Sudden Death Due to Unusual Complication of Takayasu Arteritis: An Autopsy Case.

Takayasu arteritis is an uncommon inflammatory disease with usually a good prognosis. However, sometimes, the evolution can be fatal essentially by a coronary arteries involvement. We present a case of a 19-year-old woman who died suddenly from cardiogenic shock complicating an unknown Takayasu arteritis.At the autopsy, the aorta showed a significant thickening of the wall. The coronary arteries were slightly thickened and did not show any occlusion. Microscopic examination of the aorta showed an abundant granulomatous and a lymphoplasmacytic infiltrate. Microscopic sections of other internal organs showed signs of cardiac hypertrophy and an extensive edema of the lung. Death was attributed to acute heart failure complicating a supravalvular aortic stenosis secondary to unknown Takayasu arteritis.Takayasu arteritis can be life-threatening by an occlusion of the ascending aorta and its major branches, without any coronary arteries involvement.

A single codon insertion in PICALM is associated with development of familial subvalvular aortic stenosis in Newfoundland dogs.

Familial subvalvular aortic stenosis (SAS) is one of the most common congenital heart defects in dogs and is an inherited defect of Newfoundlands, golden retrievers and human children. Although SAS is known to be inherited, specific genes involved in Newfoundlands with SAS have not been defined. We hypothesized that SAS in Newfoundlands is inherited in an autosomal dominant pattern and caused by a single genetic variant. We studied 93 prospectively recruited Newfoundland dogs, and 180 control dogs of 30 breeds. By providing cardiac screening evaluations for Newfoundlands we conducted a pedigree evaluation, genome-wide association study and RNA sequence analysis to identify a proposed pattern of inheritance and genetic loci associated with the development of SAS. We identified a three-nucleotide exonic insertion in phosphatidylinositol-binding clathrin assembly protein (PICALM) that is associated with the development of SAS in Newfoundlands. Pedigree evaluation best supported an autosomal dominant pattern of inheritance and provided evidence that equivocally affected individuals may pass on SAS in their progeny. Immunohistochemistry demonstrated the presence of PICALM in the canine myocardium and area of the subvalvular ridge. Additionally, small molecule inhibition of clathrin-mediated endocytosis resulted in developmental abnormalities within the outflow tract (OFT) of Xenopus laevis embryos. The ability to test for presence of this PICALM insertion may impact dog-breeding decisions and facilitate reduction of SAS disease prevalence in Newfoundland dogs. Understanding the role of PICALM in OFT development may aid in future molecular and genetic investigations into other congenital heart defects of various species.

The occurrence and suspected mode of inheritance of congenital subaortic stenosis and tricuspid valve dysplasia in Dogue de Bordeaux dogs.

The Dogue de Bordeaux (DdB) breed has gone through several genetic 'bottle necks' and has a relatively small effective population size. Importing new stock into Israel has been limited, further narrowing the already restricted local gene-pool and increasing the chances of inherited defects. In 56 DdB dogs examined between 2003 and 2010, the authors sought to study the proportion congenital subaortic stenosis (SAS) and tricuspid valve dysplasia (TVD). The aim was also to identify a probable mode of inheritance (MOI) using segregation and pedigree analyses of genealogical data available from 13/21 DdB dogs diagnosed with these conditions between 2004 and 2007. Among all breeds in the country, TVD was highest in the DdB breed, which also displayed the second highest proportion of SAS. Echocardiographic measurements and selected physical examination findings from 26 normal DdB dogs, 18 DdB dogs with SAS, and 12 DdB dogs with TVD are reported. Based on pedigree and segregation analyses, the most probable MOI appeared to be autosomal recessive. Pedigree analyses helped to identify three ancestors that might have introduced these two congenital heart defects into the local DdB population. Excluding those three dogs and their progeny from future mating could therefore reduce the prevalence of these diseases in the DdB population in Israel. The unusual local breeding circumstances may offer a unique opportunity to identify associated SAS and TVD genes in the DdB, as well as in other dog breeds.

Multiplanar review analysis of three-dimensional echocardiographic datasets gives new insights into the morphology of subaortic stenosis.

AIMS: Associated left ventricular structures may play a role in progression and recurrence of discrete subaortic stenosis. The availability of a new 3D echocardiography tool, multiplanar review (MPR), allows comprehensive analysis of datasets in infinite planes, and detailed examination of anatomy. We sought to evaluate the role of MPR in defining the morphology of subaortic stenosis. METHODS: Consecutive patients underwent detailed 2 and 3D echocardiographic examination using MPR. RESULTS: Sixteen patients aged 0.7-15.9 years (median 4.57) with diagnosis as follows: isolated subaortic stenosis in nine, additional defects in seven (coarctation of aorta, VSD, mitral, or aortic stenosis). Position and extent of subaortic stenosis was clearly described by multiplanar review in all patients. Additional MPR findings were: abnormalities of mitral valve leaflet or chordal apparatus attachments (14 patients), abnormal ventricular muscle band (11), abnormal increased aorto-mitral separation (two). The aortoseptal angle was significantly decreased in subaortic stenosis, mean 141 +/- 12 degrees , vs. normal subjects, mean 153 +/- 6 degrees , P = 0.02. Surgical findings correlated well with MPR findings. CONCLUSIONS: MPR analysis of 3D datasets is a sensitive and accurate mode for delineation of morphological details of discrete subaortic stenosis, providing additional information to 2D echocardiography.

