proteins | 200 | ||
| Gap Junctions | 200 | ||
| The Intercellular Space | 200 | ||
| Ion Channel Complexes That Reside at the Intercalated Disc | 201 | ||
| The Voltage-Gated Sodium Channel Complex | 201 | ||
| The α-Subunit NaV1.5 | 201 | ||
| β-Subunits of the Sodium Channel | 202 | ||
| Subcellular Heterogeneity of the Voltage-Gated Sodium Channel | 202 | ||
| Potassium Channels at the Intercalated Disc | 202 | ||
| Noncanonical Functions of Intercalated Disc Molecules | 202 | ||
| Desmosomal Proteins Are Necessary for the Formation of Functional Gap Junctions | 202 | ||
| Desmosomal Molecules Are Necessary for Sodium Channel Function | 203 | ||
| Connexin43 Regulates Sodium and Potassium Currents | 205 | ||
| Cx43 as a Microtubule Anchoring Point and the Control of Sodium Current Amplitude | 206 | ||
| AnkG and Cx43 Are Necessary to Maintain Intercellular Adhesion | 207 | ||
| The “α Personality” of the β-Subunit: Intercellular Adhesion Strength | 208 | ||
| Other Intercellular Adhesion Molecules That Crosstalk With Cardiac Ion Channels | 208 | ||
| The Intercalated Disc and the Intracellular Signaling Platforms | 208 | ||
| The Connexome, Visual Proteomics, and the Existence of “Mini-Nodes of Ranvier” at the Intercalated Disc | 208 | ||
| The Mini-Node of Ranvier and the Possibility of Ephaptic Transmission | 209 | ||
| Brugada Syndrome and Arrhythmogenic Cardiomyopathy: Bookends of a Common Spectrum | 209 | ||
| Conclusions | 209 | ||
| Acknowledgments | 210 | ||
| REFERENCES | 210 | ||
| 23 - Function and Dysfunction of Ion Channel Membrane Trafficking and\rPosttranslational Modification | 212 | ||
| Defects in Ion Channel Trafficking and Cardiac Arrhythmia | 212 | ||
| Defects in Ion Channel Processing/Folding Result in Cardiac Arrhythmia | 212 | ||
| Defects in Ion Channel Anterograde Trafficking Result in Cardiac Arrhythmia | 212 | ||
| Defects in Ion Channel/Transporter Membrane Targeting/Scaffolding Cause Arrhythmia | 213 | ||
| Channel Dysfunction Induced by Altered Posttranslational Modifications | 215 | ||
| Dysregulation of Cell Signaling in Heart Failure | 215 | ||
| Sodium Channel Dysfunction Induced by Altered Posttranslational Modifications in Heart Failure | 215 | ||
| Calcium Cycling Dysfunction Induced by Altered Posttranslational Modifications in Heart Failure | 215 | ||
| Altered Posttranslational Modifications Downstream of Defects in Ion Channel Complex | 216 | ||
| Summary | 216 | ||
| REFERENCES | 217 | ||
| 24 -\rFeedback Mechanisms for Cardiac-Specific MicroRNAs and cAMP Signaling in Electrical Remodeling | 219 | ||
| Overview of Cardiac MicroRNAs | 219 | ||
| MicroRNA Biology | 219 | ||
| MicroRNA in the Heart | 219 | ||
| Critical Roles of MicroRNAs in the Regulation of Cardiac Ion Channel Expression | 220 | ||
| MicroRNA Signature of Cardiovascular Diseases | 220 | ||
| Functional Roles of MicroRNAs in Cardiac cAMP Signaling and Electrical Remodeling | 220 | ||
| cAMP Signaling in the Heart | 220 | ||
| MicroRNA and cAMP Signaling | 220 | ||
| CRE-Binding, CRE-Modulator, and Inducible cAMP Early Repressor Proteins | 221 | ||
| Feedback Mechanisms for Cardiac MicroRNAs and cAMP Signaling in Cardiac Electrical Remodeling | 221 | ||
| Roles of MicroRNAs in Electrical Remodeling in Cardiac Hypertrophy and Failure | 221 | ||
| Roles of MicroRNAs in Electrical Remodeling in Atrial Fibrillation | 222 | ||
| Delivery of miR-1/133a Prevents Electrical Remodeling Post–Myocardial Infarction | 222 | ||
| CRE-Modulator and Inducible cAMP Early Repressor Are Targets of miR-1 | 223 | ||
| Therapeutic Potentials of MicroRNA Delivery in Cardiac Electrical Remodeling | 223 | ||
| Summary and Future Perspectives | 223 | ||
| REFERENCES | 224 | ||
| IV -\rCell Biology of Cardiac ImpulseInitiation and Propagation | 226 | ||
| 25 -\rStem Cell–Derived Sinoatrial-Like Cardiomyocytes as a Novel Pharmacological Tool | 226 | ||
| The Adult Sinoatrial Node | 226 | ||
| Sinoatrial Node Development | 227 | ||
| Sinoatrial Node Precursor | 229 | ||
| Mouse Stem Cells | 229 | ||
| Generating Sinoatrial-Like Cells From Mouse Embryonic Stem Cells | 230 | ||
| Improvements in the Generation of Sinoatrial Node–Like Cells | 230 | ||
| Cell Engineering | 230 | ||
| Pharmacological Approach | 231 | ||
| Human Stem Cells | 232 | ||
| Embryonic Stem Cells | 232 | ||
| Induced Pluripotent Stem Cells | 233 | ||
| Conclusions | 234 | ||
| REFERENCES | 234 | ||
| 26 -\rGene Therapy and Biological Pacing | 236 | ||
| Introduction | 236 | ||
| The Normal Cardiac Pacemaker | 236 | ||
| Pathologies Impacting Normal Pacemaker Function and a Brief History of Therapies | 237 | ||
| Rationale for Developing Biological Pacemakers | 238 | ||
| Strategies, Successes, and Failures in Developing Biological Pacemakers | 238 | ||
| Cell Therapy | 238 | ||
| Gene Therapy | 239 | ||
| Gene Therapies Generating Loss- or Gain-of-Function Ion Channels | 239 | ||
| Optimizing Pacemaker Gene Constructs | 239 | ||
| Hybrid Therapy | 241 | ||
| Delivery of Transcription Factors to Modify Morphology and Phenotype of Working Myocytes | 241 | ||
| Use of Cells to Carry Pacemaker Genes | 241 | ||
| Challenges | 242 | ||
| Conclusions | 244 | ||
| Acknowledgment | 244 | ||
| REFERENCES | 244 | ||
| 27 -\rCell-to-Cell Communication and Impulse Propagation | 246 | ||
| Cardiac Cell-to-Cell Communication by Gap Junctions | 246 | ||
| Cx43, Cx40, and Cx45 in the Myocardium | 246 | ||
| How Safe Is Propagation in Tissue With Reduced Cell-to-Cell Coupling? | 247 | ||
| Propagation in Tissue With Heterogeneous Connexin Expression Is Robust | 248 | ||
| Cell-to-Cell Coupling, Tissue Architecture, and Ion Currents Form an Interacting System | 248 | ||
| Ephaptic Impulse Transmission: Revival of an Old Concept to Explain Cardiac Cell-to-Cell Impulse Transfer | 253 | ||
| Coupling Between Cardiomyocytes and Nonmyocytes and Its Effect on Propagation | 255 | ||
| Remodeling Proteins of the Intercalated Disk: Interactions Between Mechanical Junctions and Gap Junctions | 256 | ||
| Summary | 256 | ||
| REFERENCES | 257 | ||
| 28 -\rMechanisms of Normal and Dysfunctional Sinoatrial Nodal Excitability and Propagation | 259 | ||
| Structural and Molecular Characteristics of the Sinoatrial Node Pacemaker Complex | 259 | ||
| Anatomy and Structure of the Human Sinoatrial Node | 259 | ||
| Molecular Characteristics of the Mammalian and Human Sinoatrial Node | 259 | ||
| Sinoatrial Conduction Pathways | 261 | ||
| Sinoatrial Node Conduction Properties During Normal Sinus Rhythm | 262 | ||
| Source–Sink Relationships Allow the Small Sinoatrial Node to Drive the Large Atria | 262 | ||
| Sinoatrial Node Conduction During Sinus Rhythm | 262 | ||
| Sinoatrial Node Pacemaker Complex Conduction Determines the Atrial Activation Pattern | 262 | ||
| Conduction Abnormalities and Arrhythmias in the Mammalian and Human Sinoatrial Node | 264 | ||
| Sinoatrial Node Entrance Block During Atrial Pacing and Atrial Fibrillation | 264 | ||
| Heterogeneous Refractoriness and Excitability in the Sinoatrial Node Pacemaker Complex | 264 | ||
| Sinoatrial Node Exit Block | 267 | ||
| Sinoatrial Node Recovery Time | 267 | ||
| Tachy–Brady Syndrome: Pacemaker Arrest or Sinoatrial Exit Block? | 267 | ||
| Sinoatrial Node Reentry | 267 | ||
| Conclusion and Future Directions | 270 | ||
| Acknowledgment | 270 | ||
| REFERENCES | 270 | ||
| 29 -\rCell Biology of the Specialized Cardiac Conduction System | 272 | ||
| Histological Analysis of the Developing Mammalian Cardiac Conduction System | 272 | ||
| Cellular Origins of the Cardiac Conduction System | 272 | ||
| Models of Cardiac Conduction System Development | 273 | ||
| Molecular Markers of the Cardiac Conduction System | 274 | ||
| Transcription Factor Regulatory Networks | 274 | ||
| The Sinoatrial Node | 275 | ||
| Proximal Ventricular Conduction System | 280 | ||
| The Purkinje Fiber Network | 281 | ||
| Conclusion | 281 | ||
| Acknowledgments | 281 | ||
| REFERENCES | 282 | ||
| 30 -\rCardiac Remodeling and Regeneration | 284 | ||
| Pathophysiology of Cardiac Remodeling | 284 | ||
| Chronic Heart Failure | 284 | ||
| Heart Failure With Preserved Ejection Fraction | 284 | ||
| Heart Failure in Ischemic Heart Disease | 285 | ||
| Cardiac Remodeling | 285 | ||
| Cardiomyocytes | 285 | ||
| Cardiac Fibroblasts and Fibrosis | 286 | ||
| Immune Cells | 286 | ||
| Vascular Remodeling: Endothelial and Smooth Muscle Cells | 286 | ||
| Cardiac Remodeling and Arrhythmias | 287 | ||
| Atrial Fibrillation | 287 | ||
| Ventricular Arrhythmia | 287 | ||
| Approaches to Enhance Cardiac Regeneration | 287 | ||
| Enhancement of Intrinsic Regeneration | 288 | ||
| Direct Reprogramming | 288 | ||
| Exogenous Cell–Based Approaches | 288 | ||
| Adult Tissue–Derived Progenitor Cell Therapy | 288 | ||
| Pluripotent Stem Cell Therapy | 289 | ||
| Discussion of Pluripotent Cell–Based Therapies | 289 | ||
| Outlook | 290 | ||
| Acknowledgments | 290 | ||
| REFERENCES | 290 | ||
| V - Models of Cardiac Excitation | 293 | ||
| 31 -\rIonic Mechanisms of Atrial Action Potentials | 293 | ||
| Ionic Bases of Atrial Action Potentials in the Healthy Myocardium | 293 | ||
| Action Potential Characteristics | 293 | ||
| The Inward, Depolarizing Currents (Na+, Ca2+) | 293 | ||
| The Outward, Repolarizing K+ Currents (K+) | 294 | ||
| Other Ion Channels | 295 | ||
| Ionic Bases of Regional Heterogeneity in Atrial Action Potentials | 295 | ||
| Ionic Bases of Atrial Action Potential Variations With Age | 296 | ||
| Action Potential and Ionic Remodeling in Chronic Atrial Fibrillation | 296 | ||
| Effect of Atrial Fibrillation on Action Potential and [Ca2+]i | 296 | ||
| Ionic Remodeling in Chronic Atrial Fibrillation | 296 | ||
| Sarcolemmal Ion Channels | 296 | ||
| Ca2+ and Na+ Handling | 298 | ||
| INCX. Increased expression11,12 and abnormal function of INCX protein11–15 have been reported in human cAF and in a sheep model ... | 298 | ||
| Ryanodine Receptors | 298 | ||
| Sarcoplasmic Reticulum Ca2+ ATPase and Phospholamban | 298 | ||
| Alterations in Atrial Electrophysiology During Ventricular Dysfunction | 298 | ||
| Ionic Basis of Reentry (Spiral Waves) in the Atrium | 299 | ||
| REFERENCES | 301 | ||
| 32 -\rGlobal Optimization Approaches to Generate Dynamically Robust Electrophysiological Models | 304 | ||
| Introduction | 304 | ||
