Cardiac Arrhythmias

This book is useful for physicians taking care of patients with cardiac arrhythmias and includes six chapters written by experts in their field. Chapter 1 discusses basic mechanisms of cardiac arrhythmias. Chapter 2 discusses the chronobiological aspects of the impact of apnoic episodes on ventricular arrhythmias. Chapter 3 discusses navigation, detection, and tracking during cardiac ablation interventions. Chapter 4 discusses epidemiology and pathophysiology of ventricular arrhythmias in several noncardiac diseases, methods used to assess arrhythmia risk, and their association with long-term outcomes. Chapter 5 discusses the treatment of ventricular arrhythmias including indications for implantation of an AICD for primary and for secondary prevention in patients with and without congestive heart failure. Chapter 6 discusses surgical management of atrial fibrillation

Atrial fibrillation: a study of substrate and triggers

1. Introduction2. History and Overview of Atrial Fibrillation3. A New Fully Implantable Goat Model of Atrial Fibrillation4. The Profibdilatory Action of Verapamil is Not Prevented by Propafenone5. Repetitive Four-Week Periods of Atrial Electrical Remodelling Promote Stability of Atrial Fibrillation -Evidence for a Second Factor Independent of Atrial Refractoriness in the Self-Perpetuation of Atrial Fibrillation6. Atrial Ectopy - The Coupling Interval of Atrial Premature Beats Following DC Cardioversion of Persistent AF Predicts Subsequent Recurrence of AF7. Atrial Ectopy -Evidence for Reversal of Atrial Electrical Remodelling8. Prevalence and Significance of Focal Sources of Atrial Arrhythmia in Patients Undergoing Cardioversion of Persistent Atrial Fibrillation9. Changes in Heart Rate Variability Following Cardioversion of Persistent Atrial Fibrillation in Ma

Perspective: a dynamics-based classification of ventricular arrhythmias

Despite key advances in the clinical management of life-threatening ventricular arrhythmias, culminating with the development of implantable cardioverter-defibrillators and catheter ablation techniques, pharmacologic/biologic therapeutics have lagged behind. The fundamental issue is that biological targets are molecular factors. Diseases, however, represent emergent properties at the scale of the organism that result from dynamic interactions between multiple constantly changing molecular factors. For a pharmacologic/biologic therapy to be effective, it must target the dynamic processes that underlie the disease. Here we propose a classification of ventricular arrhythmias that is based on our current understanding of the dynamics occurring at the subcellular, cellular, tissue and organism scales, which cause arrhythmias by simultaneously generating arrhythmia triggers and exacerbating tissue vulnerability. The goal is to create a framework that systematically links these key dynamic factors together with fixed factors (structural and electrophysiological heterogeneity) synergistically promoting electrical dispersion and increased arrhythmia risk to molecular factors that can serve as biological targets. We classify ventricular arrhythmias into three primary dynamic categories related generally to unstable Ca cycling, reduced repolarization, and excess repolarization, respectively. The clinical syndromes, arrhythmia mechanisms, dynamic factors and what is known about their molecular counterparts are discussed. Based on this framework, we propose a computational-experimental strategy for exploring the links between molecular factors, fixed factors and dynamic factors that underlie life-threatening ventricular arrhythmias. The ultimate objective is to facilitate drug development by creating an in silico platform to evaluate and predict comprehensively how molecular interventions affect not only a single targeted arrhythmia, but all primary arrhythmia dynamics categories as well as normal cardiac excitation-contraction coupling

Advances in Electrocardiograms

Electrocardiograms have become one of the most important, and widely used medical tools for diagnosing diseases such as cardiac arrhythmias, conduction disorders, electrolyte imbalances, hypertension, coronary artery disease and myocardial infarction. This book reviews recent advancements in electrocardiography. The four sections of this volume, Cardiac Arrhythmias, Myocardial Infarction, Autonomic Dysregulation and Cardiotoxicology, provide comprehensive reviews of advancements in the clinical applications of electrocardiograms. This book is replete with diagrams, recordings, flow diagrams and algorithms which demonstrate the possible future direction for applying electrocardiography to evaluating the development and progression of cardiac diseases. The chapters in this book describe a number of unique features of electrocardiograms in adult and pediatric patient populations with predilections for cardiac arrhythmias and other electrical abnormalities associated with hypertension, coronary artery disease, myocardial infarction, sleep apnea syndromes, pericarditides, cardiomyopathies and cardiotoxicities, as well as innovative interpretations of electrocardiograms during exercise testing and electrical pacing

High Resolution Multi-parametric Diagnostics and Therapy of Atrial Fibrillation: Chasing Arrhythmia Vulnerabilities in the Spatial Domain

