Characteristic Morphologies of the Bicuspid Aortic Valve in Patients with Genetic Syndromes

Published on Nov 28, 2017in Journal of The American Society of Echocardiography5.508
· DOI :10.1016/J.ECHO.2017.10.008
Talha Niaz8
Estimated H-index: 8
(Mayo Clinic),
Joseph T. Poterucha18
Estimated H-index: 18
(Mayo Clinic)
+ 6 AuthorsDonald J. Hagler88
Estimated H-index: 88
(Mayo Clinic)
Sources
Abstract
Background In patients with bicuspid aortic valve (BAV), complications including progressive aortic stenosis and aortic dilatation develop over time. The morphology of cusp fusion is one of the determinants of the type and severity of these complications. We present the association of morphology of cusp fusion in BAV patients with distinctive genetic syndromes. Methods The Mayo Clinic echocardiography database was retrospectively reviewed to identify patients (age ≤ 22 years) diagnosed with BAV from 1990 to 2016. Cusp fusion morphology was determined from the echocardiographic studies, while coexisting cardiac defects and genetic syndromes were determined from chart review. Results A total of 1,037 patients with BAV were identified: 550 (53%) had an isolated BAV, 299 (29%) had BAV and a coexisting congenital heart defect, and 188 (18%) had BAV and a coexisting genetic syndrome or disorder. There were no differences in distribution of morphology across the three groups. However, right-noncoronary (RN) cusp fusion was the predominant morphology associated with Down syndrome ( P  = .002) and right-left (RL) cusp fusion was the predominant morphology associated with Turner syndrome ( P  = .02), DiGeorge syndrome ( P  = .02), and Shone syndrome ( P  = .0007), when compared with valve morphology in patients with isolated BAV. Isolated BAV patients with RN cusp fusion had larger ascending aorta diameter ( P  = .001) and higher number of patients with ≥ moderate aortic regurgitation ( P  = .02), while those with RL cusp fusion had larger sinus of Valsalva diameter ( P  = .0006). Conclusions Morphological subtypes of BAV are associated with different genetic syndromes, suggesting distinct perturbations of developmental pathways in aortic valve malformation.
📖 Papers frequently viewed together
845 Citations
16 Citations
References28
Newest
#1Bo Yang (UM: University of Michigan)H-Index: 24
#1Bo Yang (UM: University of Michigan)
Last. Cristen J. Willer (UM: University of Michigan)H-Index: 78
view all 44 authors...
Bicuspid aortic valve (BAV) is a heritable congenital heart defect and an important risk factor for valvulopathy and aortopathy. Here we report a genome-wide association scan of 466 BAV cases and 4,660 age, sex and ethnicity-matched controls with replication in up to 1,326 cases and 8,103 controls. We identify association with a noncoding variant 151 kb from the gene encoding the cardiac-specific transcription factor, GATA4, and near-significance for p.Ser377Gly in GATA4. GATA4 was interrupted b...
53 CitationsSource
#1Talha Niaz (Mayo Clinic)H-Index: 8
#2Joseph T. Poterucha (Mayo Clinic)H-Index: 18
Last. Donald J. Hagler (Mayo Clinic)H-Index: 88
view all 8 authors...
Background Bicuspid aortic valve (BAV) occurs both as an isolated cardiac lesion and in association with congenital heart defects (CHD). Their aim was to identify the incidence and morphology of BAV in patients with coexisting CHD and compare their disease progression to patients with isolated BAV. Methods The Mayo Clinic echocardiography database was retrospectively analyzed to identify pediatric and young adult patients (≤22 years) who were diagnosed with BAV from 1990 to 2015. The morphology ...
16 CitationsSource
#1Samantha L. Freeze (IU: Indiana University)H-Index: 4
#2Benjamin J. Landis (IU: Indiana University)H-Index: 8
Last. Benjamin M. Helm (IU: Indiana University)H-Index: 7
view all 4 authors...
