Contents

Preface xv

List of Contributors xix

Foreword xxiii

Part I History

1.1 History of Cardiac Pacing 3

Earl Bakken: One Version of the First Pacemaker Story 3

The Long List of Inventions and Observations that Led to the Pacemaker 4

Pulse Theory and Observations that Bradycardia Leads to Syncope 4

Early Cardiac Pacing 5

Internal Pacemakers 6

Pacing for Nonsurgeons 7

Power Innovations 8

Programming 8

Dual-Chamber Pacing 9

Activity Rate Responders 10

Implantable Cardiac Defibrillators 10

Michel Mirowski 10

Conclusion 12

References 12

1.2 History of Defibrillation 15

Introduction: Defibrillation and Its Creators 15

Mysteries of Early Research: Abdilgaard's Chickens and Kite's Successes 17

Elucidating the Mechanism, Imagining the Cure 22

Defibrillation: From Russia and the Soviet Block 26

Defibrillation: AC to DC, in America and Beyond 30

Conclusion 35

References 38

1.3 Ventricular Fibrillation: A Historical Perspective 41

Introduction 41

Concepts, Instruments, and Institutions: Nineteenth-Century Legacy 42

The Clinic and the Laboratory 44

Ventricular Fibrillation: Experimental Evidence and Basic Concepts,

1880s-1920s 47

From Wiggers to Moe: The Multiple Wavelet Hypothesis 52

Modern Concepts of Ventricular Fibrillation 53

Concluding Remarks 54

References and Notes 54

Part II Theory of Electric Stimulation and Defibrillation

2.1 The Bidomain Theory of Pacing 63

Introduction 63

Unipolar Stimulation 63

Make and Break Excitation 64

Strength-Interval Curves 71

No-Response Phenomenon 76

Effect of Potassium on Pacing 78

Time Dependence of the Anodal and Cathodal Refractory Periods 79

Conclusion 81

Acknowledgments 81

References 81

2.2 Bidomain Model of Defibrillation 85

Introduction 85

Advancements Leading to the Development of the Bidomain Model of

Defibrillation 86

Bidomain Equations and Numerical Approaches for Large-Scale Simulations in Shock-Induced Arrhythmogenesis and Defibrillation 87

Governing Equations 88

Computational Considerations 89

Numerical Schemes 90

Linear Solvers 91

Models of the Heart in Vulnerability and Defibrillation Studies 94

Description of Myocardial Geometry and Fiber Architecture 94

Representation of Ionic Currents and Membrane Electroporation 95

Shock Electrodes and Waveforms 95

Arrhythmia Induction with an Electric Shock and Defibrillation 96

Postshock Activity in the Ventricles 97

VEP Induced by the Shock in the 3D Volume of the Ventricles 97

Postshock Activations in the 3D Volume of the Ventricles 99

ULV and LLV 100

Shock-Induced Phase Singularities and Filaments 102

Induction of Arrhythmia with Biphasic Shocks 102

Conclusion 104

Acknowledgments 105

References 105

2.3 The Generalized Activating Function 111

Introduction 111

The Activating Function 112

The Generalized Activating Function 114

Examples 116

Discussion 124

Limitations 125

Validation 126

Conclusion 126

Appendix 126

References 130

2.4 Theory of Electroporation 133

Concept of Electroporation 133

Physical Background of Electroporation 134

Pore Energy 134

Pore Creation 136

Pore Evolution 137

Postshock Pore Shrinkage and Coarsening 138

Pore Resealing 139

Mathematical Modeling of Electroporation 140

Advection-Diffusion Equation 140

Asymptotic Model of Electroporation 141

Current-Voltage Relationship of a Pore 142

Example of the Electroporation Process 144

Governing Equation for the Transmembrane Potential 144

Membrane Charging Phase 145

Pore Creation Phase 145

Pore Evolution Phase 146

Postshock Pore Shrinkage Phase 148

Pore Resealing Phase 149

Effects of Shock Strength 149

Limitations 151

Conclusion 153

Acknowledgment 153

Appendix 1: Parameters of the Electroporation Model 154

Appendix 2: Numerical Implementation 155

References 156

Part III Electrode Mapping of Defibrillation

3.1 Critical Points and the Upper Limit of Vulnerability for Defibrillation 165

Introduction 165

Mechanisms by which Shocks Induce VF 167

The Field-Recovery Critical Point 169

Inconsistencies with the Field-Recovery Critical Hypothesis for Defibrillation 180