Functional rescue of elastin insufficiency in mice by the human elastin gene: implications for mouse models of human disease.

Diseases linked to the elastin gene arise from loss-of-function mutations leading to protein insufficiency (supravalvular aortic stenosis) or from missense mutations that alter the properties of the elastin protein (dominant cutis laxa). Modeling these diseases in mice is problematic because of structural differences between the human and mouse genes. To address this problem, we developed a humanized elastin mouse with elastin production being controlled by the human elastin gene in a bacterial artificial chromosome. The temporal and spatial expression pattern of the human transgene mirrors the endogenous murine gene, and the human gene accurately recapitulates the alternative-splicing pattern found in humans. Human elastin protein interacts with mouse elastin to form functional elastic fibers and when expressed in the elastin haploinsufficient background reverses the hypertension and cardiovascular changes associated with that phenotype. Elastin from the human transgene also rescues the perinatal lethality associated with the null phenotype. The results of this study confirm that reestablishing normal elastin levels is a logical objective for treating diseases of elastin insufficiency such as supravalvular aortic stenosis. This study also illustrates how differences in gene structure and alternative splicing present unique problems for modeling human diseases in mice.

Subvalvular aortic stenosis as a cause of sudden death: two case reports.

Sudden death is defined as a death that occurs suddenly, develops during an unpredictable course, and is due to natural or unnatural causes. Although there is no universally standardized definition on how "sudden" a sudden death is, WHO defines sudden death as a death that occurs within 24 hours after the onset of symptoms. The aim of this study is to present 2 rarely reported autopsy cases and to emphasize the importance of systemic autopsy at sudden death. On macroscopic examination, crescent-shaped, thick, fibrous membranes, located 5 mm and 3 mm away from the aortic valves, were detected. Fibrous membranes extended from the ventricular septum to the left ventricular outflow tract, thus apparently narrowing this region. Left ventricular wall and septum were slightly thickened, and there were scattered grayish-white areas of a small diameter. These became more intense in the septum and myocardium of the left ventricle on the anterior plane of the myocardial sections. In both cases, the aortic valves of were thickened and also markedly narrowed on one of them. In this case, the fibrous membrane adhered to the aortic valve and extended to the anterior leaflet of the mitral valve at one side. Both aortic valves comprised 3 leaflets. Other valves and coronary arteries showed no macroscopic pathologic findings. Microscopic examination of both cases demonstrated that the fibrous membrane comprising abundant collagen fibers was situated on the ventricular septum. Hypertrophy, moderate to severe interstitial fibrosis, and focal areas of scarring were observed in the specimens taken from the septal and ventricular myocardium. No abnormality was found on the conduction system examinations. Toxicologic analysis results in blood were negative. Based on the findings, membranous-type (discrete type) subvalvular aortic stenosis, diagnosed during the autopsy, was considered as the cause of sudden death in both cases.

[Shone's anomaly Fallbericht und Hintergrund]. / Shone-Anomalie. Fallbericht und Hintergrund.

Shone's anomaly was first described in 1963 as a developmental complex of four potentially obstructive cardiac lesions including a supravalvular fibrous mitral ring, deformity of the mitral and/or subvalvular apparatus, subvalvular aortic stenosis and coarctation of the aorta. While paediatric patients with Shone's anomaly have been reported in the literature, only a few adult patients presenting with this anomaly have been described in the perioperative period. However, patients with an undiagnosed, incomplete form of Shone's anomaly might occasionally present for non-cardiac surgery as adults. In this case report we describe the anaesthetic management of an adult patient scheduled for a non-cardiac operation, who suffered from Shone's anomaly that was unrecognised prior to the operation.

Intramyocardial arterial narrowing in dogs with subaortic stenosis.

Earlier studies have described intramyocardial arterial narrowing based on hyperplasia and hypertrophy of the vessel wall in dogs with subaortic stenosis (SAS). In theory, such changes might increase the risk of sudden death, as they seem to do in heart disease in other species. This retrospective pathological study describes and quantifies intramyocardial arterial narrowing in 44 dogs with naturally occurring SAS and in eight control dogs. The majority of the dogs with SAS died suddenly (n=27); nine had died or been euthanased with signs of heart failure and eight were euthanased without clinical signs. Dogs with SAS had significantly narrower intramyocardial arteries (P<0.001) and more myocardial fibrosis (P<0.001) than control dogs. Male dogs and those with more severe hypertrophy had more vessel narrowing (P=0.02 and P=0.02, respectively), whereas dogs with dilated hearts had slightly less pronounced arterial thickening (P=0.01). Arterial narrowing was not related to age, but fibrosis increased with age (P=0.047). Dogs that died suddenly did not have a greater number of arterial changes than other dogs with SAS. This study suggests that most dogs with SAS have intramyocardial arterial narrowing and that the risk of dying suddenly is not significantly related to the overall degree of vessel obliteration.