Bicuspid aortic valve (BAV) is the most common congenital heart defect and falls in the spectrum of left-sided heart defects, also known as left ventricular outflow tract obstructive (LVOTO) defects. BAV is often identified in otherwise healthy, asymptomatic individuals, but it is associated with serious long term health risks including progressive aortic valve disease (stenosis or regurgitation) and thoracic aortic aneurysm and dissection. BAV and other LVOTO defects have high heritability. Alt...
25 CitationsSource
#1Peter S. Martin (Brigham and Women's Hospital)H-Index: 2
#2Benjamin Kloesel (Brigham and Women's Hospital)H-Index: 6
Last. Simon C. Body (Brigham and Women's Hospital)H-Index: 51
view all 6 authors...
Bicuspid aortic valve (BAV) is the most common congenital valvular heart defect with an overall frequency of 0.5%–1.2%. BAVs result from abnormal aortic cusp formation during valvulogenesis, whereby adjacent cusps fuse into a single large cusp resulting in two, instead of the normal three, aortic cusps. Individuals with BAV are at increased risk for ascending aortic disease, aortic stenosis and coarctation of the aorta. The frequent occurrence of BAV and its anatomically discrete but frequent co...
33 CitationsSource
#1Subodh Verma (London Health Sciences Centre)H-Index: 1
#1Subodh Verma (London Health Sciences Centre)H-Index: 95
Last. Samuel C. SiuH-Index: 2
view all 2 authors...
Bicuspid aortic valve is the most common congenital heart defect in adults. Dilatation of the proximal aorta, or bicuspid aortopathy, is present in approximately half these patients and can lead to complications, including aneurysm formation and aortic dissection.
270 CitationsSource
#1Elizabeth M. Bonachea (OSU: Ohio State University)H-Index: 3
#2Sheng-Wei Chang (Nationwide Children's Hospital)H-Index: 5
Last. Vidu GargH-Index: 33
view all 7 authors...
Bicuspid aortic valve (BAV) is the most common type of congenital heart disease (CHD) and has a proposed genetic etiology. BAV is categorized by cusp fusion, with right-left (R-L) cusp fusion being associated with additional CHD, and right-noncoronary cusp (R-NC) fusion being associated with aortic valve dysfunction. Loss of murine Gata5, which encodes a cardiac transcription factor, results in a partially penetrant R-NC BAV, and we hypothesize that mutations in GATA5 are associated with R-NC BA...
52 CitationsSource
#1Riti Mahadevia (NU: Northwestern University)H-Index: 6
#2Alex J. Barker (NU: Northwestern University)H-Index: 42
Last. Michael Markl (NU: Northwestern University)H-Index: 83
view all 11 authors...
Background—Aortic 3-dimensional blood flow was analyzed to investigate altered ascending aorta (AAo) hemodynamics in bicuspid aortic valve (BAV) patients and its association with differences in cusp fusion patterns (right-left, RL versus right-noncoronary, RN) and expression of aortopathy. Methods and Results—Four-dimensional flow MRI measured in vivo 3-dimensional blood flow in the aorta of 75 subjects: BAV patients with aortic dilatation stratified by leaflet fusion pattern (n=15 RL-BAV, mid A...
243 CitationsSource
#1Laura Olivieri (NIH: National Institutes of Health)H-Index: 13
#1Laura J. Olivieri (NIH: National Institutes of Health)H-Index: 9
Last. Carolyn A. Bondy (NIH: National Institutes of Health)H-Index: 88
view all 8 authors...
Background— Congenital aortic valve fusion is associated with aortic dilation, aneurysm, and rupture in girls and women with Turner syndrome. Our objective was to characterize aortic valve structure in subjects with Turner syndrome and to determine the prevalence of aortic dilation and valve dysfunction associated with different types of aortic valves. Methods and Results— The aortic valve and thoracic aorta were characterized by cardiovascular MRI in 208 subjects with Turner syndrome in an inst...
