Fully Three-Dimensional Hemodynamic Characterization of Altered Blood Flow in Bicuspid Aortic Valve Patients With Respect to Aortic Dilatation: A Finite Element Approach

Abstract

Bicuspid aortic valve (BAV) is the most common congenital heart defect (1), with an estimated prevalence between 1 and 2%, increasing in white population and men (3:1) (2). Ascending aorta (AAo) dilation is presented in approximately 50% of patients with BAV, and it is associated with the increased risk of aortic dissection, rupture, and sudden death (3, 4). The most common BAV leaflet fusion phenotypes involve the right-left cusps (BAV-RL), and right-non-coronary cups (BAV-RN), with the prevalence of around 80 and 17% (4, 5), respectively. Genetic, histological, mechanical, and hemodynamic factors related to aortopathy in patients with BAV are still poorly understood (6–9). Currently, preventive aortic surgery is indicated when the diameter of the AAo is larger than 50 [mm] in patients with any of the following risk factors: aortic coarctation, systemic hypertension, a family history of aortic dissection, or rapid aortic growth (>3–5 mm/year) in experienced hands (10). However, these indications are debatable since some aortic events occur with aortic diameters below the suggested threshold (11). Therefore, there is a need for a better understanding of the mechanisms that influence the progression of these structural changes, which may allow the development of prognostic models for risk assessment, the indication of surgical correction, and pre- and post-operative monitoring (12, 13).

Cardiovascular hemodynamic parameters quantified using 4D-flow cardiac magnetic resonance (CMR) are emerging as the essential biomarkers in the early diagnosis of cardiovascular diseases, bringing new insights about complex flows as in patients with BAV (6, 12, 14). Recent studies have provided strong evidence that altered blood flow hemodynamics and wall shear stress (WSS) in the AAo of patients with BAV are associated with histological and proteolytic changes in the aortic wall, which may induce aortic remodeling (6, 9, 15). Moreover, altered WSS has been related to aortic wall disruption (12, 15), and the separated axial (WSSA) and circumferential (WSSC) components of WSS with abnormal flow eccentricity and leaflet fusion phenotype and extent (6, 16–19). Furthermore, several other hemodynamic parameters, such as flow eccentricity, circulation, vorticity, and helicity density, have also been reported in patients with BAV. However, they have mainly been assessed in a limited number of 2D planes (14, 20) with possible unappreciation of important aspects. Some studies have shown the application of three-dimensional (3D) WSS and its association with the valvular dysfunction (21) and the elastic fiber thinning (15), but the WSS quantification has been most often limited to its magnitude, neglecting its axial and circumferential components, at least in 3D applications. Other studies have shown in 3D the relationship between the absolute local normalized helicity (22) and energy loss (23) and the aortic dilation in patients with BAV. Considering many abnormal flow descriptors proposed, it is of utmost importance to identify those deserving special attention for the follow-up of patients with BAV.

A comprehensive methodology can help to identify those parameters related to aortic dilation in patients with BAV. Previously, we have developed a seamless computational framework to obtain several 3D quantitative parameters, which have been validated in phantoms and different cohorts of patients including aortic dissection (24, 25) and transposition of the great arteries (26, 27). This study aimed to compare quantitative 3D hemodynamic parameters between healthy volunteers (HVs) and patients with BAV and their relationships with aortic dilation in clinically relevant subgroups of patients with BAV. We hypothesize that there are differences in hemodynamic parameters between clinically relevant patients with BAV subgroups (morphotypes and phenotypes), such as those with a non-dilated ascending aorta (BAV-Non-AAoD), which includes non-dilated (BAV-NonD) and root dilated (BAV-RootD), with dilation of the AAo (BAV-AAoD), BAV-RL, BAV-RN, and the group of volunteers.