Oral calcium supplements do not affect the progression of aortic valve calcification or coronary artery calcification.

PubMed

Bhakta, Mayurkumar; Bruce, Charles; Messika-Zeitoun, David; Bielak, Lawrence; Sheedy, Patrick F; Peyser, Patricia; Sarano, Maurice

2009-01-01

The use of oral calcium supplementation among the elderly for prevention and treatment of osteoporosis and osteopenia is increasing. The incidence of aortic valve disease and coronary artery disease also is increasing. No study thus far has been done to demonstrate whether this affects the progression of calcification in both the valves and vasculature. We sought to determine whether ingestion of oral calcium supplementation has an effect on aortic valve calcification (AVC) and coronary artery calcification (CAC). We performed an independent assessment of AVC, CAC, and calcium supplementation among patients enrolled in the Epidemiology of Coronary Artery Calcification study who were >60 years of age and had baseline and 4-year follow-up AVC data. In this population-based study of Olmsted County (Minnesota) residents, AVC and CAC scores were determined prospectively by electron beam computed tomography. We evaluated baseline demographic data and analyzed whether those patients using calcium supplementation had a higher rate of progression of both AVC and CAC. We identified 257 patients (mean age, 67.8+/-5.2 years), 144 of whom were women. Twenty-five patients (all women) reported using calcium supplements. Analysis of the 144 women (25 taking calcium supplementation) showed there was no difference in the progression of AVC (mean difference in baseline and follow-up AVC score; no supplement versus supplement, 30+/-9 vs 39+/-28; P=.73) or CAC (mean difference in baseline and follow-up CAC score; no supplement vs supplement, 47+/-15 vs 112+/-22; P=.154). There were no significant differences between the 2 groups with regard to baseline AVC, serum calcium, renal function, diabetes, hypertension, cholesterol, or body mass index. In this community-based observational study with a 4-year follow-up, no significant increased progression of AVC or CAC was found in women taking oral calcium supplementation. Larger prospective, randomized studies are needed to confirm these

Calcification Characteristics of Low-Flow Low-Gradient Severe Aortic Stenosis in Patients Undergoing Transcatheter Aortic Valve Replacement

PubMed Central

Stähli, Barbara E.; Nguyen-Kim, Thi Dan Linh; Gebhard, Cathérine; Frauenfelder, Thomas; Tanner, Felix C.; Nietlispach, Fabian; Maisano, Francesco; Falk, Volkmar; Lüscher, Thomas F.; Maier, Willibald; Binder, Ronald K.

2015-01-01

Low-flow low-gradient severe aortic stenosis (LFLGAS) is associated with worse outcomes. Aortic valve calcification patterns of LFLGAS as compared to non-LFLGAS have not yet been thoroughly assessed. 137 patients undergoing transcatheter aortic valve replacement (TAVR) with preprocedural multidetector computed tomography (MDCT) and postprocedural transthoracic echocardiography were enrolled. Calcification characteristics were assessed by MDCT both for the total aortic valve and separately for each leaflet. 34 patients had LFLGAS and 103 non-LFLGAS. Total aortic valve calcification volume (p < 0.001), mass (p < 0.001), and density (p = 0.004) were lower in LFLGAS as compared to non-LFLGAS patients. At 30-day follow-up, mean transaortic pressure gradients and more than mild paravalvular regurgitation did not differ between groups. In conclusion, LFLGAS and non-LFLGAS express different calcification patterns which, however, did not impact on device success after TAVR. PMID:26435875

Calcific Aortic Valve Stenosis: Methods, Models, and Mechanisms

PubMed Central

Miller, Jordan D.; Weiss, Robert M.; Heistad, Donald D.

2011-01-01

Calcific aortic valve stenosis (CAVS) is a major health problem facing aging societies. The identification of osteoblast-like and osteoclast-like cells in human tissue has led to a major paradigm shift in the field. CAVS was thought to be a passive, degenerative process, whereas now the progression of calcification in CAVS is considered to be actively regulated. Mechanistic studies examining the contributions of true ectopic osteogenesis, non-osseous calcification, and ectopic osteoblast-like cells (that appear to function differently from skeletal osteoblasts) to valvular dysfunction have been facilitated by the development of mouse models of CAVS. Recent studies also suggest that valvular fibrosis, as well as calcification, may play an important role in restricting cusp movement, and CAVS may be more appropriately viewed as a fibrocalcific disease. High resolution echocardiography and magnetic resonance imaging have emerged as useful tools for testing the efficacy of pharmacological and genetic interventions in vivo. Key studies in humans and animals are reviewed that have shaped current paradigms in the field of CAVS, and suggest promising future areas for research. PMID:21617136

Impact of different aortic valve calcification patterns on the outcome of transcatheter aortic valve implantation: A finite element study.

PubMed

Sturla, Francesco; Ronzoni, Mattia; Vitali, Mattia; Dimasi, Annalisa; Vismara, Riccardo; Preston-Maher, Georgia; Burriesci, Gaetano; Votta, Emiliano; Redaelli, Alberto

2016-08-16

Transcatheter aortic valve implantation (TAVI) can treat symptomatic patients with calcific aortic stenosis. However, the severity and distribution of the calcification of valve leaflets can impair the TAVI efficacy. Here we tackle this issue from a biomechanical standpoint, by finite element simulation of a widely adopted balloon-expandable TAVI in three models representing the aortic root with different scenarios of calcific aortic stenosis. We developed a modeling approach realistically accounting for aortic root pressurization and complex anatomy, detailed calcification patterns, and for the actual stent deployment through balloon-expansion. Numerical results highlighted the dependency on the specific calcification pattern of the "dog-boning" of the stent. Also, local stent distortions were associated with leaflet calcifications, and led to localized gaps between the TAVI stent and the aortic tissues, with potential implications in terms of paravalvular leakage. High stresses were found on calcium deposits, which may be a risk factor for stroke; their magnitude and the extent of the affected regions substantially increased for the case of an "arc-shaped" calcification, running from commissure to commissure. Moreover, high stresses due to the interaction between the aortic wall and the leaflet calcifications were computed in the annular region, suggesting an increased risk for annular damage. Our analyses suggest a relation between the alteration of the stresses in the native anatomical components and prosthetic implant with the presence and distribution of relevant calcifications. This alteration is dependent on the patient-specific features of the calcific aortic stenosis and may be a relevant indicator of suboptimal TAVI results. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Low-level overexpression of p53 promotes warfarin-induced calcification of porcine aortic valve interstitial cells by activating Slug gene transcription.

PubMed

Gao, Li; Ji, Yue; Lu, Yan; Qiu, Ming; Shen, Yejiao; Wang, Yaqing; Kong, Xiangqing; Shao, Yongfeng; Sheng, Yanhui; Sun, Wei

2018-03-09

The most frequently used oral anti-coagulant warfarin has been implicated in inducing calcification of aortic valve interstitial cells (AVICs), whereas the mechanism is not fully understood. The low-level activation of p53 is found to be involved in osteogenic transdifferentiation and calcification of AVICs. Whether p53 participates in warfarin-induced AVIC calcification remains unknown. In this study, we investigated the role of low-level p53 overexpression in warfarin-induced porcine AVIC (pAVIC) calcification. Immunostaining, quantitative PCR, and Western blotting revealed that p53 was expressed in human and pAVICs and that p53 expression was slightly increased in calcific human aortic valves compared with non-calcific valves. Terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling staining indicated that apoptosis slightly increased in calcific aortic valves than in non-calcific valves. Warfarin treatment led to a low-level increase of p53 mRNA and protein in both pAVICs and mouse aortic valves. Low-level overexpression of p53 in pAVICs via an adenovirus vector did not affect pAVIC apoptosis but promoted warfarin-induced calcium deposition and expression of osteogenic markers. shRNA-mediated p53 knockdown attenuated the pAVIC calcium deposition and osteogenic marker expression. Moreover, ChIP and luciferase assays showed that p53 was recruited to the slug promoter and activated slug expression in calcific pAVICs. Of note, overexpression of Slug increased osteogenic marker Runx2 expression, but not pAVIC calcium deposition, and Slug knockdown attenuated pAVIC calcification and p53-mediated pAVIC calcium deposition and expression of osteogenic markers. In conclusion, we found that p53 plays an important role in warfarin induced pAVIC calcification, and increased slug transcription by p53 is required for p53-mediated pAVIC calcification. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Aortic Valve Replacement for Moderate Aortic Stenosis with Severe Calcification and Left Ventricualr Dysfunction-A Case Report and Review of the Literature.

PubMed

Narang, Nikhil; Lang, Roberto M; Liarski, Vladimir M; Jeevanandam, Valluvan; Hofmann Bowman, Marion A

2017-01-01

A 55-year-old man with a history of erosive, seropositive rheumatoid arthritis (RA), and interstitial lung disease presented with shortness of breath. Echocardiography showed new-onset severe left ventricular (LV) dysfunction with an ejection fraction (EF) of 15% and moderately increased mean aortic valve gradient of 20 mmHg in a trileaflet aortic valve with severe sclero-calcific degeneration. Coronary angiography revealed no significant obstructive coronary disease. Invasive hemodynamic studies and dobutamine stress echocardiography were consistent with moderate aortic stenosis. Guideline directed medical therapy for heart failure with reduced EF was initiated; however, diuretics and neurohormonal blockade (beta-blocker and angiotensin receptor blocker) provided minimal improvement, and the patient remained functionally limited. Of interest, echocardiography performed 1 year prior to his presentation showed normal LV EF and mild aortic leaflet calcification with moderate stenosis, suggesting a rapid progressing of calcific aortic valve disease. Subsequently, the patient underwent surgical aortic valve replacement and demonstrated excellent postsurgical recovery of LV EF (55%). Calcific aortic valve disease is commonly associated with aging, bicuspid aortic valve, and chronic kidney disease. Pathophysiological mechanism for valvular calcification is incompletely understood but include osteogenic transformation of valvular interstitial cells mediated by local and systemic inflammatory processes. Several rheumatologic diseases including RA are associated with premature atherosclerosis and arterial calcification, and we speculated a similar role of RA accelerating calcific aortic valve disease. We present a case of accelerated aortic valve calcification with (only) moderate stenosis, complicated by a rapid decline in LV systolic performance. Guidelines for AVR in moderate stenosis without concomitant cardiac surgery are not well established, although it should be

Low Magnesium Levels and FGF-23 Dysregulation Predict Mitral Valve Calcification as well as Intima Media Thickness in Predialysis Diabetic Patients

PubMed Central

Jerónimo, Teresa; Fragoso, André; Silva, Claudia; Guilherme, Patrícia; Santos, Nélio; Faísca, Marília; Neves, Pedro

2015-01-01

Background. Mitral valve calcification and intima media thickness (IMT) are common complications of chronic kidney disease (CKD) implicated with high cardiovascular mortality. Objective. To investigate the implication of magnesium and fibroblast growth factor-23 (FGF-23) levels with mitral valve calcification and IMT in CKD diabetic patients. Methods. Observational, prospective study involving 150 diabetic patients with mild to moderate CKD, divided according to Wilkins Score. Carotid-echodoppler and transthoracic echocardiography were used to assess calcification. Statistical tests used to establish comparisons between groups, to identify risk factors, and to establish cut-off points for prediction of mitral valve calcification. Results. FGF-23 values continually increased with higher values for both IMT and calcification whereas the opposite trend was observed for magnesium. FGF-23 and magnesium were found to independently predict mitral valve calcification and IMT (P < 0.05). Using Kaplan-Meier analysis, the number of deaths was higher in patients with lower magnesium levels and poorer Wilkins score. The mean cut-off value for FGF-23 was 117 RU/mL and for magnesium 1.7 mg/dL. Conclusions. Hypomagnesemia and high FGF-23 levels are independent predictors of mitral valve calcification and IMT and are risk factors for cardiovascular mortality in this population. They might be used as diagnostic/therapeutic targets in order to better manage the high cardiovascular risk in CKD patients. PMID:26089881

Cardiac Hemodynamics in the Pathogenesis of Congenital Heart Disease and Aortic Valve Calcification

NASA Astrophysics Data System (ADS)

Nigam, Vishal

2011-11-01

An improved understanding of the roles of hemodynamic forces play in cardiac development and the pathogenesis of cardiac disease will have significant scientific and clinical impact. I will focus on the role of fluid dynamics in congenital heart disease and aortic valve calcification. Congenital heart defects are the most common form of birth defect. Aortic valve calcification/stenosis is the third leading cause of adult heart disease and the most common form of acquired valvular disease in developed countries. Given the high incidence of these diseases and their associated morbidity and mortality, the potential translational impact of an improved understanding of cardiac hemodynamic forces is very large. Division of Pediatric Cardiology, Rady Children's Hospital, San Diego

The long non-coding HOTAIR is modulated by cyclic stretch and WNT/β-CATENIN in human aortic valve cells and is a novel repressor of calcification genes.

PubMed

Carrion, Katrina; Dyo, Jeffrey; Patel, Vishal; Sasik, Roman; Mohamed, Salah A; Hardiman, Gary; Nigam, Vishal

2014-01-01

Aortic valve calcification is a significant and serious clinical problem for which there are no effective medical treatments. Individuals born with bicuspid aortic valves, 1-2% of the population, are at the highest risk of developing aortic valve calcification. Aortic valve calcification involves increased expression of calcification and inflammatory genes. Bicuspid aortic valve leaflets experience increased biomechanical strain as compared to normal tricuspid aortic valves. The molecular pathogenesis involved in the calcification of BAVs are not well understood, especially the molecular response to mechanical stretch. HOTAIR is a long non-coding RNA (lncRNA) that has been implicated with cancer but has not been studied in cardiac disease. We have found that HOTAIR levels are decreased in BAVs and in human aortic interstitial cells (AVICs) exposed to cyclic stretch. Reducing HOTAIR levels via siRNA in AVICs results in increased expression of calcification genes. Our data suggest that β-catenin is a stretch responsive signaling pathway that represses HOTAIR. This is the first report demonstrating that HOTAIR is mechanoresponsive and repressed by WNT β-catenin signaling. These findings provide novel evidence that HOTAIR is involved in aortic valve calcification.

CALCIFIC AORTIC VALVE DISEASE: PART 1 – MOLECULAR PATHOGENETIC ASPECTS, HEMODYNAMICS AND ADAPTIVE FEEDBACKS

PubMed Central

Pasipoularides, Ares

2016-01-01

Aortic valvular stenosis (AVS), produced by calcific aortic valve disease (CAVD) causing reduced cusp opening, afflicts mostly older persons eventually requiring valve replacement. CAVD had been considered “degenerative,” but newer investigations implicate active mechanisms similar to atherogenesis—genetic predisposition and signaling pathways, lipoprotein deposits, chronic inflammation and calcification/osteogenesis. Consequently, CAVD may eventually be controlled/reversed by lifestyle and pharmacogenomics remedies. Its management should be comprehensive, embracing not only the valve but also the left ventricle and the arterial system with their interdependent morphomechanics/hemodynamics, which underlie the ensuing diastolic and systolic LV dysfunction. Compared to even a couple of decades ago, we now have an increased appreciation of genomic and cytomolecular pathogenetic mechanisms underlying CAVD. Future pluridisciplinary studies will characterize better and more completely its pathobiology, evolution and overall dynamics, encompassing intricate feedback processes involving specific signaling molecules and gene network cascades. They will herald more effective, personalized medicine treatments of CAVD/AVS. PMID:26891845

Association between pentraxin 3 levels and aortic valve calcification.

PubMed

Norimatsu, Kenji; Miura, Shin-Ichiro; Suematsu, Yasunori; Shiga, Yuhei; Miyase, Yuiko; Nakamura, Ayumi; Zhang, Bo; Saku, Keijiro

2016-07-01

Aortic valve calcification (AVC) reflects the state of aortic valve sclerosis (AVS), which is a precursor to aortic valve stenosis (AS). Therefore, we investigated the presence of AVC in patients who underwent coronary computed tomography angiography (CTA), which is an effective tool for evaluating early-stage AVC, and examined the association between plasma levels of pentraxin 3 (PTX3) and AVC. The subjects consisted of 162 consecutive patients who underwent CTA and in whom we could measure plasma levels of PTX3. We divided the patients into an AVC group (n=42) and a non-AVC group (n=120), as assessed by CT. Furthermore, we divided the patients without AS, assessed by echocardiography, into non-AS AVC (n=23) and non-AS non-AVC groups (n=60). We analyzed the predictors of the presence of AVC in all patients by a logistic regression analysis. AVC was independently associated with PTX3, in addition to age, chronic kidney disease, and coronary artery calcification. We also examined the predictors of the presence of AVC in patients without AS. PTX3, in addition to age, was an independent predictor of the presence of AVC in patients without AS. Finally, we found that adding PTX3 to the model containing age improves the specificity and, therefore, positive predictive value for AVC. PTX3, in addition to age, was shown to be an independent predictor of AVC in patients without AS. The combination of age and PTX3 may be a better approach to the evaluation of AVC than either of these alone. Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Aortic valve calcifications on chest films: how much calcium do I need?

PubMed

Mahnken, Andreas H; Dohmen, Guido; Koos, Ralf

2011-08-01

Aortic valve calcifications (AVC) as seen on conventional chest films or on CT are associated with aortic valve stenosis (AVS). The absence of AVC on chest films does not exclude high grade AVS. The aim of this study was to analyse if there is a threshold for the detection of AVC from conventional chest films in patients suffering from high grade AVS. The explanted aortic valves of 29 patients (16 male, mean age 72.3 +/- 11.5 years) with high grade AVS were examined by dual-source CT. AVC were quantified using the Agatston AVC score. In all patients conventional chest films obtained the day before surgery were evaluated for the presence of AVC. Results were analysed with students t-test, Spearman's rank correlation and ROC analysis. On conventional chest films AVC were visible in 18 patients. On CT all specimen presented with AVC with an Agatston AVC score ranging from 40.7 to 1870 (mean 991.3 +/- 463.1). In patients with AVC visible on chest films the AVC score was significantly higher (1264.0 +/- 318.2) when compared with patients without visible calcifications (544.9 +/- 274.4; P < 0.0001). There was a strong correlation between the AVC score and the visibility of AVC on chest films (r = 0.781). ROC analysis identified an ideal threshold of 718 for AVC score to separate conventional chest films with and without visible AVC. Unlike in coronary calcifications, there is a threshold for identifying AVC from conventional chest films. This finding may be of diagnostic value, as conventional chest films may be used to semiquantitatively evaluate the extent of AVC.

Cardiac valve calcifications on low-dose unenhanced ungated chest computed tomography: inter-observer and inter-examination reliability, agreement and variability.

PubMed

van Hamersvelt, Robbert W; Willemink, Martin J; Takx, Richard A P; Eikendal, Anouk L M; Budde, Ricardo P J; Leiner, Tim; Mol, Christian P; Isgum, Ivana; de Jong, Pim A

2014-07-01

To determine inter-observer and inter-examination variability for aortic valve calcification (AVC) and mitral valve and annulus calcification (MC) in low-dose unenhanced ungated lung cancer screening chest computed tomography (CT). We included 578 lung cancer screening trial participants who were examined by CT twice within 3 months to follow indeterminate pulmonary nodules. On these CTs, AVC and MC were measured in cubic millimetres. One hundred CTs were examined by five observers to determine the inter-observer variability. Reliability was assessed by kappa statistics (κ) and intra-class correlation coefficients (ICCs). Variability was expressed as the mean difference ± standard deviation (SD). Inter-examination reliability was excellent for AVC (κ = 0.94, ICC = 0.96) and MC (κ = 0.95, ICC = 0.90). Inter-examination variability was 12.7 ± 118.2 mm(3) for AVC and 31.5 ± 219.2 mm(3) for MC. Inter-observer reliability ranged from κ = 0.68 to κ = 0.92 for AVC and from κ = 0.20 to κ = 0.66 for MC. Inter-observer ICC was 0.94 for AVC and ranged from 0.56 to 0.97 for MC. Inter-observer variability ranged from -30.5 ± 252.0 mm(3) to 84.0 ± 240.5 mm(3) for AVC and from -95.2 ± 210.0 mm(3) to 303.7 ± 501.6 mm(3) for MC. AVC can be quantified with excellent reliability on ungated unenhanced low-dose chest CT, but manual detection of MC can be subject to substantial inter-observer variability. Lung cancer screening CT may be used for detection and quantification of cardiac valve calcifications. • Low-dose unenhanced ungated chest computed tomography can detect cardiac valve calcifications. • However, calcified cardiac valves are not reported by most radiologists. • Inter-observer and inter-examination variability of aortic valve calcifications is sufficient for longitudinal studies. • Volumetric measurement variability of mitral valve and annulus calcifications is substantial.

Triglycidylamine Crosslinking of Porcine Aortic Valve Cusps or Bovine Pericardium Results in Improved Biocompatibility, Biomechanics, and Calcification Resistance

PubMed Central

Connolly, Jeanne M.; Alferiev, Ivan; Clark-Gruel, Jocelyn N.; Eidelman, Naomi; Sacks, Michael; Palmatory, Elizabeth; Kronsteiner, Allyson; DeFelice, Suzanne; Xu, Jie; Ohri, Rachit; Narula, Navneet; Vyavahare, Narendra; Levy, Robert J.

2005-01-01

We investigated a novel polyepoxide crosslinker that was hypothesized to confer both material stabilization and calcification resistance when used to prepare bioprosthetic heart valves. Triglycidylamine (TGA) was synthesized via reacting epichlorhydrin and NH3. TGA was used to crosslink porcine aortic cusps, bovine pericardium, and type I collagen. Control materials were crosslinked with glutaraldehyde (Glut). TGA-pretreated materials had shrink temperatures comparable to Glut fixation. However, TGA crosslinking conferred significantly greater collagenase resistance than Glut pretreatment, and significantly improved biomechanical compliance. Sheep aortic valve interstitial cells grown on TGA-pretreated collagen did not calcify, whereas sheep aortic valve interstitial cells grown on control substrates calcified extensively. Rat subdermal implants (porcine aortic cusps/bovine pericardium) pretreated with TGA demonstrated significantly less calcification than Glut pretreated implants. Investigations of extracellular matrix proteins associated with calcification, matrix metalloproteinases (MMPs) 2 and 9, tenascin-C, and osteopontin, revealed that MMP-9 and tenascin-C demonstrated reduced expression both in vitro and in vivo with TGA crosslinking compared to controls, whereas osteopontin and MMP-2 expression were not affected. TGA pretreatment of heterograft biomaterials results in improved stability compared to Glut, confers biomechanical properties superior to Glut crosslinking, and demonstrates significant calcification resistance. PMID:15631995

Device landing zone calcification and its impact on residual regurgitation after transcatheter aortic valve implantation with different devices.

PubMed

Seiffert, Moritz; Fujita, Buntaro; Avanesov, Maxim; Lunau, Clemens; Schön, Gerhard; Conradi, Lenard; Prashovikj, Emir; Scholtz, Smita; Börgermann, Jochen; Scholtz, Werner; Schäfer, Ulrich; Lund, Gunnar; Ensminger, Stephan; Treede, Hendrik

2016-05-01

Calcification of the device landing zone is linked to paravalvular regurgitation after transcatheter aortic valve implantation (TAVI). The mechanisms remain incompletely understood and the performance of next-generation transcatheter heart valves (THV) has not been investigated. We evaluated the impact of calcification patterns on residual aortic regurgitation (AR) after TAVI with different THV in patients with severe aortic stenosis. TAVI was performed in 537 patients at two centres. Devices implanted were the Edwards Sapien XT (n = 254), Medtronic CoreValve (n = 123), JenaValve (n = 62), Medtronic Engager (n = 56), and Symetis Acurate (n = 42) prostheses. Calcification of the device landing zone was retrospectively assessed from contrast-enhanced multidetector computed tomography data and correlated with echocardiographic and clinical data. Calcium volumes of the aortic valve and left-ventricular outflow tract were associated with residual AR: No AR, 604 mm(3) (inter-quartile range, IQR 349-916); trace AR, 639 mm(3) (IQR 368-948); mild AR, 710 mm(3) (IQR 412-2078); ≥moderate AR, 1041 mm(3) (IQR 791-1417, P = 0.001). Device landing zone calcium, particularly if located in the left-ventricular outflow tract, and a low cover index were predictive of AR. Differences in the incidence of AR were observed with regard to THV type. Higher calcium volume was associated with the need for post-dilation (n = 134, median 852 [IQR 342-945] vs. 604 [IQR 542-1207] mm(3), P < 0.001). Calcification of the device landing zone, particularly if located inferior to the annulus, was independently associated with residual AR after TAVI with all evaluated THV; however, the incidence of paravalvular leakage differed significantly between the devices implanted. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Aortic valve calcification - a commonly observed but frequently ignored finding during CT scanning of the chest.

PubMed

Raju, Prashanth; Sallomi, David; George, Bindu; Patel, Hitesh; Patel, Nikhil; Lloyd, Guy

2012-06-01

To describe the frequency and severity of Aortic valve calcification (AVC) in an unselected cohort of patients undergoing chest CT scanning and to assess the frequency with which AVC was being reported in the radiology reports. Consecutive CT scan images of the chest and the radiological reports (December 2009 to May 2010) were reviewed at the district general hospital (DGH). AVC on CT scan was visually graded on a scale ranging from 0 to IV (0 = no calcification, IV = severe calcification). Total of 416 (232 male; 184 female) CT chest scans [Contrast enhanced 302 (72%), unenhanced 114 (28%)] were reviewed. Mean age was 70.55 ± 11.48 years. AVC in CT scans was identified in 95 of the 416 patients (22.83%). AVC classification was as follows: Grade I: 60 (63.15%), Grade II: 22 (23.15%), Grade III: 9 (9.47%), Grade IV: 4 (4.21%). Only one CT report mentioned AVC. Only 31 of 95 AVC had Transthoracic echocardiogram (TTE). The interval time between CT scan and TTE was variable.   Aortic valve calcification in CT chest scans is a common finding and studies have shown that it is strongly related to the presence and severity of aortic valve disease. As CT scans are considered as a valuable additional screening tool for detection of aortic stenosis, AVC should always be commented upon in the radiology reports. Furthermore, patients with at least Grade III and IV AVC should be sent for TTE. © 2012 Blackwell Publishing Ltd.

Characterization of the calcification of cardiac valve bioprostheses by environmental scanning electron microscopy and vibrational spectroscopy.

PubMed

Delogne, Christophe; Lawford, Patricia V; Habesch, Steven M; Carolan, Vikki A

2007-10-01

Bioprosthetic heart valve tissue and associated calcification were studied in their natural state, using environmental scanning electron microscopy (ESEM). Energy dispersive X-ray micro-analysis, X-ray diffraction, Fourier-transform infrared and Raman spectroscopy were used to characterize the various calcific deposits observed with ESEM. The major elements present in calcified valves were also analyzed by inductively coupled plasma-optical emission spectroscopy. To better understand the precursor formation of the calcific deposits, results from the elemental analyses were statistically correlated. ESEM revealed the presence of four broad types of calcium phosphate crystal morphology. In addition, two main patterns of organization of calcific deposits were observed associated with the collagen fibres. Energy dispersive X-ray micro-analysis identified the crystals observed by ESEM as salts containing mainly calcium and phosphate with ratios from 1.340 (possibly octacalcium phosphate, which has a Ca/P ratio of 1.336) to 2.045 (possibly hydroxyapatite with incorporation of carbonate and metal ion contaminants, such as silicon and magnesium, in the crystal lattice). Raman and fourier-transform infrared spectroscopy also identified the presence of carbonate and the analyses showed spectral features very similar to a crystalline hydroxyapatite spectrum, also refuting the presence of precursor phases such as beta-tricalcium phosphate, octacalcium phosphate and dicalcium phosphate dihydrate. The results of this study raised the possibility of the presence of precursor phases associated with the early stages of calcification.

Mitral annular calcification in patients undergoing aortic valve replacement for aortic valve stenosis.

PubMed

Takami, Yoshiyuki; Tajima, Kazuyoshi

2016-02-01

Limited data exis t on clinical relevance of aortic valve stenosis (AVS) and mitral annular calcification (MAC), although with similar pathophysiologic basis. We sought to reveal the prevalence of MAC and its clinical features in the patients undergoing aortic valve replacement (AVR) for AVS. We reviewed 106 consecutive patients who underwent isolated AVR from 2004 to 2010. Before AVR, CT scans were performed to identify MAC, whose severity was graded on a scale of 0-4, with grade 0 denoting no MAC and grade 4 indicating severe MAC. Echocardiography was performed before AVR and at follow-up over 2 years after AVR. MAC was identified in 56 patients with grade 1 (30 %), 2 (39 %), 3 (18 %), and 4 (13 %), respectively. Patients with MAC presented older age (72 ± 8 versus 66 ± 11 years), higher rate of dialysis-dependent renal failure (43 versus 4 %), and less frequency of bicuspid aortic valve (9 versus 36 %), when compared to those without MAC. No significant differences were seen in short- and mid-term mortality after AVR between the groups. In patients with MAC, progression of neither mitral regurgitation nor stenosis was observed at follow-up of 53 ± 23 months for 102 survivors, although the transmitral flow velocities were higher than in those without MAC. In conclusion, MAC represented 53 % of the patients undergoing isolated AVR for AVS, usually appeared in dialysis-dependent elder patients with tricuspid AVS. MAC does not affect adversely upon the survival, without progression of mitral valve disease, at least within 2 years after AVR.

Aorta calcification burden: Towards an integrative predictor of cardiac outcome after transcatheter aortic valve implantation.

PubMed

Harbaoui, Brahim; Montoy, Mathieu; Charles, Paul; Boussel, Loic; Liebgott, Hervé; Girerd, Nicolas; Courand, Pierre-Yves; Lantelme, Pierre

2016-03-01

The principal objective was to determine the effect of total aortic calcification (TAC) burden on outcomes (cardiac mortality, all-cause mortality, and heart failure (HF)) after transcatheter aortic valve implantation (TAVI). The secondary aim was to assess the contribution of each segment of the aorta to these outcomes. Indications for TAVI are increasing in number. Even after procedural success, however, some patients die soon afterwards, indicating the futility of TAVI in certain cases. Aortic calcifications were measured on computed tomography in 164 patients treated by TAVI. TAC, ascending aortic calcification (AsAC), descending aorta calcifications, and abdominal aorta calcifications were expressed as tertiles and their prognostic values were assessed in a multivariable cox analysis adjusted for major confounders including EuroSCORE. Median duration of follow-up was 565 (interquartile range: 246 to 1000) days. TAC (tertile3 vs. tertile1) was significantly and strongly associated with cardiac mortality (hazard ratio [HR]: 16.74; 95% confidence interval [CI]: 2.21 to 127.05; p = 0.006) and all-cause mortality (HR: 2.39; 95% CI: 1.18 to 4.84; p = 0.015) but not with HF (HR: 1.84; 95% CI: 0.87 to 3.90; p = 0.110). Each segment was associated with cardiac mortality, while only AsAC (tertile 3 vs. tertile 1) appeared predictive of HF (hazard ratio: 2.29; 95% CI: 1.12 to 4.66; p = 0.023). TAC is an integrative predictor of cardiac and all-cause mortality after TAVI. It should be included in the assessment of patients before TAVI in order to predict cardiac outcome after valve replacement and avoid futile interventions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Neurotrophin 3 upregulates proliferation and collagen production in human aortic valve interstitial cells: a potential role in aortic valve sclerosis.

PubMed

Yao, Qingzhou; Song, Rui; Ao, Lihua; Cleveland, Joseph C; Fullerton, David A; Meng, Xianzhong

2017-06-01

Calcific aortic valve disease (CAVD) is a leading cardiovascular disorder in the elderly. Diseased aortic valves are characterized by sclerosis (fibrosis) and nodular calcification. Sclerosis, an early pathological change, is caused by aortic valve interstitial cell (AVIC) proliferation and overproduction of extracellular matrix (ECM) proteins. However, the mechanism of aortic valve sclerosis remains unclear. Recently, we observed that diseased human aortic valves overexpress growth factor neurotrophin 3 (NT3). In the present study, we tested the hypothesis that NT3 is a profibrogenic factor to human AVICs. AVICs isolated from normal human aortic valves were cultured in M199 growth medium and treated with recombinant human NT3 (0.10 µg/ml). An exposure to NT3 induced AVIC proliferation, upregulated the production of collagen and matrix metalloproteinase (MMP), and augmented collagen deposition. These changes were abolished by inhibition of the Trk receptors. NT3 induced Akt phosphorylation and increased cyclin D1 protein levels in a Trk receptor-dependent fashion. Inhibition of Akt abrogated the effect of NT3 on cyclin D1 production. Furthermore, inhibition of either Akt or cyclin D1 suppressed NT3-induced cellular proliferation and MMP-9 and collagen production, as well as collagen deposition. Thus, NT3 upregulates cellular proliferation, ECM protein production, and collagen deposition in human AVICs. It exerts these effects through the Trk-Akt-cyclin D1 cascade. NT3 is a profibrogenic mediator in human aortic valve, and overproduction of NT3 by aortic valve tissue may contribute to the mechanism of valvular sclerosis. Copyright © 2017 the American Physiological Society.

