Sudden cardiac death can have many causes, the most common being life-threatening cardiac arrhythmias. Recognizing the underlying disease in good time can save lives. Cardiologist Firat Duru conducts research at the USZ into the early detection and diagnosis of patients at risk.
The cardiac arrest comes out of the blue and without any signs. It usually affects young, apparently healthy people, mostly men, often during sport or other physical exertion. If they are lucky, first aiders can apply resuscitation measures until paramedics and an emergency doctor arrive. If the patient can be saved, a defibrillator must usually be implanted to recognize and stop the next life-threatening cardiac arrhythmia.
In most cases, sudden cardiac death in young adults is triggered by myocardial diseases that lead to life-threatening cardiac arrhythmias and heart failure. One of these diseases is arrhythmogenic right ventricular cardiomyopathy (ARVC). It is referred to as “right ventricular” because it mainly affects the right ventricle. It has been known for some time that around half of all cases of ARVC are caused by an inherited gene mutation. This gene mutation usually causes a change in the desmosome, a protein structure that holds the heart muscles together and stabilizes them. The change in the structures means that they can tear under load. This changes the muscle structures of the heart – it suddenly goes out of rhythm and eventually stops.
The life-saving diagnosis is difficult even for specialists
Patients affected by ARVC therefore have a high risk of sudden cardiac death. However, the diagnosis and treatment of this disease is a challenge even for specialists. The causes and consequences of heart attacks and other heart muscle diseases are well studied and there are usually signs of these diseases that lead to investigations being carried out. The pathological changes in the heart are also clearly visible in the examinations for the most common heart diseases. ARVC, on the other hand, rarely causes symptoms at the beginning. The predisposition often becomes apparent for the first time during a cardiac arrest. Scarring and fat deposits following earlier, usually unnoticed damage to the desmosome are difficult to detect, even by specialists using imaging techniques.
“What we know about ARVC so far is that it is often inherited and efforts such as sport can trigger the arrhythmia. More men than women also suffer sudden cardiac death due to ARVC,” says Firat Duru, summarizing the current state of knowledge. Prof. Firat Duru, MD, cardiologist at the USZ, has been researching ARVC for many years and is one of the directors of an international research program on the subject based at the USZ. “However, the diagnosis is complicated and time-consuming. ECG, stress test, long-term ECG, cardiac ultrasound, MRI and invasive electrophysiological examinations are carried out. The diagnosis can be made on the basis of all these examinations in combination with various criteria. For a definitive and reliable diagnosis, however, we would have to carry out a heart biopsy, i.e. remove heart tissue and examine it for tiny structural changes,” explains Firat Duru. “However, such an intervention is only appropriate in exceptional cases.” Because the disease is inherited with a probability of around 50 percent, a patient’s relatives should also be screened so that people at risk can be identified and treated as a precaution.
A blood test should show who carries ARVC
Firat Duru’s team is therefore researching ways of detecting the disease by other means. “It would be ideal if we could find clear biomarkers for the disease. Then it would be possible to reliably diagnose or rule out the disease with a simple blood test.” In many cases, this would mean life-saving progress for affected patients and their relatives.
In 2011, Prof. Firat Duru and his colleague Prof. Corinna Brunckhorst established a clinical program and a research program to which researchers from Johns Hopkins Hospital in Baltimore/USA and ARVC research groups from Canada, the Netherlands and China, among others, contribute data in order to collect as much data as possible from patients with the disease for the search for biomarkers. “International cooperation is our strength,” says Firat Duru. “Thanks to it, we achieve data sizes that allow us to gain meaningful insights.”
Globally unique 3D heart modeling
There is also intensive collaboration with engineers from various disciplines at ETH Zurich. Together with hydrodynamicists from ETH, Firat Duru uses the data to produce three-dimensional, functional silicone models of hearts, which can be used to study the blood flow in the heart, among other things. “We use these 3D models, which are unique in the world, to investigate cardiac flow dynamics, particularly in the right ventricle. Increased pressure during physical exertion and the associated changes in blood flow conditions in the heart can cause long-term damage to the heart muscle or exacerbate an existing heart muscle disease.”
The distribution of the disease between the sexes is still a mystery to researchers. Far more men than women suffer sudden cardiac death. In addition, men who have survived a cardiac arrest due to ARVC have a worse prognosis than women. It is known that there is a link between the male hormone testosterone and sudden cardiac death and that the female hormone oestrogen protects women against it. But the exact role that these hormones play in sudden cardiac death is being investigated in another ongoing research collaboration together with ETH and international research partners.
The research on ARVC is partially funded by the University Hospital Foundation.
