Hemodynamic Assessment in Bicuspid Aortic Valve Disease and Aortic Dilation: New Insights From Voxel-By-Voxel Analysis of Reverse Flow, Stasis, and Energetics

Abstract

Objectives: Clinical management decisions surrounding ascending aorta (AAo) dilation in bicuspid aortic valve (BAV) disease benefit from personalized predictive tools. 4D-flow MRI may provide patient-specific markers reflective of BAV-associated aortopathy. This study aims to explore novel 4D-flow MRI parametric voxel-by-voxel forward flow, reverse flow, kinetic energy and stasis in BAV disease. We hypothesize that novel parametric voxel-by-voxel markers will be associated with aortic dilation and referral for surgery and can enhance our understanding of BAV hemodynamics beyond standard metrics.Methods: A total of 96 subjects (73 BAV patients, 23 healthy controls) underwent MRI scan. Healthy controls had no known cardiovascular disease. Patients were clinically referred for AAo dilation assessment. Indexed diameters were obtained by dividing the aortic diameter by the patient’s body surface area. Patients were followed for the occurrence of aortic surgery. 4D-flow analysis was performed by a single observer in five regions: left ventricular outflow tract (LVOT), AAo, arch, proximal descending aorta (PDAo), and distal descending aorta (DDAo). In each region peak velocity, kinetic energy (KE), forward flow (FF), reverse flow (RF), and stasis were measured on a voxel-by-voxel basis. T-tests (or non-parametric equivalent) compared flow parameters between cohorts. Univariate and multivariate analyses explored associations between diameter and parametric voxel-by-voxel parameters.Results: Compared to controls, BAV patients showed reduced stasis (p < 0.01) and increased RF and FF (p < 0.01) throughout the aorta, and KE remained similar. In the AAo, indexed diameter correlated with age (R = 0.326, p = 0.01), FF (R = −0.648, p < 0.001), RF (R = −0.441, p < 0.001), and stasis (R = −0.288, p < 0.05). In multivariate analysis, FF showed a significant inverse association with AAo indexed diameter, independent of age. During a median 179 ± 180 days of follow-up, 23 patients (32%) required aortic surgery. Compared to patients not requiring surgery, they showed increased KE and peak velocity in the proximal aorta (p < 0.01), accompanied by increased RF and reduced stasis throughout the entire aorta (p < 0.01).Conclusion: Novel voxel-by-voxel reverse flow and stasis were altered in BAV patients and are associated with aortic dilation and surgical treatment.

Systolic reverse flow derived from 4D flow cardiovascular magnetic resonance in bicuspid aortic valve is associated with aortic dilation and aortic valve stenosis: a cross sectional study in 655 subjects

“…Voxel-wise reverse flow maps captured this localized BAV mediated flow disturbance in systole and diastole, even in the absence of AS and AR. This is congruence with a prior study [ 23 ], finding increased reverse flow over the whole cardiac cycle in a heterogenous cohort of BAV patients.…”

“…These include non-standardized and complex techniques, noise and error propagation, and sensitivity to aorta wall motion, segmentation and spatial resolution [ 16 , 21 , 22 ]. A prior study found that 4D flow derived reverse flow, a direct, simple measure, was increased in BAV patients and that those patients requiring surgical intervention had significantly increased reverse flow compared to those not requiring intervention [ 23 ]. However, the analysis required substantial manual interaction.…”

Bicuspid aortic valve associated aortopathy: 2022 guideline update

“…Over the past few years, there has been a wealth of data suggesting that altered haemodynamics and valve related rheological changes may be an important basis of BAV aortopathy [3,4,7,[21][22][23][24][25][26][27]29,[33][34][35][36][37][38][39]. Indeed, even a normal functioning BAV valve without stenosis or insufficiency is associated with changes in flow patterns across the valve.…”

Clinical implications of the biomechanics of bicuspid aortic valve and bicuspid aortopathy

“…Collectively, the diversity in BAV and bicuspid aortopathy complicates management as interventions must coincide with risk of developing aortic complications, which is challenging to determine in a clinically heterogenous population. Ideally, noninvasive biomarkers that have high prognostic sensitivity and specificity should be established to accurately predict the natural course of BAV-associated complications (70). Such biomarkers, which do not require invasive approaches to obtain them, can then be used to intervene on the appropriate patient at the most optimal time to prevent serious complications (71-73).…”

“…An increase in loss of both pressure and energy are known to be related to abnormal helical flow and aortic dilatation in BAV patients (Figure 3) (74,78). BAV also causes increased reverse flow and reduced stasis of blood (70). Finally, regions of high WSS also contain decreased endothelial nitric oxide synthase (eNOS) expression in non-dilated BAV, suggesting that alterations in eNOS expression occur independent of aberrant hemodynamics in BAV and may have a genetic etiology (115).…”