Relationship of Aortic Wall Distensibility to Mitral and Aortic Valve Calcification: The Multi-Ethnic Study of Atherosclerosis.

PubMed

Cohoon, Kevin P; Criqui, Michael H; Budoff, Matthew J; Lima, Joao A; Blaha, Michael J; Decker, Paul A; Durazo, Ramon; Liu, Kiang; Kramer, Holly

2018-05-01

Data are limited on whether valvular calcification is associated with aortic wall stiffness. We tested whether aortic valve calcification (AVC) and/or mitral valve calcification (MVC) is inversely associated with aortic distensibility (AD). Cross-sectional study conducted in a subset of the Multi-Ethnic Study of Atherosclerosis (MESA) included 3676 MESA participants aged 44 to 84 years with AD measured with magnetic resonance imaging and with AVC and MVC measured with noncontrast cardiac computed tomography scans. Both AVC and MVC were divided into 3 categories: zero, < median values (low), and ≥ median values (high) for patients with nonzero values. Overall, 88% (n = 3256) and 92% (n = 3365) of participants had zero AVC and MVC, while 6% (n = 211) and 4% (n = 156) had low, and 6% (n = 209) and 4% (n = 155) had high values of AVC and MVC, respectively. The AVC was independently associated with AD after adjusting for age, gender, and ethnicity ( P = .035). No association was noted between AVC groups and AD after adjustment for all covariates or MVC groups and AD in any model.

Lipoprotein(a) levels are associated with aortic valve calcification in asymptomatic patients with familial hypercholesterolaemia.

PubMed

Vongpromek, R; Bos, S; Ten Kate, G-J R; Yahya, R; Verhoeven, A J M; de Feyter, P J; Kronenberg, F; Roeters van Lennep, J E; Sijbrands, E J G; Mulder, M T

2015-08-01

Lipoprotein(a) [Lp(a)] is an independent risk factor for aortic valve stenosis and aortic valve calcification (AVC) in the general population. In this study, we determined the association between AVC and both plasma Lp(a) levels and apolipoprotein(a) [apo(a)] kringle IV repeat polymorphisms in asymptomatic statin-treated patients with heterozygous familial hypercholesterolaemia (FH). A total of 129 asymptomatic heterozygous FH patients (age 40-69 years) were included in this study. AVC was detected using computed tomography scanning. Lp(a) concentration and apo(a) kringle IV repeat number were measured using immunoturbidimetry and immunoblotting, respectively. Univariate and multivariate logistic regression were used to assess the association between Lp(a) concentration and the presence of AVC. Aortic valve calcification was present in 38.2% of patients, including three with extensive AVC (>400 Agatston units). Lp(a) concentration was significantly correlated with gender, number of apo(a) kringle IV repeats and the presence and severity of AVC, but not with coronary artery calcification (CAC). AVC was significantly associated with plasma Lp(a) level, age, body mass index, blood pressure, duration of statin use, cholesterol-year score and CAC score. After adjustment for all significant covariables, plasma Lp(a) concentration remained a significant predictor of AVC, with an odds ratio per 10-mg dL(-1) increase in Lp(a) concentration of 1.11 (95% confidence interval 1.01-1.20, P = 0.03). In asymptomatic statin-treated FH patients, plasma Lp(a) concentration is an independent risk indicator for AVC. © 2014 The Association for the Publication of the Journal of Internal Medicine.

Quantity and location of aortic valve complex calcification predicts severity and location of paravalvular regurgitation and frequency of post-dilation after balloon-expandable transcatheter aortic valve replacement.

PubMed

Khalique, Omar K; Hahn, Rebecca T; Gada, Hemal; Nazif, Tamim M; Vahl, Torsten P; George, Isaac; Kalesan, Bindu; Forster, Molly; Williams, Mathew B; Leon, Martin B; Einstein, Andrew J; Pulerwitz, Todd C; Pearson, Gregory D N; Kodali, Susheel K

2014-08-01

This study sought to determine the impact of quantity and location of aortic valve calcification (AVC) on paravalvular regurgitation (PVR) and rates of post-dilation (PD) immediately after transcatheter aortic valve replacement (TAVR). The impact of AVC in different locations within the aortic valve complex is incompletely understood. This study analyzed 150 patients with severe, symptomatic aortic stenosis who underwent TAVR. Total AVC volume scores were calculated from contrast-enhanced multidetector row computed tomography imaging. AVC was divided by leaflet sector and region (Leaflet, Annulus, left ventricular outflow tract [LVOT]), and a combination of LVOT and Annulus (AnnulusLVOT). Asymmetry was assessed. Receiver-operating characteristic analysis was performed with greater than or equal to mild PVR and PD as classification variables. Logistic regression was performed. Quantity of and asymmetry of AVC for all regions of the aortic valve complex predicted greater than or equal to mild PVR by receiver-operating characteristic analysis (area under the curve = 0.635 to 0.689), except Leaflet asymmetry. Receiver-operating characteristic analysis for PD was significant for quantity and asymmetry of AVC in all regions, with higher area under the curve values than for PVR (area under the curve = 0.648 to 0.741). On multivariable analysis, Leaflet and AnnulusLVOT calcification were independent predictors of both PVR and PD regardless of multidetector row computed tomography area cover index. Quantity and asymmetry of AVC in all regions of the aortic valve complex predict greater than or equal to mild PVR and performance of PD, with the exception of Leaflet asymmetry. Quantity of AnnulusLVOT and Leaflet calcification independently predict PVR and PD when taking into account multidetector row computed tomography area cover index. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Polymorphism in exon 6 of the human NT5E gene is associated with aortic valve calcification.

PubMed

Kochan, Zdzislaw; Karbowska, Joanna; Gogga, Patrycja; Kutryb-Zajac, Barbara; Slominska, Ewa M; Smolenski, Ryszard T

2016-12-01

NT5E encodes ecto-5'-nucleotidase (e5NT, CD73) which hydrolyses extracellular AMP to adenosine. Adenosine has been shown to play a protective role against aortic valve calcification (AVC). We identified two nonsynonymous missense single nucleotide polymorphisms (c.1126A > G, p.T376A and c.1136T > C, p.M379T) in exon 6 of the human NT5E gene. Since both substitutions might affect e5NT activity and consequently alter extracellular adenosine levels, we evaluated the association between NT5E alleles and calcific aortic valve disease in 119 patients (95 patients with AVC and 24 controls). In AVC patients, the frequency of the G allele at c.1126 and the frequency of the GG genotype as well as the frequency of the C allele at c.1136, and the frequencies of CC and TC genotypes tended to be higher as compared to controls. The allele and genotype frequencies in AVC patients and controls were also compared to those calculated from the 1000 Genomes Project data for control individuals of European ancestry (n = 503). We found that the frequency of the C allele at c.1136 is significantly higher in patients with AVC than in the European controls (0.111 vs. 0.054, P = 0.0052). Moreover, e5NT activity in aortic valves showed a trend toward lower levels in AVC patients with CC and TC genotypes than in those with the TT genotype. Our findings indicate that the genetic polymorphism of NT5E may contribute to the pathogenesis of calcific aortic valve disease and that the C allele of SNP c.1136 is associated with an increased risk of AVC.

Understanding the structural features of symptomatic calcific aortic valve stenosis: A broad-spectrum clinico-pathologic study in 236 consecutive surgical cases.

PubMed

Galli, Daniela; Manuguerra, Roberta; Monaco, Rodolfo; Manotti, Laura; Goldoni, Matteo; Becchi, Gabriella; Carubbi, Cecilia; Vignali, Giulia; Cucurachi, Nicola; Gherli, Tiziano; Nicolini, Francesco; Lorusso, Roberto; Vitale, Marco; Corradi, Domenico

2017-02-01

With age, aortic valve cusps undergo varying degrees of sclerosis which, sometimes, can progress to calcific aortic valve stenosis (AVS). To perform a retrospective clinico-pathologic investigation in patients with calcific AVS. We characterized and graded the structural remodeling in 236 aortic valves (200 tricuspid and 36 bicuspid) from patients with calcific AVS (148 males; average 72years); possible relationships between general/clinical/echocardiographic characteristics and the histopathologic changes were explored. Twenty autopsy aortic valves served as controls. In 40 cases, we also tested the immunohistochemical expression of metalloproteinases and cytokines, and characterized the inflammatory infiltrate. In 5 cases, we cultured cusp stem cells and explored their potential to differentiate into osteoblasts/adipocytes. AVS cusps showed structural remodeling as severe fibrosis (100%), calcific nodules (100%), neoangiogenesis (81%), inflammation (71%), bone metaplasia with or without hematopoiesis (6% and 53%, respectively), adipose metaplasia (16%), and cartilaginous metaplasia (7%). At multivariate analysis, AVS degree and interventricular septum thickness were the only predictors of remodeling (barring inflammation). All the tested metalloproteinases (except MMP-13) and cytokines were expressed in AVS cusps. Inflammation mainly consisted of B and T lymphocytes (CD4+/CD8+ cell ratio 3:1) and plasma cells. AVS changes were mostly different from typical atherosclerosis. Cultured mesenchymal cusp stem cells could differentiate into osteoblasts/adipocytes. Structural remodeling in AVS is peculiar and considerable, and is related to the severity of the disease. However, the different newly formed tissues-where "valvular interstitial cells" play a key role-and their well-known slow turnover suggest a reverse structural remodeling improbable. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Calcification of the mitral valve and annulus: systematic evaluation of effects on valve anatomy and function.

PubMed

Movva, Rajesh; Murthy, Kinnari; Romero-Corral, Abel; Seetha Rammohan, Harish Raj; Fumo, Peter; Pressman, Gregg S

2013-10-01

Mitral annular calcification (MAC) is common in chronic kidney disease. It is associated with cardiovascular events and can cause valvular dysfunction, but it has not been systematically characterized. The aim of this prospective study was to assess the prevalence and distribution of MAC, its effects on leaflet motion, and its association with mitral stenosis and mitral regurgitation (MR) in a hemodialysis population. Echocardiograms were obtained in 75 consecutive hemodialysis outpatients. MAC extent and distribution were graded semiquantitatively using two-dimensional and three-dimensional echocardiography. Associations with the presence and severity of mitral stenosis and MR were explored. The mean age was 60 ± 14 years; 60% were men, and 87% were African American. MAC was present in 64% (moderate to severe in 48%). Calcium extended more than halfway onto the leaflet in 37% and beyond the annulus in 40%. Leaflet motion was restricted in 37%. Mitral stenosis was present in 28%, and the extent of calcification was associated with mean mitral valve gradient (P < .0001). MR was prevalent (present in 81%) but was severe in none. The severity of MAC was greater in patients with moderate MR than in those with no or mild MR (P = .04). Three-dimensional analysis suggested an uneven distribution of annular calcium; the middle and lateral anterior segments were less often calcified than the anterior-medial or posterior segments. Calcification in any annular segment was highly associated with restricted motion of the attached leaflet segment. MAC is common and often extensive in hemodialysis patients. Calcium may be unevenly distributed among the annular segments. When present, annular calcification reduces the angle of leaflet opening and can cause valvular dysfunction. Copyright © 2013 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.

Sex differences in aortic valve calcification measured by multidetector computed tomography in aortic stenosis.

PubMed

Aggarwal, Shivani R; Clavel, Marie-Annick; Messika-Zeitoun, David; Cueff, Caroline; Malouf, Joseph; Araoz, Philip A; Mankad, Rekha; Michelena, Hector; Vahanian, Alec; Enriquez-Sarano, Maurice

2013-01-01

Aortic valve calcification (AVC) is the intrinsic mechanism of valvular obstruction leading to aortic stenosis (AS) and is measurable by multidetector computed tomography. The link between sex and AS is controversial and that with AVC is unknown. We prospectively performed multidetector computed tomography in 665 patients with AS (aortic valve area, 1.05±0.35 cm(2); mean gradient, 39±19 mm Hg) to measure AVC and to assess the impact of sex on the AVC-AS severity link in men and women. AS severity was comparable between women and men (peak aortic jet velocity: 4.05±0.99 versus 3.93±0.91 m/s, P=0.11; aortic valve area index: 0.55±0.20 versus 0.56±0.18 cm(2)/m(2); P=0.46). Conversely, AVC load was lower in women versus men (1703±1321 versus 2694±1628 arbitrary units; P<0.0001) even after adjustment for their smaller body surface area or aortic annular area (both P<0.0001). Thus, odds of high-AVC load were much greater in men than in women (odds ratio, 5.07; P<0.0001). Although AVC showed good associations with hemodynamic AS severity in men and women (all r>0.67; P<0.0001), for any level of AS severity measured by peak aortic jet velocity or aortic valve area index, AVC load, absolute or indexed, was higher in men versus women (all P≤0.01). In this large AS population, women incurred similar AS severity than men for lower AVC loads, even after indexing for their smaller body size. Hence, the relationship between valvular calcification process and AS severity differs in women and men, warranting further pathophysiological inquiry. For AS severity diagnostic purposes, interpretation of AVC load should be different in men and in women.

Serum phosphate is associated with aortic valve calcification in the Multi-ethnic Study of Atherosclerosis (MESA).

PubMed

Linefsky, Jason P; O'Brien, Kevin D; Sachs, Michael; Katz, Ronit; Eng, John; Michos, Erin D; Budoff, Matthew J; de Boer, Ian; Kestenbaum, Bryan

2014-04-01

This study sought to investigate associations of phosphate metabolism biomarkers with aortic valve calcification (AVC). Calcific aortic valve disease (CAVD) is a common progressive condition that involves inflammatory and calcification mediators. Currently there are no effective medical treatments, but mineral metabolism pathways may be important in the development and progression of disease. We examined associations of phosphate metabolism biomarkers, including serum phosphate, urine phosphate, parathyroid hormone (PTH) and serum fibroblast growth factor (FGF)-23, with CT-assessed AVC at study baseline and in short-term follow-up in 6814 participants of the Multi-Ethnic Study of Atherosclerosis (MESA). At baseline, AVC prevalence was 13.2%. Higher serum phosphate levels were associated with significantly greater AVC prevalence (relative risk 1.3 per 1 mg/dL increment, 95% confidence incidence: 1.1 to 1.5, p<0.001). Serum FGF-23, serum PTH, and urine phosphate were not associated with prevalent AVC. Average follow-up CT evaluation was 2.4 years (range 0.9-4.9 years) with an AVC incidence of 4.1%. Overall, phosphate metabolism biomarkers were not associated with incident AVC except in the top FGF-23 quartile. Serum phosphate levels are significantly associated with AVC prevalence. Further study of phosphate metabolism as a modifiable risk factor for AVC is warranted. Published by Elsevier Ireland Ltd.

Serum Phosphate is Associated with Aortic Valve Calcification in the Multi-Ethnic Study of Atherosclerosis (MESA)

PubMed Central

Linefsky, Jason P.; O’Brien, Kevin D.; Sachs, Michael; Katz, Ronit; Eng, John; Michos, Erin D.; Budoff, Matthew J.; de Boer, Ian; Kestenbaum, Bryan

2014-01-01

Objectives This study sought to investigate associations of phosphate metabolism biomarkers with aortic valve calcification (AVC). Background Calcific aortic valve disease (CAVD) is a common progressive condition that involves inflammatory and calcification mediators. Currently there are no effective medical treatments, but mineral metabolism pathways may be important in the development and progression of disease. Methods We examined associations of phosphate metabolism biomarkers, including serum phosphate, urine phosphate, parathyroid hormone (PTH) and serum fibroblast growth factor (FGF)-23, with CT-assessed AVC at study baseline and in short-term follow-up in 6,814 participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Results At baseline, AVC prevalence was 13.2%. Higher serum phosphate levels were associated with significantly greater AVC prevalence (relative risk 1.3 per 1mg/dL increment, 95% confidence incidence: 1.1 to 1.5, p < 0.001). Serum FGF-23, serum PTH, and urine phosphate were not associated with prevalent AVC. Average follow-up CT evaluation was 2.4 years (range 0.9–4.9 years) with an AVC incidence of 4.1%. Overall, phosphate metabolism biomarkers were not associated with incident AVC except in the top FGF-23 quartile. Conclusions Serum phosphate levels are significantly associated with AVC prevalence. Further study of phosphate metabolism as a modifiable risk factor for AVC is warranted. PMID:24530958

Combined presence of aortic valve calcification and mitral annular calcification as a marker of the extent and vulnerable characteristics of coronary artery plaque assessed by 64-multidetector computed tomography.

PubMed

Utsunomiya, Hiroto; Yamamoto, Hideya; Kunita, Eiji; Kitagawa, Toshiro; Ohashi, Norihiko; Oka, Toshiharu; Yamazato, Ryo; Horiguchi, Jun; Kihara, Yasuki

2010-11-01

We examined the association of aortic valve calcification (AVC) and mitral annular calcification (MAC) to coronary atherosclerosis using 64-multidetector computed tomography (MDCT). Valvular calcification is considered a manifestation of atherosclerosis. The impact of multiple heart valve calcium deposits on the distribution and characteristics of coronary plaque is unknown. We evaluated 322 patients referred for 64-MDCT, and assessed valvular calcification and the extent of calcified (CAP), mixed (MCAP), and noncalcified coronary atherosclerotic plaque (NCAP) in accordance with the 17-coronary segments model. We assessed the vulnerable characteristics of coronary plaque with positive remodeling, low-density plaque (CT density ≤38 Hounsfield units), and the presence of adjacent spotty calcification. In 49 patients with both AVC and MAC, the segment numbers of CAP and MCAP were larger than in those with a lack of valvular calcification and an isolated AVC (p<0.001 for both). Multivariate analyses revealed that a combined presence of AVC and MAC was independently associated with the presence (odds ratio [OR] 9.36, 95% confidence interval [95%CI] 1.55-56.53, p=0.015) and extent (β-estimate 1.86, p<0.001) of overall coronary plaque. When stratified by plaque composition, it was associated with the extent of CAP (β-estimate 1.77, p<0.001) and MCAP (β-estimate 1.04, p<0.001), but not with NCAP. Moreover, it was also related to the presence of coronary plaque with all three vulnerable characteristics (OR 4.87, 95%CI 1.85-12.83, p=0.001). The combined presence of AVC and MAC is highly associated with the presence, extent, and vulnerable characteristics of coronary plaque identified by 64-MDCT. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Association of aortic valve calcification severity with the degree of aortic regurgitation after transcatheter aortic valve implantation.

PubMed

Koos, Ralf; Mahnken, Andreas Horst; Dohmen, Guido; Brehmer, Kathrin; Günther, Rolf W; Autschbach, Rüdiger; Marx, Nikolaus; Hoffmann, Rainer

2011-07-15

This study sought to examine a possible relationship between the severity of aortic valve calcification (AVC), the distribution of AVC and the degree of aortic valve regurgitation (AR) after transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS). 57 patients (22 men, 81 ± 5 years) with symptomatic AS and with a logistic EuroSCORE of 24 ± 12 were included. 38 patients (67%) received a third (18F)-generation CoreValve® aortic valve prosthesis, in 19 patients (33%) an Edwards SAPIEN™ prosthesis was implanted. Prior to TAVI dual-source computed tomography for assessment of AVC was performed. To determine the distribution of AVC the percentage of the calcium load of the most severely calcified cusp was calculated. After TAVI the degree of AR was determined by angiography and echocardiography. The severity of AR after TAVI was related to the severity and distribution of AVC. There was no association between the distribution of AVC and the degree of paravalvular AR after TAVI as assessed by angiography (r = -0.02, p = 0.88). Agatston AVC scores were significantly higher in patients with AR grade ≥ 3 (5055 ± 1753, n = 3) than in patients with AR grade < 3 (1723 ± 967, p = 0.03, n = 54). Agatston AVC scores > 3000 were associated with a relevant paravalvular AR and showed a trend for increased need for second manoeuvres. There was a significant correlation between the severity of AVC and the degree of AR after AVR (r = 0.50, p < 0.001). Patients with severe AVC have an increased risk for a relevant AR after TAVI as well as a trend for increased need for additional procedures. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Sclerostin as a potential novel biomarker for aortic valve calcification: an in-vivo and ex-vivo study.

PubMed

Koos, Ralf; Brandenburg, Vincent; Mahnken, Andreas Horst; Schneider, Rebekka; Dohmen, Guido; Autschbach, Rüdiger; Marx, Nikolaus; Kramann, Rafael

2013-05-01

Sclerostin is a key negative regulator of bone formation. It was hypothesized that sclerostin might also play a potential role in the development of aortic valve calcification (AVC). The study aim was to evaluate serum sclerostin levels in patients with different degrees of AVC compared to a healthy control group, and to investigate local sclerostin expression in explanted calcified and non-calcified aortic valves. A prospective cross-sectional study was performed in 115 patients (mean age 74 +/- 7 years) with echocardiographically proven AVC. Sclerostin serum levels were measured using ELISA and compared to values obtained from a healthy control population. For quantification of AVC, all patients of the study cohort underwent non-contrast-enhanced dual-source computed tomography (DSCT). Immunohistochemistry (IHC) staining for sclerostin and mRNA sclerostin expression was analyzed in 10 calcified aortic valves and 10 non-calcified age-matched control valves. Patients with AVC showed significantly higher sclerostin serum levels as compared to healthy controls (0.94 +/- 0.45 versus 0.58 +/- 0.26 ng/ml, p < 0.001). A significant correlation between sclerostin serum levels and Agatston AVC scores as assessed by DSCT was observed (r = 0.62, p < 0.001) in the study cohort. IHC revealed positive sclerostin staining in nine calcified valves, in contrast to negative staining for sclerostin in all non-calcified valves. Quantitative real-time PCR confirmed the increased sclerostin expression on mRNA level, with a significant up-regulation of sclerostin mRNA (fold change 150 +/- 52, p < 0.001) expression being shown in calcified aortic valves compared to non-calcified control valves. Co-staining experiments revealed that sclerostin-expressing cells co-express the major osteogenic transcription factor Runx2 and the extracellular matrix protein osteocalcin. Patients with AVC showed increased sclerostin serum levels compared to a healthy reference population, and it was revealed

Aortic valve type and calcification as assessed by transthoracic and transoesophageal echocardiography.

PubMed

Yousry, Mohamed; Rickenlund, Anette; Petrini, Johan; Jenner, Jonas; Liska, Jan; Eriksson, Per; Franco-Cereceda, Anders; Eriksson, Maria J; Caidahl, Kenneth

2015-07-01

Aortic valve calcification (AVC) may predict poor outcome. Bicuspid aortic valve (BAV) leads to several haemodynamic changes accelerating the progress of aortic valve (AV) disease. To compare the diagnostic accuracy of transoesophageal echocardiography (TEE) and transthoracic echocardiography (TTE) in the assessment of aortic valve phenotype and degree of AVC, with intra-operative evaluation as a reference. We examined 169 patients (median age 65 years, 51 women) without significant coronary artery disease undergoing AV and/or aortic root surgery. TTE was performed within a week prior to surgery and TEE at the time of surgery. Compared with surgical AVC assessment, visual evaluation using a 5-grade scoring system and real-time images showed a higher correlation (TTE r = 0·83 and TEE r = 0·82) than visual (TTE r = 0·64 and TEE 0·63) or grey scale mean (GSMn) (TTE r = 0·63 and TEE r = 0·52) assessment of end-diastolic still frames. AVC assessment using real-time images showed high intraclass correlation coefficients (TTE 0·94 and TEE 0·93). With regard to BAV, TEE was superior to TTE with a higher interobserver agreement, sensitivity and specificity (0·86, 92% and 94% versus 0·57, 77% and 82%, respectively). Semi-quantitative AVC assessment of real-time cine loops from both TEE and TTE correlated well with intra-operative evaluation of AVC. Applying a predefined scoring system for AVC evaluation assures a high interobserver correlation. TEE was superior to TTE for evaluation of valve phenotype and should be considered when a diagnosis of BAV is clinically important. © 2014 The Authors. Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.

Aortic Stenosis and Vascular Calcifications in Alkaptonuria

PubMed Central

Hannoush, Hwaida; Introne, Wendy J.; Chen, Marcus Y.; Lee, Sook-Jin; O'Brien, Kevin; Suwannarat, Pim; Kayser, Michael A.; Gahl, William A.; Sachdev, Vandana

2011-01-01

Alkaptonuria is a rare metabolic disorder of tyrosine catabolism in which homogentisic acid (HGA) accumulates and is deposited throughout the spine, large joints, cardiovascular system, and various tissues throughout the body. In the cardiovascular system, pigment deposition has been described in the heart valves, endocardium, pericardium, aortic intima and coronary arteries. The prevalence of cardiovascular disease in patients with alkaptonuria varies in previous reports . We present a series of 76 consecutive adult patients with alkaptonuria who underwent transthoracic echocardiography between 2000 and 2009. A subgroup of 40 patients enrolled in a treatment study underwent non-contrast CT scans and these were assessed for vascular calcifications. Six of the 76 patients had aortic valve replacement. In the remaining 70 patients, 12 patients had aortic sclerosis and 7 patients had aortic stenosis. Unlike degenerative aortic valve disease, we found no correlation with standard cardiac risk factors. There was a modest association between the severity of aortic valve disease and joint involvement, however, we saw no correlation with urine HGA levels. Vascular calcifications were seen in the coronaries, cardiac valves, aortic root, descending aorta and iliac arteries. These findings suggest an important role for echocardiographic screening of alkaptonuria patients to detect valvular heart disease and cardiac CT to detect coronary artery calcifications. PMID:22100375

Aortic stenosis and vascular calcifications in alkaptonuria.

PubMed

Hannoush, Hwaida; Introne, Wendy J; Chen, Marcus Y; Lee, Sook-Jin; O'Brien, Kevin; Suwannarat, Pim; Kayser, Michael A; Gahl, William A; Sachdev, Vandana

2012-02-01

Alkaptonuria is a rare metabolic disorder of tyrosine catabolism in which homogentisic acid (HGA) accumulates and is deposited throughout the spine, large joints, cardiovascular system, and various tissues throughout the body. In the cardiovascular system, pigment deposition has been described in the heart valves, endocardium, pericardium, aortic intima and coronary arteries. The prevalence of cardiovascular disease in patients with alkaptonuria varies in previous reports. We present a series of 76 consecutive adult patients with alkaptonuria who underwent transthoracic echocardiography between 2000 and 2009. A subgroup of 40 patients enrolled in a treatment study underwent non-contrast CT scans and these were assessed for vascular calcifications. Six of the 76 patients had aortic valve replacement. In the remaining 70 patients, 12 patients had aortic sclerosis and 7 patients had aortic stenosis. Unlike degenerative aortic valve disease, we found no correlation with standard cardiac risk factors. There was a modest association between the severity of aortic valve disease and joint involvement, however, we saw no correlation with urine HGA levels. Vascular calcifications were seen in the coronaries, cardiac valves, aortic root, descending aorta and iliac arteries. These findings suggest an important role for echocardiographic screening of alkaptonuria patients to detect valvular heart disease and cardiac CT to detect coronary artery calcifications. Published by Elsevier Inc.

Systemic vascular load in calcific degenerative aortic valve stenosis: insight from percutaneous valve replacement.

PubMed

Yotti, Raquel; Bermejo, Javier; Gutiérrez-Ibañes, Enrique; Pérez del Villar, Candelas; Mombiela, Teresa; Elízaga, Jaime; Benito, Yolanda; González-Mansilla, Ana; Barrio, Alicia; Rodríguez-Pérez, Daniel; Martínez-Legazpi, Pablo; Fernández-Avilés, Francisco

2015-02-10

Systemic arterial load impacts the symptomatic status and outcome of patients with calcific degenerative aortic stenosis (AS). However, assessing vascular properties is challenging because the arterial tree's behavior could be influenced by the valvular obstruction. This study sought to characterize the interaction between valvular and vascular functions in patients with AS by using transcatheter aortic valve replacement (TAVR) as a clinical model of isolated intervention. Aortic pressure and flow were measured simultaneously using high-fidelity sensors in 23 patients (mean 79 ± 7 years of age) before and after TAVR. Blood pressure and clinical response were registered at 6-month follow-up. Systolic and pulse arterial pressures, as well as indices of vascular function (vascular resistance, aortic input impedance, compliance, and arterial elastance), were significantly modified by TAVR, exhibiting stiffer vascular behavior post-intervention (all, p < 0.05). Peak left ventricular pressure decreased after TAVR (186 ± 36 mm Hg vs. 162 ± 23 mm Hg, respectively; p = 0.003) but remained at >140 mm Hg in 70% of patients. Wave intensity analysis showed abnormally low forward and backward compression waves at baseline, increasing significantly after TAVR. Stroke volume decreased (-21 ± 19%; p < 0.001) and correlated with continuous and pulsatile indices of arterial load. In the 48 h following TAVR, a hypertensive response was observed in 12 patients (52%), and after 6-month follow-up, 5 patients required further intensification of discharge antihypertensive therapy. Vascular function in calcific degenerative AS is conditioned by the upstream valvular obstruction that dampens forward and backward compression waves in the arterial tree. An increase in vascular load after TAVR limits the procedure's acute afterload relief. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Serum magnesium, phosphorus, and calcium levels and subclinical calcific aortic valve disease: A population-based study.

PubMed

Hisamatsu, Takashi; Miura, Katsuyuki; Fujiyoshi, Akira; Kadota, Aya; Miyagawa, Naoko; Satoh, Atsushi; Zaid, Maryam; Yamamoto, Takashi; Horie, Minoru; Ueshima, Hirotsugu

2018-06-01

Calcific aortic valve disease (CAVD) is the most common valve disease. Although micronutrients are known to contribute to cardiovascular disease, the relationship with CAVD remains poorly evaluated. We examined the association of serum levels of magnesium, phosphorus, and calcium with prevalence, incidence, and progression of aortic valve calcification (AVC). We conducted a prospective study in a population-based sample of Japanese men aged 40-79 years without known cardiovascular disease and chronic kidney disease at baseline, and quantified AVC from serial computed tomographic images with the Agatston method. Of 938 participants at baseline (mean age, 63.7 ± 9.9 years), AVC prevalence was observed in 173 (18.4%). Of 596 participants without baseline AVC at follow-up (median duration, 5.1 years), AVC incidence was observed in 138 (23.2%). After adjustment for demographics, behaviors and cardiovascular risk factors, relative risks (95% confidence intervals) in the highest versus lowest categories of serum magnesium, phosphorus, and calcium were 0.62 (0.44-0.86), 1.45 (1.02-2.04), and 1.43 (0.95-2.15), respectively, for AVC prevalence and 0.62 (0.42-0.92), 1.93 (1.28-2.91), and 1.09 (0.77-1.55), respectively, for AVC incidence. Their linear trends of serum magnesium and phosphorus were also all statistically significant. Of 131 participants with baseline AVC, there was no association of any serum micronutrients with AVC progression. Serum magnesium was inversely associated, while serum phosphorus was positively associated with AVC prevalence and incidence, suggesting that these serum micronutrients may be potential candidates for risk prediction or prevention of CAVD, and warranting further studies. Copyright © 2018 Elsevier B.V. All rights reserved.

Matrix metalloproteinase inhibitor, doxycycline and progression of calcific aortic valve disease in hyperlipidemic mice.

PubMed

Jung, Jae-Joon; Razavian, Mahmoud; Kim, Hye-Yeong; Ye, Yunpeng; Golestani, Reza; Toczek, Jakub; Zhang, Jiasheng; Sadeghi, Mehran M

2016-09-13

Calcific aortic valve disease (CAVD) is the most common cause of aortic stenosis. Currently, there is no non-invasive medical therapy for CAVD. Matrix metalloproteinases (MMPs) are upregulated in CAVD and play a role in its pathogenesis. Here, we evaluated the effect of doxycycline, a nonselective MMP inhibitor on CAVD progression in the mouse. Apolipoprotein (apo)E(-/-) mice (n = 20) were fed a Western diet (WD) to induce CAVD. After 3 months, half of the animals was treated with doxycycline, while the others continued WD alone. After 6 months, we evaluated the effect of doxycycline on CAVD progression by echocardiography, MMP-targeted micro single photon emission computed tomography (SPECT)/computed tomography (CT), and tissue analysis. Despite therapeutic blood levels, doxycycline had no significant effect on MMP activation, aortic valve leaflet separation or flow velocity. This lack of effect on in vivo images was confirmed on tissue analysis which showed a similar level of aortic valve gelatinase activity, and inflammation between the two groups of animals. In conclusion, doxycycline (100 mg/kg/day) had no effect on CAVD progression in apoE(-/-) mice with early disease. Studies with more potent and specific inhibitors are needed to establish any potential role of MMP inhibition in CAVD development and progression.

Three-dimensional prototyping for procedural simulation of transcatheter mitral valve replacement in patients with mitral annular calcification.

