Understanding, Hemodynamics of BAV-Associated Aortopathy.

Dr. Zayed | Published : 16, April 2025.

Bicuspid aortic valve (BAV) is the most common congenital cardiac malformation, with a prevalence of 0.5–2% in the general population. It is characterized by the presence of only two functional cusps instead of the usual three in the aortic valve. Despite its relatively high occurrence, BAV exhibits striking heterogeneity in clinical presentation, disease progression, and complications, ranging from isolated valvular dysfunction to complex aortopathy involving dilation, aneurysm formation, and dissection.

The pathogenesis of BAV-associated aortopathy is multifactorial, involving both genetic predispositions and aberrant hemodynamic forces. Notably, altered Wall Shear Stress (WSS), eccentric and helical flow patterns, and increased energy turbulence arising from the malformed valve contribute to progressive structural changes in the ascending aorta. These biomechanical forces induce focal degeneration of the aortic wall, predisposing to aneurysm formation and, in certain cases, acute aortic dissection. This blog will summarize the key mechanisms underpinning BAV and its complications, with an emphasis on emerging genetic and hemodynamic insights.

BAV is inherited in an autosomal dominant pattern with reduced penetrance and variable expressivity, often presenting without syndromic features. Although no single gene explains the majority of cases, NOTCH1 was the first gene identified in familial, non-syndromic BAV, accounting for approximately 4% of cases. Mutations in GATA4, GATA5, GATA6, and ROBO4 have also been implicated in valvulogenesis, with ROBO4 particularly noteworthy for its dual association with both valve malformation and aortic aneurysm formation. 

Importantly, the genetic landscape of BAV-associated aortopathy appears to partially overlap but remain distinct from that of syndromic aortic diseases such as Marfan and Loeys-Dietz syndromes. Rare variants in FBN1, ACTA2, TGFBR1/2, and SMAD6 have been identified in select BAV cohorts, yet genotype-phenotype correlations remain elusive, suggesting a polygenic and multifactorial etiology. Despite ongoing advances in genomics, the molecular underpinnings of BAV and its associated aortic pathology remain incompletely enigmatic.

Establishing a definitive link between BAV and aortic dissection is inherently challenging due to two factors: (1) the ambiguous temporal relationship between aneurysm formation and dissection, and (2) heterogeneity in reported dissection incidence rates. A seminal retrospective study by Michelena et al. (n=416) reported a low dissection rate of 3 cases per 100,000 patient-years, which, while modest, remains '8 times higher' than in the general population. Conversely, Tzemos et al. reported a dissection incidence of 0.1% per patient-year, with the majority of events occurring in individuals with pre-existing aortic dilation.

Notably, the risk of dissection increases exponentially once the ascending aorta exceeds 45 mm, highlighting the predictive value of aortic diameter as a clinical threshold. Moreover, BAV patients remain susceptible to aortic complications even after successful aortic valve replacement (AVR). Studies suggest a 1% dissection risk over 15 years post-AVR, with continued aneurysmal progression uniquely observed in BAV, as opposed to tricuspid aortic valve (TAV) patients. This underscores the concept that "valvulopathy-associated aortopathy" in BAV is not entirely resolved by valve replacement and likely involves intrinsic aortic wall pathology.

With the advent of 4D flow magnetic resonance imaging (MRI), the intricate relationship between valve morphology and aortic wall stress can now be visualized in vivo. Wall shear stress (WSS), defined as the tangential force exerted by blood flow on the vascular endothelium, plays a central role in mechanotransduction and vascular remodeling. In BAV patients, aberrant leaflet fusion alters the trajectory of blood flow, generating eccentric flow jets, helical vortices, and turbulent energy propagation, all of which disrupt the normal WSS distribution.

These hemodynamic alterations are highly fusion-pattern dependent:

• Patients with 'right-left coronary cusp' fusion exhibit right-handed helical flow and anterolaterally directed jets, leading to focal WSS elevation in the proximal ascending aorta.

• Conversely, those with 'right coronary-non coronary cusp' fusion demonstrate left-handed helical flow and posteriorly directed jets, affecting posterior aortic segments.

Over time, these WSS abnormalities contribute to site-specific degeneration of the aortic media, promoting aneurysmal dilation in anatomically predictable zones. This reinforces the paradigm that BAV-associated aortopathy is a hemodynamically driven process superimposed on a genetically primed substrate.

From a clinical management standpoint, beta-blockers have been proposed as a first-line pharmacological intervention to mitigate aortic wall stress in BAV patients. By reducing systolic blood pressure and heart rate, these agents diminish pulsatile energy transmission and lower WSS, potentially slowing the rate of aneurysm progression. However, their efficacy remains incompletely validated in randomized trials, and ongoing studies aim to delineate which patient subgroups derive the most benefit.

Surgical intervention is generally recommended when the ascending aorta reaches ≥50 mm in asymptomatic patients, or earlier in those with rapid growth (>3 mm/year), family history of dissection, or concomitant valve dysfunction.

Interesting to Know: While BAV is classically associated with aortic stenosis, it more frequently predisposes to aortic regurgitation (AR) in younger individuals. The asymmetric cusp morphology results in malcoaptation during diastole, often due to fibrosis, cusp prolapse, or eccentric jet flow. Furthermore, dilation of the aortic root or ascending aorta, commonly seen in BAV, causes annular enlargement, exacerbating leaflet separation and regurgitation. These anatomical and flow-related abnormalities collectively lead to diastolic backflow of blood into the left ventricle, imposing a chronic volume overload and eventually precipitating left ventricular dilatation and dysfunction if left untreated.

KEYWORDS: BAV, AORTOPATHY, AORTIC CUSP MORPHOLOGY, A.DISSECTION.

REFERENCES: 

1. Michelena HI et al., Circulation, 2011 – Retrospective cohort study showing a dissection rate of 3 per 100,000 patient-years in BAV patients.

2. Tzemos N et al., New England Journal of Medicine, 2008 – Found a higher incidence of dissection (0.1% per patient-year), especially in patients with pre-existing aortic dilation.

3. Michelena HI et al., Circulation, 2011 – Also highlighted increased dissection risk with aortic diameter ≥45 mm.

4. Benedik J et al., European Journal of Cardio-Thoracic Surgery, 2017 – Reported a 1% incidence of dissection 15 years after aortic valve replacement in BAV patients.

5. Della Corte A et al., Journal of Thoracic and Cardiovascular Surgery, 2007 – Described continued aneurysm development in BAV patients post-valve replacement, unlike in TAV.