Ascending Aortic Dilatation Associated With Bicuspid Aortic Valve

Tadros, Thomas M.; Klein, Michael D.; Shapira, Oz M.

doi:10.1161/circulationaha.108.795401

Cited by 386 publications

(176 citation statements)

References 135 publications

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“…ATAA is age related and is frequently encountered in patients with hypertension, hypercholesterolemia, or diabetes mellitus 2. It is also diagnosed in young patients with genetic disorders associated with intrinsic structural abnormalities such as Marfan syndrome and bicuspid aortic valve and as a result of aortic inflammatory diseases 3, 4, 5. Much remains unknown about ATAA pathology, largely because of the wide heterogeneity underlying these abnormalities.…”

mentioning

confidence: 99%

Local Application of Leptin Antagonist Attenuates Angiotensin II–Induced Ascending Aortic Aneurysm and Cardiac Remodeling

Ben‐Zvi

Savion

Kolodgie

et al. 2016

JAHA

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BackgroundAscending thoracic aortic aneurysm (ATAA) is driven by angiotensin II (AngII) and contributes to the development of left ventricular (LV) remodeling through aortoventricular coupling. We previously showed that locally available leptin augments AngII‐induced abdominal aortic aneurysms in apolipoprotein E–deficient mice. We hypothesized that locally synthesized leptin mediates AngII‐induced ATAA.Methods and ResultsFollowing demonstration of leptin synthesis in samples of human ATAA associated with different etiologies, we modeled in situ leptin expression in apolipoprotein E–deficient mice by applying exogenous leptin on the surface of the ascending aorta. This treatment resulted in local aortic stiffening and dilation, LV hypertrophy, and thickening of aortic/mitral valve leaflets. Similar results were obtained in an AngII‐infusion ATAA mouse model. To test the dependence of AngII‐induced aortic and LV remodeling on leptin activity, a leptin antagonist was applied to the ascending aorta in AngII‐infused mice. Locally applied single low‐dose leptin antagonist moderated AngII‐induced ascending aortic dilation and protected mice from ATAA rupture. Furthermore, LV hypertrophy was attenuated and thickening of aortic valve leaflets was moderated. Last, analysis of human aortic valve stenosis leaflets revealed de novo leptin synthesis, whereas exogenous leptin stimulated proliferation and promoted mineralization of human valve interstitial cells in culture.ConclusionsAngII‐induced ATAA is mediated by locally synthesized leptin. Aortoventricular hemodynamic coupling drives LV hypertrophy and promotes early aortic valve lesions, possibly mediated by valvular in situ leptin synthesis. Clinical implementation of local leptin antagonist therapy may attenuate AngII‐induced ATAA and moderate related LV hypertrophy and pre–aortic valve stenosis lesions.Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00449306.

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mentioning

confidence: 99%

Local Application of Leptin Antagonist Attenuates Angiotensin II–Induced Ascending Aortic Aneurysm and Cardiac Remodeling

Ben‐Zvi

Savion

Kolodgie

et al. 2016

JAHA

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“…Dilatation of the aortic root is described to be relatively rare in BAV and is proposed to be the form of bicuspid aortopathy most likely to be associated with a genetic cause. 3,13,20,24,[31][32][33] The other studies reported percentages of TAA in the first-degree TAV relatives of 3-4%. 54,[65][66][67][68] This is around population risk since 2.3% of the general population, by definition, is expected to have z scores >2.…”

Section: Bicuspid Aortic Valve: Clinical and Genetic Aspectsmentioning

confidence: 95%

“…16 Dilatation of the thoracic aorta, most commonly located in the ascending aorta, has been reported in 35-80% of adult BAV patients and has rarely been observed as early as childhood. [11][12][13][14][20][21][22][23][24][25] In adults TAA is defined as an aortic diameter with a z-score of ≥2, corresponding to an observed value >1.96 standard deviations above the predicted value for age, gender, and body surface area (BSA). 26 An aortic root >4.0 cm in adults is considered to be dilated irrespective of age, gender or BSA.…”

Section: Bicuspid Aortic Valve: Clinical and Genetic Aspectsmentioning

confidence: 99%

“…This root phenotype has been proposed to be the form of bicuspid aortopathy most likely to be associated with a genetic cause. 3,13,20,24,[31][32][33] Although rare, the most feared complication in BAV patients is thoracic aortic dissection, which has been reported at young age. 34 Whereas the lifetime risk of aortic dissection in BAV patients was initially reported around 5%, recent studies show a lifetime risk of aortic dissection of less than 1% in BAV patients and a normal life expectancy.…”

Section: Bicuspid Aortic Valve: Clinical and Genetic Aspectsmentioning

confidence: 99%

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Clinical and Genetic Aspects of Bicuspid Aortic Valve: A Proposed Model for Family Screening Based on a Review of Literature

et al. 2015

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Bicuspid aortic valve (BAV) is the most common congenital cardiac defect causing serious morbidity including valvular dysfunction and thoracic aortic aneurysms (TAA) in around 30% of BAV patients. Cardiological screening of first-degree relatives is advised in recent guidelines given the observed familial clustering of BAV. However, guidelines regarding screening of family members and DNA testing are not unequivocal. The aim of this review is to provide an overview of the literature on echocardiographic screening in first-degree relatives of BAV patients and to propose a model for family screening. In addition, we provide a flowchart for DNA testing. We performed a PubMed search and included studies providing data on echocardiographic screening in asymptomatic relatives of BAV patients. Nine studies were included. In 5.8-47.4% of the families BAV was shown to be familial. Of the screened first-degree relatives 1.8-11% was found to be affected with BAV. Results regarding a potential risk of TAA in first-degree relatives with a tricuspid aortic valve (TAV) were conflicting. The reported familial clustering of BAV underlines the importance of cardiological screening in relatives. After reviewing the available family history, patient characteristics and the results of cardiological screening in relatives, follow-up in relatives with a TAV and/or DNA testing may be advised in a subset of families. In this study we propose a model for the clinical and genetic work-up in BAV families, based on the most extensive literature review on family screening performed until now.

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“…Other groups also suggest that BAV ATAA dissect and rupture at sizes comparable to non-BAV ATAAs [5,6].…”

Section: Invited Commentarymentioning

confidence: 99%

Invited Commentary

Tseng

2013

The Annals of Thoracic Surgery

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Ascending Aortic Dilatation Associated With Bicuspid Aortic Valve

Cited by 386 publications

References 135 publications

Local Application of Leptin Antagonist Attenuates Angiotensin II–Induced Ascending Aortic Aneurysm and Cardiac Remodeling

Local Application of Leptin Antagonist Attenuates Angiotensin II–Induced Ascending Aortic Aneurysm and Cardiac Remodeling

Clinical and Genetic Aspects of Bicuspid Aortic Valve: A Proposed Model for Family Screening Based on a Review of Literature

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