Inherited Ventricular Arrhythmias, the Channelopathies and SCD; Current Knowledge and Future Speculation – Epidemiology and Basic Electrophysiology

This chapter represents advanced scientific exploration in the different disciplines of SCD and channelopathy. Epidemiology of SCD and channelopathy is given special attention. The essence of detailed electrophysiological bases of the different diseases of channelopathies and the diverse cellular pathways mandated detailed discussion that can open the closed doors that we faced to the next generation(s). Special sections have been devoted to spatial as well as temporal heterogeneity of the cardiac action potential. Genetic heterogeneity and allelic heterogeneity are two prominent findings of channelopathies that confirm the fact of the major overlap in the field. The way we present the clinical findings is a true call for the next generation(s) of clinicians and researchers to revolutionize the field in the near future. Detailed management plans based on the up to date basic sciences findings for the different channelopathies give better therapeutic options for the clinicians in the field. Unique to this chapter is the new directions to look for channelopathies beyond the human body. The new understanding of the psychophysiological well-being of HRV and the sympathovagal balance extending to cosmic resonances and its possible effect on cardiac ion channels carries new era of promising preventive, diagnostic and therapeutic options.

Sudden Cardiac Death in Hereditary Dilated Cardiomyopathy

Dilated cardiomyopathy (DCM) is characterized by the phenotype of a dilated left ventricle with systolic dysfunction. It is classified as hereditary when it is deemed of genetic origin; more than 50 genes are reported to be related to the condition. Symptoms include, among others, dyspnea, fatigue, arrhythmias, and syncope. Unfortunately, sudden cardiac death may be the first manifestation of the disease. Risk stratification regarding sudden death in hereditary DCM as well as preventive management poses a challenge due to the heterogeneity of the disease. The purpose of this chapter is to present the epidemiology, risk stratification, and preventive strategies of sudden cardiac death in hereditary DCM.

Pediatric Cardiac Arrest

This chapter will focus on four important topics in pediatric cardiac arrest. We will highlight recent developments in pediatric CPR quality, medications used in cardiac arrest, ECPR, and post-cardiac arrest care (PCAC) and discuss the existing literature behind AHA guidelines and gaps in knowledge. Optimization of CPR quality is critical during cardiac arrest. We will summarize literature regarding current guidelines which target provider-centered goals and discuss evidence behind patient-centered goals. We will also discuss the evidence behind drugs used in the PALS guidelines. In cases of refractory cardiac arrest, ECMO can be lifesaving; however, there are still many gaps in our knowledge of this field. We will summarize the literature regarding determination of candidacy, cannulation strategies, resuscitation practices during ECPR, and outcomes. After a cardiac arrest, PCAC is crucial to minimize further injury from post-cardiac arrest syndrome (PCAS). The main goals of PCAC are to prevent further brain injury, treat myocardial dysfunction, and systemic ischemia/reperfusion injury. We will discuss AHA guidelines on oxygenation and ventilation goals, targeted temperature management, hemodynamic monitoring, and neuromonitoring.

Familial Dilated Cardiomyopathy: Risk Stratification for Sudden Cardiac Death

Heart failure implies a considerable burden for patients and resources for the health care system. Dilated cardiomyopathy is defined as left ventricular dilation and reduced systolic function, not solely explained by ischemic heart disease or abnormal loading conditions. Numerous genes have been identified in familial cases of dilated cardiomyopathy. Heart failure with reduced ejection fraction increases the risk for sudden cardiac death. Implantable cardioverter defibrillator therapy can provide a means of preventing sudden cardiac death in those deemed to be at high risk. Health care providers are in need of better tools in order to improve risk stratification. This chapter aims to provide an overview of the current knowledge about risk of arrhythmia and sudden death in patients with familial dilated cardiomyopathy, in particular for those patients with a specific mutation.

Inherited Ventricular Arrhythmias, the Channelopathies and SCD: Current Knowledge and Future Speculations - Risk Stratification, Management Plans and Future Speculations

Channelopathy constitutes significant proportion of SCD worldwide (around 10% or 370,000 deaths annually). It was creating a mysterious group of diseases until the second half of the last century when Anton Jervell and Fred Lange-Nielsen described Jervell Lange-Nielsen syndrome in 1957. It was late until 1995 where genetic characterization commenced. Later on, the massive genetic information with the discovery of genetic heterogeneity and allelic het¬erogeneity was a major victory in the field. The basic sciences in cellular electrophysiology and genetics complemented by meticulous clinical detection and the different clinical trials in the field opened a new era of wide therapeutic choices for clinicians. The knowledge obtained from the different experimental platforms especially the induced pluripotent stem cells is promising. The revolutionary move in SCD and channelopathies is described where correlation between the arrhythmogenesis and fluctuation in SGMA is established and must be investigated. The observation of the arrhythmogenicity of SGMA fluctuation and its effect on HRV together with the differential effect of certain sympathovagal tones (more sympathetic innervation is favoring VT/VF in LQTS1, LQTS2 and SQTS but not BrS or ERS) are all future directions to optimize our preventive, diagnostic as well as therapeutic options of SCD and channelopathy in humans.