| Limitations to the Cardiac Ionic Model Development Process | 304 | ||
| Using Complex Electrophysiological Protocols and Optimization to Generate Models | 305 | ||
| Genetic Algorithm Optimization | 305 | ||
| Example: Genetic Algorithm Optimization to Single Action Potential | 307 | ||
| Setting up a Genetic Algorithm Optimization | 307 | ||
| Use of Complex Objectives in Optimization | 307 | ||
| Voltage-Based Optimization | 308 | ||
| Current-Based Optimization | 310 | ||
| Membrane Resistance, Upstroke Velocity, and Tissue Considerations | 312 | ||
| Conclusions and Outlook | 312 | ||
| Optimization Methods | 313 | ||
| Cell- and Patient-Specific Modeling | 313 | ||
| Model Validation | 313 | ||
| REFERENCES | 313 | ||
| 33 -\rCalcium Signaling in Cardiomyocyte Models With Realistic Geometries | 314 | ||
| Electrophysiological Structure of the Ventricular Myocyte | 314 | ||
| Anatomy of the Myocyte Sarcolemma | 314 | ||
| A Brief Ultrastructural History of Cardiac Excitation–Contraction Coupling | 314 | ||
| Role of Imaging in Defining Cardiac Ultrastructure and Subcellular Modeling | 315 | ||
| Structure–Function Relationships at the Nanometer Scale (Calcium Release Unit and Couplon) | 315 | ||
| Couplon and Calcium Release Unit Microarchitecture | 315 | ||
| Three-Dimensional Imaging and Generation of Model Geometries | 317 | ||
| Subcellular Modeling at the Nanometer Scale | 317 | ||
| Reconstructing Ca2+ Sparks in Idealized Geometries | 317 | ||
| Modeling of Ca2+ Sparks in a Realistic Calcium Release Unit Geometry | 318 | ||
| Future Work | 320 | ||
| Structure–Function Relationships at the Micron Scale (T-Tubule and T-System) | 320 | ||
| T-Tubule Microanatomy and Its Role in Regulating Excitation–Contraction Coupling | 320 | ||
| Subcellular Modeling in Idealized Geometries at the Micron Scale | 321 | ||
| Modeling the Effects of Normal T-Tubule Ultrastructure on Subcellular Ca2+ Signals | 321 | ||
| Modeling Calcium Release Unit Ensemble Behavior in Realistic Geometries | 321 | ||
| Toward a Quantitative Understanding of Pathological T-tubule Remodeling | 322 | ||
| Acknowledgment | 323 | ||
| REFERENCES | 323 | ||
| 34 -\rTheory of Rotors and Arrhythmias | 325 | ||
| Basic Rotor Dynamics | 325 | ||
| Rotors in Heterogeneous Tissue | 327 | ||
| Rotors and Mechano-Electric Feedback | 328 | ||
| Rotors and Fibrosis | 328 | ||
| Response Functions of Spiral Waves | 330 | ||
| Curved-Space Approach to Cardiac Anisotropy | 331 | ||
| Application to Wave Fronts | 332 | ||
| Spiral Wave Drift | 333 | ||
| Acknowledgments | 333 | ||
| REFERENCES | 333 | ||
| 35 -\rComputational Approaches for Accurate Rotor Localization in the Human Atria | 335 | ||
| The Action Potential Rotor | 335 | ||
| Phase Representation of the Action Potential Time Course | 335 | ||
| The Frequency Representation of the Action Potential Activation Rate | 337 | ||
| The Phase–Frequency Domain Analysis of Rotor Activity | 340 | ||
| Torso Reduces Sensitivity of Rotor Detection by Body Surface Mapping | 340 | ||
| Highest Dominant Frequency-Filtering Effect on Rotor Localization | 341 | ||
| Detection of Driving Rotors in Body Surface Mapping | 343 | ||
| Concluding Remarks | 344 | ||
| REFERENCES | 344 | ||
| 36 -\rModeling the Aging Heart | 345 | ||
| Introduction | 345 | ||
| The Aging Heart | 345 | ||
| Aging, Arrhythmias, and Fibrotic Remodeling | 345 | ||
| Computer Modeling as a Tool in Arrhythmia Research | 345 | ||
| Chapter Scope | 346 | ||
| Modeling Fibrotic Remodeling in the Atria and Its Contribution to Atrial Fibrillation | 347 | ||
| Modeling of Fibrotic Remodeling in the Ventricles and the Link to Arrhythmias | 351 | ||
| Concluding Remarks | 351 | ||
| Acknowledgments | 351 | ||
| REFERENCES | 354 | ||
| VI -\rNeural Control of CardiacElectrical Activity | 356 | ||
| 37 -\rInnervation of the Sinoatrial Node | 356 | ||
| General Neuroanatomy of the Heart | 356 | ||
| Nerve Supply of the Sinoatrial Node Area | 357 | ||
| Morphology and Immunohistochemistry of the Sinoatrial Node Innervation in Humans and Other Mammals | 358 | ||
| Intrinsic Ganglia and Neuronal Somata Related With the Sinoatrial Node | 360 | ||
| Concluding Remarks | 360 | ||
| Acknowledgments | 361 | ||
| REFERENCES | 361 | ||
| 38 -\rMechanisms for Altered Autonomic and Oxidant Regulation of Cardiac Sodium Currents | 362 | ||
| Sodium Channels: Structural Aspects of Oxidant and Autonomic Regulation | 362 | ||
| Myocardial Metabolism and Oxidant Stress | 362 | ||
| Modulation of Cardiac Voltage-Dependent Sodium Channels in Health and Disease | 363 | ||
| Cardiac Metabolism, Oxidant Stress, and Voltage-Dependent Sodium Channels | 364 | ||
| Autonomic Regulation of Voltage-Dependent Sodium Channels | 366 | ||
| REFERENCES | 367 | ||
| 39 -\rPulmonary Vein Ganglia and the Neural Regulation of the Heart Rate | 370 | ||
| Intrinsic Nervous System of the Heart | 370 | ||
| Pulmonary Vein Ganglia and Heart Rate Control | 370 | ||
| Neuroanatomy | 370 | ||
| Control of Heart Rate | 370 | ||
| Modulation of Sinoatrial Node Activation Pattern | 371 | ||
| Clinical Implications | 372 | ||
| Pulmonary Vein Ganglia and Atrial Fibrillation | 373 | ||
| REFERENCES | 374 | ||
| 40 -\rNeural Activity and Atrial Tachyarrhythmias | 375 | ||
| Cardiac Autonomic Nervous System | 375 | ||
| Extrinsic Cardiac Nerves | 375 | ||
| Intrinsic Cardiac Nerves | 375 | ||
| Neural Activities in Atrial Electrophysiology and Arrhythmogenesis | 375 | ||
| Normal Neural Influences on Atrial Electrophysiology | 375 | ||
| Abnormal Neural Activities in Atrial Arrhythmogenesis | 375 | ||
| Recording Stellate Ganglion and Vagal Nerve Activity From Ambulatory Canines | 376 | ||
| Ambulatory Nerve Recording | 376 | ||
| Paroxysmal Atrial Tachyarrhythmias | 377 | ||
| Persistent Atrial Fibrillation | 378 | ||
| Recording Nerve Activities From the Skin | 379 | ||
| Subcutaneous Nerve Recording | 379 | ||
| Cutaneous Nerve Recording | 380 | ||
| Neuromodulation for Atrial Tachyarrhythmias | 380 | ||
| Ganglionated Plexi Ablation | 380 | ||
| Renal Sympathetic Denervation | 381 | ||
| Low-Level Vagus Nerve Stimulation | 383 | ||
| Other Forms of Neural Stimulation | 383 | ||
| Conclusions | 383 | ||
| Acknowledgments | 383 | ||
| REFERENCES | 385 | ||
| 41 -\rSympathetic Innervation and Cardiac Arrhythmias | 387 | ||
| Anatomy of Cardiac Sympathetic Innervation | 387 | ||
| Neural Remodeling of Sympathetic Innervation in Myocardial Pathology | 388 | ||
| Heart Failure | 388 | ||
| Myocardial Infarction | 389 | ||
| Atrial Fibrillation | 389 | ||
| Other Pathological Conditions | 390 | ||
| Assessment of Autonomic Function and Clinical Relevance | 390 | ||
| Heart Rate | 390 | ||
| Heart Rate Variability | 390 | ||
| Heart Rate Recovery | 390 | ||
| Baroreflex Sensitivity | 390 | ||
| Heart Rate Turbulence | 390 | ||
| T-Wave Alternans | 391 | ||
| Continuous Recording of Sympathetic Activity | 391 | ||
| Electrophysiological Effects of Sympathetic Stimulation | 391 | ||
| Sympathetic Modulation | 391 | ||
| Vagus Nerve Stimulation | 391 | ||
| Sympathetic Denervation | 393 | ||
| Conclusions | 393 | ||
| Acknowledgments | 393 | ||
| REFERENCES | 394 | ||
| VII -\rArrhythmia Mechanisms | 396 | ||
| 42 -\rThe Molecular Pathophysiology of Atrial Fibrillation | 396 | ||
| Etiological Determinants | 396 | ||
| Heart Disease | 396 | ||
| Genetic Determinants | 396 | ||
| Extracardiac Contributors | 396 | ||
| General Mechanisms and AtrialFibrillation Forms | 396 | ||
| Focal Ectopic Activity | 397 | ||
| Reentry | 397 | ||
| Molecular Control Mechanisms | 398 | ||
| Molecular Control of Gene Expression in Atrial Fibrillation | 398 | ||
| Molecular Determinants of Atrial Conduction Disturbances | 404 | ||
| Conduction Abnormalities due to Ion Channel Dysfunction | 404 | ||
| Structural Remodeling | 405 | ||
| Future Directions | 405 | ||
| Acknowledgments | 406 | ||
| Funding | 406 | ||
| REFERENCES | 406 | ||
| 43 -\rMyofibroblasts, Cytokines, and Persistent Atrial Fibrillation | 409 | ||
| Cardiac Fibroblasts and Myofibroblasts | 409 | ||
| Molecular Regulation of Cardiac Fibroblasts | 410 | ||
| Inflammation and Atrial Fibrillation | 411 | ||
| Cytokines and Human Atrial Fibrillation | 412 | ||
| Transforming Growth Factor-β1and Atrial Fibrillation | 412 | ||
| Angiotensin II and TransformingGrowth Factor-β1 | 413 | ||
| Effects of Other Cytokines on Ion Channels and Atrial Fibrillation | 414 | ||
| Macrophage Migration Inhibitory Factor | 414 | ||
| Effects of TNF-α on Ionic Currents | 414 | ||
| Leukemia Inhibitory Factor | 414 | ||
| Platelet-Derived Growth Factor | 414 | ||
| Myofibroblasts, Cytokines, and Myocyte Electrical Remodeling | 415 | ||
| Concluding Remarks | 416 | ||
| Acknowledgments | 417 | ||
| REFERENCES | 417 | ||
| 44 -\rRole of the Autonomic Nervous System in Atrial Fibrillation | 419 | ||
| The Cardiac Autonomic Nervous System | 419 | ||
| The Extrinsic and Intrinsic Cardiac Autonomic Nervous System | 419 | ||
| Noncholinergic, Nonadrenergic Neurotransmitters in the Intrinsic Cardiac Autonomic Nervous System | 421 | ||
| Autonomic Mechanisms of Atrial Fibrillation Initiation and Maintenance | 422 | ||
| The “Ca2+ Transient Triggering” Hypothesis | 422 | ||
| Rapid Firing From the Nonpulmonary Vein Sites: Ligament of Marshall and Superior Vena Cava | 422 | ||
| Perpetuation of Atrial Fibrillation: The First Few Hours and Beyond | 422 | ||
| Autonomic Basis for Complex Fractionated Atrial Electrograms | 423 | ||
| Ablating the Cardiac Autonomic Nervous System to Treat Atrial Fibrillation | 423 | ||
| Modulation of the Cardiac Autonomic Nervous System to Treat Atrial Fibrillation Without Destroying Autonomic Neural Elements | 424 | ||
| Perspectives | 424 | ||
| REFERENCES | 424 | ||
| 45 -\rRotors in Human Atrial Fibrillation | 426 | ||
| Mechanisms for the Initiation of Human Atrial Fibrillation | 426 | ||
| Mechanisms That Sustain Human Atrial Fibrillation | 426 | ||
| Mapping Atrial Fibrillation via Activation and Recovery: Action Potentials Versus Electrogram Surrogates | 428 | ||
| Mapping Considerations | 428 | ||
| Mapping Human Atrial Fibrillation Using Action Potentials | 428 | ||
| Electrogram-Based Mapping of Human Atrial Fibrillation | 429 | ||
| Differing Mechanisms of Human Atrial Fibrillation Revealed by Optical/Electrogram Approaches | 430 | ||
| VIII -\rMolecular Genetics and Pharmacogenomics | 473 | ||