PubMed

El Sabbagh, Abdallah; Eleid, Mackram F; Matsumoto, Jane M; Anavekar, Nandan S; Al-Hijji, Mohammed A; Said, Sameh M; Nkomo, Vuyisile T; Holmes, David R; Rihal, Charanjit S; Foley, Thomas A

2018-01-23

Three-dimensional (3D) prototyping is a novel technology which can be used to plan and guide complex procedures such as transcatheter mitral valve replacement (TMVR). Eight patients with severe mitral annular calcification (MAC) underwent TMVR. 3D digital models with digital balloon expandable valves were created from pre-procedure CT scans using dedicated software. Five models were printed. These models were used to assess prosthesis sizing, anchoring, expansion, paravalvular gaps, left ventricular outflow tract (LVOT) obstruction, and other potential procedure pitfalls. Results of 3D prototyping were then compared to post procedural imaging to determine how closely the achieved procedural result mirrored the 3D modeled result. 3D prototyping simulated LVOT obstruction in one patient who developed it and in another patient who underwent alcohol septal ablation prior to TMVR. Valve sizing correlated with actual placed valve size in six out of the eight patients and more than mild paravalvular leak (PVL) was simulated in two of the three patients who had it. Patients who had mismatch between their modeled valve size and post-procedural imaging were the ones that had anterior leaflet resection which could have altered valve sizing and PVL simulation. 3D printed model of one of the latter patients allowed modification of anterior leaflet to simulate surgical resection and was able to estimate the size and location of the PVL after inserting a valve stent into the physical model. 3D prototyping in TMVR for severe MAC is feasible for simulating valve sizing, apposition, expansion, PVL, and LVOT obstruction. © 2018 Wiley Periodicals, Inc.

Myectomy and LA-to-LV Conduit for Severe Calcific Mitral Stenosis and Hypertrophic Cardiomyopathy.

PubMed

Meghji, Zahara; Nguyen, Anita; Geske, Jeffrey B; Schaff, Hartzell V

2018-02-26

Severe calcific mitral valve stenosis can rarely occur concomitantly with obstructive hypertrophic cardiomyopathy. In these patients, surgical decalcification of the stenotic mitral valve followed by mitral valve replacement carries significant operative risk and may result in paravalvular leakage, atrioventricular groove disruption, and excessive bleeding. We report the first 2 cases of obstructive hypertrophic cardiomyopathy with severe calcific mitral valve stenosis successfully treated with concomitant transaortic septal myectomy and bypass of the stenotic mitral valve using a valved left atrium to left ventricular conduit. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Quantified degree of eccentricity of aortic valve calcification predicts risk of paravalvular regurgitation and response to balloon post-dilation after self-expandable transcatheter aortic valve replacement.

PubMed

Park, Jun-Bean; Hwang, In-Chang; Lee, Whal; Han, Jung-Kyu; Kim, Chi-Hoon; Lee, Seung-Pyo; Yang, Han-Mo; Park, Eun-Ah; Kim, Hyung-Kwan; Chiam, Paul T L; Kim, Yong-Jin; Koo, Bon-Kwon; Sohn, Dae-Won; Ahn, Hyuk; Kang, Joon-Won; Park, Seung-Jung; Kim, Hyo-Soo

2018-05-15

Limited data exist regarding the impact of aortic valve calcification (AVC) eccentricity on the risk of paravalvular regurgitation (PVR) and response to balloon post-dilation (BPD) after transcatheter aortic valve replacement (TAVR). We investigated the prognostic value of AVC eccentricity in predicting the risk of PVR and response to BPD in patients undergoing TAVR. We analyzed 85 patients with severe aortic stenosis who underwent self-expandable TAVR (43 women; 77.2±7.1years). AVC was quantified as the total amount of calcification (total AVC load) and as the eccentricity of calcium (EoC) using calcium volume scoring with contrast computed tomography angiography (CTA). The EoC was defined as the maximum absolute difference in calcium volume scores between 2 adjacent sectors (bi-partition method) or between sectors based on leaflets (leaflet-based method). Total AVC load and bi-partition EoC, but not leaflet-based EoC, were significant predictors for the occurrence of ≥moderate PVR, and bi-partition EoC had a better predictive value than total AVC load (area under the curve [AUC]=0.863 versus 0.760, p for difference=0.006). In multivariate analysis, bi-partition EoC was an independent predictor for the risk of ≥moderate PVR regardless of perimeter oversizing index. The greater bi-partition EoC was the only significant parameter to predict poor response to BPD (AUC=0.775, p=0.004). Pre-procedural assessment of AVC eccentricity using CTA as "bi-partition EoC" provides useful predictive information on the risk of significant PVR and response to BPD in patients undergoing TAVR with self-expandable valves. Copyright © 2017 Elsevier B.V. All rights reserved.

Association between aortic valve calcification measured on non-contrast computed tomography and aortic valve stenosis in the general population.

PubMed

Paulsen, Niels Herluf; Carlsen, Bjarke Bønløkke; Dahl, Jordi Sanchez; Carter-Storch, Rasmus; Christensen, Nicolaj Lyhne; Khurrami, Lida; Møller, Jacob Eifer; Lindholt, Jes Sandal; Diederichsen, Axel Cosmus Pyndt

2016-01-01

Aortic valve calcification (AVC) measured on non-contrast computed tomography (CT) has shown correlation to severity of aortic valve stenosis (AS) and mortality in patients with known AS. The aim of this study was to determine the association of CT verified AVC and subclinical AS in a general population undergoing CT. CT scans from 566 randomly selected male participants (age 65-74) in the Danish cardiovascular screening study (DANCAVAS) were analyzed for AVC. All participants with a moderately or severely increased AVC score (≥300 arbitrary units (AU)) and a matched control group were invited for a supplementary echocardiography. AS was graded by indexed aortic valve area (AVAi) on echocardiography as moderate 0.6-0.85 cm(2)/m(2) and severe < 0.6 cm(2)/m(2), respectively. ROC- and regression analyses were performed. Due to prior valve surgery, and artifacts from ICD leads 16 individuals were excluded from the AVC scoring. Moderate or severe increased AVC was observed in 10.7% (95% CI: 8.4-13.7). Echocardiography was performed in 101 individuals; 32.7% (95% CI: 21.8 to 46.0) with moderate or high AVC score had moderate or severe AS, while none with no or low AVC. A ROC analysis defined an AVC score ≥588 AU to be suggestive of moderate or severe AS (AUC 0.89 ± 0.04, sensitivity 83% and specificity 87%). In the univariate analyses, AVC was the only variable significantly associated with AS. This study indicates an association between CT verified AVC and subclinical AS. Copyright © 2016 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

Current Management of Calcific Aortic Stenosis

PubMed Central

Lindman, Brian R.; Bonow, Robert O.; Otto, Catherine M.

2014-01-01

Calcific aortic stenosis (AS) is a progressive disease with no effective medical therapy that ultimately requires aortic valve replacement (AVR) for severe valve obstruction. Echocardiography is the primary diagnostic approach to define valve anatomy, measure AS severity and evaluate the left ventricular (LV) response to chronic pressure overload. In asymptomatic patients, markers of disease progression include the degree of leaflet calcification, hemodynamic severity of stenosis, adverse LV remodeling, reduced LV longitudinal strain, myocardial fibrosis and pulmonary hypertension. The onset of symptoms portends a predictably high mortality rate unless AVR is performed. In symptomatic patients, AVR improves symptoms, improves survival and, in patients with LV dysfunction, improves systolic function. Poor outcomes after AVR are associated with low-flow low-gradient AS, severe ventricular fibrosis, oxygen dependent lung disease, frailty, advanced renal dysfunction and a high comorbidity score. However, in most patients with severe symptoms, AVR is lifesaving. Bioprosthetic valves are recommended for patients over the age of 65 years. Transcatheter AVR is now available for patients with severe comorbidities, is recommended in patients who are deemed inoperable and is a reasonable alternative to surgical AVR in high risk patients. PMID:23833296

Myocardial blood flow reserve is impaired in patients with aortic valve calcification and unobstructed epicardial coronary arteries.

PubMed

Nel, Karen; Nam, Michael C Y; Anstey, Chris; Boos, Christopher J; Carlton, Edward; Senior, Roxy; Kaski, Juan Carlos; Khattab, Ahmed; Shamley, Delva; Byrne, Christopher D; Stanton, Tony; Greaves, Kim

2017-12-01

Although calcific aortic valve disease (CAVD) is associated with coronary atherosclerosis, it is not known whether early CAVD is associated with coronary microcirculatory dysfunction (CMD). We sought to investigate the relationship between myocardial blood flow reserve (MBFR) - a measure of CMD, and early CAVD in the absence of obstructive epicardial coronary artery disease. We also determined whether this relationship was independent of coronary artery disease (CAD) and hs-CRP, a marker of systemic inflammation. 183 patients with chest pain and unobstructed coronary arteries were studied. Aortic valve calcification score (AVCS), coronary total plaque length (TPL), and coronary calcium score were quantified from multislice CT. MBFR was assessed using vasodilator myocardial contrast echocardiography. Hs-CRP was measured from venous blood using a particle-enhanced immunoassay. Mean (±SD) participant age was 59.8 (9.6) years. Mean AVCS was 68 (258) AU, TPL was 15.6 (22.2) mm, and median coronary calcification score was 43.5AU. Mean MBFR was 2.20 (0.52). Mean hs-CRP was 2.52 (3.86) mg/l. Multivariable linear regression modelling incorporating demographics, coronary plaque characteristics, MBFR, and inflammatory markers, demonstrated that age (β=0.05, 95% CI: 0.02, 0.08, P=0.007), hs-CRP (β=0.09, CI: 0.02, 0.16, P=0.010) and diabetes (β=1.03, CI: 0.08, 1.98, P=0.033), were positively associated with AVCS. MBFR (β=-0.87, CI: -1.44, -0.30, P=0.003), BMI (β=-0.11, CI: -0.21, -0.01, P=0.033), and LDL (β=-0.32, CI: -0.61, -0.03, P=0.029) were negatively associated with AVCS. TPL and coronary calcium score were not independently associated with AVCS when included in the regression model. Coronary microvascular function as determined by measurement of myocardial blood flow reserve is independently associated with early CAVD. This effect is independent of the presence of coronary artery disease and also systemic inflammation. Copyright © 2017 Elsevier B.V. All rights

When a Heart Murmur Signals Valve Disease

MedlinePlus

... in adults may be related to: Valve calcification Endocarditis Rheumatic fever In children, abnormal heart murmurs may ... Problem: Pulmonary Valve Regurgitation Heart Valves and Infective Endocarditis Left Ventricular Hypertrophy • Risks, Signs and Symptoms • Accurate ...

Calcium Signaling Pathway Genes RUNX2 and CACNA1C Are Associated With Calcific Aortic Valve Disease

PubMed Central

Guauque-Olarte, Sandra; Messika-Zeitoun, David; Droit, Arnaud; Lamontagne, Maxime; Tremblay-Marchand, Joël; Lavoie-Charland, Emilie; Gaudreault, Nathalie; Arsenault, Benoit J.; Dubé, Marie-Pierre; Tardif, Jean-Claude; Body, Simon C.; Seidman, Jonathan G.; Boileau, Catherine; Mathieu, Patrick; Pibarot, Philippe; Bossé, Yohan

2016-01-01

Background Calcific aortic valve stenosis (AS) is a life-threatening disease with no medical therapy. The genetic architecture of AS remains elusive. This study combines genome-wide association studies, gene expression, and expression quantitative trait loci mapping in human valve tissues to identify susceptibility genes of AS. Methods and Results A meta-analysis was performed combining the results of 2 genome-wide association studies in 474 and 486 cases from Quebec City (Canada) and Paris (France), respectively. Corresponding controls consisted of 2988 and 1864 individuals with European ancestry from the database of genotypes and phenotypes. mRNA expression levels were evaluated in 9 calcified and 8 normal aortic valves by RNA sequencing. The results were integrated with valve expression quantitative trait loci data obtained from 22 AS patients. Twenty-five single-nucleotide polymorphisms had P<5×10−6 in the genome-wide association studies meta-analysis. The calcium signaling pathway was the top gene set enriched for genes mapped to moderately AS-associated single-nucleotide polymorphisms. Genes in this pathway were found differentially expressed in valves with and without AS. Two single-nucleotide polymorphisms located in RUNX2 (runt-related transcription factor 2), encoding an osteogenic transcription factor, demonstrated some association with AS (genome-wide association studies P=5.33×10−5). The mRNA expression levels of RUNX2 were upregulated in calcified valves and associated with eQTL-SNPs. CACNA1C encoding a subunit of a voltage-dependent calcium channel was upregulated in calcified valves. The eQTL-SNP with the most significant association with AS located in CACNA1C was associated with higher expression of the gene. Conclusions This integrative genomic study confirmed the role of RUNX2 as a potential driver of AS and identified a new AS susceptibility gene, CACNA1C, belonging to the calcium signaling pathway. PMID:26553695

The extent of aortic annulus calcification is a predictor of postprocedural eccentricity and paravalvular regurgitation: a pre- and postinterventional cardiac computed tomography angiography study.

PubMed

Bekeredjian, Raffi; Bodingbauer, Dorothea; Hofmann, Nina P; Greiner, Sebastian; Schuetz, Moritz; Geis, Nicolas A; Kauczor, Hans U; Bryant, Mark; Chorianopoulos, Emmanuel; Pleger, Sven T; Mereles, Derliz; Katus, Hugo A; Korosoglou, Grigorios

2015-03-01

To investigate if the extent of aortic valve calcification is associated with postprocedural prosthesis eccentricity and paravalvular regurgitation (PAR) in patients undergoing transcatheter aortic valve implantation (TAVI). Cardiac computed tomography angiography (CCTA) was performed before and 3 months after TAVI in 46 patients who received the self-expanding CoreValve and in 22 patients who underwent balloon-expandable Edwards Sapien XT implantation. Aortic annulus calcification was measured with CCTA prior to TAVI and prosthesis eccentricity was assessed with post-TAVI CCTA. Standard echocardiography was also performed in all patients at 3-month follow-up exam. Annulus eccentricity was reduced during TAVI using both implantation systems (from 0.23 ± 0.06 to 0.18 ± 0.07 using CoreValve and from 0.20 ± 0.07 to 0.05 ± 0.03 using Edwards Sapien XT; P<.001 for both). With Edwards Sapien XT, eccentricity reduction at the level of the aortic annulus was significantly higher compared with CoreValve (P<.001). Annulus eccentricity after CoreValve use was significantly related to absolute valve calcification and to valve calcification indexed to body surface area (BSA) (r = 0.48 and 0.50, respectively; P<.001 for both). Furthermore, a significant association was observed between aortic valve calcification and PAR (P<.01 by ANOVA) in patients who received CoreValve. Using ROC analysis, a cut-off value over 913 mm² aortic valve calcification predicted the occurrence of moderate or severe PAR with a sensitivity of 92% and a specificity of 63% (area under the curve = 0.75). Furthermore, multivariable analysis showed that aortic valve calcification was a robust predictor of postprocedural eccentricity and PAR, independent of the aortic annulus size and native valve eccentricity and of CoreValve prosthesis size (adjusted r = 0.46 and 0.50, respectively; P<.01 for both). Such associations were not present with the Edwards Sapien XT system. The extent of native aortic

Aortic Valve Calcification and Risk of Stroke: The Rotterdam Study.

PubMed

Bos, Daniel; Bozorgpourniazi, Atefeh; Mutlu, Unal; Kavousi, Maryam; Vernooij, Meike W; Moelker, Adriaan; Franco, Oscar H; Koudstaal, Peter J; Ikram, M Arfan; van der Lugt, Aad

2016-11-01

It remains uncertain whether aortic valve calcification (AVC) is a risk factor for stroke. From the population-based Rotterdam Study, 2471 participants (mean age: 69.6 years; 51.8% women) underwent computed tomography to quantify AVC. We assessed prevalent stroke and continuously monitored the remaining participants for the incidence of stroke. Logistic and Cox regression models were used to investigate associations of AVC with prevalent stroke and risk of incident stroke. AVC was present in 33.1% of people. At baseline, 97 participants had ever suffered a stroke. During 18 665 person-years of follow-up (mean: 7.9 years), 135 people experienced a first-ever stroke. The presence of AVC was not associated with prevalent stroke (fully adjusted odds ratio: 0.97 (95% confidence interval, 0.61-1.53]) or with an increased risk of stroke (fully adjusted hazard ratio: 0.99 (95% confidence interval, 0.69-1.44]). Although AVC is a common finding in middle-aged and elderly community-dwelling people, our results suggest that AVC is not associated with an increased risk of stroke. © 2016 American Heart Association, Inc.

Coconut Atrium: Transmural Calcification of the Entire Left Atrium

PubMed Central

Campo, Carlos Del; Weinstein, Paul; Kunnelis, Constantine; DiStefano, Peter; Ebers, Gloria M.

2000-01-01

Massive calcification of the left atrium usually spares the interatrial septum, which provides a cleavage plane for surgical access to the mitral valve. Endoatriectomy with mitral valve replacement is the currently accepted corrective procedure because it affords maximum exposure while decreasing the risk of embolization and intraoperative hemorrhage. We describe a case in which the entire left atrium, including the septum, was thickly calcified and resembled a coconut shell. This condition prevented surgical correction of severe mitral stenosis. To our knowledge, this is the most severe case of left atrial calcification yet reported in the literature. Although it is not possible to establish preoperatively that the atrium is completely calcified and impossible to incise, when predisposing factors and evidence of complete transmural calcification are present, the surgeon should be aware of this possibility and should weigh carefully the decision to operate. PMID:10830629

Fibrocalcific aortic valve disease: Opportunity to understand disease mechanisms using mouse models

PubMed Central

Weiss, Robert M.; Miller, Jordan D.; Heistad, Donald D.

2013-01-01

Studies in vitro and in vivo continue to identify complex regulated mechanisms leading to overt fibrocalcific aortic valve disease (FCAVD). Assessment of the functional impact of those processes requires careful studies of models of FCAVD in vivo. Although the genetic basis for FCVAD is unknown for most patients with FCAVD, several disease-associated genes have been identified in humans and mice. Some gene products which regulate valve development in utero also protect against fibro-calcific disease during postnatal aging. Valve calcification can occur via processes that resemble bone formation. But valve calcification can also occur by non-osteogenic mechanisms, such as formation of calcific apoptotic nodules. Anti-calcific interventions might preferentially target either osteogenic or non-osteogenic calcification. Although FCAVD and atherosclerosis share several risk factors and mechanisms, there are fundamental differences between arteries and the aortic valve, with respect to disease mechanisms and responses to therapeutic interventions. Both innate and acquired immunity are likely to contribute to FCAVD. Angiogenesis is a feature of inflammation, but may also contribute independently to progression of FCAVD, possibly by actions of pericytes that are associated with new blood vessels. Several therapeutic interventions appear to be effective in attenuating development of FCAVD in mice. Therapies which are effective early in the course of FCAVD, however, are not necessarily effective in established disease. PMID:23833295

Idiopathic infantile arterial calcification in two siblings: failure of treatment with diphosphonate.

PubMed Central

Stuart, G; Wren, C; Bain, H

1990-01-01

Two siblings with idiopathic infantile arterial calcification are reported. The fetal and postnatal echocardiographic features were a large pericardial effusion, thickened pulmonary and aortic valves, poor pulsation of the descending aorta, and calcification of the great vessels. In one patient calcification was first detected at 33 weeks' gestation. Despite treatment with disodium etidronate both children died. Images PMID:2118367

Predominance of Abdominal Visceral Adipose Tissue Reflects the Presence of Aortic Valve Calcification.

PubMed

Oikawa, Masayoshi; Owada, Takashi; Yamauchi, Hiroyuki; Misaka, Tomofumi; Machii, Hirofumi; Yamaki, Takayoshi; Sugimoto, Koichi; Kunii, Hiroyuki; Nakazato, Kazuhiko; Suzuki, Hitoshi; Saitoh, Shu-Ichi; Takeishi, Yasuchika

2016-01-01

Background. Aortic valve calcification (AVC) is a common feature of aging and is related to coronary artery disease. Although abdominal visceral adipose tissue (VAT) plays fundamental roles in coronary artery disease, the relationship between abdominal VAT and AVC is not fully understood. Methods. We investigated 259 patients who underwent cardiac and abdominal computed tomography (CT). AVC was defined as calcified lesion on the aortic valve by CT. %abdominal VAT was calculated as abdominal VAT area/total adipose tissue area. Results. AVC was detected in 75 patients, and these patients showed higher %abdominal VAT (44% versus 38%, p < 0.05) compared to those without AVC. When the cutoff value of %abdominal VAT was set at 40.9%, the area under the curve to diagnose AVC was 0.626. Multivariable logistic regression analysis showed that age (OR 1.120, 95% CI 1.078-1.168, p < 0.01), diabetes (OR 2.587, 95% CI 1.323-5.130, p < 0.01), and %abdominal VAT (OR 1.032, 95% CI 1.003-1.065, p < 0.05) were independent risk factors for AVC. The net reclassification improvement value for detecting AVC was increased when %abdominal VAT was added to the model: 0.5093 (95% CI 0.2489-0.7697, p < 0.01). Conclusion. We determined that predominance of VAT is associated with AVC.

Predominance of Abdominal Visceral Adipose Tissue Reflects the Presence of Aortic Valve Calcification

PubMed Central

Oikawa, Masayoshi; Owada, Takashi; Yamauchi, Hiroyuki; Misaka, Tomofumi; Machii, Hirofumi; Yamaki, Takayoshi; Sugimoto, Koichi; Kunii, Hiroyuki; Nakazato, Kazuhiko; Suzuki, Hitoshi; Saitoh, Shu-ichi; Takeishi, Yasuchika

2016-01-01

Background. Aortic valve calcification (AVC) is a common feature of aging and is related to coronary artery disease. Although abdominal visceral adipose tissue (VAT) plays fundamental roles in coronary artery disease, the relationship between abdominal VAT and AVC is not fully understood. Methods. We investigated 259 patients who underwent cardiac and abdominal computed tomography (CT). AVC was defined as calcified lesion on the aortic valve by CT. %abdominal VAT was calculated as abdominal VAT area/total adipose tissue area. Results. AVC was detected in 75 patients, and these patients showed higher %abdominal VAT (44% versus 38%, p < 0.05) compared to those without AVC. When the cutoff value of %abdominal VAT was set at 40.9%, the area under the curve to diagnose AVC was 0.626. Multivariable logistic regression analysis showed that age (OR 1.120, 95% CI 1.078–1.168, p < 0.01), diabetes (OR 2.587, 95% CI 1.323–5.130, p < 0.01), and %abdominal VAT (OR 1.032, 95% CI 1.003–1.065, p < 0.05) were independent risk factors for AVC. The net reclassification improvement value for detecting AVC was increased when %abdominal VAT was added to the model: 0.5093 (95% CI 0.2489–0.7697, p < 0.01). Conclusion. We determined that predominance of VAT is associated with AVC. PMID:26904670

Concomitant transcatheter aortic valve and left ventricular assist device implantation.

PubMed

Baum, Christina; Seiffert, Moritz; Treede, Hendrik; Reichenspurner, Hermann; Deuse, Tobias

2013-01-01

Relevant aortic regurgitation (AR) requires surgical repair at the time of left ventricular assist device (LVAD) implantation to reduce recirculation and ensure adequate forward flow. We report here on a patient with moderate AR in a noncalcified aortic valve and extensive calcification of the ascending aorta. The latter precluded aortic-crossclamping and, thus, surgical intervention on the aortic valve. Although there were no valvular or annular calcifications, a JenaValve transcatheter heart valve was successfully placed transapically with subsequent LVAD implantation in one operation. We believe concomitant transcatheter aortic valve implantation (TAVI) and LVAD implantation is a promising hybrid procedure, even in patients with pure AR.

Insulin Resistance in Adipose Tissue but Not in Liver Is Associated with Aortic Valve Calcification.

PubMed

Jorge-Galarza, Esteban; Posadas-Romero, Carlos; Torres-Tamayo, Margarita; Medina-Urrutia, Aida X; Rodas-Díaz, Marco A; Posadas-Sánchez, Rosalinda; Vargas-Alarcón, Gilberto; González-Salazar, María Del Carmen; Cardoso-Saldaña, Guillermo C; Juárez-Rojas, Juan G

2016-01-01

Background . Insulin resistance is involved in the pathogenesis of cardiovascular disease, but its relationship with cardiovascular calcification has yielded conflicting results. The purpose of the present study was to investigate the role of hepatic and adipose tissue insulin resistance on the presence of coronary artery (CAC > 0) and aortic valve calcification (AVC > 0). Methods . In 1201 subjects (52% women, 53.6 ± 9.3 years old) without familiar and personal history of coronary heart disease, CAC and AVC were assessed by multidetector-computed tomography. Cardiovascular risk factors were documented and lipid profile, inflammation markers, glucose, insulin, and free fatty acids were measured. Hepatic insulin resistance (HOMA-IR) and adipose tissue insulin resistance (Adipo-IR) indices were calculated. Results . There was a significant relationship between HOMA-IR and Adipo-IR indices ( r = 0.758, p < 0.001). Participants in the highest quartiles of HOMA-IR and Adipo-IR indices had a more adverse cardiovascular profile and higher prevalence of CAC > 0 and AVC > 0. After full adjustment, subjects in the highest quartile of Adipo-IR index had higher odds of AVC > 0 (OR: 2.40; 95% CI: 1.30-4.43), as compared to those in the lowest quartile. Conclusions . Adipo-IR was independently associated with AVC > 0. This suggests that abnormal adipose tissue function favors insulin resistance that may promote the development and progression of AVC.

Lipoprotein(a) levels are associated with subclinical calcific aortic valve disease in Caucasian and Black individuals: The Multi-Ethnic Study of Atherosclerosis

PubMed Central

Cao, Jing; Steffen, Brian T.; Budoff, Matthew; Post, Wendy S.; Thanassoulis, George; Kestenbaum, Bryan; McConnell, Joseph P.; Warnick, Russell; Guan, Weihua; Tsai, Michael Y.

2016-01-01

Objective Lipoprotein(a) [Lp(a)] is a risk factor for calcific aortic valve disease (CAVD) but has not been evaluated across multiple races/ethnicities. This study aimed to determine whether Lp(a) cut-off values used in clinical laboratories to assess risk of cardiovascular disease identify subclinical CAVD and its severity and whether significant relations are observed across race/ethnicity. Approach and Results Lp(a) concentrations were measured using a turbidimetric immunoassay, and subclinical CAVD was measured by quantifying aortic valve calcification (AVC) through computed tomography scanning in 4,678 participants of the Multi-Ethnic Study of Atherosclerosis. Relative risk (RR) and ordered logistic regression analysis determined cross-sectional associations of Lp(a) with AVC and its severity, respectively. The conventional 30 mg/dL Lp(a) clinical cut-off was associated with AVC in Caucasian (RR: 1.56; CI: 1.24–1.96) and was borderline significant (p=0.059) in Black study participants (RR: 1.55; CI: 0.98–2.44). Caucasians with levels ≥50 mg/dL also showed higher prevalence of AVC (RR: 1.72; CI: 1.36–2.17) than those below this level. Significant associations were observed between Lp(a) and degree of AVC in both Caucasians and Black individuals. The presence of existing coronary artery calcification did not affect these associations of Lp(a) and CAVD. There were no significant findings in Hispanics or Chinese. Conclusions Lp(a) cut-off values that are currently used to assess cardiovascular risk appear to be applicable to CAVD, but our results suggest race/ethnicity may be important in cut-off selection. Further studies are warranted to determine whether race/ethnicity influences Lp(a) and risk of CAVD incidence and its progression. PMID:26941019

Bicuspid Aortic Valve Stenosis and the Effect of Vitamin K2 on Calcification Using 18F-Sodium Fluoride Positron Emission Tomography/Magnetic Resonance: The BASIK2 Rationale and Trial Design.

PubMed

Peeters, Frederique E C M; van Mourik, Manouk J W; Meex, Steven J R; Bucerius, Jan; Schalla, Simon M; Gerretsen, Suzanne C; Mihl, Casper; Dweck, Marc R; Schurgers, Leon J; Wildberger, Joachim E; Crijns, Harry J G M; Kietselaer, Bas L J H

2018-03-21

BASIK2 is a prospective, double-blind, randomized placebo-controlled trial investigating the effect of vitamin K2 (menaquinone-7;MK7) on imaging measurements of calcification in the bicuspid aortic valve (BAV) and calcific aortic valve stenosis (CAVS). BAV is associated with early development of CAVS. Pathophysiologic mechanisms are incompletely defined, and the only treatment available is valve replacement upon progression to severe symptomatic stenosis. Matrix Gla protein (MGP) inactivity is suggested to be involved in progression. Being a vitamin K dependent protein, supplementation with MK7 is a pharmacological option for activating MGP and intervening in the progression of CAVS. Forty-four subjects with BAV and mild-moderate CAVS will be included in the study, and baseline 18 F-sodiumfluoride ( 18 F-NaF) positron emission tomography (PET)/ magnetic resonance (MR) and computed tomography (CT) assessments will be performed. Thereafter, subjects will be randomized (1:1) to MK7 (360 mcg/day) or placebo. During an 18-month follow-up period, subjects will visit the hospital every 6 months, undergoing a second 18 F-NaF PET/MR after 6 months and CT after 6 and 18 months. The primary endpoint is the change in PET/MR 18 F-NaF uptake (6 months minus baseline) compared to this delta change in the placebo arm. The main secondary endpoints are changes in calcium score (CT), progression of the left ventricularremodeling response and CAVS severity (echocardiography). We will also examine the association between early calcification activity (PET) and later changes in calcium score (CT).

Protective role of Smad6 in inflammation-induced valvular cell calcification

PubMed Central

Li, Xin; Lim, Jina J.; Lu, Jinxiu; Pedego, Taylor M.; Demer, Linda; Tintut, Yin

2016-01-01

Calcific aortic vascular and valvular disease (CAVD) is associated with hyperlipidemia, the effects of which occur through chronic inflammation. Evidence suggests that inhibitory small mothers against decapentaplegic (I-Smads; Smad6 and 7) regulate valve embryogenesis and may serve as a mitigating factor in CAVD. However, whether I-Smads regulate inflammation-induced calcific vasculopathy is not clear. Therefore, we investigated the role of I-Smads in atherosclerotic calcification. Results showed that expression of Smad6, but not Smad7, was reduced in aortic and valve tissues of hyperlipidemic compared with normolipemic mice, while expression of tumor necrosis factor alpha (TNF-a) was upregulated. To test whether the effects are in response to inflammatory cytokines, we isolated murine aortic valve leaflets and cultured valvular interstitial cells (mVIC) from the normolipemic mice. By immunochemistry, mVICs were strongly positive for vimentin, weakly positive for smooth muscle alpha actin, and negative for an endothelial cell marker. TNF-a upregulated alkaline phosphatase (ALP) activity and matrix mineralization in mVICs. By gene expression analysis, TNF-a significantly upregulated bone morphogenetic protein 2 (BMP-2) expression while downregulating Smad6 expression. Smad7 expression was not significantly affected. To further test the role of Smad6 on TNF-a-induced valvular cell calcification, we knocked down Smad6 expression using lentiviral transfection. In cells transfected with Smad6 shRNA, TNF-a further augmented ALP activity, expression of BMP-2, Wnt- and redox-regulated genes, and matrix mineralization compared with the control cells. These findings suggest that TNF-a induces valvular and vascular cell calcification, in part, by specifically reducing the expression of a BMP-2 signaling inhibitor, Smad6. PMID:25864564

Relationship between sclerostin and cardiovascular calcification in hemodialysis patients: a cross-sectional study

PubMed Central

2013-01-01

Background Sclerostin is a Wnt pathway antagonist regulating osteoblast activity and bone turnover. Here, we assessed the potential association of sclerostin with the development of coronary artery (CAC) and aortic valve calcifications (AVC) in haemodialysis (HD) patients. Methods We conducted a cross-sectional multi-slice computed tomography (MS-CT) scanning study in 67 chronic HD patients (59.4 ± 14.8 yrs) for measurement of CAC and AVC. We tested established biomarkers as well as serum sclerostin (ELISA) regarding their association to the presence of calcification. Fifty-four adults without relevant renal disease served as controls for serum sclerostin levels. Additionally, sclerostin expression in explanted aortic valves from 15 dialysis patients was analysed ex vivo by immunohistochemistry and mRNA quantification (Qt-RT-PCR). Results CAC (Agatston score > 100) and any AVC were present in 65% and in 40% of the MS-CT patient group, respectively. Serum sclerostin levels (1.53 ± 0.81 vs 0.76 ± 0.31 ng/mL, p < 0.001) were significantly elevated in HD compared to controls and more so in HD patients with AVC versus those without AVC (1.78 ± 0.84 vs 1.35 ± 0.73 ng/mL, p = 0.02). Multivariable regression analysis for AVC revealed significant associations with higher serum sclerostin. Ex vivo analysis of uraemic calcified aortic valves (n = 10) revealed a strong sclerostin expression very close to calcified regions (no sclerostin staining in non-calcified valves). Correspondingly, we observed a highly significant upregulation of sclerostin mRNA in calcified valves compared to non-calcified control valves. Conclusion We found a strong association of sclerostin with calcifying aortic heart valve disease in haemodialysis patients. Sclerostin is locally produced in aortic valve tissue adjacent to areas of calcification. PMID:24112318

Transcatheter Aortic Valve Replacement for Native Aortic Valve Regurgitation

PubMed Central

Spina, Roberto; Anthony, Chris; Muller, David WM

2015-01-01

Transcatheter aortic valve replacement with either the balloon-expandable Edwards SAPIEN XT valve, or the self-expandable CoreValve prosthesis has become the established therapeutic modality for severe aortic valve stenosis in patients who are not deemed suitable for surgical intervention due to excessively high operative risk. Native aortic valve regurgitation, defined as primary aortic incompetence not associated with aortic stenosis or failed valve replacement, on the other hand, is still considered a relative contraindication for transcatheter aortic valve therapies, because of the absence of annular or leaflet calcification required for secure anchoring of the transcatheter heart valve. In addition, severe aortic regurgitation often coexists with aortic root or ascending aorta dilatation, the treatment of which mandates operative intervention. For these reasons, transcatheter aortic valve replacement has been only sporadically used to treat pure aortic incompetence, typically on a compassionate basis and in surgically inoperable patients. More recently, however, transcatheter aortic valve replacement for native aortic valve regurgitation has been trialled with newer-generation heart valves, with encouraging results, and new ancillary devices have emerged that are designed to stabilize the annulus–root complex. In this paper we review the clinical context, technical characteristics and outcomes associated with transcatheter treatment of native aortic valve regurgitation. PMID:29588674

Protective Role of Smad6 in Inflammation-Induced Valvular Cell Calcification.

