A coupled experimental and computational approach to quantify deleterious hemodynamics, vascular alterations, and mechanisms of long-term morbidity in response to aortic coarctation

Abstract

Introduction Coarctation of the aorta (CoA) is associated with morbidity despite treatment. Although mechanisms remain elusive, abnormal hemodynamics and vascular biomechanics are implicated. We present a novel approach that facilitates quantification of coarctation-induced mechanical alterations and their impact on vascular structure and function, without genetic or confounding factors. Methods Rabbits underwent thoracic CoA at 10 weeks of age ( ~9 human years) to induce a 20 mmHg blood pressure (BP) gradient using permanent or dissolvable suture thereby replicating untreated and corrected CoA. Computational fluid dynamics (CFD) was performed using imaging and BP data at 32 weeks to quantify velocity, strain and wall shear stress (WSS) for comparison to vascular structure and function as revealed by histology and myograph results. Results Systolic and mean BP was elevated in CoA compared to corrected and control rabbits leading to vascular thickening, disorganization and endothelial dysfunction proximally and distally. Corrected rabbits had less severe medial thickening, endothelial dysfunction, and stiffening limited to the proximal region despite 12 weeks of normal BP (~4 human years) after the suture dissolved. WSS was elevated distally for CoA rabbits, but reduced for corrected rabbits. Discussion These findings are consistent with alterations in humans. We are now poised to investigate mechanical contributions to mechanisms of morbidity in CoA using these methods.

Non-Invasive Hemodynamic Assessment of Aortic Coarctation: Validation with In Vivo Measurements

“…the geometry of the coarctation is considered to be invariant in time for the computation of the pressure drop, and the parameter values used in (12) need to be validated in a study involving more patients.…”

“…The start and end cross-sections of the coarctation were taken as the locations where the radius decreases under 95% of the reference value for the corresponding location, and respectively increases above 95% of the reference value for the corresponding location. The specific formulations of the viscous and the inertial term used in (12) were chosen because of their ability to take into account the shape of the coarctation. This allows us to…”

“…There has also been work to assess the mechanical alterations introduced by coarctation and their impact on vascular structure in rabbits 12 . The increased focus on in-vivo validation of such approaches is the first step towards transitioning them into clinical decision making.…”

Differential impact of local stiffening and narrowing on hemodynamics in repaired aortic coarctation: an FSI study

“…Inclusion of this characteristic hallmark in the numerical model is thus necessary in order to quantify the disease severity correctly. Most CoA studies [19,21,27,30,39,44] are, however, performed under a rigid wall assumption. That this oversimplification may corrupt insights and provide an incorrect diagnosis of CoA severity is illustrated by Figure 3.…”

“…Patients with (repaired) aortic coarctation might have intrinsic structural defects in extracellular matrix proteins due to genetic defects [42], and their aorta has been subjected to growth and remodeling [16,23] with adaptions in shape and material properties. In particular for the case of aortic coarctation, wall thickening is often observed along with a decrease in compliance of the proximal aorta due to prolonged hypertension [8,27]. As such, neither the 3D geometry, neither the assumed material constants in this paper can be considered representative for patients with (repaired) aortic coarctation.…”