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Genetic research key to address critical rates of SCD, local experts say

Sudden cardiac deaths (SCD), especially in the young, should be deemed a clinical health priority, and urgently treated as such, with general practitioners playing a bigger role in identifying patients at risk considering that 90% of such deaths are as a result of inherited disorders, local experts have urged, writes Medical Brief.

Cardiovascular diseases (CVDs) are ever-increasing, and considered one of the most concerning public health burdens worldwide. They remain the leading cause of death across the world (~17.7m deaths were reported in 2015), accounting for 31% of all global deaths.

More than 75% of these occur in low- and middle-income countries, and although CVD is an acknowledged health concern in Africa, this priority area should receive much more attention than it currently does, write leading forensic experts B Stroh van Deventer, L du Toit-Prinsloo and C van Niekerk in the South African Medical Journal.

Up to 50% of all cardiovascular deaths are a result of a sudden cardiac death (SCD), defined as “a natural death due to cardiac causes, heralded by abrupt loss of consciousness within one hour after the onset of symptoms”. The consequences of these deaths, particularly in the young, have a greater impact and health burden in terms of life-years lost than all individual cancers and other leading causes of death.

The fact that nearly 90% of SCDs are caused by an inherited disorder justifies the international focus on, and prioritisation of, the underlying genetic causes of these cardiac disorders.

Disorders linked to SCDs vary greatly between different age groups, with ischaemic heart disease being the most common cause of death in the older population. In comparison, most SCDs in the younger population (≤45 years) are due to inherited cardiomyopathies and arrhythmogenic disorders.

Unfortunately, there is a lack of clinical symptoms or warning signs, with research showing that in 75% of SCD cases, death is the first “symptom”.

Inherited cardiomyopathy- and arrhythmogenic-related SCDs result from lethal arrhythmias. These are caused by alterations (genetic variations) in genes that all play a role in cardiomyocyte excitability and contractility. Cardiomyopathy-related genetic variations affect the structure and function of the heart muscle, whereas cardiac arrhythmogenic genetic disorders are generally associated with isolated electrical dysfunction.

The four most common inherited arrhythmogenic disorders include long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia and short QT syndrome. Although each of these has a characteristic electrocardiogram (ECG) profile when experiencing an arrhythmic episode, their spontaneous and sporadic nature results in a difficult clinical diagnosis.

The same gene can be altered in different ways (different genetic variations), which can lead to vastly different clinical manifestations of a disorder. These differences are important when considering available and effective treatment for patients, as each treatment is designed to target a certain defect and/or function. Fortunately, various types of treatment are available, ranging from anti-arrhythmic medications to implantable cardioverter defibrillators and pacemakers.

Therefore, even for general practitioners (GPs), there is clinical importance in determining the underlying genetics of an inherited cardiac disorder, to allow for effective and individualised treatment of a patient and/or affected family.

Since diagnosis can be challenging, be it due to an absence of ECG abnormalities, overlap of clinical phenotypes or lack of symptoms, genetic testing in all individuals at risk for an inherited cardiomyopathy or arrhythmogenic disorder is crucial.

This is reiterated by the marked reduction in mortality associated with the administration of proper treatment. The general medical practitioner, in particular, is in a central position in SCD prevention, and plays an essential role in the multidisciplinary team tending to affected relatives.

GPs have a greater personal connection to the community, and often care for different generations of the same family, allowing for earlier recognition of subtle warning signs suggestive of an inherited cardiomyopathy or arrhythmogenic disorder.

Clinical practitioners should, especially, be cognisant of any family history of syncope, epilepsy, sudden death, deafness, heart failure or pacemaker implantation at a young age (<50 years). Primarily, the GP will be the first to recognise a possible inherited cardiac disease in an individual or family, and through appropriate genetic testing may provide the only opportunity for an early diagnosis and proper clinical management.

In an accompanying editorial to their artivle, entitled Postmortem genetic testing in young individuals: What clinical medical practitioners need to know, the authors write that when a multidisciplinary approach is taken in cases of sudden unexpected death, the benefits to family members, and society as a whole, are irrefutable.

SD is a leading cause of mortality in the young, a public health problem worldwide because of its prevalence and significant impact on society, with a global incidence in the young ranging between 1.3 and 8.5 per 100 000 person years.

In SA, a SUD is classified as an unnatural death, and therefore mandated under the Inquests Act No. 58 of 1959 to be investigated in the medico-legal environment, where the forensic medical practitioner will conduct a thorough autopsy of the case to determine a cause and mechanism of death.

It has long been assumed that ischaemic heart disease is responsible for most SDs. But data from the young population from the past decade have refuted this assumption.

Fortunately, with the rapid development of technology and our increase in genetic knowledge, postmortem genetic testing (the so-called molecular autopsy) has been an invaluable tool in identifying inherited cardiomyopathies and arrhythmogenic disorders as the cause of death in many SDs, including infant cases.

The American Heart Association, European Heart Rhythm Association and the Royal College of Pathologists of Australasia have published recommended guidelines that they consider the minimum standard required in the routine autopsy practice for adequate investigation of a SCD.

In South Africa, say the authors, the country needs to realise that SCDs, especially in the young, should be deemed a clinical health priority, and urgently treated as such.

It can be inferred that a high proportion of these SD victims were actively occupying the workforce, and thus contributing to the national economy, emphasising the impact on society.

Tackling this health concern can only be successful through a multidisciplinary approach, where all relevant stakeholders, including forensic medical practitioners, clinicians, governmental agencies and funding bodies, to name a few, accept their responsibilities and play their part.

With adequate funding and resources, and stricter referral, according to legislation, of SUDs for medico-legal death investigation, a significant increase in molecular research can be conducted into these deaths.

A direct result of this will be to enable researchers to detect with greater certainty the most prevalent genes associated with inherited cardiac diseases specifically targeted towards the SA population. The ultimate aim, through adequate research, is to reach that point of targeted genetic testing that can be used as affordable point-of-care testing, which will be of immense value to clinicians, forensic medical practitioners and society as a whole.

African medical professionals have often been at the forefront when it comes to innovative and ground-breaking medical procedures. Therefore, there is no excuse not to excel at the implementation of the molecular autopsy and reap the clinical benefits it has to offer.

B Stroh van Deventer, Department of Forensic Medicine, Faculty of Health Sciences, University of Pretoria.
L du Toit-Prinsloo, New South Wales Health Pathology, Forensic and Analytical Science Service (FASS), Newcastle, Australia.
C van Niekerk, Department of Chemical Pathology, Faculty of Health Sciences, University of Pretoria and National Health Laboratory Service, Pretoria.


SAMA article – Cardiovascular deaths: What do the genes say? (Creative Commons Licence)


SAMA article – Postmortem genetic testing in young individuals: What clinical medical practitioners need to know (Creative Commons Licence)


See more from MedicalBrief archives:


SA scientists collaborate in ‘sudden death’ gene mutation discovery


Sudden Cardiac Death and sex: Rare but not just an old man thing


Cardiac death rates in young footballers higher than previously thought


COPD sufferers face increased risk of SCD






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