| 50 -\rMechanisms in Heritable Sodium Channel Diseases | 473 | ||
| Cardiac Sodium Channel | 473 | ||
| Consequences of Sodium Channel Dysfunction | 474 | ||
| Delayed Repolarization | 475 | ||
| Congenital Long QT Syndrome | 475 | ||
| Perinatal and Neonatal LQT3 | 476 | ||
| Arrhythmia Susceptibility With Common SCN5A Variants | 476 | ||
| Impaired Impulse Propagation | 476 | ||
| Brugada Syndrome | 476 | ||
| Familial Progressive Conduction System Disease | 477 | ||
| Congenital Sick Sinus Syndrome and Atrial Standstill | 478 | ||
| Altered Intracellular Ion Homeostasis | 478 | ||
| Dilated Cardiomyopathy With Arrhythmia | 478 | ||
| Syndromes With Complex Mechanisms | 479 | ||
| REFERENCES | 480 | ||
| 51 -\rGenetic, Ionic, and Cellular Mechanisms Underlying the J Wave Syndromes | 483 | ||
| Acquired Brugada Pattern and Syndrome | 483 | ||
| Similarities and Differences Between Brugada Syndrome and Early Repolarization Syndrome | 483 | ||
| Genetics | 485 | ||
| Cellular Mechanisms Underlying Brugada Syndrome and Early Repolarization Syndrome | 485 | ||
| Therapy of Brugada Syndrome and Early Repolarization Syndrome | 488 | ||
| Pharmacological Approach to Therapy | 489 | ||
| Brugada Syndrome | 489 | ||
| Early Repolarization Syndrome | 490 | ||
| Acknowledgments | 490 | ||
| REFERENCES | 490 | ||
| 52 -\rInheritable Potassium Channel Diseases | 494 | ||
| Introduction | 494 | ||
| Long QT Syndrome | 494 | ||
| Long QT Syndrome as K+ Channel Disease | 494 | ||
| Pathophysiology of Long QT Syndrome | 495 | ||
| Long QT Syndrome Due to IKs Loss-of-Function | 496 | ||
| Long QT Syndrome Type 1 | 496 | ||
| Long QT Syndrome Type 5 | 497 | ||
| Long QT Syndrome Type 11 | 497 | ||
| Jervell and Lange-Nielsen Syndrome | 497 | ||
| Long QT Syndrome Due to IKr Loss-of-Function | 498 | ||
| Long QT Syndrome Type 2 | 498 | ||
| Long QT Syndrome Type 6 | 498 | ||
| Other Long QT Syndrome Subtypes | 499 | ||
| Long QT Syndrome Type 7 | 499 | ||
| Long QT Syndrome Type 13 | 500 | ||
| Short QT Syndrome | 500 | ||
| Short QT Syndrome Type 1 | 500 | ||
| Short QT Syndrome Type 2 | 500 | ||
| Short QT Syndrome Type 3 | 500 | ||
| Other Inheritable Potassium Channel Diseases | 500 | ||
| Brugada Syndrome and Early Repolarization Syndrome | 500 | ||
| Atrial Fibrillation | 501 | ||
| Sudden Infant Death Syndrome | 501 | ||
| Acknowledgments | 501 | ||
| REFERENCES | 502 | ||
| 53 -\rInheritable Phenotypes Associated With Altered Intracellular Calcium Regulation | 504 | ||
| Overview of Calcium Homeostasis in the Heart | 504 | ||
| Calcium Cycling in Excitation–Contraction Coupling | 504 | ||
| Adrenergic Regulation of Calcium Homeostasis | 504 | ||
| Arrhythmia due to Mutations in Calcium-Handling Proteins | 506 | ||
| Catecholaminergic Polymorphic Ventricular Tachycardia | 506 | ||
| Ryanodine Receptor 2 Mutations and Catecholaminergic Polymorphic Ventricular Tachycardia 1 | 506 | ||
| Ryanodine Receptor 2 Structure and Function | 506 | ||
| Arrhythmogenesis Because of Ryanodine Receptor 2 Mutations | 507 | ||
| Calsequestrin 2 Mutations and Catecholaminergic Polymorphic Ventricular Tachycardia 2 | 508 | ||
| Triadin Mutations and Catecholaminergic Polymorphic Ventricular Tachycardia 3 | 509 | ||
| Calmodulin Mutations and Catecholaminergic Polymorphic Ventricular Tachycardia 4 | 509 | ||
| Inherited Structural Cardiomyopathy | 510 | ||
| Conclusions and Perspectives | 511 | ||
| REFERENCES | 511 | ||
| IX -\rPharmacologic, Genetic, and Cell Therapy of Ion Channel Dysfunction | 513 | ||
| 54 -\rPharmacological Bases of Antiarrhythmic Therapy | 513 | ||
| Na+ Channel Blockers: Class I Antiarrhythmic Drugs | 513 | ||
| Atrial-Selective Na+ Channel Blockers | 515 | ||
| Late Na+ Current Inhibition | 516 | ||
| Antiarrhythmic Effects of Class I Antiarrhythmic Drugs | 517 | ||
| β-Blockers: Class II Antiarrhythmic Drugs | 517 | ||
| K+ Channel Blockers: Class III Antiarrhythmic Effects | 518 | ||
| Amiodarone and Dronedarone | 519 | ||
| Calcium Channel Blockers: Class IV Antiarrhythmic Drugs | 520 | ||
| Gap-Junction Coupling Enhancers | 520 | ||
| Stretch-Activated Channels | 520 | ||
| Modulation of Ion Channel Trafficking | 520 | ||
| Targeting Intracellular Calcium Handling | 521 | ||
| Pharmacological Treatment of Inherited Cardiac Arrhythmia Syndromes | 521 | ||
| Target Cardiac Remodeling: Upstream Therapies | 521 | ||
| Antiinflammatory Agents | 522 | ||
| Statins | 522 | ||
| Omega-3 Polyunsaturated Fatty Acids | 522 | ||
| Antifibrotic Agents | 522 | ||
| X -\rDiagnostic Evaluation | 559 | ||
| 59 -\rAssessment of the Patient With a Cardiac Arrhythmia | 559 | ||
| Taking History of a Patient With Suspected Arrhythmia | 559 | ||
| Symptoms and Signs of Arrhythmia | 559 | ||
| General | 559 | ||
| Palpitations | 559 | ||
| Differentiation Between Skipped Beats Versus Sustained Palpitation | 559 | ||
| Impact of Associated Cardiac or Systemic Diseases | 560 | ||
| Signs of Presyncope and Syncope | 560 | ||
| Sudden Cardiac Death (see Chapters 98 and 99 | 561 | ||
| Exercise, Swimming, Emotions, and Auditory Stimuli | 561 | ||
| Physical Examination | 561 | ||
| Physical Manifestations of Atrioventricular Dissociation | 561 | ||
| Atrioventricular Block (see Chapter 106) | 561 | ||
| Carotid Sinus Massage and Valsalva | 562 | ||
| Laboratory Tests | 562 | ||
| Rationale for the Use of Ambulatory Electrocardiography (see Chapter 66) | 562 | ||
| Correlation With Cardiac Arrhythmias on 24-Hour and Long-Term Electrocardiographic Monitoring | 563 | ||
| Twenty-Four–Hour Holter Recordings | 563 | ||
| Continuous Event Recording Versus 24- to 48-Hour Holter Monitoring | 563 | ||
| Autotriggered Continuous Event Recording Versus Traditional Continuous Event Recording Versus Holter Recording | 563 | ||
| Insertable Loop Recorder | 563 | ||
| Electrophysiological Study | 564 | ||
| Stress Testing and Other Noninvasive Studies | 564 | ||
| Tests Indicated for Specific Symptoms | 564 | ||
| Syncope | 564 | ||
| Postural Orthostatic Tachycardia Syndrome (see Chapter 104) | 564 | ||
| Bradyarrhythmias | 565 | ||
| Tachyarrhythmias | 565 | ||
| Cryptogenic Stroke Associated With Paroxysmal Atrial Fibrillation | 565 | ||
| Evaluation of Athletes | 565 | ||
| Summary | 565 | ||
| REFERENCES | 566 | ||
| 60 -\rDifferential Diagnosis of Narrow and Wide Complex Tachycardias | 567 | ||
| Narrow QRS Tachycardias | 567 | ||
| Diagnostic Possibilities | 567 | ||
| History and Physical Examination | 567 | ||
| Electrocardiographic Differential Diagnosis | 567 | ||
| Special Cases | 569 | ||
| Wide QRS Tachycardias | 569 | ||
| Diagnostic Possibilities | 569 | ||
| History and Physical Examination | 569 | ||
| Electrocardiographic Differential Diagnosis | 570 | ||
| Special Cases | 572 | ||
| Other Sources of Electrocardiographic Material | 572 | ||
| Remaining Problems | 572 | ||
| Summary | 572 | ||
| REFERENCES | 573 | ||
| 61 -\rElectroanatomical Mapping for Arrhythmias | 574 | ||
| Why Do We Use Mapping Systems? | 574 | ||
| When Are Mapping Systems Useful? | 574 | ||
| Principles of Electroanatomical Mapping: Point Acquisition | 574 | ||
| What Do We Map? | 574 | ||
| How to Acquire an Accurate Point | 575 | ||
| Reference | 575 | ||
| Window | 575 | ||
| Annotating Points | 576 | ||
| Mapping Technologies | 576 | ||
| Carto | 576 | ||
| Visitag | 579 | ||
| UNIVU | 580 | ||
| Passo | 580 | ||
| EnSite | 580 | ||
| EnSite: NavX Versus Velocity | 580 | ||
| Rhythmia | 581 | ||
| Principles of Electroanatomical Mapping: Optimizing Creation of a Valid Map | 582 | ||
| Respiratory Compensation | 582 | ||
| Use of Multipolar Catheters and Automated Annotation Versus Point-by-Point Mapping | 582 | ||
| Considering Anatomically Proximate Structures | 582 | ||
| Map Shifts | 582 | ||
| Contact Force | 584 | ||
| Integration of Computed Tomography and Magnetic Resonance Imaging | 584 | ||
| Additional Considerations in Modern Mapping Techniques | 584 | ||
| Integrated Intracardiac Echocardiography With Electroanatomical Mapping | 584 | ||
| Rotor Mapping | 586 | ||
| Conclusion | 586 | ||
| REFERENCES | 586 | ||
| 62 -\rComputed Tomography for Electrophysiology | 587 | ||
| Technical Background of Cardiac Computed Tomography Imaging | 587 | ||
| Image Integration | 588 | ||
| Fundamental Concepts of Image Integration | 588 | ||
| Technical Aspects of Image Segmentationand Registration | 588 | ||
| Steps for Image Integration With Commercially Available Mapping Systems | 590 | ||
| Current Applications of Cardiac Computed Tomography in Cardiac Electrophysiology | 592 | ||
| Pre- and Periprocedural Computed Tomography Imaging for Guiding Atrial and Ventricular Arrhythmia Ablations | 592 | ||
| Atrial Ablations | 592 | ||
| Ventricular Ablations | 593 | ||
| Cardiac Computed Tomography for Pacing and Cardiac Resynchronization Therapy | 595 | ||
| Assessment of Procedural Complications | 596 | ||
| Pulmonary Vein Stenosis | 596 | ||
| Atrioesophageal Fistula | 596 | ||
| Periesophageal Vagal Injury | 597 | ||
| Phrenic Nerve Injury | 597 | ||
| Stroke and Transient Ischemic Attack | 597 | ||
| Future Applications and Evolving Technology | 598 | ||
| Assessment of Myocardial Fibrosis and Periinfarct Border Zone | 598 | ||
| Lesion Imaging | 599 | ||
| Real-Time Computed Tomography in theElectrophysiology Laboratory | 599 | ||
| REFERENCES | 599 | ||
| 63 -\rComputed Tomography and Magnetic Resonance Imaging for Electrophysiology | 601 | ||
| Basics of Cardiac Computed Tomography | 601 | ||
| Basics of Cardiac Magnetic Resonance Imaging | 601 | ||
| Advantages of Each Imaging Modality in the Electrophysiology Setting | 602 | ||
| Imaging the Arrhythmia Substrate: Implications for Diagnosis and Prognosis | 602 | ||
| Ischemic Cardiomyopathy | 602 | ||
| Nonischemic Cardiomyopathy | 603 | ||
| Cardiac Sarcoidosis | 603 | ||
| Myocarditis | 603 | ||
| Hypertrophic Cardiomyopathy | 604 | ||
| Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy | 604 | ||
| Surgical Scar | 604 | ||
| Chagas Disease | 604 | ||
| Procedure Guidance | 604 | ||
| Atrial Fibrillation | 604 | ||
| Ventricular Tachycardia | 605 | ||
| Mechanical Dyssynchrony and Cardiac Resynchronization Therapy | 606 | ||
| Summary | 606 | ||
| REFERENCES | 606 | ||
| 64 - Intracardiac Echocardiography for Electrophysiology | 608 | ||
| Intracardiac Echocardiographic Platforms | 608 | ||
