Expression Patterns of Circulating MicroRNAs in the Risk Stratification of Bicuspid Aortopathy

Objective: Aortic size-based criteria are of limited value in the prediction of aortic events, while most aortic events occur in patients with proximal aortic diameters < 50 mm. Serological biomarkers and especially circulating microRNAs (miRNAs) have been proposed as an elegant tool to improve risk stratification in patients with different aortopathies. Therefore, we aimed to evaluate the levels of circulating miRNAs in a surgical cohort of patients presenting with bicuspid aortic valve disease and distinct valvulo-aortic phenotypes. Methods: We prospectively examined a consecutive cohort of 145 patients referred for aortic valve surgery: (1) Sixty three patients (mean age 47 ± 11 years, 92% male) with bicuspid aortic valve regurgitation and root dilatation (BAV-AR), (2) thirty two patients (mean age 59 ± 11 years, 73% male) with bicuspid aortic valve stenosis (BAV-AS), and (3) fifty patients (mean age 56 ± 14 years, 55% male) with tricuspid aortic valve stenosis and normal aortic root diameters (TAV-AS) who underwent aortic valve+/-proximal aortic surgery at a single institution. MicroRNAs analysis included 11 miRNAs, all published previously in association with aortopathies. Endpoints of our study were (1) correlation between circulating miRNAs and aortic diameter and (2) comparison of circulating miRNAs in distinct valvulo-aortic phenotypes. Results: We found a significant inverse linear correlation between circulating miRNAs levels and proximal aortic diameter in the whole study cohort. The strongest correlation was found for miR-17 (r = −0.42, p < 0.001), miR-20a (r = −0.37, p < 0.001), and miR-106a (r = −0.32, p < 0.001). All miRNAs were significantly downregulated in BAV vs. TAV with normal aortic root dimensions Conclusions: Our data demonstrate a significant inverse correlation between circulating miRNAs levels and the maximal aortic diameter in BAV aortopathy. When comparing miRNAs expression patterns in BAV vs. TAV patients with normal aortic root dimensions, BAV patients showed significant downregulation of analyzed miRNAs as compared to their TAV counterparts. Further multicenter studies in larger cohorts are needed to further validate these results.

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161 * PREDICTING THE AORTOPATHY IN PATIENTS WITH BICUSPID AORTIC VALVE STENOSIS: FOCUS ON THE FUNCTIONAL ANALYSIS OF AORTIC ROOT

Interactive Cardiovascular and Thoracic Surgery ◽

10.1093/icvts/ivu276.161 ◽

2014 ◽

Vol 19 (suppl 1) ◽

pp. S49-S50

Author(s):

E. Girdauskas ◽

M. Rouman ◽

K. Disha ◽

G. Dubslaff ◽

B. Fey ◽

...

Keyword(s):

Functional Analysis ◽

Aortic Valve ◽

Bicuspid Aortic Valve ◽

Aortic Valve Stenosis ◽

Aortic Root

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Aortopathy in patients with bicuspid aortic valve stenosis: role of aortic root functional parameters

European Journal of Cardio-Thoracic Surgery ◽

10.1093/ejcts/ezv123 ◽

2015 ◽

Vol 49 (2) ◽

pp. 635-644 ◽

Cited By ~ 20

Author(s):

Evaldas Girdauskas ◽

Mina Rouman ◽

Kushtrim Disha ◽

Andres Espinoza ◽

Georg Dubslaff ◽

...

Keyword(s):

Aortic Valve ◽

Bicuspid Aortic Valve ◽

Aortic Valve Stenosis ◽

Aortic Root ◽

Functional Parameters

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Circulating microRNAs vs. aortic diameter in bicuspid aortic valve aortopathy

Asian Cardiovascular and Thoracic Annals ◽

10.1177/0218492320927233 ◽

2020 ◽

pp. 021849232092723

Author(s):

Shiho Naito ◽

Johannes Petersen ◽

Tatiana Sequeira-Gross ◽

Tanja Zeller ◽

Hermann Reichenspurner ◽

...

