Cardiac Electrophysiology: From Cell to Bedside: Expert Consult - Online and Print, Fifth Edition

Cover......Page 1
Copyright
......Page 2
Contributors......Page 6
Preface......Page 18
Implantable Cardioverter-Defibrillator......Page 19
Antiarrhythmic Drugs......Page 20
Atrial Fibrillation......Page 21
Implementing Successful Therapy......Page 23
References......Page 24
Three-Dimensional Structure of Sodium Channels......Page 27
Sodium Channel Function......Page 28
The Inner Pore and Local Anesthetic-Antiarrhythmic Drug Receptor Site......Page 29
Fast Inactivation......Page 30
Sodium Channel Genes......Page 31
Expression, Localization, and Function of Sodium Channel Subtypes......Page 32
References......Page 34
Calcium Channel Types......Page 37
Molecular Characterization of Calcium Channels......Page 39
Calcium Channel Selectivity and Permeation......Page 40
ICa Inactivation......Page 41
Amount of Ca2+ Entry through Calcium Channels......Page 43
References......Page 44
Mechanism of Activation Gating......Page 47
Inactivation Gating......Page 48
U-Type Inactivation......Page 49
α Pore-Forming Subunits......Page 50
Auxiliary (Accessory) Subunits......Page 51
Physiologic Role of Transient Outward Current......Page 53
Regulation of Ito,f Function and Expression......Page 54
Molecular Basis for Delayed Rectifier Currents......Page 55
Molecular Basis of Inward Rectifier......Page 56
Voltage-Regulated Potassium Channels in Cardiac Disease......Page 57
References......Page 58
Cardiomyocyte Local Membrane Organization: Form Fits Function......Page 61
Ankyrin-B Coordinates Local Organization of Na+-Ca2+ Exchanger, Na+,K+-ATPase, and InsP3 Receptor......Page 62
Caveolae Compartmentalize Local Signaling Complexes......Page 63
Calmodulin-Dependent Protein Kinase II Targets CaV1.2 by Way of an Adapter Sequence Embedded in β Subunits......Page 64
References......Page 65
Physiology and Regulation......Page 69
Biochemistry and Molecular Biology......Page 70
Pharmacology......Page 71
Physiology......Page 72
Physiologic Role of Na+-Ca2+ Exchange......Page 73
Transport Mechanism......Page 74
Role of Na+-Ca2+ Exchange in Cardiac Pathophysiology......Page 75
Outlook and Future Directions......Page 76
References......Page 77
Ca2+ Imaging......Page 83
Structure and Components of the Ryanodine Receptor-2 Macromolecular Complex......Page 84
Activation and Gating of Ryanodine Receptor-2......Page 85
Inactivation and Termination of SR Calcium Release......Page 86
SR Ca2+ Content......Page 87
Ryanodine Receptor Mutations......Page 88
Monovalent Cation Channels......Page 89
References......Page 90
Voltage Dependence of Activation......Page 95
Other Cellular Factors Modulating HCN Channels......Page 96
If Blockers as Bradycardic Drugs......Page 97
HCN4......Page 98
Physiologic Role of HCN Channels in Humans......Page 99
References......Page 100
Adherens Junctions......Page 103
The Intercalated Disk as a Functional Unit......Page 104
Molecular Structure of Connexin 43......Page 105
Correlating the Primary Sequence with the High-Order Structure of the Channel Pore......Page 106
Connexin Structure during Gap Junction Regulation......Page 107
References......Page 109
FAST GATING PROCESSES: A SYMPHONY OF STRUCTURE AND FUNCTION......Page 111
Slow Inactivation: A Concerted Rearrangement in the Pore......Page 113
Long QT Syndrome Mutations: Gating Mutations That Enhance Sodium Current......Page 114
Brugada Syndrome: Gating Mutations That Reduce Sodium Current......Page 115
New Motifs and Modulators for Structure and Function......Page 116
Slow Inactivation and the P Segments: A Mechanism for Local Anesthetic Use Dependence?......Page 118
The Future: A Dynamic Cardiac Sodium Channel Structure......Page 119
References......Page 120
Ultrarapid Delayed Rectifier Channel......Page 123
Slow Delayed Rectifier Channel......Page 124
Structural Features of Voltage-Gated Potassium Channels......Page 125
HERG......Page 127
KCNQ1-MinK......Page 128
References......Page 129
Mechanical Induction of Nonphysiologic Rhythms......Page 133
Mechanical Termination of Nonphysiologic Rhythms......Page 136
Types of Mechanosensitive Ion Channels......Page 137
Cellular-Level Responses......Page 138
Tissue- and Organ-Level Effects......Page 140
Acknowledgment......Page 141
References......Page 142
Ionic Currents and Ion Channels in the Sinoatrial Node......Page 145
Sodium and Calcium Channels......Page 146
Transient Outward Potassium Channels......Page 149
Calcium-Handling Proteins......Page 151
Postnatal Development......Page 152
Aging......Page 153
Interfacing the Sinoatrial Node with the Atrial Muscle......Page 154
References......Page 155
Acetylcholine-Activated Potassium Current: IKACh......Page 157
Kir2.1 Channels......Page 158
Kir2.2 Channels......Page 159
Kir3 Subfamily Underlies IKACh......Page 160
