Aortic Valve Malformation Research Articles

The Congenitally Malformed Aortic Valve in Type A Aortic Dissection: Its Frequency and Consequences

A congenitally malformed aortic valve, unicuspid (UAV) or bicuspid (BAV), occurs in about 1% of the population and is known to be more frequent in patients with aortic dissection. The clinical and operative findings in a series of 134 patients with spontaneous, acute Type A aortic dissection (TAAD) were studied, comparing patients with normal and abnormal aortic valve morphology. The aortic valve was normal in 123/134 (92%) patients and abnormal in 11/134 (8%) patients: BAV in 10/134 (7.5%) and UAV in 1/134 (0.7%). Demographics were similar between groups except for a lower frequency of systemic hypertension in the UAV/BAV group (46 vs. 82%, p<0.01). Penn class stratification was also similar in the 2 groups. The UAV/BAV group had a greater frequency of aortic root enlargement (64 vs. 18%, p<0.01) and a larger median root diameter (5.7 vs. 4.6cm, p=0.02). In the UAV/BAV group, the entry tear was more frequently in proximal (intrapericardial) zone 0 (91 vs. 62%, p=0.049). The frequency of abnormal aortic media histology was similar. The rate of root replacement was higher in the UAV/BAV group and early mortality was similar. The frequency of congenitally malformed aortic valve in this series was 8x the normal population. The one UAV in the series was the only severely stenotic valve. In TAAD patients with a congenitally malformed valve, aortic root aneurysm was more common and the entry tear was nearly always proximal.

Aortic leaflet remodeling for the repair of congenitally malformed aortic valve

ObjectiveAortic valve repair techniques are still evolving with better understanding of aortic root and leaflet imaging. This study seeks to present the results of an additional new technique in aortic valve repair of patients with congenital heart disease. The technique entails remodeling of the leaflet by intentional peeling of the myxomatous tissue to remodel the thickened leaflets (from the ventricular side of the aortic valve along with thinning and plication of the central region of the leaflets). Other repair techniques are added to complete the repair. MethodsWe performed a retrospective chart analysis of 19 patients who underwent aortic valve remodeling for aortic regurgitation and received advanced imaging preoperative assessment from January 2022 to February 2024. Institutional Review Board approval was obtained under expedited review for retrospective studies. ResultsAll patients with a wide range of congenital pathologies underwent leaflet remodeling; 9 patients (47%) underwent additional valve-sparing root replacement, and 6 patients (32%) received subaortic annuloplasty. Fifteen patients (79%) had moderate or severe aortic insufficiency at the time of presentation. Mean clinical follow-up was 10 months (range, 1.9-31). At follow-up, 7 patients did not have aortic regurgitation on echocardiogram, and the remaining 12 patients had mild regurgitation. None of the patients had more than mild regurgitation. All patients assessed for left ventricular ejection fraction at follow-up had an ejection fraction greater than 50%. None of the patients required reoperation. ConclusionsLeaflet remodeling by intentional peeling of myxomatous tissue expands leaflet dimensions by freeing tethered portions and improves mobility and coaptation. This additional technique will preserve more valves from replacement. However, further follow-up is needed.

“One-stop” interventional therapy for quadricuspid aortic valve combined with severe coronary artery disease: a case report

Congenital Quadricuspid Aortic Valve (QAV) malformation is a relatively rare cardiac valve malformation, especially with abnormal coronary opening and severe stenosis of Coronary Artery Disease (CAD). The patient underwent “one-stop” interventional treatment with transcatheter aortic valve replacement and percutaneous coronary stent implantation. Follow up for 12-month with good outcomes.

Identification of congenital aortic valve malformations in juvenile natriuretic peptide receptor 2-deficient mice using high-frequency ultrasound.

