Cardiac Bioelectric Therapy. Mechanisms and Practical Implications

Foreword
Preface
	Reductionist Approach to Arrhythmia
	Integrative Approach
Contents
Contributors
Part I: History of Electrotherapy
	1: History of Cardiac Pacing
		Earl Bakken: One Version of the First Pacemaker Story
		The Long List of Inventions and Observations That Led to the Pacemaker
			Pulse Theory and Observations that Bradycardia Leads to Syncope
		Early Cardiac Pacing
		Internal Pacemakers
		Pacing for Nonsurgeons
		Power Innovations
		Programming
		Dual-Chamber Pacing
		Activity Rate Responders
		Implantable Cardiac Defibrillators
		Michel Mirowski
		Leadless Pacing
		Conclusion
		References
	2: History of Defibrillation
		Introduction: Defibrillation and Its Creators
		Mysteries of Early Research: Abdilgaard’s Chickens and Kite’s Successes
		Elucidating the Mechanism, Imagining the Cure
		Defibrillation: From Russia and the Soviet Bloc
		Defibrillation: AC to DC, in America and Beyond
		Summary
		References
	3: The History of Mapping
		Introduction
		Origins and Initial Development
		Transition Period to Modern Excitation Mapping (1950–1990)
			Excitation of the Normal Heart Beat
			Excitation of the Abnormal/Arrhythmic Heart
			New Recording Technology
		Clinical Mapping Becomes a Standard Therapeutic Technique
			Clinical Mapping for Diagnosis and Therapy of Arrhythmias
			Electroanatomical Mapping
		Phase Mapping
		Noninvasive Mapping
		Conclusion
		References
	4: History of Optical Mapping
		Origins
		Optical Mapping
		Evolution
		Fluorescent Dyes
		Electromechanical Uncoupling
		Future Applications
		References
Part II: Theory of Electric Stimulation and Defibrillation
	5: The Bidomain Theory of Stimulation
		Introduction
		Unipolar Stimulation
		Make and Break Excitation
		Strength-Interval Curve
		No-response Phenomenon
		Effect of Potassium on Pacing
		Time Dependence of the Refractory Period
		Burst Pacing
		Conclusion
		References
	6: Bidomain Model of Defibrillation
		Introduction
		Advancements Leading to the Development of the Bidomain Model of Defibrillation
		Bidomain Equations and Numerical Approaches for Large-Scale Simulations in Shock-Induced Arrhythmogenesis and Defibrillation
		Governing Equations
		Computational Considerations
		Numerical Schemes
		Linear Solvers
		Models of the Heart in Vulnerability and Defibrillation Studies
		Description of Myocardial Geometry and Fiber Architecture
		Representation of Ionic Currents and Membrane Electroporation
		Shock Electrodes and Waveforms
		Arrhythmia Induction with an Electric Shock and Defibrillation
		Postshock Activity in the Ventricles
			VEP Induced by the Shock in the 3D Volume of the Ventricles
			Postshock Activations in the 3D Volume of the Ventricles
		ULV and LLV
		Shock-Induced Phase Singularities and Filaments
		Induction of Arrhythmia with Biphasic Shocks
		Conclusion
		References
	7: The Generalized Activating Function
		Introduction
		The Activating Function
		The Generalized Activating Function
		Examples
		Discussion
		Limitations
		Validation
		Conclusion
		Appendix
		References
Part III: Electrode Mapping and Defibrillation
	8: Extracellular Mapping of Arrhythmias
		Introduction
		Historic Note
		Theoretical Considerations
		Electrodes and Recording System
		Signal Conditioning
		Analysis of Activation
		Display of Data
		Other Forms of Analysis
		Post-Processing of Maps
		Strategies for Mapping Arrhythmias
		Summary
		References
	9: The Upper Limit of Vulnerability and Critical Points for Defibrillation
		Introduction
		Mechanisms by Which Shocks Induce VF
		The Field-Recovery Critical Point
		Inconsistencies with the Field-Recovery Critical Hypothesis for Defibrillation
		The Virtual Electrode Critical Point
		Other Possible Mechanisms for Defibrillation
		References
	10: His-Purkinje Involvement in Arrhythmias and Defibrillation
		Arrhythmia Initiation
		Arrhythmia Maintenance
		Ventricular Tachycardia
		Ventricular Fibrillation
		Short-Duration Ventricular Fibrillation
		Long-Duration Ventricular Fibrillation
		The Purkinje System and Post-Shock Arrhythmia
		Modeling of His–Purkinje System
		Modeling the Purkinje System
		Modeling the Response to Electric Shock
		Arrhythmia Onset
		References
Part IV: Optical Mapping of Stimulation and Defibrillation
	11: The Role of Microscopic Tissue Structure in Defibrillation
		Introduction
		The Concept of the Virtual Electrode
		The Microstructure of the Heart and Virtual Electrodes: From the Single Cell to the Whole Heart
		Do Cell Boundaries Form Resistive Obstacles that Produce Secondary Sources?
