Paradoxical Cerebral Air Embolism after Cardiac Ablation in Williams-Beuren Syndrome: A Clinico-Pathological Correlation.

Non-traumatic neurological deterioration is a medical emergency that may arise from diverse causes, to include cerebral infarction or intracranial hemorrhage, meningoencephalitis, seizure, hypoxic-ischemic or toxic/metabolic encephalopathy, poisoning, or drug intoxication. We describe the abrupt onset of neurological deterioration in a 53-year-old man with Williams-Beuren syndrome, a sporadically occurring genetic disorder caused by chromosomal microdeletion at 7q11.23. The clinical phenotype of Williams-Beuren syndrome is suggested by distinctive elfin facies, limited intellect, unique personality features, growth abnormalities, and endocrinopathies. The causative microdeletion of chromosomal material will frequently involve loss of the elastin gene, ELN, with resulting arteriopathy, supravalvular aortic stenosis, non-ischemic cardiopathy, and atrial fibrillation. Our patient sustained acute neurological decline within one month after undergoing a cardiac ablative procedure to convert atrial fibrillation to sinus rhythm. We present our findings in the setting of a clinico-pathological correlation, in which we reveal the cause of the abrupt neurological deterioration and discuss how our patient was affected by an uncommon stroke disorder.

Spontaneous Rupture of Mesenteric Vasculature Associated with Fibromuscular Dysplasia in a 28-Year-Old Male.

Spontaneous rupture of mesenteric vasculature associated with fibromuscular dysplasia is an unreported phenomenon. We describe a case in a 28-year-old male with a history of chronic abdominal pain who presented to our facility in hemorrhagic shock secondary to a ruptured transverse mesocolon middle colic aneurysm status postemergent transverse colectomy. He was found to have chronic vertebral, renovisceral, and iliac aneurysms as well as acute superior and inferior mesenteric artery dissection and chronic bilateral vertebral artery dissections. He subsequently developed disseminated intravascular coagulopathy, resulting in saddle pulmonary embolus as well as right renal artery and splenic artery thrombosis. Ultimately, the patient expired.

Angiotensin II induces region-specific medial disruption during evolution of ascending aortic aneurysms.

Angiotensin II (Ang II) promotes development of ascending aortic aneurysms (AAs), but progression of this pathology is undefined. We evaluated factors potentially involved in progression, and determined the temporal sequence of tissue changes during development of Ang II-induced ascending AAs. Ang II infusion into C57BL/6J mice promoted rapid expansion of the ascending aorta, with significant increases within 5 days, as determined by both in vivo ultrasonography and ex vivo sequential acquisition of tissues. Rates of expansion were not significantly different in LDL receptor-null mice fed a saturated fat-enriched diet, demonstrating a lack of effect of hypercholesterolemia. Augmenting systolic blood pressure with norepinephrine infusion had no significant effect on ascending aortic expansion. Pathological changes observed within 5 days of Ang II infusion included increased medial thickness and intramural hemorrhage characterized by erythrocyte extravasation in outer lamellar layers of the media. Intramedial hemorrhage was not observed after prolonged Ang II infusion, although partial medial disruption was present. Elastin fragmentation and transmural medial breaks of the ascending aorta were observed with continued Ang II infusion, which were restricted to anterior aspects. CD45(+) cells accumulated in adventitia but were minimal in media. Similar pathology was observed in tissues obtained from patients with ascending AAs. In conclusion, Ang II promotes ascending AAs through region-specific changes that are independent of hypercholesterolemia or systolic blood pressure.

Inflammation, neovascularization and intra-plaque hemorrhage are associated with increased reparative collagen content: implication for plaque progression in diabetic atherosclerosis.

Sustained inflammation may stimulate a reparative process increasing early reparative type III collagen synthesis, promoting atherosclerotic plaque progression. We evaluated inflammation, neovascularization, intra-plaque hemorrhage (IPH), and collagen deposition in human aortic atherosclerotic plaques from patients with and without diabetes mellitus (DM). Plaques were procured at autopsy from lower thoracic and abdominal aorta from DM (n = 20) and non-DM (n = 22) patients. Inflammation and neovascularization were quantified by double-label immunochemistry and the IPH grade was scored using H&E-stained sections. Type I and type III collagens were quantified using Picro-Sirius red stain with polarization microscopy and computerized planimetry. In non-DM plaques, 27%, 40%, and 33% had mild, moderate and severe inflammation in the fibrous cap and shoulder compared with 2%, 30% and 68% in DM plaques (p < 0.001). The geometric mean neovessel count was increased in DM versus non-DM plaques (140 [95% CI: 119-165] versus 59 [95% CI: 51-70]; p < 0.001). The IPH grade was increased in DM verses non-DM plaques (0.82 ± 0.11 versus 0.29 ± 0.11; p < 0.001) (percentage grade). The density of type III was increased in DM plaques (0.16 ± 0.01 versus 0.06 ± 0.01; p < 0.001) with a non-significant reduction in type I density in DM when compared with non-DM (0.28 ± 0.03 versus 0.33 ± 0.03; p = 0.303) (content per mm²). The increase in type III collagen content correlated with total neovessel content (r = 0.58; p < 0.001) in DM plaques. In conclusion, our study suggests that enhanced type III collagen deposition was associated with inflammation, neovascularization and IPH, and may be a contributing factor in DM plaque progression.