Mouse models of congenital aortic valve malformations are useful for studying disease pathobiology, but most models have incomplete penetrance [e.g., ∼2 to 77% prevalence of bicuspid aortic valves (BAVs) across multiple models]. For longitudinal studies of pathologies associated with BAVs and other congenital valve malformations, which manifest over months in mice, it is operationally inefficient, economically burdensome, and ethically challenging to enroll large numbers of mice in studies without first identifying those with valvular abnormalities. To address this need, we established and validated a novel in vivo high-frequency (30 MHz) ultrasound imaging protocol capable of detecting aortic valvular malformations in juvenile mice. Fifty natriuretic peptide receptor 2 heterozygous mice on a low-density lipoprotein receptor-deficient background (Npr2+/-;Ldlr-/-; 32 males and 18 females) were imaged at 4 and 8 wk of age. Fourteen percent of the Npr2+/-;Ldlr-/- mice exhibited features associated with aortic valve malformations, including 1) abnormal transaortic flow patterns on color Doppler (recirculation and regurgitation), 2) peak systolic flow velocities distal to the aortic valves reaching or surpassing ∼1,250 mm/s by pulsed-wave Doppler, and 3) putative fusion of cusps along commissures and abnormal movement elucidated by two-dimensional (2-D) imaging with ultrahigh temporal resolution. Valves with these features were confirmed by ex vivo gross anatomy and histological visualization to have thickened cusps, partial fusions, or Sievers type-0 bicuspid valves. This ultrasound imaging protocol will enable efficient, cost effective, and humane implementation of studies of congenital aortic valvular abnormalities and associated pathologies in a wide range of mouse models.NEW & NOTEWORTHY We developed a high-frequency ultrasound imaging protocol for diagnosing congenital aortic valve structural abnormalities in 4-wk-old mice. Our protocol defines specific criteria to distinguish mice with abnormal aortic valves from those with normal tricuspid valves using color Doppler, pulsed-wave Doppler, and two-dimensional (2-D) imaging with ultrahigh temporal resolution. This approach enables early identification of valvular abnormalities for efficient and ethical experimental design of longitudinal studies of congenital valve diseases and associated pathologies in mice.

Congenital unicuspid aortic valve in adults: Minireview and case series.

A unicuspid aortic valve (UAV) in adults is a very rare form of aortic valve (AV) malformation. UAV has two distinct subtypes, acommissural UAV and unicommissural, and can be differentiated by anatomical features, imaging modalities, and clinical presentation. With the development of significant AV lesion (s), surgical or transcatheter intervention will be required. The first part is a summarized review of UAV (anatomical features, clinical presentation, diagnostic modalities, and management). In the second part, we present a series of four patients diagnosed with UAV (3 unicommissural and 1 acommissural). The first case underwent balloon aortic valvuloplasty during childhood and surgical AV replacement later, with the progression to severe aortic stenosis (AS). The second case underwent a Ross procedure. The third and fourth cases were asymptomatic with moderate AS and mild-to-moderate AR and were kept on follow-up. In all the cases, transesophageal echocardiography confirmed the diagnosis of UAV with detailed morphological and functional assessment of AV.

Connecting the dots: molecular pathways in bicuspid aortopathy explored

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Junta de Andalucía, Ministerio de Ciencia e Innovación Background Bicuspid aortic valve (BAV) is the most common congenital cardiac malformation. It predisposes to thoracic aortic dilatation (TAD), aneurysm and dissection. The current consensus is that the genetic defect that leads to the aortic valve malformation also causes structural anomalies of the ascending aorta. Altered hemodynamics caused by the abnormal valve morphology would accelerate aortic media degeneration. Molecular markers and pathways involved in the aetiology and pathophysiology of bicuspid aortopathy are poorly understood. Objective To elucidate the molecular and cellular mechanisms of the disease and to identify potential predictive molecular markers using a well-established isogenic hamster model (T strain) with a high (∼40%) incidence of BAV TAD. Methods Comparative 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 exploring independently the genetic and hemodynamic effects on the aorta in genetically homogeneous populations. Results The major molecular defect in the aorta of genetically homogeneous BAV individuals is PI3K/AKT overactivation caused by alterations in the EGF, ANGII and TGF-β signalling pathways. PI3K/AKT affects the 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 the T strain, which mainly show downregulation of the WNT pathway. Conclusions We 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 a shift of smooth muscle cells towards the synthetic phenotype induced by endothelial-to-mesenchymal transition, oxidative stress and inflammation. WNT signalling represents a genetic factor that may cause aortic structural abnormalities and aneurysm predisposition, whereas hemodynamics is the main trigger of molecular changes, likely determining the progression of aortopathy. We identify twenty-seven novel potential biomarkers with high predictive value.