| Basic Intracardiac EchocardiographicImaging Planes | 608 | ||
| Established Clinical Uses | 608 | ||
| Transseptal Puncture | 608 | ||
| Atrial Fibrillation | 609 | ||
| Atrial Flutter | 609 | ||
| Ventricular Tachycardia | 609 | ||
| Left Ventricular Outflow Tract. The ablation of ventricular arrhythmias arising from the LV ostium presents unique challenges, d... | 609 | ||
| Detecting and Preventing Complications | 612 | ||
| Novel/Clinical Uses in Development | 613 | ||
| Left Atrial Appendage Visualization | 613 | ||
| Low/Zero Fluoroscopy Procedures | 613 | ||
| Lesion Assessment | 613 | ||
| Lead Management | 614 | ||
| Summary | 614 | ||
| REFERENCES | 614 | ||
| 65 -\rExercise-Induced Arrhythmias | 615 | ||
| Physiological Changes During Exercise Related to Arrhythmia Development | 615 | ||
| Exercise-Induced Supraventricular Arrhythmias | 615 | ||
| Diagnostic Approach | 616 | ||
| Therapeutic Approach in Athletes With Atrial Fibrillation | 616 | ||
| Other Supraventricular Arrhythmias | 616 | ||
| Exercise-Induced Ventricular Arrhythmias | 617 | ||
| Premature Ventricular Contractions and Nonsustained Ventricular Tachycardia in Apparently Healthy Subjects | 617 | ||
| Outflow Tract Ventricular Tachycardia | 617 | ||
| Idiopathic Left Ventricular Tachycardia | 617 | ||
| Conditions Associated With Increased Risk of Exercise-Induced Arrhythmias and Sudden Cardiac Death | 618 | ||
| Patients With Coronary Artery Disease | 618 | ||
| Patients With Coronary Anomalies | 618 | ||
| Arrhythmogenic Right Ventricular Cardiomyopathy | 618 | ||
| Hypertrophic Cardiomyopathy | 619 | ||
| Long QT Syndrome | 619 | ||
| Conclusion | 621 | ||
| REFERENCES | 621 | ||
| 66 -\rCardiac Monitoring: Short- and Long-Term Recording | 623 | ||
| Short-Term Recording | 623 | ||
| Holter Monitoring | 623 | ||
| Intermittent Event Recorders | 624 | ||
| Intermediate Duration Monitoring | 624 | ||
| Patch Recording Devices | 624 | ||
| Hand-Held and Wrist Recorders | 624 | ||
| Extended Holter | 624 | ||
| External Loop Recorders | 625 | ||
| Vest Technology | 625 | ||
| Prolonged Monitoring: Insertable Cardiac Monitors | 626 | ||
| Clinical Studies | 626 | ||
| Event Classification | 627 | ||
| Emerging Role of Extended Monitoring in Atrial Fibrillation | 627 | ||
| Additional Uses of Extended Monitoring Technologies | 628 | ||
| Future Directions | 628 | ||
| Conclusion | 628 | ||
| REFERENCES | 629 | ||
| 67 -\rHead-up Tilt Table Testing | 630 | ||
| Historical Background | 630 | ||
| Transient Loss of Consciousness and Syncope | 630 | ||
| Pathophysiology of Loss of Consciousness | 630 | ||
| Approach to the Diagnosis of Syncope | 631 | ||
| Physiological Impact of Upright Posture | 631 | ||
| Reflex Faints | 632 | ||
| Head-up Tilt as a Useful Model of Spontaneous Vasovagal Syncope | 632 | ||
| Pathophysiology of Orthostatic Hypotension | 633 | ||
| Orthostatic Provocation for Assessing Susceptibility to Vasovagal Syncope and Orthostatic Hypotension | 633 | ||
| Protocols for Head-up Tilt Table Testing and Active Standing Test | 633 | ||
| Passive Drug-Free Tilt Testing | 634 | ||
| Adenosine and Adenosine Triphosphate | 635 | ||
| Shifting Patient Patterns in the Tilt Table Testing Laboratory | 635 | ||
| Video-Electroencephalogram Monitoring | 635 | ||
| Laboratory Environment and Patient Preparation | 635 | ||
| Recordings | 635 | ||
| Tilt Table Design | 635 | ||
| Tilt Angle and Duration | 636 | ||
| Personnel | 636 | ||
| Active Standing Versus Head-up Tilt Test | 636 | ||
| Reproducibility of Head-up Tilt Table T | 636 | ||
| Risks and Complications | 636 | ||
| Head-up Tilt Testing and Treatment of Vasovagal Syncope | 636 | ||
| Overview of Uses for Head-up Tilt Table Testing | 636 | ||
| Conclusions | 636 | ||
| Acknowledgment | 637 | ||
| REFERENCES | 637 | ||
| 68 -\rAutonomic Regulation and Cardiac Risk | 638 | ||
| Heart Rate Variability | 638 | ||
| Baroreflex | 639 | ||
| Other Indices | 641 | ||
| Conclusion | 642 | ||
| REFERENCES | 643 | ||
| 69 -\rT-Wave Alternans | 644 | ||
| History of Cardiac Alternans | 644 | ||
| Mechanisms Underlying T-Wave Alternans | 644 | ||
| Cellular Mechanisms of Alternans | 644 | ||
| Methodology of T-Wave Alternans Assessment | 645 | ||
| The Spectral Analysis Approach | 646 | ||
| Classification of Spectral Analysis Test Results | 646 | ||
| Classification of Modified Moving Average Test Results | 646 | ||
| Clinical Studies on Microvolt T-Wave Alternans | 646 | ||
| XI -\rSupraventricular Tachyarrhythmias: Mechanisms, Clinical Features, and Management | 674 | ||
| 72 -\rSinus Node Abnormalities | 674 | ||
| The Sinus Node | 674 | ||
| Sinus Node Disease | 674 | ||
| Electrophysiological and Structural Abnormalities | 676 | ||
| Atrial Abnormalities in Sinus Node Disease | 676 | ||
| Familial Sick Node Disease | 677 | ||
| SCN5A Mutations | 677 | ||
| HCN4 Mutations | 677 | ||
| ANK2 Mutations | 677 | ||
| MYH6 Mutations | 677 | ||
| Other Mutations | 678 | ||
| Sinus Node Remodeling | 678 | ||
| Aging | 678 | ||
| XII -\rVentricular Tachyarrhythmias:Mechanisms, Clinical Features, and Management | 776 | ||
| 80 -\rPremature Ventricular Complexes | 776 | ||
| Mechanism | 776 | ||
| Epidemiology | 776 | ||
| History | 776 | ||
| Prevalence and Frequency | 776 | ||
| Prognosis | 776 | ||
| Diagnosis | 777 | ||
| Clinical Presentation | 777 | ||
| Electrocardiography | 777 | ||
| Clinical Management | 777 | ||
| Decision to Treat | 777 | ||
| Pharmacotherapy | 777 | ||
| Catheter Ablation | 778 | ||
| Techniques | 778 | ||
| Outcomes | 778 | ||
| Complications | 780 | ||
| Conclusions and Future Directions | 780 | ||
| REFERENCES | 780 | ||
| 81 -\rOutflow Tract Ventricular Tachyarrhythmias: Mechanisms, Clinical Features, and Management | 782 | ||
| Anatomy | 782 | ||
| Right Ventricular Outflow Tract | 782 | ||
| Relationship to Coronary Arteries | 782 | ||
| Left Ventricular Outflow Tract | 782 | ||
| Aortic and Pulmonary Valve Cusps | 782 | ||
| Epicardial and Perivascular Sites | 782 | ||
| Epidemiology | 783 | ||
| Symptoms | 783 | ||
| Triggers | 783 | ||
| Mechanism | 783 | ||
| Diagnosis | 784 | ||
| Right Ventricular Outflow Tract | 784 | ||
| Left Ventricular Outflow Tract | 785 | ||
| Prognosis | 786 | ||
| Management | 787 | ||
| Medical Therapy | 787 | ||
| Mapping and Catheter Ablation | 787 | ||
| REFERENCES | 791 | ||
| 82 -\rFascicular Ventricular Arrhythmias | 793 | ||
| Verapamil-Sensitive Fascicular Ventricular Tachycardia | 793 | ||
| Clinical Manifestation | 793 | ||
| Classification | 793 | ||
| Mechanism and Ventricular Tachycardia Circuit | 793 | ||
| Anatomical Substrate | 794 | ||
| Differential Diagnosis | 794 | ||
| Therapy | 794 | ||
| Focal Ventricular Tachycardia and Ventricular Premature Contraction Originating From the Purkinje System | 796 | ||
| Mechanism | 796 | ||
| Therapy | 796 | ||
| Ventricular Premature Contractions and Ventricular Fibrillation Triggered From the Purkinje System | 796 | ||
| Bundle Branch Reentry and Interfascicular Reentry | 797 | ||
| Conclusions | 797 | ||
| REFERENCES | 798 | ||
| 83 -\rBundle Branch Reentry Tachycardia | 799 | ||
| Surface Electrogram and Classification | 799 | ||
| Pathophysiology | 799 | ||
| Initiation of Tachycardia | 801 | ||
| Diagnosis | 803 | ||
| Mapping | 804 | ||
| Differential Diagnosis | 804 | ||
| Catheter Ablation | 807 | ||
| Right Bundle Branch Ablation | 807 | ||
| Left Bundle Branch Ablation | 808 | ||
| Ablation of Interfascicular Tachycardia | 809 | ||
| Clinical Outcomes | 809 | ||
| Complications | 811 | ||
| Conclusions | 811 | ||
| REFERENCES | 813 | ||
| 84 -\rIschemic Heart Disease | 814 | ||
| Electroanatomical Substrate | 814 | ||
| Ventricular Tachycardia Mechanisms | 815 | ||
| Initiation | 815 | ||
| Resetting and Entrainment | 815 | ||
| Clinical Presentation and Acute Management | 818 | ||
| Chronic Management and Areas of Uncertainty | 818 | ||
| Implantable Cardioverter Defibrillator | 818 | ||
| Antiarrhythmic Medications | 818 | ||
| Neuromodulation | 818 | ||
| Catheter Ablation | 818 | ||
| Acknowledgment | 818 | ||
| REFERENCES | 819 | ||
| 85 -\rVentricular Tachycardia in Patients With Dilated Cardiomyopathy | 820 | ||
| Definition, Etiology, and Genetics of Dilated Cardiomyopathy | 820 | ||
| Familial Forms of Dilated Cardiomyopathy Associated With Arrhythmias or Conduction Disturbances | 820 | ||
| LMNA-Associated Dilated Cardiomyopathy | 820 | ||
| TTN-Associated Dilated Cardiomyopathy | 820 | ||
| X-Linked Forms of Dilated Cardiomyopathy | 820 | ||
| Ventricular Arrhythmias in Nonischemic Dilated Cardiomyopathy | 821 | ||
| Bundle Branch Reentry Ventricular Tachycardia | 821 | ||
| Tachycardia-Induced Dilated Cardiomyopathy | 821 | ||
| Sudden Cardiac Death Risk Stratification in Nonischemic Dilated Cardiomyopathy | 821 | ||
| Left Ventricular Ejection Fraction and New York Heart Association Functional Class | 822 | ||
| Role of Cardiac Magnetic ResonanceImaging in Risk Stratification for Sudden Cardiac Death | 822 | ||
| Electroanatomical Substrate forVentricular Tachycardia in Patients With Dilated Cardiomyopathy | 822 | ||
| Ablation Targets and Outcomes ofVentricular Tachycardia Ablation in Patients With Dilated Cardiomyopathy | 823 | ||
| Management of Ventricular Tachycardia in Patients With Dilated Cardiomyopathy and Left Ventricular Assist Devices | 824 | ||
| Specific Pharmacological Therapy for Ventricular Tachycardia in Dilated Cardiomyopathy | 824 | ||
| Defibrillator Therapy for Prevention of Sudden Cardiac Death in Dilated Cardiomyopathy | 826 | ||
| Wearable Cardioverter Defibrillators in Patients With Dilated Cardiomyopathy and at High Risk for Sudden Cardiac Death | 827 | ||
| Conclusion | 827 | ||
| REFERENCES | 827 | ||
| 86 -\rVentricular Arrhythmias in Hypertrophic Cardiomyopathy: Sudden Death, Risk Stratification, and Prevention With Implantable Defib... | 829 | ||
| Clinical Presentation and Sudden Cardiac Death | 829 | ||
| Myocardial Substrate | 829 | ||
| Ventricular Tachyarrhythmias | 829 | ||
| Initiatives for Sudden Death Prevention | 831 | ||
| Drugs | 831 | ||
| Introduction and Evolution of the Implantable Cardioverter Defibrillator | 831 | ||
| Implantable Cardioverter Defibrillators in the Hypertrophic Cardiomyopathy Population | 831 | ||
