Text: Marianne Alfsen/Felix Media
Photo: Fredrik Naumann/Felix Features
“We’re recycling hearts,” says doctor and PhD student Henrik B. Dukefoss.
Joke aside, what he is referring to is possibly game changing heart research at the Institute for Experimental Medical Research (IEMR) in Oslo. Through collaborative and translational cardiac research, spanning several medical and life science disciplines, they are trying to figure out the enigma of one of the most complex organs of the body. Here, «impossible» is not part of the vocabulary. Several departments at Oslo University Hospital (OUS) are collaborating on the complex so-called RELAX project, including the Departments of Cardiology and Thoracic Surgery, the Intervention Center and the Research Institute of Internal Medicine.
“We want to understand the heart better, in order to develop new diagnostic methods and new treatments,” says Dukefoss, who is working on a multidisciplinary PhD project, in collaboration with doctor and PhD student Markus Borge Harbo. Both belong to the research group headed by Professor Ivar Sjaastad. The project is part of KG Jebsen Center for Cardiac Research, the OUS strategic area for fibrosing diseases, and FibroPET, an UiO Lifescience Convergence environment.
Doctor and PhD student Henrik Dukefoss.
Before and after
“What’s unique about the RELAX project is that we systematically study the same sick hearts before and after the transplant,” explains Dukefoss’ main supervisor, Emil Espe, who is a postdoctoral researcher at IEMR.
This is the first study of this kind, world wide.“We approach all patients who meet the criteria for a heart transplant in Norway, about 30 a year,” adds Dukefoss.
The scientists first do a series of tests on the sick heart, prior to the transplant – including an MRI and ultrasound, as well as new, promising tests not yet validated for use in diagnostic medicine. Then, the waiting game starts. When the patient is up for a transplant, Dukefoss and four medical students get a call from the transplant team at Rikshospitalet.
Main supervisor Emil Espe.
Time is of the essence
“We are on call, around the clock. Even Christmas Eve.” says Dukefoss.
As the patient is wheeled into the operating theatre, Dukefoss and the medical students who were available when the call came, are already there, waiting, ice box in hand.
“Degradation of the heart tissue starts as soon as the heart is removed, so time is of the essence,” says Dukefoss.
TIME SENSITIVE: Medical students Henrik Romundstad (right) and Herman Sætersdal Grødem with precious cargo; a newly harvested heart.
The team immediately prepares the heart for the deep freezer at IEMR. First, they dissect the coronary artery and the left ventricle and septum. Then, they take about 90 carefully selected tissue samples, to be able to match MRI and ultrasound data prior to the transplant with the harvested heart tissue. Finally, the samples are transferred to liquid nitrogen, keeping them cold until they can be placed in the freezer at IEMR.
MASSIVE JOB: 90 tissue samples are carefully selected from each heart and meticulously registered for storage.
READY FOR TRANSPORT: Tissue samples are transferred to liquid nitrogen, to keep them cold until they reach the freezer at IEMR.
Collaboration is paramount
“To successfully carry out this complex project, we are totally reliant on our great collaborators. We are by no means doing this alone,” says Dukefoss.
Ever since the first heart transplant in Norway 40 years ago, in 1983, Oslo University Hospital, Rikshospitalet, has been the only hospital in Norway performing the procedure. The collaboration with the experienced transplant team at the Department of Cardiothoracic Surgery and the cardiologists at the Department of Cardiology is paramount to the project. As is the collaboration with other major departments at OUS, such as the Research Institute of Internal Medicine. Vital to the project are also physicists from the Department of Physics and Computation Radiology and the imaging experts at the Intervention Centre, who have been instrumental in developing RELAX’s MRI protocols.
Since the start in 2021, as of November 2023, the team has included 36 patients in the study, 12 of whom have already gone through a heart transplant. All patients are of interest, regardless of underlying diseases.
“The fact that the patients suffer from different heart diseases is important to us, as we can compare them,” says Dukefoss, adding:
“We will include a lot more patients, of all ages, in the years to come.”
Heart stiffness
The project has one main goal: To develop methods for early diagnosis of heart stiffness.“This is one of the great unsolved challenges of cardiac treatment. More than half of all patients diagnosed with heart failure are primarily suffering from heart stiffness. We know surprisingly little about when and why heart stiffness occurs, or how to diagnose and treat it,” Espe says, adding that research on heart stiffness is a strategic priority at IEMR.
“A lot of research has gone into understanding the damage a heart that pumps poorly can do, and we have good medication to help the heart pump better. However, we are increasingly realising that it is an equally big problem when the heart muscles become stiff and are unable to relax, preventing the heart from filling properly before the next heartbeat,” explains Espe.
Heart stiffness typically occurs long before symptoms of heart diseases develop and can be diagnosed. Currently, physicians are unable to discover heart stiffness at an early stage through ultrasound or MRI.
“If we are able to diagnose heart stiffness at an earlier stage, we can start treatment before heart function decreases. That is the main goal of our particular research,” explains Dukefoss.
“For instance, the team is relating gene expression and proteins involved in disease progression to radiological findings. Fibrosis is one of the most important components of stiffness and is central to the research strategy of IEMR. We are also securing tissue for detailed investigation of molecular pathways for various aetiologies,” Dukefoss continues.
A bank of hearts
The current and specific IEMR research is one thing. The data and heart tissue collected will be available for years to come to other cardiac scientists trying to solve new heart puzzles.
“The tissue we collect constitutes a unique biobank for future research,” says Emil Espe.
“To maximise the scientific utility of our biobank, we are actively seeking collaboration with other scientists. This facilitates answering new questions and will advance cardiac research for the benefit of the patients,” Dukefoss adds.
“The fact that we know so much about the patient we collect the tissue from – such as former surgery and medication they have taken – makes it even more valuable to other scientists,” says Espe.
The IEMR scientists are already collaborating with one of the world’s foremost experts on stiffness imaging, Ralph Sinkus. He is a professor of biomedical engineering at King’s College London and research director CNRS at INSERM in Paris.
“Currently, we are in the process of implementing a new MRI method for measuring heart stiffness in patients, in collaboration with professor Sinkus,” says Espe.
BIOBANK: Here, the gold is stored – tissue from discarded hearts after transplants. The freezer keeps a steady minus 80 degrees celsius, keeping the tissue healthy for decades.
Happy patients
What do the patients think?
“These are very sick patients, who are asked to participate in research that does not benefit them personally. Still, almost every single patient we have approached has said yes to participate. That surprised us. They are motivated by the prospect that other heart patients might be diagnosed earlier, eliminating the need for a heart transplant,” says Dukefoss.
The team’s dream scenario is to find a diagnostic method that can be used by general practitioners to diagnose heart stiffness – in order to prevent heart failure, one of the most common causes of death in an ageing population.