An 18-year evolution of congenital heart disease in China: An echocardiographic database-based study

ObjectiveData on the evolution of congenital heart disease (CHD) in China remain scarce. Based on a Chinese echocardiography database, we analyzed the observed rate (OR) and spectrum changes of CHD over the past 18 years with a focus on the congenital aortic valve malformation (CAVM) and Adult CHD (ACHD). Methods and resultsThe transthoracic echocardiographic data of 682,565 records from 2003 to 2020 were retrospectively reviewed at Fujian Medical University Union Hospital, China. A total of 37,200 CHD cases were recruited in this study. Over the three periods (from 2003 to 2008, 2009–2014, to 2015–2020), the OR of Total CHD decreased (106.72, 90.64, and 67.43 per 1000 cases, respectively); the proportion of Simple CHD to Total CHD increased (80.96%, 83.41%, and 87.97%, respectively), with a decrease in the proportion of Complex CHD (18.11%, 15.51%, and 10.42%, respectively) (p < 0.05 for all). The proportion of ACHD increased in most types of CHD [Total CHD: 25.79%, 27.84%, and 31.43%; CAVM: 69.02%, 73.42%, and 78.16%; CAVM with aortic stenosis (AS): 67.42%, 70.73%, and 79.25%; respectively, p < 0.05 for all], with a much higher proportion in both CAVM and CAVM with AS than in the other CHD types. The proportion of CHD patients receiving intervention increased over the designated periods. ConclusionsThis study depicts the longitudinal changes of CHD in the Chinese population with a single-center echocardiographic data, revealing an increased proportion of Simple CHD, ACHD (including CAVM and CAVM with AS), and a decreased OR of Total CHD and proportion of Complex CHD.

Novel pathogenic variant in LMNA gene identified in a six-generation family causing atrial cardiomyopathy and associated right atrial conduction arrhythmias.

To characterize the cardiac phenotype associated with the novel pathogenic variant (c.1526del) of LMNA gene, which we identified in a large, six-generation family. A family tree was constructed. The clinical data of living and deceased family members were collected. DNA samples from 7 family members were analyzed for LMNA mutations using whole-exome high-throughput sequencing technology. The clinical presentation of pathogenic variant carriers was evaluated. In this six-generation family (n = 67), one member experienced sudden death at the age of 40-years-old. Three pathogenic variant carriers were identified to possess a novel heterozygous deletion mutation in LMNA gene (HGVS: NM_170707.4, c.1526del) located at exon 9 of LMNA chr1:156137145, which creates a premature translational stop signal (p.Pro509Leufs*39) in the LMNA gene and results in an mutant lamin A protein product. The main symptoms of the pathogenic variant carriers were palpitation, fatigue, and syncope, which typically occurred around 20-years-old. AV-conduction block and non-sustained ventricular tachycardia were the first signs of disease and would rapidly progress to atrial standstill around 30-years-old. Significant right atrial enlargement and bicuspid aortic valve malformation was also commonly seen in patients who carried this pathogenic variant. The pathogenic variant of c.1526del p.P509Lfs*39 was a frameshift deletion located at exon 9 of LMNA chr1:156137145 and causes severe right atrial enlargement, sick sinus syndrome, atrial standstill, ventricular tachycardia, and bicuspid aortic valve malformation. Our findings expand the phenotypic spectrum of novel LMNA gene mutations.

Histopathological findings of diseased ascending aortae with clinicopathological correlation – A single-centre study of 160 cases

