Case Of Bicuspid Aortic Valve Research Articles

GATA6 Regulates Aortic Valve Remodeling, and Its Haploinsufficiency Leads to Right-Left Type Bicuspid Aortic Valve.

Bicuspid aortic valve (BAV), the most common congenital heart defect affecting 1% to 2% of the population, is a major risk factor for premature aortic valve disease and accounts for the majority of valve replacement. The genetic basis and mechanisms of BAV etiology and pathogenesis remain largely undefined. Cardiac structure and function was assessed in mice lacking a Gata6 allele. Human GATA6 gene variants were analyzed in 452 BAV cases from the BAV consortium and 1849 controls from the Framingham GWAS (Genome Wide Association Study). GATA6 expression was determined in mice and human tissues using quantitative real-time polymerase chain reaction and immunohistochemistry. Mechanistic studies were carried out in cultured cells. Gata6 heterozygous mice have highly penetrant right-left (RL)-type BAV, the most frequent type in humans. GATA6 transcript levels are lower in human BAV compared with normal tricuspid valves. Mechanistically, Gata6 haploinsufficiency disrupts valve remodeling and extracellular matrix composition through dysregulation of important signaling molecules, including matrix metalloproteinase 9. Cell-specific inactivation of Gata6 reveals an essential role for GATA6 in secondary heart field myocytes because loss of 1 Gata6 allele from Isl- 1-positive cells-but not from endothelial or neural crest cells-recapitulates the phenotype of Gata6 heterozygous mice. The data identify a new cellular and molecular mechanism underlying BAV. The availability of an animal model for the most frequent human BAV opens the way for the elucidation of BAV pathogenesis and the development of much needed therapies.

Coexistence of bicuspid aortic valve, aberrant right subclavian artery and common origin of carotid arteries.

Prevalence of bicuspid aortic valve (BAV) and right aberrant sub-clavian artery (ASA) separately is relatively common in general population, and much higher in some disorders. Surprisingly, coexistence of both valve and vessel anomalies has only been reported in single cases. From 2008 to 2016, in a single, high-volume tertiary cardiac centre, patients who underwent chest computed tomography (CT) for various reasons, were retrospectively screened for the presence of right ASA. Seventy-two patients with either right or left ASA were identified by CT. Among them 7 cases of BAV and right ASA coexistence were identified. Additionally, 1 case with coexisting common origin of carotid arteries (COCA) was visualised in this subgroup. Although coexistence of ASA and BAV has not been reported in paediatric population, it has been diagnosed in very few adults as well as in our series. Additional presence of COCA in this group seems to be very rare. From practical point of view, heart cannulation via the radial artery and subsequent ASA may be challenging. Similarly, COCA presence may have surgical implications during corrective procedures.

Protein-altering and regulatory genetic variants near GATA4 implicated in bicuspid aortic valve

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 by CRISPR-Cas9 in induced pluripotent stem cells from healthy donors. The disruption of GATA4 significantly impaired the transition from endothelial cells into mesenchymal cells, a critical step in heart valve development.

A case of bicuspid aortic valve with coarctation of aorta

A 28-year-old male patient presented with angina on exertion for 3 years, dyspnea on exertion for 2 years. On examination patient was average built, having slow rising pulse, with ejection systolic murmur over aortic area, radiating to carotids. Blood investigations were normal, ECG was suggestive of LV strain pattern, Chest X ray was suggestive of LV type apex with notching of inferior margins of ribs. 2D Echocardiography was done, and was suggestive of thickened calcified bicuspid aortic valve, aortic annulus 21 mm, ascending aorta 42 mm, Gradient across aortic valve Peak 100 mmHg, Mean 64 mmHg. Patient was referred for Aortic valve replacement. However, in view of borderline dilated ascending aorta, CT aortography was done, and was suggestive of membranous juxtaductal Coarctation of aorta with no antegrade contrast opacification suggesting total aortic occlusion with reformation of aorta through large systemic thoracic wall and mediastinal collaterals.

