Wednesday, February 15, 2023
Atrial fibrillation is the most common cardiac arrhythmia. The risk of atrial fibrillation is higher in some families and can even occur at a young age or without other medical conditions. In about 20 percent of patients, atrial fibrillation is hereditary. It is unclear in most cases what causes this so-called ‘familial atrial fibrillation’.
In some rare cases, it has been shown that changes in certain genes may be responsible. But more research is needed to clarify the genetic factors associated with familial atrial fibrillation and to find out what the (functional) consequences are for the heart muscle cells. This will allow the role of these genes in the development of atrial fibrillation to be investigated.
Researchers of the scientific program Medical Delta Cardiac Arrhythmia Lab therefore opened at Erasmus MC the first outpatient clinic specifically for patients with familial atrial fibrillation in the Netherlands. This outpatient clinic is part of a national network for research into familial atrial fibrillation. The first families have now been examined; the outpatient clinic was officially opened on Tuesday, February 14. The interdisciplinary research team working in the outpatient clinic includes cardiologist-electrophysiologists, molecular biologists, clinical geneticists and engineers from Erasmus MC, TU Delft, Amsterdam UMC and UMC Utrecht. The Atrial Fibrillation Innovation Platform (AFIP) foundation is also involved.
Different perspectives needed for the complete picture
From different angles, the researchers are looking for the possible causes of familial atrial fibrillation. The first step toward diagnosing familial atrial fibrillation is to rule out other causes of atrial fibrillation. The cardiologist does this by examining the function of the heart muscle, heart valves and coronary arteries. They also ask extensively about triggering and maintaining factors of atrial fibrillation. Examples include intense exercise, smoking or alcohol consumption.
It is generally believed that several genetic variations may underlie familial atrial fibrillation. Together with the clinical geneticist, these variations are mapped out. The molecular biologist is the essential link here, because he will investigate the relationship between the genetic variations and the effects in a heart muscle cell in cultured human atrial cells and fruit flies.
This altered function of a heart muscle cell can translate into abnormalities in electrical conduction, which can cause atrial fibrillation. These electrical abnormalities are measured with special electrodes designed by engineers. A technical physician develops analysis software for these complex electrical signals.
"This whole pathway from physician to biologist to engineer comes together in the Medical Delta program and thus now also reflected in the research in the outpatient clinic," says Prof. dr. Natasja de Groot (Erasmus MC, TU Delft), Medical Delta professor and one of Scientific Leaders of the Medical Delta Cardiac Arrhythmia Lab scientific program.
Family members with atrial fibrillation easy to find
Through the atrial fibrillation foundation, the first patients have now registered and the first patients have also been examined. One of the first observations is that it is very easy to find people with family members who have atrial fibrillation. However, this does not necessarily mean that everyone has familial atrial fibrillation. For example, it could also be that everyone in the family has the same risk factors such as high blood pressure or obesity.
For Prof. dr. Bianca Brundel (Amsterdam UMC), one of Scientific Leaders of the Medical Delta Cardiac Arrhythmia Lab scientific program, these are important leads. "Gaining more insight into the origin of familial atrial fibrillation is important. The outpatient clinic is the first in the Netherlands to investigate the circular relationship between gene variant and the development of atrial fibrillation from patient to laboratory and from the laboratory back to the patient. It is also very special that this outpatient clinic was started in co-creation with patients through the AFIP foundation. With our research, we hope to be able to unravel and understand the molecular causes of hereditary atrial fibrillation. That knowledge could potentially help develop new therapies for this heart rhythm disorder in the near future."
Heart rhythm disorders within families
The idea to start the outpatient clinic arose after observations by the scientists and after questions from patients. "We regularly get patients in the clinic where no clear cause or explanation can be found for atrial fibrillation. They are young, live healthy lives and have no further cardiovascular abnormality," said De Groot. "Upon inquiry, it often turns out that immediate family members also have a cardiac arrhythmia. That piqued our interest."
As the research progresses, the scientists hope to determine the effects of gene variations on atrial function. "All in all, in a few years we hope to understand the mechanism of familial atrial fibrillation. If we know what causes it and understand how it affects the heart, that may offer clues for treatment," De Groot said. "This will require examining many people with suspected familial atrial fibrillation and their immediate families. In this special outpatient clinic, we can facilitate this."
Investigations have now begun in more than ten families. "It is a large and long-term study and requires a lot from the participants, but we find that for the benefit of science people are eager to cooperate for a longer period of time."
