A novel source of arterial valve cells linked to bicuspid aortic valve without raphe in mice.

Abnormalities of the arterial valve leaflets, predominantly bicuspid aortic valve, are the commonest congenital malformations. Although many studies have investigated the development of the arterial valves, it has been assumed that, as with the atrioventricular valves, endocardial to mesenchymal transition (EndMT) is the predominant mechanism. We show that arterial is distinctly different from atrioventricular valve formation. Whilst the four septal valve leaflets are dominated by NCC and EndMT-derived cells, the intercalated leaflets differentiate directly from Tnnt2-Cre+/Isl1+ progenitors in the outflow wall, via a Notch-Jag dependent mechanism. Further, when this novel group of progenitors are disrupted, development of the intercalated leaflets is disrupted, resulting in leaflet dysplasia and bicuspid valves without raphe, most commonly affecting the aortic valve. This study thus overturns the dogma that heart valves are formed principally by EndMT, identifies a new source of valve interstitial cells, and provides a novel mechanism for causation of bicuspid aortic valves without raphe.

Valvular heart disease (VHD) is a major cause of morbidity and premature death from cardiovascular diseases, making it an important clinical entity. Despite a dramatic decline in the incidence of rheumatic heart disease in industrialized countries, VHD remains highly prevalent. Although many VHDs are acquired during adult life, familial clustering and heritability have been noted for common heart valve defects, such as bicuspid aortic valve and myxomatous mitral valve prolapse, denoting an underlying genetic basis. Over the past decade, advances in our understanding of the genetic basis of familial VHD have been made through the unraveling of gene network and molecular mechanisms regulating normal valve development. Important progress has also arisen from a series of elegant studies that have focused on linkage analyses of large families with VHD, transgenic animal models, in vitro studies, and, more recently, microRNA and transcriptomic assessment of diseased tissues. Identification of the genes and molecular pathways responsible for the development of VHD has important implications in terms of improving current therapeutic strategies, as well as guiding the management of at-risk family members, with the ultimate aim to reduce the health burden of VHD. This article will summarize the current state of knowledge regarding the genetic basis of 2 common familial VHDs, namely mitral valve prolapse and bicuspid aortic valve, and highlight some of the recent findings that shed light on the pathogenesis of these diseases. Valvular heart disease (VHD) is a major cause of disability, diminished quality of life, and premature death from cardiovascular disease,1 making it an important clinical entity. Despite a dramatic decline in the incidence of rheumatic heart disease in industrialized countries, VHD remains highly prevalent.2 Although many VHDs are acquired during adult life, congenital forms present with abnormal valve structures at birth, yet may not manifest as valvular dysfunction …

The aortic arch and its branches form during the third week of embryogenesis, which involves a complex process. Abnormalities of the arch branching pattern arise by persistence of segments of arches that normally disappear or the disappearance of segments of arches that normally remain, or both [1]. The most common human aortic arch branching pattern has the innominate artery, the left common carotid artery and the left subclavian artery all as separate branches (Fig. 1). The most common variant branching pattern involves the left common carotid artery arising in a common origin with the innominate artery (Fig. 2), and the next most common the similar left common carotid artery originating from the innominate artery itself (Fig. 3). A true bovine arch involves a single common brachiocephalic trunk arising from the arch which then splits into the right subclavian artery, a bicarotid trunk and a left subclavian artery (Fig. 4), and is actually extremely uncommon in humans [2]. Originally the variations of t...

The purpose of this study is to evaluate the diagnostic performance of CT, compared with that of echocardiography and surgery, for differentiating between bicuspid and tricuspid aortic valves. Forty-seven patients with bicuspid valve and 47 patients with tricuspid aortic valve underwent retrospectively ECG-gated dual-source CT and echocardiography. Thirty-four (72%) of the 47 patients with bicuspid aortic valve underwent valve surgery. Two independent blinded observers assessed the CT image quality of the aortic valve during diastole and systole on a 4-point scale, determined which phase allowed the differentiation of valve type, distinguished between tricuspid and bicuspid aortic valves, and assessed for the presence of a raphe. Diagnostic performance of CT was determined using echocardiography and surgery as the reference standard. According to echocardiography and surgery, seven (15%) of the 47 bicuspid aortic valves had no raphe, and 40 (85%) had a raphe. CT image quality was diagnostic (i.e., scores of 1-3) in all 94 patients in both diastole and systole. Among patients with bicuspid aortic valve and no raphe, differentiation between tricuspid and bicuspid aortic valves could be performed in diastole in 100% (7/7) of cases. Among patients with bicuspid aortic valve and raphe, differentiation was possible only in systole in 5% (2/40) of cases and when combining diastole and systole in 95% (38/40) of cases. In three bicuspid aortic valves with raphe, the valve was misclassified by CT as tricuspid aortic valve. Overall sensitivity and specificity of CT for the diagnosis of bicuspid aortic valve were 94% and 100%. CT is highly accurate for differentiation between bicuspid and tricuspid aortic valves. For bicuspid aortic valves without raphe, diastolic reconstructions are sufficient, whereas in those with a raphe, additional reconstructions in systole are required.

