Nonsyndromic genetic predisposition to aortic dissection: a newly recognized, diagnosable, and preventable occurrence in families

The major diseases affecting the aorta are aortic aneurysms and dissections, with patients with acute dissections often presenting in the emergency department (ED). Recent studies demonstrate a strong genetic predisposition to thoracic aortic aneurysms and dissections, independent of syndromes traditionally considered to predispose to aortic disease (such as Marfan syndrome). Nonsyndromic familial thoracic aortic aneurysms and dissections are inherited in families as an autosomal dominant disorder and a variable age of onset of the aortic disease. The case reported here illustrates the critical importance of obtaining a family history of thoracic aortic aneurysms and dissections, along with unexplained sudden death, when assessing an individual with chest pain in the ED, regardless of age and in the absence of a known genetic syndrome.     

Genetic basis of thoracic aortic aneurysms and dissections

The major diseases affecting the aorta are aortic aneurysms and dissections, which are classified based on anatomic location. Diseases affecting the ascending aorta, such as thoracic aortic aneurysms and type I and II dissections, are primarily associated with medial necrosis on pathologic examination. Medial necrosis is characterized by fragmentation and loss of elastic fibers, loss of smooth muscle cells, and interstitial collections of collagenous tissue and basophilic ground substance. Medial necrosis occurs as part of the normal aging of the aorta but is accelerated by other conditions, including hypertension and genetic alterations that predispose persons to these aortic diseases. The etiologies of many of the genetic syndromes, such as Marfan syndrome, that predispose persons to thoracic aortic aneurysms and dissections are understood. Studies are just beginning to elucidate the genes that predispose persons without known syndromes to these aortic diseases, and a major locus for this condition, termed the TAAD1 locus, has been mapped to 5q13-14. Future characterization of this gene and others will enhance the ability to determine persons at risk for aortic aneurysms and dissections and will define molecular mechanisms involved in the pathogenesis of this disorder.     

Actual management of patients with familial ascending aortic aneurysms and type-A aortic dissections

BACKGROUND: There are few families with the diagnosis of ascending aortic aneurysm and acute type-A aortic dissection inherited as an autosomal-dominant disorder in the absence of a known genetic syndrome. METHODS: We investigated a family with 26 members in whom ascending aortic aneurysms and acute type-A aortic dissections occurred over three generations. Examinations were performed to identify family members at specific risk. RESULTS: Six members presented with acute type-A aortic dissections and three relatives had ascending aortic aneurysms. Clinical examinations showed no characteristics of a known genetic syndrome. Molecular genetic analysis revealed no mutations known to cause a form of autosomal-dominant inherited aortic disease. CONCLUSION: Adequate diagnostic measures are mandatory in families with ascending aortic aneurysms or type-A aortic dissections to identify or exclude family members at risk for aortic diseases. Even in the absence of identifiable mutations causing isolated aortic aneurysms or aortic dissections, we recommend standardised examinations of all first-degree relatives of affected families. An indication for prophylactic aortic root replacement should be considered for patients at risk.     

Are aortic aneurysms caused by atherosclerosis?

BACKGROUND. The emerging controversy concerning the causal role of atherosclerosis in the development of aortic aneurysms was examined using the accumulated clinical and autopsy data obtained during a 20-year follow-up of a cohort of more than 8,000 men of Japanese ancestry in Hawaii. METHODS AND RESULTS. Analyses of 174 clinical incident events indicated that there were two types of aneurysmal disease, 151 aortic aneurysms and 23 aortic dissections. The baseline risk factors that predicted the clinical aortic aneurysms were the same factors that predicted aortic atherosclerosis in the same cohort, namely, high blood pressure, high serum cholesterol, and cigarette smoking. These same risk factors were also significantly associated with the occurrence of 27 aortic aneurysms among 293 autopsied men. The less common aortic dissections had an age-specific incidence pattern indicative of an innate susceptibility precipitated by an exposure to another factor. This pattern was consistent with the findings that the incidence of aortic dissections was predicted mainly by baseline high blood pressure. CONCLUSIONS. From the perspective of prevention, it appears that the risk factors for aortic atherosclerosis and probably atherosclerosis itself are necessary elements in the causal pathway for the great majority of aortic aneurysms in this cohort.     