Magnesium- and Polyamine-Induced Rectification......Page 161
Rectification Properties are Related to Electrostatic Interactions in the Cytoplasmic Pore of a Kir Channel......Page 162
Rectification Properties of Kir2.x Subfamily......Page 163
References......Page 164
Multichannel Properties......Page 167
Single-Channel Properties......Page 168
Homomeric-Heterotypic Channels......Page 170
Heteromeric-Homotypic and Heteromeric-Heterotypic Channels......Page 171
References......Page 172
The ‘‘Resting’’ Membrane Potential......Page 175
G Protein-Activated Potassium Channels......Page 176
Delayed Rectifier Potassium Currents......Page 177
L-type Calcium Channels......Page 178
Sodium Channels......Page 179
Intracellular Calcium Homeostasis......Page 180
The Na+-Ca2+ Exchanger......Page 181
Perspectives and Future Directions......Page 182
References......Page 184
Inhibition of Sodium Channels......Page 187
Molecular Mechanisms for Use-Dependent Block......Page 189
Block of Late Sodium Channels......Page 190
References......Page 191
Overview of L-type and T-type Calcium Channels......Page 193
Structure......Page 194
Drug-Binding Sites......Page 195
Mechanisms of Actions of L-type Calcium Channel Agonists and Antagonists......Page 196
Dual Effects of Drugs on the L-type Calcium Channel......Page 197
Effects of β-Adrenergic (cAMP/PKA) Signaling Pathways on the L-type Calcium Channel......Page 198
Abnormalities of L-type Calcium Channel Regulation in Diseased Hearts......Page 200
Summary......Page 201
References......Page 202
Leucine-Isoleucine Zippers Coordinate Protein-Protein Interactions......Page 205
Disruption of IKs/Yotiao Complex by KCNQ1 Mutations in Patients with Long QT Syndrome......Page 206
Disruption of IKs/Yotiao Complex by a Yotiao Mutation in Patients with Long QT Syndrome......Page 208
Uncoupling of IKs Channels from Sympathetic Nervous System-Mediated Regulation: Novel Mechanisms of Arrhythmia......Page 209
References......Page 210
Drug-Induced Long QT Syndrome......Page 213
Mechanism of Drug-Induced QT Interval Prolongation and Torsade de Pointes......Page 214
Drugs Affecting Multiple Ion Channels......Page 216
References......Page 219
Glycyrrhizic Acid Metabolites......Page 223
Molecular Approaches to Reduction of Cell-Cell Coupling......Page 224
Peptide-Based Strategies for Reduction of Gap Junction-Mediated Intercellular Communication......Page 225
Antiarrhythmic Peptides......Page 226
The Carboxyl-Terminal Domain of Connexin43 as a Target for Drug Design......Page 227
References......Page 229
Ventricular Fibrosis......Page 233
Cardiac Activity Modulation by Heterocellular Electrotonic Coupling......Page 234
Heterocellular Coupling and Conduction Velocity......Page 235
Initiation of Arrhythmias......Page 236
References......Page 238
The Normal Pacemaker of the Heart......Page 241
Pathologies Affecting Normal Pacemaker Function and a Brief History of Therapies......Page 242
Viral Vector-Based Delivery of Constructs......Page 243
Optimizing Biologic Pacemaker Function......Page 245
Challenges......Page 246
Conclusions......Page 249
References......Page 250
CHAPTER 23 - A New Functional Paradigm for the Heart’s Pacemaker: Mutual Entrainment of Intracellular Calcium Clocks and Surface Membrane Ion Channel Clocks......Page 253
Myogenic Origin of Cardiac Impulse Initiation......Page 254
Membrane Clock of Sinoatrial Nodal Cells, the Heart’s Primary Pacemaker Cells......Page 255
The Plot Thickens: Intracellular Ca2+ Involvement in Normal Pacemaker Function......Page 256
Factors That Govern the Calcium Clock’s Ticking Speed and Payload: Calcium and Protein Kinase A-Dependent Protein Phosphorylation......Page 257
Interfering with the Calcium Clock or Critical Components of the Membrane Clock Prevents Normal Automaticity and Rate Regulation......Page 260
Numeric Modeling of the Membrane Clock: Limitations and Previous Attempts of Integration with Intracellular Processes......Page 261
An Additional Level of Complexity of Cardiac Pacemaker Function Arises within the Sinoatrial Nodal Tissue......Page 262
References......Page 263
Structure and Function of the Atrioventricular Junction......Page 267
Sodium Current and Voltage-Gated Sodium Channels......Page 268
Summary......Page 269
Functional Heterogeneity of the Atrioventricular Junction......Page 270
Mechanisms of Atrioventricular Conduction......Page 271
Dual Pathways......Page 272
His Bundle Excitation in the Context of Dual Pathways......Page 273
Pacemaking Activity in the Atrioventricular Junction......Page 274
References......Page 275
The Anisotropic Cellular Network......Page 277
The Safety Factor for Propagation......Page 278
Conduction Slowing Due to Cell-to-Cell Uncoupling......Page 279
Field Effect Propagation of the Cardiac Impulse......Page 280
Uniform versus Nonuniform Cell-to-Cell Coupling......Page 281