| Implantable Cardioverter Defibrillator Efficacy in Hypertrophic Cardiomopathy | 831 | ||
| Cohort Survival With Implantable Cardioverter Defibrillators | 832 | ||
| Selecting Patients for Implantable Cardioverter Defibrillators | 833 | ||
| Conventional Risk Markers | 833 | ||
| Modifiable Risk Markers (see Fig. 86.3) | 836 | ||
| Other Disease Variables | 836 | ||
| Clinical Decision-Making | 836 | ||
| Ambiguous Zones | 836 | ||
| Counting Risk Factors | 837 | ||
| Implantable Cardioverter Defibrillator Complications | 838 | ||
| Statistically Based Risk Predictors | 838 | ||
| REFERENCES | 838 | ||
| 87 -\rVentricular Tachycardias in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy | 840 | ||
| Clinical Presentation and Natural History | 840 | ||
| Etiology | 840 | ||
| Pathogenesis | 841 | ||
| Management | 846 | ||
| Establishing an Accurate Diagnosis | 846 | ||
| Risk Stratification and Deciding When to Implant an Implantable Cardioverter Defibrillator | 847 | ||
| Minimizing Symptoms and Preventing Implantable Cardioverter Defibrillator Therapies | 847 | ||
| Pharmacological Therapy | 847 | ||
| Catheter Ablation | 848 | ||
| Exercise Restriction | 848 | ||
| Prevent Progression | 848 | ||
| Cardiac Transplantation | 848 | ||
| Summary | 848 | ||
| REFERENCES | 849 | ||
| 88 -\rVentricular Tachycardias in Catecholaminergic Cardiomyopathy (Catecholaminergic Polymorphic Ventricular Tachycardia) | 850 | ||
| Historical Background | 850 | ||
| Diagnosis | 850 | ||
| Clinical Manifestations | 850 | ||
| Clinical Presentation | 850 | ||
| Cardiologic Examination | 851 | ||
| Supraventricular Disease Manifestations | 852 | ||
| Natural Course | 852 | ||
| Genetic Basis | 852 | ||
| Cardiac Ryanodine Receptor (CPVT 1) | 852 | ||
| Cardiac Calsequestrin (CPVT 2) | 853 | ||
| Triadin | 853 | ||
| Calmodulin | 853 | ||
| Genetic Testing | 853 | ||
| Differential Diagnosis | 854 | ||
| Clinical Management | 854 | ||
| Risk Stratification | 854 | ||
| Lifestyle | 855 | ||
| β-Adrenoceptor Blockade | 855 | ||
| Flecainide | 855 | ||
| Left Cardiac Sympathetic Denervation | 855 | ||
| Implantable Cardioverter Defibrillator | 856 | ||
| Other and Future Therapies | 856 | ||
| REFERENCES | 856 | ||
| 89 -\rVentricular Arrhythmias in Heart Failure | 858 | ||
| Etiology | 858 | ||
| EtiologyPatients Presenting With Ventricular Arrhythmias and Reduced Ejection Fraction Without Prior Heart Failure Diagnosis | 858 | ||
| General Evaluation | 858 | ||
| Inflammatory Myocarditis | 858 | ||
| Genetic Cardiomyopathy | 860 | ||
| Amyloidosis | 860 | ||
| Potentially Reversible Causes of Cardiomyopathy | 860 | ||
| Hemodynamic Triage and Management Prior to Procedures | 861 | ||
| Hemodynamic Profiles: Filling and Flow | 861 | ||
| Look at the Right Ventricle | 862 | ||
| Initial Hemodynamic Optimization | 862 | ||
| Limited Role of Cardiac Transplantation | 863 | ||
| Treatment of Tachyarrhythmias in Heart Failure | 864 | ||
| Antiarrhythmic Drugs in Heart Failure | 864 | ||
| Tracking the Heart Failure Journey | 865 | ||
| Enhanced Survival With Current Therapies | 865 | ||
| Increasing Prevalence of End-Stage Heart Failure | 866 | ||
| Shared Decision-Making | 866 | ||
| Risk Scores and Uncertainty | 866 | ||
| Annual Review and Milestones | 866 | ||
| Procedures and the Implantable Cardioverter-Defibrillator in Advanced Heart Failure | 867 | ||
| Summary | 867 | ||
| REFERENCES | 868 | ||
| 90 -\rArrhythmias and Conduction Disturbances in Noncompaction Cardiomyopathy | 870 | ||
| Pathology of Left Ventricular Noncompaction | 870 | ||
| Incidence of Left Ventricular Noncompaction | 870 | ||
| Clinical Features and Diagnosis of Left Ventricular Noncompaction | 871 | ||
| Subtypes of Left Ventricular Noncompaction | 871 | ||
| Imaging of Left Ventricular Noncompaction | 871 | ||
| Electrocardiography in Left Ventricular Noncompaction | 873 | ||
| Arrhythmias in Left Ventricular Noncompaction | 873 | ||
| Clinical Genetics of Left Ventricular Noncompaction | 874 | ||
| Molecular Genetics of Left Ventricular Noncompaction | 874 | ||
| Therapy and Outcome | 875 | ||
| Heart Failure | 875 | ||
| Specific Conditions | 876 | ||
| Antithrombotic Therapy | 876 | ||
| Arrhythmias | 876 | ||
| Genetic Counseling | 876 | ||
| Acknowledgments | 876 | ||
| REFERENCES | 876 | ||
| 91 -\rVentricular Arrhythmias in Takotsubo Cardiomyopathy | 878 | ||
| Clinical Characteristics of Takotsubo Cardiomyopathy | 878 | ||
| Electrocardiographic Changes | 878 | ||
| Ventricular Arrhythmias | 879 | ||
| Pathogenesis of Ventricular Arrhythmias | 881 | ||
| Management | 881 | ||
| Conclusions | 882 | ||
| REFERENCES | 882 | ||
| 92 -\rBrugada Syndrome | 883 | ||
| Electrocardiographical Features | 883 | ||
| Genetics | 883 | ||
| Genetic and Environmental Modulators | 884 | ||
| Overlapping Syndromes | 885 | ||
| Early Repolarization Syndrome | 886 | ||
| Lev-Lenègre Syndrome | 886 | ||
| Sick Sinus Syndrome | 886 | ||
| Atrial Fibrillation | 886 | ||
| Long QT Syndrome Type 3 | 886 | ||
| Epilepsy | 886 | ||
| Myotonic Phenotypes | 886 | ||
| Risk Stratification | 887 | ||
| Postulated Noninvasive Markers of Arrhythmic Risk in Brugada Syndrome | 887 | ||
| Therapeutic Options and Recommendations for Brugada Syndrome Patients | 888 | ||
| Implantable Cardioverter Defibrillator | 888 | ||
| Pharmacological Treatment in Brugada Syndrome | 888 | ||
| Radiofrequency Catheter Ablation in Brugada Syndrome | 888 | ||
| External Factors and Brugada Syndrome | 888 | ||
| Brugada Syndrome and Pregnancy | 889 | ||
| Brugada Syndrome in Children | 889 | ||
| Diagnostic and Clinical Presentation | 889 | ||
| Drug Challenge Test | 889 | ||
| Electrophysiological Study in Children | 889 | ||
| Therapeutic Implications and Implantable Cardioverter Defibrillator Implantation | 889 | ||
| Familial Screening | 889 | ||
| Brugada Syndrome in Older Individuals | 889 | ||
| The Future | 890 | ||
| REFERENCES | 890 | ||
| 93 -\rLong and Short QT Syndromes | 893 | ||
| Long QT Syndrome | 893 | ||
| Genetic Basis of Long QT Syndrome | 893 | ||
| Potassium-Related Long QT Syndrome:The Most Common Forms | 893 | ||
| Sodium-Related Long QT Syndrome: The Most Eclectic Forms | 893 | ||
| Calcium-Related Long QT Syndrome: The Most Complex and Dangerous Forms | 894 | ||
| Prevalence | 895 | ||
| Clinical Presentation | 895 | ||
| Cardiac Events and Their Relation to Genotype | 895 | ||
| Electrocardiographic Aspects | 896 | ||
| QT Interval Duration | 896 | ||
| T Wave Morphology | 896 | ||
| T Wave Alternans | 896 | ||
| Heart Rate and Its Reflex Control | 896 | ||
| Echocardiographic Abnormalities | 897 | ||
| Jervell and Lange-Nielsen Syndrome | 897 | ||
| Clinical Diagnosis | 897 | ||
| Molecular Diagnosis in Long QT Syndrome | 898 | ||
| Who Should Be Screened for Long QT Syndrome and Medicolegal Implications | 898 | ||
| Molecular Genetics and Risk Stratification | 898 | ||
| Sudden Infant Death Syndrome and Neonatal Electrocardiogram Screening | 899 | ||
| Therapy | 900 | ||
| Antiadrenergic Interventions | 900 | ||
| β-Adrenergic Blockade | 900 | ||
| Left Cardiac Sympathetic Denervation | 900 | ||
| Cardiac Pacing | 900 | ||
| Implantable Cardioverter Defibrillators | 901 | ||
| Gene-Specific Therapy and Management | 901 | ||
| Asymptomatic Long QT Syndrome Patients and Patients With a Normal QTc | 901 | ||
| Short QT Syndrome | 901 | ||
| Genetic Basis of Short QT Syndrome | 901 | ||
| Clinical Presentation | 902 | ||
| Clinical Diagnosis | 902 | ||
| Risk Stratification and Therapy | 903 | ||
| REFERENCES | 903 | ||
| 94 -\rAndersen-Tawil Syndrome | 905 | ||
| Andersen-Tawil Syndrome | 905 | ||
| Clinical Manifestations | 905 | ||
| Phenotypic Overlap Between Andersen-Tawil Syndrome and Catecholaminergic Polymorphic Ventricular Tachycardia | 905 | ||
| Molecular Correlate of IK1 | 907 | ||
| Cellular Basis | 907 | ||
| Treatment Options | 908 | ||
| REFERENCES | 909 | ||
| 95 - T imothy Syndrome | 910 | ||
| Pathophysiology | 910 | ||
| Genetics of Timothy Syndrome | 910 | ||
| Novel CACNA1c Mutations and Nonsyndromic Timothy Syndrome | 910 | ||
| Functional Characterization of CACNA1c Mutations in Timothy Syndrome | 910 | ||
| Calcium Channel Structure and Function | 910 | ||
| Pathophysiology of the Extracardiac Manifestations of Timothy Syndrome | 914 | ||
| Clinical Presentation | 914 | ||
| Clinical Phenotype of Typical Timothy Syndrome | 914 | ||
| Cardiac Manifestations | 915 | ||
| Facial, Skeletal, and Muscular Findings | 915 | ||
| Neurological | 915 | ||
| Metabolic | 915 | ||
| Timothy Syndrome and LQTS | 915 | ||
| Cardiac Events and Mortality | 915 | ||
| Therapy | 916 | ||
| Summary | 916 | ||
| REFERENCES | 916 | ||
| 96 - J-Wave Syndromes | 917 | ||
| Acquired J-Wave Syndromes: Hypothermia and Ischemic Ventricular Fibrillation | 917 | ||
| Congenital J-Wave Syndromes: Brugada Syndrome and Idiopathic Ventricular Fibrillation With Early Repolarization | 918 | ||
| Early Repolarization in Healthy Individuals and J-Waves in Idiopathic Ventricular Fibrillation | 918 | ||
| Arrhythmic Risk for Patients With Early Repolarization in Large Prospective Population Studies | 920 | ||
| Approach to the Patient With J-Waves | 922 | ||
| Gender | 922 | ||
| History of Familial Sudden Death | 922 | ||
| J-Wave Amplitude | 922 | ||
| Pattern of Early Repolarization | 922 | ||
| REFERENCES | 924 | ||
| 97 - Idiopathic Ventricular Fibrillation | 925 | ||
| Definition | 925 | ||
| Phenotype and Triggers of Idiopathic Ventricular Fibrillation | 925 | ||
| Electrocardiogram Phenomenology | 925 | ||
| Molecular Mechanisms | 926 | ||
| Diagnostic Evaluation | 926 | ||
| Interaction With Other Inherited Arrhythmias | 928 | ||
| Management and Follow-up | 929 | ||
| Future Directions | 931 | ||
| REFERENCES | 931 | ||
| 98 - Sudden Infant Death Syndrome | 932 | ||
| Arrhythmia as a Cause of Sudden Infant Death Syndrome | 932 | ||
| Sudden Infant Death Syndrome, Long QT Syndrome, and Environmental Factors | 932 | ||
| Sudden Infant Death Syndrome and Other Inherited Arrhythmia Syndromes | 933 | ||
| Sudden Infant Death Syndrome and Channelopathies: Frequency and Spectrum | 934 | ||
| Implications for Screening, Therapy, and Further Research | 935 | ||
| REFERENCES | 936 | ||
| 99 - Sudden Cardiac Death in Adults | 937 | ||
| Sudden Cardiac Death as a PublicHealth Burden | 937 | ||
