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Human genetics

Introduction Historical background Genetics is a very new science, changing rapidly by the day with advances in technology. Although humans have long been aware of some form of heredity, the mechanisms have only recently become clear. Early philosophers talked about the male ripening the female, or seeds being produced in various organs to be transmitted to the child. In the early 18th century, scientists were divided…

Pharmacology

Introduction Pharmacology is the science that covers the actions, mechanisms of action, uses, adverse effects and fate of drugs in animals and man. The word ‘pharmacology’ comes from the ancient Greek word ‘pharmakon’ and is the science of what drugs do to the body and how the body reacts to xenobiotics, which covers any biologically active substance that is taken with the intent of producing a…

Energy metabolism

Introduction to Metabolism The human organism needs a constant supply of energy to enable a number of processes that are essential to survival. The central issue in metabolism is that the demand for energy is constant but the supply intermittent. Mechanisms are in place which ensure that when metabolic fuel is available in quantities greater than needed immediately, the fuel is stored, and when it is…

Biochemistry and cell biology

Introduction Cell biology tells us about the structure and functions of the cell and its organelles, whereas biochemistry addresses the chemical basis of the composition of the human body, its structure and its functions, and also the preservation and continuity of the structure and function through generations. The body is an open system and, thus, there are the interfaces with surroundings that are both sensory and…

Introduction and homeostasis

Disease ensues when normal physiological mechanisms and processes are disrupted. These processes take place in the basic unit of living organisms: the cell. It is therefore essential that all clinicians understand normal cellular and molecular mechanisms and processes in order to understand disease. The following chapters address specific mechanisms related to particular areas of human function and systems of the body. The basic science concepts that…

Drug Discovery for Myocardial Diseases and Cardiac Arrhythmias Using Zebrafish

Challenges in Cardiovascular Drug Discovery Despite the significant decline in cardiovascular disease mortality over the past several decades due to more effective medications and surgical procedures, cardiovascular diseases remain one of the leading causes of death and a major economic burden to the health care system globally. , Surprisingly, investment in cardiovascular drug development, particularly for myocardial diseases and arrhythmias, has stagnated, and approvals for new…

Neuromodulation for the Treatment of Arrhythmias

The autonomic nervous system plays a significant role in the genesis and maintenance of ventricular arrhythmias (VAs) and powerfully modulates the underlying substrate in a dynamic manner. Blockade of the sympathetic nervous system, whether through medications or neuraxial modulation, has been extensively studied and associated with a reduction in the risk for sudden cardiac death (SCD) and burden of VAs, whereas pharmacologic sympathetic blockade is standard-of-care…

Surgery for Ventricular Arrhythmias

Historical Perspective Open-heart surgery was commonly used in the past to treat refractory ventricular arrhythmias (VAs). The predominant population subjected to this management strategy was made up of patients with healed myocardial infarcts who experienced sustained ventricular tachycardia (VT). The original technique used resection of the dyskinetic/akinetic scarred myocardial tissue (aneurysmectomy) and had only modest success (∼40%) for long-term arrhythmia control. Subsequent mapping studies revealed that…

Surgery for Atrial Fibrillation and Other Supraventricular Tachycardias

Atrial Fibrillation The treatment of atrial fibrillation (AF) with antiarrhythmic medications have been limited by modest efficacies, proarrhythmic side effects, and systemic toxicities. Conversely, rate-control strategies leave patients in AF and do not address the impaired hemodynamics or symptoms associated with this arrhythmia. This strategy may also render subsequent attempts at rhythm-control therapies less effective because patients may suffer irreversible atrial remodeling after a prolonged duration…

Epicardial Approach in Electrophysiology

The first invasive studies of cardiac electrophysiology (EP) in humans were performed epicardially. During its golden age (1970s to 1980s), electrical activation maps were acquired in the operating room by surgeons. These studies greatly advanced our understanding of the predominant mechanisms underlying common atrial and ventricular arrhythmias and paved the way for the first curative surgical procedures for electrical disorders. This approach would eventually be superseded…