The Role of Coexpression of Connexins43, 45, and 40 in Ventricular and Atrial Propagation......Page 283
References......Page 284
Fibroblasts and Myofibroblasts in the Working Myocardium......Page 287
Connexin Expression by Myofibroblasts......Page 288
Myofibroblasts Reestablish Conduction in Severed Cardiac Tissue......Page 289
Myofibroblasts Slow Impulse Conduction......Page 290
Myofibroblasts Elicit Ectopic Activity......Page 291
Implications, Open Questions, and Perspectives......Page 293
References......Page 294
Alternans in Heart Disease......Page 297
The Action Potential Duration Restitution Hypothesis......Page 298
The Calcium-Cycling (Calcium Restitution) Hypothesis......Page 299
Calcium Uptake into the Sarcoplasmic Reticulum......Page 300
Mechanisms Linking Alternans to Arrhythmogenesis......Page 301
Mechanisms of Discordant Alternans between Cells......Page 302
Intracellular Uncoupling......Page 303
Long-QT Syndrome......Page 304
References......Page 305
CHAPTER 28 - Heterogeneous Expression of Repolarizing Potassium Currents in the Mammalian Myocardium......Page 311
Diversity of Myocardial Voltage-Gated K+ (Kv) Currents......Page 314
Further Molecular Diversity of Kv Channels: Accessory β Subunits......Page 316
Relation between Kv Channel Subunits and Cardiac Transient Outward K+ Channels......Page 318
Relation between Kv Channel Subunits and Cardiac Delayed Rectifier K+ Channels......Page 319
Two-Pore Domain K+ Channels......Page 320
References......Page 321
Connexin43......Page 325
Transcriptional Regulation of Cardiac Connexins......Page 326
Connexin43......Page 328
Analysis of Connexin43 Phosphorylation......Page 329
Gap Junction Remodeling......Page 330
Summary......Page 331
References......Page 332
Fast Sodium Current......Page 335
L-type Calcium Current......Page 337
Rapid Delayed Rectifier Potassium Current......Page 339
Summary and Conclusions......Page 342
References......Page 344
Geometry of the Spiral Wave......Page 347
Spiral Waves in Heterogeneous Tissue......Page 349
Initiation of Spiral Waves......Page 351
Induced Drift of Spiral Waves......Page 352
Model Used for Illustrations......Page 353
References......Page 354
Dynamics Due to Restitution of Action Potential Duration......Page 357
Dynamics Due to Intracellular Ca2+ Cycling......Page 360
Vulnerability to Spiral Wave Reentry......Page 361
Spiral and Scroll Wave Stabilities......Page 362
Dynamic Wave Stability and Termination of Arrhythmias......Page 364
References......Page 365
Phase Mapping, Phase Singularities, and Rotors......Page 367
Mouse......Page 368
Guinea Pig......Page 369
Rabbit......Page 370
Studies in Normal Dogs......Page 371
Studies in Isolated Hearts......Page 372
Studies in Isolated Hearts......Page 373
Human......Page 374
References......Page 375
Brief Historical Overview of Defibrillation Mechanisms......Page 379
Virtual Electrode Polarization Induced by the Shock in the Three-Dimensional Volume of the Ventricles......Page 380
Activity Originating from the Virtual Electrode Polarization Established by the Shock......Page 383
Mechanisms for the Isoelectric Window Following Shocks Near the Upper Limit of Vulnerability......Page 386
Shock-Induced Phase Singularities and Filaments......Page 387
References......Page 389
G-Protein Coupled Receptors......Page 391
Specificity and Integration of Adrenergic Signaling via Compartmentalization......Page 392
Voltage-Gated Sodium Channels......Page 393
Rapidly Activating Delayed-Rectifier Potassium Channel......Page 394
Pacemaker Current......Page 395
Acetylcholine-Sensitive Inward Rectifier Potassium Channel......Page 396
References......Page 397
Cardiac Nerves......Page 399
Mechanisms of Sympathetic Neural Remodeling......Page 400
Alteration of Sympathetic Innervation and Cardiac Arrhythmia......Page 401
Arrhythmogenic Mechanism of Sympathetic Nerve Sprouting after MI......Page 403
Interaction between Sympathetic Neural Remodeling and Electrical Remodeling......Page 404
References......Page 405
Autonomic Nervous System......Page 409
Affinity......Page 410
Principles of Tomographic Imaging......Page 411
Quantification of Autonomic Nervous System Function......Page 412
Presynaptic Radiotracer Studies......Page 413
Postsynaptic Radiotracer Studies......Page 416
References......Page 417
Autonomic Neural Mechanisms......Page 423
Sinus Bradycardia and Tachycardia (Patient Studies)......Page 424
Atrial Fibrillation (Animal Studies)......Page 425
Supraventricular Tachycardia and Atrial Fibrillation (Patient Studies)......Page 426
Ventricular Tachycardia and Ventricular Fibrillation (Animal Studies)......Page 427
Ventricular Tachycardia and Ventricular Fibrillation (Patient Studies)......Page 428
References......Page 429
Mechanisms of Arrhythmogenicity of Pulmonary Veins......Page 433
