Aortic Valve Aneurysm Research Articles

Bicuspid Aortic Valve and Thoracic Aortic Aneurysm: Three Patient Populations, Two Disease Phenotypes, and One Shared Genotype

Bicuspid aortic valve (BAV) and thoracic aortic aneurysm (TAA) are two discrete cardiovascular phenotypes characterized by latent progressive disease states. There is a clear association between BAV and TAA; however the nature and extent of this relationship is unclear. There are both distinct and overlapping developmental pathways that have been established to contribute to the formation of the aortic valve and the aortic root, and the mature anatomy of these different tissue types is intimately intertwined. Likewise, human genetics studies have established apparently separate and common contributions to these clinical phenotypes, suggesting complex inheritance and a shared genetic basis and translating 3 patient populations, namely, BAV, TAA, or both, into a common but diverse etiology. A better understanding of the BAV-TAA association will provide an opportunity to leverage molecular information to modify clinical care through more sophisticated diagnostic testing, improved counseling, and ultimately new pharmacologic therapies.

Perforated Mitral Valve Aneurysm in the Posterior Leaflet without Infective Endocarditis

Aneurysm of the mitral valve, although uncommon, occurs most commonly in association with infective endocarditis of the aortic valve and true mitral valve aneurysm is a rare cause of mitral regurgitation. We report a case with perforated mitral valve aneurysm in the posterior leaflet without concurrent infective endocarditis initially mistaken diagnosis of cystic mass, which was confirmed at operation with successful mitral valve annuloplasty.

Bicuspid Aortic Valve and Dilatation of the Ascending Aorta

The aortic valve is a complex structure that relies on coordinated interactions between its component parts. It is now established that the cells within, and on the cusps, play a key role in the optimal performance of the valve within the unique mechanical environment in which it is required to function. In the majority of individuals, the valve opens and closes over 3 billion times without any significant problems. The importance of the relationship between structure and function is illustrated by the inability of a valve that has structural malformations to function normally throughout life. Valves that have only two valve functional cusps, as opposed to the usual three, are associated with accelerated disease and failure at a young age. The presence of bicuspid aortic valves represents a significant issue, since they are estimated to occur in 1-2% of live births. In addition to the development of stenotic disease at a young age, the presence of a bicuspid valve is also associated with diseases of the aorta. This special issue contains a number of review articles and original manuscripts that specifically address the issues related with bicuspid aortic valves and associated dilatation of the ascending aorta. The papers include two general reviews of the subject that covers embryology, structure genetics of bicuspid valve formation, clinical aspects of bicuspid valves, and highlights of where gaps in our knowledge exist. Subsequent contributions focus more specifically on the morphology of bicuspid valves and how different valve configurations relate to different pathophysiological outcomes with regard to the defects in the medial wall of the ascending aorta, dilation of the proximal aorta, and their effect on the flow patterns across the valve. The association between the presence a bicuspid aortic valve and thoracic aortic aneurysms is the subject of another paper. Whiles these are two separate entities, they share common developmental pathways. The paper sets out to explore how these shared genetic pathways can manifest individual patient populations. The management of the patients with a bicuspid aortic valve, aortic aneurysms, or both, represents a specific clinical challenge. These challenges are assessed with regard to the anatomical differences in the phenotype of the bicuspid valve, the pathophysiology, and natural history of the patients. In addition to the review articles on the bicuspid valve and aortic aneurysms, this issue also contains papers that present original data. S. A. Mohamed et al. examine the expression of nitric oxide synthase in aortic aneurysms from patients with bicuspid and tricuspid valves. The regional differences reported on nitric oxide synthase expression in the two groups suggest dysregulation of the nitric oxide system in patients with bicuspid aortic valves. This study is of interest due to the reported incidence of bicuspid valve formation in mice lacking the endothelial nitric oxide synthase gene. The second original study by J. Benedik et al. examines parameters relating to thickness of the aortic wall, diameters at different regions of the aortic root wall, and the cohesion of the aortic wall of 190 patients undergoing valve surgery. While some differences existed in the geometry of the aortic root and wall thickness, they report no difference in the tensile strength curves between bicuspid and tricuspid valves, suggesting that the pathology of the aorta and valve is unrelated. The only current treatment for individuals who develop disease in their bicuspid valve or aortic aneurysms remains surgical repair or replacement of the valve and or aorta. The current guidelines for treatment, and importantly when to treat asymptomatic patients, are reviewed by C. D. Etz et al. in the last paper of this issue. The papers in this issue are a reflection of the different areas of research and treatment that are pertinent to understanding the development and functional consequences of having a bicuspid aortic valve. Additional studies are required to understand the genetics of this condition and why bicuspid valves have an association with aortic aneurysms. Ultimately, this will lead to more effective treatment of patients affected with these conditions. Martin Misfeld Ani C. Anyanwu Adrian H. Chester