34 CitationsSource
#1Carolyn A. Bondy (NIH: National Institutes of Health)H-Index: 88
#2Vladimir K. Bakalov (NIH: National Institutes of Health)H-Index: 28
Last. Andrew E. Arai (NIH: National Institutes of Health)H-Index: 80
view all 6 authors...
Background Congenital heart disease (CHD) is a cardinal feature of X chromosome monosomy, or Turner syndrome (TS). Haploinsufficiency for gene(s) located on Xp have been implicated in the short stature characteristic of the syndrome, but the chromosomal region related to the CHD phenotype has not been established. Design We used cardiac MRI to diagnose cardiovascular abnormalities in four non-mosaic karyotype groups based on 50-metaphase analyses: 45,X (n=152); 46,X,del(Xp) (n=15); 46,X,del(Xq) ...
55 CitationsSource
#1Christine Ackerman (OHSU: Oregon Health & Science University)H-Index: 1
#2Adam E. Locke (Emory University)H-Index: 30
Last. Cheryl L. Maslen (OHSU: Oregon Health & Science University)H-Index: 26
view all 13 authors...
About half of people with trisomy 21 have a congenital heart defect (CHD), whereas the remainder have a structurally normal heart, demonstrating that trisomy 21 is a significant risk factor but is not causal for abnormal heart development. Atrioventricular septal defects (AVSD) are the most commonly occurring heart defects in Down syndrome (DS), and ∼65% of all AVSD is associated with DS. We used a candidate-gene approach among individuals with DS and complete AVSD (cases = 141) and DS with no C...
78 CitationsSource
Cited By11
Newest
#1Yidong Wang (Xi'an Jiaotong University)
#2Yuan Fang (Xi'an Jiaotong University)
Last. Bin Zhou (Albert Einstein College of Medicine)H-Index: 78
view all 0 authors...
NOTCH intercellular signaling mediates the communications between adjacent cells involved in multiple biological processes essential for tissue morphogenesis and homeostasis. The NOTCH1 mutations are the first identified human genetic variants that cause congenital bicuspid aortic valve (BAV) and calcific aortic valve disease (CAVD). Genetic variants affecting other genes in the NOTCH signaling pathway may also contribute to the development of BAV and the pathogenesis of CAVD. While CAVD occurs ...
Source
#1Saarwaani Vallabhajosyula (Mayo Clinic)H-Index: 13
#2Margaret Fuchs (Cleveland Clinic)
Last. Hector I. Michelena (Mayo Clinic)H-Index: 47
view all 0 authors...
Objective null To compare the prevalence and patterns of anomalous coronary artery origin from the opposite sinus (ACAOS) in patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV). null Methods null Retrospective review of consecutive patients with surgically excised BAV and TAV was performed from 1994 to 2015. Clinical notes, echocardiograms, coronary angiograms, CT angiographies, and pathology reports were reviewed. ACAOS included right coronary artery from the left cusp, l...
Source
#1Talha NiazH-Index: 8
#2Jonathan N. Johnson (Mayo Clinic)H-Index: 30
Last. Donald J. Hagler (Mayo Clinic)H-Index: 88
view all 5 authors...
1. Talha Niaz, MBBS* 2. Jonathan N. Johnson, MD*,† 3. Frank Cetta, MD*,† 4. Timothy M. Olson, MD*,† 5. Donald J. Hagler, MD*,† 1. *Division of Pediatric Cardiology, Department of Pediatric and Adolescent Medicine, and 2. †Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN * Abbreviations: AHA : : American Heart Association BAV : : bicuspid aortic valve TTE : : transthoracic echocardiography Bicuspid aortic valve is the most common congenital heart defect in children, adolescents, ...
Source
Although in many ways the arterial and atrioventricular valves are similar, both being derived for the most part from endocardial cushions, we now know that the arterial valves and their surrounding structures are uniquely dependent on progenitors from both the second heart field (SHF) and neural crest cells (NCC). Here, we will review aspects of arterial valve development, highlighting how our appreciation of NCC and the discovery of the SHF have altered our developmental models. We will highli...