Catheter Ablation of the Pulmonary Veins......Page 434
Superior Vena Cava in Initiating and Maintaining Atrial Fibrillation......Page 435
Vein of Marshall as an Arrhythmogenic Structure......Page 437
Coronary Sinus in Arrhythmogenesis......Page 438
Inferior Vena Cava......Page 439
References......Page 440
Relation between Activity in the Left and Right Atria......Page 443
Frequency-Dependent Breakdown of Propagation......Page 445
Spatial Distribution of Dominant Frequencies during Atrial Fibrillation in Patients......Page 446
High Dominant Frequency Sites and Maintenance of Atrial Fibrillation......Page 448
Activation Frequency and Driver Mechanisms......Page 450
Summary and Future Directions......Page 451
References......Page 452
Fractionation of Atrial Electrograms: General Mechanism......Page 455
Transverse, Longitudinal, and Zigzag Conduction......Page 456
Relation between Frequency and Fractionation: Boundary of the High-Frequency Domains......Page 457
References......Page 459
Mitral Regurgitation......Page 461
Acute Atrial Ischemia......Page 462
Spatiotemporal Organization in the Different Models of Atrial Fibrillation......Page 463
Congestive Heart Failure......Page 464
Mitral Regurgitation......Page 465
Comparison of the Atrial Fibrillation Models......Page 466
Clinical Data......Page 467
Conclusion......Page 468
References......Page 469
Paradigms of Atrial Fibrillation Maintenance......Page 471
Atrial Structural Remodeling......Page 472
Molecular Determinants of Alterations to L-type Calcium Current......Page 473
Mechanisms of Altered Voltage-Gated Potassium Currents......Page 474
Platelet-Derived Growth Factor......Page 475
Profibrotic Signaling in Various Atrial Fibrillation Paradigms......Page 476
Ionic Determinants of Ectopic Firing in Conditions That Produce Chronic Atrial Fibrillation......Page 477
Conclusions......Page 479
References......Page 480
Electrocardiographic Imaging Methodology......Page 485
Activation and Repolarization of the Normal Human Heart......Page 486
Epicardial Potentials During Ventricular Activation......Page 487
Ventricular Repolarization......Page 488
References......Page 490
Rotors and Their Breakup......Page 491
Inwardly Rectifying Potassium Current Controls Ventricular Fibrillation Frequency......Page 492
Dynamics of Fibrillatory Conduction......Page 494
IKs and Postrepolarization Refractoriness......Page 495
Clinical Implications......Page 496
Conclusions......Page 497
References......Page 498
Border Zones of Ischemia and Associated Heterogeneities......Page 501
Triggers......Page 502
Formation of Reentry and Wave Breaks......Page 503
Cellular Factors in the Evolution of Ventricular Fibrillation......Page 504
Future Directions......Page 506
References......Page 507
Ventricular Tachycardia Triggered by Acute Delay of Repolarization in a Proarrhythmic Substrate......Page 509
Proarrhythmic Substrate in Andersen-Tawil Syndrome......Page 510
Proarrhythmic Substrate with Functional Exaggeration of Heterogeneity......Page 511
Ventricular Tachycardia Induced by Phase 2 Reentry in Brugada Syndrome......Page 512
Ventricular Tachycardia by Transmural Reentry During Arterial Occlusion and Reperfusion......Page 514
References......Page 515
Mechanisms by Which Defibrillation Shocks Alter the Transmembrane Potential......Page 517
Ionic Currents Responsible for the Changes of Transmembrane Potential During Defibrillation Shocks......Page 519
Mechanisms by Which Defibrillation Shocks Reinitiate Reentry and Ventricular Fibrillation......Page 521
Mechanisms by Which a Shock Defibrillates......Page 522
References......Page 525
Primer on Molecular Genetics and Single Nucleotide Polymorphisms......Page 527
Clinical Relevance of Common Potassium Channel Single Nucleotide Polymorphisms......Page 528
Clinical Relevance of Common Sodium Channel Single-Nucleotide Polymorphisms......Page 531
Functional Common Polymorphisms within Non-Ion-Channel Genes......Page 534
References......Page 535
Molecular Genetics......Page 537
Relationship of LQT3 with Sudden Infant Death Syndrome......Page 538
Genotype-Phenotype Correlation......Page 539
Congenital Sick Sinus Syndrome and Atrial Standstill......Page 540
Clinical Significance of Common SCN5A Variants......Page 541
References......Page 542
Pathophysiology of QT Interval Prolongation and Arrhythmias......Page 545
Clinical Phenotype......Page 546
Treatment......Page 548
Atrial Fibrillation......Page 549
References......Page 550
Catecholaminergic Polymorphic Ventricular Tachycardia Causing Mutations in the RyR2 Gene......Page 553
Pathophysiology......Page 554
In Vitro Studies of RYR2 Mutations......Page 557
In Vitro Studies of CASQ2 Mutations......Page 559
CASQ2 Knockout and Knockin Mouse Models......Page 560
Electrophysiologic Mechanisms in Autosomal Recessive Catecholaminergic Polymorphic Ventricular Tachycardia......Page 561