Ascending thoracic aneurysms are associated with decreased systemic atherosclerosis

STUDY OBJECTIVES: We noted clinically that patients with aortic root aneurysms and dissections seemed to have little systemic atherosclerosis. It is our objective to determine whether there is a negative association between ascending thoracic aneurysms and systemic atherosclerosis. DESIGN: Atherosclerosis was quantified by evaluating non-contrast CT images of the chest and scoring the degree of calcifications as a marker for atherosclerosis in the coronary arteries and aorta. PATIENTS: The degree of calcification was compared in 64 patients with aortic root aneurysm (annuloaortic ectasia, 31 patients; type A dissection, 33 patients) vs 86 control subjects. Multivariable analysis was applied to test for an association between aortic root aneurysms and systemic calcification independent of risk factors for atherosclerosis. RESULTS: Multivariable analysis revealed that patients with ascending aortic aneurysms of the annuloaortic ectasia type and patients with type A dissections had significantly lower overall calcification scores in their arterial vessels compared to patients in the control group (p = 0.03 and p < 0.0001, respectively). These results were independent of all other risk factors for atherosclerosis. Smoking, dyslipidemia, diabetes, and age were all found to increase the degree of atherosclerosis (p < 0.01 to 0.05). CONCLUSIONS: Aortic root pathology (annuloaortic ectasia or type A dissection) is associated with decreased systemic atherosclerosis. It is possible that a mechanism exists whereby the same genetic mutations predisposing patients to ascending aortic aneurysms also exert a protective effect against systemic atherosclerosis.     

Ascending aortic arch aneurysms and dissections: discussion and nursing management

Ascending aortic arch aneurysms and aortic dissections are serious conditions with high mortality and morbidity. Aneurysms can be defined according to morphology or location and are usually precipitated by atherosclerosis or cystic medial necrosis. Intact aortic aneurysms are often asymptomatic, while chest pain is frequently the predominant symptom associated with aortic dissections. The diverse clinical presentation of aneurysms and dissections makes diagnosis difficult. When the aneurysm is large or the patient is symptomatic, surgical intervention is the preferred treatment and consists of replacing a segment of the aorta with a synthetic graft. Postoperative nursing care focuses on altered tissue perfusion, fluid volume deficit, potential respiratory insufficiency and patient teaching.     

Ultrafast computed tomography in the diagnosis of aortic aneurysms and dissections

UFCT, by virtue of its 50 to 400 millisecond acquisition times, 0.75 to 1.5 mm resolution, and excellent vascular opacification, provides a rapid, minimally invasive method for assessing aortic aneurysms and dissections. During a 3.5-year period, 50 patients with suspected thoracic, thoracoabdominal, and abdominal aortic aneurysms or dissections were evaluated using the Imatron C-100 UFCT scanner. Eighteen patients had thoracic or thoracoabdominal aneurysms. 17 had thoracic or thoracoabdominal dissections, 7 had abdominal aneurysms, and in 8 no aneurysms or dissections were found. In 23 of the 35 patients with thoracic or thoracoabdominal aneurysms or dissections, the UFCT findings accurately reflected the findings at aortography, surgery, or autopsy. There was one false-positive examination. The remaining 11 patients with UFCT findings of aneurysm or dissection were followed clinically. In the 7 patients with abdominal aneurysms, 4 were confirmed by angiography or surgery, and 3 were followed clinically. Of the 8 patients with negative UFCT examinations, 2 had subsequent angiography that failed to show an aneurysm, and 6 were followed from 6 to 30 months without developing findings suggestive of aneurysm. UFCT appears to be a useful, minimally invasive technique for detecting and following aortic aneurysms and dissections.     