PubMed

Li, Xin; Lim, Jina; Lu, Jinxiu; Pedego, Taylor M; Demer, Linda; Tintut, Yin

2015-10-01

Calcific aortic vascular and valvular disease (CAVD) is associated with hyperlipidemia, the effects of which occur through chronic inflammation. Evidence suggests that inhibitory small mothers against decapentaplegic (I-Smads; Smad6 and 7) regulate valve embryogenesis and may serve as a mitigating factor in CAVD. However, whether I-Smads regulate inflammation-induced calcific vasculopathy is not clear. Therefore, we investigated the role of I-Smads in atherosclerotic calcification. Results showed that expression of Smad6, but not Smad7, was reduced in aortic and valve tissues of hyperlipidemic compared with normolipemic mice, while expression of tumor necrosis factor alpha (TNF-α) was upregulated. To test whether the effects are in response to inflammatory cytokines, we isolated murine aortic valve leaflets and cultured valvular interstitial cells (mVIC) from the normolipemic mice. By immunochemistry, mVICs were strongly positive for vimentin, weakly positive for smooth muscle α actin, and negative for an endothelial cell marker. TNF-α upregulated alkaline phosphatase (ALP) activity and matrix mineralization in mVICs. By gene expression analysis, TNF-α significantly upregulated bone morphogenetic protein 2 (BMP-2) expression while downregulating Smad6 expression. Smad7 expression was not significantly affected. To further test the role of Smad6 on TNF-α-induced valvular cell calcification, we knocked down Smad6 expression using lentiviral transfection. In cells transfected with Smad6 shRNA, TNF-α further augmented ALP activity, expression of BMP-2, Wnt- and redox-regulated genes, and matrix mineralization compared with the control cells. These findings suggest that TNF-α induces valvular and vascular cell calcification, in part, by specifically reducing the expression of a BMP-2 signaling inhibitor, Smad6. © 2015 Wiley Periodicals, Inc.

Aortic annulus eccentricity before and after transcatheter aortic valve implantation: Comparison of balloon-expandable and self-expanding prostheses.

PubMed

Schuhbaeck, Annika; Weingartner, Christina; Arnold, Martin; Schmid, Jasmin; Pflederer, Tobias; Marwan, Mohamed; Rixe, Johannes; Nef, Holger; Schneider, Christian; Lell, Michael; Uder, Michael; Ensminger, Stephan; Feyrer, Richard; Weyand, Michael; Achenbach, Stephan

2015-07-01

The geometry of the aortic annulus and implanted transcatheter aortic valve prosthesis might influence valve function. We investigated the influence of valve type and aortic valve calcification on post-implant geometry of catheter-based aortic valve prostheses. Eighty consecutive patients with severe aortic valve stenosis (mean age 82 ± 6 years) underwent computed tomography before and after TAVI. Aortic annulus diameters were determined. Influence of prosthesis type and degree of aortic valve calcification on post-implant eccentricity were analysed. Aortic annulus eccentricity was reduced in patients after TAVI (0.21 ± 0.06 vs. 0.08 ± 0.06, p<0.0001). Post-TAVI eccentricity was significantly lower in 65 patients following implantation of a balloon-expandable prosthesis as compared to 15 patients who received a self-expanding prosthesis (0.06 ± 0.05 vs. 0.15 ± 0.07, p<0.0001), even though the extent of aortic valve calcification was not different. After TAVI, patients with a higher calcium amount retained a significantly higher eccentricity compared to patients with lower amounts of calcium. Patients undergoing TAVI with a balloon-expandable prosthesis show a more circular shape of the implanted prosthesis as compared to patients with a self-expanding prosthesis. Eccentricity of the deployed prosthesis is affected by the extent of aortic valve calcification. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

CT predictors of post-procedural aortic regurgitation in patients referred for transcatheter aortic valve implantation: an analysis of 105 patients.

PubMed

Marwan, Mohamed; Achenbach, Stephan; Ensminger, Stefan M; Pflederer, Tobias; Ropers, Dieter; Ludwig, Josef; Weyand, Michael; Daniel, Werner G; Arnold, Martin

2013-06-01

Cardiac computed tomography (CT) allows accurate and detailed analysis of the anatomy of the aortic root and valve, including quantification of calcium. We evaluated the correlation between different CT parameters and the degree of post-procedural aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) using the balloon-expandable Edwards Sapien prosthesis. Pre-intervention contrast-enhanced dual source CT data sets of 105 consecutive patients (48 males, mean age 81 ± 6 years, mean logEuroSCORE 34 ± 13%) with symptomatic severe aortic valve stenosis referred for TAVI using the Edwards Sapien prosthesis (Edwards lifesciences, Inc., CA, USA) were analysed. The degrees of aortic valve commissural calcification and annular calcification were visually assessed on a scale from 0 to 3. Furthermore, the degree of aortic valve calcification as quantified by the Agatston score, aortic annulus eccentricity, aortic diameter at the level of the sinus of valsalva and at the sinotubular junction were assessed. Early post-procedural AR was assessed using aortography. Significant AR was defined as angiographic AR of at least moderate degree (AR ≥ 2). Visual assessment of the degree of aortic annular calcification as well as the Agatston score of aortic valve calcium correlated weakly, yet significantly with the degree of post-procedural AR (r = 0.31 and 0.24, p = 0.001 and 0.013, respectively). Compared to patients with AR < 2, patients with AR ≥ 2 showed more severe calcification of the aortic annulus (mean visual scores 1.9 ± 0.6 vs. 1.5 ± 0.6, p = 0.003) as well as higher aortic valve Agatston scores (1,517 ± 861 vs. 1,062 ± 688, p = 0.005). Visual score for commissural calcification did not differ significantly between both groups (mean scores 2.4 ± 0.5 vs. 2.5 ± 0.5, respectively, p = 0.117). No significant correlation was observed between the degree of AR and commissural calcification, aortic annulus eccentricity index or aortic diameters

The early and midterm function of decellularized aortic valve allografts.

PubMed

da Costa, Francisco D A; Costa, Ana Claudia B A; Prestes, Roberta; Domanski, Ana Carolina; Balbi, Eduardo Mendel; Ferreira, Andreia D A; Lopes, Sergio Veiga

2010-12-01

This study evaluates the early and midterm results of decellularized aortic valve allografts (DAVA) as an aortic valve replacement. Between October 2005 and February 2010, 41 patients, 28 of whom were male, with a median age of 34 years (range, 0.1 to 71), had aortic valve replacement with DAVA. Decellularization was obtained with a 0.1% sodium dodecyl sulfate solution. Postoperative evaluation was performed with serial echocardiograms, magnetic resonance imaging, and multislice computed tomography studies to evaluate valve hemodynamics, allograft conduit dimensions, and calcification scores. There were 3 early deaths and 1 late death, with a mean follow-up of 19 months (range, 1 to 53). There was 1 reoperation due to a failed mitral valve repair. By echocardiography in all patients, the median immediate postoperative peak gradient was 7 mm Hg (range, 1 to 26 mm Hg), and at last follow-up it was 4 mm Hg (range, 1 to 16 mm Hg); valvular regurgitation was graded as none or trivial in all but 1 patient, who had a regurgitation graded as mild to moderate. By magnetic resonance imaging (n = 4), mean root dimensions were stable at the annulus (24 mm), sinus of Valsalva (33 mm), and sinotubular junction (28 mm). By computed tomography (n = 22), there was only discrete conduit calcification (median calcium score 63 Hounsfield units [HU]; range, 0 to 894 HU) to 3 years of follow-up. Conduit biopsy in the patient who underwent reoperation demonstrated well-preserved wall structure, absence of calcification, and limited in vivo host repopulation. The early and midterm results with DAVA demonstrated stable structural integrity, low rate of calcification, and adequate hemodynamics. Although longer periods of observation are necessary, DAVA appears to be a promising alternative for aortic valve replacement in selected patients. Copyright © 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Associations between Aspirin and other non-steroidal anti-inflammatory drugs and aortic valve or coronary artery calcification: The Multi-Ethnic Study of Atherosclerosis and the Heinz Nixdorf Recall Study

PubMed Central

Delaney, Joseph A; Lehmann, Nils; Jöckel, Karl-Heinz; Elmariah, Sammy; Psaty, Bruce M; Mahabadi, Amir; Budoff, Matt; Kronmal, Richard A; Nasir, Khurram; O’Brien, Kevin D.; Möhlenkamp, Stefan; Moebus, Susanne; Dragano, Nico; Winterstein, Almut; Erbel, Raimund; Kälsch, Hagen

2013-01-01

Background The association between non-steroidal anti-inflammatory drugs (NSAIDs) and the incidence of valvular and arterial calcification is not well established despite known associations between these drugs and cardiovascular events. Objective To compare the association between the baseline use of aspirin with other NSAID class medications with the incidence and prevalence of aortic valve calcification (AVC) and coronary artery calcium (CAC). Methods The relationship of NSAID use to AVC and CAC detected by computed tomography was assessed in 6,814 participants within the Multi-Ethnic Study of Atherosclerosis (MESA) using regression modeling. Results were adjusted for age, sex, ethnicity, study site, anti-hypertensive medication use, education, income, health insurance status, diabetes, smoking, exercise, body mass index, blood pressure, serum lipids, inflammatory markers, fasting glucose, statin medication use, and a simple diet score. Medication use was assessed by medication inventory at baseline which includes the use of non-prescription NSAIDs. MESA collects information on both incident and prevalent calcification. The 4,814 participants of the Heinz Nixdorf Recall (HNR) Study, a German prospective cohort study with similar measures of calcification, were included in this analysis to enable replication. Results Mean age of the MESA participants was 62 years (51% female). After adjustment for possible confounding factors, a possible association between aspirin use and incident AVC (Relative Risk(RR): 1.60; 95%Confidence Interval (CI): 1.19–2.15) did not replicate in the HNR cohort (RR: 1.06; 95%CI: 0.87–1.28). There was no significant association between aspirin use and incident CAC in the MESA cohort (RR 1.08; 95%CI: 0.91–1.29) or in the HNR cohort (RR 1.24; 95%CI: 0.87–1.77). Non-aspirin NSAID use was not associated with either AVC or CAC in either cohort. There were no associations between regular cardiac dose aspirin and incident calcification in

Beyond Framingham risk factors and coronary calcification: does aortic valve calcification improve risk prediction? The Heinz Nixdorf Recall Study.

PubMed

Kälsch, Hagen; Lehmann, Nils; Mahabadi, Amir A; Bauer, Marcus; Kara, Kaffer; Hüppe, Patricia; Moebus, Susanne; Möhlenkamp, Stefan; Dragano, Nico; Schmermund, Axel; Stang, Andreas; Jöckel, Karl-Heinz; Erbel, Raimund

2014-06-01

Aortic valve calcification (AVC) is considered a manifestation of atherosclerosis. In this study, we investigated whether AVC adds to cardiovascular risk prediction beyond Framingham risk factors and coronary artery calcification (CAC). A total of 3944 subjects from the population based Heinz Nixdorf Recall Study (59.3±7.7 years; 53% females) were evaluated for coronary events, stroke, and cardiovascular disease (CVD) events (including all plus CV death) over 9.1±1.9 years. CT scans were performed to quantify AVC. Cox proportional hazards regressions and Harrell's C were used to examine AVC as event predictor in addition to risk factors and CAC. During follow-up, 138 (3.5%) subjects experienced coronary events, 101 (2.6%) had a stroke, and 257 (6.5%) experienced CVD events. In subjects with AVC>0 versus AVC=0 the incidence of coronary events was 8.0% versus 3.0% (p<0.001) and the incidence of CVD events was 13.0% versus 5.7% (p<0.001). The frequency of events increased significantly with increasing AVC scores (p<0.001). After adjustment for Framingham risk factors, high AVC scores (3rd tertile) remained independently associated with coronary events (HR 2.21, 95% CI 1.28 to 3.81) and CVD events (HR 1.67, 95% CI 1.08 to 2.58). After further adjustment for CAC score, HRs were attenuated (coronary events 1.55, 95% CI 0.89 to 2.69; CVD events 1.29, 95% CI 0.83 to 2.00). When adding AVC to the model containing traditional risk factors and CAC, Harrell's C indices did not increase for coronary events (from 0.744 to 0.744) or CVD events (from 0.759 to 0.759). AVC is associated with incident coronary and CVD events independent of Framingham risk factors. However, AVC fails to improve cardiovascular event prediction over Framingham risk factors and CAC. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Arterial wave reflection and aortic valve calcification in an elderly community-based cohort.

PubMed

Sera, Fusako; Russo, Cesare; Iwata, Shinichi; Jin, Zhezhen; Rundek, Tatjana; Elkind, Mitchell S V; Homma, Shunichi; Sacco, Ralph L; Di Tullio, Marco R

2015-04-01

Aortic valve calcification (AVC) without stenosis is common in the elderly, is associated with cardiovascular morbidity and mortality, and may progress to aortic valve stenosis. Arterial stiffness and pulse-wave reflection are important components of proximal aortic hemodynamics, but their relationship with AVC is not established. To investigate the relationship of arterial wave reflection and stiffness with AVC, pulse wave analysis and AVC evaluation by echocardiography were performed in 867 participants from the Cardiovascular Abnormalities and Brain Lesions study. Participants were divided into four categories on the basis of the severity and extent of AVC: (1) none or mild focal AVC, (2) mild diffuse AVC, (3) moderate to severe focal AVC, and (4) moderate to severe diffuse AVC. Central blood pressures and pulse pressure, total arterial compliance, augmentation index, and time to wave reflection were assessed using applanation tonometry. Indicators of arterial stiffness and wave reflection were significantly associated with AVC severity, except for central systolic and diastolic pressures and time to reflection. After adjustment for pertinent covariates (age, sex, race/ethnicity, and estimated glomerular filtration rate), only augmentation pressure (P = .02) and augmentation index (P = .002) were associated with the severity of AVC. Multivariate logistic regression analysis revealed that augmentation pressure (odds ratio per mm Hg, 1.14; 95% confidence interval, 1.02-1.27; P = .02) and augmentation index (odds ratio per percentage point, 1.07; 95% confidence interval, 1.01-1.13; P = .02) were associated with an increased risk for moderate to severe diffuse AVC, even when central blood pressure value was included in the same model. Arterial wave reflection is associated with AVC severity, independent of blood pressure values. Increased contribution of wave reflection to central blood pressure could be involved in the process leading to AVC. Copyright © 2015

Arterial Wave Reflection and Aortic Valve Calcification in an Elderly Community-Based Cohort

PubMed Central

Sera, Fusako; Russo, Cesare; Iwata, Shinichi; Jin, Zhezhen; Rundek, Tatjana; Elkind, Mitchell S.V.; Homma, Shunichi; Sacco, Ralph L.; Di Tullio, Marco R.

2015-01-01

Background Aortic valve calcification (AVC) without stenosis is common in the elderly, is associated with cardiovascular morbidity and mortality, and may progress to aortic valve stenosis. Arterial stiffness and pulse wave reflection are important components of proximal aortic hemodynamics, but their relationship with AVC is not established. Methods To investigate the relationship of arterial wave reflection and stiffness with AVC, pulse wave analysis and AVC evaluation by echocardiography were performed in 867 participants from the Cardiovascular Abnormalities and Brain Lesions (CABL) study. Participants were divided into 4 categories based on the severity and extent of AVC: 1) none or mild focal AVC; 2) mild diffuse AVC; 3) moderate-severe focal AVC; and 4) moderate-severe diffuse AVC. Central blood pressures and pulse pressure, total arterial compliance, augmentation index, and time to wave reflection were assessed using applanation tonometry. Results Indicators of arterial stiffness and wave reflection were significantly associated with AVC severity, except for central systolic and diastolic pressures and time to reflection. After adjustment for pertinent covariates (age, sex, race/ethnicity, and eGFR), only augmentation pressure (P = .02) and augmentation index (P = .002) were associated with the severity of AVC. Multivariable logistic regression analysis revealed that augmentation pressure (odds ratio per mmHg = 1.14; 95% confidence interval, 1.02–1.27; P = .02) and augmentation index (odds ratio per percentage point = 1.07; 95% confidence interval, 1.01–1.13; P = .02) were associated with an increase risk of moderate-severe diffuse AVC, even when central blood pressure value was included in the same model. Conclusions Arterial wave reflection is associated with AVC severity, independent of blood pressure values. Increased contribution of wave reflection to central blood pressure could be involved in the process leading to AVC. PMID:25600036

Transapical Mitral Valve Implantation for Native Mitral Valve Stenosis Using a Balloon-Expandable Prosthesis.

PubMed

Kiefer, Philipp; Noack, Thilo; Seeburger, Joerg; Hoyer, Alexandro; Linke, Axel; Mangner, Norman; Lehmkuhl, Lukas; Mohr, Friedrich Wilhelm; Holzhey, David

2017-12-01

Transcatheter mitral valve implantation (TMVI) is still in its infancy and is mainly limited to valve-in-valve or valve-in-ring implantations. We present the early experience with TMVI for severe calcified native MV stenosis. Between January 2014 and June 2015, 6 of 11 patients screened (mean age, 77.4 ± 6.3 years; 66% men) with severe native mitral valve (MV) stenosis (mean gradient [Pmean], 11.1 ± 2.1 mm Hg; mean effective orifice area [EOA], 0.9 ± 0.12 cm 2 ) underwent transcatheter MV replacement at our institution as a bailout procedure. Conventional surgical procedures were denied in all patients because of severe annular calcification and extensive comorbidities (mean logistic EuroScore, 31.4% ± 8.3%). The Edwards SAPIEN 3 (29 mm) (Edwards Lifesciences, Irvine, CA) was used in all cases. Procedural access was transapical in 5 cases and concomitant to aortic valve replacement through the left atrium through a sternotomy in 1 case. Initial implantation was successful in 100% of the cases. Because of early migration, 1 patient needed a valve-in-valve procedure. Postoperative echocardiography showed no residual mitral regurgitation in 4 cases (66%) and mild regurgitation in 2 cases (34%). Mean gradients were reduced to 4.2 ± 0.6 mm Hg (mean EOA, 2.8 ± 0.4 cm 2) . No patient had a stroke during hospitalization, and 30-day mortality was seen in 1 patient (17%) resulting from pneumonia. TMV implantation using the SAPIEN 3 aortic prosthesis in patients with heavy annular calcification is feasible and represents a reasonable bailout option for inoperable patients. However, several limitations need to be considered in this special patient population. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Active tissue stiffness modulation controls valve interstitial cell phenotype and osteogenic potential in 3D culture.

PubMed

Duan, Bin; Yin, Ziying; Hockaday Kang, Laura; Magin, Richard L; Butcher, Jonathan T

2016-05-01

Calcific aortic valve disease (CAVD) progression is a highly dynamic process whereby normally fibroblastic valve interstitial cells (VIC) undergo osteogenic differentiation, maladaptive extracellular matrix (ECM) composition, structural remodeling, and tissue matrix stiffening. However, how VIC with different phenotypes dynamically affect matrix properties and how the altered matrix further affects VIC phenotypes in response to physiological and pathological conditions have not yet been determined. In this study, we develop 3D hydrogels with tunable matrix stiffness to investigate the dynamic interplay between VIC phenotypes and matrix biomechanics. We find that VIC populated within hydrogels with valve leaflet like stiffness differentiate towards myofibroblasts in osteogenic media, but surprisingly undergo osteogenic differentiation when cultured within lower initial stiffness hydrogels. VIC differentiation progressively stiffens the hydrogel microenvironment, which further upregulates both early and late osteogenic markers. These findings identify a dynamic positive feedback loop that governs acceleration of VIC calcification. Temporal stiffening of pathologically lower stiffness matrix back to normal level, or blocking the mechanosensitive RhoA/ROCK signaling pathway, delays the osteogenic differentiation process. Therefore, direct ECM biomechanical modulation can affect VIC phenotypes towards and against osteogenic differentiation in 3D culture. These findings highlight the importance of the homeostatic maintenance of matrix stiffness to restrict pathological VIC differentiation. We implement 3D hydrogels with tunable matrix stiffness to investigate the dynamic interaction between valve interstitial cells (VIC, major cell population in heart valve) and matrix biomechanics. This work focuses on how human VIC responses to changing 3D culture environments. Our findings identify a dynamic positive feedback loop that governs acceleration of VIC calcification, which

Structural deterioration of the Freestyle aortic valve: mode of presentation and mechanisms.

PubMed

Mohammadi, Siamak; Baillot, Richard; Voisine, Pierre; Mathieu, Patrick; Dagenais, François

2006-08-01

Structural valve deterioration is the major cause of bioprosthetic valve failure. Because of the unique design features and anti-calcification treatment of the Freestyle (Medtronic Inc, Minneapolis, Minn) stentless bioprosthesis, development of structural valve deterioration may differ in comparison with other bioprosthetic valves. This study evaluates the mechanisms and clinical presentation of structural valve deterioration in the Freestyle stentless bioprosthesis. Between January 1993 and August 2005, 608 patients underwent aortic valve replacement with a Freestyle stentless bioprosthesis. The implantation technique was subcoronary in 475 patients and a root replacement in 133 patients. Mean overall follow-up was 5.6 +/- 3.4 years. Follow-up was complete in all patients. Clinical and echocardiographic follow-ups were conducted prospectively. Freedom from structural valve deterioration was 95.8% at 10 years. Twelve patients showed evidence of structural valve deterioration and underwent reoperation for aortic regurgitation (n = 10) or aortic stenosis (n = 2). The mean age of patients with structural valve deterioration was significantly lower than patients without structural valve deterioration (62.6 +/- 8.2 years vs 68.6 +/- 8.3 years, P = .02). The median time between implantation and explantation was 8.7 years (range: 1.9-13.3 years). Eleven structural valve deteriorations occurred after subcoronary implantation, and 1 structural valve deterioration occurred after root implantation (P = .4). The mechanisms of structural valve deterioration were leaflet tears in 10 patients (6 in the left coronary cusp and 4 in the right coronary cusp), severe valve calcification in 1 patient, and cusp fibrosis in 1 patient. The interval between onset of symptoms and reoperation was acute or subacute in 10 patients. At 10 years, the Freestyle stentless bioprosthesis shows excellent freedom from structural valve deterioration. Structural valve deterioration in the Freestyle

[Aortic valve calcification prevalence and association with coronary risk factors and atherosclerosis in Mexican population].

PubMed

Acuña-Valerio, Jorge; Rodas-Díaz, Marco A; Macias-Garrido, Enrico; Posadas-Sánchez, Rosalinda; Juárez-Rojas, Juan G; Medina-Urrutia, Aida X; Cardoso-Saldaña, Guillermo C; Joge-Galarza, Esteban; Torres-Tamayo, Margarita; Vargas-Alarcón, Gilberto; Posadas-Romero, Carlos

The prevalence of aortic valve calcification (AVC), strongly influenced by ethnicity, is unknown in Mexican population. The aim of this study was to investigate the prevalence of AVC and its associations with cardiovascular risk factors and coronary artery calcification (CAC), in Mexican subjects. In 1,267 subjects (53% women) without known coronary heart disease, aged 35 to 75 years, AVC and CAC were assessed by multidetector-computed tomography using the Agatston score. Cardiovascular risk factors were documented in all participants. The associations of AVC with CAC and risk factors were assessed by multivariable logistic regression analyses. The overall prevalence of AVC and CAC was 19.89% and 26.5%, respectively. AVC and CAC increased with age and were found more frequently in men (25.5% and 37.1%, respectively) than in women (14.9% and 13.0%, respectively). AVC was observed in only 8.5% of subjects without CAC, while those with CAC 1-99, 100-399, and >400 Agatston units had AVC prevalences of 36.8%, 56.8%, and 84.0%, respectively. The multivariable logistic regression analyses, adjusted for age, gender, obesity, physical inactivity, hypertension, dyslipidemia and high insulin levels, showed that the presence of CAC (OR [CI95%]: 3.23 [2.26-4.60]), obesity (1.94 [1.35-2.79]), male gender (1.44 [1.01-2.05]) and age (1.08 [1.03-1.10]), were significant independent predictors of AVC. Prevalence of AVC is high and significantly associated with atherosclerotic risk factors and CAC in this Mexican population. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

Association of aortic valve calcification to the presence, extent, and composition of coronary artery plaque burden: from the Rule Out Myocardial Infarction using Computer Assisted Tomography (ROMICAT) trial.

PubMed

Mahabadi, Amir A; Bamberg, Fabian; Toepker, Michael; Schlett, Christopher L; Rogers, Ian S; Nagurney, John T; Brady, Thomas J; Hoffmann, Udo; Truong, Quynh A

2009-10-01

Aortic valve calcification (AVC) is associated with cardiovascular risk factors and coronary artery calcification. We sought to determine whether AVC is associated with the presence and extent of overall plaque burden, as well as to plaque composition (calcified, mixed, and noncalcified). We examined 357 subjects (mean age 53 +/- 12 years, 61% male) who underwent contrast-enhanced electrocardiogram-gated 64-slice multidetector computed tomography from the ROMICAT trial for the assessment of presence and extent of coronary plaque burden according to the 17-coronary segment model and presence of AVC. Patients with AVC (n = 37, 10%) were more likely than those without AVC (n = 320, 90%) to have coexisting presence of any coronary plaque (89% vs 46%, P < .001) and had a greater extent of coronary plaque burden (6.4 vs 1.8 segments, P < .001). Those with AVC had >3-fold increase odds of having any plaque (adjusted odds ratio [OR] 3.6, P = .047) and an increase of 2.5 segments of plaque (P < .001) as compared to those without AVC. When stratified by plaque composition, AVC was associated most with calcified plaque (OR 5.2, P = .004), then mixed plaque (OR 3.2, P = .02), but not with noncalcified plaque (P = .96). Aortic valve calcification is associated with the presence and greater extent of coronary artery plaque burden and may be part of the later stages of the atherosclerosis process, as its relation is strongest with calcified plaque, less with mixed plaque, and nonsignificant with noncalcified plaque. If AVC is present, consideration for aggressive medical therapy may be warranted.

Taurine suppresses osteoblastic differentiation of aortic valve interstitial cells induced by beta-glycerophosphate disodium, dexamethasone and ascorbic acid via the ERK pathway.

PubMed

Feng, Xiang; Li, Jian-ming; Liao, Xiao-bo; Hu, Ye-rong; Shang, Bao-peng; Zhang, Zhi-yuan; Yuan, Ling-qing; Xie, Hui; Sheng, Zhi-feng; Tang, Hao; Zhang, Wei; Gu, Lu; Zhou, Xin-min

2012-10-01

Aortic valve calcification (AVC) is an active process characterized by osteoblastic differentiation of the aortic valve interstitial cells (AVICs). Taurine is a free β-amino acid and plays important physiological roles including protective effect of cardiovascular events. To evaluate the possible role of taurine in AVC, we isolated human AVICs from patients with type A dissection without leaflet disease. We demonstrated that the cultured AVICs express SM α-actin, vimentin and taurine transporter (TAUT), but not CD31, SM-myosin or desmin. We also established the osteoblastic differentiation model of the AVICs induced by pro-calcific medium (PCM) containing β-glycerophosphate disodium, dexamethasone and ascorbic acid in vitro. The results showed that taurine attenuated the PCM-induced osteoblastic differentiation of AVICs by decreasing the alkaline phosphate (ALP) activity/expression and the expression of the core binding factor α1 (Cbfα1) in a dose-dependent manner (reaching the maximum protective effect at 10 mM), and taurine (10 mM) inhibited the mineralization level of AVICs in the form of calcium content significantly. Furthermore, taurine activated the extracellular signal-regulated protein kinase (ERK) pathway via TAUT, and the inhibitor of ERK (PD98059) abolished the effect of taurine on both ALP activity/expression and Cbfα1 expression. These results suggested that taurine could inhibit osteoblastic differentiation of AVIC via the ERK pathway.

Transcatheter treatment of tricuspid regurgitation by caval valve implantation--experimental evaluation of decellularized tissue valves in central venous position.

PubMed

Lauten, Alexander; Laube, Adrian; Schubert, Harald; Bischoff, Sabine; Nietzsche, Sandor; Horstkötter, Kim; Poudel-Bochmann, Bhawana; Franz, Marcus; Lichtenberg, Artur; Figulla, Hans R; Akhyari, Payam

2015-01-01

Caval valve implantation has been suggested for transcatheter treatment of severe tricuspid regurgitation (TR). Combining the interventional technique with the promising surgical experience with decellularized valves, we sought to evaluate the functional and structural outcome of decellularized pericardial tissue valves (dTVs) in the low-pressure venous circulation in a chronic model of TR. Sixteen pericardial tissue valves were heterotopically implanted in the inferior and superior vena cava in a sheep model (54-98 kg; median 74.5 kg, n = 8) of severe TR. The devices were assembled using self-expanding nitinol stents and bovine pericardia decellularized by a detergent-based protocol (group dTV; n = 8). Glutaraldehyde-fixed pericardial tissue valves served as control (GaTV, n = 8). After 6 months, device function and structural maturation were analyzed using echocardiographic, histologic, immunohistologic, and electron microscopic approaches. After implantation, cardiac output increased significantly from 3.7 ± 1.1 l/min to 4.8 ± 1.1 l/min (P < 0.05) and competent valve function was verified by angiography. At 6 months, angiographic and echocardiographic evaluation revealed moderate to severe regurgitation in all GaTV. In contrast, five of the eight dTVs functioned well with only minor regurgitation. In these animals, autopsy revealed preserved valve structure with tender leaflets without signs of thrombosis or calcification. Conversely, GaTV showed severe degeneration with large calcification areas. Microscopic and histologic analysis confirmed endothelial repopulation in both valve types. However, additional interstitial reseeding was observed in decellularized valves. In the venous circulation in severe TR, decellularized valves show superior functional performance compared to Ga-fixed tissue valves. Macroscopic and microscopic analyses suggest preserved structural integrity and advanced endothelial and interstitial repopulation with

Effects of lectins on calcification by vesicles isolated from aortas of cholesterol-fed rabbits.

PubMed

Hsu, H H; Tawfik, O; Sun, F

2000-04-05

Advanced vascular calcification in atherosclerosis weakens arterial walls, thereby imposing a serious rupturing effect. However, the mechanism of dystrophic calcification remains unknown. Although accumulating morphological and biochemical evidence reveals a role for calcifiable vesicles in plaque calcification, the mechanism of vesicle-mediated calcification has not been fully explored. To study whether vesicles' membrane components, such as carbohydrates, may have a role in vesicle-mediated calcification, the effect of sugar-binding lectins on calcification was investigated. Atherosclerosis was developed by feeding rabbits with a diet supplemented with 0.5% cholesterol and 2% peanut oil for 4 months. Calcifiable vesicles were then isolated from thoracic aortas by collagenase digestion. The histological examination of aortas with hematoxylin counter-staining indicated abnormal formation of large plaques enriched with macrophage-derived foam cells. Fourier transform spectroscopy revealed mild calcification in aortas indicating that advanced stages of heavy calcification have yet to be reached. However, vesicles isolated from the aortas were capable of calcification in the presence of physiological levels of Ca(2+), Pi, and ATP. Thus, at this stage of atherosclerosis, aortas may start to produce calcifiable vesicles, but at a level insufficient for substantial formation of mineral in aortas. The assessments by FT-IR analysis and Alizarin red staining indicated that concanavalin A (Con A) substantially increased mineral formation by isolated vesicles. Con A also exerted a marked stimulatory effect on (45)Ca and (32)Pi deposition in a dose-dependent fashion with a half-maximal effect at 6-10 microg/ml. Either alpha-methylmannoside or alpha-methylglucoside, but not mannitol, at 10 mM abolished the stimulation. Con A stimulation was abolished after Con A was removed from calcifying media, suggesting that covalent binding may not be involved in the effect. Galactosides

C-reactive protein in degenerative aortic valve stenosis

PubMed Central

Sanchez, Pedro L; Mazzone, AnnaMaria

2006-01-01

Degenerative aortic valve stenosis includes a range of disorder severity from mild leaflet thickening without valve obstruction, "aortic sclerosis", to severe calcified aortic stenosis. It is a slowly progressive active process of valve modification similar to atherosclerosis for cardiovascular risk factors, lipoprotein deposition, chronic inflammation, and calcification. Systemic signs of inflammation, as wall and serum C-reactive protein, similar to those found in atherosclerosis, are present in patients with degenerative aortic valve stenosis and may be expression of a common disease, useful in monitoring of stenosis progression. PMID:16774687

Vascularization of bioprosthetic valve material

NASA Astrophysics Data System (ADS)

Boughner, Derek R.; Dunmore-Buyze, Joy; Heenatigala, Dino; Lohmann, Tara; Ellis, Chris G.

