Sudden Cardiac Death in the Young | Ten Points to Remember

Semsarian C, Ingles J, Wilde AA.
Sudden Cardiac Death in the Young: The Molecular Autopsy and a Practical Approach to Surviving Relatives. Eur Heart J 2015;Mar 12:[Epub ahead of print].

The following are 10 things to remember about sudden cardiac death (SCD) of the young (defined as occurring at the age of 40 or less):

  1. Hypertrophic cardiomyopathy remains the most common structural cause of SCD in the young, although in some regions of the world, arrhythmogenic right ventricular cardiomyopathy (ARVC) is more prevalent. Myocarditis, congenital heart diseases including coronary artery anomalies, and coronary artery disease are other structural causes of SCD. Structural cardiac abnormalities account for approximately 70% of cases of SCD.
  2. Normal postmortem examination at autopsy including normal histology and negative toxicology testing is present in the remaining 30% of SCD cases, and suggests a primary arrhythmia as the cause of death. Termed sudden arrhythmic death syndrome (SADS), these deaths are due to familial long-QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), Brugada syndrome (BrS), idiopathic ventricular fibrillation, and short-QT syndrome.
  3. Heart Rhythm Society/European Heart Rhythm Association guidelines recommend postmortem genetic testing, also referred to as a molecular autopsy, in SADS cases, if circumstantial evidence points towards a clinical diagnosis of LQTS or CPVT. This includes direct DNA sequencing of the protein coding exons of four genes, i.e., the three major LQTS genes (KCNQ1, KCNH2, SCN5A) and the CPVT gene (RYR2). Mutations in the SCN5A gene also cause BrS.
  4. While initial studies in selected SADS populations reported detection rates for a causative mutation of up to 34%, more recent population-based studies suggest that the detection rate with the four-gene molecular autopsy is more likely to be up to 15–20%.
  5. Clinical evaluation of SCD of the young should include medical history and a comprehensive third-generation family pedigree. Pertinent positives include family history of suspicious deaths (e.g., sudden infant death syndrome [SIDS] cases, drowning, motor vehicle accidents, and epilepsy). It is important to investigate the circumstances of SCD, including activity at the time of death, the level of physical activity, and symptoms immediately preceding the death.
  6. Postmortem examination should be undertaken in all cases of sudden death in the young. This includes macroscopic evaluation of the heart, lung, and brain.
  7. Over 95% of cardiac genetic disorders in the general population are inherited as an autosomal-dominant trait such that first-degree relatives have a 50% chance of inheriting the same gene mutation.
  8. All first-degree relatives, obligate carriers, and symptomatic relatives of SCD victims should have a comprehensive medical and family history, physical examination, resting and exercise electrocardiograms (ECGs), and an echocardiogram. Depending on the clinical situation, further second tier investigations may include cardiac magnetic resonance (CMR) imaging (e.g., suspected ARVC), 24-hour Holter, signal-averaged ECG, and pharmacological challenge tests, such as a flecainide/ajmaline challenge in suspected BrS patients.
  9. Postmortem computed tomography scanning and CMR imaging may be useful if an autopsy is not possible due to religious, logistic, personal, or cultural reasons.
  10. Survivors of family members who were victims of SCD suffer significant psychological issues even years after the death. Counseling by a psychologist, either within the multidisciplinary specialized clinic team or outside of it, should be strongly considered.

Clinical Topics: Arrhythmias and Clinical EP, Dyslipidemia, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Atherosclerotic Disease (CAD/PAD), Genetic Arrhythmic Conditions, SCD/Ventricular Arrhythmias, Lipid Metabolism, Magnetic Resonance Imaging

Keywords: Arrhythmogenic Right Ventricular Dysplasia, Autopsy, Brugada Syndrome, Cardiomyopathy, Hypertrophic, Cause of Death, Coronary Artery Disease, Counseling, Death, Sudden, Cardiac, Electrocardiography, Genetic Testing, Magnetic Resonance Imaging, Mutation, Myocarditis, Physical Examination, Ryanodine Receptor Calcium Release Channel, Sequence Analysis, DNA, Survivors, Tachycardia, Ventricular, Tomography, Ventricular Fibrillation

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