Contemporary Reviews in Cardiovascular Medicine Sudden Cardiac Arrest Without Overt Heart Disease

The topic of sudden unexplained cardiac arrest without overt heart disease is a highly emotive and important subject with a rapidly advancing knowledge base. The correct identification of those conditions predisposing to cardiac arrest is paramount, and is part of the role of every practicing cardiologist. This review article is designed to give the practicing cardiologist an up-to-date insight into a subspecialized field of cardiac electrophysiology and cardiac genetics. It seeks to help to formulate diagnoses with advanced electrophysiological testing and genetic profiling and also with a reminder of basic clinical presentations and pathophysiological features of the conditions in question. This article seeks to encapsulate the field in general and at the same time to provide a select amount of useful detail, both contemporary and historical, and to provide references from a resource of excellent reviews in the literature. We hope that the reader will develop confidence in identifying rare causes of cardiac arrest and an insight into the sort of patients that should be referred to subspecialist clinics. Structural or coronary heart disease is by far the most common cause of sudden cardiac arrest.1 Once overt heart disease has been excluded in the cardiac arrest survivor, the differential diagnosis includes manifest or latent primary electrical disease and latent structural causes (Tables 1 and 2). These conditions predispose the patient to recurrent ventricular arrhythmia and cardiac arrest without overt heart disease. The overriding immediate concern in these patients is recurrence of unheralded ventricular tachycardia or fibrillation. Every effort must be made to define the underlying pathophysiology in order to understand prognosis, direct therapy, and identify family members who may be at risk if the culprit is an inherited condition. The conditions in question are largely those causing abnormalities in cardiac depolarization or repolarization, usually due to inherited, drug-, metabolic-, or electrolyteinduced ion channel dysfunction. They have loosely been termed the channelopathies or primary electric diseases. Often included in the category of cardiac arrest without overt heart disease are patients with subclinical structural diseases such as myocarditis, coronary spasm, arrhythmogenic right ventricular cardiomyopathy (ARVC), and sarcoidosis.2 Although these conditions may be readily diagnosed with overt evidence of a structural cause of cardiac arrest, structural abnormalities may be subtle or even undetectable with standard testing early in their course, requiring a high index of suspicion to discern. Survivors of cardiac arrest without overt heart disease typically come under the care of an electrophysiologist because of the need for implantation of an implantable cardioverterdefibrillator (ICD). Care is ideally delivered by a team of individuals with expertise in genetics, electrophysiology, and cardiomyopathies, with input from imaging experts as well. This team deals with survivors of cardiac arrest, their family members when an inherited cause is identified, and the less fortunate families when sudden death occurs without overt heart disease and families are sent for screening.3–6 This is often referred to as cascade family screening.4,7 It should be recognized, however, that even when each of the known causes of cardiac arrest without overt heart disease has been systematically excluded with in-depth testing, nearly half of the causes of cardiac arrest in these patients will remain unexplained.2