The most common reason for ascending aorta resection is an aneurysm or dissection. Aortic dissection is a life-threatening condition in which an aneurysm is a crucial risk factor. The essential criteria for aneurysm resection include the diameter, genetic predisposition, and aortic valve disease. This study aimed to compare the histological findings in aneurysms and dissections and correlate them with clinical parameters to determine whether histopathological findings correspond with the current clinical approach. A total of 160 ascending aorta surgical specimens, separate or with an aortic valve, were collected and divided into four groups: aneurysm-tricuspid (n = 40; median 67 y), aneurysm-malformed (n = 68; median 50 y), dissection-tricuspid (n = 48; median 65.5 y), and dissection-malformed (n = 4; median 52.5 y). Male preponderance was observed in all groups; the youngest patients were in the aneurysm-malformed group. None of the specimens showed normal aortic histology. The most common finding in the aortic samples was medial degeneration, which was the most severe and most common in dissection. The mildest findings were found in the aneurysm-malformed group. Atherosclerosis was predominant and most severe in the aneurysm-tricuspid group, while only mild in both dissection groups, suggesting its protective effect against this complication. Chronic aortitis was the least common pathology, found only in the aneurysm-tricuspid group. The aortic valve was resected and examined simultaneously with the ascending aorta in 76 cases, most commonly in the aneurysm-malformed group (n = 53). Myxoid degeneration was the major finding in the tricuspid aortic valves, with calcifications in the malformed. Comparing the histopathological results with the clinical aspects, aneurysms with a malformed aortic valve seem to be managed appropriately, with the findings not reaching the severity as in patients with a tricuspid valve. In contrast, in patients with a tricuspid valve, there were more dissections than aneurysms, with a significant subset of aneurysms showing histological findings almost identical to those of dissections. Supported by histological findings, patients with a diseased ascending aorta and tricuspid aortic valve represent an underdiagnosed risk group that would benefit from earlier diagnosis and intervention to prevent dissection. There is a need to find a marker for dissection risk other than the aortic diameter.

Computed Tomography Scan of the Aorta to Predict Type B Aortic Dissection.

The purpose of this study is to find the high-risk morphological features in type B aortic dissection (TBAD) population and to establish an early detection model. From June 2018 to February 2022, 234 patients came to our hospital because of chest pain. After examination and definite diagnosis, we excluded people with previous cardiovascular surgery history, connective tissue disease, aortic arch variation, valve malformation, and traumatic dissection. Finally, we included 49 patients in the TBAD group and 57 in the control group. The imaging data were retrospectively analyzed by Endosize (Therevna 3.1.40) software. The aortic morphological parameters mainly include diameter, length, direct distance, and tortuosity index. Multivariable logistic regression models were performed and systolic blood pressure (SBP), aortic diameter at the left common carotid artery (D3), and length of ascending aorta (L1) were chosen to build a model. The predictive capacity of the models was evaluated through the receiver operating characteristic (ROC) curve analysis. The diameters in the ascending aorta and aortic arch are larger in the TBAD group (33.9 ± 5.9 vs. 37.8 ± 4.9 mm, p < 0.001; 28.2 ± 3.9 vs. 31.7 ± 3.0 mm, p < 0.001). The ascending aorta was significantly longer in the TBAD group (80.3 ± 11.7 vs. 92.3 ± 10.6 mm, p < 0.001). Besides, the direct distance and tortuosity index of the ascending aorta in the TBAD group increased significantly (69.8 ± 9.0 vs. 78.7 ± 8.8 mm, p < 0.001; 1.15 ± 0.05 vs. 1.17 ± 0.06, p < 0.05). Multivariable models demonstrated that SBP, aortic diameter at the left common carotid artery (D3), and length of ascending aorta (L1) were independent predictors of TBAD occurrence. Based on the ROC analysis, area under the ROC curve of the risk prediction models was 0.831. Morphological characteristic including diameter of total aorta, length of ascending aorta, direct distance of ascending aorta, and tortuosity index of ascending aorta are valuable geometric risk factors. Our model shows a good performance in predicting the incidence of TBAD.

Surgical treatment of bicuspid aortic valve with aortic stenosis

Background: Patients with bicuspid aortic valve may develop isolated aortic valve disease, including isolated aortic stenosis. This disease progresses over a long period of time leading to simultaneous damage of the valves and aorta. Surgery is an effective treatment of both lesions simultaneously. This study objective is to describe the characteristic features of the diagnosis and surgery results of this disease.&#x0D; Methods: All of patients diagnosed aortic stenosis due to bicuspid aortic valve were performed aortic valve replacement and asscociated aortic lesions. This retrospective descritptive study used data from the Hanoi Medical Uninversity Hospital from 3/2020 to 3/2023.&#x0D; Results: This study include 25 patients who met review criteria. Aortic stenosis was in all of patients associated with ascending aortic aneurysm. Mean aortic gradient was 56,7mmHg and 36,0% of patients had ascending aortic diameter above 45mm. The most common morphology of bicuspid aortic valve was right – left coronary leaflet. 8,0% of patients had poor left ventricle function (EF &lt; 30%). 36,0% of patients were perfomed single aortic valve replacement, 60,0% were corrected simultaneously lesions of aortic valve and ascending aorta in which 24,0% using wrapping with dacron graft. Complications: One death due to intraoperative Stanford A aortic dissection; one bleeding due to lateral wound close distal aortic anastomosis required an operation and one of sternal instability require a sternal plasty. 96,0% of patients have discharged uneventfully.&#x0D; Conclusions: Surgery is an effective treatment of both lesions simultaneously of aortic valve and descending aorta in aortic stenosis due to bicuspid aortic valve malformation. Wrapping of the ascending aorta may be useful in patients who need to undergo aortic valve surgery without increasing the risk of surgery.