Isolated necrotizing aortitis presenting as incidental thoracoabdominal aortic aneurysm: a case report.

Noninfectious aortitis is frequently asymptomatic yet often leads to the development of ascending aortic aneurysms requiring repair. We present the case of a 64-year-old Caucasian woman who presented to our medical center with an incidentally discovered thoracoabdominal aneurysm. She had previously been in good health and had not complained of chest pain or been otherwise symptomatic. At presentation to our clinic, her ascending aorta measured 5 cm at the sinotubular junction (STJ) with dilation of her descending thoracic aorta to 6 cm. Her coronary angiogram was normal. Cross-sectional imaging was notable for thickening of the aortic wall along its length. The entity of isolated noninfectious aortitis is increasingly being recognized as an identifiable factor leading to ascending aneurysmal disease. In reviewing this case, we outline current understanding and guidelines for management and follow-up of this pathology. Operative repair of the ascending arch was conducted using an interpositional graft. The aortic valve apparatus was normal and the proximal anastomosis was created at the STJ. Intraoperatively, an inflammatory obliteration of the aortopulmonary window was noted. It was not possible to completely excise the posterior aortic wall. Our patient had an uneventful recovery and final pathology revealed necrotizing aortitis (NA). She is currently undergoing routine surveillance of her descending thoracoabdominal aneurysm. Recent case series indicate that NA is a histologically distinct process, which is associated commonly with development of ascending aneurysm, and although it is most commonly an isolated finding, it may be associated with other vascular abnormalities including stenoses of branch vessels. There is a growing body of literature suggesting that NA represents a distinct clinical entity, associated with the development of ascending aortic aneurysms. Further research is required to determine the optimal follow-up and value of medical therapies.

Association of altered collagen content and lysyl oxidase expression in degenerative mitral valve disease.

BACKGROUND: Collagen cross-linking is mediated by lysyl oxidase (LOX) enzyme in the extracellular matrix (ECM) of mitral valve leaflets. Alterations in collagen content and LOX protein expression in the ECM of degenerative mitral valve may enhance leaflet expansion and disease severity. METHODS: Twenty posterior degenerative mitral valve leaflets from patients with severe mitral regurgitation were obtained at surgery. Five normal posterior mitral valve leaflets procured during autopsy served as controls. Valvular interstitial cells (VICs) density was quantified by immunohistochemistry, collagen Types I and III by picro-sirius red staining and immunohistochemistry, and proteoglycans by alcian blue staining. Protein expression of LOX and its mediator TGFß1 were quantified by immunofluorescence and gene expression by PCR. RESULTS: VIC density was increased, structural Type I collagen density was reduced, while reparative Type III collagen and proteoglycan densities were increased (P<.0001) with an increase in spongiosa layer thickness in myxomatous valves. These changes were associated with a reduction in LOX (P<.0001) and increase in TGFß1 protein expression (P<.0001). However, no significant change was seen in gene expression. Linear regression analysis identified a correlation between Type I collagen density and LOX grade (R2=0.855; P<.0001). CONCLUSIONS: Reduced Type I collagen density with a simultaneous increase in Type III collagen and proteoglycan densities possibly contributes to spongiosa layer expansion resulting in incompetent mitral valve leaflets. Observed changes in Type I and III collagen densities in Degenerative Mitral Valve Disease may be secondary to alterations in LOX protein expression, contributing to disorganization of ECM and disease severity.

Relation of Internal Elastic Lamellar Layer Disruption to Neointimal Cellular Proliferation and Type III Collagen Deposition in Human Peripheral Artery Restenosis.

