Histology of the aortic media in dissecting aneurysms

Sections of the ascending aorta of 27 cases of dissecting aneurysm were compared histologically with the ascending aortae of 27 age- and sex-matched normotensive controls and 27 age- and sex-matched hypertensive controls. Elastic fragmentation and loss was seen to a similar degree in each series. Strip-like areas of muscle necrosis appeared to be associated as much with hypertension as with dissection. Two cases of dissecting aneurysm showed giant-cell aortitis. Mucopolysaccharide `cysts' were seen more frequently, but by no means invariably, in the dissecting series. The only abnormality that distinguished the dissecting aortae from the normotensive and hypertensive controls with any constancy was an increase in the degree of metachromasia of the ground substance.     

Patterns of expression of fibrinolytic genes and matrix metalloproteinase-9 in dissecting aortic aneurysms.

Although extensive tissue remodeling occurs during the various phases of aortic dissection, the underlying proteinases remain to be identified. Matrix metalloproteinase-9 (MMP-9) and components of the fibrinolytic system have been implicated in numerous tissue remodeling events and were therefore analyzed in surgical specimens of acute (n = 9), subacute (n = 4), and chronic (n = 7) aortic dissection by in situ hybridization. In the acute phase, intense plasminogen activator inhibitor 1 (PAI-1) gene expression was apparent in areas interfacing the dissecting hematoma, but no tissue-type PA (t-PA), urokinase-type PA (u-PA), or MMP-9 mRNAs were detected. Although PAI-1 mRNA was still present in the subacute phase, t-PA, u-PA, and MMP-9 mRNAs were now obvious, with PA gene expression co-localizing with areas of PAI-1 gene expression. In the chronic phase, PAI-1 mRNA was demonstrated around erythrocyte extravasations and surrounding bands of medial degeneration. However, there was little expression of PAs in these areas, and no MMP-9 was detected. Thus, fibrinolytic genes and MMP-9 are differentially expressed during the progression of aortic dissections. The kinetics of expression are consistent with acute fibrinolytic shutdown in response to the initial injury, a secondary subacute phase with active proteolysis, and finally, a chronic hypofibrinolytic state. Extensive neovascularization in the chronic phase may further reduce the physical stability of the dissected wall.     

Abdominal aortic aneurysms

Although the number of elective operations for abdominal aortic aneurysms (AAA) is increasing, the sex- and age-standardised mortality rate of AAAs continues to rise, especially among men aged 65 years or more. The lethality of ruptured AAA continues to be 80-95%, compared with 5-7% by elective surgery of symptomfree AAA. In order to fulfil all WHO, European, and Danish criteria for screening, a randomised hospitalbased screening trial of 12,639 65-73 year old men in Viborg County (Denmark) was initiated in 1994. It seemed that US screening is a valid, suitable and acceptable method of screening. The acceptance rate was 77%, and 95% accept control scans. Furthermore, persons at the highest risk of having an AAA attend screening more frequently. We found that 97% of the interval cases developed from aortas that initially measured 2.5-2.9 cm - i.e. approx. only 5% attenders need re-screening at 5-year intervals. Two large RCTs have given clear indications of operation. Survivors of surgery enjoy the same quality of life as the background population, and only 2-5% of patients refuse an offer of surgery. Early detection seems relevant since the cardiovascular mortality is more than 4 times higher in AAA patients without previous hospital discharge diagnoses due to cardiovascular disease than among similar men without AAA. The absolute risk difference after 5 years was 16%. So, they will benefit from general cardiovascular preventive action as smoking cessation, statins and low-dose aspirin, which could inhibit further AAA progression. All 4 existing RCTs point in the same direction, viz. in favour of screening of men aged 65 and above. We found that screening significantly reduced AAA-related mortality by 67% within the first five years (NNT = 352). Restriction of screening to men with previous cardiovascular or pulmonary hospital discharge diagnoses would request only 27% of the relevant male population study to be invited, but would only have prevented 46.7% of the AAA-related deaths. However, the benefit was similar, and low risk screening reduced AAA specific mortality by 78% compared to 52% in the high risk group after 14 years. Despite attractive sustained benefit and improved cost effectiveness was reported by MASS trial after 10 years, cost effectiveness continues to be discussed. We found after 14 years that screening had reduced AAA-specific mortality by 66% (NNT = 135). The cost per life year gained was 157 euro [1,170 DKK] and the cost per QALY at 178 euro [1,326 DKK]. In all, the ethical dilemma of the prophylactic operation, and the limited psychological side effects seem not to outweigh the benefits of screening. Conclusively, we found that offering men aged 65-73 years screening for AAA seems acceptable according to criteria from WHO, Council of Europe, and the Danish National Board of Health. In US, UK, and Sweden national programmes are implemented. In Denmark, a flawed HTA from the region of Mid Denmark based upon an economic model, which excluded large AAAs, emergency operations of unruptured cases, and costs for intensive care beyond 48 hours are blocking a qualified decision. Future topics for will be creation and validation of multivariate models predicting need for later repair. We found AAA-size, wall calcification, smoking, tPA and antibodies against C. pneumoniae to be such candidates. Antibiotic treatment for chlamydial infection are disappointing, and we found no sign of C. pneumoniae in AAA walls but rather signs of proteins cross-reacting with chlamydial antibodies indicating "molecular mimicry" as an autoimmune reaction, which calls for further attention. More precise methods for measuring the degree of wall calcification must be developed and validated.     