References......Page 562
Drug Transport Is an Active Process......Page 565
Loading Doses......Page 566
Mutations......Page 567
Polymorphisms......Page 568
Emerging Approaches in Genomic Medicine......Page 569
References......Page 570
The Heart in the Chest and the Atria......Page 573
Structure of the Right Atrium......Page 574
Structure of the Left Atrium......Page 577
Myoarchitecture and Interatrial Connections......Page 579
Cardiac Conduction System: Sinus Node and Atrioventricular Node......Page 580
Conclusions......Page 581
References......Page 582
Insights from Animal Models of Atrial Flutter......Page 585
Atrial Flutter in Humans......Page 586
Entrainment of Atrial Flutter......Page 587
Incidence and Clinical Setting......Page 588
Types of Atrial Flutter......Page 589
Techniques of Rapid Atrial Pacing to Interrupt......Page 590
Summary......Page 592
References......Page 593
Pulmonary Veins......Page 595
High-Frequency Sources or Rotors......Page 596
Rate versus Rhythm Control......Page 597
Statins, Polyunsaturated Fatty Acids, and Inhibitors of the Renin-Angiotensin-Aldosterone System......Page 598
Tailored, Stepwise, Electrogram-Guided Ablation......Page 599
Related Structures of Thoracic Veins, Coronary Sinus, Superior Vena Cava, and the Ligament of Marshall and Right Atrium......Page 601
Surgical Ablation......Page 602
Thromboembolic Risk......Page 603
Long-Term Anticogulation after Catheter Ablation......Page 604
References......Page 605
Focal Atrial Tachycardias......Page 607
Electrocardiographic Localization of Focal Atrial Tachycardia......Page 609
Atrial Tachycardia Arising from the Coronary Sinus......Page 611
Atrial Tachycardia Arising from the Atrial Septum......Page 612
Electrophysiologic Differential Diagnosis of Focal Atrial Tachycardia......Page 613
Classification......Page 616
Electrocardiographic Characterization of Macro-reentrant Atrial Tachycardia......Page 617
Specific Types of Macro-reentrant Atrial Tachycardia......Page 619
References......Page 620
Clinical Presentation......Page 623
Electrocardiographic Characterization......Page 624
Findings during Sinus Rhythm......Page 626
Findings during Tachycardia......Page 627
Mapping and Ablation of Accessory Pathways......Page 629
Summary......Page 630
References......Page 631
Fast Atrioventricular Nodal Pathway......Page 633
Slow Atrioventricular Nodal Pathway......Page 637
Rightward Inferior Extension Slow/Fast Atrioventricular Nodal Reentrant Tachycardia......Page 644
Leftward Inferior Extension Slow/Fast Atrioventricular Nodal Reentrant Tachycardia......Page 649
Slow/Slow and Fast/Slow Atrioventricular Nodal Reentrant Tachycardia......Page 650
Slow/Slow Atrioventricular Nodal Reentrant Tachycardia......Page 651
Fast/Slow Atrioventricular Nodal Reentrant Tachycardia......Page 652
Rightward-Leftward Inferior Extension Atrioventricular Nodal Reentrant Tachycardia......Page 654
Differentiating Atrioventricular Nodal Reentrant Tachycardia from Orthodromic Atrioventricular Reentrant Tachycardia and Atrial Tachycardia......Page 655
Management of Atrioventricular Nodal Reentrant Tachycardia......Page 658
References......Page 662
Overview......Page 665
Epidemiology and Natural History......Page 666
Electrocardiographic Manifestations......Page 667
Studies of Clinical Mechanism......Page 668
Catheter Ablation......Page 670
Surgical Therapy......Page 671
Bradycardia......Page 672
References......Page 673
Mechanism......Page 675
Clinical Characteristics and Evaluation......Page 676
Electrophysiologic Diagnosis......Page 678
Treatment......Page 679
Clinical Characteristics......Page 680
Mechanism......Page 681
Therapy......Page 683
References......Page 684
Pathophysiologic Substrate......Page 687
Mechanism of Sustained Ventricular Tachycardia......Page 688
Response to Programmed Stimulation......Page 689
Long-Term Management......Page 690
References......Page 691
Genetics......Page 693
Mechanisms of Ventricular Tachycardia......Page 694
Insights from Electroanatomic Mapping......Page 695
Mechanisms of Sudden Death......Page 696
Clinical Predictors of Mortality......Page 697
Noninvasive Electrocardiographic Predictors......Page 698
Adrenergic Receptor-Blocking Agents......Page 699
Antiarrhythmic Drug Therapy......Page 700
Biventricular Pacing......Page 701
Catheter Ablation......Page 702
Conclusions......Page 703
References......Page 704
Cell-Cell Adhesion Proteins and Apoptosis......Page 707
Wnt Family Signaling Pathway......Page 708
Genotype......Page 709
Phenotype......Page 711
Histology......Page 713
Summary......Page 714
References......Page 715
Ventricular Tachycardia......Page 717
Mechanisms of Sudden Death......Page 718
Implantable Defibrillator......Page 719
Complications......Page 721
References......Page 723
Conduction Properties......Page 725
