Unstable ‘fluttering’ predicts aortic aneurysm

“Our collective lack of understanding makes it hard to monitor aneurysm progression,” Zhao said. “Doctors need to regularly track the size of an aneurysm by imaging its location every one to five years depending on how fasts it grew previously and whether the patient has any associated diseases. Over this ‘wait and see’ period, an aneurysm can fatally burst.”

To remove the guesswork from predicting future aneurysms, Patankar, Zhao and their collaborators sought to capture the fundamental physics underlying the problem. In extensive mathematical work and analyses, they discovered that problems arise when the fluttering vessel wall transitions from stable to unstable. This instability either causes or signals an aneurysm.

“Fluttering is a mechanical signature of future growth,” Patankar said.

Capturing the underlying physics

To quantify the transition from stability to instability, the researchers combined blood pressure, aorta size, stiffness of the aortic wall, shear stress on the wall and pulse rate. The resulting number (or FIP) characterizes the exact interaction between blood pressure and wall stiffness that ultimately triggers fluttering instability.

“Physicians have known that these factors — blood pressure, heartbeat frequency and aortic size — were involved, but they didn’t know how to quantify it,” Patankar said. “It turns out the combination of the factors is what’s important. A patient might have an unstable wall but a normal-sized aorta, so their doctor would not even realize there was a problem.”

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

“We show that the less stiff it is, then the more at-risk the patient is for future growth and rupture,” Zhao said. “This is because once the aorta reaches a certain size, the body tries to stiffen it up to seemingly 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.”

Validating the metric

To test the new metric, the researchers reviewed 4D 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 metric, zero marks the threshold between stable and unstable.

For patients with an FIP below zero, their aorta was unlikely to experience abnormal growth. Researchers predicted that patients with an FIP higher than zero, however, would experience abnormal growth and future rupture.

“In establishing prognostic value of this quantitative metric for cardiovascular 4D flow MRI, we can significantly improve the value of imaging offered as standard of care to patients with aneurysms,” said Dr. Ethan Johnson, the study’s co-first author 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 physician diagnoses, they discovered their predictions were accurate in 98% of the cases. Although the FIP predicted future growth on average three years after the initial MRI (when the FIP was calculated), the researchers say this metric may even offer a more granular view of heart health on a daily or monthly basis.

“The period of one to eight years is the time range in which our clinical data sits,” Zhao said. “Not the total time interval in which the FIP is necessarily effective.”

Next, Patankar, Zhao and their team plan to explore if the FIP can provide clues into how other heart conditions develop. They also are studying if patient-specific FIP can indicate which prevention methods are most effective in stopping aneurysm progression.

The research, “Blood-wall fluttering instability as a physiomarker of the progression of thoracic aortic aneurysms,” was supported by the National Heart, Lung and Blood Institute of the National Institutes of Health (award number F32HL162417).