The Virtual Electrode Critical Point 182

Other Possible Mechanisms for Defibrillation 185

Acknowledgment 185

References 185

3.2 The Role of Shock-Induced Nonregenerative Depolarizations 189

Brief Historical Perspectives 189

The Era of Computerized Cardiac Mapping: New Insights 194

Initiation of VF by Electrical Stimuli 195

Different Proposed Hypotheses of Defibrillation 196

The Graded Response Hypothesis of Fibrillation and Defibrillation 199

Graded Response Characteristics 199

Conclusions and Future Directions 211

Acknowledgment 212

References 212

Part IV Optical Mapping of Stimulation and Defibrillation

4.1 Mechanisms of Isolated Cell Stimulation 221

Introduction 221

Transmembrane Potential (Vm) Responses of an Isolated Cell 222

Theoretical Framework of Field Stimulation 222

Experimental Responses During Field Stimulation 225

Single Cells Versus Tissue Responses: Similarities and Differences 236

Field-Induced Responses of an Isolated Cell-Pair: Sawtooth Effect 237

Theoretical Treatment of Sawtooth Effect 238

Experimental Measurement of Sawtooth Effect 239

Sawtooth Effect's Role in Tissue: "Fact or Fantasy" 241

Effect of Electric Fields on Intracellular Calcium 243

Measurement of Intracellular Ca ^ Transients Using

Fluorescent Probes 244

Effect of Field Stimulation on Intracellular Ca + Transients at Rest 244

Effect of Field Stimulation on Intracellular Ca ^ Transients

During Plateau 248

Implications of Field-Induced Ca + Gradients 248

Conclusion 249

References 249

4.2 The Role of Microscopic Tissue Structure in Defibrillation 255

Introduction 255

Possible Mechanisms of Intramural Shock-Induced Vm Changes 256

The Role of Microscopic Tissue Structure in the Shock Effects:

Experiments in Cell Cultures 258

The Role of Cell Boundaries in Shock Effects 259

The Role of Intercellular Clefts in the Shock Effects 261

Shock-Induced A Vm in Cell Strands 263

Measurements of Intramural Shock-Induced A Vm in

Wedge Preparations 270

Comparison between Microscopic and Macroscopic

AVm Measurements 275

Conclusion 277

References 277

4.3 Virtual Electrode Theory of Pacing 283

Introduction 283

Virtual Electrodes during Unipolar Stimulation of Cardiac Tissue 284

Anode and Cathode Make and Break Excitation 290

Strength-Interval Curves 293

Quatrefoil Reentry 296

Defibrillation 301

The No-Response Phenomenon and the Upper Limit of Vulnerability 306

Influence of Physical Electrodes During a Shock 306

The Effect of Fiber Curvature on Stimulation of Cardiac Tissue 307

Heterogeneities 310

Averaging over Depth During Optical Mapping 311

Boundary Conditions and the Bidomain Model 312

The Magnetic Field Produced by Cardiac Tissue 313

Conclusion 315

Acknowledgments 316

References 317

4.4 The Virtual Electrode Hypothesis of Defibrillation 331

Introduction 331

Historical Overview of Defibrillation Therapy 331

Bidomain Model 332

Fluorescent Optical Mapping 333

Virtual Electrodes and the Activating Function 334

Mechanisms of Defibrillation 335

Theories of Defibrillation 335

Virtual Electrode Hypothesis of Defibrillation: The Role of

Deexcitation and Reexcitation 336

Virtual Electrode-Induced Phase Singularity Mechanism 337

Chirality of Shock-Induced Reentry Predicted by VEP Not the Repolarization

Gradient 340

Shock-Induced VEP as a Mechanism for Defibrillation Failure 343

The Role of Electroporation 344

Clinical Implications of the Virtual Electrode Hypothesis of Defibrillation 344

The Role of Virtual Electrodes and Shock Polarity 344

Waveform Optimization 345

Toward Low-Energy Defibrillation 347

Conclusion 351

References 351

4.5 Simultaneous Optical and Electrical Recordings 357

Introduction to Electrooptical Measurements 357

ITO Properties 358

Ratiometric Optical Mapping 359

Role of the Second Spatial Derivative of the Extracellular Potential in Field Stimulation 360

Stimulatory Effects of a Spatial Variation of Extracellular Conductance in an Electric Field 364