		Estimation of the Minimal Size of a Resistive Boundary Acting as a Source of Electrical Excitation
		The Time Course of the Change in Transmembrane Voltage Is Related to Microstructure
		Do Disease States Change Virtual Electrodes in a Predictable Manner?
		References
	12: Virtual Electrode Theory of Pacing
		Introduction
		Virtual Electrodes During Unipolar Stimulation of Cardiac Tissue
		Anode and Cathode Make and Break Excitation
		Strength-Interval Curves
		Quatrefoil Reentry
		Defibrillation
		The No-Response Phenomenon and the Upper Limit of Vulnerability
		Influence of Physical Electrodes During a Shock
		The Effect of Fiber Curvature on Stimulation of Cardiac Tissue
		Cellular and Tissue-Scale Heterogeneities
		Regional High K+ Leads to Instability and Conduction Block
		Averaging Over Depth During Optical Mapping
		Boundary Conditions and the Bidomain Model
		The Magnetic Field Produced by Cardiac Tissue
		Conclusion
		References
	13: The Virtual Electrode Hypothesis of Defibrillation
		Introduction
		Historical Overview of Defibrillation Therapy
		Bidomain Model
		Fluorescent Optical Mapping
		Virtual Electrodes and the Activating Function
		Mechanisms of Defibrillation
		Theories of Defibrillation
		Virtual Electrode Hypothesis of Defibrillation: The Role of Deexcitation and Reexcitation
		Virtual Electrode-Induced Phase Singularity Mechanism
		Chirality of Shock-Induced Reentry Predicted by VEP Not the Repolarization Gradient
		Shock-Induced VEP as a Mechanism for Defibrillation Failure
		The Role of Electroporation
		Clinical Implications of the Virtual Electrode Hypothesis of Defibrillation
		The Role of Virtual Electrodes and Shock Polarity
		Waveform Optimization
		Toward Low-Energy Defibrillation
		Conclusion
		References
	14: Advanced Three-Dimensional Optical Mapping
		Introduction
		Optical Upstroke Morphology and Subsurface Wavefront Orientation
		The Transillumination Approach
		Near-Infrared Voltage-Sensitive Dyes and Dual Wavelength Epi-Fluorescence Mapping
		Optical Tomography
		Alternating Transillumination
		Conclusions
		References
Part V: Methodology
	15: The Bidomain Model of Cardiac Tissue: From Microscale to Macroscale
		Introduction
		Microscopic Modeling Cardiac Tissue
		Macroscopic Modeling Cardiac Tissue
		Homogenization
		Bidomain Model of Cardiac Tissue
		Bidomain Properties at the Tissue Level
		Bidomain Properties at the Heart Level
		Challenges to Classical Bidomain Predictions
		Conclusion
		References
	16: Newer Models of Cardiac Tissue
		Introduction
		In Vivo Cardiac Models
		Ex Vivo Cardiac Models
		In Silico Cardiac Models
		References
	17: The Role of Electroporation
		Role of Electroporation in Defibrillation
		Contribution of Electroporation to Optically Recorded Cellular Responses
		Electroporation Assessment by Membrane-Impermeable Dye Diffusion
		Role of Electroporation in Pacing
		Irreversible Electroporation in Cardiac Surgery
		Conclusion
		References
	18: Frequency and Phase Domains Methods for Mechanisms of Fibrillation
		Introduction
		The Frequency Representation of the Tissue Activation Rate
		Representing Cardiac Activity in the Phase Domain
		The Phase-Frequency Domain Analysis of Rotor Activity During Atrial Fibrillation
		The Body Surface Mapping to Study Mechanisms of Atrial Fibrillation
		Frequency and Phase Domain Methods in Ventricular Fibrillation
		Concluding Remarks
		References
	19: Lessons Learned from Implantable Cardioverter-Defibrillator Recordings
		Introduction
		ICD Electrograms
		Interpretation of ICD Recordings