Transluminal endovascular stent grafting of aortic dissections and aneurysms: a concise review of the major trials

Transluminal endovascular repair of the vascular system is rapidly emerging as a leading therapeutic modality for aortic dissections and aneurysms. The use of transluminal endovascular stent grafting has been used to intervene successfully on the aorta and its major branch vessels. There have been several studies examining transluminal endovascular stent grafting of thoracic aortic aneurysms, dissections, and abdominal aortic aneurysms. This paper reviews some of the major trials of transluminal endovascular stent grafting as well as its major limitation, endoleak.     

Stenting Versus Surgery of the Thoracic Aorta

Aneurysms and dissections of the aorta represent a potentially life-threating situation. Surgical resection and interposition of vascular prostheses (Gortex or Dacron) has long been considered the only treatment option. Although there have been great strides during the past decades in the management of patients with thoracic aortic aneurysms and dissections by new surgical techniques, postoperative morbidity and mortality remain high. The afflicted population is usually of older age and present with a variety of comorbidities and significant impact on postsurgical outcome. Postoperative complications, such as paraplegia and renal insufficiency, contribute to prolonged hospital stays and higher medical costs. Conversely, interventional stent-graft placement may be a promising nonsurgical strategy for the treatment of thoracic aortic aneurysms and dissections. The endovascular stent-graft prostheses is based on the concept of a metal grid covered with vessel graft material. The initiation of the natural healing process by exclusion of an aneurysm or sealing of the proximal entry in dissection induces remodeling of the aortic wall and consolidation of the false lumen. Although the initial results of stent-graft treatment of thoracic aortic aneurysms and dissections are promising, the concept of nonsurgical reconstruction must be subjected to a randomized long-term study.     

The complementary role of magnetic resonance imaging, Doppler echocardiography, and computed tomography in the diagnosis of dissecting thoracic aneurysms

Non-ECG gated MRI was compared with 2DE and/or CT scans in 10 patients with dissecting aneurysms proven by angiography and/or surgery. Patient ages ranged from 48 to 85 years (mean 69.6). Six had DeBakey type I dissections and four had DeBakey type III dissections. MRI was diagnostic for aortic dissection in nine cases and suggestive in the tenth. 2DE was diagnostic in six out of nine patients, suggestive in two patients, and nondiagnostic in one patient. CT was diagnostic in the three cases in which it was employed. MRI demonstrated a dilated ascending aorta with thickened walls in all type I dissections as well as an intimal flap and slow flow in the false channel in four patients. In the other two patients with type I dissection, MRI detected the intimal flap in the descending aorta but not in the ascending aorta, whereas 2DE revealed the ascending aortic intimal flap in both of these patients and CT showed it in one of them. In the type III dissections, MRI demonstrated a thickened wall and thrombus in the lumen in all four cases, and the intimal flap in three out of the four. 2DE excluded ascending aortic involvement in all three type III dissections. Six other patients with fusiform dilated ascending aortas had no evidence of dissection by MRI, 2DE, and aortography. Thus, non-ECG gated MRI alone or in combination with 2DE and/or CT is useful in the diagnosis of dissecting thoracic aneurysm and in assessing the extent of the dissection. In addition, the differentiation of dissecting aneurysms of the aorta from fusiform dilatation of the aorta is made possible by these noninvasive techniques.     

Successes and challenges of using whole exome sequencing to identify novel genes underlying an inherited predisposition for thoracic aortic aneurysms and acute aortic dissections

Thoracic aortic aneurysms involving the aortic root and/or ascending aorta can lead to acute aortic dissections. Approximately 20% of patients with thoracic aortic aneurysms and dissections (TAAD) have a family history of the disease, referred to as familial TAAD (FTAAD) that can be inherited in an autosomal dominant manner with variable expression with respect to disease presentation, age of onset and associated features. Whole exome sequencing (WES) has been used to identify causative mutations in novel genes for TAAD. The strategy used to reduce the large number of rare variants identified using WES is to sequence distant relatives with TAAD and filter for heterozygous rare variants that are shared between the relatives, predicted to disrupt protein function and segregate with the TAAD phenotype in other family members. Putative genes are validated by identifying additional families with a causative mutation in the genes. This approach has successfully identified novel genes for FTAAD.     