Abstract 17616: Recurrent Copy Number Variants are Enriched in Bicuspid Aortic Valve and Affect Cardiac Developmental Genes

Introduction: Bicuspid Aortic Valve (BAV) is the most common adult congenital heart defect. The spectrum of BAV ranges from chromosomal disorders such as Turner syndrome to sporadic isolated disease of unknown cause. We hypothesized that genomic copy number variants (CNVs) contribute causally to BAV. Methods: We conducted genome-wide SNP array analyses of BAV cases in six European American cohorts (3533 total subjects, 31% BAV, 45% female, ages 1-94 years) with sporadic or familial thoracic aortic aneurysms (37%), congenital left ventricular outflow tract obstructive defects (47%) or Turner syndrome (10%). Genotyping was performed on Illumina Omni microarrays, using PennCNV, Nexus and CNVPartition for CNV detection. Thresholds were set at a minimum of six consecutive SNPs for CNVs that were identified by at least two algorithms and intersect with known genes. A total of 1380 BAV cases were compared to 1065 cases with tricuspid aortic valves and 7013 dbGAP controls without a history of cardiovascular disease using association tests for rare CNVs as implemented in PLINK. Pathway and functional analyses of rare CNVs were performed using the ToppGene analysis suite. Genes within rare CNVs were prioritized by their connectivity to genes in the Notch pathway or established roles in human or animal cardiac phenotypes. Results: We identified 12 rare CNV regions that were recurrent in at least three different BAV groups and were absent or extremely rare (frequency <0.1%) in controls. Four of these regions involved genes that cause aortic valve or outflow tract defects when mutated. The largest and most prevalent of the recurrent CNVs were at Xq28 (four duplications and two deletions), at 22q11.21, telomeric to the DiGeorge syndrome critical region (four deletions, three duplications), and at 7p15.2 (four deletions). The percentage of individuals harboring rare CNVs was significantly greater in BAV cases than in tricuspid or dbGAP controls. Conclusions: We identified multiple loci affected by rare CNVs in BAV subjects, demonstrating the genetic heterogeneity of BAV and implicating alterations of candidate genes at these loci in the pathogenesis of BAV.

Influence of the aortic valve leaflets on the fluid-dynamics in aorta in presence of a normally functioning bicuspid valve.

In this work, we consider the blood fluid-dynamics in the ascending aorta in presence of a normally functioning bicuspid aortic valve (BAV). In particular, we perform an unsteady finite element study in real geometries with physiological velocity boundary conditions at the inlet to assess the effect of the inclusion of the leaflets on the fluid-dynamic abnormalities characterizing BAV cases. To this aim, we perform a comparison in two geometries (a dilated and a non-dilated ones) among three scenarios which are built up for each geometry: BAV without leaflets, BAV with leaflets, and tricuspid case with leaflets. For each case, we compute four indices quantifying flow asymmetry, reversal flows, helical patterns, and wall shear stresses. Our results show that the inclusion of the leaflets increases the fluid-dynamics abnormalities, especially for the non-dilated configuration, which presents a greater increment of the indices. In particular, we observe that the values of the time-averaged wall shear stress and of the systolic jet asymmetry increase by approximatively 100 and 40%, respectively, when considering the leaflets.

Intraoperative Detection of Ascending Aortic Dissection by Transesophageal Echocardiography in a Patient with Bicuspid Aortic Valve and Ascending Aortic Aneurysm

ABSTRACT Bicuspid aortic valve is a common congenital heart defect frequently associated with complications of aortic valve and dilatation of ascending aorta. High index of suspicion is required for diagnosis of aortic dissection in patient with bicuspid aortic valve and ascending aortic dilatation. We present a case of bicuspid aortic valve with ascending aortic aneurysm in which aortic dissection was detected by intraoperative transesophageal echocardiography (TEE). A careful review of patient's preoperative computed tomography (CT) scan showed dissection flap in the ascending aorta, which was overlooked in CT reporting. We present how intraoperative TEE helped in surgical planning for the patient. How to cite this article Vishwakarma RK, Raj R, Puri GD. Intraoperative Detection of Ascending Aortic Dissection by Transesophageal Echocardiography in a Patient with Bicuspid Aortic Valve and Ascending Aortic Aneurysm. J Perioper Echocardiogr 2015;3(1):29-31.

Use of a targeted, combinatorial next-generation sequencing approach for the study of bicuspid aortic valve.