Effect of Unipolar Stimulation in the Tissue under the Electrode 365

Electrooptical Mapping of Cardiac Excitation 368

Method of Electrooptical Mapping 369

Electrooptical Mapping of Epicardially Paced Beats and Sinus Beats 370

Electrooptical Mapping of Fibrillation 375

Conclusion 378

References 378

4.6 Optical Mapping of Multisite Ventricular Fibrillation Synchronization 381

Pacing to Terminate Ventricular Fibrillation 382

New Opportunities in Improving Ventricular Defibrillation 382

Optical Mapping of Multisite Synchronization of Ventricular Fibrillation 383

Optical Recording-Guided Pacing to Create Functional Block during VF 387

Improvement of Defibrillation Efficacy with Synchronized Multisite Pacing 389

Conclusion 393

References 393

Part V Methodology

5.1 The Bidomain Model of Cardiac Tissue: From Microscale to Macroscale 401

Introduction 401

Microscopic Modeling Cardiac Tissue 403

Macroscopic Modeling Cardiac Tissue 404

Homogenization 406

Bidomain Model of Cardiac Tissue 410

Bidomain Properties at the Tissue Level 411

Bidomain Properties at the Heart Level 416

Conclusion 417

References 418

5.2 Multielectrode Mapping of the Heart 423

Introduction 423

Methods 424

Determining Activation Time 425

Generating Contours 432

Conclusion 437

References 438

5.3 The Role of Electroporation 441

Role of Electroporation in Defibrillation 441

Contribution of Electroporation to Optically Recorded Cellular Responses 446

Electroporation Assessment by Membrane Impermeable Dye Diffusion 448

Role of Electroporation in Pacing 451

Irreversible Electroporation in Cardiac Surgery 451

Conclusion 451

References 452

Part VI Implications for Implantable Devices

6.1 Lessons for the Clinical Implant 459

Electrical Parameters of Defibrillation Waveforms 459

Parameters that Influence Defibrillation 459

Parameters that Influence ICD Design 459

Principles of Capacitive Discharge Waveforms 461

Truncation 461

Stored Versus Delivered Energy 463

Optimizing Waveforms with the RC Network Model 464

Minimizing Shock Energy Without Electronic Constraints 465

The Predicted Optimal Monophasic Shock 465

The Predicted Optimal Biphasic Shock 468

Optimizing Capacitive Discharge Waveforms 468

Optimizing Duration: Monophasic Shock and First Phase of Biphasic

Shock with a Fixed Capacitance 468

Optimizing Capacitance 471

Optimizing Phase Two of the Biphasic Waveform 472

Truncation by Duration Versus Truncation by Tilt 473

Waveform Polarity 478

Waveforms in Commercially Available ICDs 480

Other Considerations in Optimizing Waveforms 483

The Misunderstood Superior Vena Cava Coil 484

Conclusion 485

References 486

6.2 Resonance and Feedback Strategies for Low-Voltage Defibrillation 493

Introduction 493

Localized Stimulation: Induced Drift of Spiral Waves 493

Delocalized Stimulation: Resonant Drift of Spiral Waves 495

Feedback-Controlled Resonant Drift 498

Three-Dimensional Aspects 501

Pinning and Unpinning 502

"Black-Box" Approaches 507

Conclusion 507

Acknowledgments 508

References 508

6.3 Pacing Control of Local Cardiac Dynamics 511

Introduction 511

Chaos Control 511

Alternans Control 515

APD Alternans 515

Conduction Velocity Alternans 520

References 521

6.4 Advanced Methods for Assessing the Stability and Control of Alternans 525

Introduction 525

What Is an Eigenmode? 528

Characterization and Control of Alterans in Isolated Cardiac Myocytes 531

Application of the Eigenmode Method 531

The Ion Channel Mechanism Underlying Alternans 534

Development and Testing of a Control Algorithm 537

Characterization and Control of Spiral Wave Instabilities 540

Nature of Spiral Wave Instabilities 540

Elimination of Alternans in a Rotating Spiral Wave 542

Summary and Implications for Treatment of Cardiac Arrhythmias 543

Appendix: Mathematical Details 544

References 547

6.5 The Future of the Implantable Defibrillator 551

Sensing and Detection 551

Reduction of Ventricular Oversensing 551

Active SVT-VT Discrimination 552

Hemodynamic Sensors for ICDs 552

Implant Testing 553

Vulnerability Testing 555

State of the Art 557

After the Implant 559

Novel Waveform Strategies 559

Defibrillation Threshold Reduction 559

Cardioversion Pain Reduction 561

Medium Voltage Therapy 562

Novel Packaging Strategies 562

Subcutaneous ICDs 562

Percutaneous, Fully Transvenous ICD 563

Conclusion 563

References 563

6.6 Lessons Learned from Implantable Cardioverter-Defibrillators Recordings 571

Introduction 571

ICD Electrograms 572

Interpretation of ICD Recordings 573

Lessons Learned from ICD Treatment of Ventricular Tachyarrhythmias 575

Incidence of Ventricular Tachyarrhythmias 575

Therapy Efficacy and Failure Modes 578

Therapy Efficacy: Defibrillation 579

Therapy Efficacy: Cardioversion 581

Therapy Efficacy: Antitachycardia Pacing 583

Investigating the Causes of Tachyarrhythmia 586

Lessons Learned from Inappropriately Treated ICD Episodes 591

Inappropriate Detection Due to Oversensing 591

Inappropriate Detection and Therapy Due to Nonsustained VT/VF 593

Inappropriate Detection Due to Supraventricular Tachycardia 593

Inappropriate ICD Therapies and Changing Patient Population 597

Lessons Learned from Appropriately Treated AT/AF Episodes 597

Atrial Tachyarrhythmia Detection and Termination Accuracy 597

Efficacy of Device-Based Therapies for AT/AF 600

AT/AF Therapy Efficacy: Impact of Early Recurrence of Atrial Fibrillation 600

Atrial ATP Therapy Efficacy 600

Atrial Defibrillation Shock Efficacy 603

Conclusion 604

References 604

Index 615

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