Sudden Cardiac Death - A Current Perspective

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Abstract

Heart disease is the leading cause of death in the US with 700,000 deaths annually, of which 460,000 are attributable to sudden cardiac death (SCD). SCD is usually attributed to ventricular fibrillation (VF). Despite recent reductions in cardiac mortality from other causes, the incidence of SCD remains high with minimal decline in the last decade. The large majority of patients who suffer life-threatening ventricular arrhythmias have advanced left ventricular (LV) systolic dysfunction. Coronary artery disease is the most common predisposing condition in developed countries, accounting for up to 75% to 80% of all cases. Non-ischemic cardiomyopathy and other cardiomyopathic disorders account for 10% to 15% of cases. Inflammatory disorders (i.e. myocarditis), structural heart disease (i.e. valvular or congenital heart disease), and infiltrative disorders (i.e. sarcoidosis) account for about 3% to 5% of cases. There are also comparatively rare but important heritable disorders that can cause SCD in the absence of structural abnormalities of the left ventricle. These include the long QT syndrome (LQTS), Brugada syndrome, and arrhythmogenic right ventricular dysplasia (ARVD), which account for approximately 1% to 2% of cases.

Citation
US Cardiology 2006;2005:2(1):177-181

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Heart disease is the leading cause of death in the US with 700,000 deaths annually, of which 460,000 are attributable to sudden cardiac death (SCD). SCD is usually attributed to ventricular fibrillation (VF). Despite recent reductions in cardiac mortality from other causes, the incidence of SCD remains high with minimal decline in the last decade. The large majority of patients who suffer life-threatening ventricular arrhythmias have advanced left ventricular (LV) systolic dysfunction. Coronary artery disease is the most common predisposing condition in developed countries, accounting for up to 75% to 80% of all cases. Non-ischemic cardiomyopathy and other cardiomyopathic disorders account for 10% to 15% of cases. Inflammatory disorders (i.e. myocarditis), structural heart disease (i.e. valvular or congenital heart disease), and infiltrative disorders (i.e. sarcoidosis) account for about 3% to 5% of cases. There are also comparatively rare but important heritable disorders that can cause SCD in the absence of structural abnormalities of the left ventricle. These include the long QT syndrome (LQTS), Brugada syndrome, and arrhythmogenic right ventricular dysplasia (ARVD), which account for approximately 1% to 2% of cases.

Identifying Patients at Risk for SCD Genetic Markers of SCD

Genetically inherited disorders should be considered when evaluating patients with syncope or unexplained loss of consciousness and family history of SCD. These patients are often relatively young and have no overt evidence of structural heart disease. For example, the LQTS is a monogenetic disorder associated with prolonged ventricular repolarization, malignant ventricular arrhythmias, typically torsades de pointes, and SCD. In this subset of patients, genetic screening is currently available to identify patients at risk for SCD. Linkage analysis in the early 1990s heralded the identification of several mutations responsible for LQTS phenotypes. LQT1 is due to a mutation in KCNQ1, the alpha subunit of the potassium ion channel, and responsible for cardiac slowly activated delayed rectifying potassium current (IKs). LQT2 is associated with mutation in the human ether-a-go-go gene (HERG), the protein responsible for rapidly activated delayed rectifying potassium current (IKr). LQT5 and LQT6 are due to mutation in KCNE1, the beta subunit of IKs,and KCNE2, the beta subunit of IKr respectively. Mutation in SCN5a, the alpha subunit of the cardiac sodium channel, is responsible for LQT3 and LQT4 is due to mutation in ankyrin B, a cytoskeletal protein that anchors ion channels to cell membrane. Brugada syndrome is characterized by electro-cardiogram (ECG) features of ST elevation in right precordial leads with right bundle branch pattern, and is caused by mutation in SCN5a. More recently, mutation in genes encoding the ryanodine receptor, or calsequestrin, was identified as the cause of catecholaminergic polymorphic ventricular tachycardia.

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