1999-04-01

Cell membrane remnants represent a probable nucleation site for calcium deposition in bioprosthetic heart valves. Calcification is a primary failure mode of both bovine pericardial and porcine aortic heterograft bioprosthesis but the nonuniform pattern of calcium distribution within the tissue remains unexplained. Searching for a likely cellular source, we considered the possibility of a previously overlooked small blood vessel network. Using a videomicroscopy technique, we examined 5 matched pairs of porcine aortic and pulmonary valves and 14 samples from 6 bovine pericardia. Tissue was placed on a Leitz Metallux microscope and transilluminated with a 75 watt mercury lamp. Video images were obtained using a silicon intensified target camera equipped with a 431 nm interference filter to maximize contrast of red cells trapped in a capillary microvasculature. Video images were recorded for analysis on a Silicon Graphics Image Analysis work station equipped with a video frame grabber. For porcine valves, the technique demonstrated a vascular bed in the central spongiosa at cusp bases with vessel sizes from 6-80 micrometers . Bovine pericardium differed with a more uniform distribution of 7-100 micrometers vessels residing centrally. Thus, small blood vessel endothelial cells provide a potential explanation patterns of bioprosthetic calcification.

Interleukin-37 suppresses the osteogenic responses of human aortic valve interstitial cells in vitro and alleviates valve lesions in mice.

PubMed

Zeng, Qingchun; Song, Rui; Fullerton, David A; Ao, Lihua; Zhai, Yufeng; Li, Suzhao; Ballak, Dov B; Cleveland, Joseph C; Reece, T Brett; McKinsey, Timothy A; Xu, Dingli; Dinarello, Charles A; Meng, Xianzhong

2017-02-14

Calcific aortic valve disease is a chronic inflammatory process, and aortic valve interstitial cells (AVICs) from diseased aortic valves express greater levels of osteogenic factors in response to proinflammatory stimulation. Here, we report that lower cellular levels of IL-37 in AVICs of diseased human aortic valves likely account for augmented expression of bone morphogenetic protein-2 (BMP-2) and alkaline phosphatase (ALP) following stimulation of Toll-like receptor (TLR) 2 or 4. Treatment of diseased AVICs with recombinant human IL-37 suppresses the levels of BMP-2 and ALP as well as calcium deposit formation. In mice, aortic valve thickening is observed when exposed to a TLR4 agonist or a high fat diet for a prolonged period; however, mice expressing human IL-37 exhibit significantly lower BMP-2 levels and less aortic valve thickening when subjected to the same regimens. A high fat diet in mice results in oxidized low-density lipoprotein (oxLDL) deposition in aortic valve leaflets. Moreover, the osteogenic responses in human AVICs induced by oxLDL are suppressed by recombinant IL-37. Mechanistically, reduced osteogenic responses to oxLDL in human AVICs are associated with the ability of IL-37 to inhibit NF-κB and ERK1/2. These findings suggest that augmented expression of osteogenic factors in AVICs of diseased aortic valves from humans is at least partly due to a relative IL-37 deficiency. Because recombinant IL-37 suppresses the osteogenic responses in human AVICs and alleviates aortic valve lesions in mice exposed to high fat diet or a proinflammatory stimulus, IL-37 has therapeutic potential for progressive calcific aortic valve disease.

Interleukin-37 suppresses the osteogenic responses of human aortic valve interstitial cells in vitro and alleviates valve lesions in mice

PubMed Central

Zeng, Qingchun; Song, Rui; Fullerton, David A.; Ao, Lihua; Zhai, Yufeng; Li, Suzhao; Ballak, Dov B.; Cleveland, Joseph C.; Reece, T. Brett; McKinsey, Timothy A.; Xu, Dingli; Dinarello, Charles A.; Meng, Xianzhong

2017-01-01

Calcific aortic valve disease is a chronic inflammatory process, and aortic valve interstitial cells (AVICs) from diseased aortic valves express greater levels of osteogenic factors in response to proinflammatory stimulation. Here, we report that lower cellular levels of IL-37 in AVICs of diseased human aortic valves likely account for augmented expression of bone morphogenetic protein-2 (BMP-2) and alkaline phosphatase (ALP) following stimulation of Toll-like receptor (TLR) 2 or 4. Treatment of diseased AVICs with recombinant human IL-37 suppresses the levels of BMP-2 and ALP as well as calcium deposit formation. In mice, aortic valve thickening is observed when exposed to a TLR4 agonist or a high fat diet for a prolonged period; however, mice expressing human IL-37 exhibit significantly lower BMP-2 levels and less aortic valve thickening when subjected to the same regimens. A high fat diet in mice results in oxidized low-density lipoprotein (oxLDL) deposition in aortic valve leaflets. Moreover, the osteogenic responses in human AVICs induced by oxLDL are suppressed by recombinant IL-37. Mechanistically, reduced osteogenic responses to oxLDL in human AVICs are associated with the ability of IL-37 to inhibit NF-κB and ERK1/2. These findings suggest that augmented expression of osteogenic factors in AVICs of diseased aortic valves from humans is at least partly due to a relative IL-37 deficiency. Because recombinant IL-37 suppresses the osteogenic responses in human AVICs and alleviates aortic valve lesions in mice exposed to high fat diet or a proinflammatory stimulus, IL-37 has therapeutic potential for progressive calcific aortic valve disease. PMID:28137840

The angiotensin II type 1 receptor blocker losartan attenuates bioprosthetic valve leaflet calcification in a rabbit intravascular implant model.

PubMed

Shin, Hong Ju; Kim, Dae-Hyun; Park, Han Ki; Park, Young Hwan

2016-12-01

There is evidence that angiotensin II type I receptor blocker (ARB) could reduce structural valve deterioration. However, the anticalcification effect on the bioprosthetic heart valve (BHV) has not been investigated. Thus, we investigated the effects of losartan (an ARB) on calcification of implanted bovine pericardial tissue in a rabbit intravascular implant model. A total of 16 male New Zealand White rabbits (20 weeks old, 2.98-3.34 kg) were used in this study. Commercially available BHV leaflet of bovine pericardium was trimmed to the shape of a 3-mm triangle and implanted to both external jugular veins of the rabbit. The ARB group (n = 8) was given 25 mg/kg of powdered losartan daily until 6 weeks after surgery by direct administration in the buccal pouch of the animals. The control group (n = 8) was given 5 ml of normal saline by the same method. After 6 weeks, quantitative calcium determination, histological evaluation and western blot analysis of interleukin-6 (IL-6), osteopontin and bone morphogenetic protein 2 (BMP-2) were performed to investigate the mechanisms of the anticalcification effect of losartan. No deaths or complications such as infection or haematoma were recorded during the experiment. All animals were euthanized on the planned date. The calcium measurement level in the ARB group (2.28 ± 0.65 mg/g) was significantly lower than that in the control group (3.68 ± 1.00 mg/g) (P = 0.0092). Immunohistochemistry analyses revealed that BMP-2-positive reactions were significantly attenuated in the ARB group. Western blot analysis showed that losartan suppressed the expression of IL-6, osteopontin and BMP-2. Our results indicate that losartan significantly attenuates postimplant degenerative calcification of a bovine pericardial bioprosthesis in a rabbit intravascular implant model. Further studies are required to assess the effects of ARBs on BHV tissue in orthotopic implantations using a large animal model. © The Author 2016. Published by Oxford

DNA methylation of a PLPP3 MIR transposon-based enhancer promotes an osteogenic program in calcific aortic valve disease.

PubMed

Mkannez, Ghada; Gagné-Ouellet, Valérie; Nsaibia, Mohamed Jalloul; Boulanger, Marie-Chloé; Rosa, Mickael; Argaud, Deborah; Hadji, Fayez; Gaudreault, Nathalie; Rhéaume, Gabrielle; Bouchard, Luigi; Bossé, Yohan; Mathieu, Patrick

2018-05-02

Calcific aortic valve disease (CAVD) is characterized by the osteogenic transition of valve interstitial cells (VICs). In CAVD, lysophosphatidic acid (LysoPA), a lipid mediator with potent osteogenic activity, is produced in the aortic valve (AV) and is degraded by membrane-associated phospholipid phosphatases (PLPPs). We thus hypothesized that a dysregulation of PLPPs could participate to the osteogenic reprograming of VICs during CAVD. The expression of PLPPs was examined in human control and mineralized AVs and comprehensive analyses were performed to document the gene regulation and impact of PLPPs on the osteogenic transition of VICs. We found that PLPP3 gene and enzymatic activity were downregulated in mineralized AVs. Multidimensional gene profiling in 21 human AVs showed that expression of PLPP3 was inversely correlated with the level of 5-methylcytosine (5meC) located in an intronic mammalian interspersed repeat element (MIR). Bisulfite pyrosequencing in a larger series of 67 AVs confirmed that 5meC in intron 1 was increased by 2.2-fold in CAVD compared to control AVs. In isolated cells, epigenome editing with CRISPR-Cas9 system containing a deficient Cas9 fused with DNA methyltransferase (dCas9-DNMT) was used to increase 5meC in the intronic enhancer and showed that it reduced significantly the expression of PLPP3. Knockdown experiments showed that lower expression of PLPP3 in VICs promotes an osteogenic program. DNA methylation of a MIR-based enhancer downregulates the expression of PLPP3 and promotes the mineralization of the AV.

Shear-Sensitive Genes in Aortic Valve Endothelium

PubMed Central

Fernández Esmerats, Joan; Heath, Jack

2016-01-01

Abstract Significance: Currently, calcific aortic valve disease (CAVD) is only treatable through surgical intervention because the specific mechanisms leading to the disease remain unclear. In this review, we explore the forces and structure of the valve, as well as the mechanosensors and downstream signaling in the valve endothelium known to contribute to inflammation and valve dysfunction. Recent Advances: While the valvular structure enables adaptation to dynamic hemodynamic forces, these are impaired during CAVD, resulting in pathological systemic changes. Mechanosensing mechanisms—proteins, sugars, and membrane structures—at the surface of the valve endothelial cell relay mechanical signals to the nucleus. As a result, a large number of mechanosensitive genes are transcribed to alter cellular phenotype and, ultimately, induce inflammation and CAVD. Transforming growth factor-β signaling and Wnt/β-catenin have been widely studied in this context. Importantly, NADPH oxidase and reactive oxygen species/reactive nitrogen species signaling has increasingly been recognized to play a key role in the cellular response to mechanical stimuli. In addition, a number of valvular microRNAs are mechanosensitive and may regulate the progression of CAVD. Critical Issues: While numerous pathways have been described in the pathology of CAVD, no treatment options are available to avoid surgery for advanced stenosis and calcification of the aortic valve. More work must be focused on this issue to lead to successful therapies for the disease. Future Directions: Ultimately, a more complete understanding of the mechanisms within the aortic valve endothelium will lead us to future therapies important for treatment of CAVD without the risks involved with valve replacement or repair. Antioxid. Redox Signal. 25, 401–414. PMID:26651130

Predictive Value of Aortic Valve Calcification for Periprocedural Myocardial Injury in Patients Undergoing Percutaneous Coronary Intervention.

PubMed

Shibata, Yohei; Ishii, Hideki; Suzuki, Susumu; Tanaka, Akihito; Tatami, Yosuke; Harata, Shingo; Ota, Tomoyuki; Shimbo, Yusaku; Takayama, Yohei; Kunimura, Ayako; Hirayama, Kenshi; Harada, Kazuhiro; Osugi, Naohiro; Murohara, Toyoaki

2017-05-01

Previous studies have shown that aortic valve calcification (AVC) was associated with cardiovascular events and mortality. On the other hand, periprocedural myocardial injury (PMI) in percutaneous coronary intervention (PCI) is a well-known predictor of subsequent mortality and poor clinical outcomes. The purpose of the study was to assess the hypothesis that the presence of AVC could predict PMI in PCI. This study included 370 patients treated with PCI for stable angina pectoris. AVC was defined as bright echoes ＞1 mm on one or more cusps of the aortic valve on ultrasound cardiography (UCG). PMI was defined as an increase in high-sensitivity troponin T level of ＞5 times the upper normal limit (＞0.070 ng/ml) at 24 hours after PCI. AVC was detected in 45.9% of the patients (n=170). The incidence of PMI was significantly higher in the patients with AVC than in those without AVC (43.5% vs 21.0%, p＜0.001). The presence of AVC independently predicted PMI after adjusting for other significant variables (odds ratio 2.26, 95% confidence interval 1.37-3.74, p=0.002). Other predictors were male sex, age, estimated glomerular filtration rate, and total stent length. Furthermore to predict PMI, adding AVC to the established risk factors significantly improved the area under the receiver operating characteristic curves, from 0.68 to 0.72, of the PMI prediction model (p=0.025). The presence of AVC detected in UCG could predict the incidence of PMI.

Predictive Value of Aortic Valve Calcification for Periprocedural Myocardial Injury in Patients Undergoing Percutaneous Coronary Intervention

PubMed Central

Shibata, Yohei; Suzuki, Susumu; Tanaka, Akihito; Tatami, Yosuke; Harata, Shingo; Ota, Tomoyuki; Shimbo, Yusaku; Takayama, Yohei; Kunimura, Ayako; Hirayama, Kenshi; Harada, Kazuhiro; Osugi, Naohiro; Murohara, Toyoaki

2017-01-01

Aims: Previous studies have shown that aortic valve calcification (AVC) was associated with cardiovascular events and mortality. On the other hand, periprocedural myocardial injury (PMI) in percutaneous coronary intervention (PCI) is a well-known predictor of subsequent mortality and poor clinical outcomes. The purpose of the study was to assess the hypothesis that the presence of AVC could predict PMI in PCI. Methods: This study included 370 patients treated with PCI for stable angina pectoris. AVC was defined as bright echoes > 1 mm on one or more cusps of the aortic valve on ultrasound cardiography (UCG). PMI was defined as an increase in high-sensitivity troponin T level of > 5 times the upper normal limit (> 0.070 ng/ml) at 24 hours after PCI. Results: AVC was detected in 45.9% of the patients (n = 170). The incidence of PMI was significantly higher in the patients with AVC than in those without AVC (43.5% vs 21.0%, p < 0.001). The presence of AVC independently predicted PMI after adjusting for other significant variables (odds ratio 2.26, 95% confidence interval 1.37–3.74, p = 0.002). Other predictors were male sex, age, estimated glomerular filtration rate, and total stent length. Furthermore to predict PMI, adding AVC to the established risk factors significantly improved the area under the receiver operating characteristic curves, from 0.68 to 0.72, of the PMI prediction model (p = 0.025). Conclusion: The presence of AVC detected in UCG could predict the incidence of PMI. PMID:27733732

[Pannus Formation Six-years after Aortic and Mitral Valve Replacement with Tissue Valves;Report of a Case].

PubMed

Nakamura, Makoto; Muraoka, Arata; Aizawa, Kei; Akutsu, Hirohiko; Kurumisawa, Soki; Misawa, Yoshio

2015-07-01

A 77-year-old man presented with exertional dyspnea. He had undergone aortic and mitral valve replacement with tissue valves 6-years earlier. The patient's hemoglobin level was 9.8 g/dl and serum aspartate aminotransferase (70 mU/ml) and lactate dehydrogenase (1,112 mU/ml) were elevated. Echocardiography revealed stenosis of the prosthetic valve in the aortic position with peak flow velocity of 3.8 m/second and massive mitral regurgitation. The patient underwent repeat valve replacement. Pannus formation around both implanted valves was observed. The aortic valve orifice was narrowed by the pannus, and one cusp of the prosthesis in the mitral position was fixed and caused the regurgitation, but they were free from cusp laceration or calcification. The patient's postoperative course was uneventful, and he continues to do well 14 months after surgery.

P650Influence of fetunin-a level on progression of calcific aortic valve stenosis The COFRASA - GENERAC Study.

PubMed

Kubota, N; David Messika-Zeitoun, Dmz

2016-12-01

In recent years, pathophysiology of aortic stenosis (AS) has been considered as a possibly active inflammatory process, but its determinants remain unclear. Calcium tissue deposition observed in dilaysis patients have been linked to low level of Fetuin-A, a powerful inhibitor of ectopic calcification. It is thus suspected to play a role in development of aortic stenosis. To assess correlation between Fetuin-A level and AS progression in a prospective cohort of AS patients, COFRASA (clinicalTrial.gov_number_NCT00338676) and GENERAC (clinicalTrial.gov_number_NCT00647088). A comprehensive clinical evaluation and Fetuin-A plasma level measurement was performed at baseline. AS severity was evaluated at baseline and yearly thereafter using echocardiography (mean pressure gradient (MPG)) and computed tomography (degree of aortic valve calcification or AVC). Annual progression was calculated as [(final measurement - baseline measurement)/follow-up duration] for both MPG and AVC measurements. We enrolled 296 patients with at least 1 year of follow-up. Mean age was 74±10 years, 217 (73%) were men. Mean Fetuin-A level was 0.55±0.15 g/L. After a mean follow-up of 3.0±1.7 years, no correlation was found between AS progression and Fetuin-A level, using either MPG (r=0.015, p=0.82) or AVC (r=0.014, p=0.82). This was also true when comparing patients with lower level of Fetuin-A (≤0.53 g/L, the median in our cohort) with patients with higher level(+3±5 mmHg/year (median 2, [0-5] vs +4±4 mmHg/year (median 2, [1-6]) p=0.06, and +205±290 AUC/year (median 122, [32-269]) vs +240±310 AUC/year (median 145, [50-313], p=0.24). This was true also after adjustment for baseline severity and valve antomy. In our prospective cohortot of AS patients we found no impact of Fetuin-A on both hemodynamic and anatomic AS progression. Despite strong capacity to inhibit ectopic calcium deposition, Fetuin-A plasma level seems to have minor influence on AS progression. Published on behalf of the

Nano-analytical electron microscopy reveals fundamental insights into human cardiovascular tissue calcification

NASA Astrophysics Data System (ADS)

Bertazzo, Sergio; Gentleman, Eileen; Cloyd, Kristy L.; Chester, Adrian H.; Yacoub, Magdi H.; Stevens, Molly M.

2013-06-01

The accumulation of calcified material in cardiovascular tissue is thought to involve cytochemical, extracellular matrix and systemic signals; however, its precise composition and nanoscale architecture remain largely unexplored. Using nano-analytical electron microscopy techniques, we examined valves, aortae and coronary arteries from patients with and without calcific cardiovascular disease and detected spherical calcium phosphate particles, regardless of the presence of calcific lesions. We also examined lesions after sectioning with a focused ion beam and found that the spherical particles are composed of highly crystalline hydroxyapatite that crystallographically and structurally differs from bone mineral. Taken together, these data suggest that mineralized spherical particles may play a fundamental role in calcific lesion formation. Their ubiquitous presence in varied cardiovascular tissues and from patients with a spectrum of diseases further suggests that lesion formation may follow a common process. Indeed, applying materials science techniques to ectopic and orthotopic calcification has great potential to lend critical insights into pathophysiological processes underlying calcific cardiovascular disease.

Heart valve bioprosthesis durability: a challenge to the new generation of porcine valves.

PubMed

Valente, M; Minarini, M; Maizza, A F; Bortolotti, U; Thiene, G

1992-01-01

Long-term experience with first generation porcine valve xenografts enabled identification of the major limitations to their durability: (1) prosthetic-ventricular mismatch due to the high profile of the stent in patients with mitral stenosis and a small left ventricle; (2) high-pressure fixation with loss of natural collagen crimping in the fibrosa, and wash-out of proteoglycans in the spongiosa; (3) xenograft tissue autolysis, due to the long interval between animal slaughter and aortic valve removal fixation; (4) muscle shelf in the right coronary cusp, which created a gradient and could undergo accelerated calcification and/or spontaneous perforation with time; (5) a flexible polypropylene stent, which could creep or even fracture with consequent inward bending of the stent; (6) progressive time-related dystrophic calcification; (7) host fibrous tissue ingrowth. An awareness of these limitations stimulated technical modifications, which frequently brought about distinct improvements: (1) the reduction of the stent profile eliminated the problem of mismatch, but resulted in a higher tendency towards cusp prolapse and earlier commissural tearing; (2) natural collagen waviness, proteoglycans and cusp extensibility were preserved by employing low or even zero pressure during the fixation process; (3) earlier valve fixation enabled preservation of cell integrity; (4) a new orifice for small valves was designed by replacing the right muscular cusp, thus achieving less gradient and avoiding muscle-shelf-related complications; (5) polypropylene was replaced by Delrin as stent material; (6) calcium-retarding agents like T6 and toluidine blue were applied during commercial processing and storage in order to mitigate tissue mineralization.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlation of two-dimensional echocardiography and pathologic findings in porcine valve dysfunction.

PubMed

Forman, M B; Phelan, B K; Robertson, R M; Virmani, R

1985-02-01

Two-dimensional echocardiographic findings in porcine valve dysfunction were compared with pathologic findings in 10 patients (12 valves). Three specific echocardiographic findings were identified in patients with regurgitant lesions: prolapse, fracture and flail leaflets. Prolapse was associated pathologically with thinning of the leaflets, longitudinal tears close to the ring margin and acid mucopolysaccharide accumulation. Valve fracture was seen with and without prolapse and was accompanied pathologically by small pinpoint perforations or tears of the leaflet. A flail leaflet was seen with a linear tear of the free margin and was associated with calcific deposits. Mild degrees of fracture seen pathologically were missed on the echocardiographic study in five patients. Thickening or calcification, when present in moderate or severe amounts, was correctly identified by echocardiography. When all abnormal features were considered collectively, two-dimensional echocardiography correctly identified at least one of them in all patients. Therefore, two-dimensional echocardiography may prove useful in assessing the source of valvular regurgitation in patients with bioprosthetic valves.

Protective effects of estrogen against vascular calcification via estrogen receptor α-dependent growth arrest-specific gene 6 transactivation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nanao-Hamai, Michiko; Son, Bo-Kyung; Institute of Gerontology, The University of Tokyo, Tokyo

Vascular calcification is one of the major complications of cardiovascular disease and is an independent risk factor for myocardial infarction and cardiac death. Postmenopausal women have a higher prevalence of vascular calcification compared with premenopausal women, suggesting protective effects of estrogen (E2). However, the underlying mechanisms of its beneficial effects remain unclear. In the present study, we examined the inhibitory effects of E2 on vascular smooth muscle cell (VSMC) calcification, and found that growth arrest-specific gene 6 (Gas6), a crucial molecule in vascular calcification, is transactivated by estrogen receptor α (ERα) in response to E2. In human aortic smooth musclemore » cells, physiological levels of E2 inhibited inorganic phosphate (Pi)-induced calcification in a concentration-dependent manner. This inhibitory effect was significantly abolished by MPP, an ERα-selective antagonist, and ERα siRNA, but not by PHTPP, an ERβ-selective antagonist, and ERβ siRNA, implicating an ERα-dependent action. Apoptosis, an essential process for Pi-induced VSMC calcification, was inhibited by E2 in a concentration-dependent manner and further, MPP abolished this inhibition. Mechanistically, E2 restored the inhibited expression of Gas6 and phospho-Akt in Pi-induced apoptosis through ERα. Furthermore, E2 significantly activated Gas6 transcription, and MPP abrogated this E2-dependent Gas6 transactivation. E2-BSA failed to activate Gas6 transcription and to inhibit Ca deposition in VSMC, suggesting beneficial actions of genomic signaling by E2/nuclear ERα. Taken together, these results indicate that E2 exerts inhibitory effects on VSMC apoptosis and calcification through ERα-mediated Gas6 transactivation. These findings indicate a potential therapeutic strategy for the prevention of vascular calcification, especially in postmenopausal women. - Highlights: • E2 inhibits Pi-induced calcification in vascular smooth muscles cells. • E2

Using Na3PO4 to Enhance In vitro Animal Models of Aortic Valve Calcification.

PubMed

Lerman, Daniel Alejandro; Prasad, Sai; Alotti, Nasri

2016-01-07

The pathogenesis of calcific aortic valvular disease (CAVD) involves an active inflammatory process of valvular interstitial cells (VICs) characterized by the activation of specific osteogenic signaling pathways and apoptosis. This process can be studied by analyzing certain molecular markers and gene expression pathways of spontaneous calcification. The purpose of our study is to investigate the role of sodium phosphate (Na3PO4) as a calcification promoter, with the aim of improving in vitro animal models for testing potential calcification inhibitors. VICs were extracted from 6 healthy 6-month-old fresh porcine hearts by serial collagenase digestion. Quantitative polymerase chain reaction (qPCR) was used to quantify trans-differentiation of genes of interest during spontaneous calcification of VICs. Spontaneous calcification of VICs was increased by adding Na 3 PO 4 (3 mM, pH 7.4). The degree of calcification was estimated by Alizarin Red staining for calcium deposition, and Sirius Red staining for collagen. Colorimetric techniques were used to determine calcium and collagen deposition quantitatively. Additionally, the enzymatic activity of alkaline phosphatase (ALP) was measured by a kinetic assay. For statistical analysis we used SPSS and Microsoft Office Excel 2013. Porcine VICs calcify spontaneously with demonstrable calcium and collagen deposition. In this study we observed an increase of calcium and collagen deposition from day 0 to day 14 (calcium: 376%; P<0.001, collagen: 3553%; P<0.001). qPCR analysis of mRNA by day 14 showed the following results: α-actin, a marker of myoblast phenotype, was increased to 1.6-fold; P<0.001. Runx2, an osteoblast marker, rose to 1.3 fold; P<0.05, TGF-β, a promoter of osteogenesis, increased to 3.2-fold; P<0.001, and RhoA, a regulator of nodular formation in myoblasts, increased to 4.5-fold; P<0.001, compared to their levels at day 0. RANKL mRNA and calponin did not change significantly. Treatment of porcine VICs with Na3

Smad2-dependent glycosaminoglycan elongation in aortic valve interstitial cells enhances binding of LDL to proteoglycans.

PubMed

Osman, Narin; Grande-Allen, K Jane; Ballinger, Mandy L; Getachew, Robel; Marasco, Silvana; O'Brien, Kevin D; Little, Peter J

2013-01-01

Calcific aortic valve disease is a progressive condition that shares some common pathogenic features with atherosclerosis. Transforming growth factor-β1 is a recognized mediator of atherosclerosis and is expressed in aortic valve lesions. Transforming growth factorβ1 stimulates glycosaminoglycan elongation of proteoglycans that is associated with increased lipid binding. We investigated the presence of transforming growth factor-β1 and downstream signaling intermediates in diseased human aortic valves and the effects of activated transforming growth factor-β1 receptor signaling on aortic valve interstitial cell proteoglycan synthesis and lipid binding as a possible mechanism for the initiation of the early lesion of calcific aortic valve disease. Diseased human aortic valve leaflets demonstrated strong immunohistochemical staining for transforming growth factor-β1 and phosphorylated Smad2/3. In primary porcine aortic valve interstitial cells, Western blots showed that transforming growth factor-β1 stimulated phosphorylation in both the carboxy and linker regions of Smad2/3, which was inhibited by the transforming growth factor-β1 receptor inhibitor SB431542. Gel electrophoresis and size exclusion chromatography demonstrated that SB431542 decreased transforming growth factor-β1-mediated [(35)S]-sulfate incorporation into proteoglycans in a dose-dependent manner. Further, in proteoglycans derived from transforming growth factor-β1-treated valve interstitial cells, gel mobility shift assays demonstrated that inhibition of transforming growth factor-β1 receptor signaling resulted in decreased lipid binding. Classic transforming growth factor-β1 signaling is present in human aortic valves in vivo and contributes to the modification of proteoglycans expressed by valve interstitial cells in vitro. These findings suggest that transforming growth factor-β1 may promote increased low-density lipoprotein binding in the early phases of calcific aortic valve disease

Chlamydia pneumoniae antibody titers and cardiac calcifications: a cross-sectional serological-echocardiographic correlative study.

PubMed

Atar, Shaul; Tolstrup, Kirsten; Cercek, Bojan; Siegel, Robert J

2007-07-01

Chlamydia pneumoniae has previously been associated with higher prevalence of valvular and cardiac calcifications. To investigate a possible association of seropositivity for C. pneumoniae and the presence of cardiac calcifications (mitral annular or aortic root calcification, and aortic valve sclerosis). We retrospectively analyzed serological data (immunoglobulin G TWAR antibodies) from the AZACS trial (Azithromycin in Acute Coronary Syndromes), and correlated the serological findings according to titer levels with the presence of cardiac calcifications as detected by transthoracic echocardiography. In 271 patients, age 69 +/- 13 years, who underwent both serological and echocardiographic evaluation, we found no significant association between the "calcification sum score" (on a scale of 0-3) in seropositive compared to seronegative patients (1.56 +/- 1.15 vs.1.35 +/- 1.15, respectively, P = 0.26). The median calcification sum score was 1 (interquartile range 0-3) for the seronegative group, and 2 (interquartile range 0-3) for the seropositive group (P = 0.2757). In addition, we did not find a significant correlation of any of the individual sites of cardiac calcification and C. pneumoniae seropositivity. Our findings suggest that past C. pneumoniae infection may not be associated with the pathogenesis of valvular and cardiac calcifications.

Early development of calcific aortic valve disease and left ventricular hypertrophy in a mouse model of combined dyslipidemia and type 2 diabetes mellitus.

PubMed

Le Quang, Khai; Bouchareb, Rihab; Lachance, Dominic; Laplante, Marc-André; El Husseini, Diala; Boulanger, Marie-Chloé; Fournier, Dominique; Fang, Xiang Ping; Avramoglu, Rita Kohen; Pibarot, Philippe; Deshaies, Yves; Sweeney, Gary; Mathieu, Patrick; Marette, André

2014-10-01

This study aimed to determine the potential impact of type 2 diabetes mellitus on left ventricular dysfunction and the development of calcified aortic valve disease using a dyslipidemic mouse model prone to developing type 2 diabetes mellitus. When compared with nondiabetic LDLr(-/-)/ApoB(100/100), diabetic LDLr(-/-)/ApoB(100/100)/IGF-II mice exhibited similar dyslipidemia and obesity but developed type 2 diabetes mellitus when fed a high-fat/sucrose/cholesterol diet for 6 months. LDLr(-/-)/ApoB(100/100)/IGF-II mice showed left ventricular hypertrophy versus C57BL6 but not LDLr(-/-)/ApoB(100/100) mice. Transthoracic echocardiography revealed significant reductions in both left ventricular systolic fractional shortening and diastolic function in high-fat/sucrose/cholesterol fed LDLr(-/-)/ApoB(100/100)/IGF-II mice when compared with LDLr(-/-)/ApoB(100/100). Importantly, we found that peak aortic jet velocity was significantly increased in LDLr(-/-)/ApoB(100/100)/IGF-II mice versus LDLr(-/-)/ApoB(100/100) animals on the high-fat/sucrose/cholesterol diet. Microtomography scans and Alizarin red staining indicated calcification in the aortic valves, whereas electron microscopy and energy dispersive x-ray spectroscopy further revealed mineralization of the aortic leaflets and the presence of inflammatory infiltrates in diabetic mice. Studies showed upregulation of hypertrophic genes (anp, bnp, b-mhc) in myocardial tissues and of osteogenic genes (spp1, bglap, runx2) in aortic tissues of diabetic mice. We have established the diabetes mellitus -prone LDLr(-/-)/ApoB(100/100)/IGF-II mouse as a new model of calcified aortic valve disease. Our results are consistent with the growing body of clinical evidence that the dysmetabolic state of type 2 diabetes mellitus contributes to early mineralization of the aortic valve and calcified aortic valve disease pathogenesis. © 2014 American Heart Association, Inc.

Relationship between aortic valve calcification and the severity of coronary atherosclerotic disease.