BackgroundBicuspid aortic valve (BAV) is the most common type of congenital heart disease with a population prevalence of 1-2%. While BAV is known to be highly heritable, mutations in single genes (such as GATA5 and NOTCH1) have been reported in few human BAV cases. Traditional gene sequencing methods are time and labor intensive, while next-generation high throughput sequencing remains costly for large patient cohorts and requires extensive bioinformatics processing. Here we describe an approach to targeted multi-gene sequencing with combinatorial pooling of samples from BAV patients.MethodsWe studied a previously described cohort of 78 unrelated subjects with echocardiogram-identified BAV. Subjects were identified as having isolated BAV or BAV associated with coarctation of aorta (BAV-CoA). BAV cusp fusion morphology was defined as right-left cusp fusion, right non-coronary cusp fusion, or left non-coronary cusp fusion. Samples were combined into 19 pools using a uniquely overlapping combinatorial design; a given mutation could be attributed to a single individual on the basis of which pools contained the mutation. A custom gene capture of 97 candidate genes was sequenced on the Illumina HiSeq 2000. Multistep bioinformatics processing was performed for base calling, variant identification, and in-silico analysis of putative disease-causing variants.ResultsTargeted capture identified 42 rare, non-synonymous, exonic variants involving 35 of the 97 candidate genes. Among these variants, in-silico analysis classified 33 of these variants as putative disease-causing changes. Sanger sequencing confirmed thirty-one of these variants, found among 16 individuals. There were no significant differences in variant burden among BAV fusion phenotypes or isolated BAV versus BAV-CoA. Pathway analysis suggests a role for the WNT signaling pathway in human BAV.ConclusionWe successfully developed a pooling and targeted capture strategy that enabled rapid and cost effective next generation sequencing of target genes in a large patient cohort. This approach identified a large number of putative disease-causing variants in a cohort of patients with BAV, including variants in 26 genes not previously associated with human BAV. The data suggest that BAV heritability is complex and polygenic. Our pooling approach saved over $39,350 compared to an unpooled, targeted capture sequencing strategy.

Sequencing of NOTCH1, GATA5, TGFBR1 and TGFBR2genes in familial cases of bicuspid aortic valve

BackgroundThe purpose of our study was to investigate the potential contribution of germline mutations in NOTCH1, GATA5 and TGFBR1 and TGFBR2 genes in a cohort of Italian patients with familial Bicuspid Aortic Valve (BAV).MethodsAll the coding exons including adjacent intronic as well as 5′ and 3′ untranslated (UTR) sequences of NOTCH1, GATA5, TGFBR1 and TGFBR2 genes were screened by direct gene sequencing in 11 index patients (8 males; age = 42 ± 19 years) with familial BAV defined as two or more affected members.ResultsTwo novel mutations, a missense and a nonsense mutation (Exon 5, p.P284L; Exon 26, p.Y1619X), were found in the NOTCH1 gene in two unrelated families. The mutations segregated with the disease in these families, and they were not found on 200 unrelated chromosomes from ethnically matched controls. No pathogenetic mutation was identified in GATA5, TGFBR1 and TGFBR2 genes.ConclusionsTwo novel NOTCH1 mutations were identified in two Italian families with BAV, highlighting the role of a NOTCH1 signaling pathway in BAV and its aortic complications. These findings are of relevance for genetic counseling and clinical care of families presenting with BAV. Future studies are needed in order to unravel the still largely unknown genetics of BAV.

A case of bicuspid aortic valve with two raphes

A 60-year-old woman was referred to our hospital for exertional shortness of breath. She was made aware of a heart murmur as a high school student. She had exertional dyspnea and chest pain. Her symptoms were getting worse over the previous year. On admission, her blood pressure was 160/54 mmHg, heart rate was 72 bpm, and grade 3/6 regurgitant murmur over the precordium was present. She was diagnosed with severe aortic regurgitation by transthoracic echocardiography and the other clinical examination. Transthoracic echocardiography showed severe aortic regurgitation with normal left ventricular systolic function. Two raphes of the aortic valve were not diagnosed by transthoracic echocardiography because of poor quality echo images. Two-dimensional transesophageal echocardiograms showed a bicuspid aortic valve (BAV) with fused cusps between the two components of the right and noncoronary cusps (Fig. 1). Furthermore there were two raphes on the fused cusps. Real-time three-dimensional echocardiograms showed two commissures and two raphes on the fused area in systole and diastole (Fig. 2a, b). The perioperative findings were exactly the same as the information obtained by three-dimensional transesophageal echocardiography (Fig. 2c). Discussion