104 Aortic root management in patients with bicuspid aortic valve disease and aneurysm of the ascending aorta: A comparative analysis of 3 strategies

104 Aortic root management in patients with bicuspid aortic valve disease and aneurysm of the ascending aorta: A comparative analysis of 3 strategies

Aortic valve aneurysm: a result or reason?

Aortic valve aneurysm: a result or reason?

Mitral and aortic valve aneurysms secondary to infective endocarditis: impressive images of a rare echocardiographic finding

Mitral and aortic valve aneurysms are uncommon, but the coexistence of both mitral and aortic valve aneurysms in the same patient is a rather unusual finding in the literature. We report a rare clinical case of a patient with both mitral and aortic valve aneurysms and a rupture of the mitral valve aneurysm, as the main echocardiographic manifestations of infective endocarditis. This clinical case emphasizes infective endocarditis as the most frequent cause of valve aneurysms, reminding that this diagnosis should be suspected even in the absence of vegetations. This case demonstrates that transoesophageal echocardiography plays a major role on diagnosis of valve aneurysms, revealing the rupture of the mitral valve aneurysm and defining this rupture as the main mechanism of mitral valve regurgitation. This case also underlines the role of transoesophageal echocardiography on management decisions, allowing a morphological evaluation of the mitral valve and selection of the appropriate surgical strategy.

Subaortic Pseudoaneurysm of the Left Ventricle Complicating Staphyloccal Endocarditis*

Subaortic pseudoaneurysms are rare but can be a cause of sudden death in young individuals. This case report involves a 20-year-old Vietnamese male who died suddenly from rupture of a subaortic pseudoaneurysm with resultant hemopericardium with tamponade. He had a history of bicuspid aortic valve with recent but healed Staphylococcal endocarditis. A review of the literature reveals few similar cases and enlightens the association between aortic bicuspid valve, endocarditis, and subvalvular aortic aneurysm. The pathogenesis as well as recent studies that identified aneurysm predisposing genes in patients with bicuspid aortic valve will be discussed.

009 CLINICAL AND EPIDEMIOLOGICAL PREDICTORS OF STAPHYLOCOCCUS AUREUS, VIRIDANS STREPTOCOCCAL, AND ENTEROCOCCAL NATIVE VALVE ENDOCARDITIS AT INITIAL CLINICAL EVALUATION

A 53-year-old man who presented with an embolic stroke was found to have new mild to moderate aortic valve regurgitation on transthoracic echocardiography. Subsequent transesophageal echocardiography revealed an isolated aortic valve aneurysm, without evidence of valve vegetations. Four of 4 blood cultures grew Enterococcus faecalis. This unique case represents the first report of an aortic valve aneurysm associated with enterococcal endocarditis. An important teaching point is the need to investigate for endocarditis in patients with valve aneurysms of unknown etiology, even in the absence of valve vegetations on transesophageal echocardiography.

