Perspective:

This two-part opinion/review discusses current understanding of bicuspid aortic valve with what the authors term as barriers hampering the advancement of science, and a proposed roadmap to discovery based on imaging, molecular biology, and genetic tools. The following are 10 points to remember:

1. Bicuspid aortic valve has a heterogeneous presentation, ranging from murmur or an incidental finding on echocardiography to severe valve dysfunction, congestive heart failure, and thoracic aortic aneurysm.

2. Bicuspid aortic valve should be considered to be a valvuloaortopathy, with risk of both valve dysfunction and aortic aneurysm. A majority of patients with bicuspid aortic valve and aortic aneurysm exhibit enlargement of the tubular ascending aorta, with involvement of the aortic root (sinuses of Valsalva) and arch in fewer patients. (The aortopathy associated with bicuspid valve was recently well summarized [see Verma S, et al. N Engl J Med 2014;370:1920-9]).

3. Bicuspid aortic valve can be associated with other cardiovascular abnormalities, including aortic coarctation, Shone complex, and ventricular septal defect.

4. There is evidence that bicuspid aortic valve is inherited in an autosomal dominant pattern with variable expression and incomplete penetrance of families. The authors question whether bicuspid aortic valve could be a byproduct of a more widespread genetic alteration of the aorta and cardiac structures, such that the bicuspid valve is an ‘innocent bystander.’

5. Knowledge of the natural history of bicuspid aortic valve comes from population-based and tertiary-referral-based retrospective studies, with the inevitable exclusion of people with undiagnosed bicuspid aortic valve. With that limitation, the 25-year outcome of a general population of patients with bicuspid aortic valve following echocardiographic diagnosis is not different from the general population.

6. The authors discuss whether bicuspid aortic valve is a ‘victim of parsimony.’ That is, the authors note that bicuspid valve-related aortopathy is assumed to be clinically equivalent to the aortopathy of Marfan syndrome; but point out that, despite pathological similarities between the two aortopathies, they do not have clinically equivalent implications.

7. The authors discuss whether bicuspid valve is a ‘victim of compartmentalization.’ That is, the authors suggest that a failure to recognize the heterogeneity of clinical outcomes associated with bicuspid aortic valve has made the condition a casualty of efforts to explain its complications from oversimplified and rigid viewpoints.

8. The authors summarize the current clinical approach to the adult patient with bicuspid aortic valve. This includes:

1. Echocardiographic screening of first-degree relatives for bicuspid valve and for aortopathy.
   
   
2. Echocardiographic or computed tomography (CT) exclusion of aortic coarctation.
   
   
3. Echocardiographic monitoring of bicuspid aortic valve according to current guidelines.
   
   
4. Appropriate dental hygiene for infective endocarditis prophylaxis.
   
   
5. Surgical intervention for bicuspid aortic valve following current guidelines.
   
   
6. CT or magnetic resonance imaging (MRI) assessment of the aorta if it is ≥40 mm on echocardiography.
   
   
7. Aggressive treatment of hypertension, and tobacco cessation, among patients with bicuspid valve aortopathy.
   
   
8. Surgical aortic intervention for aorta diameter >55 mm (without family history of aortic dissection), ≥45 mm at the time of aortic valve replacement, or for aortic growth ≥5 mm/year.
   
   
9. Genetic consultation for selected patients with aortic dilation and family history of thoracic aortic disease.
   
   
10. Screening every 3-5 years for bicuspid valve with neither valve dysfunction nor aortopathy.
    
    
11. Screening of the aortic arch and descending thoracic aorta every 3-5 years after ascending aorta repair.
    

9. The authors discuss that parsimony, compartmentalization, and more importantly a lack of data are responsible for current controversies surrounding the indication and timing of elective intervention for bicuspid aortopathy. The authors call for a collaborative multicenter retrospective and prospective bicuspid aortic valve patient registry with homogeneous and rigorous entry criteria.

10. The authors discuss that advancing the science on understanding bicuspid aortic valve and bicuspid aortopathy requires cardiac imaging (including echocardiography/Doppler, CT, and MRI), and research involving pathobiology and genetics.