After a century of research, atrial fibrillation (AF) remains a challenging disease to study and exceptionally resilient to treatment. Unfortunately, AF is becoming a massive burden on the health care system with an increasing population of susceptible elderly patients and expensive unreliable treatment options. Pharmacological therapies continue to be disappointingly ineffective or are hampered by side effects due to the ubiquitous nature of ion channel targets throughout the body. Ablative therapy for atrial tachyarrhythmias is growing in acceptance. However, ablation procedures can be complex, leading to varying levels of recurrence, and have a number of serious risks. The high recurrence rate could be due to the difficulty of accurately predicting where to draw the ablation lines in order to target the pathophysiology that initiates and maintains the arrhythmia or an inability to distinguish sub-populations of patients who would respond well to such treatments. There are electrical cardioversion options but there is not a practical implanted deployment of this strategy. Under the current bioelectric therapy paradigm there is a trade-off between efficacy and the pain and risk of myocardial damage, all of which are positively correlated with shock strength. Contrary to ventricular fibrillation, pain becomes a significant concern for electrical defibrillation of AF due to the fact that a patient is conscious when experiencing the arrhythmia. Limiting the risk of myocardial injury is key for both forms of fibrillation. In this project we aim to address the limitations of current electrotherapy by diverging from traditional single shock protocols. We seek to further clarify the dynamics of arrhythmia drivers in space and to target therapy in both the temporal and spatial domain; ultimately culminating in the design of physiologically guided applied energy protocols. In an effort to provide further characterization of the organization of AF, we used transillumination optical mapping to evaluate the presence of three-dimensional electrical substrate variations within the transmural wall during acutely induced episodes of AF. The results of this study suggest that transmural propagation may play a role in AF maintenance mechanisms, with a demonstrated range of discordance between the epicardial and endocardial dynamic propagation patterns. After confirming the presence of epi-endo dyssynchrony in multiple animal models, we further investigated the anatomical structure to look for regional trends in transmural fiber orientation that could help explain the spectrum of observed patterns. Simultaneously, we designed and optimized a multi-stage, multi-path defibrillation paradigm that can be tailored to individual AF frequency content in the spatial and temporal domain. These studies continue to drive down the defibrillation threshold of electrotherapies in an attempt to achieve a pain-free AF defibrillation solution. Finally, we designed and characterized a novel platform of stretchable electronics that provide instrumented membranes across the epicardial surface or implanted within the transmural wall to provide physiological feedback during electrotherapy beyond just the electrical state of the tissue. By combining a spatial analysis of the arrhythmia drivers, the energy delivered and the resulting damage, we hope to enhance the biophysical understanding of AF electrical cardioversion and xiii design an ideal targeted energy delivery protocol to improve upon all limitations of current electrotherapy

Cardiac Arrhythmias

The most intimate mechanisms of cardiac arrhythmias are still quite unknown to scientists. Genetic studies on ionic alterations, the electrocardiographic features of cardiac rhythm and an arsenal of diagnostic tests have done more in the last five years than in all the history of cardiology. Similarly, therapy to prevent or cure such diseases is growing rapidly day by day. In this book the reader will be able to see with brighter light some of these intimate mechanisms of production, as well as cutting-edge therapies to date. Genetic studies, electrophysiological and electrocardiographyc features, ion channel alterations, heart diseases still unknown , and even the relationship between the psychic sphere and the heart have been exposed in this book. It deserves to be read

Atrial arrhythmogenesis in a murine model of mitochondrial insufficiency

Age-related atrial arrhythmias including atrial fibrillation are frequently encountered in clinical practice and are associated with significant mortality and morbidity. A putative role for chronic mitochondrial impairment in their pathogenesis was investigated using a murine model with homozygous deficiency of the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator-1 β (Pgc-1β-/-). Pgc-1β regulates mitochondrial biogenesis and function, and unlike other murine models of mitochondrial dysfunction Pgc-1β-/- mice have a mild cardiac phenotype, devoid of confounding contractile dysfunction. All experiments were performed in young (12-16 weeks) and aged (>52 weeks) Pgc-1β-/- mice and compared to aged-matched wild type (WT) controls. Sharp microelectrode recordings of cellular action potentials (AP) in a whole-heart Langendorff-perfused system revealed that the Pgc-1β-/- genotype was associated with an atrial arrhythmic phenotype that progressed with age. Young and aged Pgc-1β-/- hearts showed evidence of slowed AP conduction at the cellular level, through deficits in maximum rates of AP depolarization (dV/dt)max, and at the tissue level through prolonged AP latencies. Action potential duration (APD) was also significantly shorter in Pgc-1β-/- hearts at high heart rates. APD restitution has been linked to the pathogenesis of ventricular fibrillation and more recently AF. However in the present work the incidence of alternans or steepness of the restitution curves did not correlate with arrhythmic tendency. Loose patch clamp measurements demonstrated that Pgc-1β−/− atria had significantly lower inward Na+ currents than that of WT preparations, correlating to the differences in (dV/dt)max values. No differences in delayed outward (K+) currents were evident. Morphometric analysis revealed that Pgc-1β deficiency was associated with accelerated fibrosis, with aged Pgc-1β-/- hearts displaying the greatest fibrotic change. The Pgc-1β-/- murine model of chronic mitochondrial impairment results in an age-related atrial arrhythmic phenotype through adverse electrical and structural remodelling producing an atrial substrate promoting AP reentry and arrhythmia persistence.Wellcome Trust Clinical Research Training Fellowship (105727/Z/14/Z

Multichannel Analysis of Intracardiac Electrograms - Supporting Diagnosis and Treatment of Cardiac Arrhythmias

Cardiologists diagnose and treat atrial tachycardias using electroanatomical mapping systems. These can be combined with multipolar catheters to record intracardiac electrograms. Within this thesis, various signal processing techniques were implemented and benchmarked to analyze electrograms. They support the physician in diagnosis and treatment of atrial flutter and atrial fibrillation. The developed methods were assessed using simulated data and demonstrated on clinical cases