3例主动脉瘤及主动脉夹层合并主动脉良性肿瘤及瘤样病变的临床病理学分析

目的:发生在主动脉的良性肿瘤并伴有主动脉疾病(主动脉瘤、主动脉夹层及马方综合征)是少见病例。本文总结分析伴有主动脉疾病的主动脉良性肿瘤及瘤样病变的临床病理特点,复习发生于主动脉良性肿瘤的文献,探讨其发生与主动脉疾病之间的关系。方法:回顾性分析我院病理科2006年至2012年,手术切除的胸主动脉瘤及胸主动脉夹层的标本129例,通过复习临床病历,观察HE染色切片,辅以弹力/VG及Masson等组织化学染色及SMA、CD31及CD34等免疫组织化学染色,对主动脉壁结构的改变进行分析。结果:所有病例主动脉壁均发生了结构的改变,主要是中膜弹力纤维、平滑肌及基质的变化,但有3例标本内膜增生明显,1例形成了平滑肌瘤,另2例发生了内膜下弹力纤维瘤样增生及平滑肌瘤样增生。结论:主动脉壁内不同组成成分的改变,使得主动脉壁重构,导致主动脉瘤及主动脉夹层的形成,而某一单一成分过度增生可形成主动脉腔内的肿瘤。     

Aortic aneurysms excluding Marfan's syndrome

The causal factors of aneurysm are not the same in the ascending and abdominal aorta. Atheroma is the dominant lesion in the abdominal aorta and genetic abnormalities predisposing to "mediacystic necrosis" are more frequently observed in ascending aortic aneurysms. The causal genetic abnormalities are multiple: abnormalities of fibrillin type I in Marfan's syndrome, collagen abnormalities in the Ehlers-Danlos syndrome, abnormalities of microfibrils, possible metallo-proteases, with many gene candidates. Finally, some ascending aortic aneurysms are associated with bicuspid aortic valves, some of which are familial. Familial factors are less evident in abdominal aortic aneurysms: genes favoring atheroma may be responsible but the factors which predispose to dilatation and non stenosis are not well known: they would seem to be general factors because the tendency to arterial dilatation is diffuse. In all cases, because of the high risk of disease in a close relative, a familial enquiry would seem to be justified with echocardiography for close relatives of affected subjects, especially when young and female.     

Endovascular repair of lesions of descending thoracic aorta: aneurysms and dissections

The morbidity and mortality of open repair of descending thoracic aortic lesions remains uncomfortably high. Shortly after the advent of an endovascular approach for infrarenal abdominal aortic aneurysms, attempts have been made to apply similar technologies to the thoracic aorta. Early experiences with endovascular grafts for thoracic aortic aneurysms have met with good to moderate success but have provided a framework for development of improved technologies specifically designed for this anatomic region. Early studies with second generation devices have shown more promise. Aortic dissections, a disease state associated with an exceptionally high morbidity and mortality, represent another condition that is readily treated with an endovascular approach.     

Electron beam computed tomographic imaging of aortic aneurysms and dissections

Electron Beam Computed Tomography (EBCT), like conventional CT has the capability to acquire high resolution images of the aorta. The millisecond image acquisition time characteristic of EBCT makes it an ideal modality to evaluate patients with suspected aneurysms or dissections of the aorta. Unlike conventional CT, electron beam technology produces images with excellent resolution, minimal respiratory artifact, and superior vascular enhancement. Compared with alternative modalities, EBCT probably represents a superior tool in the workup of aortic pathology. Whether in the acute or chronic setting, the reliability, speed, ease, and reproducibility of EBCT makes it truly superior in the diagnosis and follow-up of aortic aneurysms and dissections.     

