July 5, 2024

Unveiling the Hidden Dangers: Unstable “Fluttering” Predicts Aortic Aneurysm with 98% Accuracy

Researchers at Northwestern University have devised a groundbreaking metric based on physics that can predict the likelihood of an individual developing an aortic aneurysm, a dangerous condition that often remains asymptomatic until it ruptures. In this novel study, the researchers identified abnormal growth of the aorta by analyzing subtle fluttering in a patient’s blood vessel. The flow of blood through the aorta can prompt the vessel wall to flutter, resembling how a banner moves in the wind. The researchers found that while stable blood flow signifies normal, natural growth, unstable fluttering indicates a high probability of future abnormal growth and potential rupture.

This newly developed metric, known as the flutter instability parameter (FIP), accurately predicted the occurrence of an aneurysm with 98% accuracy on average, three years after the initial measurement of the FIP. Calculating a personalized FIP only requires a single 4D flow magnetic resonance imaging (MRI) scan. By utilizing this clinically measurable and predictive metric, doctors can prescribe medications to high-risk patients, potentially intervening and preventing the aorta from reaching a dangerous size.

Often referred to as “silent killers,” aortic aneurysms can go undetected until they result in catastrophic dissection or rupture, explained Neelesh A. Patankar, senior author of the study at Northwestern University. The underlying physics behind aneurysms has remained elusive, resulting in a lack of clinically approved protocols for predicting them. This physics-based metric stands as evidence of the potential effectiveness in predicting cardiac pathologies.

Neelesh A. Patankar, an expert in fluid dynamics and a professor of mechanical engineering at Northwestern’s McCormick School of Engineering, collaborated with Dr. Tom Zhao, a specialist in first principles biomechanics, as co-leaders of the study. An aortic aneurysm occurs when the aorta, the body’s largest artery, expands to more than 1.5 times its original size. As the aorta grows, the integrity of its walls weakens. Eventually, the walls become too fragile to withstand the pressure of blood flow, leading to a rupture. Although rare, an aortic rupture is typically unpredictable and almost always fatal.

Notable figures, including Grant Wahl, a sports journalist who died suddenly during the 2022 FIFA World Cup, as well as John Ritter, Lucille Ball, and Albert Einstein, have all succumbed to aortic aneurysms. Most individuals remain unaware of their condition until it is incidentally detected during a scan for an unrelated issue, stated Patankar. Physicians can suggest lifestyle changes or prescribe medication to lower blood pressure, heart rate, and cholesterol if the aneurysm is discovered. If left undiagnosed, a rupture could occur, resulting in immediate catastrophic consequences.

Dr. Tom Zhao further added that if the rupture occurs when the patient is not in a hospital, the fatality rate is close to 100% since the blood supply to vital organs such as the brain ceases, and their proper functions are compromised. At present, physicians estimate the risk of rupture based on factors such as age or smoking history, alongside the size of the aorta. To monitor an expanding aorta, doctors regularly employ imaging scans. If the aorta grows rapidly or reaches a certain size, patients often undergo invasive procedures, such as a surgical graft, to reinforce the vessel walls, which also carries its own set of risks.

The uncertainty surrounding the progression of aneurysms makes monitoring them a challenge, explained Dr. Tom Zhao. Physicians need to regularly monitor the aneurysm’s size through imaging scans at intervals of one to five years, depending on the rate of growth and any associated diseases. Within this observation period, an aneurysm could unexpectedly rupture.

To eliminate the guesswork associated with predicting future aneurysms, Patankar, Zhao, and their collaborators endeavored to capture the fundamental physics underlying the issue. Through extensive mathematical work and analysis, they discovered that problems emerged when the fluttering vessel walls transitioned from being stable to unstable. This instability either leads to or indicates the presence of an aneurysm.

According to Patankar, fluttering serves as a mechanical indicator of future growth. To measure the transition from stability to instability, the researchers combined factors such as blood pressure, aorta size, the stiffness of the aortic walls, shear stress on the walls, and pulse rate. The resulting number, known as the FIP, characterizes the precise interaction between blood pressure and wall stiffness, ultimately triggering fluttering instability.

While doctors already recognize the involvement of blood pressure, heartbeat frequency, and aortic size, they previously lacked a quantification method, Patankar noted. The researchers’ discovery lies in the importance of combining these factors. A patient may possess an unstable wall but have a normal-sized aorta, which means their doctor would be unaware of any issues.

Surprisingly, the researchers found that instability occurs more frequently when the walls are more flexible. This finding contradicts conventional knowledge that regards aortic stiffness as an indication of disease.

Zhao explained that their findings demonstrate that less stiffness increases the patient’s vulnerability to future growth and rupture. He added that once the aorta reaches a certain size, the body attempts to increase stiffness as a protective measure against further expansion. However, the ones that continue growing remain less stiff. Fluttering of the aorta’s wall occurs when it is more compliant.

To evaluate the accuracy of the new metric, the researchers analyzed 4D flow MRI data from 117 patients who underwent cardiac imaging for heart disease monitoring, as well as 100 healthy volunteers. Based on the MRI scans, each patient received a personalized FIP. In this metric, zero serves as the threshold between stability and instability.

Patients with an FIP below zero were unlikely to experience abnormal growth in their aorta, and those with an FIP exceeding zero were predicted to undergo abnormal growth and future rupture.

Dr. Ethan Johnson, co-first author of the study and a postdoctoral fellow in cardiovascular imaging at Northwestern University Feinberg School of Medicine, stated that the prognostic value of this quantitative metric for cardiovascular 4D flow MRI significantly enhances the standard of care imaging provided to patients with aneurysms. When comparing these predictions with follow-up MRIs or physician diagnoses, the researchers observed a 98% accuracy rate. Although the FIP predicted future growth on average three years after the initial MRI and FIP measurement, the researchers speculate that this metric might offer a more detailed assessment of heart health on a daily or monthly basis.

Dr. Patankar, Dr. Zhao, and their team plan to investigate whether the FIP can offer insights into the development of other heart conditions in the future. Additionally, they are exploring whether patient-specific FIP can determine the most effective prevention methods for halting aneurysm development.

The research, titled “Blood-wall fluttering instability as a physiomarker of the progression of thoracic aortic aneurysms,” was published in the journal Nature Biomedical Engineering.

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