Single ventricle, bicuspid aorta and interatrial wall aneurysm as a rare complex adult congenital heart disease: a case report

BackgroundSingle ventricle, bicuspid aortic valve and interatrial wall aneurysm in adulthood are a rare and unique case in medical literature. This presented case with congenital heart disease has never been treated surgically and clinical consequences seriously presented in adulthood.Case presentationA 27 year old man with complex congenital heart disease presented. At the age of six, the single ventricle was ultrasonographly diagnosed, but at age 27 clinical consequences started to be seriously present. We explored his history, clinical course, physical examination, laboratory findings, medical treatments and actual patient condition.ConclusionThe possibilities for surgical evaluation are presented.

Enterococcal Endocarditis Presenting as an Isolated Aortic Valve Aneurysm: Case Report and Review of Literature

A 53-year-old man who presented with an embolic stroke was found to have new mild to moderate aortic valve regurgitation on transthoracic echocardiography. Subsequent transesophageal echocardiography revealed an isolated aortic valve aneurysm, without evidence of valve vegetations. Four of 4 blood cultures grew Enterococcus faecalis. This unique case represents the first report of an aortic valve aneurysm associated with enterococcal endocarditis. An important teaching point is the need to investigate for endocarditis in patients with valve aneurysms of unknown etiology, even in the absence of valve vegetations on transesophageal echocardiography.

Subcoronary Implantation of a Stentless Valve in Patients with Aortic Aneurysms

Experience with a new operation for patients with aortic valve disease and aneurysm or dissection of the ascending aorta is described. Twenty-four patients aged 66-87 years were operated on using a subcoronary implantation technique with a stentless aortic valve bioprosthesis and an extension using a vascular tube prosthesis. No major adverse cardiac events were observed in the postoperative period. This operation offers a safe alternative to the technically more demanding procedures of composite bioprosthetic ascending aortic replacement or full root replacement.

Unicuspid Aortic Valve and Aortic Arch Aneurysm in a Patient with Turner Syndrome

Unicuspid Aortic Valve and Aortic Arch Aneurysm in a Patient with Turner Syndrome

Bicuspid aortic valve: clinical approach and scientific review of a common clinical entity

Bicuspid aortic valve (BAV) disease is becoming increasingly respected by clinicians. This enhanced appreciation is based on recognition of how common and virulent this disease really is. This disease is now known to be the most common congenital lesion affecting the human heart (with potential competition in frequency posed by mitral valve prolapse). It is estimated that the BAV lesion alone accounts for more morbidity and mortality than all the other congenital cardiac lesions combined. Many authorities feel that this disease is so virulent that every individual with a BAV will, given enough time, develop aortic stenosis, aortic insufficiency or aortic aneurysm/dissection related to the bicuspid valve disease. This review looks in detail at clinical issues related to BAV disease, including genetics, pathophysiology, diagnosis, management and surgical decision making. The picture emerging from basic and clinical studies is of a defect in collagen metabolism affecting not only the aortic valve, but also the wall of the aorta itself. Timely intervention for bicuspid-related aortic valve disease or aneurysm can preserve both duration of life and quality of life in affected individuals.

Over-expression of Matrix Metalloproteinase-10 is Associated with Vascular Smooth Muscle Cell loss in Marfan Syndrome and Bicuspid Aortic Valve Aneurysm

Thoracic aortic aneurysm associated with Marfan syndrome (MFS) or bicuspid aortic valve (BAV) is characterized by over-expression of matrix metalloproteinases (especially MMP-2 and MMP-9). Up-regulated MMP-10 has been linked to reduced cell–matrix interaction, cell detachment, dilation and rupture of blood vessels. We investigated MMP-10 expression in aortic aneurysm tissue and cultured VSMCs and its relation to VSMC apoptosis. Aortic tissue and cultured VSMCs were derived from subjects with MFS (five males, two females; 40 ± 22 years, mean ± S.D.) and BAV (five males, two females; 60 ± 16 years), and normal subjects (three males, six females; 44 ± 14 years). Caspase-3 was used as a marker of cells undergoing apoptosis. Specific staining of aortic tissue showed increased expression of MMP-10 in MFS and BAV (P < 0.05). Similar results were obtained in cultured VSMCs. In VSMCs characterized by cell shrinkage of cell and nuclear condensation there was enhanced staining of MMP-10. The same VSMCs showed caspase-3 labelling in alternate serial sections. The proportion of apoptotic VSMCs in aneurysm tissue was significantly increased in the aneurysm wall of patient groups compared to normal subjects (P < 0.05). Gelatin zymography showed no active form of MMP-10 and Western blot indicated the presence of the MMP-10 pro-form only with higher levels of expression in VSMC conditioned media from patients compared to normals (P < 0.05). The study suggests that expression of MMP-10 is related to progression of aortic wall aneurysm in MFS and BAV.