Keyword(s):

Aortic Valve ◽

Risk Stratification ◽

Bicuspid Aortic Valve ◽

Treatment Guidelines ◽

Aortic Disease ◽

Current Evidence ◽

Diagnostic Tools ◽

Circulating Micrornas ◽

Prediction Tools ◽

Improve Risk Stratification

There is growing clinical need and interest to implement novel risk prediction tools in bicuspid aortic valve-associated proximal aortic disease, so-called bicuspid aortic valve aortopathy. Inherent limitations of the diameter-based risk stratification for adverse aortic events in bicuspid aortic valve aortopathy patients have recently been recognized. Therefore, alternative diagnostic tools and subsequent adjustments in the treatment guidelines are urgently needed. Herein, we summarize the current evidence on recent diagnostic developments to improve risk stratification in bicuspid aortic valve aortopathy, including circulating microRNAs as biomarkers to predict the progression of aortic disease.

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Aneurysmatic aortic root in bicuspid aortic valve stenosis: mini-invasive approach with sutureless prosthesis

Monaldi Archives for Chest Disease ◽

10.4081/monaldi.2014.53 ◽

2015 ◽

Vol 82 (2) ◽

Author(s):

Francesco Pollari ◽

Giuseppe Santarpino ◽

Steffen Pfeiffer ◽

Theodor Fischlein

Keyword(s):

Aortic Valve ◽

Bicuspid Aortic Valve ◽

Aortic Valve Stenosis ◽

Coronary Sinus ◽

Aortic Root ◽

Minimal Invasive ◽

Sinus Of Valsalva ◽

Invasive Approach ◽

First Case

The implantation of sutureless bioprosthesis is currently not recommended in patients affected by bicuspid aortic valve because lacking data and follow up. We report the first case of a patient affected by bicuspid aortic valve stenosis and aneurysm of non coronary sinus of Valsalva that underwent a successful substitution of aneurysmatic sinus and minimal invasive sutureless implantation.

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Bicuspid aortic valve fusion length correlates with maximum aortic diameter and heamodynamic abnormalities: a 4D flow CMR study

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeab090.106 ◽

2021 ◽

Vol 22 (Supplement_2) ◽

Author(s):

A Guala ◽

G Teixido-Tura ◽

L Dux-Santoy ◽

A Ruiz-Munoz ◽

F Valente ◽

...

Keyword(s):

Aortic Valve ◽

Risk Stratification ◽

Aortic Arch ◽

Bicuspid Aortic Valve ◽

Ascending Aorta ◽

Aortic Diameter ◽

Aortic Blood Flow ◽

4D Flow ◽

Prospective Longitudinal ◽

Cine Cmr

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Guala A. received funding from the Spanish Ministry of Science, Innovation and Universities. Background Bicuspid aortic valve (BAV), a congenital heart defect, is associated with ascending aorta dilation, possibly via alteration of aortic blood flow [1]. In BAV abnormal flow condition have been associated with aortic extracellular matrix dysregulation and elastic fiber degeneration [2]. Current morphological classification of BAV patients with aortic valve with a single fusion between two adjacent leaflets does not allow for risk stratification. Purpose This research work tested whether the extent of fusion between leaflets is related to AAo diameter and flow alterations. Methods Ninety BAV patients free from moderate and severe aortic valve disease and with no previous aortic or aortic valve surgery or replacement were prospectively enrolled. A comprehensive magnetic resonance protocol comprised a stack of double-oblique 2D balanced steady-state free-precession (bSSFP) cine CMR of the aortic valve, which was used to measure the length of the fusion between leaflets, a cine CMR at the level of the pulmonary bifurcation to assess aortic diameter and 4D flow MRI sequence to assess flow characteristics and regional stiffness [3]. Jet angle and flow radial displacement, quantifying the extent of flow eccentricity, and systolic flow reversal ratio (SFRR), assessing the relative amount of backward flow during systole, were computed at 8 equidistant planes in the ascending aorta and 4 equidistant planes in the aortic arch [4]. A two-tailed p-value < 0.05 was considered statistically significant. Results The length of leaflet fusion varied widely (median 7.7 mm, inter-quartile range [5.5; 10.2]), Table 1). In bivariate analysis, fusion length was also associated to ascending aortic diameter (R = 0.391, p < 0.001), age (R = 0.313, p = 0.005) and body surface area (R = 0.396, p < 0.001). It was also positively related to flow abnormalities: like displacement in the proximal and distal ascending aorta, jet angle in the mid ascending aorta, and SFRR in the ascending aorta and the aortic arch (see Figure 1). The association between fusion length and ascending aorta diameter persisted in multivariate analysis after correction for age (p = 0.006). Conclusions Bicuspid aortic valve fusion extent varies greatly and it is associated with aortic diameter, possibly through flow alterations. Prospective longitudinal studies are needed to establish whether fusion length may allow for risk stratification in bicuspid aortic valve patients.

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