Sudden Cardiac Death: The Impact of Genetics

Sudden Cardiac Death is caused by a sudden cessation of cardiac activity, which can occur in people with or without previous cardiovascular disease. This cessation of activity is usually caused by a disturbance in the electrical activity of the heart in the form of arrhythmia or asystole that interrupts blood flow to the brain and the rest of the body, resulting in death if not treated within minutes.

When an episode of SCD occurs, autopsy may reveal a cardiac etiology, but sometimes the cause cannot be determined. The causes of SCD vary according to age group. In persons younger than 35 years, only 40% of cases are related to coronary artery disease and cardiomyopathies. Several studies have observed that, in young adults, SCD cases are usually caused by a previously undiagnosed congenital or hereditary condition. However, if we consider any age population, coronary artery disease and cardiomyopathies are the underlying cause in more than 85% of SCD cases.

Types of hereditary heart disease

Hereditary heart diseases (CH) are cardiovascular diseases characterized by a genetic basis, familial presentation and heterogeneous clinical presentation, since there is a complex interaction between triggering factors that influences the clinical presentation and prognosis of patients. Within CH there are 2 main groups:

1. Diseases affecting the structure and function of the heart muscle (cardiomyopathies):

• Hypertrophic cardiomyopathy.
• Arrhythmogenic arrhythmogenic right ventricular cardiomyopathy
• Dilated cardiomyopathy
• Non-compaction left ventricular cardiomyopathy
• Aortic root rupture (Marfan and Loeys-Dietz syndromes)

2. Nonstructural diseases that affect the electrical activity of the heart and predispose to malignant arrhythmias (channelopathies):

• Long QT síndrome
• Brugada síndrome
• Catecholaminergic polymorphic ventricular tachycardia.
• Idiopathic ventricular fibrillation
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In general, the diseases most commonly related to SCD are, in descending order: coronary pathologies, cardiomyopathies and channelopathies.

Incidence of Sudden Cardiac Death

SCD is responsible for approximately 350,000 to 700,000 cases of death in Europe, with slight variations between European countries. Worldwide, the annual incidence ranges from 4 to 5 million cases per year; and in the USA it accounts for 7-18% of all deaths. Although it can occur at any age, its incidence increases with age, being more common in people over 35 years of age.

The impact of genetics

CH usually present an autosomal dominant inheritance pattern so that in most cases the risk of inheriting and transmitting the mutation is 50%. The different types of CH are related to mutations in different genes, so it is important to perform genetic studies that include a heterogeneous group of genes associated with hereditary heart disease.

It is important to mention that the field of genetics is advancing day by day, so it is possible that, even if all genes with scientific evidence related to a type of CH are studied, it is possible that no genetic alteration is detected. The report of results is always based on the most recent scientific information, but it is possible that there are genes related to CH that have not yet been identified.

When a hereditary disease is suspected in a family, it is most appropriate to perform the genetic study in the person presenting the disease and if there are several affected members, it is recommended to start the study in the person with the most severe symptoms or the one with the earliest onset. In these cases, the role of the genetic counselor is key to carry out a correct evaluation of the personal and family history and to request the necessary molecular tests to facilitate the patient’s diagnosis.

Veritas offers the specialist a complete portfolio of genetic tests for cardiovascular diseases such as cardiomyopathies, channelopathies, among others. For more information about Veritas tests, do not hesitate to contact us.