March 17, 2025 – by Santina Russo
One of the most significant human health advancements of the past 50 years is the combining of modern medicine and healthier lifestyles. “Today, 60- and 70-year-olds are fitter and more active than they used to be,” says Dominik Obrist, professor for cardiovascular engineering at the ARTORG Center for Biomedical Engineering Research at the University of Bern. This also means that medical care must adapt to fitter, aging patients.
One example where this comes into play is heart valve implants — more specifically, the increased risk of thrombosis associated with the procedure. Obrist and his group recently investigated how thrombosis develops after minimally invasive valve implantation by using high-fidelity simulations performed on CSCS’s “Piz Daint” supercomputer. They found a clue that could help doctors identify high-risk patients in advance.
Treating heart disease leads to new health risks
Heart valve replacements are necessary for patients suffering from aortic valve stenosis, a heart disease that most often develops in older age due to calcium deposits in the valve tissue. Consequently, the aortic valve — the gate from the left heart chamber to the body's main artery — no longer opens fully. This reduces blood flow to the aorta and the rest of the body. Without treatment, aortic valve stenosis can lead to life-threatening complications.
The most common treatment for the disease is a heart valve implant. However, mechanical heart valves, which are made of metal or carbon, are particularly prone to causing thrombosis. In the worst case, such a blood clot can detach, travel to the brain and cause a stroke. This is why patients with a mechanical valve implant are urged to take strong anti-coagulant drugs — medication with its own risks, such as continued bleeding after an injury — for the rest of their lives.
Thrombosis risk higher than previously assumed
Contrastingly, researchers and doctors believed biological valves made of animal tissue had much lower risk of thrombosis than mechanical valves. However, recent research shows that the risks associated with one type of biological valves, the so-called transcatheter aortic valves (TAV), were underestimated.
TAV are implanted using a minimally invasive method, during which the new valve is fitted to the heart’s aortic wall. Unlike in conventional heart valve replacement, doctors do not remove the old, diseased valve. It is instead displaced to the side of the aortic wall. While this approach is much gentler for patients, it also creates a new sinus portion — a cavity around the valve leaflets. This so-called “neo-sinus” raises the risk for developing thrombosis.
“Although only three percent of TAV patients suffer clinical symptoms after the intervention, findings during routine checkups and unrelated examinations have uncovered thrombosis in up to one third of patients,” says Obrist. “This means thrombosis must now be considered more carefully.”
In a previous project on CSCS’s “Piz Daint” supercomputer, Obrist and his team already investigated blood flow and risk of thrombosis based on various aortic traits, particularly its diameter. “From one patient to the next, the diameter of the aorta can differ by five to ten millimetres,” says Obrist. People with heart valve disease often have an enlarged aorta due to the narrowed valve opening and altered blood pressure. The researchers found that such a dilated aorta may lead to a higher risk of thrombosis.
In their new project, the team also included a neo-sinus into their high-fidelity simulations on “Piz Daint”, which allows them to differentiate between the effects of a dilated aorta and the neo-sinus introduced by the TAV surgery. In addition, they improved their model to monitor the trajectories and state of the individual blood platelets, allowing them to uncover the mechanism driving thrombosis formation.
Recognizing patients at higher risk requires a supercomputer
Specifically, the simulations showed that the neo-sinus leads to an increased backflow of blood platelets, which have been activated at the interface between the ascending flow and returning flow due to strong shear forces. If these activated platelets are carried back into the neo-sinus and stagnate there, they aggregate and ultimately form blood clots. The simulations also showed that a dilated aorta further reduces sinus washout, increasing the risk of thrombosis due to the combination of activated and stagnated platelets.
“These insights were only possible because our direct numerical simulations use high-order numerics and achieve a much higher resolution than more common aortic simulations that run on desktop or laptop computers,” explains Obrist. “If you want to analyse platelet activation, this level of detail, which requires supercomputing resources, is necessary.”
What do these results mean in practice? First, the findings explain why thrombosis could occur more frequently in TAV implants than in other biological valve implants. Second, the findings highlight the importance of monitoring aortic dilation to estimate risk. “Aortic diameters are routinely measured to plan the intervention,” says Obrist, “and with the insights gained from our findings, these measurements could help identify patients at higher risk of thrombosis before surgery. The key message for doctors is: If a patient already has a dilated aorta, their risk of thrombosis may be elevated.” And after surgery, the awareness of the thrombosis risk will help doctors choose a safer, more suitable anti-coagulation scheme.
References:
K-M. Bornemann, S.E. Jahren and D. Obrist: The relation between aortic morphology and transcatheter aortic heart valve thrombosis: Particle tracing and platelet activation in larger aortic roots with and without neo-sinus. Comput. Biol. Med. (2024), 179, 108828, DOI: https://doi.org/10.1016/j.compbiomed.2024.108828
S.E. Jahren, C. Demirel, K-M. Bornemann, P. Corso, S. Stortecky and D. Obrist: Altered blood flow due to larger aortic diameters in patients with transcatheter heart valve thrombosis APL Bioengineering (2023), 7, 046120, DOI: https://doi.org/10.1063/5.0170583
This visualisation of the fluid dynamics of bioprosthetic aortic valves is based on past simulations run on “Piz Daint” by the group led by Dominik Obrist at the University of Bern. It shows the turbulent flow created by the bioprosthetic valves, which is suspected to lower their durability and performance. The visualisation earned the Obrist group the APS/DFD Gallery of Fluid Motion Award.
(Credit: K.-M. Bornemann and D. Obrist https://gfm.aps.org/meetings/dfd-2024/673e5f58d88f375e670eb4c2)