Sudden cardiac death shortens life, often without warning. The example of N., 36, shows how brutal it can be. Feeling bad, she decided to run a hot bath. Soon after, her heart stopped beating. Her partner and then paramedics administered CPR, but were ultimately unable to save her. She died of severe brain damage due to lack of oxygen a few days later. M also went about his daily business when he went out for his usual jog. The 40-year-old, who had been exercising regularly for years, collapsed and died a short time later.
When young people die unexpectedly, their loved ones are traumatized. The pain and suffering that such a tragic event brings to families is evident. “We must do everything possible to prevent such deadly diseases,” says geneticist Cordula Haas of the UZH Institute of Forensic Medicine. Together with Jacqueline Neubauer, cardiologist Ardan Saguner from the University Hospital of Zurich (USZ) and other specialists, as well as the Zurich public prosecutor’s office, she recently concluded a pilot project to research cases of sudden cardiac death, or SCD .
“We analyzed SCD cases to be able to provide advice to immediate family,” says Haas. Genetics often play a key role when young people suffer sudden cardiac arrest, an earlier study by Jacqueline Neubauer has shown. This is why it is important to screen victims for certain genetic mutations. Once the mutations are identified, researchers can check if any direct relatives of the deceased have the same mutations and potentially prevent further tragedy.
Collapsed on the ground
The subject garnered wide attention last summer when Denmark’s Christian Eriksen suffered 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 resuscitating him, as half the world watched. With immediate CPR and shocks from a defibrillator, the 29-year-old footballer was brought back. If he had collapsed jogging alone in the woods, he probably wouldn’t have survived. Eriksen even started playing professionally again.
Although the exact details of his case are not known, cardiologist Ardan Saguner believes his cardiac arrest may have been caused by an arrhythmia, either hereditary or due to an infection. If genetic mutations were involved, the USZ arrhythmia specialist would suspect ion channel disease or cardiomyopathy as possible causes. Both affect the propagation 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 begin to quiver or twitch instead of contracting normally. Such irregularities can be corrected by administering electric shocks.
Scar tissue on the heart
These genetic diseases cannot be detected outside the heart. They can even go unnoticed in professional athletes despite thorough medical examinations. Christian Eriksen has been fitted with an implantable cardioverter defibrillator (ICD), a small device that monitors his heartbeat and can reset the heart’s electrical conduction if necessary. This 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 main groups of inherited heart diseases, the second being cardiomyopathy or disorders of the heart muscle. These are characterized by more easily detectable changes, such as thickening of the heart muscle. Various forms of these disorders are known. Arrhythmogenic cardiomyopathy, or ACM, for example, is a condition in which heart muscle cells are replaced by both scar and fatty tissue. “There are scars on the heart,” says Saguner. Fairly common in young athletes, the disease can be triggered by mutations in one or more genes. The effects of these mutations range from minor symptoms to ventricular fibrillation and even cardiac death.
Cordula Haas and her team focus on diseases hidden in these two groups. In their pilot study, the researchers looked at the unexpected deaths of young people aged 45 or younger between 2018 and 2020. After excluding cases of suicide, substance abuse, asthma and acquired heart defects, they were left with 10 cases, including the two examples mentioned. above. Researchers from the Institute of Forensic Medicine and the Institute of Medical Molecular Genetics then analyzed these 10 cases of defective genes.
“Our research was very much like detective work, because the genetic starting point is so complex,” says Jacqueline Neubauer, who specializes in molecular genetic autopsy. No less than 400 genes are currently known to be linked to these heart diseases, and this number continues to grow. The researchers’ study involved a lot of specialist knowledge and time-consuming interpretations of genome scans. In the end, they found defective genetic variants in five of the 10 cases. The 36-year-old woman had two genetic mutations, while the 40-year-old man had a suspicious variant. In both cases, the cause of death was MCA.
Coping with grief
The researchers’ next step was to share their findings with the families of the deceased and offer them cardio-genetic counseling. In the case of the woman, the analyzes 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 oversees the family’s care, says: “We were able to take meaningful medical measures and significantly reduce the risk of further cardiac arrests.
Not all patients need a defibrillator to be implanted; in fact, most cases can be corrected with medication or lifestyle change, such as giving up competitive sports. Of course, family members also have the right not to know, Ardan Saguner points out. “Nobody is obliged to undergo cardiological or genetic tests”, specifies the cardiologist. In his experience, however, most people welcome the tests — and the same goes for thorough autopsies of the deceased. Knowing what caused the death of someone you love makes it easier to grieve, says Saguner.
Meanwhile, the study’s leaders have drawn clear conclusions from their pilot study. “Genetic testing should become standard practice whenever young people experience cardiac arrest, if other causes can be ruled out,” says Cordula Haas. Unfortunately, this is not yet the case. Forensic science is primarily about determining causes of death and eliminating the possibility of foul play. Prosecutors don’t care whether cardiac arrest occurred as a result of an acquired disease or an inherited genetic mutation. “But our research shows it makes a huge difference for family members,” Haas says.
Current practice also has a lot to do with the costs of the tests, which can be quite high and are not covered by mutuals if the insured is no longer alive. This is why genetic testing is not done very often, even when recommended by medical professionals. But thanks to the pilot study, this practice is changing, at least in Zurich. Genetic tests are now routinely performed in cases of sudden cardiac death if a hereditary disease may be involved. And these tests are certainly worth doing, considering the pain and suffering that can be avoided.