A New Understanding of Aortic Aneurysm Progression: Insights from Physics and Experimental Validation

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Aneurysms, characterized by a persistent dilation of the vascular wall resulting from artery wall lesions or damage, pose a significant yet often silent threat to individuals worldwide. While this condition is frequently asymptomatic, its potential to lead to fatal artery ruptures cannot be underestimated (Schmitz-Rixen et al., 2016; Liu et al., 2020). Shockingly, an estimated 200,000 aneurysm-related deaths occur globally each year, emphasizing the urgency of understanding and addressing this medical issue (Liu et al., 2020).

Recent literature has increasingly highlighted the gender-related aspects of aortic diseases, including aneurysms (Sweeting et al., 2012; Deery et al., 2017; Boese et al., 2018). Notably, abdominal aortic aneurysms have been shown to exhibit gender-specific differences. Men are more prone to developing these aneurysms, yet women face a greater risk of rupture and a more ominous prognosis.

Moreover, female patients diagnosed with abdominal aortic aneurysms tend to be older than their male counterparts (Boese et al., 2018). Understanding these gender and age disparities is pivotal for devising more accurate prognostic methods that cater to the unique needs of patients.

Hyperlipidemia, a pathological condition characterized by elevated lipid concentrations resulting from disrupted lipid metabolism, represents another critical facet of cardiovascular health (He and Ye, 2020). Clinical studies have extensively linked hyperlipidemia to adverse cardiovascular outcomes, including the promotion of atherosclerosis and an increased risk of non-ischemic heart failure and coronary heart disease (El-Tantawy and Temraz, 2019; Yao et al., 2020).

However, intriguingly, some studies have suggested a potential protective effect of hyperlipidemia on the mortality of aneurysm patients. Despite this observation, comprehensive investigations into the complex relationship between hyperlipidemia and aneurysm-related deaths, considering diverse age groups and gender differences, remain scarce (Cheng et al., 2019; Huber et al., 2019).

Understanding how hyperlipidemia influences the survival of aneurysm patients across various age and gender categories is essential for improving prognosis and tailoring interventions to different populations.

In the past decade, the global number of deaths caused by aortic aneurysms has surged by a staggering 29%, raising alarm bells in the medical community. This increase in mortality has left healthcare professionals grappling with the challenge of effectively monitoring and managing this silent killer.

The root cause of aneurysm progression has remained an enigma, hindering proactive intervention. Consequently, clinical practices have largely relied on retrospective measurements of aortic diameters taken at intervals of one or more years, which often leads to decisions being made only after the occurrence of abnormal growth, dissection, or rupture.

With no effective prevention or treatment strategies available, surgery remains the sole clinically proven method of intervention, placing a heavy burden on accurately predicting aneurysm outcomes to balance the risks associated with surgical repair against disease progression.

Predicting Aneurysm Growth: Current State of the Art

The current state of the art in predicting aneurysm growth revolves around regression analysis and machine learning techniques. However, these approaches face significant limitations due to the constraints imposed by the size, diversity, and availability of the data used. Factors such as age, sex, smoking history, congenital diseases, aortic regurgitation, and ejection fraction, among others, are often included as input variables. But without a fundamental understanding of the core mechanism driving aneurysm development, an exhaustive list of physiological features and demographic information must be considered to achieve any predictive capability.

A New Approach: Unveiling the Physics of Aneurysm Progression

In response to this knowledge gap, a groundbreaking proposal emerges, suggesting that the physics of aneurysm progression originates from a blood-aortic wall instability induced by the pulsatile forces of the human heart. This instability can be precisely identified through a linear stability analysis of blood flow within the aorta, leading to the derivation of the “flutter instability parameter.” This parameter, a dimensionless number in relation to its critical threshold, serves as an indicator of the onset of the “fluttering” instability within the blood vessel.

The flutter instability parameter depends on various physiological properties, including pulse wave velocity, pressure-driven flow acceleration, blood viscosity, aortic area, pulse rate, and more. This aortic flutter concept draws parallels to the fluttering of a banner in the wind, with physical attributes like stiffness, wind acceleration, air viscosity, banner area, and wind pulsation mirroring their physiological counterparts.

Unlike traditional approaches relying on machine learning and statistical correlations, the flutter instability parameter is derived analytically, eliminating the need for extensive data inputs.

