European Sudden Cardiac Arrest network will look at gender-based prevention and treatment

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Researchers will use a European network of 90,000 patients, including 20,000 DNA samples, to look at different approaches for prevention and treatment of sudden cardiac arrest for men and women.

Sudden cardiac arrest is the consequence of the heart rhythm disorder ventricular fibrillation, and there are around 400,000 cases a year in Europe. If left untreated it is deadly within minutes and survival rates are just 5–20%, meaning that there is a large medical need to improve sudden cardiac arrest outcomes, including prevention and treatment.

Designing effective individualised prevention and treatment strategies requires knowledge on inherited, acquired, and environmental risk factors.

So far, these efforts have been hampered by the lack of sufficiently large study cohorts of sudden cardiac arrest patients with detailed information. Obtaining sudden cardiac arrest patient samples is challenging as the condition happens suddenly and unexpectedly.

The European Suddent Cardiac Arrest network (ESCAPE-NET) has pooled the patient populations of 16 organisations across Europe. The resulting database of sudden cardiac arrest in the community is sufficiently large to study causes, treatments and prevention strategies (such as AED [automated external defibrillator], lay rescuers and ventricular fibrillation analysis based resuscitation), and how these vary between women and men.

The main aims of the ESCAPE-NET project are to build a database of over 90,000 sudden cardiac arrest patients including 20,000 DNA samples of them, by combining existing European databases and infrastructures, to identify risk factors (inherited, acquired, environmental) and first-response treatment strategies that may explain the differences in sudden cardiac arrest occurrence and survival between European countries, and to collaborate with professional networks, such as the European Heart Rhythm Association and European Resuscitation Council, to translate the outcomes into European clinical practice for the prevention of sudden cardiac arrest, and European infrastructures to improve survival after sudden cardiac arrest.

The electrical properties of the heart differ between men and women. The heart beats by an electrical conduction system in which the movement of potassium ions back and forth across channels in the membranes of heart cells plays an important role. Women have fewer potassium channels than men.

Commonly prescribed drugs that work by blocking ion channels can increase the risk of ventricular fibrillation and sudden cardiac arrest. For potassium channel blockers, such as selective serotonin reuptake inhibitors (SSRIs) for depression, antibiotics including erythromycin, antifungal medications, and domperidone, the increased risk of sudden cardiac arrest may be larger in women.

“Doctors want to know when these drugs can be safely prescribed in women in general, and to which individual with her specific set of inherited and acquired risk factors, in particular,” said Hanno Tan, ESCAPE-NET project leader and cardiologist, Academic Medical Centre, Amsterdam, the Netherlands.

One of the aims of ESCAPE-NET is to create a risk score that includes age, sex, comorbidities and genetic profile. Doctors will be able to use the score to determine the risk, for example, of prescribing erythromycin for a female patient.

Tan said, “We think that sudden cardiac arrest is caused by the interaction of various risk factors. Our research will uncover which factors are relevant in women and men and use this information to develop a risk score.”

There is also evidence that women are more likely to die from sudden cardiac arrest than men because they are less likely to be resuscitated by a bystander. This appears to be due to sociological factors rather than biological sex. For example, women are more likely to be living alone because they have outlived their spouse. Such factors alone, however, cannot fully explain the difference between men and women. Thus, biological factors must also play a role.

ESCAPE-NET will identify specific reasons for differences in survival between men and women and which factors might be changed.

Tan said: “The major strength of ESCAPE-NET is the large number of patients. These cohorts are normally very difficult to collect because sudden cardiac arrest occurs quickly and unexpectedly.”

The European Sudden Cardiac Arrest network is backed by the European Heart Rhythm Association (EHRA), a branch of the European Society of Cardiology (ESC), and the European Resuscitation Council (ERC).

ESCAPE-NET has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No° 730731.

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