Age-dependent phenotypic modulation of smooth muscle cells in the normal ascending aorta.

Ascending aortic aneurysms are associated with pre-existing conditions, including connective tissue disorders (i.e., Marfan syndrome) and bicuspid aortic valves. The underlying mechanisms remain uncertain. Even less is known regarding ascending aortic aneurysms in individuals with normal (i.e., tricuspid) aortic valves (TAV), and without known aneurysm-associated disorders. Regardless of etiology, the risk of aortic complications increases with biological age. Phenotypic modulation of smooth muscle cells (SMCs) is a feature of ascending aortic aneurysms, whereby contractile SMCs are replaced with synthetic SMCs that are capable of degrading the aortic wall. We asked whether age itself causes dysfunctional SMC phenotype modulation, independent of aortic dilatation or pre-existing aneurysm-associated diseases. Non-dilated ascending aortic samples were obtained intra-operatively from 40 patients undergoing aortic valve surgery (range: 20-82 years old, mean: 59.1 ± 15.2). Patients with known genetic diseases or aortic valve malformations were excluded. Tissue was divided, and a portion was formalin-fixed and immunolabeled for alpha-smooth muscle actin (ASMA), a contractile SMC protein, and markers of synthetic (vimentin) or senescent (p16/p21) SMCs. Another fragment was used for SMC isolation (n = 10). Cultured SMCs were fixed at cell passage 2 and stained for phenotype markers, or were cultured indefinitely to determine replicative capacity. In whole tissue, ASMA decreased (R2 = 0.47, P < 0.0001), while vimentin increased (R2 = 0.33, P = 0.02) with age. In cultured SMCs, ASMA decreased (R2 = 0.35, P = 0.03) and vimentin increased (R2 = 0.25, P = 0.04) with age. p16 (R2 = 0.34, P = 0.02) and p21 (R2 = 0.29, P = 0.007) also increased with age in SMCs. Furthermore, the replicative capacity of SMCs from older patients was decreased compared to that of younger patients (P = 0.03). By investigating non-dilated aortic samples from individuals with normal TAVs, we found that age itself has a negative impact on SMCs in the ascending aortic wall, whereby SMCs switched from the contractile phenotype to maladaptive synthetic or senescent states with increased age. Therefore, based on our findings, modification of SMC phenotype should be studied as a therapeutic consideration against aneurysms in the future, regardless of etiology.

Endocardium in Hypoplastic Left Heart Syndrome: Implications from In Vitro Study.

Endocardium lines the inner layer of the heart ventricle and serves as the source of valve endothelial cells and interstitial cells. Previously, endocardium-associated abnormalities in hypoplastic left heart syndrome (HLHS) have been reported, including endocardial fibroelastosis (EFE) and mitral and aortic valve malformation. However, few mechanistic studies have investigated the molecular pathological changes in endocardial cells. Recently, the emergence of a powerful in vitro system-induced pluripotent stem cells (iPSCs)-was applied to study various genetic diseases, including HLHS. This review summarized current in vitro studies in understanding the endocardial pathology in HLHS, emphasizing new findings of the cellular phenotypes and underlying molecular mechanisms. Lastly, a future perspective is provided regarding the better recapitulation of endocardial phenotypes in a dish.

Medial degeneration and atherosclerosis show discrete variance around the circumference of ascending aorta aneurysms.

