Sudden arrhythmic death syndrome

Warning signs that precede SADS may include palpitations, dizziness and syncope. Sometimes syncope can be mistaken for seizure activity, which can prompt investigation for epilepsy.

The cause of SADS may include underlying conditions such as:

• catecholaminergic polymorphic ventricular tachycardia (CPVT);
• long QT syndrome (LQTS);
• Brugada syndrome;
• short QT syndrome (SQTS);
• progressive cardiac conduction disease (PCCD); and
• Wolff-Parkinson-White syndrome.

• SADS is characterised by the absence of any phenotype at post-mortem. The associated genes are predominantly those that cause arrhythmogenic conditions such as LQTS and CPVT. Because fatal arrhythmia may be the first presentation, certain genetic variants that cause arrhythmogenic cardiomyopathy are also implicated.
• Genomic testing using DNA from SADS cases is undertaken using a ‘super panel’, comprised of the gene panels for LQTS, SQTS, Brugada syndrome, PCCD, CVPT and cardiomyopathies (hypertrophic, arrhythmogenic and dilated cardiomyopathy) – see the National Genomic Test Directory for more information. Clinically actionable pathogenic or likely pathogenic variants have been identified in up to 13% of cases, and the KCNQ1, KCNH2, SCN5A and RYR2 genes are implicated the most frequently.
• Genomic testing in sudden cardiac death victims with a phenotype for a specific condition should be targeted to that condition (such as R131 if a clinical phenotype for hypertrophic cardiomyopathy is present), rather than considering a broader gene panel. The eligibility criteria can be found in the test directory; see Adult with hypertrophic cardiomyopathy for more information about testing.
• It is essential that genomic testing is conducted alongside expert phenotyping of surviving first-degree relatives, because this may help clarify the likely cause of death in the deceased.

The inherited cardiac conditions responsible for SADS are mostly inherited in an autosomal dominant pattern, which means that there is a 50% chance of affected parents passing the condition to each child. Taking a three-generation family history of sudden unexplained death and inherited cardiac conditions and identifying any previously known familial pathogenic variants is important for genomic counselling and appropriate management.

Patients who survive a cardiac arrest will usually be offered an implantable cardioverter-defibrillator for secondary prevention of sudden death. Otherwise, management varies depending on the underlying condition. Usually it involves lifestyle measures and medication (for example, beta-blockers in LQTS and CPVT).

For clinicians

• NHS England: National Genomic Test Directory

References:

• Fellmann F, van El CG, Charron P and others. ‘European recommendations integrating genetic testing into multidisciplinary management of sudden cardiac death‘. European Journal of Human Genetics 2019: issue 27, pages 1,763–1,773. DOI: 10.1038/s41431-019-0445-y
• Wilde AAM, Semsarian C, Márquez MF and others. ‘European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases‘. EP Europace 2022: volume 24, issue 8, pages 1,307–1,367. DOI: 10.1093/europace/euac030
• Zeppenfeld K, Tfelt-Hansen J, de Riva M and others. ‘2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: Developed by the task force for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death of the European Society of Cardiology (ESC) endorsed by the Association for European Paediatric and Congenital Cardiology (AEPC)‘. European Heart Journal 2022: volume 43, issue 40, pages 3,997–4,126. DOI: 10.1093/eurheartj/ehac262

For patients

• British Heart Foundation: Sudden arrhythmic death syndrome
• Cardiac Risk in the Young: SADS
• SADS Foundation