PubMed

Qian, Juying; Chen, Zhangwei; Ge, Junbo; Ma, Jianying; Chang, Shufu; Fan, Bing; Liu, Xuebo; Ge, Lei

2010-07-01

Aortic valve calcification (AVC), which has been confirmed to be associated with various risk factors of cardiac disease, is common in the elderly and associated with increased cardiovascular mortality. It has been hypothesized that AVC is associated with coronary atherosclerotic disease, and its severity. Between July 2007 and November 2007, a total of 235 patients with chest pain or chest distress were admitted to the authors' institution for coronary angiography. The severity of coronary atherosclerotic disease (CAD) was evaluated by the Gensini score, the number of stenosed vessels, and the prevalence of total occlusion. All patients underwent transthoracic echocardiography to detect AVC. Patients with CAD had a higher prevalence of AVC than those without CAD (44% versus 26%, p = 0.005). Likewise, the prevalence of AVC was significantly higher in patients with a higher Gensini score than in those with a lower score. Patients with AVC had a higher prevalence of CAD, and higher Gensini scores and numbers of stenosed coronary arteries, even after stratification by age (65 years). On multivariable logistic regression analysis for CAD, the odds ratio (OR) of AVC was 2.315 (95% confidence interval (CI): 1.158-4.629, p = 0.018); this value was higher than that for total cholesterol (OR = 1.637, p = 0.008), lipoprotein-a (OR = 1.003, p = 0.015) and fibrinogen (OR = 1.009, p = 0.006), and marginally less than that for male gender (OR = 2.665, p = 0.005). Patients with AVC had a higher prevalence and greater severity of CAD.

Calcification resistance for photooxidatively crosslinked acellular bovine jugular vein conduits in right-side heart implantation.

PubMed

Lü, Wei-Dong; Wang, An-Ping; Wu, Zhong-Shi; Zhang, Ming; Hu, Tie-Hui; Lei, Guang-Yan; Hu, Ye-Rong

2012-10-01

This study aimed to investigate the effect of decellularization plus photooxidative crosslinking and ethanol pretreatment on bioprosthetic tissue calcification. Photooxidatively crosslinked acellular (PCA) bovine jugular vein conduits (BJVCs) and their photooxidized controls (n = 5 each) were sterilized in a graded concentration of ethanol solutions for 4 h, and used to reconstruct dog right ventricular outflow tracts. At 1-year implantation, echocardiography showed similar hemodynamic performance, but obvious calcification for the photooxidized BJVC walls. Further histological examination showed intense calcium deposition colocalized with slightly degraded elastic fibers in the photooxidized BJVC walls, with sparsely distributed punctate calcification in the valves and other areas of walls. But PCA BJVCs had apparent degradation of elastic fibers in the walls, with only sparsely distributed punctate calcification in the walls and valves. Content assay demonstrated comparable calcium content for the two groups at preimplantation, whereas less calcium for the PCA group in the walls and similar calcium in the valvular leaflets compared with the photooxidized group at 1-year retrieval. Elastin content assay presented the conduit walls of PCA group had less elastin content at preimplantation, but similar content at 1-year retrieval compared with the photooxidized group. Phospholipid analysis showed phospholipid extraction by ethanol for the PCA group was more efficacious than the photooxidized group. These results indicate that PCA BJVCs resist calcification in right-side heart implantation owing to decellularization, further photooxidative crosslinking, and subsequent phospholipid extraction by ethanol at preimplantation. Copyright © 2012 Wiley Periodicals, Inc.

Association of inflammatory, lipid and mineral markers with cardiac calcification in older adults.

PubMed

Bortnick, Anna E; Bartz, Traci M; Ix, Joachim H; Chonchol, Michel; Reiner, Alexander; Cushman, Mary; Owens, David; Barasch, Eddy; Siscovick, David S; Gottdiener, John S; Kizer, Jorge R

2016-07-13

Calcification of the aortic valve and adjacent structures involves inflammatory, lipid and mineral metabolism pathways. We hypothesised that circulating biomarkers reflecting these pathways are associated with cardiac calcification in older adults. We investigated the associations of various biomarkers with valvular and annular calcification in the Cardiovascular Health Study. Of the 5888 participants, up to 3585 were eligible after exclusions for missing biomarker, covariate or echocardiographic data. We evaluated analytes reflecting lipid (lipoprotein (Lp) (a), Lp-associated phospholipase A 2 (LpPLA 2 ) mass and activity), inflammatory (interleukin-6, soluble (s) CD14) and mineral metabolism (fetuin-A, fibroblast growth factor (FGF)-23) pathways that were measured within 5 years of echocardiography. The relationships of plasma biomarkers with aortic valve calcification (AVC), aortic annular calcification (AAC) and mitral annular calcification (MAC) were assessed with relative risk (RR) regression. Calcification was prevalent: AVC 59%, AAC 45% and MAC 41%. After adjustment, Lp(a), LpPLA 2 mass and activity and sCD14 were positively associated with AVC. RRs for AVC per SD (95% CI) were as follows: Lp(a), 1.051 (1.022 to 1.081); LpPLA 2 mass, 1.036 (1.006 to 1.066) and LpPLA 2 activity, 1.037 (1.004 to 1.071); sCD14, 1.039 (1.005 to 1.073). FGF-23 was positively associated with MAC, 1.040 (1.004 to 1.078) and fetuin-A was negatively associated, 0.949 (0.911 to 0.989). No biomarkers were significantly associated with AAC. This study shows novel associations of circulating FGF-23 and fetuin-A with MAC, and LpPLA 2 and sCD14 with AVC, confirming that previously reported for Lp(a). Further investigation of Lp and inflammatory pathways may provide added insight into the aetiology of AVC, while study of phosphate regulation may illuminate the pathogenesis of MAC. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a

Aortic annulus and root characteristics in severe aortic stenosis due to bicuspid aortic valve and tricuspid aortic valves: implications for transcatheter aortic valve therapies.

PubMed

Philip, Femi; Faza, Nadine Nadar; Schoenhagen, Paul; Desai, Milind Y; Tuzcu, E Murat; Svensson, Lars G; Kapadia, Samir R

2015-08-01

Patients with severe aortic stenosis due to BAV are excluded from transcatheter aortic valve replacement (TAVR) due to concern for asymmetric expansion and valve dysfunction. We sought to characterize the aortic root and annulus in bicuspid aortic valve (BAV) and tricuspid aortic valves (TAV). We identified patients with severe AS who underwent multi-detector computed tomographic (MDCT) imaging prior to surgical aortic valve replacement (SAVR, n = 200) for BAV and TAVR (n = 200) for TAV from 2010 to 2013. The presence of a BAV was confirmed on surgical and pathological review. Annulus measurements of the basal ring (short- and long-axis, area-derived diameter), coronary ostia height, sinus area (SA), sino-tubular junction area (STJ), calcification and eccentricity index (EI, 1-short axis/long axis) were made. Patients with TAV were older (78.8 years vs. 57.8 years, P = 0.04) than those with BAV. The aortic annulus area (5.21 ± 2.1 cm(2) vs. 4.63 ± 2.0 cm(2) , P = 0.0001), sinus of Valsalva diameter (3.7 ± 0.9 cm vs. 3.1 ± 0.1 cm, P = 0.001) and ascending aorta diameter (3.5 ± 0.7 cm vs. 2.97 ± 0.6 cm, P = 0.001) were significantly larger with BAV. Bicuspid aortic annuli were significantly less elliptical (EI, 1.24 ± 0.1 vs. 1.29 ± 0.1, P = 0.006) and more circular (39% vs. 4%, P < 0.001) compared to the TAV annulus. There was more eccentric annular calcification in BAV vs. TAV (68% vs. 32%, P < 0.001). The mean distance from the aortic annulus to the left main coronary ostium was less than the right coronary ostium. Less than 10% of the BAV annuli would not fit a currently available valved stents. Bicuspid aortic valves have a larger annulus size, sinus of Valsalva and ascending aorta dimensions. In addition, the BAV aortic annuli appear circular and most will fit currently available commercial valved stents. © 2015 Wiley Periodicals, Inc.

Exposure to ambient air pollution and calcification of the mitral annulus and aortic valve: the multi-ethnic study of atherosclerosis (MESA).

PubMed

Tibuakuu, Martin; Jones, Miranda R; Navas-Acien, Ana; Zhao, Di; Guallar, Eliseo; Gassett, Amanda J; Sheppard, Lianne; Budoff, Matthew J; Kaufman, Joel D; Michos, Erin D

2017-12-21

Long-term exposure to high ambient air pollution has been associated with coronary artery calcium (CAC), a marker of cardiovascular disease (CVD). Calcifications of left-sided heart valves are also markers of CVD risk. We investigated whether air pollution was associated with valvular calcification and its progression. We studied 6253 MESA participants aged 45-84 years who underwent two cardiac CT scans 2.5 years apart to quantify aortic valve calcium (AVC) and mitral annular calcium (MAC). CAC was included for the same timeframe for comparison with AVC/MAC. Ambient particulate matter <2.5 μm (PM 2.5 ) and oxides of nitrogen (NO x ) concentrations were predicted from residence-specific spatio-temporal models. The mean age (SD) of the study sample was 62 (10) years, 39% were white, 27% black, 22% Hispanic, and 12% Chinese. The prevalence of AVC and MAC at baseline were 13% and 9% respectively, compared to 50% prevalence of CAC. The adjusted prevalence ratios of AVC and MAC for each 5 μg/m 3 higher PM 2.5 was 1.19 (95% CI 0.87, 1.62) and 1.20 (0.81, 1.77) respectively, and for CAC was 1.14 (1.01, 1.27). Over 2.5 years, the mean change in Agatston units/year for each 5 μg/m 3 higher PM 2.5 concentration was 0.29 (-5.05, 5.63) for AVC and 4.38 (-9.13, 17.88) for MAC, compared to 8.66 (0.61, 16.71) for CAC. We found no significant associations of NOx with AVC and MAC. Our findings suggest a trend towards increased 2.5-year progression of MAC with exposure to outdoor PM 2.5 , although this association could not be confirmed. Additional well-powered studies with longer periods of follow-up are needed to further study associations of air pollution with valvular calcium. Although MESA is not a clinical trial, this cohort is registered at ClinicalTrials.gov Identifier: NCT00005487; Date of registration May 25, 2000.

Elastin Calcification and its Prevention with Aluminum Chloride Pretreatment

PubMed Central

Vyavahare, Narendra; Ogle, Matthew; Schoen, Frederick J.; Levy, Robert J.

1999-01-01

Elastin, an abundant structural protein present in the arterial wall, is prone to calcification in a number of disease processes including porcine bioprosthetic heart valve calcification and atherosclerosis. The mechanisms of elastin calcification are not completely elucidated. In the present work, we demonstrated calcification of purified elastin in rat subdermal implants (Ca2+ = 89.73 ± 9.84 μg/mg after 21 days versus control, unimplanted Ca2+ = 0.16 ± 0.04 μg/mg). X-ray diffraction analysis along with resolution enhanced FTIR spectroscopy demonstrated the mineral phase to be a poorly crystalline hydroxyapatite. We investigated the time course of calcification, the effect of glutaraldehyde crosslinking on calcification, and mechanisms of inhibition of elastin calcification by pretreatment with aluminum chloride (AlCl3). Glutaraldehyde pretreatment did not affect calcification (Ca2+ = 89.06 ± 17.93 μg/mg for glutaraldehyde crosslinked elastin versus Ca2+ = 89.73 ± 9.84 μg/mg for uncrosslinked elastin). This may be explained by radioactive (3H) glutaraldehyde studies showing very low reactivity between glutaraldehyde and elastin. Our results further demonstrated that AlCl3 pretreatment of elastin led to complete inhibition of elastin calcification using 21-day rat subdermal implants, irrespective of glutaraldehyde crosslinking (Ca2+ = 0.73–2.15 μg/mg for AlCl3 pretreated elastin versus 89.73 ± 9.84 for untreated elastin). The AlCl3 pretreatment caused irreversible binding of aluminum ions to elastin, as assessed by atomic emission spectroscopy. Moreover, aluminum ion binding altered the spatial configuration of elastin as shown by circular dichroism (CD), Fourier transform infrared (FTIR), and 13C nuclear magnetic resonance (NMR) spectroscopy studies, suggesting a net structural change including a reduction in the extent of β sheet structures and an increase in coil-turn conformations. Thus, it is concluded that purified elastin calcifies in rat

[Pannus Formation Two Years after Bioprosthetic Aortic Valve Implantation;Report of a Case].

PubMed

Ono, Kimiyo; Kuroda, Hiroaki

2015-08-01

We report a case of early deterioration of the bioprosthetic aortic valve 23 months postoperatively. A 77-year-old man who had undergone aortic valve replacement with a 23-mm Epic valve( St. Jude Medical [SJM])presented to us after a syncopal episode. Echocardiography revealed severe aortic stenosis, and redo aortic valve replacement with a 21-mm SJM mechanical valve was performed. All 3 cusps of the tissue valve were thickened by fibrous pannus overgrowth. Neither calcification nor invasion of inflammatory cells was observed. The cause of pannus formation at such an early stage after implantation remains unknown.

The Ross operation: the autologous pulmonary valve in the aortic position.

PubMed

Gonzalez-Lavin, L; Robles, A; Graf, D

1988-03-01

Aortic valve replacement (AVR) with a pulmonary valve autograft (PVA) was first reported by Donald N. Ross (DNR) in 1967. The expectation of this procedure was to avoid degenerative changes seen in other biological tissue valves such as calcification, attenuation, and rupture of the leaflets. Recent reports by the original investigator's group have confirmed the lack of degenerative changes in PVA. To corroborate their conclusions, the fate of 12 patients undergoing AVR with PVA by one of us (LGL) has been ascertained. From March 1969 to June 1971, 12 patients underwent AVR with PVA. The right ventricular outflow tract (RVOT) was reconstructed with an aortic homograft valved conduit. The mean age was 42.7 years (range 21 to 52 years). The mean follow-up for 11 hospital survivors is 12.4 years. Three PVA have been replaced; one following infective endocarditis at 13 years, and two at 15 and 73 months due to technical malalignment. There was no evidence of PVA degeneration during histological examination of these explanted PVAs. Six patients are alive and retain the original PVA at 12 years (55%). This analysis corroborates the conclusions of the DNR report and strongly suggests an immunological mechanism in the process of calcification of other biological tissue valves. The Ross operation is advocated for AVR in young patients as valve durability is of paramount importance especially in this group.

Metal Ion-Loaded Nanofibre Matrices for Calcification Inhibition in Polyurethane Implants

PubMed Central

Singh, Charanpreet; Wang, Xungai

2017-01-01

Pathologic calcification leads to structural deterioration of implant materials via stiffening, stress cracking, and other structural disintegration mechanisms, and the effect can be critical for implants intended for long-term or permanent implantation. This study demonstrates the potential of using specific metal ions (MI)s for inhibiting pathological calcification in polyurethane (PU) implants. The hypothesis of using MIs as anti-calcification agents was based on the natural calcium-antagonist role of Mg2+ ions in human body, and the anti-calcification effect of Fe3+ ions in bio-prosthetic heart valves has previously been confirmed. In vitro calcification results indicated that a protective covering mesh of MI-doped PU can prevent calcification by preventing hydroxyapatite crystal growth. However, microstructure and mechanical characterisation revealed oxidative degradation effects from Fe3+ ions on the mechanical properties of the PU matrix. Therefore, from both a mechanical and anti-calcification effects point of view, Mg2+ ions are more promising candidates than Fe3+ ions. The in vitro MI release experiments demonstrated that PU microphase separation and the structural design of PU-MI matrices were important determinants of release kinetics. Increased phase separation in doped PU assisted in consistent long-term release of dissolved MIs from both hard and soft segments of the PU. The use of a composite-sandwich mesh design prevented an initial burst release which improved the late (>20 days) release rate of MIs from the matrix. PMID:28644382

Evaluation of serum 25-hydroxyvitamin D levels in calcific rheumatic mitral stenosis- A cross sectional study.

PubMed

Yusuf, Jamal; P, Jothinath; Mukhopadhyay, Saibal; Vignesh, Vickram; Tyagi, Sanjay

Rheumatic mitral stenosis (RMS) is an autoimmune, progressive destructive valve disease occurring as a sequele of streptococcal infection. Epidemiological studies support an association of vitamin D deficiency with initial susceptibility and severity of autoimmune diseases. The aim of the present study was to assess serum level of 25 hydroxyvitamin D in subjects of RMS and assess if any correlation exists with serum levels of vitamin D and severity of disease along with calcification assessed semi-quantitatively by echocardiography by applying Wilkins score. Fifty five patients of RMS without any calcification of the valves (Group A) assessed by echocardiography along with fifty five patients of RMS with mild to moderately calcified valves (Group B, Wilkins calcium score 1 or 2) and 55 patients with severely calcified valves (Group C, Wilkins calcium score 3 or 4) were enrolled for the study. All subjects underwent clinical, echocardiographic, and biochemical evaluation. The total Wilkins score, Wilkins calcium score along with serum level of 25 hydroxyvitamin D was evaluated in all the patients. The median serum level of 25 hydroxyvitamin D was significantly lower in Group B (20.4ng/ml, p<0.001) and group C (11.4ng/ml, p<0.001) compared to Group A patients (27.9ng/ml). Similarly serum level of 25 hydroxyvitamin D in Group C patients were significantly less than Group B patients (p<0.001). A significant inverse correlation was identified between serum level of 25 hydroxyvitamin D and total Wilkins score (r=-0.65, p<0.001) as well as Wilkins calcium score (r=-0.69, p<0.001). But no correlation was identified between 25 hydroxyvitamin D levels and other echocardiographic parameters of RMS. Our study showed a significantly lower level of 25 hydroxyvitamin D in subjects of RMS with severely damaged and calcified valves as compared to those with less severely damaged non-calcified valves and it correlated with both Wilkins score and Wilkins calcification score. Thus a

Balloon expandable transcatheter aortic valve implantation with or without pre-dilation of the aortic valve - rationale and design of a multicenter registry (EASE-IT).

PubMed

Bramlage, Peter; Strauch, Justus; Schröfel, Holger

2014-11-18

In patients with severe calcific aortic stenosis, balloon aortic valvuloplasty (BAV) is routinely performed in order to pre-dilate the stenosed aortic valve prior to transcatheter aortic valve implantation (TAVI). Although pre-dilation is considered to be essential for the preparation of the valve landing zone, there is no clear evidence to support its clinical value. In contrast, BAV has been suggested to be linked to several complications. Notably, while preliminary evidence has supported the feasibility and safety of TAVI without pre-dilation, larger studies directly comparing the benefit/risk profile of TAVI in the presence and absence of pre-dilation are required. Therefore, a prospective, two-armed, multicenter registry (EASE-IT) was designed to obtain essential data concerning procedural success rates, adverse events, and mortality in a large cohort of patients undergoing transapical (TA)-TAVI using the Edwards SAPIEN 3 balloon expandable heart valves with and without pre-ballooning. Data provided by EASE-IT will be used to assess the relevance of BAV during the TAVI procedure and to investigate associations between patient characteristics and outcomes. Therefore, results obtained from the EASE-IT registry could contribute to reduced rates of TAVI-associated morbidity and mortality in patients with severe, calcific aortic stenosis. ClinicalTrials.gov Identifier: NCT02127580.

Association of body mass index and visceral fat with aortic valve calcification and mortality after transcatheter aortic valve replacement: the obesity paradox in severe aortic stenosis.

PubMed

Mancio, Jennifer; Fonseca, Paulo; Figueiredo, Bruno; Ferreira, Wilson; Carvalho, Monica; Ferreira, Nuno; Braga, Pedro; Rodrigues, Alberto; Barros, Antonio; Falcao-Pires, Ines; Leite-Moreira, Adelino; Ribeiro, Vasco Gama; Bettencourt, Nuno

2017-01-01

Previous studies showed that metabolic syndrome is associated with aortic valve calcification (AVC) and poor outcomes in aortic stenosis (AS). However, if these associations change and how body fat impacts the prognosis of patients in late stage of the disease have been not yet explored. To determine the association of body mass index (BMI) and visceral fat with AVC and mortality after transcatheter aortic valve replacement (TAVR). This was a prospective cohort of 170 severe AS patients referred to TAVR. We quantified AVC mass score and fat depots including epicardial adipose tissue, intrathoracic fat, and abdominal visceral (VAF) and subcutaneous fats by computed tomography. Fat depots were indexed to body surface area. All-cause and cardiovascular-related deaths after TAVR were recorded over a median follow-up of 1.2 years. Higher AVC mass was independently associated with low BMI and low VAF. All-cause mortality risk increased with the decrease of BMI and increment of VAF. A stratified analysis by obesity showed that in non-obese, VAF was inversely associated with mortality, whereas in obese, high VAF was associated with higher mortality (p value for interaction < 0.05). At long-term, hazard ratio [HR] with non-obese/low VAF was 2.3 (95% confidence interval [CI] 1.1-4.9; p = 0.021) and HR with obese/high VAF was 2.5 (95% CI 1.1-5.8; p = 0.031) compared with obese/low VAF patients. In AS patients submitted to TAVR, BMI and VAF were inversely associated with AVC. Pre-intervention assessment of VAF by computed tomography may provide a better discrimination of mortality than BMI alone.

Study of normal, fibrous and calcified aortic valve tissue by Raman and reflectance spectroscopy

NASA Astrophysics Data System (ADS)

Rodrigues, Kátia Calligaris; Munin, Egberto; Alves, Leandro P.; Silveira, Fabrício L.; Junior, Landulfo S.; De Lima, Carlos J.; Lázzaro, João C.; De Souza, Genivaldo C.; Piotto, José A. B.; Pacheco, Marcos T. T.; Zângaro, Renato A.

2007-02-01

Several studies have identified the degree of aortic valve calcification as a strong predictor both for the progression and outcome of aortic stenosis. In industrialized countries, aortic valve stenosis is most frequently caused by progressive calcification and degeneration of aortic cusps. However, there are no accurate methods to quantify the extent of aortic valve calcification. To provide a non-invasive alternative to biopsy, a range of optical methods have been investigated, including Raman and reflectance spectroscopy. A Raman spectrum can be used to access the molecular constitution of a particular tissue and classify it. Raman spectroscopy is largely used in the quantification and evaluation of human atherosclerosis, being a powerful technique for performing biochemical analysis without tissue removal. Nevertheless, increased thickness and disorganization of the collagen fibre network and extracellular matrix are known to affect the diffuse spectral reflectance of the tissue. A catheter with the "6 around 1" configuration, the central fiber transmit laser radiation to the sample and the scattered light is collected by the other six surrounding fibers, was used both for Raman and reflectance spectroscopy. A white light (krypton lamp, flashtube Model FX 1160 Perkin Elmer, USA) excitation was used for reflectance measurements. A Ti-sapphire (785nm, Spectra Physics, model 3900S, USA) laser, pumped by an argon laser (Spectra Physics, model Stabilite 2017, USA) was used as the near infrared Raman set up. Several ex-vivo spectra of aortic valve samples were analyzed. The results show a promising way to differentiate normal, fibrous and calcified tissue in aortic valve.

Systolic hypertension and progression of aortic valve calcification in patients with aortic stenosis: results from the PROGRESSA study

PubMed Central

Tastet, Lionel; Capoulade, Romain; Clavel, Marie-Annick; Larose, Éric; Shen, Mylène; Dahou, Abdellaziz; Arsenault, Marie; Mathieu, Patrick; Bédard, Élisabeth; Dumesnil, Jean G.; Tremblay, Alexe; Bossé, Yohan; Després, Jean-Pierre; Pibarot, Philippe

2017-01-01

Aims Hypertension is highly prevalent in patients with aortic stenosis (AS) and is associated with worse outcomes. The current prospective study assessed the impact of systolic hypertension (SHPT) on the progression of aortic valve calcification (AVC) measured by multidetector computed tomography (MDCT) in patients with AS. Methods and results The present analysis includes the first series of 101 patients with AS prospectively recruited in the PROGRESSA study. Patients underwent comprehensive Doppler echocardiography and MDCT exams at baseline and after 2-year follow-up. AVC and coronary artery calcification (CAC) were measured using the Agatston method. Patients with SHPT at baseline (i.e. systolic blood pressure ≥140 mmHg; n = 37, 37%) had faster 2-year AVC progression compared with those without SHPT (i.e. systolic blood pressure <140 mmHg) (AVC median [25th percentile–75th percentile]: +370 [126–824] vs. +157 [58–303] AU; P = 0.007, respectively). Similar results were obtained with the analysis of AVC progression divided by the cross-sectional area of the aortic annulus (AVCdensity: +96 [34–218] vs. +45 [14–82] AU/cm2, P = 0.01, respectively). In multivariable analysis, SHPT remained significantly associated with faster progression of AVC or AVCdensity (all P = 0.001). There was no significant difference between groups with respect to progression of CAC (+39 [3–199] vs. +41 [0–156] AU, P = 0.88). Conclusion This prospective study shows for the first time that SHPT is associated with faster AVC progression but not with CAC progression in AS patients. These findings provide further support for the elaboration of randomized clinical trials to assess the efficacy of antihypertensive medication to slow the stenosis progression in patients with AS. PMID:26896413

Systolic hypertension and progression of aortic valve calcification in patients with aortic stenosis: results from the PROGRESSA study.

PubMed

Tastet, Lionel; Capoulade, Romain; Clavel, Marie-Annick; Larose, Éric; Shen, Mylène; Dahou, Abdellaziz; Arsenault, Marie; Mathieu, Patrick; Bédard, Élisabeth; Dumesnil, Jean G; Tremblay, Alexe; Bossé, Yohan; Després, Jean-Pierre; Pibarot, Philippe

2017-01-01

Hypertension is highly prevalent in patients with aortic stenosis (AS) and is associated with worse outcomes. The current prospective study assessed the impact of systolic hypertension (SHPT) on the progression of aortic valve calcification (AVC) measured by multidetector computed tomography (MDCT) in patients with AS. The present analysis includes the first series of 101 patients with AS prospectively recruited in the PROGRESSA study. Patients underwent comprehensive Doppler echocardiography and MDCT exams at baseline and after 2-year follow-up. AVC and coronary artery calcification (CAC) were measured using the Agatston method. Patients with SHPT at baseline (i.e. systolic blood pressure ≥140 mmHg; n = 37, 37%) had faster 2-year AVC progression compared with those without SHPT (i.e. systolic blood pressure <140 mmHg) (AVC median [25th percentile-75th percentile]: +370 [126-824] vs. +157 [58-303] AU; P = 0.007, respectively). Similar results were obtained with the analysis of AVC progression divided by the cross-sectional area of the aortic annulus (AVC density : +96 [34-218] vs. +45 [14-82] AU/cm 2 , P = 0.01, respectively). In multivariable analysis, SHPT remained significantly associated with faster progression of AVC or AVC density (all P = 0.001). There was no significant difference between groups with respect to progression of CAC (+39 [3-199] vs. +41 [0-156] AU, P = 0.88). This prospective study shows for the first time that SHPT is associated with faster AVC progression but not with CAC progression in AS patients. These findings provide further support for the elaboration of randomized clinical trials to assess the efficacy of antihypertensive medication to slow the stenosis progression in patients with AS. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Calcific Aortic Valve Disease: Part 2—Morphomechanical Abnormalities, Gene Reexpression, and Gender Effects on Ventricular Hypertrophy and Its Reversibility

PubMed Central

2016-01-01

In part 1, we considered cytomolecular mechanisms underlying calcific aortic valve disease (CAVD), hemodynamics, and adaptive feedbacks controlling pathological left ventricular hypertrophy provoked by ensuing aortic valvular stenosis (AVS). In part 2, we survey diverse signal transduction pathways that precede cellular/molecular mechanisms controlling hypertrophic gene expression by activation of specific transcription factors that induce sarcomere replication in-parallel. Such signaling pathways represent potential targets for therapeutic intervention and prevention of decompensation/failure. Hypertrophy provoking signals, in the form of dynamic stresses and ligand/effector molecules that bind to specific receptors to initiate the hypertrophy, are transcribed across the sarcolemma by several second messengers. They comprise intricate feedback mechanisms involving gene network cascades, specific signaling molecules encompassing G protein-coupled receptors and mechanotransducers, and myocardial stresses. Future multidisciplinary studies will characterize the adaptive/maladaptive nature of the AVS-induced hypertrophy, its gender- and individual patient-dependent peculiarities, and its response to surgical/medical interventions. They will herald more effective, precision medicine treatments. PMID:27184804

Association between aortic valve calcification and myocardial ischemia, especially in asymptomatic patients.

PubMed

Yamazato, Ryo; Yamamoto, Hideya; Tadehara, Futoshi; Teragawa, Hiroki; Kurisu, Satoshi; Dohi, Yoshihiro; Ishibashi, Ken; Kunita, Eiji; Utsunomiya, Hiroto; Oka, Toshiharu; Kihara, Yasuki

2012-08-01

Aortic valve calcification (AVC) is recognized as a manifestation of systemic arteriosclerosis. However, it is unclear whether AVC is associated with myocardial ischemia. Stress myocardial perfusion SPECT (MPS) is widely used for the diagnosis of myocardial ischemia. However, routine MPS is not recommended, particularly in asymptomatic patients. Accordingly, we investigated the hypothesis that the presence of AVC is strongly associated with inducible myocardial ischemia, even among asymptomatic patients. We investigated 669 consecutive patients who underwent both adenosine stress (201)Tl MPS and echocardiography. We evaluated the extent and severity of myocardial ischemia by the summed difference score (SDS). We defined the presence of myocardial ischemia as SDS ≥ 3 and moderate to severe ischemia as SDS ≥ 8. We classified the severity of AVC according to the number of affected aortic leaflets. We also compared the mean SDS and the prevalence of SDS ≥ 3 and SDS ≥ 8 among patients stratified by the severity of AVC. The presence of AVC was significantly associated with myocardial ischemia (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.10-2.23; P = 0.013) and moderate to severe ischemia (OR, 2.16; 95% CI, 1.26-3.80; P = 0.0061). In 311 asymptomatic patients, AVC was strongly associated with moderate to severe ischemia (OR, 4.31; 95% CI, 1.67-12.8; P = 0.0043). However, the SDS value and the prevalence of SDS ≥ 3 and SDS ≥ 8 did not increase with increasing number of affected aortic leaflets. The presence of AVC may be associated with the presence of myocardial ischemia, particularly in asymptomatic patients. However, we found no association between the extent of AVC and inducible myocardial ischemia. The presence of AVC may be a useful anatomic marker to help identify patients at high risk of myocardial ischemia, particularly asymptomatic patients.

[Initial experience of transcatheter implantation with a new aortic valve in sheep].

PubMed

Wang, Jian-ming; Yang, Jian; Yang, Li-fang; Zhang, Xue-xin; Hu, Yun; Liu, Jin-cheng; Yu, Shi-qiang; Yi, Ding-hua

2011-11-01

To evaluate the feasibility and short-term results of transcatheter aortic valve implantation (TAVI) using a new transcatheter valve. Twenty healthy adult sheep received general anesthesia. Under the guidance of X-ray and transthoracic echocardiography (TTE), the new anti-calcification transcatheter valve was released from delivery system and implanted at the level of native aortic annulus via left common carotid artery. Position and function of the new anti-calcification transcatheter valve were evaluated by angiography and TTE immediately after intervention. Thirty day survival rate of animals was obtained. New transcatheter valves were implanted in all sheep. Fifteen sheep (75%) survived up to 30 days and post-operative examination showed that the transcatheter valve was in optimal position without migration and mitral valve impingement. The native coronary artery was patent in these animals. There was a slight paravalvular leak in 5 sheep. Postoperative echocardiography showed reflux percentage was significantly increased (P < 0.05) compared pre-intervention. Effective orifice area, aortic systolic pressure, diastolic aortic pressure, mean aortic pressure, left ventricular systolic pressure, left ventricular end diastolic pressure and heart rate were similar between post and pre-intervention (all P < 0.05). Five sheep died after TAVI within 30 days, including one fatal ventricular fibrillation occurred immediately after releasing the transcatheter valve and another sheep died of acute myocardial infarction due to left main coronary artery occlusion evidenced by angiography. Two sheep died of severe mitral regurgitation at 8 and 12 hours post-operation and one died of infective endocarditis at 26 days after intervention. Our favorable preliminary results showed that it was feasible to perform TAVI using the new transcatheter valve.