Abstract 1563: Angiotensin II Type 2 Receptor Expression and CD34 Progenitor Cell Co-localization in Aortic Aneurysm

Altered expression of angiotensin II type-1 and type-2 receptors (AT1, AT2) has been implicated in the development of aortic aneurysm. We used immunohistochemistry to examine the expression of AT1 and AT2 in thoracic and abdominal aortic aneurysm. Thoracic and abdominal aortic tissue samples were collected from organ donor subjects (normal controls; 4M, 9F; age 40±12yr, mean ± SD), and subjects with Marfan syndrome (MFS; 6M, 3F; 42±24yr), bicuspid aortic valve (BAV; 10M, 4F; 62±17yr) or abdominal aortic aneurysm (AAA; 8M, 2F; 72±10). In each type of aneurysm there was mild expression of AT1 and moderate expression of AT2 associated with intimal thickening and the tunica adventitia compared to mild expression of AT1 and negligible expression of AT2 in control aorta. In aneurysm tissue AT1 and AT2 expression, transforming growth factor (TGF)-beta1 expression and progenitor cell (CD34+) localization were also present in areas of tissue remodeling associated with focal medial degeneration, angiogenesis and areas of inflammation. In cell culture experiments aortic fibroblasts (AF) derived from adventitial aneurysm tissue showed moderate expression of AT1 and strong expression of AT2 while control AF showed mild expression of AT1 and negligible expression of AT2. Negligible to mild expression of active TGF-beta1 was observed in all cultured AF. Interestingly adventitial aneurysm cultured in endothelial growth media resulted in the appearance of spindle shaped cells with CD31+ endothelial colonies sprouting among them. Moderate active TGF-beta1 and AT1 and strong AT2 expression were observed in these CD31+ cells. Cultured control adventitia only had spindle cell outgrowth and negligible active TGF-beta1, AT1 and AT2 expression. In summary aneurysm tissue and cultured AF and CD31+ cells of aneurysm origin showed increased expression of AT2 and an absence of increased AT1 expression. Increased AT2 expression in areas of pathological remodeling suggests an active role for AT2 in aneurysm development. Co-localization of increased AT2 with active TGF-beta1 expression and CD34+ cells suggests a role for AT2 in endothelial differentiation and angiogenesis.

Novel NOTCH1 mutations in patients with bicuspid aortic valve disease and thoracic aortic aneurysms