| Pathological Substrates in Sudden Cardiac Death Victims | 941 | ||
| Prediction and Strategies for Prevention of Sudden Cardiac Death | 942 | ||
| Prediction of Risk of Sudden Cardiac Death in Coronary Heart Disease | 943 | ||
| Sudden Cardiac Death Risk in Nonischemic Dilated Cardiomyopathy | 944 | ||
| Inherited Basis of Sudden Cardiac Death Risk in Adults | 944 | ||
| Epidemiological Paradigms for Sudden Cardiac Death Prediction | 945 | ||
| Interventional Epidemiology of Sudden Cardiac Death Risk | 946 | ||
| REFERENCES | 948 | ||
| 100 - Arrhythmia in Neurological Disease | 949 | ||
| Neurological Disorders With Transient Arrhythmia Manifestations | 949 | ||
| Neurogenic Heart Disease | 949 | ||
| Autonomic Nervous System and Neuronal Networks | 949 | ||
| Pathophysiology of Neurogenic Heart Disease | 949 | ||
| Pathology | 949 | ||
| Acute Cerebrovascular Disease | 950 | ||
| XIII -\rSyncope and Bradyarrhythmias | 983 | ||
| 103 - Syncope | 983 | ||
| Definitions and Scope | 983 | ||
| Definitions | 983 | ||
| Significance of Syncope | 983 | ||
| Etiologies and Pathophysiology | 983 | ||
| Pathophysiology of Neurally Mediated Syncope | 983 | ||
| Orthostatic Hypotension | 983 | ||
| Carotid Hypersensitivity | 983 | ||
| Cardiac Etiologies of Syncope | 983 | ||
| Arrhythmias | 983 | ||
| Structural Heart Disease | 984 | ||
| Distinguishing Seizure From Syncope | 984 | ||
| Psychiatric Etiologies of Syncope | 984 | ||
| Clinical Evaluation | 984 | ||
| Acute Considerations | 984 | ||
| Goals of Clinical Evaluation | 984 | ||
| History and Physical Examination | 984 | ||
| Diagnostic Testing | 984 | ||
| Risk Stratification Approaches | 985 | ||
| Syncope While Driving | 985 | ||
| Difficulties With Syncope Evaluation | 985 | ||
| Treatment of Vasovagal Syncope | 985 | ||
| Conservative Treatment | 985 | ||
| Pharmacological Treatment | 987 | ||
| Midodrine | 987 | ||
| β-Blockers | 987 | ||
| Fludrocortisone | 988 | ||
| Other Medications | 988 | ||
| Nonpharmacological Treatment | 988 | ||
| Permanent Pacemaker Implantation | 988 | ||
| Autonomic Modulation | 988 | ||
| Conclusion | 988 | ||
| REFERENCES | 989 | ||
| 104 - Postural Orthostatic Tachycardia Syndrome | 990 | ||
| Autonomic Nervous System | 990 | ||
| Historical Perspective | 991 | ||
| Definitions | 991 | ||
| Classification | 992 | ||
| Evaluation and Management | 993 | ||
| Conclusions | 995 | ||
| REFERENCES | 995 | ||
| 105 - Progressive Conduction System Disease | 996 | ||
| Etiology and Pathophysiology | 996 | ||
| Idiopathic Isolated Conduction Disease (Progressive Familial Heart Block Type IA and IB) | 996 | ||
| Overlapping Genetic Arrhythmia Syndromes | 997 | ||
| Congenital Heart Deformities | 999 | ||
| Neuromuscular Disorders | 999 | ||
| Autoimmune Disorders | 1000 | ||
| Infectious Disorders | 1000 | ||
| Calcific Valve Disease | 1000 | ||
| Other Disorders | 1000 | ||
| Management | 1001 | ||
| REFERENCES | 1001 | ||
| 106 - Atrioventricular Block | 1003 | ||
| Types and Levels | 1003 | ||
| Clinical Manifestations | 1005 | ||
| Pathophysiology | 1006 | ||
| Congenital Atrioventricular Block | 1006 | ||
| Acquired Atrioventricular Block | 1006 | ||
| Progressive Cardiac Conduction Disease | 1006 | ||
| Ischemic Heart Disease | 1007 | ||
| Inflammatory and Infectious Diseases | 1008 | ||
| Infiltrative Processes | 1008 | ||
| Vagal-Mediated Atrioventricular Block | 1008 | ||
| Iatrogenic Atrioventricular Block | 1008 | ||
| Prognosis | 1009 | ||
| Management of Atrioventricular Block | 1009 | ||
| Acknowledgment | 1009 | ||
| REFERENCES | 1009 | ||
| XIV -\rArrhythmias in Special Populations | 1011 | ||
| 107 - Sex Differences in Arrhythmias | 1011 | ||
| Basic Electrophysiology | 1011 | ||
| Cellular Electrophysiology | 1011 | ||
| Ion Channels | 1011 | ||
| Action Potentials | 1012 | ||
| Electrocardiography | 1012 | ||
| Baseline Intervals | 1012 | ||
| Heart Rate and Heart Rate Variability | 1013 | ||
| Electrophysiological Study | 1013 | ||
| Sinus Node Function | 1013 | ||
| Atrioventricular Conduction Intervals | 1013 | ||
| Electrophysiological Properties of the Atria and Ventricles | 1013 | ||
| Presentation and Management of Specific Arrhythmias | 1013 | ||
| Sinus Node Dysfunction/Tachycardia | 1013 | ||
| Supraventricular Tachyarrhythmias | 1013 | ||
| Atrial Fibrillation | 1013 | ||
| Atrial Flutter | 1014 | ||
| Atrial Tachycardia | 1014 | ||
| Atrioventricular Nodal Reentrant Tachycardia | 1014 | ||
| Atrioventricular Reentrant Tachycardia | 1014 | ||
| Ventricular Arrhythmias | 1015 | ||
| Structurally Normal Hearts | 1015 | ||
| Structural Heart Disease | 1015 | ||
| Inducibility at Electrophysiological Study | 1015 | ||
| Sudden Cardiac Death | 1015 | ||
| Inherited Arrhythmia Syndromes | 1015 | ||
| Long QT Syndrome | 1015 | ||
| Brugada Syndrome | 1015 | ||
| Arrhythmogenic Right Ventricular Cardiomyopathy | 1015 | ||
| Other Inherited Syndromes | 1015 | ||
| Syncope | 1016 | ||
| Evaluation and Diagnostic Testing | 1016 | ||
| Treatment and Outcome | 1016 | ||
| Pharmacotherapy | 1016 | ||
| Antiarrhythmic Drugs | 1016 | ||
| Acquired Long QT Syndrome | 1016 | ||
| Anticoagulation | 1016 | ||
| Implantable Device Therapy | 1017 | ||
| Implantable Cardioverter Defibrillators | 1017 | ||
| XV - Pharmacologic Therapy | 1062 | ||
| 112 - Standard Antiarrhythmic Drugs | 1062 | ||
| Mechanism-Based Approach to Treatment of Arrhythmias | 1062 | ||
| Genetic Approaches to Defining Underlying Mechanisms of Arrhythmias | 1063 | ||
| Linkage Analysis | 1063 | ||
| Candidate Gene Studies | 1063 | ||
| Association Studies | 1063 | ||
| Impact of Genetic Studies on Pharmacotherapy of Arrhythmias | 1065 | ||
| Identification of Novel Therapeutic Targets | 1066 | ||
| Principles of Antiarrhythmic Therapy | 1067 | ||
| Evaluating Risk Versus Benefit of Antiarrhythmic Therapy | 1067 | ||
| Classification of Antiarrhythmic Drugs | 1068 | ||
| Pharmacokinetic Principles | 1068 | ||
| Pharmacodynamic Principles | 1069 | ||
| Class I Antiarrhythmic Drugs | 1069 | ||
| Class IA Antiarrhythmic Drugs | 1069 | ||
| Procainamide | 1070 | ||
| Pharmacodynamics. Procainamide is a blocker of open Na+ channels, with an intermediate time constant of recovery from block. It ... | 1070 | ||
| Disopyramide | 1071 | ||
| Pharmacodynamics. Disopyramide is a Na+ channel blocker with onset and offset kinetics similar to those of quinidine. It also pr... | 1071 | ||
| Class IB Antiarrhythmic Drugs | 1071 | ||
| Pharmacokinetics | 1071 | ||
| Mexiletine | 1071 | ||
| Pharmacodynamics. Originally developed as an anticonvulsant, mexiletine is an oral congener of lidocaine used in the treatment o... | 1071 | ||
| Class IC Antiarrhythmic Drugs | 1071 | ||
| Propafenone | 1072 | ||
| Pharmacodynamics. Propafenone is a potent Na+ channel blocker with slow onset and offset kinetics. Like flecainide, propafenone ... | 1072 | ||
| Adverse Effects | 1072 | ||
| Class III Antiarrhythmic Drugs | 1072 | ||
| Amiodarone | 1072 | ||
| Dofetilide | 1073 | ||
| Pharmacodynamics. Dofetilide is a potent and specific blocker of IKr with no other significant pharmacological action. Because o... | 1073 | ||
| Ibutilide | 1074 | ||
| Pharmacodynamics. Ibutilide is a methanesulfonamide derivative with structural similarities to sotalol. This drug increases APD ... | 1074 | ||
| Sotalol | 1074 | ||
| Pharmacodynamics. Sotalol is a class III antiarrhythmic that also has nonselective β-blocking effects. This drug is a racemic mi... | 1074 | ||
| Acknowledgment | 1074 | ||
| REFERENCES | 1075 | ||
| 113 - Innovations in Antiarrhythmic Drug Therapy | 1076 | ||
| Background and Current Clinical Context | 1076 | ||
| Main Effects of Antiarrhythmic Drugs | 1076 | ||
| Hybrid Rhythm Control Therapy | 1076 | ||
| Inhibition of Multiple Ion Channels | 1076 | ||
| New Ion Channel Targets for Antiarrhythmic Drugs | 1077 | ||
| Clinical Innovation by Off-Label Use | 1078 | ||
| Modification of the Arrhythmogenic Substrate | 1078 | ||
| Treatment of Heart Failure | 1078 | ||
| Reducing Cardiac Stress and Strain | 1078 | ||
| Intelligent Timing of Antiarrhythmic Drug Therapy | 1079 | ||
| The Longer, the Better? Half-Life of Antiarrhythmic Drugs | 1079 | ||
| The Need for Personalized Arrhythmia Management | 1079 | ||
| Outlook | 1081 | ||
| Acknowledgments | 1081 | ||
| REFERENCES | 1081 | ||
| 114 - Impact of Nontraditional Antiarrhythmic Drugs on Sudden Cardiac Death | 1084 | ||
| Assessing the Impact of Nontraditional Antiarrhythmic Drugs on Sudden Cardiac Death | 1084 | ||
| β-Adrenergic Blockers | 1085 | ||
| Renin–Angiotensin–Aldosterone System | 1087 | ||
| Angiotensin-Converting Enzyme Inhibitors | 1087 | ||
| Angiotensin Receptor Blockers | 1087 | ||
| Aldosterone Receptor Antagonists | 1088 | ||
| Combined Angiotensin-Neprilysin Inhibition | 1088 | ||
| Modulators of Cholesterol and Inflammation | 1088 | ||
| 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibitors | 1088 | ||
| Polyunsaturated Fatty Acids | 1089 | ||
| Other | 1089 | ||
| Treatment of Diabetes | 1089 | ||
| Magnesium | 1089 | ||
| Conclusion | 1090 | ||
| REFERENCES | 1090 | ||
| 115 - Prevention of Stroke in Atrial Fibrillation: Warfarin and New Oral Anticoagulants | 1092 | ||
| Risk Stratification in Atrial Fibrillation | 1092 | ||
| Stroke Risk Scores | 1092 | ||
| Bleeding Risk | 1092 | ||
| Stroke Prevention | 1092 | ||
| Antithrombotic Therapy | 1092 | ||
| Aspirin | 1092 | ||
| Combination of Aspirin and Clopidogrel | 1092 | ||
| Vitamin K Antagonist Therapy for Stroke Prevention in Atrial Fibrillation | 1093 | ||
| New Oral Anticoagulants | 1093 | ||
| Thrombin Inhibitors: Dabigatran | 1093 | ||
| Xa Inhibitors | 1094 | ||
| Rivaroxaban | 1094 | ||
| Apixaban | 1094 | ||
| Edoxaban | 1095 | ||
| Guidelines Summary | 1095 | ||
| Special Groups | 1096 | ||
| Antithrombotic Therapy for Patients With Atrial Fibrillation and Valvular Disease | 1096 | ||
| The Elderly | 1097 | ||
| Left Atrial Appendage Closure | 1098 | ||
| Cardioversion | 1098 | ||
| Future Directions | 1099 | ||
| REFERENCES | 1099 | ||
| XVI - Cardiac ImplantableElectronic Devices | 1101 | ||
| 116 - Implantable Cardioverter Defibrillators: Technical Aspects | 1101 | ||
| System Elements | 1101 | ||
| Battery | 1102 | ||
| Capacitors | 1103 | ||
| Electrodes | 1103 | ||
| Nonthoracotomy or Transvenous Leads | 1103 | ||
| Tachyarrhythmia Detection | 1104 | ||