Polymeric trileaflet prosthetic heart valves: evolution and path to clinical reality

PubMed Central

Claiborne, Thomas E; Slepian, Marvin J; Hossainy, Syed; Bluestein, Danny

2013-01-01

Present prosthetic heart valves, while hemodynamically effective, remain limited by progressive structural deterioration of tissue valves or the burden of chronic anticoagulation for mechanical valves. An idealized valve prosthesis would eliminate these limitations. Polymeric heart valves (PHVs), fabricated from advanced polymeric materials, offer the potential of durability and hemocompatibility. Unfortunately, the clinical realization of PHVs to date has been hampered by findings of in vivo calcification, degradation and thrombosis. Here, the authors review the evolution of PHVs, evaluate the state of the art of this technology and propose a pathway towards clinical reality. In particular, the authors discuss the development of a novel aortic PHV that may be deployed via transcatheter implantation, as well as its optimization via device thrombogenicity emulation. PMID:23249154

Mechanism of valve failure and efficacy of reintervention through catheterization in patients with bioprosthetic valves in the pulmonary position

PubMed Central

Callahan, Ryan; Bergersen, Lisa; Baird, Christopher W; Porras, Diego; Esch, Jesse J; Lock, James E; Marshall, Audrey C

2017-01-01

Background: Surgical and transcatheter bioprosthetic valves (BPVs) in the pulmonary position in patients with congenital heart disease may ultimately fail and undergo transcatheter reintervention. Angiographic assessment of the mechanism of BPV failure has not been previously described. Aims: The aim of this study was to determine the mode of BPV failure (stenosis/regurgitation) requiring transcatheter reintervention and to describe the angiographic characteristics of the failed BPVs and report the types and efficacy of reinterventions. Materials and Methods: This is a retrospective single-center review of consecutive patients who previously underwent pulmonary BPV placement (surgical or transcatheter) and subsequently underwent percutaneous reintervention from 2005 to 2014. Results: Fifty-five patients with surgical (41) and transcutaneous pulmonary valve (TPV) (14) implantation of BPVs underwent 66 catheter reinterventions. The surgically implanted valves underwent fifty reinterventions for indications including 16 for stenosis, seven for regurgitation, and 27 for both, predominantly associated with leaflet immobility, calcification, and thickening. Among TPVs, pulmonary stenosis (PS) was the exclusive failure mode, mainly due to loss of stent integrity (10) and endocarditis (4). Following reintervention, there was a reduction of right ventricular outflow tract gradient from 43 ± 16 mmHg to 16 ± 10 mmHg (P < 0.001) and RVp/AO ratio from 0.8 ± 0.2 to 0.5 ± 0.2 (P < 0.001). Reintervention with TPV placement was performed in 45 (82%) patients (34 surgical, 11 transcatheter) with no significant postintervention regurgitation or paravalvular leak. Conclusion: Failing surgically implanted BPVs demonstrate leaflet calcification, thickness, and immobility leading to PS and/or regurgitation while the mechanism of TPV failure in the short- to mid-term is stenosis, mainly from loss of stent integrity. This can be effectively treated with a catheter-based approach

Multidetector computed tomography sizing of aortic annulus prior to transcatheter aortic valve replacement (TAVR): Variability and impact of observer experience.

PubMed

Le Couteulx, S; Caudron, J; Dubourg, B; Cauchois, G; Dupré, M; Michelin, P; Durand, E; Eltchaninoff, H; Dacher, J-N

2018-05-01

To evaluate intra- and inter-observer variability of multidetector computed tomography (MDCT) sizing of the aortic annulus before transcatheter aortic valve replacement (TAVR) and the effect of observer experience, aortic valve calcification and image quality. MDCT examinations of 52 consecutive patients with tricuspid aortic valve (30 women, 22 men) with a mean age of 83±7 (SD) years (range: 64-93 years) were evaluated retrospectively. The maximum and minimum diameters, area and circumference of the aortic annulus were measured twice at diastole and systole with a standardized approach by three independent observers with different levels of experience (expert [observer 1]; resident with intensive 6 months practice [observer 2]; trained resident with starting experience [observer 3]). Observers were requested to recommend the valve prosthesis size. Calcification volume of the aortic valve and signal to noise ratio were evaluated. Intra- and inter-observer reproducibility was excellent for all aortic annulus dimensions, with an intraclass correlation coefficient ranging respectively from 0.84 to 0.98 and from 0.82 to 0.97. Agreement for selection of prosthesis size was almost perfect between the two most experienced observers (k=0.82) and substantial with the inexperienced observer (k=0.67). Aortic valve calcification did not influence intra-observer reproducibility. Image quality influenced reproducibility of the inexperienced observer. Intra- and inter-observer variability of aortic annulus sizing by MDCT is low. Nevertheless, the less experienced observer showed lower reliability suggesting a learning curve. Copyright © 2017. Published by Elsevier Masson SAS.

Prevalence and severity of coronary artery disease in diabetic patients with aortic valve calcification.

PubMed

Chen, Zhang-wei; Qian, Ju-ying; Jian, Ying; Ge, Lei; Liu, Xue-bo; Shu, Xian-hong; Ge, Junbo

2011-02-01

Aortic valve calcification (AVC) is common in the elderly and associated with increased cardiovascular mortality, while diabetes is one of the confirmed risk factors for coronary artery disease (CAD). In this study, we aimed to evaluate the prevalence and severity of CAD in type-2 diabetic patients with AVC. From June to December in 2007, a total of 325 consecutive patients with chest pain or chest distress were admitted for coronary angiography. The severity of CAD was evaluated by the Gensini score and the number of stenosed vessels. All patients underwent transthoracic echocardiography for detecting AVC. Compared with the patients without diabetes (n = 221), the type-2 diabetic patients (n = 104) had a similar prevalence of CAD (66.5% vs. 72.1%, P = 0.312). Further classified by the presence of AVC, patients with AVC had a higher prevalence of CAD, average Gensini score and the number of stenosed vessels, both in the group with and without diabetes. It was also demonstrated that the odds ratio (OR) of AVC for CAD in the diabetic patients was higher than in the non-diabetic ones (3.405 vs 2.515) after chi-square analysis (single-variable). However, at multivariable logistic regression analysis for CAD, the OR of AVC was 3.757 (P = 0.03) in diabetic group, while it did not achieve statistical significance in the non-diabetic group (OR = 2.130, P= 0.074). Type-2 diabetic patients with AVC had a higher prevalence of and more severe CAD.

In vivo canine studies of a Sinkhole valve and vascular graft coated with biocompatible PU-PEO-SO3.

PubMed

Han, D K; Lee, K B; Park, K D; Kim, C S; Jeong, S Y; Kim, Y H; Kim, H M; Min, B G

1993-01-01

PU-PEO-SO3 was applied as a coating material over a newly designed Sinkhole bileaflet PU heart valve and a porous PU vascular graft. Performance and biocompatibility were evaluated using an in vivo canine shunt system between the right ventricle and pulmonary artery. The survival periods in three implantations were 14, 24, and 39 days, during which no mechanical failure occurred in any Sinkhole valve or vascular graft. Scanning electron microscopy (SEM) studies demonstrated much less platelet adhesion and thrombus formation on PU-PEO-SO3 grafts than on PU vascular grafts. Cracks in the valve leaflet were occasionally observed on PU surfaces, but not on PU-PEO-SO3. After a 39 day implantation, calcium deposition on vascular grafts was decreased as compared with valve leaflets, and calcification on PU-PEO-SO3 was much lower than on PU. These results suggest that Sinkhole valves and vascular grafts are promising, and PU-PEO-SO3 as a coating material is more blood compatible, biostable, and calcification resistant in vivo than in untreated PU.

Development of a Risk Score Based on Aortic Calcification to Predict 1-year Mortality After Transcatheter Aortic Valve Replacement.

PubMed

Lantelme, Pierre; Eltchaninoff, Hélène; Rabilloud, Muriel; Souteyrand, Géraud; Dupré, Marion; Spaziano, Marco; Bonnet, Marc; Becle, Clément; Riche, Benjamin; Durand, Eric; Bouvier, Erik; Dacher, Jean-Nicolas; Courand, Pierre-Yves; Cassagnes, Lucie; Dávila Serrano, Eduardo E; Motreff, Pascal; Boussel, Loic; Lefèvre, Thierry; Harbaoui, Brahim

2018-05-11

The aim of this study was to develop a new scoring system based on thoracic aortic calcification (TAC) to predict 1-year cardiovascular and all-cause mortality. A calcified aorta is often associated with poor prognosis after transcatheter aortic valve replacement (TAVR). A risk score encompassing aortic calcification may be valuable in identifying poor TAVR responders. The C 4 CAPRI (4 Cities for Assessing CAlcification PRognostic Impact) multicenter study included a training cohort (1,425 patients treated using TAVR between 2010 and 2014) and a contemporary test cohort (311 patients treated in 2015). TAC was measured by computed tomography pre-TAVR. CAPRI risk scores were based on the linear predictors of Cox models including TAC in addition to comorbidities and demographic, atherosclerotic disease and cardiac function factors. CAPRI scores were constructed and tested in 2 independent cohorts. Cardiovascular and all-cause mortality at 1 year was 13.0% and 17.9%, respectively, in the training cohort and 8.2% and 11.8% in the test cohort. The inclusion of TAC in the model improved prediction: 1-cm 3 increase in TAC was associated with a 6% increase in cardiovascular mortality and a 4% increase in all-cause mortality. The predicted and observed survival probabilities were highly correlated (slopes >0.9 for both cardiovascular and all-cause mortality). The model's predictive power was fair (AUC 68% [95% confidence interval [CI]: 64-72]) for both cardiovascular and all-cause mortality. The model performed similarly in the training and test cohorts. The CAPRI score, which combines the TAC variable with classical prognostic factors, is predictive of 1-year cardiovascular and all-cause mortality. Its predictive performance was confirmed in an independent contemporary cohort. CAPRI scores are highly relevant to current practice and strengthen the evidence base for decision making in valvular interventions. Its routine use may help prevent futile procedures. Copyright �

4D optical coherence tomography of aortic valve dynamics in a murine mouse model ex vivo

NASA Astrophysics Data System (ADS)

Schnabel, Christian; Jannasch, Anett; Faak, Saskia; Waldow, Thomas; Koch, Edmund

2015-07-01

The heart and its mechanical components, especially the heart valves and leaflets, are under enormous strain during lifetime. Like all highly stressed materials, also these biological components undergo fatigue and signs of wear, which impinge upon cardiac output and in the end on health and living comfort of affected patients. Thereby pathophysiological changes of the aortic valve leading to calcific aortic valve stenosis (AVS) as most frequent heart valve disease in humans are of particular interest. The knowledge about changes of the dynamic behavior during the course of this disease and the possibility of early stage diagnosis could lead to the development of new treatment strategies and drug-based options of prevention or therapy. ApoE-/- mice as established model of AVS versus wildtype mice were introduced in an ex vivo artificially stimulated heart model. 4D optical coherence tomography (OCT) in combination with high-speed video microscopy were applied to characterize dynamic behavior of the murine aortic valve and to characterize dynamic properties during artificial stimulation. OCT and high-speed video microscopy with high spatial and temporal resolution represent promising tools for the investigation of dynamic behavior and their changes in calcific aortic stenosis disease models in mice.

Association of Inflammatory, Lipid, and Mineral Markers with Cardiac Calcification in Older Adults

PubMed Central

Bortnick, Anna E.; Bartz, Traci M.; Ix, Joachim H.; Chonchol, Michel; Reiner, Alexander; Cushman, Mary; Owens, David; Barasch, Eddy; Siscovick, David S.; Gottdiener, John S.; Kizer, Jorge R.

2016-01-01

Objective Calcification of the aortic valve and adjacent structures involves inflammatory, lipid, and mineral metabolism pathways. We hypothesized that circulating biomarkers reflecting these pathways are associated with cardiac calcification in older adults. Methods We investigated the associations of various biomarkers with valvular and annular calcification in the Cardiovascular Health Study. Of 5888 participants, up to 3585 were eligible after exclusions for missing biomarker, covariate, or echocardiographic data. We evaluated analytes reflecting lipid (lipoprotein [Lp] (a), lipoprotein-associated phospholipase A2 [LpPLA2] mass and activity), inflammatory (interleukin-6, soluble [s] CD14), and mineral metabolism (fetuin-A, fibroblast growth factor [FGF]-23) that were measured within 5 years of echocardiography. The relationships of plasma biomarkers with aortic valve calcium (AVC), aortic annular calcium (AAC) and mitral annular calcium (MAC) were assessed with relative risk (RR) regression. Results Calcification was prevalent: AVC 59%, AAC 45% and MAC 41%. After adjustment, Lp(a), LpPLA2 mass and activity, and sCD14 were positively associated with AVC. RRs for AVC per SD (95% CI) were: Lp(a), 1.051 (1.022–1.081); LpPLA2 mass, 1.036 (1.006–1.066), and activity, 1.037 (1.004–1.071); sCD14, 1.039 (1.005–1.073). FGF-23 was positively associated with MAC, 1.040 (1.004–1.078), and fetuin-A was negatively associated, 0.949 (0.911–0.989). No biomarkers were significantly associated with AAC. Conclusions This study shows novel associations of circulating FGF-23 and fetuin-A with MAC, and LpPLA2 and sCD14 with AVC, confirming that previously reported for Lp(a). Further investigation of lipoprotein and inflammatory pathways may provide added insight into the etiology AVC, while study of phosphate regulation may illuminate the pathogenesis of MAC. PMID:27411840

Pulmonary valve autotransplantation (the Ross operation).

PubMed

Ross, D

1988-09-01

In 1967, homografts had been in place five years and the early nonviable and natant freeze-dried valves were showing irrefutable signs of degeneration and calcification. For this reason, in 1967, we moved to reserving both viability and tissue integrity by cryopreservation. To overcome the problems of procurement, the next logical step was to transfer the patient's own pulmonic valve to the aortic area. In the past twenty years, 249 operations have been performed. Of the 249 patients, there have been 16 operative deaths (6.5%), but no operative deaths in the past ten years. There have been no details related to primary tissue failure in the aortic area. There have been 36 reoperations (14.4%).

Echocardiographic aortic valve calcification and outcomes in women and men with aortic stenosis

PubMed Central

Thomassen, Henrik K; Cioffi, Giovanni; Gerdts, Eva; Einarsen, Eigir; Midtbø, Helga Bergljot; Mancusi, Costantino; Cramariuc, Dana

2017-01-01

Objective Sex differences in risk factors of aortic valve calcification (AVC) by echocardiography have not been reported from a large prospective study in aortic stenosis (AS). Methods AVC was assessed using a prognostically validated visual score and grouped into none/mild or moderate/severe AVC in 1725 men and women with asymptomatic AS in the Simvastatin Ezetimibe in Aortic Stenosis study. The severity of AS was assessed by the energy loss index (ELI) taking pressure recovery in the aortic root into account. Results More men than women had moderate/severe AVC at baseline despite less severe AS by ELI (p<0.01). Moderate/severe AVC at baseline was independently associated with lower aortic compliance and more severe AS in both sexes, and with increased high-sensitive C reactive protein (hs-CRP) only in men (all p<0.01). In Cox regression analyses, moderate/severe AVC at baseline was associated with a 2.5-fold (95% CI 1.64 to 3.80) higher hazard rate of major cardiovascular events in women, and a 2.2-fold higher hazard rate in men (95% CI 1.54 to 3.17) (both p<0.001), after adjustment for age, hypertension, study treatment, aortic compliance, left ventricular (LV) mass and systolic function, AS severity and hs-CRP. Moderate/severe AVC at baseline also predicted a 1.8-fold higher hazard rate of all-cause mortality in men (95% CI 1.04 to 3.06, p<0.05) independent of age, AS severity, LV mass and aortic compliance, but not in women. Conclusion In conclusion, AVC scored by echocardiography has sex-specific characteristics in AS. Moderate/severe AVC is associated with higher cardiovascular morbidity in both sexes, and with higher all-cause mortality in men. Trial registration number ClinicalTrials.gov identifier: NCT00092677 PMID:28698175

Cardiac Calcifications on Echocardiography Are Associated with Mortality and Stroke.

PubMed

Lu, Marvin Louis Roy; Gupta, Shuchita; Romero-Corral, Abel; Matejková, Magdaléna; De Venecia, Toni; Obasare, Edinrin; Bhalla, Vikas; Pressman, Gregg S

2016-12-01

Calcium deposits in the aortic valve and mitral annulus have been associated with cardiovascular events and mortality. However, there is no accepted standard method for scoring such cardiac calcifications, and most existing methods are simplistic. The aim of this study was to test the hypothesis that a semiquantitative score, one that accounts for all visible calcium on echocardiography, could predict all-cause mortality and stroke in a graded fashion. This was a retrospective study of 443 unselected subjects derived from a general echocardiography database. A global cardiac calcium score (GCCS) was applied that assigned points for calcification in the aortic root and valve, mitral annulus and valve, and submitral apparatus, and points for restricted leaflet mobility. The primary outcome was all-cause mortality, and the secondary outcome was stroke. Over a mean 3.8 ± 1.7 years of follow-up, there were 116 deaths and 34 strokes. Crude mortality increased in a graded fashion with increasing GCCS. In unadjusted proportional hazard analysis, the GCCS was significantly associated with total mortality (hazard ratio, 1.26; 95% CI, 1.17-1.35; P < .0001) and stroke (hazard ratio, 1.23; 95% CI, 1.07-1.40; P = .003). After adjusting for demographic and clinical factors (age, gender, body mass index, diabetes, hypertension, dyslipidemia, smoking, family history of coronary disease, chronic kidney disease, history of atrial fibrillation, and history of stroke), these associations remained significant. The GCCS is easily applied to routinely acquired echocardiograms and has clinically significant associations with total mortality and stroke. Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

A Quantitative Study of Simulated Bicuspid Aortic Valves

NASA Astrophysics Data System (ADS)

Szeto, Kai; Nguyen, Tran; Rodriguez, Javier; Pastuszko, Peter; Nigam, Vishal; Lasheras, Juan

2010-11-01

Previous studies have shown that congentially bicuspid aortic valves develop degenerative diseases earlier than the standard trileaflet, but the causes are not well understood. It has been hypothesized that the asymmetrical flow patterns and turbulence found in the bileaflet valves together with abnormally high levels of strain may result in an early thickening and eventually calcification and stenosis. Central to this hypothesis is the need for a precise quantification of the differences in the strain rate levels between bileaflets and trileaflet valves. We present here some in-vitro dynamic measurements of the spatial variation of the strain rate in pig aortic vales conducted in a left ventricular heart flow simulator device. We measure the strain rate of each leaflet during the whole cardiac cycle using phase-locked stereoscopic three-dimensional image surface reconstruction techniques. The bicuspid case is simulated by surgically stitching two of the leaflets in a normal valve.

Outcomes following transcatheter aortic valve replacement in patients with native aortic valve regurgitation

PubMed Central

Bob-Manuel, Tamunoinemi; Kadire, Siri; Heckle, Mark R.; Wang, Jiajing

2018-01-01

Due to the absence of annular calcification for device anchoring, it is presumed that transcatheter aortic valve replacement (TAVR) is not suitable for the treatment of native aortic valve regurgitation (NAVR) resulting in very limited data and experience concerning its safety and efficacy. We sought to review published data on the safety and efficacy of TAVR in high-risk patients with NAVR. Studies including case reports, case series and original articles published between 2002 and 2016 on TAVR in patients with NAVR were identified with a systematic electronic search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Only studies reporting data on demographic and procedural characteristics, management and follow up outcomes were analyzed. A total of 30 publications describing 182 patients were identified. Most patients (54%) were men, with a mean age of 70.1±2.6 years, mean logistic European System for Cardiac Operative Risk Evaluation score (EuroSCORE) of 21.8%±4.5% and mean Society of Thoracic Surgeons (STS) score of 8%±1.8% for mortality. The majority (87%) of patients had severe NAVR with no valvular calcification. TAVR was mostly performed through the femoral (58.8%) and apical (33.1%) approach. Device success, defined by VARC-2, was achieved in 86.3% of our study population. A second valve was required in 17 patients (9.3%) during the index procedure for residual aortic regurgitation or malposition. Post-procedure aortic regurgitation of grade 1 or less was present in 80 patients (81%). Pacemaker implantation was required post procedure in 17 patients (9.3%). The 30-day and 1-year mortality was 11.9% and 16.2%, respectively. TAVR is associated with favorable pacemaker implantation and 1-year mortality rates with a high 30-day mortality among selected patients with NAVR. PMID:29404354

Amyloid substance within stenotic aortic valves promotes mineralization.

PubMed

Audet, Audrey; Côté, Nancy; Couture, Christian; Bossé, Yohan; Després, Jean-Pierre; Pibarot, Philippe; Mathieu, Patrick

2012-10-01

Accumulation of apolipoproteins may play an important role in the pathobiology of calcific aortic valve disease (CAVD). We aimed to explore the hypothesis that apolipoprotein-derived amyloid could play a role in the development of CAVD. In 70 explanted CAVD valves and 15 control non-calcified aortic valves, we assessed the presence of amyloid by using Congo red staining. Immunohistochemistry was performed to document the presence of apolipoprotein AI (Apo-AI). Apoptosis was documented by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) studies performed in control and CAVD valves. Control valves were free of amyloid. Deposition of amyloid was detected in all CAVD valves, and the amount was positively correlated with plasma high-density lipoprotein and Apo-AI levels. Apo-AI within CAVD valves co-localized with intense staining of fibrillar amyloid. In turn, deposition of amyloid co-localized with apoptosis near mineralized areas. Isolation of amyloid fibrils confirmed that Apo-AI is a major component of amyloid deposits in CAVD. In vitro, CAVD-derived amyloid extracts increased apoptosis and mineralization of isolated aortic valvular interstitial cells. Apo-AI is a major component of amyloid substance present within CAVD valves. Furthermore, amyloid deposits participate in mineralization in CAVD by promoting apoptosis of valvular interstitial cells. © 2012 Blackwell Publishing Ltd.

Deformation Differences between Tricuspid and Bicuspid Aortic Valves in Vitro

NASA Astrophysics Data System (ADS)

Szeto, Kai; Rodriguez-Rodriguez, Javier; Pastuszko, Peter; Nigam, Vishal; Lasheras, Juan C.

2011-11-01

It has been shown in clinical studies that patients with congenital bicuspid aortic valves (CBAVs) develop degenerative calcification of the leaflets at young ages compared to patients with the normal tricuspid aortic valves (TAVs). It has been hypothesized that the asymmetrical geometry of the leaflets in CBAVs, flow shear stresses (SS), disturbed flow, and excessive strain rate levels are possible causes for the early calcification and stenosis. Central to the validation of this hypothesis is the need to quantify the differences in strain rate levels between the BAVs and TAVs. We simulate the CBAVs by surgically stitching two of the leaflets of a porcine aortic valve together. To quantify strain differences, we performed in-vitro experiments in both trileaflet and bileaflet valves by tracking the motion of small ink dots marked on each leaflet surface. We then used phase-locked stereo photogrammetry to reconstruct at each instant of time the 3D surface of the leaflets and measure the strain rates in both radial and circumferential directions during the whole cardiac cycle. Our results indicate that the total strain rate of the simulated BAVs is about 15 to 20% higher than the normal leaflets of TAVs at systole. In the BAVs' case, the fused leaflet stretches radially up to 25% higher than the reference length. The excessive stretching in both directions in the fused leaflet results in large changes in the flow patterns and associated wall SS.

Warfarin use and the risk of valvular calcification.

PubMed

Lerner, R G; Aronow, W S; Sekhri, A; Palaniswamy, C; Ahn, C; Singh, T; Sandhu, R; McClung, J A

2009-12-01

Warfarin affects the synthesis and function of the matrix Gla-protein, a vitamin K-dependent protein, which is a potent inhibitor of tissue calcification. To investigate the incidence of mitral valve calcium (MVC), mitral annular calcium (MAC) and aortic valve calcium (AVC) in patients with non-valvular atrial fibrillation (AF) treated with warfarin vs. no warfarin. Of 1155 patients, mean age 74 years, with AF, 725 (63%) were treated with warfarin and 430 (37%) without warfarin. The incidence of MVC, MAC and AVC was investigated in these 1155 patients with two-dimensional echocardiograms. Unadjusted logistic regression analysis was conducted to examine the association between the use of warfarin and the incidence of MVC, MAC or AVC. Logistic regression analyses were also conducted to investigate whether the relationship stands after adjustment for confounding risk factors such as age, sex, race, ejection fraction, smoking, hypertension, diabetes, dyslipidemia, coronary artery disease (CAD), glomerular filtration rate, calcium, phosphorus, calcium-phosphorus product, alkaline phosphatase, use of aspirin, beta blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and statins. There was a significant association between the use of warfarin and the risk of calcification [unadjusted odds ratio = 1.71, 95% CI = (1.34-2.18)]. The association still stands after adjustment for confounding risk factors. MVC, MAC or AVC was present in 473 of 725 patients (65%) on warfarin vs. 225 of 430 patients (52%) not on warfarin (P < 0.0001). Whether this is a causal relationship remains unknown. Use of warfarin in patients with AF is associated with an increased prevalence of MVC, MAC or AVC.

Anatomic characteristics of bileaflet mitral valve prolapse--Barlow disease--in patients undergoing mitral valve repair.

PubMed

Rostagno, Carlo; Droandi, Ginevra; Rossi, Alessandra; Bevilacqua, Sergio; Romagnoli, Stefano; Montesi, Gian Franco; Stefàno, Pier Luigi

2014-01-01

Barlow disease is a still challenging pathology for the surgeon. Aim of the present study is to report anatomic abnormalities of mitral valve in patients undergoing mitral valve repair. Between January 1st, 2007, and December 31st, 2010, 85 consecutive patients (54 men and 31 women, mean age 59 +/- 14 years--range: 28-85 years) with the features of a Barlow mitral valve disease underwent mitral repair Forty seven percent of patients were in New York Heart Association functional class III or IV. Preoperative transesophageal echocardiography was compared with anatomical findings at the moment of surgery. Transthoracic echocardiography diagnosis of Barlow disease according to the criteria described by Carpentier was confirmed at anatomical inspection. Annular calcifications were found in 28 patients while 7 patients presented single or multiple clefts. A flail posterior mitral leaflet was detected in 32 subjects, while a flail anterior leaflet in 8. Elongation of chordae tendineae was demonstrated in 45 patients and chordal rupture in 31. All patients showed at trans esophageal echocardiography the typical features of Barlow disease. Seventy-seven (90.6%) patients had severe mitral valve regurgitation, in the remaining 9.4% it was moderate to severe. Transesophageal echocardiography failed to identify clefts in 2/7 and chordal rupture in 4/31. bileaflet prolapse > 2 mm, billowing valve with excess tissue and thickened leaflets > or = 3 mm, and severe annular dilatation, are characteristics of Barlow disease, however the identification of the associated and complex abnormalities of mitral valve is necessary to obtain optimal valve repair.

Will Catheter Interventions Replace Surgery for Valve Abnormalities?

PubMed Central

O’Byrne, Michael L; Gillespie, Matthew J

2015-01-01

Purpose of Review Catheter-based valve technologies have evolved rapidly over the last decade. Transcatheter aortic valve replacement (TAVR) has become a routine procedure in high-risk adult patients with calcific aortic stenosis. In patients with congenital heart disease (CHD), transcatheter pulmonary valve replacement represents a transformative technology for right ventricular outflow tract dysfunction with the potential to expand to other indications. This review aims to summarize 1) the current state of the art for transcatheter valve replacement (TVR) in CHD, 2) the expanding indications for TVR, and 3) the technological obstacles to optimizing TVR. Recent findings Multiple case series have demonstrated that TVR with the Melody transcatheter pulmonary valve in properly selected patients is safe, effective, and durable in short-term follow-up. The Sapien transcatheter heart valve represents an alternative device with similar safety and efficacy in limited studies. Innovative use of current valves has demonstrated the flexibility of TVR, while highlighting the need for devices to address the broad range of post-operative anatomies either with a single device or strategies to prepare the outflow tract for subsequent device deployment. Summary The potential of TVR has not been fully realized, but holds promise in treatment of CHD. PMID:24281347

Regression of aortic valve stenosis by ApoA-I mimetic peptide infusions in rabbits

PubMed Central

Busseuil, D; Shi, Y; Mecteau, M; Brand, G; Kernaleguen, A-E; Thorin, E; Latour, J-G; Rhéaume, E; Tardif, J-C

2008-01-01

Background and purpose: Aortic valve stenosis (AVS) is the most common valvular heart disease, and standard curative therapy remains open heart surgical valve replacement. The aim of our experimental study was to determine if apolipoprotein A-I (ApoA-I) mimetic peptide infusions could induce regression of AVS. Experimental approach: Fifteen New Zealand White male rabbits received a cholesterol-enriched diet and vitamin D2 until significant AVS was detected by echocardiography. The enriched diet was then stopped to mimic cholesterol-lowering therapy and animals were allocated randomly to receive saline (control group, n=8) or an ApoA-I mimetic peptide (treated group, n=7), three times per week for 2 weeks. Serial echocardiograms and post mortem valve histology were performed. Key results: Aortic valve area increased significantly by 25% in the treated group after 14 days of treatment (P=0.012). Likewise, aortic valve thickness decreased by 21% in the treated group, whereas it was unchanged in controls (P=0.0006). Histological analysis revealed that the extent of lesions at the base of valve leaflets and sinuses of Valsalva was smaller in the treated group compared with controls (P=0.032). The treatment also reduced calcification, as revealed by the loss of the positive relationship observed in the control group (r=0.87, P=0.004) between calcification area and aortic valve thickness. Conclusions and implications: Infusions of ApoA-I mimetic peptide lead to regression of experimental AVS. These positive results justify the further testing of high-density lipoprotein (HDL)-based therapies in patients with valvular aortic stenosis. Regression of aortic stenosis, if achieved safely, could transform the clinical treatment of this disease. PMID:18414386

Particle Image Velocimetry studies of bicuspid aortic valve hemodynamics

NASA Astrophysics Data System (ADS)

Saikrishnan, Neelakantan; Yap, Choon-Hwai; Yoganathan, Ajit P.

2010-11-01

Bicuspid aortic valves (BAVs) are a congenital anomaly of the aortic valve with two fused leaflets, affecting about 1-2% of the population. BAV patients have much higher incidence of valve calcification & aortic dilatation, which may be related to altered mechanical forces from BAV hemodynamics. This study aims to characterize BAV hemodynamics using Particle Image Velocimetry(PIV). BAV models are constructed from normal explanted porcine aortic valves by suturing two leaflets together. The valves are mounted in an acrylic chamber with two sinuses & tested in a pulsatile flow loop at physiological conditions. 2D PIV is performed to obtain flow fields in three planes downstream of the valve. The stenosed BAV causes an eccentric jet, resulting in a very strong vortex in the normal sinus. The bicuspid sinus vortex appears much weaker, but more unstable. Unsteady oscillatory shear stresses are also observed, which have been associated with adverse biological response; characterization of the hemodynamics of BAVs will provide the first step to understanding these processes better. Results from multiple BAV models of varying levels of stenosis will be presented & higher stenosis corresponded to stronger jets & increased aortic wall shear stresses.

Echocardiographic aortic valve calcification and outcomes in women and men with aortic stenosis.

PubMed

Thomassen, Henrik K; Cioffi, Giovanni; Gerdts, Eva; Einarsen, Eigir; Midtbø, Helga Bergljot; Mancusi, Costantino; Cramariuc, Dana

2017-10-01

Sex differences in risk factors of aortic valve calcification (AVC) by echocardiography have not been reported from a large prospective study in aortic stenosis (AS). AVC was assessed using a prognostically validated visual score and grouped into none/mild or moderate/severe AVC in 1725 men and women with asymptomatic AS in the Simvastatin Ezetimibe in Aortic Stenosis study. The severity of AS was assessed by the energy loss index (ELI) taking pressure recovery in the aortic root into account. More men than women had moderate/severe AVC at baseline despite less severe AS by ELI (p<0.01). Moderate/severe AVC at baseline was independently associated with lower aortic compliance and more severe AS in both sexes, and with increased high-sensitive C reactive protein (hs-CRP) only in men (all p<0.01). In Cox regression analyses, moderate/severe AVC at baseline was associated with a 2.5-fold (95% CI 1.64 to 3.80) higher hazard rate of major cardiovascular events in women, and a 2.2-fold higher hazard rate in men (95% CI 1.54 to 3.17) (both p<0.001), after adjustment for age, hypertension, study treatment, aortic compliance, left ventricular (LV) mass and systolic function, AS severity and hs-CRP. Moderate/severe AVC at baseline also predicted a 1.8-fold higher hazard rate of all-cause mortality in men (95% CI 1.04 to 3.06, p<0.05) independent of age, AS severity, LV mass and aortic compliance, but not in women. In conclusion, AVC scored by echocardiography has sex-specific characteristics in AS. Moderate/severe AVC is associated with higher cardiovascular morbidity in both sexes, and with higher all-cause mortality in men. ClinicalTrials.gov identifier: NCT00092677. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

3D Printed Cardiac Phantom for Procedural Planning of a Transcatheter Native Mitral Valve Replacement

PubMed Central

Izzo, Richard L.; O’Hara, Ryan P.; Iyer, Vijay; Hansen, Rose; Meess, Karen M.; Nagesh, S.V. Setlur; Rudin, Stephen; Siddiqui, Adnan H.; Springer, Michael; Ionita, Ciprian N.