Bicuspid aortic valve is a common condition and is associated with a significantly increased risk of developing thoracic aortic aneurysms and acute aortic dissection. Patient-specific prediction of the risk of developing thoracic aortic aneurysm, however, is imprecise. We hypothesize that genotypic variations in patients with bicuspid aortic valves contribute to this observed variability in aortic phenotype. We, therefore, investigated the potential relationship between mutations in regions of NOTCH1 recently reported to be associated with bicuspid aortic valve and the phenotype of bicuspid aortic valve and thoracic aortic aneurysms in unrelated patients undergoing surgical repair. We performed a targeted mutational analysis of NOTCH1 using genomic DNA from 48 unrelated subjects with concomitant bicuspid aortic valve and thoracic aortic aneurysm using denaturing high-performance liquid chromatography and DNA sequencing. We focused on exons in which mutations associated with bicuspid aortic valve have been reported previously. Results were compared with control subjects with trileaflet aortic valves (n = 94), bicuspid aortic valves, and normal aortas (n = 22) and in subjects with tricuspid aortic valves and thoracic aortic aneurysms (n = 28). Four unique, nonsynonymous (3 novel) variants were identified in 5 (10.4%) of 48 patients with concomitant bicuspid aortic valves and thoracic aortic aneurysms compared with only 3 (2.1%) of 144 control subjects (P = .02). Of these, 2 novel missense mutations, A1343V and P1390T, were observed only in patients with bicuspid aortic valves and tricuspid aortic aneurysms. This targeted analysis involving NOTCH1 exons previously implicated in familial and sporadic bicuspid aortic valve demonstrates overrepresentation of NOTCH1 missense variants among patients with bicuspid aortic valves and thoracic aortic aneurysms. Identification of aneurysm-predisposing susceptibility genes may lead to gene-directed surgical therapy of the ascending aorta for patients with bicuspid aortic valves.

Valve-Sparing Operation for Aortic Root Aneurysm Late After Mustard Procedure

The aortic valve reimplantation technique leads to excellent clinical outcome in patients with aortic valve incompetence and aneurysms of the ascending aorta. This technique is now applied for aneurysms of ascending aorta, aortic dissection type A, and even dilatation of pulmonary autograft after the Ross operation. We report a case of aortic root dilatation late after a Mustard operation for transposition of the great arteries that was successfully managed by valve-sparing aortic root reimplantation.

Abnormal expression of stromelysin-2 (MMP10) in Marfan syndrome (MFS) and bicuspid aortic valve (BAV) aneurysm

Malcolm West. Department of Medicine, University of Queensland, Prince Charles Hospital, Brisbane, Australia

Aortic operation after previous coronary artery bypass grafting

Aortic surgery for progressive aortic valve disease or aortic aneurysm after previous coronary artery bypass grafting (CABG) is a challenging procedure. We report the outcome of aortic reoperation after previous CABG and evaluate our management of patent grafts and our methods for obtaining myocardial protection. From February 2001 to July 2003, 6 patients with progressive aortic valve disease and aneurysm of the thoracic aorta were operated on. The group comprised 3 men and 3 women with a mean age of 67.6 years. There were 4 patients with an aneurysm of the aortic arch, 1 with chronic ascending aortic dissection, and 1 with progressive aortic valve stenosis. The interval between previous CABG and aortic surgery was 74.0 +/- 44.2 months. All reoperations were performed via median resternotomy. Myocardial protection was obtained by hypothermic perfusion of patent in-situ arterial grafts following cold-blood cardioplegia administration via the aortic root under aortic cross clamping. The operative procedure was aortic arch replacement in 4 patients, ascending aortic replacement with double CABG in 1, and aortic valve replacement in 1. All patients survived the reoperation. Postoperative maximum creatine kinase-MB was 49.2 +/- 29.8 and no new Q-waves occurred in the electrocardiogram nor were any new wall motion abnormalities recognized on echocardiography. There were no late deaths during a follow-up of 30.7 months. Reoperative aortic procedures after CABG can be performed safely with myocardial protection via hypothermic perfusion of a patent in-situ arterial graft.

Transesophageal Echocardiographic Recognition of Mitral Valve Aneurysm

Aneurysm of the mitral valve leaflet is typically a complication of aortic valve endocarditis because of the anatomic relationship between the anterior mitral leaflet and the left ventricular outflow tract. 1 - 4 The aortic regurgitant jet or vegetation prolapsing into the left ventricular outflow tract infects the anterior leaflet of the mitral valve. This occurrence has been termed the jet lesion or kissing lesions effect. Transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) are the preferred diagnostic procedures. Transesophageal echocardiography offers better resolution of mitral valve morphologic characteristics and aneurysmal structure. Herein, we describe a case of infective endocarditis that had the typical features of aortic valve endocarditis coexisting with aortic valve regurgitation and aneurysm of the anterior mitral leaflet, which were diagnosed by TEE.