| Sensing | 1104 | ||
| Band-Pass Filtering | 1104 | ||
| Frequency and Amplitude | 1104 | ||
| Autogain and Autothreshold | 1105 | ||
| Estimation of Adequate Amplitude | 1105 | ||
| Detection Algorithms | 1105 | ||
| Rate and Duration | 1105 | ||
| Sudden Onset | 1105 | ||
| Cycle Length Stability | 1105 | ||
| Morphology and QRS Width | 1106 | ||
| Atrial Lead Criteria | 1106 | ||
| Tachyarrhythmia Therapy | 1106 | ||
| Pacing Therapy | 1106 | ||
| Shock Therapy | 1107 | ||
| Defibrillation Threshold and Safety Margin | 1107 | ||
| Monophasic Waveforms | 1108 | ||
| Biphasic Waveforms | 1108 | ||
| System Malfunction | 1109 | ||
| Recent and Future Directions | 1110 | ||
| Remote Monitoring | 1110 | ||
| Remote Device Programming | 1111 | ||
| Long-Distance Telemetric Communication | 1111 | ||
| Investigational Shock Waveforms | 1111 | ||
| Magnetic Resonance Imaging–Conditional Implantable Cardioverter Defibrillators | 1111 | ||
| Adjunctive Sensor Technology | 1111 | ||
| Battery Technologies | 1111 | ||
| REFERENCES | 1112 | ||
| 117 -Implantable Cardioverter Defibrillator: Clinical Aspects | 1113 | ||
| Indications and Use | 1113 | ||
| Implantable Cardioverter Defibrillator System Selection | 1113 | ||
| Transvenous Defibrillation Leads | 1115 | ||
| Dual Coil Versus Single Coil | 1115 | ||
| Integrated Versus Dedicated Sensing Bipoles | 1115 | ||
| Implant Procedure and Testing | 1115 | ||
| Testing Sensing in Ventricular Fibrillation | 1115 | ||
| Testing Defibrillation Efficacy | 1115 | ||
| Methods | 1115 | ||
| Clinical Utility, Necessity, and Recommendations | 1115 | ||
| Implant Complications | 1115 | ||
| Programming Sensing, Detection, and Therapies for Shock Reduction | 1117 | ||
| Sensing | 1118 | ||
| Detection | 1118 | ||
| Detection Rate and Duration | 1118 | ||
| Zones for Detection and Therapy | 1118 | ||
| Supraventricular Tachycardia Versus Ventricular Tachycardia Discriminators | 1120 | ||
| Strategic Programming and Clinical Outcomes | 1121 | ||
| Patient Alerts, Clinical Follow-up, and Remote Monitoring | 1121 | ||
| Patient Alerts | 1121 | ||
| Remote Monitoring | 1121 | ||
| Troubleshooting | 1121 | ||
| Ventricular Oversensing: Diagnosis and Management | 1121 | ||
| Oversensing Nonphysiological Signals from Lead Problems | 1122 | ||
| Lead Integrity Diagnostics That Incorporate Oversensing | 1123 | ||
| Pace-Sense Impedance | 1123 | ||
| High-Voltage Impedance | 1123 | ||
| Clinical Presentations of Lead Failure | 1124 | ||
| Imaging | 1124 | ||
| Approach to the Patient | 1124 | ||
| Clinical Lead Failure. Fig. 117.10 summarizes the approach to the diagnosis of patients with electrical findings suggestive of l... | 1124 | ||
| Shocks: Diagnosis and Management | 1126 | ||
| Diagnosing Shocks | 1126 | ||
| Approach to the Patient With Shocks | 1126 | ||
| Unsuccessful Shocks | 1127 | ||
| Failure to Deliver Therapy or Delayed Therapy | 1127 | ||
| Other Common Clinical Issues | 1127 | ||
| Psychosocial, Lifestyle, and End-of-Life Issues | 1127 | ||
| Nonmedical Sources | 1128 | ||
| Medical Sources | 1128 | ||
| REFERENCES | 1128 | ||
| 118 - Subcutaneous Implantable Cardioverter Defibrillators | 1130 | ||
| Early Development | 1130 | ||
| Characteristics of the Subcutaneous Implantable Cardioverter Defibrillator System | 1130 | ||
| Initial Observational Studies/IDE Submission Trial | 1132 | ||
| Practical Clinical Aspects | 1133 | ||
| Pooled IDE/EFFORTLESS and Longer-Term CE Datasets | 1134 | ||
| Sensing and Discrimination | 1134 | ||
| Bradycardia Support and Antitachycardia Pacing | 1135 | ||
| Shock Size | 1135 | ||
| Infection | 1136 | ||
| Future Developments | 1136 | ||
| Conclusions | 1137 | ||
| Commercial and Funding Relationships | 1137 | ||
| Acknowledgments | 1137 | ||
| REFERENCES | 1137 | ||
| 119 - Implantable Pacemakers | 1139 | ||
| History of Pacing | 1139 | ||
| Pacemaker Nomenclature | 1139 | ||
| Indications for Cardiac Pacing | 1139 | ||
| Acquired Atrioventricular Block | 1139 | ||
| Congenital Complete Heart Block | 1140 | ||
| Sinus Node Dysfunction | 1140 | ||
| Neurocardiogenic Syncope | 1140 | ||
| Carotid Sinus Hypersensitivity | 1141 | ||
| Nonbradycardic Indications for Pacing | 1141 | ||
| Pacing for Atrial Fibrillation | 1141 | ||
| Resynchronization Therapy | 1141 | ||
| Hypertrophic Cardiomyopathy | 1141 | ||
| Basic Pacemaker Function and Modes | 1141 | ||
| Ventricular Inhibited Pacing | 1141 | ||
| Atrial Inhibited Pacing | 1141 | ||
| DDD Pacing | 1142 | ||
| Selecting the Appropriate Pacing Mode | 1143 | ||
| Selection Criteria | 1143 | ||
| Selecting the Appropriate Sensor for Rate-Adaptive Pacing | 1143 | ||
| Activity and Accelerometer Sensors | 1143 | ||
| Minute-Ventilation Sensor | 1143 | ||
| Stimulus-T or QT-Sensing Sensor | 1143 | ||
| Peak Endocardial Acceleration Sensor | 1144 | ||
| Right Ventricular Impedance-Based Sensor | 1144 | ||
| Dual-Sensor Combinations | 1144 | ||
| Pacemaker Complications | 1144 | ||
| Troubleshooting Electrocardiographic Abnormalities | 1144 | ||
| Automatic Pacemaker Function | 1145 | ||
| Atrial Arrhythmia Detection and Automatic Mode Switching | 1145 | ||
| Intrinsic Conduction Preference | 1146 | ||
| Automatic Testing and Data Storage | 1146 | ||
| Routine Follow-up and Remote Monitoring | 1148 | ||
| Electromagnetic Interference | 1148 | ||
| Magnetic Resonance Imaging | 1148 | ||
| Leadless Pacemakers | 1148 | ||
| End-of-Life Considerations | 1148 | ||
| Summary | 1148 | ||
| 120 - Use of QRS Fusion Complex Analysis in Cardiac Resynchronization Therapy | 1150 | ||
| Wave Interference for QRS Fusion | 1151 | ||
| Clinical Implications | 1158 | ||
| REFERENCES | 1165 | ||
| 121 - Applications of Cardiac Pacemakers and Extracardiac Stimulation | 1167 | ||
| Pacing for Specific Cardiac Conditions | 1167 | ||
| Hypertrophic Cardiomyopathy | 1167 | ||
| Neurocardiogenic Syncope | 1167 | ||
| Long QT Syndrome | 1167 | ||
| Preventing Remodeling After Myocardial Infarction | 1169 | ||
| Vagal Stimulation for the Treatment of Heart Failure | 1169 | ||
| Indication for Pacemakers After Cardiac Procedures | 1170 | ||
| Novel Approaches and Technology for Cardiac Pacing | 1171 | ||
| Leadless Pacemakers | 1171 | ||
| Biological Pacemakers | 1172 | ||
| Conclusions | 1172 | ||
| 122 - Remote Monitoring of Cardiac Implantable Electronic Devices | 1173 | ||
| Evolution of Remote Monitoring | 1173 | ||
| Logistics of Remote Monitoring | 1173 | ||
| Patient Participation | 1173 | ||
| Remote Monitoring and Patient Outcomes | 1177 | ||
| Mortality | 1177 | ||
| Health Care Utilization | 1177 | ||
| Time to Clinical Decision Making | 1177 | ||
| Inappropriate Shocks | 1178 | ||
| Special Role of Remote Monitoring in Device Advisories and Recalls | 1178 | ||
| Remote Monitoring and Disease Management | 1178 | ||
| Heart Failure | 1178 | ||
| Atrial Fibrillation | 1179 | ||
| Cost Effectiveness | 1180 | ||
| Mega-Cohorts and “Big Data” | 1180 | ||
| Relevant Guidelines and Recommendations | 1181 | ||
| The Future of Remote Monitoring | 1181 | ||
| Conclusion | 1181 | ||
| Conflicts of Interest | 1181 | ||
| REFERENCES | 1183 | ||
| XVII -\rCatheter Ablation | 1185 | ||
| 123 - Catheter Ablation: Technical Aspects | 1185 | ||
| Historical Context of Catheter Ablation | 1185 | ||
| Radiofrequency Ablation | 1185 | ||
| Radiofrequency Energy Sources | 1185 | ||
| Heat Transfer to Tissue in Radiofrequency Ablation | 1185 | ||
| Radiofrequency Ablation With Irrigated Catheters | 1188 | ||
| Cryoablation | 1188 | ||
| Laser Catheter Ablation | 1189 | ||
| High-Intensity Focused Ultrasound Catheter Ablation | 1189 | ||
| Microwave Catheter Ablation | 1191 | ||
| Robotic Catheter Ablation | 1191 | ||
| Future Directions in Catheter Ablation | 1192 | ||
| REFERENCES | 1192 | ||
| 124 - Catheter Ablation: Clinical Aspects | 1194 | ||
| Preprocedural Management | 1194 | ||
| Atrial Fibrillation | 1196 | ||
| Preprocedural Drug Therapy | 1197 | ||
| Pre- and Periprocedural Anticoagulation | 1197 | ||
| Antiarrhythmic Drug Therapy | 1199 | ||
| β-Blockers | 1199 | ||
| Preprocedural Imaging | 1199 | ||
| Intraprocedural Management | 1199 | ||
| Sedation and Anesthesia | 1199 | ||
| Venous Access | 1200 | ||
| Transseptal Access | 1200 | ||
| Arterial Access | 1200 | ||
| Pericardial Access | 1201 | ||
| Catheter Manipulation and the Role of Intraoperative Imaging Techniques | 1201 | ||
| Management of Intraprocedural Thromboembolic Risk | 1201 | ||
| Temperature Monitoring | 1202 | ||
| Ablation Targets During Atrial Fibrillation Ablation | 1202 | ||
| Ablation Endpoints During Atrial Fibrillation Ablation | 1203 | ||
| Intraprocedural Radiofrequency Power Titration | 1204 | ||
| Ablation Targets During Ventricular Tachycardia Ablation | 1204 | ||
| Ablation Endpoints During Ventricular Tachycardia Ablation | 1205 | ||
| Postprocedural Management | 1206 | ||
| Monitoring for Recurrences: Methods and Relative Merits | 1206 | ||
| Postablation Use of Antiarrhythmic Drugs | 1206 | ||
| Postablation Anticoagulation | 1206 | ||
| Other Postprocedural Management Considerations | 1207 | ||
| Role of Repeat Ablation Procedures | 1207 | ||
| Ventricular Tachycardia | 1207 | ||
| Monitoring for Recurrences: Methods and Relative Merits | 1207 | ||
| Postablation Use of Antiarrhythmic Drugs | 1208 | ||
| Role of Repeat Ablation Procedures | 1208 | ||
| Conclusions | 1208 | ||
| REFERENCES | 1208 | ||
| 125 - Ablation for Atrial Fibrillation | 1211 | ||
| Historical Context | 1211 | ||
| Indications and Preprocedure Assessment | 1211 | ||
| Pulmonary Vein Isolation | 1212 | ||
| Atrial Substrate Ablation | 1213 | ||
| Dominant Frequency | 1215 | ||
| Stable Sources Maintaining Atrial Fibrillation | 1216 | ||
| Autonomic Ganglionic Plexi | 1216 | ||
| Linear Ablation | 1216 | ||
| Technique for Ablation of the Mitral Isthmus | 1216 | ||
| Technique for Ablation of the Left Atrial Roof | 1217 | ||
| Stepwise Ablation Approach | 1217 | ||
| New Methods to Identify Drivers | 1217 | ||
| Complications | 1219 | ||
| Clinical Results | 1219 | ||
| Conclusion | 1219 | ||
| REFERENCES | 1220 | ||
| 126 - Ablation of Supraventricular Tachyarrhythmias\r | 1222 | ||
| Ablation of Atrioventricular Nodal Reentrant Tachycardia | 1222 | ||
| Indications | 1222 | ||
| General Principles | 1222 | ||
| Slow Pathway Ablation | 1222 | ||
