Researchers search for the tremors that stop the heart

Breaking new ground 6. dec 2018 3 min PhD, Postdoc Eva Zander Hesselkilde Written by Morten Busch

Cardiovascular diseases cause more deaths than any other in Denmark. Narrowing of the coronary artery can lead to a blood clot blocking the blood flowing to the heart. Balloon angioplasty saves many people’s lives, but 1 in 10 have fibrillation inside the heart – often resulting in death. Researchers are now finding early electrical irregularities that can predict heart fibrillation before it occurs.

The heart is life’s rhythm box. Electric impulses increase or decrease the heart rate depending on our activity and mood. But sometimes the electrical activity in the heart becomes so rapid or uneven that the heart cannot pump blood throughout the body. This is called atrial fibrillation, and if it occurs inside the heart, it can lead to a sudden heart attack, often causing death.

“In Denmark, about 9000 people per year have a blood clot in the heart, and 1 in 10 of these die suddenly. We want to understand why they die suddenly from a heart attack, while other people who receive treatment within 1–2 hours go home the day after,” explains Stefan Sattler, Cardiologist and Guest Researcher, Rigshospitalet, Copenhagen.

The first critical minutes

Researchers have conducted epidemiological studies and identified some of the factors, including alcohol consumption, that increase the risk of a sudden heart attack. Drinking more than 20 standard drinks per week increases this risk. Taking drugs to treat mental disorders also increases the risk.

“We are very interested in what happens when someone has a blood clot in the heart, how it develops and why some people have a heart attack while others do not. We hope that elucidating the mechanisms that lead to a heart attack can prevent them,” explains Eva Zander Hesselkilde, Research Assistant and veterinarian, Department of Biological Sciences, University of Copenhagen.

The researchers have therefore tried to detect early signs in the heart’s electrical signals in the first critical minutes after a heart attack. To solve this, they artificially induced a heart attack in a pig so they could then record all the signals that arise inside and outside the heart.

“We installed some sensors in the left side of the heart so that we could measure what was happening inside. This means that we could determine what the anatomical structure looked like and how the electrical impulses spread out inside.”

Since the heart wall is very thick, the researchers also measure using electrodes outside the heart. This enables them to determine how the electrical impulses spread both inwards and outwards every time the heart contracts.

Creating a blood clot with a balloon

“Using a tiny balloon, we found one of the major arteries that oxygenates and supplies blood to the heart. By inflating the balloon, we could simulate a heart attack or an infarction inside the heart.”

A blood clot prevents blood from reaching the rest of the heart muscle. Arrhythmia can occur in this phase, and the heart may stop.

“When the pigs undergo surgery, they get general anaesthesia and do not feel anything. I therefore do not think that the surgery hurts the animals. You could say: is it a waste that a pig has to die for the sake of research? The alternative was that it would have been turned into bacon, so my view is that developing scientific knowledge that ultimately may save people’s lives makes the pigs’ lives more meaningful than simply being turned into pork roast,” says Eva Zander Hesselkilde.

Invisible to the naked eye

The researchers tried to discover how a healthy heart becomes sick and especially how this can be discovered in good time. Today, not very many early markers indicate whether a person is about to experience ventricular fibrillation.

“Some tiny electrical changes arise that are invisible to the naked eye, but our research teaches us what to look for. A doctor in an ambulance can attach an electrocardiograph and, within a few minutes, can see whether the patient has a myocardial infarction and a greater risk of sudden death. Patients in the risk group can thus be treated to prevent ventricular fibrillation,” explains Stefan Sattler.

The researchers have already shown that the changes a blood clot causes are confined to the area in which the blood clot arises, while the rest of the heart remains almost unchanged.

“We can identify the triggers inducing ventricular fibrillation that result in sudden death.”

Life-saving medicine

If the researchers succeed in developing an effective screening method for detecting early markers for ventricular fibrillation, then it may be possible to treat the arrhythmia before it starts.

“Several drugs have been used on humans in the past decade, but we do not know whether we can treat people who have had an infarction to prevent ventricular fibrillation. In addition, some of the drugs have side-effects, such as reducing blood pressure. This is undesirable for people with myocardial infarction.”

There are no approved drugs for preventing ventricular fibrillation. The experiments can show how to develop new types of medicine.

“When a new drug is discovered with the potential to prevent the sudden death of people with infarction, we can use our method to test drugs and see whether they have the predicted effect and whether they will be useful clinically.”

The goal is to identify the people with increased risk and then give them the life-saving medicine in the ambulance on the way to the hospital.

Endocardial Mapping of Spontaneous Ventricular Fibrillation during Acute Myocardial Infarction in a Porcine Model is a collaborative project between Rigshospitalet, the University of Copenhagen, Ludwig Maximilian University of Munich and University College London. In 2013, the Novo Nordisk Foundation awarded a grant to Jacob Tfelt-Hansen of Rigshospitalet, a principal investigator of the project GEVAMI (Genetic Causes of Ventricular Arrhythmia in Patients during First ST-elevation Myocardial Infarction). In 2018, the Foundation awarded a grant to another participant, Thomas Jespersen, for the project Sudden Arrhythmogenic Death Syndrome in the Young (SADS-Young).

Research areas have mainly focused on large animal models of cardiac arrhythmias, including a chronic model of atrial fibrillation in horses and sudde...

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