Scientists have cracked the genetic code of a sudden death cardiac killer.
As a result, researchers in Newfoundland have developed a unique prevention program in which people with no symptoms, but with a suspect gene and a family history, are being implanted with internal cardiac defibrillators (ICDs), which can restart their hearts if they stop.
“Our discovery has led to a targeted genetic screening and individualized therapy that is significantly improving survival rates,” Dr. Sean Connors told the Canadian Cardiovascular Congress 2010, co-hosted by the Heart and Stroke Foundation and the Canadian Cardiovascular Society.
“It’s allowing people with the condition to live normal, longer lives. Individualized genetic therapies like this are the future of medicine.”
The excitement among cardiologists concerns a rare genetic condition – arrhythmogenic right ventricular cardiomyopathy (ARVC).
Arrhythmogenic right ventricular cardiomyopathy (ARVC)
“Newfoundlanders likely have the highest incidence in the world of this disease,” Dr. Connors, a cardiologist and associate professor of medicine at Memorial University in Newfoundland, told the Congress.
The term arrhythmogenic refers to deadly cardiac rhythms that can be triggered by electrical impulses within the heart. Cardiomyopathy is a worsening condition where heart muscle is slowly replaced by scar and fat tissue.
The combination of the two is lethal, Dr. Connors says.
“People who are at risk often have no symptoms, so the first time we know they have this disease is when they die.”
The surest sign that a disease is genetic in origin is when it is manifests itself in family histories, showing up in generation after generation.
Arrhythmogenic right ventricular cardiomyopathy (ARVC)
“Our diagnostic testing showed that some members of these families have a specific, genetic, electrocardiogram (ECG) mutation – ARVD5,” said Dr. Connors.
There is a 50 per cent chance that children of those with the condition will also be carriers of the gene. It is considered the second-most common cause of sudden cardiac death in young people.
The mutation causes premature sudden cardiac death in males: 50 per cent die by age 40 years and 80 per cent by 50 years. For women the rate is five per cent and 20 per cent.
Given those figures, Dr. Connors realized nothing would be lost by implanting ICDs in asymptomatic patients with ARVD5 to maintain normal heart rhythms.
Arrhythmogenic right ventricular cardiomyopathy (ARVC)
Arrhythmogenic right ventricular dysplasia (AVRD), also called arrhythmogenic right ventricular cardiomyopathy (ARVC) or arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), is an inherited heart disease.
AVRD is caused by genetic defects of the parts of heart muscle (also called myocardium or cardiac muscle) known as desmosomes, areas on the surface of heart muscle cells which link the cells together. The desmosomes are composed of several proteins, and many of those proteins can have harmful mutations.
The disease is a type of nonischemic cardiomyopathy that involves primarily the right ventricle. It is characterized by hypokinetic areas involving the free wall of the right ventricle, with fibrofatty replacement of the right ventricular myocardium, with associated arrhythmias originating in the right ventricle.
AVRD is often found in association with diffuse palmoplantar keratoderma, and woolly hair, because their genes are nearby and often inherited together.
ARVC/D is an important cause of ventricular arrhythmias in children and young adults. It is seen predominantly in males, and 30-50% of cases have a familial distribution. It is usually inherited in an autosomal dominant pattern, with variable expression. Novel studies showed that mutations (point mutations) in genes encoding for desmosomal proteins (see Intercalated Disc) are the main causatives for the development of this disease.
Arrhythmogenic right ventricular cardiomyopathy (ARVC)
The penetrance is 20-35% in general, but significantly higher in Italy. Seven gene loci have been implicated in ARVD. However, about 50% of families that express ARVD that undergo genetic screening do not show linkage with any of the known chromosomal loci. It is unclear whether the pathogenesis varies with the different loci involved. Standard genetic screening test are currently tested and evaluated in different state of the art cardiovascular research centres and hospitals.