Left ventricular outflow tract obstructions (LVOTOs) encompass a series of stenotic lesions starting in the anatomic left ventricular outflow tract (LVOT) and stretching to the descending portion of the aortic arch (Figure 1). Obstruction may be subvalvar, valvar, or supravalvar. These obstructions to forward flow may present alone or in concert, as in the frequent association of a bicuspid aortic valve with coarctation of the aorta. All of these lesions impose increased afterload on the left ventricle and, if severe and untreated, result in hypertrophy and eventual dilatation and failure of the left ventricle. LVOTOs are congenital in the vast majority of individuals younger than 50 years in the United States; some variants of subaortic obstruction are the exception. It is imperative to consider all patients with LVOTO at a high risk for developing infective endocarditis, and one should always institute appropriate measures for prophylaxis. The present article is intended as a contemporary review of the causes, manifestations, treatments, and outcomes of LVOTO; it will not address LVOTO in the pediatric population or genetic hypertrophic cardiomyopathy but will focus strictly on congenital malformations in the adult. Figure 1. Artist’s rendering of the LVOTO lesions in sequence as viewed from a superolateral orientation. A, Gradient echo cardiac MR image as viewed from the frontal projection demonstrating flow acceleration at a site of supravalvar aortic stenosis (white arrow) in a patient with Williams syndrome. The black arrow identifies the level of the unrestricted aortic valve. B, Classic radiological signs of coarctation of the aorta: rib notching (white arrows) as seen on a posteroanterior chest x-ray in a patient with coarctation of the aorta. The rib notching is caused by erosion of the inferior rib margins by dilated pulsatile posterior intercostals collateral arteries. The black arrow points to the Figure 3 silhouette that …

Time-resolved, 3D, phase-contrast magnetic resonance imaging (4D flow) is an effective means of evaluating dynamic multidirectional blood flow in the thoracic aorta.1 We have used the technique for characterization of abnormal flow features in a 14-year-old boy with aortic coarctation and bicuspid aortic valve (BAV) but without evidence of aortic stenosis or regurgitation. In addition to the expected flow disturbance in the region of the juxtaductal coarctation (Figure 1), we show an unusual flow feature in the ascending aorta that has not been previously reported in this clinical setting and that may be unique to BAV: 2 discrete nested helices of midsystolic blood flow in a nonaneurysmal aorta (Figure 2). Figure 1. Fourteen-year-old boy with BAV and aortic coarctation. A, Three-dimensional contrast-enhanced magnetic resonance angiography that demonstrates a focal juxtaductal coarctation and prominent internal mammary and …

Discussion: Session 1—Ascending Aorta

The art of aortic valve repair

Acquired Stenosis of All Four Heart Valves in a Boxer Mix Dog

A bicuspid aortic valve is found in approximately 2 % of the population. The data in the literature concerning the incidence of clinical manifestations are inconsistent, and a detailed comparison with patients with tricuspid aortic valve is not yet available. We analyzed the clinical manifestations and demographic data of patients with bicuspid and tricuspid aortic valves who underwent an operation on the aortic valve and/or the ascending aorta over a five-year period. The subjects were 2570 adult patients, of whom 555 (21.6 %) had a bicuspid aortic valve. The patients with a bicuspid aortic valve were, on average, 10 years younger at surgery than those with a tricuspid aortic valve (57.0 +/- 13.1 vs. 66.4 +/- 11.8 years, P < 0.0001). The spectrum of diseases necessitating aortic valve surgery was the same in both groups of patients. An increased diameter of the ascending aorta > or = 4.5 cm was seen significantly more often in patients with bicuspid aortic valve (22.7 % vs. 5.5 %, P < 0.0001). We conclude that there are important differences in clinical manifestations between patients with bicuspid and tricuspid aortic valves, so that patients with bicuspid valve need special attention.

Isolated Bicuspid Aortic Valve Repair With Double Annuloplasty: How I Teach It

Matrix metalloproteinase activity in thoracic aortic aneurysms associated with bicuspid and tricuspid aortic valves

Invited Commentary

Surgical treatment of bicuspid aortic valve disease: Knowledge gaps and research perspectives

We describe a case of native valve endocarditis caused by Staphylococcus lugdunensis, a perineal skin commensal, and review 28 other cases from the medical literature. Correctly identifying this coagulase-negative organism is critical because endocarditis is usually associated with left sided valvular disruption and life-threatening embolic complications, reminiscent of disease caused by Staphylococcus aureus. Urgent surgical intervention is necessary in most cases.