Fibrosis/Matrix......Page 726
ATP-Gated Potassium Channels......Page 727
Remodeling of Ca2+ Dynamics in Heart Failure......Page 728
Protein Expression and Modification......Page 729
Early and Delayed Afterdepolarizations......Page 730
References......Page 731
Anatomy and Surgical Technique......Page 735
Inducible Ventricular Tachycardia and Sudden Death......Page 736
Treatment of Ventricular Tachycardia in the Postoperative Patient......Page 737
References......Page 739
Diagnosis......Page 741
Etiology and Genetics......Page 742
Pathophysiology......Page 744
Syncope......Page 745
Programmed Ventricular Stimulation......Page 746
References......Page 747
KCNQ1 (LQT1) and KCNE1 (LQT5)......Page 749
Cardiac Events and Their Relation to Genotype......Page 750
T Wave Morphology......Page 751
Heart Rate and Its Reflex Control......Page 752
Clinical Presentation of the Jervell and Lange-Nielsen Syndrome......Page 753
Clinical Diagnosis......Page 754
The International Registry......Page 755
Left Cardiac Sympathetic Denervation......Page 756
Gene-Specific Therapy and Management......Page 757
Molecular Genetics of Short QT Syndrome......Page 758
Therapy......Page 759
References......Page 760
Diagnostic Value of Exercise Stress Testing......Page 763
Mutations in the Cardiac Ryanodine Receptor......Page 764
Mutations in Cardiac Calsequestrin: CASQ2......Page 765
KCNJ2 Disease: Andersen-Tawil Syndrome......Page 766
References......Page 767
Molecular Correlate of IK1......Page 771
Cellular Basis for the Clinical Syndrome......Page 772
References......Page 773
Genetics of Timothy Syndrome......Page 775
Therapy for Timothy Syndrome......Page 778
References......Page 779
Diagnostic Evaluation......Page 781
General Findings......Page 782
Triggers......Page 783
Follow-up and Therapy......Page 784
References......Page 785
Genetic Predisposition......Page 787
Drug-Induced Long QT Syndrome......Page 788
Mechanism of Acquired Torsades de Pointes......Page 789
Sodium Channel Blocker-Related Toxicity......Page 791
Acquired Brugada Syndrome......Page 792
Digitalis Toxicity......Page 793
References......Page 794
Cardiac Sodium Channel Gene SCN5A......Page 797
Mutations in Other Ion Channels......Page 799
Transcription Factors and Cardiac Conduction Disease......Page 801
DMPK Mutations and Cardiac Conduction Disease......Page 802
References......Page 803
Linking Sudden Infant Death Syndrome and Arrhythmia......Page 807
Sudden Infant Death Syndrome and Long QT Syndrome......Page 809
Sudden Infant Death Syndrome and Brugada Syndrome, Catecholaminergic Polymorphic Ventricular Tachycardia, and Short QT Syndrome......Page 810
Implications for Screening, Therapy, and Further Research......Page 811
References......Page 812
Sudden Cardiac Death as a Public Health Burden: Estimates of Incidence......Page 815
Causes and Clinical Expressions of Sudden Cardiac Death......Page 816
Pathologic Findings in Sudden Cardiac Death Victims......Page 817
Prediction and Strategies for Prevention of Sudden Cardiac Death......Page 818
Prediction of Risk of Sudden Cardiac Death in Coronary Heart Disease......Page 819
Epidemiologic Paradigms for Sudden Cardiac Death Prediction......Page 821
The Inherited Basis of Sudden Cardiac Death Risk......Page 822
Interventional Epidemiology of Sudden Cardiac Death Risk......Page 824
References......Page 825
Arrhythmia Manifestations......Page 827
Genetics and Cardiac Pathophysiology......Page 828
Arrhythmia Manifestations......Page 829
Treatment and Prognosis......Page 830
Arrhythmia Manifestations......Page 831
References......Page 832
Classic Parasystole......Page 835
Electrocardiographic Characteristics of Modulated Ventricular Parasystole......Page 836
Parasystolic Entrainment......Page 837
Intermittency of Manifest Parasystolic Activity: Recapitulation......Page 838
‘‘Parasystolic Alienation’’ and the Withering of Parasystole......Page 839
References......Page 840
Distinguishing Features of Wide QRS Complex Tachycardia......Page 841
Supraventricular Tachycardia versus Ventricular Tachycardia: History and Physical Examination......Page 842
Differentiation of Supraventricular Tachycardia with Aberration from Ventricular Tachycardia: Electrocardiographic Criteria......Page 843
Practical Approaches to Diagnosis of Wide Complex Tachycardia......Page 847
References......Page 848
Palpitations......Page 849
Syncope......Page 850
Carotid Sinus Massage......Page 851
Stress Testing and Other Noninvasive Studies......Page 852
Tachyarrhythmias......Page 853
Summary......Page 854
Augmentation of the Calcium Transient......Page 855
Verapamil-Sensitive Fascicular Tachycardia......Page 857
Catecholaminergic Polymorphic Ventricular Tachycardia......Page 858
Prognostic Value of Exercise-Induced Arrhythmias......Page 859
References......Page 861