The relationship of resting S-T segment depression to the severity of subvalvular aortic stenosis and the presence of ventricular premature complexes in the dog.

Electrocardiograms (ECG) from 35 dogs with subvalvular aortic stenosis (SAS) with a left ventricular outflow tract pressure gradient (PG) of > or =50 mm Hg were retrospectively evaluated for S-T segment depression (STD, > or =0.2 mV in lead II). Pressure gradient, age, heart rate (HR), and number of ventricular premature complexes (VPCs) on a 24-hour ambulatory ECG for dogs with STD were not significantly different from those for dogs without STD. The S-T segment deviation did not correlate significantly with PG, age, HR, or VPCs. The significance of STD in the dog with SAS remains uncertain. Long-term prospective studies are needed to fully understand this observation.

Subaortic stenosis: recurrence of a fibrous ring after 28 years.

Aortic stenosis is a common cardiac problem. Morphological aortic stenosis can be due to valvular, subvalvular and supravalvular causes. Subvalvular causes include subaortic rings and membranes, which usually manifest at a young age, depending on the size of the ring and the degree of obstruction. Recurrent (post-operative) stenosis is a rare potential problem. A case of recurrent subaortic stenosis due to a subaortic ring, 28 years after the initial surgical excision of the ring is presented.

Failure to detect Chlamydia pneumoniae in senile calcific aortic stenosis or calcified congenital bicuspid aortic valve by immunofluorescence, polymerase chain reaction and electron microscopy.

INTRODUCTION: Chlamydia pneumoniae has been identified in arterial atherosclerosis. Aortic valves affected by senile calcific aortic stenosis (SCAS) or calcification of a congenital bicuspid valve (CCBAV) may have interior environments similar to atherosclerosis. This study aimed to detect C. pneumoniae within either SCAS or CCBAV. METHODS: 60 valves showing either SCAS (n=36) or CCABV (n=22) and control valves (n=2) were studied for the presence of C. pneumoniae by the following three techniques: (1) indirect immunofluorescence (IF) was performed on 36 SCAS valves, 22 CCBAV valves and 2 control aortic valves using a HEp-2 cell line infected with C. pneumoniae as a positive control. Negative controls comprised duplicate slides of the same valves with omission of the primary antibody step. A section of human stomach was also used as a negative control. A semiquantitative scoring method was used to grade positive IF staining. (2) Polymerase chain reaction (PCR) was performed on 30 SCAS valves, 20 CCBAV valves and 1 control valve using C. pneumoniae as a positive control and negative controls comprised a Ureaplasma sp. and human DNA from peripheral blood mononuclear cells. (3) Electron microscopy (EM) was performed upon 13 SCAS, 8 CCBAV and 2 control valves. RESULTS: All three methods failed to detect the presence of C. pneumoniae in any of the 60 aortic valves examined. False positive IF staining was encountered in 81% of test valves and in 76% of negative control valve sections (positive in calcified material due to nonspecific binding of FITC-conjugated secondary antibody). No staining was observed in the negative control stomach sections. CONCLUSIONS: This study failed to detect C. pneumoniae within aortic valves showing SCAS or CCBAV. Studies using IF alone to detect C. pneumoniae in calcified tissues should be interpreted with caution, since nonspecific binding of FITC-conjugated secondary antibody by calcium in the cusps may be misinterpreted as evidence of Chlamydia. The use of appropriate controls and ancillary methods for the identification of C. pneumoniae are important in this regard.

[Sub-valvular aortic stenosis by a discrete membrane]. / La sténose sous-valvulaire aortique d'origine membraneuse.

We report the case of a 55 year old patient presenting a discrete obstructive sub-aortic membrane. After clinical examination, complete echocardiographic evaluation and cardiac catheterisation, an operative procedure was decided and the sub-aortic membrane was resected. The results were satisfactory but the literature reports risks of re-obstruction of the left ventricular outflow tract. The article points out the importance of an early diagnosis and further stresses the major role played by transoesophageal echocardiography in the evaluation of the patient.

Clinical and pathological findings of severe subvalvular aortic stenosis and mitral dysplasia in a rottweiler puppy.

Subvalvular aortic stenosis (SAS) and mitral dysplasia were diagnosed in an asymptomatic eight-week-old rottweiler. Clinical and pathological findings were compatible with a fixed and dynamic obstruction of the left ventricular outflow tract. Gross and microscopic pathological findings were consistent with the most severe form of SAS, described previously in Newfoundland dogs over six months of age. These observations demonstrate that very young asymptomatic puppies may suffer a severe complex form of SAS.