Novel Approaches for BAV Aortopathy Prediction—Is There a Need for Cohort Studies and Biomarkers?

Abstract

Bicuspid aortic valve (BAV) disease is the most common congenital malformation of the human heart with a prevalence of 1–2% in the general population. More than half of patients with a BAV present with a dilated proximal aorta (so-called bicuspid aortopathy) which is associated with an enhanced risk of life-threatening aortic complications. Up to now, the pathogenesis of bicuspid aortopathy as well as the risk stratification of aortic complications has not yet been sufficiently clarified. Recent findings have shown that bicuspid aortopathy features phenotypic heterogeneity. Two distinct valvulo-aortic phenotypes, the so-called root phenotype, as well as a dilation of the tubular ascending aorta, coincide with a significantly different risk for aortal complications. However, the phenotype-based classification that is only based on these two clinical forms is not sufficient to estimate the risk of aortal complications in a prognostically relevant way. Therefore, there is growing clinical interest to assess novel approaches in BAV research and to introduce circulating biomarkers as an elegant diagnostic tool to improve risk stratification in BAV aortopathy. A large scale epidemiological cohort study, ranking from apparently healthy individuals to disease patients, and comprehensive biobanks provide the opportunity to study BAV disease and its complications and to identify novel biomarkers for BAV aortopathy surveillance and prognosis. Firstly, the data indicate that several protein-based biomarkers and non-coding RNA molecules, in particular circulating microRNAs, can serve as relevant molecular biomarkers to predict the course of BAV-associated aortopathy. Here, we review the current literature and knowledge about BAV from a clinical point of view, and report about novel approaches in BAV biomarker research.

Circulating soluble receptor of advanced glycation end product is associated with bicuspid aortic aneurysm progression via NF-κB pathway

“…It may offer a significant benefit in the stratification and monitoring of patients with small yet, fast-growing BAV aneurysm and high risk of dissection or rupture. Considering the lack of information on the risk of aortopathies from common imaging techniques, our new findings hint at exploration of sRAGE as a potential biomarker to predict the presence, progression and prognosis of BAV aneurysm that would be especially important for patients with high risk [ 28 ].…”

Epigenetic influences on genetically triggered thoracic aortic aneurysm

“…This is reflected in a more recent study in which the expression of seven miRNAs was analysed according to distinct BAV phenotypic subgroups; those with aortic root dilatation and concomitant insufficiency versus BAV with severe aortic stenosis (Girdauskas et al 2018a). Within the root dilatation subgroup, circulating miR-17 and 106a were significantly increased in the less dilated (< 50 mm) compared to severely dilated (> 50 mm) aortas; however, when compared overall to the aortic stenosis cohort, significant differences were observed in all seven miRNAs (miR-17, miR-16a, miR19a, miR-20a, miR-21, miR-106a and miR-145) (Girdauskas et al 2018b). While the lack of a control cohort in this study limits further interpretation, it is clear that there are likely different miRNA profiles associated with different BAV phenotypes, and this should be factored in to future experimental design in BAV studies.…”

Non-Coding RNAs as Blood-Based Biomarkers in Cardiovascular Disease

“…Bicuspid aortic valve disease (BAV), the most common anomaly of the human heart, results from an anomaly during valvulogenesis that is characterized by no splitting between two adjacent cusps, and it is frequently accompanied by dilation of the ascending aorta [85]. The most prominent miRNAs in adult BAV patients seem to be miR-122, miR-130a, and miR-486, and miR-718, with the latter being altered in BAV patients and inversely correlating with the diameter of the ascending aorta and, therefore, suggested as a potential biomarker of aortic dilation [86].…”