When a person collapses with sudden cardiac arrest, genetic testing may determine whether family members are also at risk. Danish research shows how genetic testing and preventive treatment can save people’s lives.
Of 117 young Danes with a hereditary heart disease, almost half were saved by an electric shock from an implanted pacemaker (implantable cardioverter-defibrillator or ICD). This is the conclusion of a study in which researchers investigated whether ICDs implanted in young people really save lives.
The conclusion is clear: they do.
All participants had a hereditary gene variant that weakens their heart functioning. The study is part of a larger research project, in which researchers try to combine genetic testing with various types of treatment to prevent sudden cardiac arrest among young people so they do not suddenly collapse on the street.
“Every year, about 500 Danes younger than 50 years experience sudden cardiac arrest, and many die as a result. Our research is based on genetically testing individuals who experience sudden cardiac arrest to determine whether they have hereditary heart disease. If they do, we would very much like to genetically test their family members to investigate whether they also have the same genetic variants and begin preventive treatment if they do,” explains the researcher behind the study, Henrik Kjærulf Jensen, Clinical Professor, Department of Clinical Medicine, Aarhus University and Consultant, Department of Cardiology, Aarhus University Hospital.
The study has been published in Europace.
Finding the genes that predispose to cardiac arrest
We return to this study later, but first we will look at the bigger picture.
Henrik Kjærulf Jensen’s research sets out to develop molecular genetic studies, in which doctors use a blood test to determine whether individuals have genetic variants that increase their risk of sudden and unexpected cardiac arrest.
If these tests show that a person is genetically predisposed to experiencing sudden cardiac arrest, doctors may intervene with preventive treatment in the form of medicine or an implanted ICD.
Heart disease is the second most common cause of death in Denmark and includes many unknown genetic disorders that cause cardiac arrest among young people..
Genetic disorders can trigger irregularities in the electrical signals that pace the heart’s rhythm. Other genetic disorders can make the heart muscle thick or weak so that it does not function properly.
“The problem with many of these genetic disorders is that the first symptom of the resulting disease is often death. We would very much like to intervene with a diagnosis earlier in the process so that we can prevent this from happening,” explains Henrik Kjærulf Jensen.
Connecting clinical practice and basic research
Henrik Kjærulf Jensen’s research operates in the interface between clinical practice and basic research. He takes blood samples from people younger than 50 years and subjects them to whole-genome sequencing at the Department of Molecular Medicine of Aarhus University Hospital to determine whether any of the genetic building blocks are disordered and whether any of these disorders are in heart-related genes.
This enables the researchers not only to learn about the genetic disorders that can lead to heart problems. They can also directly compare the genetic profiles of the individuals experiencing sudden cardiac arrest with those of the family members and determine whether any are predisposed for it.
“When we have a blood sample, we can construct a risk profile of family members and initiate the appropriate preventive treatment. The family members of young people experiencing sudden cardiac arrest end up being both incredibly upset and concerned about whether the disease is hereditary and whether it will affect any of them. We can help to clarify this,” says Henrik Kjærulf Jensen.
Recreating heart disorders in zebrafish
Henrik Kjærulf Jensen has published several articles on finding genes that can be linked to hereditary heart disease.
When Henrik Kjærulf Jensen identifies potential genes that may be associated with heart disorders, he and his colleagues conduct comprehensive laboratory tests of the genes by, among other things, creating the same genetic variants in zebrafish and then examining how they affect the hearts of the zebrafish.
People and zebrafish are genetically similar enough that the genetic variants causing problems for a zebrafish’s heart will probably do this for people too.
The discoveries do not just help the immediate family members clarify their risk of heart disorders; they are also fed into databases of known genetic variants that increase the risk of sudden cardiac arrest. These databases are gold mines in improving doctors’ ability to use genetic testing to make a diagnosis and start preventive treatment.
Report has made genetic testing standard after sudden cardiac arrest
In a working group under the Danish Society of Cardiology, Henrik Kjærulf Jensen, together with other cardiologists, has prepared a report that contains guidelines for all cases of sudden heart-related deaths among young people in Denmark.
According to the guidelines, these people must be autopsied, with the possibility of genetically testing a stored blood sample later.
If the blood sample turns out to indicate something abnormal, family members are also offered a blood test and the associated genetic analysis to clarify whether they have the same genetic variant.
“What’s new is that we now routinely perform these genetic tests so that they are an integral part of the clinical work after a young person experiences sudden cardiac arrest,” says Henrik Kjærulf Jensen.
Doctors have good opportunities to keep people with heart disease alive
However, all the work to identify genetic variants and then search for them among relatives would make no sense if the doctors could not offer any treatment to the family members at greater risk.
Fortunately, this is available in Denmark, and Henrik Kjærulf Jensen says that doctors in Denmark almost always have a treatment option for hereditary heart disease.
“We have excellent opportunities for treatment, and investigating whether the people with heart disease have a hereditary genetic variant is therefore valuable,” he says.
Defibrillators save lives
The study introduced previously included 117 young Danes with an average age of 30 years. They had all experienced heart problems in connection with a hereditary heart disorder. They had either collapsed with cardiac arrest or fainted.
After diagnosis, they had an ICD implanted in their chest, and the researchers followed them for 17 years to see how often the ICDs automatically gave them an electric shock to keep their heart in rhythm.
After 1 year, 17% experienced such a life-saving shock and 48% after 10 years.
“Many survived because they had an ICD implanted. This is the type of preventive treatment we would also like to offer to the relatives of the people who experienced sudden cardiac arrest if they have the same genetic variant. Some may never need an electric shock, but for others it can save their lives,” says Henrik Kjærulf Jensen.
“Implantable cardioverter-defibrillator therapy and device-related complications in young patients with inherited cardiomyopathies or channelopathies: a 17-year cohort study” has been published in Europace. In 2018, the Novo Nordisk Foundation awarded a grant to Henrik Kjærulf Jensen, Consultant, Aarhus University Hospital for the project Preventing Deaths in Inherited Heart Disease by Improving Clinical and Molecular Genetic Diagnosis.