Medial degeneration is the most common histological finding in ascending aortic aneurysms with lesser but significant involvement by atherosclerosis. The overall extent and severity can be potentially underrated because of their uneven distribution and macroscopic inconspicuousness of medial degeneration. This study aims to compare the distribution of degenerative and atherosclerotic lesions around ascending aorta circumference, also considering aortic valve cuspidity. We evaluated 88 cases of resected ascending aortae, 25 with a tricuspid aortic valve and 63 with a malformed aortic valve, oriented by a cardiac surgeon and sent for pathological examination. We applied the consensus documents from 2015 and 2016 for microscopic evaluation of aortic specimens. The medial degeneration and atherosclerosis were graded semi-quantitatively for each aortic quadrant: convexity, anterior wall, concavity, and posterior wall. Nearly all quadrants showed at least mild medial degeneration; more severe findings of medial degeneration and atherosclerosis were in the aneurysms associated with the tricuspid valve. In the aneurysms with the tricuspid aortic valve, there was more frequent and more severe atherosclerosis at the concavity than at the anterior wall (p = .046); the frequency and severity of medial degeneration did not differ significantly. The aneurysms with a malformed aortic valve showed more severe medial degeneration at the concavity compared to the convexity (p = .011); atherosclerosis was less common and did not show any significant differences. More than half of the samples also revealed at least a one-grade (mostly one-grade) difference among the quadrants in individual cases for both atherosclerosis and medial degeneration. Extreme differences were rare except for atherosclerosis in the tricuspid group. The results revealed only slight overall differences around the aortic circumference, with concavity being the most susceptible. Still, thanks to occurring inter- and intraindividual variability, the examination of all quadrants seems meaningful not to miss the most severe changes and to underscore the findings.

Normal and abnormal development of the aortic valve and ascending aortic wall: a comprehensive overview of the embryology and pathology of the bicuspid aortic valve.

A bicuspid aortic valve (BAV) is the most prevalent congenital cardiac anomaly, in which the valve has only two leaflets, instead of the normal three. Patients with a BAV have an increased risk of aneurysm formation and the development of an aortic dissection. Vascular smooth muscle cells in both the non- and dilated aortic wall are characterized by a maturation defect in all BAV patients, as compared to patients with a tricuspid aortic valve, which can contribute to inherent developmental susceptibility. Besides structural abnormalities of the vascular wall, a turbulent blood flow, caused by bicuspid valve geometry, could expedite the pathological process in the aortic wall, leading to aortopathy. Although the risk for aortopathy is significant, not all BAV patients experience (acute) aortic complications in their lifespan, highlighting the complexity of the pathogenetic process. Recent studies have focused on the embryonic development of semilunar valves and the ascending aortic wall. Their findings highlight that a defect in the embryogenesis could not only explain the development of a malformed aortic valve but also the increased risk for ascending aorta and arch pathology. This review presents an overview of the normal and abnormal development of the aortic valve and the aortic wall: a common defect in early embryogenesis causes the development of a BAV and associated aortopathy.

Elucidation of the genetic causes of bicuspid aortic valve disease.

The present study aims to characterize the genetic risk architecture of bicuspid aortic valve (BAV) disease, the most common congenital heart defect. We carried out a genome-wide association study (GWAS) including 2236 BAV patients and 11 604 controls. This led to the identification of a new risk locus for BAV on chromosome 3q29. The single nucleotide polymorphism rs2550262 was genome-wide significant BAV associated (P = 3.49 × 10-08) and was replicated in an independent case-control sample. The risk locus encodes a deleterious missense variant in MUC4 (p.Ala4821Ser), a gene that is involved in epithelial-to-mesenchymal transformation. Mechanistical studies in zebrafish revealed that loss of Muc4 led to a delay in cardiac valvular development suggesting that loss of MUC4 may also play a role in aortic valve malformation. The GWAS also confirmed previously reported BAV risk loci at PALMD (P = 3.97 × 10-16), GATA4 (P = 1.61 × 10-09), and TEX41 (P = 7.68 × 10-04). In addition, the genetic BAV architecture was examined beyond the single-marker level revealing that a substantial fraction of BAV heritability is polygenic and ∼20% of the observed heritability can be explained by our GWAS data. Furthermore, we used the largest human single-cell atlas for foetal gene expression and show that the transcriptome profile in endothelial cells is a major source contributing to BAV pathology. Our study provides a deeper understanding of the genetic risk architecture of BAV formation on the single marker and polygenic level.