Studies on Aortic and Aortic Valve Diseases

Bicuspid aortic valve (BAV) is the most common congenital cardiac malformation, with an estimated incidence of 1%–2% in the general population. Patients with BAV are predisposed to early and frequent stenosis, regurgitation, and endocarditis, often accompanied by aneurysm and dissection. A family-based genome-wide analysis found that BAV was linked to chromosomal regions 5q, 13q, and 18q, with autosomal dominant inheritance, reduced penetrance and a non-Mendelian inheritance pattern. Mutations in the transmembrane receptor-encoding gene NOTCH1 have been detected in familial and sporadic BAV cases. Mutations in the vascular smooth muscle cell alpha actin gene (ACTA2) have also been identified in BAV patients. Expression of UFD1L, a gene that is highly expressed in the outflow tract during embryogenesis, was downregulated in the cusps of BAV patients compared with those of controls. BAV is associated with left ventricular outflow tract abnormality, including aortic coarctation, arch hypoplasia, and supravalvular and mitral valve stenosis. A male predominance of more than 3:1 has been reported for BAV. This anomaly is very frequent in X0 Turner’s syndrome. Many studies have observed similarities between the histology of aortic aneurysmal tissue in the connective tissue disorder Marfan syndrome (MFS) and the histology of the corresponding tissue in BAV. In this lecture, we review our present understanding of BAV malformation and ascending thoracic aortic aneurysm pathogenesis. We discuss the genetic basis and the basic pathology underlying BAV and aortopathy and compare these with known mechanisms underlying MFS.

Focus on the unique mechanisms involved in thoracic aortic aneurysm formation in bicuspid aortic valve versus tricuspid aortic valve patients: clinical implications of a pilot study

The involvement of different factors in the onset of thoracic aortic aneurysm (TAA) in patients with a bicuspid aortic valve (BAV) vs those with a tricuspid aortic valve (TAV) is well recognized. However, the molecular, genetic and cellular mechanisms driving TAA remain unclear. The aim of this study was to identify the different mechanisms involved in TAA development in patients with BAV vs TAV. Aorta specimens and DNA samples were collected from 24 BAV (18 men and 6 women; mean age: 54.2 ± 14.39 years) and 110 TAV (79 men and 31 women, mean age: 66 ± 9.8 years) patients. A control group of 128 subjects (61 men and 67 woman, mean age: 61.1 ± 5.8 years) was also enrolled. Histopathological and immunohistochemical analyses were performed, as well as genotyping of 10 polymorphisms. In BAV-associated ascending aortas, significant severe plurifocal apoptosis of smooth muscle cells and matrix metalloproteinase-9 (MMP-9) amounts were detected. In contrast, TAV-associated ascending aortas were characterized by a significant severity of elastic fragmentation, cystic medial necrosis, medial fibrosis and inflammation. In addition, in BAV cases, the -1562TMMP-9 and -735TMMP-2 alleles represent independent risk factors for TAA. The effects of these genotypes combined with hypertension and smoking in BAV cases result in an increase in both the apoptosis (P = 0.0001) and levels of MMP-9 (P = 0.001). In TAV cases, the D angiotensin-converting enzyme and +896A Toll-like receptor-4 alleles seem to be the predictive factors for TAA risk. They, combined with hypertension and age, significantly increase both the microscopic lesions and inflammation. Our data seem to suggest that TAA in BAV and TAV patients arises from different molecular, cellular and genetic mechanisms. They might help to identify the potential molecular and genetic biomarkers that are useful to detect BAV subjects at high TAA risk, to monitor and treat them differently from those with TAV, with approaches such as the complete removal of the ascending aorta, including the aortic root with or without dilatation.

Helical flows and asymmetry of blood jet in dilated ascending aorta with normally functioning bicuspid valve

Bicuspid aortic valve (BAV) is associated with aortic dilatation and aneurysm. Several studies evidenced an eccentric systolic flow in ascending aorta associated with increased wall shear stresses (WSS) and the occurrence of an helical systolic flow. This study seeks to elucidate the connections between jet asymmetry and helical flow in patients with normally functioning BAV and dilated ascending aorta. We performed a computational parametric study by varying, for a patient-specific geometry, the valve area and the flow rate entering the aorta and drawing also a tricuspid valve (TAV). We considered also phase-contrast magnetic resonance imaging of four BAV and TAV patients. Measurement of normalized flow asymmetry index, systolic WSS and of a new index (positive helix fraction, PHF) quantifying the presence of a single a single helical flow were performed. In our computation, BAV cases featured higher values of all indices with respect to TAV in both numerical and imaged-based results. Moreover, all indices increased with decreasing valve area and/or with increasing flow rate. This allowed to separate the BAV and TAV cases with respect to the jet asymmetry, WSS localization and helical flow. Interestingly, these results were obtained without modeling the leaflets.