		Lessons Learned from ICD Treatment of Ventricular Tachyarrhythmias
			Incidence of Ventricular Tachyarrhythmias
			Therapy Efficacy and Failure Modes
			Therapy Efficacy: Defibrillation
			Therapy Efficacy: Cardioversion
			Therapy Efficacy: Antitachycardia Pacing
		Investigating the Causes of Tachyarrhythmia
		Lessons Learned from Inappropriately Treated ICD Episodes
		Inappropriate Detection Due to Oversensing
		Inappropriate Detection and Therapy Due to Nonsustained VT/VF
		Inappropriate Detection Due to Supraventricular Tachycardia
		Inappropriate ICD Therapies and Changing Patient Population
		Lessons Learned from Appropriately Treated AT/AF Episodes
		Atrial Tachyarrhythmia Detection and Termination Accuracy
		Efficacy of Device-Based Therapies for AT/AF
		AT/AF Therapy Efficacy: Impact of Early Recurrence of Atrial Fibrillation
		Atrial ATP Therapy Efficacy
		Atrial Defibrillation Shock Efficacy
		Conclusion
		References
	20: Radiofrequency Versus Cryoablation
		Introduction
		Lesion Formation
			Radiofrequency Ablation
			Cryothermal Ablation
		Monitoring Lesion Growth
			Radiofrequency Ablation
			Cryoballoon Ablation
				Pre-ablation
				During Ablation
				After Ablation
		Clinical
		References
Part VI: Novel and Future Cardiac Electrotherapies
	21: Multistage Defibrillation Therapy
		Defibrillation
		Preclinical Atrial Defibrillation Studies
		Atrioverter (Atrial Defibrillator)
		Defibrillation Mechanisms
		Virtual Electrode Polarization (VEP)
		Development of the Virtual Electrode Polarization Theory
		VEP Generated Wavefronts
		Multipulse Therapy (MPT)
		MPT in an In Vivo Chronic AF Model
		First-In-Man Study of Multipulse Therapy
		Conclusion
		References
	22: Leadless Pacing
		Background
			History of Pacing
			Shortfalls in Lead-Based Pacing
		Definition of Leadless Pacemakers
		Leadless Pacemaker Devices
			The Leadless Cardiac Pacemaker (LCP)
				System Description
				Clinical Efficacy
			Micra Transcatheter Pacing System (TPS)
				System Description
				Clinical Efficacy
			WiCS®-LV System
				System Description
				Clinical Efficacy
			Empower™ Leadless Pacemaker
		Clinical Evidence
			Device Implantation
			Complications
			Device Performance
		Patient Populations
			Previous CIED Infection
			Dialysis Patients
			Vasovagal Syncope
		End of Device Life Management
		Future Developments
		Conclusions
		References
	23: His Purkinje Conduction System Pacing: Methods, Mechanisms, and Best Practices
		Introduction
		Anatomy of the AV Conduction System
			Variations in HB Anatomy
			Longitudinal Dissociation of the His Bundle
		Implantation Technique
			HBP Implant Technique
			Best Practices and Tips for HBP
			LBBP Implant Technique
		Nomenclature for HP-CSP
		Conclusions
		References
	24: State of the Art in Artificial Intelligence and Machine Learning Techniques for Improving Patient Outcomes Pertaining to the Cardiovascular and Respiratory Systems
		Introduction
			Artificial Intelligence: Machine/Deep Learning
		AI/ML/DL in Medicine
			Motivation
			Recent Development of AI in Medicine
		AI in Cardiovascular and Respiratory Systems
			Cardiovascular System
				Cardiac Imaging
				Disease Classification
				Electrocardiography
				In-Hospital Monitoring
				Mobile and Wearable Technology
				Precision Medicine
				Risk Prediction
			Respiratory System
				Chest Imaging
				Disease Classification
				Precision Medicine
				Respiratory Sound Analysis
				Risk Prediction
		Limitations and Challenges in Applying AI
		Future of AI in the Cardiovascular and Respiratory Systems