Cardiac Radioablation

Background: Why Develop a New Technique for Cardiac Ablation? Cardiac ablation using thermal energy is a mainstay of interventional electrophysiology (EP) today. Extremes of heat or cooling can be delivered through the tip of an invasive catheter, causing largely irreversible local tissue destruction. During this process, the thermal energy is first generated at the surface of the heart, either directly with cryoablation or using resistive heating…

Transvascular Ethanol Ablation

Introduction Radiofrequency ablation (RFA) has become the standard of care for catheter ablation of cardiac arrhythmias. Other ablative technologies, including cryoablation and lasers, are variably used depending on the anatomic features of the tissue being targeted. Common to all is the requirement of contact between an intracardiac catheter and a destructive energy of physical nature. The historic evolution of catheter ablation, however, commenced with the concept…

Cryoablation and Other Radiofrequency Alternatives

Cryoablation Mechanism of Tissue Injury Cryoablation is the removal of heat that results in destruction of tissue. Cryotherapy was invented to treat cancers in the mid 19th century. Cryoablation causes tissue damage by direct and indirect mechanisms: the direct mechanism involves direct injury to the cells, and the indirect mechanisms make the cellular microenvironment hostile to cell viability. There are several ways in which these biocidal…

Radiofrequency Ablation

Radiofrequency (RF) current is the most common source of ablative energy used for the treatment of cardiac arrhythmias. Its origins began with electrosurgery and have since been refined to treat all cardiac arrhythmias. Over time, with greater understanding of resistive and conductive heating, several modifications of RF ablation (RFA) or catheters have been developed. This chapter discusses the biophysical principles of RFA and the state of…

Mapping Scar-Related Arrhythmias

Areas of fibrosis that are common to many cardiac disease states predispose to reentry. Dense fibrosis can create areas of fixed conduction block that define parts of a reentry path (see Fig. 129.2A ). Alternatively, reentry circuits can be defined by functional conduction block or collision of wavefronts in regions where conduction is slowed (see Fig. 129.2B ). Both mechanisms of conduction block may occur within…

Electroanatomic Mapping for Arrhythmias

The software and hardware related to mapping technologies for cardiac arrhythmias have evolved considerably over the past decades. The history of cardiac mapping dates back to the mid-1900s when Durrer and others used the isolated heart models perfected by Langendorff and colleagues to map ventricular wall excitation via handheld and needle electrodes. Since these initial studies, multiple technologies to optimize the mapping of cardiac arrhythmias have…

Electrogram Recording and Signal Processing

Introduction The quality of electrograms (EGMs) determines an electrophysiologist’s ability to interpret data. Nevertheless, there are a myriad of factors that influence the quality of EGMs. Consequently, it is important to have a basic knowledge of the recording circuitry and signal processing involved in their generation. This chapter focuses on basic principles of EGM recording, amplification circuitry, and signal processing. Basic Circuitry Overview Electrophysiologic (EP) procedures…

Management of Implanted Device Infections

Introduction As the population ages and indications for implantation of cardiac implantable electronic devices (CIEDs) expand, increasing numbers of CIEDs are implanted with some data suggesting the rate of CIED infection is outpacing the rate of implant. CIED infection carries a significant risk for morbidity and mortality, and CIED-related endocarditis raises this risk even further. This chapter will review the pathogenesis, management, and prevention of CIED…

Cardiac Resynchronization

Cardiac resynchronization therapy (CRT) is a device-based, electrical therapy for heart failure (HF) that has been available in clinical practice for the last quarter century. Delivery of CRT via biventricular (BiV) pacing has been validated in multiple large-scale randomized controlled trials (RCTs) and CRT is one of the most well-studied device therapies in modern medicine. The efficacy of CRT has primarily been shown in promoting ventricular…

Wearable Defibrillators

Introduction Risk stratification of sudden cardiac death (SCD) remains challenging, with only a small proportion of high-risk individuals identified through conventional discriminators, such as ejection fraction (EF). Yet sudden death continues to be the leading cause of quality-adjusted life years lost because of any medical illness. Implantable cardioverter-defibrillators (ICDs) have demonstrated clinical efficacy in the prevention of SCD in various populations, including those with ischemic and…