Rare non-synonymous variations in the transcriptional activation domains of GATA5 in bicuspid aortic valve disease

Bicuspid aortic valve (BAV) is the commonest congenital heart disease and a highly heritable trait; however, only the NOTCH1 gene has been linked to limited cases of BAV in humans. Recently, the transcription factor GATA5 has been shown to have an essential role in aortic valve development, and targeted deletion of Gata5 in mice is associated with partially penetrant BAV formation. Here, we investigated the relationship between GATA5 gene variants and BAV with its associated aortopathy. One hundred unrelated individuals with confirmed BAV were prospectively recruited. Following collection of clinical information and DNA extraction, the coding regions and splice signal sequences of the GATA5 gene were screened for sequence variations. The clinical characteristics of the cohort included a male predominance (77%), mean age of diagnosis 29±22years, associated aortopathy in 59% and positive family history for BAV in 13%. Genetic analysis identified the presence of 4 rare non-synonymous variations within the GATA5 transcriptional activation domains, namely Gln3Arg, Ser19Trp, Tyr142His and Gly166Ser, occurring in one patient each. Gln3Arg and Tyr142His substitutions affect highly conserved and functionally relevant residues, and are likely to impact on the transcriptional activation of GATA5 target regions. A novel Ser19Trp variation was identified at a highly conserved amino acid residue in one patient, while the Gly166Ser variant was found in a familial case of BAV and associated aortopathy. Rare non-synonymous variations in the functionally important GATA5 transcriptional activation domains may be important in the pathogenesis of BAV disease in humans.

Usefulness of three-dimensional transthoracic echocardiography for the classification of congenital bicuspid aortic valve in children

Because the classification of congenital bicuspid aortic valve (BAV) is of importance to predict a possible valvular dysfunction, we sought to assess the feasibility, the reproducibility, and the accuracy of three-dimensional transthoracic echocardiography (3D-TTE) to accurately depict the morphology of the leaflets in a BAV. Seventy-two consecutive children, who were suspected of having a BAV on two-dimensional transthoracic echocardiography (2D-TTE), were included in this prospective study. 2D-TTE and 3D-TTE views of a BAV were recorded by the same investigator, and then were analysed separately by two confirmed paediatric cardiologists. For each of these two imaging techniques, the spatial position of cusps and raphes was noted for each patient. Intra-observer concordance and inter-observer concordance were evaluated to assess the reproducibility of the techniques. Feasibility of 3D-TTE was 100%. Median acquisition time of 3D-TTE was 117 (98.5-176.8) s. Image quality seemed to be better with 3D-TTE compared with 2D-TTE. When using 3D-TTE, the diagnosis was reconsidered for 12 patients (17%). Only 44.4% of uncertain BAV cases identified by 2D-TTE were confirmed by 3D-TTE. Furthermore, 3D-TTE seems to provide a better visualization of the leaflet morphology, leading to reclassification for 34.4% (95% CI 22.9-47.3) of the patients. Agreement for the BAV classification between 2D-TTE and 3D-TTE was therefore moderate (κ = 0.46). Both inter-observer concordance and intra-observer concordance were good (κ = 0.91 and κ = 0.93, respectively) for 3D-TTE. 3D-TTE is feasible and provides accurate description of a BAV in children. Compared with 2D-TTE, 3D-TTE seems to enable a better visualization of the structural geometry of the leaflets.

Loss of Gata5 in mice leads to bicuspid aortic valve

Bicuspid aortic valve (BAV), the leading congenital heart disease, occurs in 1%-2% of the population. Genetic studies suggest that BAV is an autosomal-dominant disease with reduced penetrance. However, only 1 gene, NOTCH1, has been linked to cases of BAV. Here, we show that targeted deletion of Gata5 in mice leads to hypoplastic hearts and partially penetrant BAV formation. Endocardial cell-specific inactivation of Gata5 led to BAV, similar to that observed in Gata5-/- mice. In all cases, the observed BAVs resulted from fusion of the right-coronary and noncoronary leaflets, the subtype associated with the more severe valve dysfunction in humans. Neither endocardial cell proliferation nor cushion formation was altered in the absence of Gata5. Rather, defective endocardial cell differentiation, resulting from the deregulation of several components of the Notch pathway and other important endocardial cell regulators, may be the underlying mechanism of disease. The results unravel a critical cell-autonomous role for endocardial Gata5 in aortic valve formation and identify GATA5 as a potential gene responsible for congenital heart disease in humans. Mice with mutated Gata5 alleles represent unique models to dissect the mechanisms underlying degenerative aortic valve disease and to develop much-needed preventive and therapeutic interventions.