Cardiac Findings at Necropsy in Acute Type A Aortic Dissection

Described herein are necropsy findings in 97 patients aged 22 to 82 years (mean 55), 37 women, 60 men, studied at necropsy with acute aortic dissection (AD) with the intimal-medial tear in the ascending aorta. The cases were studied from 1966 to 1989, a period when echocardiography and computed tomography were relatively infrequently available for diagnosis of AD. Arteriography was the method for diagnosis in most cases. Of the 97 cases, 30(31%) had operative intervention and 67 did not. Most appeared to have had systemic hypertension before the acute AD; only 4 had previous heart failure; only 8 had considerable atherosclerotic coronary disease; only 4 had a left ventricular (LV) scar and in each it was small; most (96%) had a normal-sized LV cavity (suggesting normal cardiac indices in them), and the other 4 had only a mildly dilated cavity; the heart weight in all 97 patients was increased; the quantity of subepicardial adipose tissue was increased in most patients, and the frequency of a congenitally malformed aortic valve was much higher than in the general population (6% - vs- 1%), but still uncommon. Thus, in > 90% of patients with acute Type A AD, coronary atherosclerosis was insignificant, myocardial fibrosis is absent, and the aortic valve has 3 cusps without stenosis.

Understanding the Aortic Root Using Computed Tomographic Assessment: A Potential Pathway to Improved Customized Surgical Repair.

There is continued interest in surgical repair of both the congenitally malformed aortic valve, and the valve with acquired dysfunction. Aortic valvar repair based on a geometric approach has demonstrated improved durability and outcomes. Such an approach requires a thorough comprehension of the complex 3-dimensional anatomy of both the normal and congenitally malformed aortic root. In this review, we provide an understanding of this anatomy based on the features that can accurately be revealed by contrast-enhanced computed tomographic imaging. We highlight the complimentary role that such imaging, with multiplanar reformatting and 3-dimensional reconstructions, can play in selection of patients, and subsequent presurgical planning for valvar repair. The technique compliments other established techniques for perioperative imaging, with echocardiography maintaining its central role in assessment, and enhances direct surgical evaluation. This additive morphological and functional information holds the potential for improving selection of patients, surgical planning, subsequent surgical repair, and hopefully the subsequent outcomes.

A case of bicuspid aortic valve malformation combined with Turner syndrome

A case of bicuspid aortic valve malformation combined with Turner syndrome

Endothelial nitric oxide synthase alterations are independent of turbulence in the aorta of patients with a unicuspid aortic valve

ObjectivesCertain aortic valve malformations predispose to ascending aortic aneurysm, although the mechanisms are incompletely understood. The aim of this study was to determine whether turbulence across the unicuspid aortic valve (UAV) contributes to regional differences in endothelial nitric oxide (eNOS) signaling in the ascending aortic wall. MethodsSamples were collected intraoperatively from the convex and concave ascending aortic wall from 64 patients with tricuspid aortic valves (TAVs; 25 nondilated, 17 dilated), or UAVs (9 nondilated, 13 dilated). ResultsIn normal-sized aortas, eNOS protein was decreased in UAV compared with TAV (P = .02) whereas mRNA was similar (P = .62). eNOS protein was increased in UAV-dilated aortas compared with UAV-nondilated aortas (P = .04), whereas dilatation had no impact on eNOS protein levels in TAV aortas (P = .73). Comparing only aneurysmal aortas, we found no difference in eNOS mRNA or protein between dilated TAV and UAV aortas (P = .26, P = .76). For eNOS mRNA and protein levels in normal and dilated UAV-associated aortas, no differences were found between concavity and convexity (all P > .05). This differed from dilated TAV aortas, which showed decreased eNOS mRNA in the convexity (P = .004) whereas eNOS protein levels were similar (P = .75). ConclusionseNOS downregulation is observed in the UAV-associated ascending aorta and is apparently independent of dilatation. No regional differences were found, however, which would be expected if eNOS changes occur due to wall shear stress. This implies a congenital defect in eNOS signaling that may be stronger than turbulence-induced expression patterns. Further research should define the role of eNOS in aortopathy associated with aortic valve disease.