Implanted Loop Recorders......Page 863
Clinical Trials......Page 865
Event Classification......Page 866
References......Page 867
Methods......Page 869
Ventricular Late Potentials......Page 870
Prognostic Value of Late Potential Measurements after Acute Myocardial Infarction......Page 872
Abnormal Intra-QRS Potentials......Page 873
Summary......Page 874
References......Page 875
Transient Loss of Consciousness and Syncope......Page 877
Physiologic Impact of Upright Posture......Page 878
Pathophysiology of Vasovagal Syncope......Page 879
Passive Drug-Free Tilt Testing......Page 881
Passive Tilt Testing with Pharmacologic Provocation......Page 882
Pharmacologic Provocation......Page 883
Reproducibility of Head-up Tilt Table Testing Results......Page 884
Test Supervision......Page 885
Conclusions......Page 886
References......Page 887
Statistical and Spectral Assessment......Page 889
Nonlinear Methods......Page 890
Deceleration Capacity......Page 891
Heart Rate Turbulence and Baroreflex Sensitivity......Page 892
Risk Stratification Based on Other Baroreflex Tests......Page 893
Angle of the Ventricular Gradient......Page 894
Multivariate Risk Prediction......Page 895
References......Page 896
Monophasic Action Potential Recording in the Animal Research Laboratory......Page 899
Use Dependence of Antiarrhythmic Drugs: Action Potential Duration and Refractoriness......Page 900
Monophasic Action Potential Recordings during Atrial Flutter and Fibrillation......Page 901
Electrical Remodeling......Page 902
References......Page 903
Mechanisms Underlying T Wave Alternans......Page 905
Cellular Basis of Action Potential Alternans......Page 906
Classification and Interpretation of Microvolt T Wave Alternans Recordings......Page 907
Applicability of Microvolt T Wave Alternans Assessment......Page 908
Microvolt T Wave Alternans Assessment for Risk Stratification......Page 909
Survivors of Acute Myocardial Infarction......Page 910
Patients with Ischemic and Nonischemic Cardiomyopathy......Page 911
Future Role of Microvolt T Wave Alternans Assessment......Page 912
References......Page 913
Entrainment Mapping......Page 915
Noncontact Mapping......Page 916
Other Electrospatial Mapping Technologies......Page 917
Magnetic Navigation......Page 918
Transesophageal Echocardiography......Page 919
Rotational Angiography......Page 920
References......Page 921
Overview......Page 923
Scar-Related Atypical Atrial Flutter......Page 924
Focal Left Ventricular Tachycardia......Page 925
Heart Failure and Cardiac Resynchronization Therapy......Page 926
References......Page 930
Differential Diagnosis......Page 931
Standard Electrocardiogram......Page 933
Echocardiograms......Page 934
Evaluation of Sinus Node Function......Page 935
Significance of a Normal Response to Electrophysiologic Testing......Page 936
Selected Issues Concerning the Treatment of Syncope......Page 937
References......Page 939
Acute Triggering of Sudden Cardiac Death with Athletic Activity......Page 941
Remodeling and Conditioning......Page 942
Electrocardiograms in Athletes......Page 943
Commotio Cordis......Page 944
Screening......Page 946
Supplements......Page 947
References......Page 948
Supraventricular Tachycardia......Page 951
Atrial Fibrillation......Page 952
Ventricular Arrhythmias and Sudden Cardiac Death......Page 953
Acquired Long-QT Syndrome: Drug-Induced Proarrhythmia......Page 954
References......Page 955
Tachycardia Mediated by the Accessory Pathway......Page 959
Atrioventricular Node......Page 960
Ventricular Arrhythmias......Page 962
Pediatric Therapeutic Concerns......Page 963
Pacing and Device Therapy......Page 964
Special Considerations in Fetal Arrhythmias......Page 966
Conclusion......Page 967
References......Page 968
Pathophysiology......Page 969
Bradyarrhythmias......Page 970
Bradyarrhythmias......Page 971
Ventricular Arrhythmias and Sudden Cardiac Death......Page 972
Obstructive Sleep Apnea......Page 973
References......Page 974
Mechanism-Based Approaches......Page 977
Classification of Antiarrhythmic Drugs......Page 978
Proarrhythmia Due to QT Prolongation......Page 980
Proarrhythmia due to Sodium Channel Block......Page 981
Pharmacodynamics......Page 982
Pharmacokinetics......Page 984
Pharmacokinetics......Page 985
Efficacy......Page 986
Pharmacodynamics......Page 987
Pharmacodynamics......Page 988
Pharmacodynamics......Page 989
References......Page 990
Trigger Suppression in Atrial Fibrillation......Page 993
Reversal of Electrical Remodeling by Prolonging Duration of Action Potential......Page 994
Modulation of Myocardial Calcium Homeostasis: A Target to Prevent Sudden Death?......Page 995
Other Novel Antiarrhythmic Drugs......Page 996
Targeted Reversal of Electrical Remodeling after Cardioversion......Page 997
References......Page 998
Pathophysiology......Page 1001