Smooth muscle cell proliferation and extracellular matrix formation are responsible for disease progression in de novo and restenotic atherosclerosis. Internal elastic lamella (IEL) layer maintains the structural integrity of intima, and disruption of IEL may be associated with alterations in neointima, type III collagen deposition, and lesion progression in restenosis. Nineteen restenotic plaques (12 patients) procured during peripheral interventions were compared with 13 control plaques (12 patients) without restenosis. Hematoxylin & Eosin and elastic trichrome stains were used to measure length and percentage of IEL disruption, cellularity, and inflammation score. Type I and III collagens, smooth muscle cell (smc), fibroblast density, and nuclear proliferation (Ki67) percentage were evaluated by immunohistochemistry. IEL disruption percentage (28 ± 3.6 vs 6.1 ± 2.4; p = 0.0006), type III collagen content (0.33 ± 0.06 vs 0.17 ± 0.07; p = 0.0001), smc density (2014 ± 120 vs 923 ± 150; p = 0.0001), fibroblast density (2,282 ± 297 vs 906 ± 138; p = 0.0001), and Ki67 percentage (21.6 ± 2 vs 8.2 ± 0.65; p = 0.0001) were significantly increased in restenotic plaques compared to de novo plaques. Logistic regression analysis identified significant correlation between IEL disruption and neointimal smc density (r = 0.45; p = 0.01) and with type III collagen deposition (r = 0.61; p = 0.02) in restenosis. Increased IEL disruption may trigger cellular proliferation, altering collagen production, and enhancing restenotic neointima. In conclusion, understanding the pathologic and molecular basis of restenosis and meticulous-guided interventions oriented to minimize IEL damage may aid to reduce neointimal proliferation and the occurrence of restenosis.

Intimomedial interface damage and adventitial inflammation is increased beneath disrupted atherosclerosis in the aorta: implications for plaque vulnerability.

BACKGROUND: Atherosclerotic plaque progression is frequently accompanied by compensatory enlargement to preserve the lumen. These enlarging plaques develop features of vulnerability, however, leading to disruption and lumen obstruction. This complex transition from compensatory expansion to plaque disruption may not derive solely from progressive intimal disease. Concurrent changes at the intimomedial interface and within the tunica media and adventitia may play a role in plaque instability. We tested this hypothesis by investigating whether interface changes, including internal elastic lamina (IEL) rupture, and medial and adventitial changes, including inflammation, fibrosis, and atrophy, more frequently accompany disrupted than nondisrupted atherosclerotic plaques. METHODS AND RESULTS: Computerized planimetry and ocular micrometry were used for systematic quantification of intimal, medial, and adventitial histopathological features in 598 human aortic plaques according to the AHA classification. Disrupted plaques exhibited larger plaque and lipid pool areas (P=0.0001) and a higher incidence of rupture of the IEL (P=0.0001). Medial and adventitial inflammation (P=0.01), medial fibrosis (P=0.0001), and medial atrophy (P=0.0001) were also higher in disrupted plaques. Furthermore, medial thickness was reduced in disrupted plaques (P=0.0001). Logistic regression analysis identified rupture of the IEL as an independent predictor for fibrous cap disruption (P=0.0001). CONCLUSIONS: Compared with nondisrupted plaques, disrupted plaques have an increased incidence of IEL rupture, medial and adventitial inflammation, medial fibrosis, and medial atrophy. These intimomedial interface and adventitial changes may play a role in the natural history of complex atherosclerotic lesions. The interaction between medial and adventitial pathology and the intimal atherosclerotic process deserves further investigation.

Plaque neovascularization is increased in ruptured atherosclerotic lesions of human aorta: implications for plaque vulnerability.

BACKGROUND: Growth of atherosclerotic plaques is accompanied by neovascularization from vasa vasorum microvessels extending through the tunica media into the base of the plaque and by lumen-derived microvessels through the fibrous cap. Microvessels are associated with plaque hemorrhage and may play a role in plaque rupture. Accordingly, we tested this hypothesis by investigating whether microvessels in the tunica media, the base of the plaque, and the fibrous cap are increased in ruptured atherosclerotic plaques in human aorta. METHODS AND RESULTS: Microvessels, defined as CD34-positive tubuloluminal capillaries recognized in cross-sectional and longitudinal profiles, were quantified in 269 advanced human plaques by bicolor immunohistochemistry. Macrophages/T lymphocytes and smooth muscle cells were defined as CD68/CD3-positive and alpha-actin-positive cells. Total microvessel density was increased in ruptured plaques when compared with nonruptured plaques (P=0.0001). Furthermore, microvessel density was increased in lesions with severe macrophage infiltration at the fibrous cap (P=0.0001) and at the shoulders of the plaque (P=0.0001). In addition, microvessel density was also increased in lesions with intraplaque hemorrhage (P=0.04) and in thin-cap fibroatheromas (P=0.038). Logistic regression analysis identified plaque base microvessel density (P=0.003) as an independent correlate to plaque rupture. CONCLUSIONS: Thus, neovascularization as manifested by the localized appearance of microvessels is increased in ruptured plaques in the human aorta. Furthermore, microvessel density is increased in lesions with inflammation, with intraplaque hemorrhage, and in thin-cap fibroatheromas. Microvessels at the base of the plaque are independently correlated with plaque rupture, suggesting a contributory role for neovascularization in the process of plaque rupture.