1 CitationsSource
#1Li-Tan Yang (Mayo Clinic)H-Index: 1
#1Li Tan Yang (Mayo Clinic)H-Index: 11
Last. Hector I. Michelena (Mayo Clinic)H-Index: 47
view all 11 authors...
Abstract The congenital bicuspid aortic valve (BAV) is a heterogeneous condition that is better understood considering 3 types of valvulo-aortopathy presentations: A typical-presentation valvulo-aortopathy, a complex-presentation valvulo-aortopathy and an uncomplicated/undiagnosed-presentation. The burden of BAV-related complications has been elucidated in patients with the typical-presentation valvulo-aortopathy and is discussed in this review. These patients enjoy an overall normal expected lo...
1 CitationsSource
#1Katia Bravo-Jaimes (University of Texas Health Science Center at Houston)H-Index: 3
#2Siddharth K. Prakash (University of Texas Health Science Center at Houston)H-Index: 27
Abstract Bicuspid aortic valve (BAV) is the most common congenital heart defect, found in up to 2% of the population and associated with a 30% lifetime risk of complications. BAV is inherited as an autosomal dominant trait with incomplete penetrance and variable expressivity due to a complex genetic architecture that involves many interacting genes. In this review, we highlight the current state of knowledge about BAV genetics, principles and methods for BAV gene discovery, clinical applications...
3 CitationsSource
#1María Teresa Soto-Navarrete (UMA: University of Málaga)H-Index: 3
#2Miguel A. López-Unzu (UMA: University of Málaga)H-Index: 4
Last. Borja Fernández (UMA: University of Málaga)H-Index: 19
view all 4 authors...
Abstract Bicuspid aortic valve (BAV) is the most common congenital cardiac malformation, frequently associated with aortopathies and valvulopathies. The congenital origin of BAV is suspected to impact the development of the disease in the adult life. During the last decade, a number of studies dealing with the embryonic development of congenital heart disease have significantly improved our knowledge on BAV etiology. They describe the developmental defects, at the molecular, cellular and morphol...
6 CitationsSource
#1Talha Niaz (Mayo Clinic)H-Index: 8
#2Susan M. Fernandes (Stanford University)H-Index: 33
Last. Donald J. Hagler (Mayo Clinic)H-Index: 88
view all 5 authors...
Abstract Bicuspid aortic valve (BAV) is one of the most common congenital heart defects in children, adolescents and adults. BAV can occur as an isolated lesion or in association with other congenital heart defects, such as coarctation of the aorta or genetic syndromes like Turner syndrome. Although the majority of long term complications associated with BAV manifest later in life, children and adolescents may present with early onset valvular dysfunction or dilation of the aorta. BAV is a heter...
1 CitationsSource
#1Hyeonju Jeong (Hanyang University)H-Index: 3
#2Chi Young Shim (Yonsei University)H-Index: 31
Last. Jong-Won Ha (Yonsei University)H-Index: 53
view all 8 authors...
Purpose The present study aimed to investigate the prevalence, characteristics, and clinical significance of concomitant specific cardiomyopathies in subjects with bicuspid aortic valves (BAVs).
2 CitationsSource
#1Jeroen C. Vis (Ciber)H-Index: 1
#2José Rodríguez-Palomares (Ciber)H-Index: 22
Last. Arturo Evangelista (Ciber)H-Index: 13
view all 11 authors...
Background Transthoracic echocardiography (TTE) and magnetic resonance imaging (MRI) have yielded excellent results in aortic root diameter measurement in patients with tricuspid aortic valve. However, accuracy in bicuspid aortic valve (BAV), often associated with aortic root asymmetry, is not fully defined. The aim of this study was to determine the agreement between TTE and MRI in proximal ascending aortic diameters in patients with BAVs. Methods Seventy-six consecutive patients with BAVs (mea...
8 CitationsSource