Efficacy of β-Blockers after Myocardial Infarction......Page 1002
Angiotensin-Converting Enzyme Inhibitors......Page 1004
3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibitors......Page 1005
Polyunsaturated Fatty Acids......Page 1006
References......Page 1007
Battery......Page 1009
Nonthoracotomy or Transvenous Leads......Page 1010
Sensing......Page 1011
Rate and Duration......Page 1012
Pacing Therapy......Page 1013
Defibrillation Threshold and Safety Margin......Page 1014
Monophasic Waveforms......Page 1015
Recent and Future Directions......Page 1016
References......Page 1017
Sensing......Page 1019
Defibrillation Efficacy......Page 1020
Perspective......Page 1021
Patients with High Defibrillation Thresholds......Page 1022
Supraventricular Tachycardia and Ventricular Tachycardia Discriminators......Page 1023
Oversensing......Page 1025
Unsuccessful Shocks......Page 1027
Medical Sources......Page 1028
References......Page 1029
Acquired Atrioventricular Block......Page 1033
Neurocardiogenic Syncope......Page 1034
Atrial Inhibited (AAI) Pacing......Page 1035
Selection Criteria......Page 1036
Activity and Accelerometer Sensors......Page 1037
Troubleshooting Electrocardiographic Abnormalities......Page 1038
Atrial Arrhythmia Detection and Automatic Mode Switching......Page 1040
Electromagnetic Interference......Page 1041
References......Page 1042
Atrioventricular Decoupling......Page 1045
Intraventricular Conduction Delay......Page 1046
Improved Ventricular Mechanics due to Reduction in Ventricular Conduction Delay......Page 1048
Reduction in Functional Mitral Regurgitation......Page 1049
Approach to Transvenous Left Ventricular Lead Placement......Page 1050
Coronary Sinus Cannulation......Page 1051
Techniques for Overcoming Factors Limiting Successful Transvenous Left Ventricular Lead Placement......Page 1052
Pacing Modes......Page 1053
Loss of Cardiac Resynchronization: Causes and Corrective Actions......Page 1054
Responders and Nonresponders......Page 1056
Nonresponders......Page 1057
References......Page 1058
Atrioventricular Synchrony......Page 1061
Biventricular Pacing (Cardiac Resynchronization Therapy)......Page 1062
Atrial Fibrillation......Page 1063
Long-QT Syndrome......Page 1064
Conclusions......Page 1065
References......Page 1066
Heat Transfer to Tissue......Page 1069
Limitations of Catheter-Based Radiofrequency Ablation......Page 1071
Cryoablation......Page 1072
High-Intensity Focused Ultrasound......Page 1073
Other Energy Sources and Approaches for Lesion Formation......Page 1074
References......Page 1075
Complex Fractionated Electrograms......Page 1077
Dominant Frequency Electrograms......Page 1078
Ablation of the Coronary Sinus and Inferior Left Atrium......Page 1079
Monitoring Progress of Ablation Using Atrial Fibrillatory Cycle Length......Page 1080
Linear Ablation......Page 1081
Technique for Ablation of the Left Atrial Roof......Page 1082
Pulmonary Vein Ablation Plus Linear Ablation......Page 1083
Autonomic Ganglia......Page 1084
Conclusion......Page 1086
References......Page 1087
Endpoints......Page 1089
Posterior and Mitral Isthmus Lines......Page 1090
Preprocedure Preparation......Page 1091
Current Electroanatomic Mapping Systems: Advantages and Disadvantages......Page 1093
Challenging Ablation Targets......Page 1095
Postablation Atrial Tachycardia......Page 1096
Remote Mapping and Ablation with Stereotaxis......Page 1097
Conclusions......Page 1098
References......Page 1099
Endpoints for Slow Pathway Ablation......Page 1101
Accessory Pathway Localization......Page 1102
Left-Sided Accessory Pathways......Page 1103
Septal Accessory Pathways......Page 1104
Approach to Isthmus Ablation......Page 1105
Ablation of Non-Cavo-Tricuspid Isthmus Atrial Macro-reentry......Page 1106
Other Mapping Techniques......Page 1107
References......Page 1108
Electrophysiologic Evaluation......Page 1111
Epicardial Mapping and Ablation......Page 1114
Substrate Mapping—Electrograms and Pace Mapping......Page 1115
Activation Mapping and Electrograms......Page 1117
Acute Procedural Endpoints and Outcomes......Page 1118
Summary......Page 1119
References......Page 1120
Basics......Page 1123
Techniques......Page 1124
Energy Source......Page 1125
Clinical Spectrum and Patient Selection......Page 1126
Techniques......Page 1127
References......Page 1129
Mapping Systems......Page 1131
Energy Sources and Catheter Techniques......Page 1132
Atrioventricular Node Reentry Tachycardia......Page 1133
Congenital Heart Disease......Page 1134
Indications......Page 1135
References......Page 1137
A......Page 1141
B......Page 1146
C......Page 1147
D......Page 1151
E......Page 1152
G......Page 1153
H......Page 1154
I......Page 1155
L......Page 1158
M......Page 1159
O......Page 1161
P......Page 1162
Q......Page 1164
R......Page 1165
S......Page 1166
T......Page 1169
V......Page 1171
Z......Page 1173