Bicuspid Aortic Valve Prevalence In A Large Series Of Echocardiograms In The Area Of Frequent Consanguineous Marriage

Bicuspid aortic valve (BAV) is one of the most common congenital anomalies of the heart, though its definitive prevalence is not clear. We sought to determine the prevalence of BAV in a large database of echocardiographic measurements from a single institution in the area of frequent consanguineous marriage (South-east Anatolia region) and we present the frequencies of BAV-related complications such as stenosis, regurgitation, and assendan aorta dilatation. We retrospectively analyzed 31.265 echocardiograms performed at our academic institution between 2004 and 2007 for various indications. BAV is often associated with aortic stenosis, regurgitation, and ascending aorta dilatation and BAV is an independent risk factor for infective endocarditis. The prevalence of BAV was calculated, and the frequency of aortic stenosis, regurgitation, and ascending aorta dilatation among BAV cases was determined. Our database revealed a gender distribution of 11.339 males (47%) and 12.926 (53%) females.The total prevalence of BAV was 0.57% (n = 180). The rate of consanguineous marriage is 20.9% in overeall Turkey. The rate of consanguineous marriage is 40.4% in our region The gender-specific prevalence was 1.08% in males and 0.44% in females. Regurgitation was observed in 58.3% (28.9% mild, 29.4% severe) of BAV cases, stenosis in 40% (17.8% mild, 22.2% severe), and dilatation in 33.3%. The prevalence determined in our study is similar to the prevalence determined in other recent echocardiography and autopsy studies, suggesting a lower incidence of BAV than previously thought despite high rate of consanguineous marriage. Regurgitation was the most common valvular complication in our database.

Valve Repair for Bicuspid Aortic Valve Regurgitation: An Option?

Bicuspid aortic valve is the most common form of congenital heart disease. It is associated with both valvular pathology and aortic disease. Aortic regurgitation caused by a bicuspid aortic valve can be corrected by surgical valve repair, which has good short-term results. However, the significant rate of aortic regurgitation recurrence found on long-term follow-up remains a problem, partly because of the progressive aortic dilatation that is characteristic of this disease. We report three different cases of bicuspid aortic valve treated by surgical valve repair at our centre.

Effect of G-Force on Bicuspid Aortic Valve in Aviators

Background and Aims: Bicuspid aortic valve (BAV) is a common congenital cardiac malformation. The major complications are aortic stenosis (AS), aortic regurgitation (AR), infectious endocarditis and aortic dissection. This paper aims to assess the hemodynamic importance of incidentally-found BAV in military aviators and evaluate the effect of high G-force on disease progression. Methods: Aviators with BAV were detected by reviewing all cardiac assessment records between 1987 and 2005. All aviators underwent annual flight surgeon examination. Echocardiography was performed as recommended by our cardiologists and flight surgeons. Results: Eight newly diagnosed cases of BAV were found. All of the aviators continued active aviation throughout the study period. Repeat echocardiography demonstrated progressive widening of the aortic diameter in five of the eight aviators. No worsening of valve dysfunction was seen in those with mild aortic regurgitation at diagnosis. Left ventricular dimensions and function did not deteriorate. No new valve complications, including infectious endocarditis, were seen. The age at diagnosis strongly correlated with the root diameter change; both total (r = 0.74, p = 0.02) and annualized (r = 0.78, p = 0.02) change. Over a mean follow-up period of 12.1 years, no difference was seen in the progression of BAV in high-performance as compared to low-performance aviators. Conclusions: Exposure to G-force and anti-G maneuvers does not appear to worsen cardiac and valve function in aviators with BAV.

Clefted bicuspid aortic valve

We report an unusual case of bicuspid aortic valve in a 67-year-old man who had aortic valve replacement for combined severe aortic stenosis with moderate aortic regurgitation. Both preoperative echocardiography and angiocardiography failed to recognize the bicuspid nature of the aortic valve, which was discovered only at surgical pathology examination. The atypical anatomic findings of the valve consisted of a “cleft-like” appearance of the ventral leaflet formed by the two conjoined cusps together with a fenestrated rudimental raphe.