Bicuspid Aortic Valve (BAV) study

Motivation for the study

Currently, there is still limited data on the etiology of bicuspid aortic valve (BAV) disease. Some patients may live relatively unhindered by the valvular defect, whilst others may experience early symptoms that may sometimes even require surgery. Blood and imaging biomarkers may predict such outcome in these patients. Possibly different etiologic subtypes of BAV display measurable biologic differences that can be used to distinguish between these disease processes. These biomarkers can provide information to unravel the exact mechanism behind aortic dilatation and the progression of aortic stenosis in individual BAV patients. 
  

Goal of the study

The goal of this study is to evaluate trends in blood biomarkers and their relation with aortic root diameter, aortic valve abnormalities and left ventricular function in patients with BAV disease. Furthermore, we aim to identify and validate new potentially important blood biomarkers, which can be implemented in the clinical management of these patients. Furthermore, certain imaging biomarkers may precede clinical deterioration. Therefore we aim to establish imaging parameters associated with aortic valve dysfunction or aortic dilatation.  
  

Impact on patient care

The knowledge gained in this study will help us to individualize current treatment protocols and to derive novel therapeutic strategies. Patients at low risk of complications could be seen less frequently, and those at high risk could be seen more frequently and treated more timely if necessary.
    

Study funding

This study is funded by a grant of the Dutch Heart Foundation

Bicuspid Aortic Valve (BAV)

BAV, a heart valve with only two leaflets instead of three, is the most common congenital heart malformation. BAV may remain asymptomatic but often the valve will become dysfunctional. Additionally, aortic aneurysm , a potentially fatal dilatation of the aorta, is frequently observed in BAV patients. Historically, it was hypothesized that abnormal blood flow across the BAV led to aneurysm formation. Nowadays, the probability of genetic predisposition is more accepted. BAV has also an intriguing gender bias: BAV is three times more common in males than females. There are currently no detailed explanations for this gender difference. 
   

Turner syndrome (TS)

In this study, we will also perform specific analysis of a cohort of Turner syndrome (TS) patients. TS occurs in 50 per 100,000 live- born females. The principally clinical diagnosis rests on the coexistence of partial or complete absence of an X-chromosome with classical traits that include short stature, estrogen deficiency, and infertility. Common congenital heart defects in patients with TS include BAV (30%) and aortic coarctation (12%). Outcomes with a bicuspid aortic valve are generally favorable in childhood, with the likelihood of associated morbidity increasing with age. 
   

Advanced imaging predictors

Several potential imaging predictors of adverse outcome in BAV patients  have been hypothesized. First, it has been suggested flow patterns in the aorta can predict aortic dilatation. Second, over time outflow obstruction results in left ventricular hypertrophy and eventually contractile dysfunction. Thirdly, BAV morphology is not uniform and clinical phenotyping by echocardiography is challenging in some patients, due to limited spatial resolution, calcification artifacts and insufficient acoustic access. The ability of ECG-synchronized CT to visualize cardiovascular anatomy is unmatched by any other noninvasive imaging technique. 
   

Aortic dissection

Aortic dissection occurs in 1 or 2 of 100 females with Turner syndrome. Incidence rates are increased up to 100-fold when compared with the female background population and peak in the third to fifth decades of life. Aortic dissection has been observed as early as the first decade of life. Aortic dissection in Turner syndrome occurs in young individuals at smaller aortic diameters than in the general population or other forms of genetically triggered aortopathy. Risk stratification for aortic dissection is still inadequate due to a lack of insight into the natural course of the syndrome-associated aortopathy.

This study was funded by a grant of the Dutch Heart Foundation (The Hague, The Netherlands, grant number: 2013T093).

Radboud UMC – Nijmegen
LUMC – Leiden

1. Coronary anatomy in Turner syndrome versus patients with isolated bicuspid aortic valves – W.M.C. Koenraadt
2. Intermodality variation of aortic dimensions: How, where and when to measure the ascending aorta – L.R. Bons 
3. Aortic dilatation and outcome in women with Turner syndrome - A.L Duijnhouwer
4. Partial anomalous pulmonary venous return in Turner syndrome – A.T. van den Hoven
5. Transthoracic 3D echocardiographic left heart chamber quantification in patients with bicuspid aortic valve disease - A.T. van den Hoven
6. Adverse outcome of coarctation stenting in patients with Turner syndrome - A.T. van den Hoven

Allard van den Hoven
Lidia Bons
Toon Duijnhouwer
Annemien van den Bosch
Jolien Roos-Hesselink