The extreme compartmentalization applied to cardiovascular pathology often causes a loss of perspective. At times, it can give the impression that the heart’s role is merely to pump into a void. Consequently, circulatory pathology is frequently limited to the aortic root, disregarding essential aspects of major vessels, peripheral arteries, pulmonary vessels, microvasculature, lymphatic vessels, and the superficial and deep venous networks, all of which are integral to blood circulation.

This limited perspective has led to the aorta being regarded less as a blood vessel and more as a mere conduit, with its pathology often reduced to simplistic measures of diameter in cross-sectional cuts, much like a sausage. While increasing diameters do correlate with a heightened risk of acute events across all levels of the aorta and major vessels. Salmasi et al. propose a review not aimed at comprehensive updates but as an impetus to generate evidence focused on the functional analysis of aortic pathology.

The authors effectively delineate aortic pathology, wisely interrelating often independently managed concepts. For instance, aortic diameter remains the primary basis for surgical indication and a major predictor of acute aortic events. However, half of all acute aortic events occur in aortas with diameters below the surgical threshold, a fact possibly explained by two additional factors: parietal degeneration and genetic predisposition. In terms of degeneration, the breakdown of medial collagen layers can lead to wall failure, both chronically through inverse remodeling (aneurysmal pathology) and acutely (acute aortic syndrome). For aneurysms, parietal stress is exacerbated by Laplace’s overpressure. However, unlike hydrostatic (arterial) pressure, this does not act symmetrically across the vessel due to variations in curvature along a non-cylindrical section. Parietal degeneration may also be genetically predisposed. While various syndromes and implicated genes have been described recently, over 80% of acute aortic events occur sporadically, in patients with no known genetic mutations, which suggests that current knowledge is likely incomplete.

Given this pathophysiological disconnect between the three phenomena, a unifying principle is required. The key lies in flow. Multiple studies of aortic flow have revealed greater medial degeneration in areas with elevated wall stress, leading to weakened zones prone to inverse remodeling (dilation) or structural failure (acute aortic syndrome). Genetics, as currently understood, plays a predisposing role in these degenerative processes, based on the balance between metalloproteinase-mediated resorption and fibroblastic activity for collagen quality and quantity in the aortic wall layers. In other words, aortic pathology shares more similarities with osteoporosis/osteopenia than with other vascular pathologies like atherosclerosis. While atherosclerosis is primarily endothelial, in its advanced stages, it extends into the media layer, becoming intertwined with these degenerative processes of the aortic wall.

From a clinical perspective, two primary methods assess aortic flow: 4D-flow magnetic resonance imaging and angiographic flow simulation, the latter also applied to coronary flow assessment. Despite limited literature on the subject, the authors synthesize valuable insights into aortic physiology, elucidating the mechanisms by which pathology manifests:

1. Wall stress is highest in the descending aorta, followed by the ascending aorta and aortic arch, corresponding to the prevalence and incidence of both chronic and acute aortic pathology. Wall stress also decreases from proximal to distal in the descending aorta, explaining the greater frequency of thoracic than abdominal aortic dissection and the higher incidence of types I and II thoracoabdominal aneurysms, per Crawford’s classification.
2. In healthy volunteers, peak wall stress occurs on the anterior aspect of the ascending aorta, with lower-stress regions at the proximal curvature of the lesser curvature and distal curvature of the greater curvature at the arch’s entry. This flow pattern correlates with the site of type A aortic dissection flap origin and, in bicuspid aortic valves, with various dilation patterns depending on commissural fusion/orientation.
3. Aneurysms exhibit reduced wall stress compared to healthy aortas. As such, wall stress increases as diameter decreases. However, rather than a protective mechanism against progression, the role of Laplace’s overpressure likely becomes more significant as diameter increases.
4. Aneurysmal aortas experience prolonged stress during the cardiac cycle, with a lower systolic-to-diastolic stress ratio due to delayed peak systolic stress, implying prolonged pressurization and reduced diastolic relaxation.
5. In Marfan syndrome patients, flow patterns tend to be particularly eccentric, even in the absence of aneurysmal and/or valvular pathology, due to potential misalignment of the outflow tract associated with the genetic defect. This generates elevated wall stress on the proximal curvature of the lesser curve and distal curvature of the greater curve, which may accelerate parietal degeneration in the aortic arch and sinotubular junction. Potentially explaining the increased pathology prevalence in these areas compared to unaffected individuals.

Despite these advances, flow models still treat the aorta as a rigid structure, potentially overestimating wall stress, particularly in the ascending aorta. Emerging models that incorporate fluid-structure interaction offer a more realistic perspective. However, the descending portion still exhibits a stiffer interaction, aligning with a higher prevalence of pathology in that region.

The authors conclude that understanding aortic flow’s impact on the wall is critical for identifying cases at risk of adverse events. A multimodal clinical approach—considering predisposing factors, clinical aspects (age, blood pressure control, atherosclerotic load), radiological imaging (including diameters), functional aspects, and biomarkers—will better predict aneurysmal pathology progression and acute syndrome onset. This marks a new frontier in 21st-century aortic pathology, potentially revolutionizing an area still grounded in 19th-century principles.

COMMENTARY:

This article offers an inspirational rather than in-depth review, serving as a non-systematic literature survey on the primary findings from functional aortic flow analysis using non-invasive (4D-flow MRI) and invasive (angiographic flow analysis) tests as a primary prevention strategy for aortic degenerative and/or acute complications. Although pioneering, Evangelista’s work over a decade ago emphasized the need for functional flow analysis, particularly using transesophageal echography, for secondary prevention in patients with residual dissection post type A repair or type B dissections in the descending aorta.

Aortic pathology deserves a shift in approach, likely to be achieved in improved methods of flow analysis. Until then, what has sometimes been an uncharted territory has at other times attracted many stakeholders (cardiovascular surgery, vascular surgery, interventional radiology, and even interventional cardiology). It is evident that aortic pathology demands better study, monitoring, and management. It is clear that diameter assessment is obsolete, and cardiovascular surgery should take a leading role in this paradigm shift, both therapeutically (as it offers the full range of therapeutic options suited to aortic pathology anatomy) and diagnostically and in follow-up.

REFERENCE
Salmasi MY, Pirola S, Asimakopoulos G, Nienaber C, Athanasiou T. Aortic Mechanobiology Working Group. Risk prediction for thoracic aortic dissection: Is it time to go with the flow? J Thorac Cardiovasc Surg. 2023 Oct;166(4):1034-1042. doi: 10.1016/j.jtcvs.2022.05.016.