Mechanisms of Aortic Dilation in Patients With Bicuspid Aortic Valve

Rodríguez-Palomares, José F.; Dux-Santoy, Lydia; Guala, Andrea; Galián-Gay, Laura; Evangelista, Arturo

doi:10.1016/j.jacc.2022.10.042

Cited by 21 publications

(6 citation statements)

References 144 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It can then be proposed that genetic factors predispose to BAV aortopathy, whereas hemodynamics determine the progression of the disease. This hypothesis agrees with the observed higher prevalence of aortic dilatation in children with valve disfunction 61,62 .…”

Section: Discussionsupporting

confidence: 91%

Unraveling the Molecular Complexity of Bicuspid Aortopathy: Lessons from Comparative Proteomics

Pozo-Vilumbrales,

Martín-Chaves,

López-Unzu

et al. 2023

Preprint

View full text Add to dashboard Cite

BackgroundMolecular markers and pathways involved in the etiology and pathophysiology of bicuspid aortopathy are poorly understood. The aim here is to delve into the molecular and cellular mechanisms of the disease and identify potential predictive molecular markers using a well-established isogenic hamster model (T-strain) of bicuspid aortic valve (BAV) and thoracic aortic dilatation (TAD).MethodsComparative quantitative proteomics combined with western blot and morpho-molecular analyses in the ascending aorta of tricuspid aortic valve (TAV) and BAV animals from the T-strain, and TAV animals from a control strain. This strategy allows discriminating between genetic and hemodynamic factors in genetically homogeneous populations.ResultsThe major molecular alteration in the aorta of genetically homogeneous BAV individuals is PI3K/AKT overactivation caused by changes in the EGF, ANGII and TGF-β pathways. PI3K/AKT affects downstream eNOS, MAP2K1/2, NF-κB, mTOR and WNT pathways. Most of these alterations are seen in independent patient studies with different clinical presentations, but not in TAV hamsters from T-strain that mainly exhibit WNT pathway downregulation.ConclusionsWe identify a combination of defective interconnected molecular pathways, directly linked to the central PI3K/AKT pathway, common to both BAV-associated TAD patients and hamsters. The defects indicate smooth muscle cell shift towards the synthetic phenotype induced by endothelial-to-mesenchymal transition, oxidative stress and inflammation. WNT signaling represent one genetic factor that may cause structural aortic abnormalities and aneurysm predisposition, whereas hemodynamics is the main trigger of molecular alterations, probably determining aortopathy progression. We identify twenty-seven novel potential biomarkers with a high predictive value.

show abstract

Section: Discussionsupporting

confidence: 91%

Unraveling the Molecular Complexity of Bicuspid Aortopathy: Lessons from Comparative Proteomics

Pozo-Vilumbrales,

Martín-Chaves,

López-Unzu

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…We, therefore, hypothesize that there is little additional effect of exercise volume in the development of valvulo‐aortopathy in patients with BAV and that it is primarily caused by a combination of the genetic and hemodynamic changes associated with BAV disease. 37 …”

Section: Discussionmentioning

confidence: 99%

Associations of Lifelong Exercise Characteristics With Valvular Function and Aortic Diameters in Patients With a Bicuspid Aortic Valve