		Conclusion
		References
	25: State of the Art on Wearable and Implantable Devices for Cardiac and Respiratory Monitoring
		Introduction
		Technologies for Mobile and Continuous Monitoring
			Implantable Devices
			Wearable Devices
				Devices for Respiratory Monitoring
				Monitoring with Sensor Data Fusion and Algorithmic Processing
				Devices Aimed to Diagnose Sleep Apnea
				Devices Aimed to Diagnose Stress
				Devices Aimed to Diagnose Cardiac Arrhythmias
			Smartphone-Based Diagnostics
		Effectiveness and Adoption
		Current Limits and Future Outlook
		Conclusion
		References
	26: Optogenetic Control of Arrhythmias
		Introduction
			Opsin-Based Optogenetic Tools
			Channelrhodopsins
				Anion Channelrhodopsins
				Light-Activated Ion Pumps
			Gene Delivery Vectors for Optogenetics
		Correcting Abnormal AP Waveforms with Optogenetic Tools
		Optogenetic Cardiac Pacing
		Optogenetic Defibrillation
			Optogenetic Termination of Reentry In Vitro
			Ventricular Defibrillation in Rodent Hearts
			Optogenetic Defibrillation in Atrial Fibrillation
		Future Perspectives
			Gene Delivery
			Delivering Light to the Human Heart
			Clinical Perspectives for Optogenetics
		Summary
		References
	27: Conformal Electronics Therapy for Defibrillation
		Introduction
		Conformal Electronics Device Fabrication
		Defibrillation Using Conformal Electronics
		Future Perspective
		Conclusion
		References
	28: The Future of the Implantable Cardioverter-Defibrillator
		Future ICD Leads and Electrodes
			Improved Engineering Standards for Transvenous Leads
			Subcutaneous ICD
			Substernal ICD
		Ensuring Appropriate Therapy
			Reducing Inappropriate Shocks
				Reducing Inappropriate Shocks Caused by SVT in Transvenous ICDs
				Reducing Inappropriate Shocks Caused by Oversensing in Transvenous ICDs
				Reducing Inappropriate Shocks Caused by Oversensing in Extravascular ICDs
			Ensuring Therapy of VT/VF
				Failure to Treat VT/VF in Functioning ICD Systems
				Failure to Treat VT/VF Due to High-Voltage Insulation Breach
					The Problem
					High-Frequency Impedance
					Impedance of Ultrashort High-Voltage Pulse
			Preventing Fatal Proarrhythmia from ICD Lead Dislodgement
		Remote Monitoring and Remote Patient Management
			Remote Monitoring of ICD Functions
			Remote Monitoring Strategies
			Monitoring Comorbidities: Atrial Fibrillation and Heart Failure
			Remote Patient Management
		Prediction and Prevention of VT and VF
			Risk Stratification and Indications for ICD Therapy
				Patients Who Qualify for ICDs Under Present Guidelines but Do Not Benefit
				Patients Who Die Suddenly But Do Not Qualify for ICDs Under Present Guidelines
			Short-Term Prediction and Prevention of VT/VF
				Prediction
				Prevention
		References
	29: Cybersecurity of Cardiac Implantable Electronic Devices
		Introduction
		Cybersecurity Landscape
		Medical Device and Data Vulnerabilities
		Motivations of Hackers
		Common Hacking Attacks
		Infrastructure to Reduce Risks and Identify Vulnerabilities
			US Food and Drug Administration
				FDA Guidance for Premarket Management of Cybersecurity in Medical Devices
				FDA Guidance for Postmarket Management of Cybersecurity in Medical Devices
		The Association for the Advancement of Medical Instrumentation
		Evaluation Process for Potential Vulnerabilities
		NIST Cybersecurity Framework
		Role of Supply Chain Management
		Archimedes Center for Medical Device Security
		Role of Healthcare Providers
		Coordinated Disclosure
		Privacy Regulations
		Conclusion
		References
Index