Different roles of arteriosclerosis in the rupture of intracranial dissecting aneurysms

AIMS: Although intracranial dissecting aneurysm (IDA) is a newly described variant of the brain aneurysms that affects mainly the vertebrobasilar arterial system, its pathogenesis remains obscure. We aimed to clarify the role of arteriosclerosis in the pathogenesis of IDA based on histopathological findings in seven autopsy cases of IDA. METHODS AND RESULTS: All cases exhibited systemic hypertension or left ventricular hypertrophy. Macroscopically, all cases exhibited subarachnoid haemorrhage. Two types of dissection were recognized in the vertebral artery. Six of seven IDA cases showed a widespread disruption of the entire thickness of the arterial wall with the formation of a dilated pseudoaneurysm, which consisted of thin adventitia (arterial wall disruption type). Medial disruption of the arterial wall and subadventitial dissecting haemorrhage were also found, resulting in the formation of a false lumen and stenosis of the 'true' lumen of the artery. However, these lesions were connected to the site of rupture of the entire arterial wall. Within 1 day after onset of IDA, the autopsy cases showed formation of fibrin thrombus, marked leucocyte infiltration and necrosis of the arterial wall at the site of the lesion. Cases that survived more than 1 week showed smooth muscle cell proliferation, macrophage accumulation and lymphocytic infiltration in the lesions. These cases showed no atherosclerotic plaque, but non-atherosclerotic fibrocellular intima. The thickness of intima and media was significantly less in the vertebral artery of IDA patients than that of non-IDA patients with systemic hypertension. On the other hand, the remaining case showed severe atherosclerosis with haemorrhage into the lipid core without connection to the arterial lumen (intra-atheromatous plaque haemorrhage type). However, unusual arterioles and neovascularization of the intra-and peri-arterial walls were observed. CONCLUSIONS: Our results suggest that disruption of the entire arterial wall may be a critical event in the development of IDA and result in the medial disruption and subadventitial haemorrhage. Non-atheromatous intima might function as a protective factor in arterial wall disruption. On the other hand, atherosclerosis may predispose to intra-atheromatous plaque haemorrhage type of IDA through intramural haemorrhage originating from the newly formed vessels.     

Collagen in dissecting aneurysms of the human thoracic aorta. Increased collagen content and decreased collagen concentration may be predisposing factors in dissecting aneurysms

Biochemical investigations were made into dissecting aneurysms of the thoracic aorta by taking samples at 12 specific sites from aortas of 10 patients who had dissected with fatal results in comparison with samples from 10 matched controls. When sites actually involved in dissection were compared with corresponding sites in controls, there were highly significant increases in dry weight, amount of collagen, and total protein (all p less than 0.001) and a significant decrease in collagen concentration (p = 0.016). In contrast, when samples from sites within dissected aortas, but not involved in dissection, were compared with corresponding sites in controls, there were no significant differences. We therefore conclude that in dissecting aneurysms of the thoracic aorta, there is localized expansion of the aortic matrix, due to deposition of collagen and other proteins, which decreases the concentration of matrix constituents, including collagen. Clearly, the deposition of collagen could be a cause but not a consequence of dissection. The altered composition means that the aortic wall becomes weaker and less able to withstand the mechanical stresses constantly imposed upon it.     