Detection of lipid pool, thin fibrous cap, and inflammatory cells in human aortic atherosclerotic plaques by near-infrared spectroscopy.

BACKGROUND: A method is needed to identify nonstenotic, lipid-rich coronary plaques that are likely to cause acute coronary events. Near-infrared (NIR) spectroscopy can provide information on the chemical composition of tissue. We tested the hypothesis that NIR spectroscopy can identify plaque composition and features associated with plaque vulnerability in human aortic atherosclerotic plaques obtained at the time of autopsy. METHODS AND RESULTS: A total of 199 samples from 5 human aortic specimens were analyzed by NIR spectroscopy. Features of plaque vulnerability were defined by histology as presence of lipid pool, thin fibrous cap (<65 microm by ocular micrometry), and inflammatory cell infiltration. An InfraAlyzer 500 spectrophotometer was used. Spectral absorbance values were obtained as log (1/R) data from 1100 to 2200 nm at 10-nm intervals. Principal component regression was used for analysis. An algorithm was constructed with 50% of the samples used as a reference set; blinded predictions of plaque composition were then performed on the remaining samples. NIR spectroscopy sensitivity and specificity for histological features of plaque vulnerability were 90% and 93% for lipid pool, 77% and 93% for thin cap, and 84% and 89% for inflammatory cells, respectively. CONCLUSIONS: NIR spectroscopy can identify plaque composition and features associated with plaque vulnerability in postmortem human aortic specimens. These results support efforts to develop an NIR spectroscopy catheter system to detect vulnerable coronary plaques in living patients.

Congenital bronchial artery to pulmonary artery fistula presenting as hemoptysis.

A 51-year-old male presented with 2 weeks of hemoptysis. Pulmonary angiography was performed and identified a bronchial artery to pulmonary artery fistula of the right upper lobe. Despite angioembolization, the hemoptysis recurred 1 year later. It was hypothesized that the recurrence occurred due to retrograde filling from the pulmonary arterial side of the abnormality. Right upper lobectomy was performed and resulted in resolution of hemoptysis. We present a case report of a rare, congenital bronchial artery to pulmonary artery fistula.

Estabilização da placa aterosclerótica por stents farmacológicos e não-farmacológicos em modelo experimental de fibroateroma de capa fina em coelhos / Plaque stabilization by bare metal and drug-eluting stents in an experimental rabbit model of thin cap fibroatheroma

Introdução: Stents farmacológicos e stents não-farmacológicos (SNF) são utilizados no tratamento de placas ateroscleróticas instáveis e podem levar à estabilização dos fibroateromas de capa fina (FACF). Este estudo foi desenhado para avaliar os efeitos estabilizadores dos SNF e dos stents farmacológicos em modelo experimental de FACF. Método: O estudo avaliou 16 coelhos hipercolesterolêmicos da raça Nova Zelândia, acompanhados por quatro anos, dos quais 6 receberam SNF, 5 receberam stents SNF, 5 receberam stents com liberação de everolimus (SLE) e 5, stents com liberação de 17-b estradiol (SLB) (Guidant - Santa Clara, California, Estados Unidos). Um Stent com polímero também foi implantado em cada animal. Análises histológicas aos 28 dias dos FACF não tratados vs. FACF com implante de SLE, SLB e SNF foram realizadas. Resultados: Os FACF tratados com SNF, SLE e SLB mostraram redução da área lipídica de 62 por cento, 67 por cento e 61 por cento e aumento da espessura da capa de 188 por cento, 98 por cento e 140 por cento, respectivamente...

Background: Bare metal stents (BMS) and drug-eluting stents (DES) are used to treat unstable plaques and may stabilize thin cap fibroatheromas (TCFA). This study was designed to evaluate stabilizing effects of bare compared to Everolimus (EES) and Beta-Estradiol (BES) eluting stents in a chronic atherosclerotic experimental animal model of TCFA. Methods: Sixteen New Zealand hypercholesterolemic rabbits followed for 4 years were studied. Six animals received BMS, 5 EES and 5 BES (Guidant ­ Santa Clara, CA, USA). One polymer stent per animal was also implanted. Histologic analysis at 28 days of de-novo vs. BMS, EES, and BES stented TCFA were performed. Results: BMS, EES, and BES stented TCFA showed reductions in lipid area by 62%, 67%, and 61%, and increases in cap thickness by 188%, 98%, and 140% respectively (p < 0.0001 for all). Strut-induced ruptured TCFA was found in 63% of stented sections and was associated with increased neointima in BMS (p = 0.03) but not in EES or BES (p = ns). Conclusions: Stenting thin cap fibroatheroma with BMS, EES and BES reduces lipid accumulation and increases cap thickness. Strut-induced fibrous cap rupture was frequently found...