Schreurs,

Hopman,

Bakker

et al. 2024

JAHA

View full text Add to dashboard Cite

Background The potential impact of exercise on valvular function and aortic diameters in patients with a bicuspid aortic valve remains unclear. Therefore, we assessed the association between lifelong exercise characteristics, valvular dysfunction, and aortic dilatation in patients with a bicuspid aortic valve. Methods and Results In this cross‐sectional study, exercise volume (metabolic equivalent of task minutes per week), exercise intensity, and sport type were determined from the age of 12 years to participation using a validated questionnaire. Echocardiography was used to assess aortic stenosis or aortic regurgitation and to measure diameters at the sinuses of Valsalva and ascending aorta. Aortic dilatation was defined as a Z ‐score ≥2. Four hundred and seven patients (42±17 years, 60% men) were included, of which 133 were sedentary (<500 metabolic equivalent of task minutes per week), 94 active (500–1000 metabolic equivalent of task minutes per week), and 180 highly active (≥1000 metabolic equivalent of task minutes per week). Moderate‐to‐severe aortic stenosis or aortic regurgitation was present in 23.7% and 20.0%, respectively. Sinuses of Valsalva and ascending aorta diameters were 34.8±6.6 and 36.5±8.1 mm, whereas aortic dilatation was found in 21.6% and 53.4%, respectively. Exercise volume was not associated with valve dysfunction or aortic dilatation. Vigorous intensity and mixed sports were associated with a lower prevalence of aortic stenosis (adjusted odds ratios, 0.43 [0.20–0.94] and adjusted odds ratios, 0.47 [0.23–0.95]). Exercise intensity and sport type were not associated with aortic regurgitation and aortic dilatation. Conclusions We found no deleterious associations between lifelong exercise characteristics, valvular dysfunction, and aortic dilatation in patients with a bicuspid aortic valve. Vigorous intensity and exercise in mixed sports were associated with a lower prevalence of moderate‐to‐severe aortic stenosis. These observations suggest that lifelong exercise does not appear to induce adverse cardiovascular effects in patients with a bicuspid aortic valve.

show abstract

“…However, limited data exist regarding the degree of aortic dilation in BAV patients that would warrant concurrent ascending aortic replacement during SAVR. Several studies have explored the risk of progressive aortic dilation and dissection following SAVR in BAV patients, but definitive conclusions are lacking (2)(3)(4).…”

Section: Discussionmentioning

confidence: 99%

Case report: Unveiling the unforeseen: a catastrophic encounter of giant aortic aneurysm rupture during re-sternotomy in a patient with bicuspid aortic valve and previous surgical aortic valve replacement

Niu,

Liu,

Gong

et al. 2023

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Due to structural abnormalities in the leaflets, patients with bicuspid aortic valve (BAV) may develop isolated aortic valve disease, such as aortic regurgitation, aortic stenosis, or a combination of both. In addition to valvular pathology, numerous studies have indicated that approximately 40% of BAV patients exhibit aortic pathologies characterized by aortic dilatation. According to guidelines for valvular diseases, patients with BAV who require surgical aortic valve replacement (SAVR) and have a diameter of the aortic sinuses or ascending aorta ≥4.5 cm are recommended to undergo concomitant replacement of the aortic sinuses or ascending aorta. However, we encountered a case in 2020 involving a patient with severe aortic regurgitation due to BAV and an ascending aortic diameter of 4.2 cm. This patient underwent SAVR and ascending aortoplasty surgery at our center. Remarkably, three years postoperatively, the patient's aortic diameter rapidly expanded by nearly threefold, which also suggests the risk of encountering a giant aortic root aneurysm during reoperation. Unfortunately, a fatal rupture of a giant aortic root aneurysm was encountered during re-sternotomy. Fortunately, with adequate preoperative planning, we successfully managed to avert this perilous situation. The patient recovered without complications and was discharged on the 8th day. Individualized surgical plans were formulated based on a comprehensive evaluation of the perioperative conditions.

show abstract

Mechanisms of Aortic Dilation in Patients With Bicuspid Aortic Valve

Cited by 21 publications

References 144 publications

Unraveling the Molecular Complexity of Bicuspid Aortopathy: Lessons from Comparative Proteomics

Unraveling the Molecular Complexity of Bicuspid Aortopathy: Lessons from Comparative Proteomics

Associations of Lifelong Exercise Characteristics With Valvular Function and Aortic Diameters in Patients With a Bicuspid Aortic Valve

Case report: Unveiling the unforeseen: a catastrophic encounter of giant aortic aneurysm rupture during re-sternotomy in a patient with bicuspid aortic valve and previous surgical aortic valve replacement

Contact Info

Product

Resources

About