Hypotheses and Their Implications

Based on this new theory, two crucial hypotheses are proposed. First, it is suggested that the flutter instability parameter accurately identifies the transition from stable flow to unstable fluttering. Second, it is conjectured that the resulting aortic flutter either triggers abnormal growth by subjecting the aortic wall to significant local stresses and strains or acts as a signal for growth, indicating the presence of an underlying mechanism responsible for abnormal dilatation.

Experimental Validation: Shaping the Future of Aneurysm Management

Previous research demonstrated the clinical utility of the flutter instability parameter as an aneurysm physiomarker for forecasting aneurysmal dilatation. However, these underlying assumptions had not been physically validated until now. A series of in vitro experiments were conducted to confirm the physical conjectures forming the basis of the aneurysm physiomarker. These experiments aimed to prove that the parameter accurately signals the onset of fluid-structure instability and to verify its role in aneurysm growth, dissection, and rupture.

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

Key Findings and Clinical Implications

The experimental results offer two significant clinical insights. First, they reveal that flutter can be distinctly visualized through imaging, potentially enabling the measurement of flutter in-vivo via techniques like echocardiograms. This offers an alternative modality for tracking aneurysm progression.

Secondly, when the aneurysm physiomarker surpasses a secondary empirically measured threshold, strain patterns localize along the synthetic artery, aligning with the length scale associated with clinical aortic dissection. A tertiary, empirically measured threshold marks the onset of rupture for the synthetic artery. These findings suggest that the flutter instability parameter can be used as a measurable, treatable, and predictive surrogate for aneurysm progression. The physiological properties contributing to this parameter can be managed to optimize its value for individual patients, potentially preventing dissection and rupture.

In conclusion, this work represents a significant leap forward in our understanding of aortic aneurysm progression. Through rigorous experimentation, we have successfully validated the existence of a pulsatile fluid-structure instability, a phenomenon previously predicted solely by theoretical models. This accomplishment not only reinforces the importance of theory in guiding our scientific endeavors but also highlights the practical implications of our findings.

One of the key outcomes of this research is the identification and validation of the flutter instability parameter, denoted as Nω,sp = 0. This parameter, derived from an ab-initio linear stability analysis of the conservation laws, serves as a precise indicator of instability onset within the aortic system. Its clinical significance cannot be understated, as it offers a measurable and reliable tool for diagnosing and monitoring aortic aneurysms.

On the clinical front, our study has shed light on the complex relationship between instability and arterial dilatation. We have demonstrated that even low levels of instability, coupled with the history of instability experienced, can lead to permanent arterial dilatation. This phenomenon underscores the need for proactive intervention, even in cases where material remodeling is not evident.

Furthermore, our investigation has revealed that aneurysm dissection appears to be associated with an intermediate instability regime, characterized by Nω,sp ≳ 2. This regime induces pronounced strain localization, aligning with the observations of intimal tears seen in dissecting aortas. This insight could prove invaluable in identifying patients at risk of aneurysm dissection.

Perhaps most crucially, we have observed that aneurysm rupture can occur in a severe instability regime, beginning at Nω,sp ≳ 10. This final stage of failure can manifest through modes previously observed in ruptured aortic aneurysms. The understanding of these instability regimes and their association with clinical outcomes offers a critical opportunity for intervention and prevention.

In light of these significant findings, our work paves the way for further clinical investigations into the use of the aneurysm physiomarker in diagnosing and treating patients with or at risk of aneurysm formation. The defined thresholds for the aneurysm physiomarker leading to growth, dissection, and rupture provide clinicians with powerful tools for forecasting and intercepting these different stages of aneurysm progression.

In conclusion, this research not only deepens our understanding of the complex mechanisms driving aortic aneurysm progression but also holds the promise of improving patient outcomes through earlier diagnosis, intervention, and ultimately, the prevention of catastrophic events such as dissection and rupture. The integration of theory and experimentation has brought us closer to addressing the silent threat of aortic aneurysms, offering hope for a future where lives can be saved through targeted and informed medical interventions.


reference link : https://arxiv.org/pdf/2311.00652.pdf

https://www.frontiersin.org/articles/10.3389/fphys.2023.1081395/full

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