Unstable ‘flutter’ predicts aortic aneurysm with 98% accuracy

Unstable ‘flutter’ predicts aortic aneurysm with 98% accuracy

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The fluttering instability parameter can predict where the abnormal growth in the aorta will occur. Credit: Tom Chow/Northwestern University

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The fluttering instability parameter can predict where the abnormal growth in the aorta will occur. Credit: Tom Chow/Northwestern University

Researchers from Northwestern University have developed the first physics-based measure to predict whether a person might one day suffer from an aortic aneurysm, a fatal condition that often causes no symptoms until it ruptures.

In the new study, researchers predicted abnormal aortic growth by measuring the tiny “flutter” in a patient’s blood vessels. When blood flows through the aorta, it can cause the vessel wall to flutter, similar to the waves of a flag in the breeze. The researchers found that while stable flow predicted normal growth, unstable flutter was highly predictive of future abnormal growth and potential rupture.

This new measure is called the flutter instability parameter (FIP), and it predicts future aneurysms with an average of 98% accuracy three years after FIP is first measured. To calculate personalized FIP, patients only need one 4D magnetic resonance imaging (MRI) scan.

Using a clinically measurable predictive scale, doctors can prescribe medications to high-risk patients to intervene and potentially prevent the aorta from swelling to a dangerous size.

The research was published this week (December 11) in the journal Nature of biomedical engineering.

Nilesh A said. “Aortic aneurysms are colloquially referred to as ‘silent killers’ because they often go undetected until catastrophic dissection or rupture occurs,” said Dr. Patankar, of Northwestern University, lead author of the study. “The basic physics that causes aneurysms is unknown. As a result, there is no clinically approved protocol for predicting them. Now, we have demonstrated the effectiveness of a physics-based measure that helps predict future growth. This could be transformative in predicting heart disease.”

Patankar, an expert in fluid dynamics, is a professor of mechanical engineering at Northwestern’s McCormick School of Engineering. He co-led the study with Dr. Tom Chow, who specializes in first principles of biomechanics.

Increased risk

An aortic aneurysm occurs when the aorta (the largest artery in the human body) swells to more than 1.5 times its original size. As it grows, the wall of the aorta weakens. Eventually, the wall becomes so weak that it can no longer handle the pressure of blood flowing through it, causing the aorta to rupture. Although rare, aortic rupture is usually unpredictable and often fatal.

Several notable people have died of aortic aneurysms, including Grant Wahl, the sports journalist who died suddenly one year ago at the 2022 FIFA World Cup. Other celebrity deaths include John Ritter, Lucille Ball, and Albert Einstein.

“Most people don’t realize they have an aneurysm unless it is accidentally discovered when they receive a scan for an unrelated problem,” Patankar said. “If doctors detect it, they can suggest lifestyle changes or prescribe medication to lower blood pressure, heart rate and cholesterol. If it goes undetected, it can rupture, which is an immediate catastrophic event.”

“If it ruptures while the person is out of the hospital, the mortality rate is close to 100 percent,” Zhao added. “Blood flow to the body stops, so vital organs such as the brain can no longer perform their functions.”

Remove the guesswork

By current standards of care, doctors estimate the likelihood of rupture based on risk factors (such as age or smoking history) and the size of the aorta. To monitor the growth of the aorta, doctors track it with regular imaging tests. If the aorta begins to grow too quickly or becomes too large, the patient often undergoes surgery to reinforce the vessel wall, a surgical procedure that carries its own risks.

“Our collective lack of understanding makes it difficult to monitor aneurysm development,” Zhao said. “Doctors need to regularly track the size of an aneurysm by imaging its location every one to five years depending on how quickly it grew previously and whether the patient has any associated diseases. During the ‘wait and see’ period, an aneurysm can rupture deadly”. “.

Watch the blood move through the aorta. Credit: Ethan Johnson/Northwestern University

To take the guesswork out of predicting future aneurysms, Patankar, Zhao and their collaborators sought to understand the basic physics behind the problem. Through extensive mathematical work and analysis, they discovered that problems arise when the blood vessel wall transitions from stable to unstable. This instability either causes or signals an aneurysm.

“Flapping is a mechanical sign of future growth,” Patankar said.

Capture basic physics

To determine the extent of the transition from stability to instability, researchers combined blood pressure, aortic volume, aortic wall stiffness, wall shear stress, and pulse rate. The resulting number (or FIP) describes the precise interaction between blood pressure and wall stiffness that ultimately leads to instability.

“Doctors knew that these factors — blood pressure, heart frequency, aortic size — played a role, but they didn’t know how to measure them,” Patankar said. “It turns out it’s a combination of factors that matters. A patient may have an unstable wall but the aorta is a normal size, so his doctor won’t even realize there’s a problem.”

Surprisingly, the researchers discovered that instability tends to appear when the wall is more flexible. This finding directly contradicts the common knowledge that aortic stiffness is a sign of disease.

“We showed that the less stiff the condition is, the more risk the patient has for growth and rupture in the future,” Zhao said. “This is because once the aorta reaches a certain size, the body tries to stiffen it to apparently protect it from future growth. But the ones that are still growing are less stiff. The aorta will flutter if the wall is more compliant.”

Validation of the scale

To test the new measure, researchers reviewed 4-D flow MRI data from 117 patients who underwent cardiac imaging to monitor heart disease and from 100 healthy volunteers. Based on this MRI, the researchers assigned each patient a personalized FIP. In this scale, zero represents the threshold between stable and unstable.

For patients with a FIP less than zero, the aorta is unlikely to have abnormal growth. The researchers predicted that patients with a FIP higher than zero would suffer from abnormal growth and rupture in the future.

“By determining the predictive value of this quantitative MRI measure of 4D cardiovascular flow, we can significantly improve the value of imaging provided as the standard of care for patients with aneurysms,” said Dr. Ethan Johnson, co-first author of the study and a postdoctoral fellow. . in Cardiovascular Imaging at Northwestern University Feinberg School of Medicine.

When the researchers compared these predictions to follow-up MRIs or doctor’s diagnoses, they discovered that their predictions were accurate 98% of the time. Although FIP predicted future growth on average three years after the initial MRI (when FIP was calculated), researchers say this measure may provide a more detailed look at heart health on a daily or monthly basis.

“One to eight years is the time range in which our clinical data exists,” Zhao said. “It is not necessarily the total time interval over which FIP is effective.”

Next, Patankar, Zhao and their team plan to explore whether FIP can provide clues about how other heart diseases develop. They are also studying whether a patient’s FIP can indicate which prevention methods are most effective in stopping aneurysm progression.

The research is titled “Blood wall flutter instability as a physical indicator of the development of thoracic aortic aneurysm.”

more information:
Tom Way. Zhao et al., Blood wall instability as a physical indicator of thoracic aortic aneurysm development, Nature of biomedical engineering (2023). doi: 10.1038/s41551-023-01130-1

Magazine information:
Nature of biomedical engineering

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