Cardiopulmonary Resuscitation: Recent Advances

Cardiac arrest is the most significant reason for mortality and morbidities worldwide. With a better understanding of the pathophysiology of cardiac arrest, simple adaptations in basic life support to upcoming modifications in post-resuscitation care have been proposed by various resuscitation councils throughout the globe. Role of point of care cardiac ultrasound during cardiopulmonary resuscitation (CPR) has been explored and its contribution for identifying reversible causes and its real time management has been explored. A higher blood and tissue oxygenation levels contributed to an increased rate of return of spontaneous circulation (ROSC) which has to lead us to explore more options to increase the oxygenation. Starting from the CPR training, the use of sensors for spirometric feedback in ventilation maneuvers can help improve the quality of CPR. High flow nasal oxygenation during CPR has shown promising results. Extracorporeal CPR is another entity that has shown survival benefits in a selected group of patients. The aim of the newer advances has always been to decrease the morbidity and improve survival outcomes in terms of neurological deficit as well. These guidelines are reviewed and updated regularly to improve knowledge and training based on the current evidence. This chapter shall focus on recent advances in cardiopulmonary resuscitation.

Sudden Cardiac Death in Young Athletes

Sudden death (SD) is the most dangerous and irreversible outcome of diseases in clinical as well as in sports medicine. Between 1980 and 2011, the Sudden Death in Young Athletes Registry in the USA, which was developed based on mass media information, recorded 2406 cases of sudden death, which were observed in 29 diverse sports. In the USA 80% of all SD occurred in high school/middle school or collegiate student athletes, and 20% were engaged in organized youth, postgraduate. Statistical data vary greatly in different countries: SCD incidence rate in the USA is 7.47 and 1.33 per 1,000,000 exercising male and female school-age athletes, respectively, whereas in Italy, the rate is 2.6 cases in men and 1.1 in women per 100,000 individuals per year who are involved in active competitive sports. The European Heart Rhythm Association (EHRA) position paper concluded that as an overall estimate, 1–2 out of 100,000 athletes between of age of 12 and 35 years old die suddenly each year. It was shown that the risk of SCD is significantly higher in athletes than in nonathletes with the same heart condition in the general population, by more than five times for ARVC, 2.6 times for coronary artery disease, 1.5 times for myocarditis, and more than 2 times for cardiac conduction system diseases.

The Wearable Cardioverter-Defibrillator

The wearable cardioverter-defibrillator (WCD) is a rechargeable external device that can be worn under the clothing all day long and protects the wearer from potentially life-threatening ventricular tachyarrhythmias. When a dangerous arrhythmia is detected, the WCD can deliver high-energy shocks. The WCD has been shown to be effective in accurately detecting and appropriately treating ventricular tachycardia (VT) and ventricular fibrillation (VF). It is intended for temporary use as a bridge to an implantable cardioverter-defibrillator (ICD), heart transplantation, or left ventricular assist device; patients with heart failure with reduced ejection fraction may benefit from the WCD while their condition improves. It can be used temporarily after explant of an ICD until reimplantation is deemed possible. In select patients with myocardial infarction, a WCD may be useful during the immediate period after infarction. It is indicated for use when a permanently implanted ICD must be explanted because of infection; the patient can use the WCD until the infection resolves, and a new ICD can be implanted. The role of the WCD is emerging as an important therapeutic option to protect patients at elevated risk of sudden cardiac death (SCD).

Mechanisms of Diabetes Mellitus-Induced Sudden Cardiac Death

More than 450 million people worldwide have diabetes mellitus (DM), a metabolic disorder characterized by an increase in blood glucose level (hyperglycemia) that arises from insufficient insulin secretion or resistance to insulin’s action. More than 70% of individuals with chronic DM will develop cardiovascular diseases (CVDs) including atherosclerosis and coronary artery diseases (CADs), hypertension, cardiac arrhythmias, cardiomyopathy (heart failure), stroke, and chronic kidney disease. A significant number of these individuals will also succumb to sudden cardiac death (SCD). SCD usually occurs in early morning from abnormal heart rhythms or arrhythmias and ventricular fibrillation. When the pumping action of the heart becomes erratic, a reduction in oxygenated blood to the brain leads to unconsciousness and brain damage. SCD is independent of age and sex and positively correlates with impairment in cardiac metabolism, muscle damage, fibrosis, apoptosis, hypertrophy, ischemia, and deranged cation signaling. This review centers on mechanisms by which intracellular cations (Na+, K+, and Ca2+) handling, inflammation, and oxidative and carbonyl stresses due to diabetes-induced hyperglycemia can lead to the deterioration of excitation/contraction coupling (ECC), impaired contractility, arrhythmias, and SCD in DM patients. It also discusses the beneficial effects of exercise training to attenuate the risk of SCD.