Sudden cardiac death cuts lives short, often without warning. The example of 36-year-old N. shows just how abrupt this can be. Feeling unwell, she decided to run a warm bath. Soon after, her heart stopped beating. Her partner and then the paramedics administered CPR, but ultimately couldn’t save her. She died of severe brain damage from lack of oxygen a few days later. M. was also just going about his daily life when he went out for his usual jog. The 40-year-old, who for years had taken regular exercise, collapsed and passed away soon after.
When young people die unexpectedly, their loved ones are left traumatized. The pain and suffering such a tragic event brings to the families is obvious. “We must do everything we can to prevent such fatal diseases,” says geneticist Cordula Haas of the UZH Institute of Forensic Medicine. Together with Jacqueline Neubauer, cardiologist Ardan Saguner from the UniversityHospital Zurich (USZ) and further specialists, as well as the Zurich public prosecutor’s office, she recently wrapped up a pilot project researching cases of sudden cardiac death, or SCD.
“We analyzed cases of SCD to be able to provide counseling to the immediate family,” says Haas. Genetics often play a key role when young people suffer sudden cardiac arrest, an earlier study conducted by Jacqueline Neubauer showed. That’s why it is important to examine the victims for certain gene mutations. Once the mutations are identified, the researchers can check whether any direct relatives of the deceased have the same mutations and potentially prevent further tragedy.
The topic garnered widespread attention last summer, when Denmark’s Christian Eriksen suffered a cardiac arrest during a Euro 2020 game against Finland and collapsed on the pitch. His team formed a circle around him and the team doctor began to reanimate him, as half the world looked on. Thanks to immediate CPR and shocks from a defibrillator, the 29-year-old footballer was able to be brought back. Had he collapsed while jogging alone in the woods, he more than likely wouldn’t have survived. Eriksen has even gone back to playing at a professional level again.
While the exact details of his case aren’t known, cardiologist Ardan Saguner believes his cardiac arrest may have been caused by arrhythmia, either inherited or from an infection. If gene mutations were involved, the USZ arrhythmia specialist would suspect ion channel disease or cardiomyopathy as possible causes. Both affect the spread of electrical impulses in the heart muscle and disrupt the organ’s natural rhythm. This can lead to dangerous arrhythmia or ventricular fibrillation, in which the ventricles of the heart start to quiver or twitch instead of contracting normally. Such irregularities can be remedied by administering electrical shocks.
These genetic diseases can’t be detected on the outside of the heart. They may even go unnoticed in professional athletes despite in-depth medical examinations. Christian Eriksen was fitted with an implantable cardioverter defibrillator (ICD), a small device that monitors his heart rhythm and can reset the heart’s electrical conduction if necessary. This has allowed the footballer to return to the football pitch, now in the English Premier League rather than Serie A in Italy.
Ion channel disorders are one of the major groups of hereditary heart disease, the second being cardiomyopathy, or heart muscle disorders. These are characterized by changes that are more easily detected, such as thickening of the heart muscle. Various forms of these disorders are known. Arrhythmogenic cardiomyopathy, or ACM, for example, is a condition where heart muscle cells are replaced by both scar and fat tissue. “There is scarring on the heart,” says Saguner. Quite common in young athletes, the disease can be triggered by mutations in one or several genes. The effects of these mutations range from minor symptoms to ventricular fibrillation and even cardiac death.
Cordula Haas and her team are focusing on the hidden diseases in these two groups. In their pilot study, the researchers examined unexpected deaths of young people 45 years or younger between 2018 and 2020. Once they excluded cases of suicide, drug abuse, asthma and acquired heart defects, they were left with 10 cases, including the two examples mentioned above. The researchers at the Institute of Forensic Medicine and the Institute of Medical Molecular Genetics then analyzed these 10 cases for defective genes.
“Our research felt a lot like detective work, since the genetic starting point is so complex,” says Jacqueline Neubauer, who specializes in molecular-genetic autopsy. No fewer than 400 genes are currently known to be linked to these heart diseases, and this number is constantly growing. The researchers’ study involved a great deal of specialist knowledge and time-consuming interpretations of genome analyses. In the end, they found defective gene variants in five of the 10 cases. The 36-year-old woman had two gene mutations, while the 40-year-old man had one suspicious variant. In both cases, the cause of death was ACM.
The researchers’ next step was to share their findings with the families of the deceased and offer them cardio-genetic counseling. In the woman’s case, analyses revealed that several family members were at risk, including a son and several siblings. Two of the siblings have since been fitted with a defibrillator, while others have started taking medication. Cardiologist Ardan Saguner, who is overseeing the family’s care, says: “We were able to take meaningful medical action and significantly reduce the risk of further cardiac arrests.”
Not all patients require a defibrillator to be implanted; in fact, most cases can be remedied through drugs or a change in lifestyle, for example by giving up competitive sports. Of course, family members also have the right not to know, stresses Ardan Saguner. “Nobody is forced to undergo cardiological or genetic testing,” says the heart specialist. In his experience, however, most people welcome the tests – and the same also goes for the in-depth autopsies of the deceased. Knowing what caused the death of someone you love makes it easier to grieve, explains Saguner.
Meanwhile, the study leaders have drawn clear conclusions from their pilot study. “Conducting genetic analyses should become standard practice whenever young people suffer cardiac arrest, if other causes can be ruled out,” says Cordula Haas. Unfortunately, this is not yet the case. Forensic science is mostly about determining causes of death and eliminating the possibility of foul play. Public prosecutors don’t care whether a cardiac arrest occurred as a result of an acquired disease or a hereditary genetic mutation. “But our research shows that it makes a huge difference to family members,” Haas says.
The current practice also has a lot to do with the costs of the tests, which can be quite high and aren’t covered by health insurance companies if the insured person is no longer alive. This is why genetic analyses aren’t performed very often, even when they’re recommended by medical professionals. Thanks to the pilot study, however, this practice is currently changing, at least in Zurich. Genetic tests are now routinely carried out in cases of sudden cardiac death if hereditary disease might be involved. And these tests are certainly worth doing, considering the pain and suffering that can be prevented.