A novel <Emphasis Type="Italic">COL3A1</Emphasis> gene mutation in patient with aortic dissected aneurysm and cervical artery dissections

A considerable proportion of aortic aneurysms are shown to have genetic backgrounds. The COL3A1 gene, which encodes type III procollagen and causes Ehlers-Danlos syndrome (EDS) type IV, is one of the candidate genes associated with aortic aneurysms. The COL3A1 gene is also associated with cervical artery dissections (CAD) mostly as a part of manifestations of EDS type IV. We describe a 34-year-old Korean woman with both abdominal dissected aortic aneurysm and CAD accompanying atrial septal defect and multiple cysts in ovary and thyroid glands. She lacked cardinal manifestations of EDS type IV other than the vascular abnormalities, but molecular analyses of the COL3A1 gene confirmed a de novo heterozygous missense mutation that has not been reported before (c. 781G > A; Gly261Ser). This case suggested that the COL3A1 gene could be one of etiologically linked genes in isolated vasculopathies such as aortic dissected aneurysm or CAD, although being rare.     

Auscultatory bedside tests for thoracic aortic disease

Auscultation for thoracic aortic aneurysms and dissections is largely limited to listening to praecordium, neck and axillae associated with disease located at the ascending aorta and root, typically overlooking the descending thoracic aorta. We report a new test and protocol for differentiating aortic root and descending aortic disease by adding auscultation over the back as part of the cardiovascular examination.     

Abdominal Aortic dissections: anatomic and clinical features and therapeutic options

Isolated abdominal aortic dissections are rare events. Their anatomic and clinical features are different from those of atherosclerotic aneurysms. We report 4 cases of isolated abdominal aortic dissection that were successfully treated with surgical or endovascular intervention. The anatomic and clinical features and a review of the literature are also presented.     

Ten years of surgery of aortic dissections and aneurysms. Clinical experience and original contributions.

From January '82 to April '91, 117 patients with aortic disease were operated upon at our University Hospital in Genoa, Italy. Thirty-seven had arch dissections or aneurysms; 66 had acute aortic dissection type A and 14 had aortic dissections or aneurysms type B, acute and chronic. Patients with arch or type B aortic pathology but without surgical indication and cases of post-traumatic aortic transections are not included. There were 84 male and 33 female patients with a mean age of 52 (6 min and 74 max). In the acute patients, the mean interval between clinical onset and surgery was 34 hours (6 min-72 max). All patients with primary arch disease had surgical repair with the aid of deep hypothermia and circulatory arrest (17-96 min). Type A dissections were treated with standard CPBP at 28 degrees C. Surgical techniques included direct suture of intimal tear alone, direct suturing of the two aortic stumps; interposition of Dacron tubular prosthesis; Bentall repair; separated valve and aortic replacement; an original aortic bulb aortoplasty with valve repair; arch replacement with resuturing of one or more aortic trunks. Human fibrin glue (Tissucol) was employed either as haemostatic agent, widely spread over the suture lines or as tissue adhesion agent between dissected aortic layers. Human fibrin glue is adopted because it gathers high glueing capacity and maintenance of the elastic property of the vessel wall. Hospital mortality (30 days) has been 25% in ascending aortic dissections (16/66 patients) and 50% in patients with arch disease (18/37 patients) who needed circulatory arrest. Late mortality 5/83 (6%). Reoperations for aortic valve insufficiency or re-dissection have been 7 (8.4%). Early diagnosis (increasing reliability of 2D-Echo and CT scans), aggressive surgery, meticulous myocardial and cerebral protection and introduction in clinical use of biological glues seem to be the milestones of present and further improvements in surgical results.     

Acquired diseases of aberrant subclavian arteries

The anatomic, clinical, and radiologic findings of aberrant subclavian arteries (ASAs) are well known. Acquired diseases such as aneurysms, dissections, or stenosis can complicate these anomalies. We propose that these complications are a result of atherosclerosis caused by abnormal turbulence around the ASA. Comparisons of computed tomographic and angiographic measurements of subclavian arteries in adults with and without arch anomalies and angiographic measurements of ASAs in children show that ASAs dilate in older patients. We describe six patients with acquired diseases of ASAs or the aorta adjacent to the ASA. Aneurysms, aortic dissections, and stenosis were each found in two patients. Problems in the radiologic diagnosis and clinical management of these diseases are emphasized. Radiologists should be cognizant of the significance of ASAs in patients with aortic aneurysms and dissections.