Aortic dissecting aneurysms: causative factors in 204 subjects

The pathogenesis of dissecting aneurysms of the aorta is controversial. We reviewed the records of the 204 patients with aortic dissecting aneurysms who underwent autopsy at the John Hopkins Hospital, Baltimore, from 1889 to the present and compared them with age-, race-, and sex-matched controls. The results show that hypertension, Marfan's syndrome, and traumatic, atherosclerotic, or inflammatory injuries of the aortic media are factors associated with dissection. The gross and histologic findings and associated circumstances suggest that most spontaneous aortic dissections originate from tears of the inner layers of the aorta followed by intramural cleavage. In other patients, rupture of the intra-aortic course of branch arteries or vasa vasorum may lead to dissection. Thus, no pathogenetic mechanism is common to all aortic dissections.     

Spontaneous dissecting aneurysms of coronary arteries in a cardiac allograft

Dissecting aneurysms of coronary arteries are a rare finding and have never been reported in a cardiac allograft. We found two spontaneous dissecting aneurysms on the middle third of both the left anterior descending and the right coronary arteries in a female cardiac transplantation recipient. She died 43 days after cardiac transplantation after developing human cytomegalovirus pneumonia and pancreatitis. Dissecting coronary aneurysms, microfoci of subendocardial coagulative necrosis, and area of subepicardial dystrophic calcifications were discovered at necropsy examination.     

Ascending aortic aneurysms in unicommissural aortic valve disease

BackgroundAneurysms of the ascending aorta occur as result of intrinsic changes in the aortic wall and have been well documented in patients with bicuspid aortic valve (BAV). In few reported clinical studies, documenting aneurysmal dilatation in unicommissural aortic valves (UAV); there have been no comments on the aortic wall pathology. This study presents the pathological findings of the ascending aorta in patients with UAV.Materials and MethodsThe clinical data from 39 patients with concomitant excision of the UAV and aneurysmal aortic tissue were reviewed. In all cases, the gross features of the valve and aortic segments were noted and submitted for histology. The sections of the aorta were semi-quantitatively graded for the extent of medionecrosis, cystic medial change, fibrosis, and elastic tissue changes (fragmentation/ loss) in the media. The medial alterations were correlated with patient age, gender, and valvular dysfunction, and compared to aneurysmal disease in BAV and three-cuspid aortic valves (TAV) excised over a 3-year period.ResultsAmong 39 patients studied, a majority were males (92.3%), with a mean age at surgery of 39.92 years. Only three patients (7.69%) were above the age of 50 years. Eighteen patients (46.1%) had aortic stenosis with regurgitation. Ascending aorta diameters ranged from 4 to 5.5 cm. The overall pattern of medial changes was nearly the same in all cases of UAV, irrespective of age and nature of valvular dysfunction. Most cases showed mild histological changes, with medionecrosis and fibrosis being the more common and consistent features. However, varying grades of change affected different portions of the media and/or the aortic wall in the same patient. The changes in UAV aortae were comparable to the changes seen in the TAV and BAV, but these differed with the age of onset.ConclusionsThis study demonstrates the presence of medial changes in the ascending aortic tissue in all patients of UAV with aneurysms. These changes, while mild to moderate in degree, likely have a similar pathogenetic mechanism as those seen in BAV disease. The significant difference in age, at the time of surgery, suggests a more rapid progression of the aortic changes.     

Genetic basis of thoracic aortic aneurysms and aortic dissections

Ascending thoracic aortic aneurysms leading to type A dissections (TAAD) can occur in association with a genetic syndrome, such as Marfan syndrome (MFS), or as an autosomal dominant disorder in the absence of syndromic features, termed familial TAAD. Familial TAAD demonstrates genetic heterogeneity, and linkage studies have identified three TAAD loci at 5q13-14 (TAAD1), 11q23 (FAA1), and 3p24-25 (TAAD2). The underlying genetic heterogeneity of TAAD is reflected in the phenotypic variation associated with familial TAAD with respect to age of onset, progression, penetrance, and association with additional cardiac and vascular features. Recently, mutations in the TGFBR2 gene have been identified as the cause of disease linked to the TAAD2 locus, supporting the hypothesis that dysregulation of TGFbeta signaling is a mechanism leading to aneurysms and dissections. The recent identification of the TGFbeta pathway as a key target in the molecular pathogenesis of TAAD has opened new avenues for future genetic and therapeutic research.