| Endpoints for Slow Pathway Ablation | 1223 | ||
| Risk for Atrioventricular Block | 1224 | ||
| Outcome | 1224 | ||
| Ablation of Atrioventricular Reentrant Tachycardia | 1224 | ||
| Indications | 1224 | ||
| Accessory Pathway Localization | 1224 | ||
| Free Wall Accessory Pathways | 1225 | ||
| Septal Accessory Pathways | 1226 | ||
| Epicardial Accessory Pathways | 1226 | ||
| Rare Forms of Variant Accessory Pathways | 1230 | ||
| Outcome | 1230 | ||
| Ablation of Typical Atrial Flutter and Non–Isthmus-Dependent Macroreentrant Atrial Tachycardia | 1230 | ||
| Indications | 1230 | ||
| Cavotricuspid Isthmus–Dependent Atrial Flutter | 1230 | ||
| Catheter Ablation | 1230 | ||
| Procedural Endpoints | 1231 | ||
| Lower Loop Reentry | 1231 | ||
| Outcome | 1231 | ||
| Ablation of Non–IsthmusI-Dependent Macroreentrant Atrial Tachycardia and Atypical Atrial Flutter | 1231 | ||
| Mapping Techniques | 1231 | ||
| Catheter Ablation | 1234 | ||
| Ablation of Focal Atrial Tachycardia | 1234 | ||
| Indications | 1234 | ||
| Mapping Techniques | 1235 | ||
| Catheter Ablation | 1237 | ||
| Outcome | 1237 | ||
| Conclusions | 1237 | ||
| REFERENCES | 1237 | ||
| 127 - Catheter Ablation for Ventricular Tachycardia With or Without Structural Heart Disease\r | 1239 | ||
| Preprocedure Preparation and Consideration of Risks | 1239 | ||
| Approach to Mapping and Ablation | 1239 | ||
| Focal Origin Ventricular Arrhythmias | 1240 | ||
| Reentrant Ventricular Tachycardias Related to the Purkinje System | 1241 | ||
| Scar-Related Reentry | 1241 | ||
| Mapping During Ventricular Tachycardia | 1242 | ||
| Other Ablation Targets | 1246 | ||
| Ablation Strategies and Acute Endpoints for Scar-Related Ventricular Tachycardia | 1246 | ||
| Ablation in Specific Diseases | 1248 | ||
| Prior Myocardial Infarction | 1248 | ||
| Dilated Cardiomyopathy and Valvular Heart Disease | 1250 | ||
| Right Ventricular Cardiomyopathies | 1250 | ||
| Other Diseases | 1250 | ||
| Ablation for Polymorphic Ventricular Tachycardia and Ventricular Fibrillation | 1250 | ||
| Summary | 1250 | ||
| REFERENCES | 1251 | ||
| 128 - Epicardial Approach in Electrophysiology\r | 1253 | ||
| Anatomy | 1253 | ||
| Indications | 1253 | ||
| Previous Failure of Endocardial Ablation | 1253 | ||
| Predictive Electrocardiographic Criteria | 1253 | ||
| Type of Cardiomyopathy Scar Localization on Magnetic Resonance Imaging | 1254 | ||
| Chagas Disease | 1254 | ||
| Myocarditis Sequelae | 1254 | ||
| Arrhythmogenic Right Ventricular Cardiomyopathy | 1255 | ||
| Nonischemic Cardiomyopathy | 1255 | ||
| Ischemic Cardiomyopathy | 1255 | ||
| Brugada Syndrome | 1256 | ||
| Hypertrophic Cardiomyopathy | 1256 | ||
| Left Ventricular Noncompaction | 1257 | ||
| Situations at Risk | 1257 | ||
| Practical Aspects | 1257 | ||
| Preparation | 1257 | ||
| Access | 1257 | ||
| Mapping | 1259 | ||
| Ablation | 1259 | ||
| Postprocedure | 1259 | ||
| Results | 1259 | ||
| Access | 1259 | ||
| Epicardial Ablation Success | 1259 | ||
| Ischemic Cardiomyopathy | 1259 | ||
| Nonischemic Cardiomyopathy | 1260 | ||
| Arrhythmogenic Right Ventricular Dysplasia | 1260 | ||
| Hypertrophic Cardiomyopathies | 1260 | ||
| Myocarditis Sequelae | 1260 | ||
| Complications | 1260 | ||
| Early Complications Related to the Puncture | 1260 | ||
| Pericardial Bleeding | 1260 | ||
| Infradiaphragmatic Injuries | 1260 | ||
| Pleuropulmonary Complications | 1260 | ||
| Early Complications Related to the Ablation | 1260 | ||
| Postprocedure Complications | 1261 | ||
| Conclusion | 1261 | ||
| REFERENCES | 1261 | ||
| 129 - Ventricular Fibrillation\r | 1263 | ||
| Ablation of Purkinje Triggers in Nonstructural Heart Disease | 1263 | ||
| Idiopathic Ventricular Fibrillation | 1263 | ||
| Outcome of Purkinje Ablation in Idiopathic Ventricular Fibrillation | 1264 | ||
| Long QT Syndrome | 1264 | ||
| Brugada Syndrome | 1265 | ||
| Early Repolarization Syndrome | 1265 | ||
| Ablation of Purkinje Triggers in Various Types of Structural Heart Disease | 1266 | ||
| Ischemic Heart Disease | 1266 | ||
| Dilated Cardiomyopathy | 1267 | ||
| Hypertrophic Cardiomyopathy | 1267 | ||
| Other Structural Heart Disease | 1267 | ||
| Technical Aspects | 1268 | ||
| Challenges | 1268 | ||
| Future Directions | 1268 | ||
| Conclusions | 1268 | ||
| Acknowledgment | 1268 | ||
| REFERENCES | 1268 | ||
| 130 - Ablation in Pediatrics\r | 1270 | ||
| Indications for Ablation in thePediatric Age Group | 1270 | ||
| Incidence of Heart Rhythm Abnormalities by Age and Congenital Heart Disease | 1270 | ||
| General Procedural Success and Complication Rates That Inform Indications | 1270 | ||
| Consensus Indications (Class I, II, III) for Catheter Ablation in Children | 1271 | ||
| Preparation for the Procedure | 1272 | ||
| Developmental and Psychosocial Considerations and Procedure Consent | 1272 | ||
| Preprocedural Studies | 1272 | ||
| Laboratory Setting | 1272 | ||
| Sedation and Anesthesia | 1272 | ||
| Radiation Concerns | 1272 | ||
| Recording and Mapping Systems | 1272 | ||
| Energy Sources | 1272 | ||
| Child-Specific Resources | 1273 | ||
| Clinical and Procedural Considerations Related to Specific Pediatric Ablation Procedures | 1274 | ||
| General Technical Considerations | 1274 | ||
| Wolff-Parkinson-White Syndrome and Concealed Accessory Pathways\r | 1274 | ||
| Atrioventricular Nodal Reentrant Tachycardia | 1276 | ||
| Automatic Focus Tachycardias, Especially Junctional Ectopic Tachycardia | 1278 | ||
| Follow-up | 1278 | ||
| REFERENCES | 1278 | ||
| 131 - Catheter Ablation in Congenital Heart Disease\r | 1280 | ||
| Technical Challenges | 1280 | ||
| Ablation of Supraventricular Tachycardia | 1280 | ||
| Ablation of Atrial Macroreentrant Tachycardia | 1280 | ||
| Ablation of Focal Atrial Tachycardia | 1282 | ||
| Ablation of Atrial Fibrillation | 1283 | ||
| Ablation of Atrioventricular Nodal Reentry | 1283 | ||
| Ablation of Accessory Pathways inEbstein Anomaly | 1283 | ||
| Ablation of Ventricular Tachycardia | 1284 | ||
| Summary | 1286 | ||
| REFERENCES | 1286 | ||
| 132 - Anesthesiology Considerations for the Electrophysiology Laboratory\r | 1288 | ||
| Setting the Stage for an Effective Partnership | 1288 | ||
| Anesthesiologists and Anesthesiology: Who We Are and What We Do | 1288 | ||
| Preprocedural Evaluation of Patients | 1289 | ||
| Intraprocedural Considerations | 1289 | ||
| Local Anesthetics | 1289 | ||
| Toxicity | 1290 | ||
| Levels of Sedation: What Do They Mean? | 1290 | ||
| General Anesthesia and General Endotracheal Anesthesia: Definitions and Risks/Benefits | 1291 | ||
| Inhalational Agents | 1291 | ||
| Intravenous General Anesthetics | 1292 | ||
| Impact of Technique on Ablation | 1292 | ||
| Postprocedural Planning and Disposition | 1293 | ||
| Summary | 1293 | ||
| REFERENCES | 1294 | ||
| XVIII -\rSurgery for Arrhythmias | 1295 | ||
| 133 - Surgery for Atrial Fibrillation and Other Supraventricular Tachycardias\r | 1295 | ||
| Atrial Fibrillation | 1295 | ||
| Development of Surgery for Atrial Fibrillation | 1295 | ||
| Surgical Ablation Technology | 1297 | ||
| Cryoablation | 1297 | ||
| Radiofrequency Energy | 1297 | ||
| Indications for Surgical Ablation of Atrial Fibrillation | 1298 | ||
| The Cox-Maze Procedure | 1299 | ||
| Surgical Technique | 1299 | ||
| Surgical Results | 1300 | ||
| Left Atrial Lesion Sets | 1300 | ||
| Surgical Technique | 1300 | ||
| XIX -\rNew Approaches | 1316 | ||
| 135 - Vagus Nerve Stimulation for the Treatment of Heart Failure | 1316 | ||
| Effects of Vagus Nerve Stimulation on Left Ventricular Function and Chamber Remodeling in Experimental Heart Failure | 1316 | ||
| Mechanisms That Underlie the Benefits of Vagus Nerve Stimulation in Heart Failure | 1318 | ||
| Heart Rate Reduction | 1318 | ||
| Proinflammatory Cytokines | 1318 | ||
| Nitric Oxide Signaling | 1319 | ||
| Vagus Nerve Stimulation and Ventricular Arrhythmias | 1320 | ||
| Early Experience of Vagus Nerve Stimulation in Patients With Heart Failure | 1320 | ||
| New Approaches and Instrumentation for Neuromodulation in Heart Failure | 1321 | ||
| Approaches to Neuromodulation in Heart Failure Other Than Vagus Nerve Stimulation | 1321 | ||
| Conclusions | 1321 | ||
| Acknowledgments | 1321 | ||
| REFERENCES | 1321 | ||
| 136 - Baroreceptor Stimulation\r | 1323 | ||
| Anatomical Aspects | 1323 | ||
| Methods to Investigate Baroreceptor Activity in Humans and Physiological Background | 1323 | ||
| Novel Interventional Therapies to Modulate the Autonomic Tone | 1324 | ||
| Results of Clinical Studies and Clinical Trials | 1325 | ||
| Baroreflex Activation Therapy in Hypertension | 1325 | ||
| Baroreflex Activation Therapy in Heart Failure | 1325 | ||
| Conclusions | 1326 | ||
| REFERENCES | 1327 | ||
| 137 - Spinal Cord Stimulation for Heart Failure and Arrhythmias\r | 1328 | ||
| Background | 1328 | ||
| How Spinal Cord Stimulation Affects the Cardiac Autonomic Tone | 1328 | ||
| Preclinical Studies | 1328 | ||
| Clinical Trials | 1329 | ||
| Conclusions | 1330 | ||
| REFERENCES | 1330 | ||
| 138 - Renal Sympathetic Denervation\r | 1331 | ||
| Renal Sympathetic System | 1331 | ||
| Renal Sympathetic Denervation | 1331 | ||
| Renal Sympathetic Denervation and Atrial Fibrillation | 1331 | ||
| Preclinical Data | 1332 | ||
| Clinical Data | 1332 | ||
| Renal Sympathetic Denervation and Ventricular Arrhythmias | 1332 | ||
| Preclinical Data | 1333 | ||
| Clinical Data | 1333 | ||
| Percutaneous Techniques for Renal Sympathetic Denervation | 1333 | ||
| Conclusion | 1335 | ||
| REFERENCES | 1336 | ||
| 139 - Left Atrial Appendage Closure | 1337 | ||
| Left Atrial Appendage Anatomy | 1339 | ||
| Imaging of the Left Atrial Appendage | 1340 | ||
| Echocardiographic Assessment | 1340 | ||
| Computed Tomography | 1341 | ||
| Left Atrial Appendage Closure Techniques | 1341 | ||
| Surgical | 1341 | ||
| Percutaneous: the Watchman Experience | 1341 | ||
| Conclusion | 1343 | ||
| REFERENCES | 1344 | ||
| INDEX | 1345 | ||
| A | 1345 | ||
| B | 1352 | ||
| C | 1353 | ||
| D | 1360 | ||
| E | 1360 | ||
| F | 1363 | ||
| G | 1364 | ||
| H | 1365 | ||
| I | 1366 | ||
| J | 1369 | ||
| K | 1370 | ||
| L | 1370 | ||
| M | 1372 | ||
| N | 1374 | ||
| O | 1375 | ||
| P | 1376 | ||
| Q | 1379 | ||
| R | 1379 | ||
| S | 1381 | ||
| T | 1385 | ||
| U | 1387 | ||
| V | 1387 | ||
| W | 1389 | ||
| X | 1389 | ||
| Z | 1389 |