2017-01-01

3D printing an anatomically accurate, functional flow loop phantom of a patient’s cardiac vasculature was used to assist in the surgical planning of one of the first native transcatheter mitral valve replacement (TMVR) procedures. CTA scans were acquired from a patient about to undergo the first minimally-invasive native TMVR procedure at the Gates Vascular Institute in Buffalo, NY. A python scripting library, the Vascular Modeling Toolkit (VMTK), was used to segment the 3D geometry of the patient’s cardiac chambers and mitral valve with severe stenosis, calcific in nature. A stereolithographic (STL) mesh was generated and AutoDesk Meshmixer was used to transform the vascular surface into a functioning closed flow loop. A Stratasys Objet 500 Connex3 multi-material printer was used to fabricate the phantom with distinguishable material features of the vasculature and calcified valve. The interventional team performed a mock procedure on the phantom, embedding valve cages in the model and imaging the phantom with a Toshiba Infinix INFX-8000V 5-axis C-arm bi-Plane angiography system. Results After performing the mock-procedure on the cardiac phantom, the cardiologists optimized their transapical surgical approach. The mitral valve stenosis and calcification were clearly visible. The phantom was used to inform the sizing of the valve to be implanted. Conclusion With advances in image processing and 3D printing technology, it is possible to create realistic patient-specific phantoms which can act as a guide for the interventional team. Using 3D printed phantoms as a valve sizing method shows potential as a more informative technique than typical CTA reconstruction alone. PMID:28615797

3D Printed Cardiac Phantom for Procedural Planning of a Transcatheter Native Mitral Valve Replacement.

PubMed

Izzo, Richard L; O'Hara, Ryan P; Iyer, Vijay; Hansen, Rose; Meess, Karen M; Nagesh, S V Setlur; Rudin, Stephen; Siddiqui, Adnan H; Springer, Michael; Ionita, Ciprian N

2016-02-27

3D printing an anatomically accurate, functional flow loop phantom of a patient's cardiac vasculature was used to assist in the surgical planning of one of the first native transcatheter mitral valve replacement (TMVR) procedures. CTA scans were acquired from a patient about to undergo the first minimally-invasive native TMVR procedure at the Gates Vascular Institute in Buffalo, NY. A python scripting library, the Vascular Modeling Toolkit (VMTK), was used to segment the 3D geometry of the patient's cardiac chambers and mitral valve with severe stenosis, calcific in nature. A stereolithographic (STL) mesh was generated and AutoDesk Meshmixer was used to transform the vascular surface into a functioning closed flow loop. A Stratasys Objet 500 Connex3 multi-material printer was used to fabricate the phantom with distinguishable material features of the vasculature and calcified valve. The interventional team performed a mock procedure on the phantom, embedding valve cages in the model and imaging the phantom with a Toshiba Infinix INFX-8000V 5-axis C-arm bi-Plane angiography system. After performing the mock-procedure on the cardiac phantom, the cardiologists optimized their transapical surgical approach. The mitral valve stenosis and calcification were clearly visible. The phantom was used to inform the sizing of the valve to be implanted. With advances in image processing and 3D printing technology, it is possible to create realistic patient-specific phantoms which can act as a guide for the interventional team. Using 3D printed phantoms as a valve sizing method shows potential as a more informative technique than typical CTA reconstruction alone.

3D printed cardiac phantom for procedural planning of a transcatheter native mitral valve replacement

NASA Astrophysics Data System (ADS)

Izzo, Richard L.; O'Hara, Ryan P.; Iyer, Vijay; Hansen, Rose; Meess, Karen M.; Nagesh, S. V. Setlur; Rudin, Stephen; Siddiqui, Adnan H.; Springer, Michael; Ionita, Ciprian N.

2016-03-01

3D printing an anatomically accurate, functional flow loop phantom of a patient's cardiac vasculature was used to assist in the surgical planning of one of the first native transcatheter mitral valve replacement (TMVR) procedures. CTA scans were acquired from a patient about to undergo the first minimally-invasive native TMVR procedure at the Gates Vascular Institute in Buffalo, NY. A python scripting library, the Vascular Modeling Toolkit (VMTK), was used to segment the 3D geometry of the patient's cardiac chambers and mitral valve with severe stenosis, calcific in nature. A stereolithographic (STL) mesh was generated and AutoDesk Meshmixer was used to transform the vascular surface into a functioning closed flow loop. A Stratasys Objet 500 Connex3 multi-material printer was used to fabricate the phantom with distinguishable material features of the vasculature and calcified valve. The interventional team performed a mock procedure on the phantom, embedding valve cages in the model and imaging the phantom with a Toshiba Infinix INFX-8000V 5-axis Carm bi-Plane angiography system. Results: After performing the mock-procedure on the cardiac phantom, the cardiologists optimized their transapical surgical approach. The mitral valve stenosis and calcification were clearly visible. The phantom was used to inform the sizing of the valve to be implanted. Conclusion: With advances in image processing and 3D printing technology, it is possible to create realistic patientspecific phantoms which can act as a guide for the interventional team. Using 3D printed phantoms as a valve sizing method shows potential as a more informative technique than typical CTA reconstruction alone.

Transcatheter Pulmonary Valve Replacement by Hybrid Approach Using a Novel Polymeric Prosthetic Heart Valve: Proof of Concept in Sheep

PubMed Central

Xu, Tong-yi; Zhang, Zhi-gang; Li, Xin; Han, Lin; Xu, Zhi-yun

2014-01-01

Background Since 2000, transcatheter pulmonary valve replacement has steadily advanced. However, the available prosthetic valves are restricted to bioprosthesis which have defects like poor durability. Polymeric heart valve is thought as a promising alternative to bioprosthesis. In this study, we introduced a novel polymeric transcatheter pulmonary valve and evaluated its feasibility and safety in sheep by a hybrid approach. Methods We designed a novel polymeric trileaflet transcatheter pulmonary valve with a balloon-expandable stent, and the valve leaflets were made of 0.1-mm expanded polytetrafluoroethylene (ePTFE) coated with phosphorylcholine. We chose glutaraldehyde-treated bovine pericardium valves as control. Pulmonary valve stents were implanted in situ by a hybrid transapical approach in 10 healthy sheep (8 for polymeric valve and 2 for bovine pericardium valve), weighing an average of 22.5±2.0 kg. Angiography and cardiac catheter examination were performed after implantation to assess immediate valvular functionality. After 4-week follow-up, angiography, echocardiography, computed tomography, and cardiac catheter examination were used to assess early valvular function. One randomly selected sheep with polymeric valve was euthanized and the explanted valved stent was analyzed macroscopically and microscopically. Findings Implantation was successful in 9 sheep. Angiography at implantation showed all 9 prosthetic valves demonstrated orthotopic position and normal functionality. All 9 sheep survived at 4-week follow-up. Four-week follow-up revealed no evidence of valve stent dislocation or deformation and normal valvular and cardiac functionality. The cardiac catheter examination showed the peak-peak transvalvular pressure gradient of the polymeric valves was 11.9±5.0 mmHg, while that of two bovine pericardium valves were 11 and 17 mmHg. Gross morphology demonstrated good opening and closure characteristics. No thrombus or calcification was seen

Mitral valve pericardioplasty—a long-term follow-up study

PubMed Central

Van Der Spuy, J. C.

1972-01-01

Posterior (17) and anterior (3) mitral cusp pericardioplasties were performed in 20 patients between 6 December 1961 and 10 July 1963. A long-term follow-up study was done in nine patients. In six of these, mitral valvectomy with Starr-Edwards ball valve replacement was required after intervals varying between two years and three months and seven years and three months. In only one of the six cases did the pericardium macroscopically appear normal. In four it was obviously thickened and in two of the four there was also evidence of calcification in the pericardium only. In one of these, calcification was gross, causing complete immobility of the whole 2 × 0·6 in (5 × 1·7 cm) pericardial inlay. In only one of the six cases had the pericardium become larger and thinner and this also was in the only patient with a dilated mitral ring. Only three patients remain with the pericardium as inserted into the posterior mitral cusp between eight years and eight years and eleven months previously, but in all three there is clinical evidence of progressive pathology in the mitral valve. The progressive mitral valve involvement in this series could well have been caused by progression of the pre-existing pathology in the cusps and chordae tendineae but the involvement of the pericardial inlay was much more extensive than that of the rest of the cusp. Images PMID:5034597

Relationship of aortic valve calcification with coronary artery calcium severity: the Multi-Ethnic Study of Atherosclerosis (MESA).

PubMed

Nasir, Khurram; Katz, Ronit; Al-Mallah, Mouaz; Takasu, Junichiro; Shavelle, David M; Carr, Jeffery J; Kronmal, Richard; Blumenthal, Roger S; O'Brien, Kevin; Budoff, Matthew J

2010-01-01

Aortic valve calcification (AVC) and atherosclerosis share causative and pathologic features. We evaluated the relationship between AVC and coronary artery calcium (CAC) severity in the Multi-Ethnic Study of Atherosclerosis (MESA). Men and women aged 45-84 years (n=6809; mean age, 62 years) were studied. The presence and burden of AVC and CAC were determined by noncontrast cardiac computed tomography. Relative risk regression was used to model the probability of AVC as a function of CAC > 0 as well as CAC categories (0, 1-99, 100-399, and > or = 400) with the reference group being CAC=0. The prevalence of AVC and CAC was 13% and 50%, respectively. Among those without CAC, the prevalence of AVC was 5% and increased across levels of CAC severity such that 14%, 25%, and 38% had AVC with increasing CAC scores of 1-99, 100-399, and > or = 400, respectively (P for trend<0.0001). After controlling for patient demographic factors and cardiovascular risk factors, the prevalence ratio of AVC among those with mild CAC (1-99) was 1.83 (95% CI, 1.45-2.31) and increased to 3.36 (95% CI, 2.56-4.42) for CAC > or = 400. Similar statistically significant increased risk of AVC was found when CAC was assessed as a continuous variable. Our study shows that AVC is independently associated with increasing severity of CAC. 2010 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

Nucleotide Catabolism on the Surface of Aortic Valve Xenografts; Effects of Different Decellularization Strategies.

PubMed

Kutryb-Zajac, Barbara; Yuen, Ada H Y; Khalpey, Zain; Zukowska, Paulina; Slominska, Ewa M; Taylor, Patricia M; Goldstein, Steven; Heacox, Albert E; Lavitrano, Marialuisa; Chester, Adrian H; Yacoub, Magdi H; Smolenski, Ryszard T

2016-04-01

Extracellular nucleotide metabolism controls thrombosis and inflammation and may affect degeneration and calcification of aortic valve prostheses. We evaluated the effect of different decellularization strategies on enzyme activities involved in extracellular nucleotide metabolism. Porcine valves were tested intact or decellularized either by detergent treatment or hypotonic lysis and nuclease digestion. The rates of ATP hydrolysis, AMP hydrolysis, and adenosine deamination were estimated by incubation of aorta or valve leaflet sections with substrates followed by HPLC analysis. We demonstrated relatively high activities of ecto-enzymes on porcine valve as compared to the aortic wall. Hypotonic lysis/nuclease digestion preserved >80 % of ATP and AMP hydrolytic activity but reduced adenosine deamination to <10 %. Detergent decellularization completely removed (<5 %) all these activities. These results demonstrate high intensity of extracellular nucleotide metabolism on valve surface and indicate that various valve decellularization techniques differently affect ecto-enzyme activities that could be important in the development of improved valve prostheses.

Impact of Aortic Valve Calcification, as Measured by MDCT, on Survival in Patients With Aortic Stenosis

PubMed Central

Clavel, Marie-Annick; Pibarot, Philippe; Messika-Zeitoun, David; Capoulade, Romain; Malouf, Joseph; Aggarval, Shivani; Araoz, Phillip A.; Michelena, Hector I.; Cueff, Caroline; Larose, Eric; Miller, Jordan D.; Vahanian, Alec; Enriquez-Sarano, Maurice

2014-01-01

BACKGROUND Aortic valve calcification (AVC) load measures lesion severity in aortic stenosis (AS) and is useful for diagnostic purposes. Whether AVC predicts survival after diagnosis, independent of clinical and Doppler echocardiographic AS characteristics, has not been studied. OBJECTIVES This study evaluated the impact of AVC load, absolute and relative to aortic annulus size (AVCdensity), on overall mortality in patients with AS under conservative treatment and without regard to treatment. METHODS In 3 academic centers, we enrolled 794 patients (mean age, 73 ± 12 years; 274 women) diagnosed with AS by Doppler echocardiography who underwent multidetector computed tomography (MDCT) within the same episode of care. Absolute AVC load and AVCdensity (ratio of absolute AVC to cross-sectional area of aortic annulus) were measured, and severe AVC was separately defined in men and women. RESULTS During follow-up, there were 440 aortic valve implantations (AVIs) and 194 deaths (115 under medical treatment). Univariate analysis showed strong association of absolute AVC and AVCdensity with survival (both, p < 0.0001) with a spline curve analysis pattern of threshold and plateau of risk. After adjustment for age, sex, coronary artery disease, diabetes, symptoms, AS severity on hemodynamic assessment, and LV ejection fraction, severe absolute AVC (adjusted hazard ratio [HR]: 1.75; 95% confidence interval [CI]: 1.04 to 2.92; p = 0.03) or severe AVCdensity (adjusted HR: 2.44; 95% CI: 1.37 to 4.37; p = 0.002) independently predicted mortality under medical treatment, with additive model predictive value (all, p ≤ 0.04) and a net reclassification index of 12.5% (p = 0.04). Severe absolute AVC (adjusted HR: 1.71; 95% CI: 1.12 to 2.62; p = 0.01) and severe AVCdensity (adjusted HR: 2.22; 95% CI: 1.40 to 3.52; p = 0.001) also independently predicted overall mortality, even with adjustment for time-dependent AVI. CONCLUSIONS This large-scale, multicenter outcomes study of

Bicuspid aortic valves: diagnostic accuracy of standard axial 64-slice chest CT compared to aortic valve image plane ECG-gated cardiac CT.

PubMed

Murphy, David J; McEvoy, Sinead H; Iyengar, Sri; Feuchtner, Gudrun; Cury, Ricardo C; Roobottom, Carl; Baumueller, Stephan; Alkadhi, Hatem; Dodd, Jonathan D

2014-08-01

To assess the diagnostic accuracy of standard axial 64-slice chest CT compared to aortic valve image plane ECG-gated cardiac CT for bicuspid aortic valves. The standard axial chest CT scans of 20 patients with known bicuspid aortic valves were blindly, randomly analyzed for (i) the appearance of the valve cusps, (ii) the largest aortic sinus area, (iii) the longest aortic cusp length, (iv) the thickest aortic valve cusp and (v) valve calcification. A second blinded reader independently analyzed the appearance of the valve cusps. Forty-two age- and sex-matched patients with known tricuspid aortic valves were used as controls. Retrospectively ECG-gated cardiac CT multiphase reconstructions of the aortic valve were used as the gold-standard. Fourteen (21%) scans were scored as unevaluable (7 bicuspid, 7 tricuspid). Of the remainder, there were 13 evaluable bicuspid valves, ten of which showed an aortic valve line sign, while the remaining three showed a normal Mercedes-Benz appearance owing to fused valve cusps. The 35 evaluable tricuspid aortic valves all showed a normal Mercedes-Benz appearance (P=0.001). Kappa analysis=0.62 indicating good interobserver agreement for the aortic valve cusp appearance. Aortic sinus areas, aortic cusp lengths and aortic cusp thicknesses of ≥ 3.8 cm(2), 3.2 cm and 1.6mm respectively on standard axial chest CT best distinguished bicuspid from tricuspid aortic valves (P<0.0001 for all). Of evaluable scans, the sensitivity, specificity, positive and negative predictive values of standard axial chest CT in diagnosing bicuspid aortic valves was 77% (CI 0.54-1.0), 100%, 100% and 70% respectively. The aortic valve is evaluable in approximately 80% of standard chest 64-slice CT scans. Bicuspid aortic valves may be diagnosed on evaluable scans with good diagnostic accuracy. An aortic valve line sign, enlarged aortic sinuses and elongated, thickened valve cusps are specific CT features. Copyright © 2014 Elsevier Ireland Ltd. All rights

Impact of Vascular Hemodynamics on Aortic Stenosis Evaluation: New Insights Into the Pathophysiology of Normal Flow-Small Aortic Valve Area-Low Gradient Pattern.

PubMed

Côté, Nancy; Simard, Louis; Zenses, Anne-Sophie; Tastet, Lionel; Shen, Mylène; Clisson, Marine; Clavel, Marie-Annick

2017-07-07

About 50% of normal-flow/low-gradient patients (ie, low mean gradient [MG] or peak aortic jet velocity and small aortic valve area) have severe aortic valve calcification as measured by computed tomography. However, they are considered to have moderate aortic stenosis (AS) in current American College of Cardiology/American Heart Association guidelines. The objective was thus to evaluate the effect of hypertension and reduced arterial compliance (rAC) on MG and V peak measurements. Doppler-echocardiography was performed in 4 sheep with experimentally induced severe and critical AS at: (1) normal aortic pressure, (2) during hypertension, and (3) with rAC. Hypertension and rAC induced a substantial decrease in MG/V peak compared with normal stage (both P ≤0.03) despite a stable transvalvular flow ( P >0.16). Hypertension and rAC resulted in a greater reduction of MG in critical (-42%) compared with severe (-35%) AS ( P ˂0.0001). Comprehensive Doppler-echocardiography and computed tomography were performed in 220 AS patients (mean age: 69±13 years; MG 29±18 mm Hg) with normal flow. The population was divided in 3 groups according to the presence of hypertension and rAC. The slope of the linear association between MG/V peak and aortic valve calcification divided by the cross-sectional area of the aortic annulus was significantly reduced in patients with hypertension and/or rAC compared with normotensive/normal AC patients ( P <0.01). Accordingly, patients with normal-flow/low-gradient and severe aortic valve calcification density were more frequent in hypertension and rAC groups compared with the normotensive/normal-AC group (16% and 12% compared with 2%; P =0.03). Hypertension and rAC are associated with a substantial reduction in MG/V peak for similar aortic valve calcification (ie, similar AS anatomic severity), which may lead to underestimation of AS hemodynamic severity. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by

Denosumab could be a Potential Inhibitor of Valvular Interstitial Cells Calcification in vitro.

PubMed

Lerman, Daniel Alejandro; Prasad, Sai; Alotti, Nasri

2016-01-03

Denosumab is a fully human monoclonal antibody and novel antiresorptive agent that works by binding receptor activator of nuclear factor kappa-β ligand (RANKL) and inhibiting the signaling cascade that causes osteoclast maturation, activity, and survival. We aimed to elucidate the effect of Denosumab in the process of spontaneous and induced calcification in an in vitro porcine valvular interstitial cells (VICs) model. VICs were extracted from fresh porcine hearts by serial collagenase digestion. Spontaneous calcification of VICs was increased in vitro by adding Na 3 PO 4 (3 mM, pH 7.4) and different concentrations (0.1, 1 and 10 ng/ml) of transforming growth factor beta (TGFß). The degree of calcification before and after treatment with Denosumab was estimated by Alizarin Red staining for calcium deposition, and Sirius Red staining for collagen. Colorimetric techniques were used to determine calcium and collagen deposition quantitatively. For statistical analysis we used SPSS and Microsoft Office Excel 2013. Porcine aortic VICs in vitro were induced to calcify by the addition of either 3 mM Na 3 PO 4 , showing a 5.2 fold increase by 14 days (P<0.001), or 3 mM Na 3 PO 4 + 10 ng/ml of TGFβ, showing a 7 fold increase by Day 14 (P<0.001). Denosumab inhibited induced calcification by 3 mM Na 3 PO 4 and 3 mM Na 3 PO 4 with the addition of TGFß at either 0.1, 1 or 10 ng/ml to basal levels only at a concentration of 50 μg/ml (P<0.001). This study has proved that Denosumab could be a potential inhibitor of the calcification of VICs in vitro . A fuller understanding of the actions of Denosumab may identify a novel therapeutic strategy for clinical intervention against aortic valve calcification and aortic stenosis.

Aortic valve cell seeding into decellularized animal pericardium by perfusion-assisted bioreactor.

PubMed

Amadeo, Francesco; Boschetti, Federica; Polvani, Gianluca; Banfi, Cristina; Pesce, Maurizio; Santoro, Rosaria

2018-04-27

Animal-derived pericardium is the elective tissue employed in manufacturing heart valve prostheses. The preparation of this tissue for biological valve production consists of fixation with aldehydes, which reduces, but not eliminates, the xenoantigens and the donor cellular material. As a consequence, especially in patients below 65-70 years of age, the employment of valve substitutes contaning pericardium is not indicated due to progressive calcification that causes tissue degeneration and recurrence of valve insufficiency. Decellularization with ionic or nonionic detergents has been proposed as an alternative procedure to prepare aldehyde- or xenoantigen-free pericardium for biological valve manufacturing. In the present contribution, we optimized a decellularization procedure that is permissive for seeding and culturing valve competent cells able to colonize and reconstitute a valve-like tissue. A high-efficiency cellularization was achieved by forcing cell penetration inside the pericardium matrix using a perfusion bioreactor. Because the decellularization procedure was found not to alter the collagen composition of the pericardial matrix and cells seeded in the tissue constructs consistently grew and acquired the phenotype of "quiescent" valve interstitial cells, our investigation sets a novel standard in pericardium application for tissue engineering of "living" valve implants. Copyright © 2018 John Wiley & Sons, Ltd.

Totally biological composite aortic stentless valved conduit for aortic root replacement: 10-year experience

PubMed Central

2011-01-01

Objectives To retrospectively analyze the clinical outcome of a totally biological composite stentless aortic valved conduit (No-React® BioConduit) implanted using the Bentall procedure over ten years in a single centre. Methods Between 27/10/99 and 19/01/08, the No-React® BioConduit composite graft was implanted in 67 patients. Data on these patients were collected from the in-hospital database, from patient notes and from questionnaires. A cohort of patients had 2D-echocardiogram with an average of 4.3 ± 0.45 years post-operatively to evaluate valve function, calcification, and the diameter of the conduit. Results Implantation in 67 patients represented a follow-up of 371.3 patient-year. Males were 60% of the operated population, with a mean age of 67.9 ± 1.3 years (range 34.1-83.8 years), 21 of them below the age of 65. After a mean follow-up of 7.1 ± 0.3 years (range of 2.2-10.5 years), more than 50% of the survivors were in NYHA I/II and more than 60% of the survivors were angina-free (CCS 0). The overall 10-year survival following replacement of the aortic valve and root was 51%. During this period, 88% of patients were free from valved-conduit related complications leading to mortality. Post-operative echocardiography studies showed no evidence of stenosis, dilatation, calcification or thrombosis. Importantly, during the 10-year follow-up period no failures of the valved conduit were reported, suggesting that the tissue of the conduit does not structurally change (histology of one explant showed normal cusp and conduit). Conclusions The No-React® BioConduit composite stentless aortic valved conduit provides excellent long-term clinical results for aortic root replacement with few prosthesis-related complications in the first post-operative decade. PMID:21699696

Genetics in Arterial Calcification

PubMed Central

Rutsch, Frank; Nitschke, Yvonne; Terkeltaub, Robert

2011-01-01

Artery calcification reflects an admixture of factors such as ectopic osteochondral differentiation with primary host pathological conditions. We review how genetic factors, as identified by human genome-wide association studies, and incomplete correlations with various mouse studies, including knockout and strain analyses, fit into “pieces of the puzzle” in intimal calcification in human atherosclerosis, and artery tunica media calcification in aging, diabetes mellitus, and chronic kidney disease. We also describe in sharp contrast how ENPP1, CD73, and ABCC6 serve as “cogs in a wheel” of arterial calcification. Specifically, each is a minor component in the function of a much larger network of factors that exert balanced effects to promote and suppress arterial calcification. For the network to normally suppress spontaneous arterial calcification, the “cogs” ENPP1, CD73, and ABCC6 must be present and in working order. Monogenic ENPP1, CD73, and ABCC6 deficiencies each drive a molecular pathophysiology of closely related but phenotypically different diseases (generalized arterial calcification of infancy (GACI), pseudoxan-thoma elasticum (PXE) and arterial calcification caused by CD73 deficiency (ACDC)), in which premature onset arterial calcification is a prominent but not the sole feature. PMID:21852556

The Interpretation of Mg/Ca in Ostracode Valves: Biokinetic vs. Thermodynamic Controls

NASA Astrophysics Data System (ADS)

Dettman, D. L.; Palacios-Fest, M. R.; Cohen, A. S.

2004-12-01

The geochemistry of the calcite valves of ostracodes (a group of micro-crustacean) is often used to reconstruct the history of aqueous environments in both marine and fresh-water settings. These benthic animals can be very abundant in lakes and ponds and their low-Mg calcite valves are easily recovered from sediment cores. Many studies have used minor-element ratios (Mg/Ca and Sr/Ca) as indicators of temperature and/or salinity change through time and numerous calibration studies have been undertaken. There is considerable disagreement on the interpretation of both historical data and calibration studies because of differing views on what controls elemental ratios in ostracode valves. Here we focus on Mg/Ca ratios and critique the dominant assumption that Mg/Ca ratios in ostracode calcite are interpretable as a temperature-dependant distribution (or partition) coefficient. The use of a distribution coefficient, usually defined as a ratio of shell-to-water Mg/Ca ratios, assumes that the ratio in the water plays a significant role in the resultant ratio in the shell. Ostracode biomineralization is most commonly viewed as equivalent to inorganic precipitation of low-Mg calcite from solution, a system in which distribution coefficients are probably valid models. However, a re-examination of published studies shows that in many cases Mg/Ca(water) has no statistically demonstrable affect on the Mg/Ca ratio of ostracode valve calcite. The valve Mg/Ca ratio is most often a function of ambient temperature. In a number of studies the importance of the water's Mg/Ca ratio cannot be determined due to auto-correlation with other environmental factors. This implies that there is considerable biological control on the minor element chemistry of the ostracode valve. This is supported by a number of observations: valve calcification is rapid and initiated by the animal; Mg/Ca ratios within the valve vary greatly on a microscopic scale; the earliest carbonate formed during

Vitamin K2 inhibits rat vascular smooth muscle cell calcification by restoring the Gas6/Axl/Akt anti-apoptotic pathway.

PubMed

Qiu, Cuiting; Zheng, Haijun; Tao, Huiren; Yu, Wenjun; Jiang, Xiaoyu; Li, Aiqin; Jin, Hui; Lv, Anlin; Li, Huan

2017-09-01

Vascular calcification is associated with cardiovascular disease as a complication of hypertension, hyperlipidemia, diabetes mellitus, and chronic kidney disease. Vitamin K2 (VK2) delays vascular calcification by an unclear mechanism. Moreover, apoptosis modulates vascular smooth muscle cell (VSMC) calcification. This paper aimed to study VK2-modified VSMC calcification and survival cell signaling mediated by growth arrest-specific gene 6 (Gas6) and its tyrosine kinase receptor Axl. Primary-cultured VSMCs were dose-dependently treated with VK2 in the presence of calcification medium for 8 days, or pre-treated for 1 h with/without the Axl inhibitor R428 (2 μmol/L) or the caspase inhibitor Z-VAD-fmk (20 μmol/L) followed by treatment with VK2 (10 μmol/L) or rmGas6 (200 nmol/L) in calcification medium for 8 days. Calcium deposition was determined by the o-cresolphthalein complexone assay and Alizarin Red S staining. Apoptosis was determined by TUNEL and flow cytometry using Annexin V-FITC and propidium iodide staining. Western blotting detected the expressions of Axl, Gas6, p-Akt, Akt, and Bcl2. VK2 significantly inhibited CaCl 2 - and β-sodium glycerophosphate (β-GP)-induced VSMC calcification and apoptosis, which was dependent on restored Gas6 expression and activated downstream signaling by Axl, p-Akt, and Bcl2. Z-VAD-fmk significantly inhibited CaCl 2 - and β-GP-induced VSMC calcification and apoptosis. Augmented recombinant mouse Gas6 protein (rmGas6) expression significantly reduced VSMC calcification and apoptosis. Furthermore, the Gas6/Axl interaction was inhibited by R428, which abolished the preventive effect of VK2 on CaCl 2 - and β-GP-induced apoptosis and calcification. These results suggest that Gas6 is critical in VK2-mediated functions that attenuate CaCl 2 - and β-GP-induced VSMC calcification by blocking apoptosis.

Carotenoids Co-Localize with Hydroxyapatite, Cholesterol, and Other Lipids in Calcified Stenotic Aortic Valves. Ex Vivo Raman Maps Compared to Histological Patterns

PubMed Central

Bonetti, A.; Bonifacio, A.; Mora, A. Della; Livi, U.; Marchini, M.; Ortolani, F.

2015-01-01

Unlike its application for atherosclerotic plaque analysis, Raman microspectroscopy was sporadically used to check the sole nature of bioapatite deposits in stenotic aortic valves, neglecting the involvement of accumulated lipids/lipoproteins in the calcific process. Here, Raman microspectroscopy was employed for examination of stenotic aortic valve leaflets to add information on nature and distribution of accumulated lipids and their correlation with mineralization in the light of its potential precocious diagnostic use. Cryosections from surgically explanted stenotic aortic valves (n=4) were studied matching Raman maps against specific histological patterns. Raman maps revealed the presence of phospholipids/triglycerides and cholesterol, which showed spatial overlapping with one another and Raman-identified hydroxyapatite. Moreover, the Raman patterns correlated with those displayed by both von-Kossa-calcium- and Nile-blue-stained serial cryosections. Raman analysis also provided the first identification of carotenoids, which co-localized with the identified lipid moieties. Additional fit concerned the distribution of collagen and elastin. The good correlation of Raman maps with high-affinity staining patterns proved that Raman microspectroscopy is a reliable tool in evaluating calcification degree, alteration/displacement of extracellular matrix components, and accumulation rate of different lipid forms in calcified heart valves. In addition, the novel identification of carotenoids supports the concept that valve stenosis is an atherosclerosis-like valve lesion, consistently with their previous Raman microspectroscopical identification inside atherosclerotic plaques. PMID:26150160

Carotenoids co-localize with hydroxyapatite, cholesterol, and other lipids in calcified stenotic aortic valves. Ex vivo Raman maps compared to histological patterns.

PubMed

Bonetti, A; Bonifacio, A; Della Mora, A; Livi, U; Marchini, M; Ortolani, F

2015-04-20

Unlike its application for atherosclerotic plaque analysis, Raman microspectroscopy was sporadically used to check the sole nature of bioapatite deposits in stenotic aortic valves, neglecting the involvement of accumulated lipids/lipoproteins in the calcific process. Here, Raman microspectroscopy was employed for examination of stenotic aortic valve leaflets to add information on nature and distribution of accumulated lipids and their correlation with mineralization in the light of its potential precocious diagnostic use. Cryosections from surgically explanted stenotic aortic valves (n=4) were studied matching Raman maps against specific histological patterns. Raman maps revealed the presence of phospholipids/triglycerides and cholesterol, which showed spatial overlapping with one another and Raman-identified hydroxyapatite. Moreover, the Raman patterns correlated with those displayed by both von-Kossa-calcium- and Nile-blue-stained serial cryosections. Raman analysis also provided the first identification of carotenoids, which co-localized with the identified lipid moieties. Additional fit concerned the distribution of collagen and elastin. The good correlation of Raman maps with high-affinity staining patterns proved that Raman microspectroscopy is a reliable tool in evaluating calcification degree, alteration/displacement of extracellular matrix components, and accumulation rate of different lipid forms in calcified heart valves. In addition, the novel identification of carotenoids supports the concept that valve stenosis is an atherosclerosis-like valve lesion, consistently with their previous Raman microspectroscopical identification inside atherosclerotic plaques.

Valve Repair Is Superior to Replacement in Most Patients With Coexisting Degenerative Mitral Valve and Coronary Artery Diseases.

PubMed

Javadikasgari, Hoda; Gillinov, A Marc; Idrees, Jay J; Mihaljevic, Tomislav; Suri, Rakesh M; Raza, Sajjad; Houghtaling, Penny L; Svensson, Lars G; Navia, José L; Mick, Stephanie L; Desai, Milind Y; Sabik, Joseph F; Blackstone, Eugene H

2017-06-01

For mitral regurgitation (MR) from degenerative mitral disease in patients with coexisting coronary artery disease, the appropriate surgical strategy remains controversial. From 1985 to 2011, 1,071 adults (age 70 ± 9.3 years, 77% men) underwent combined coronary artery bypass grafting and either mitral valve repair (n = 872, 81%) or replacement (n=199, 19%) for degenerative MR. Propensity matching (177 patient pairs, 89% of possible matches) was used to compare early outcomes and time-related recurrence of MR after mitral valve repair, mitral valve reoperation, and mortality. Risk factors for death were identified with multivariable, multiphase hazard-function analysis. Patients undergoing valve replacement were older, with more valve calcification and a higher prevalence of preoperative atrial fibrillation and heart failure (all p < .0001). Among matched pairs, mitral replacement versus repair was associated with higher hospital mortality (5.0% vs 1.0%, p = .0001) and more postoperative renal failure (7.0% vs 3.2%, p = .01), reexplorations for bleeding (6.0% vs 3.1%, p = .05), and respiratory failure (14% vs 4.7%, p < .0001). Of matched patients undergoing repair, 18% had MR above 3+ by 5 years. Mitral valve durability was similar between matched groups, but survival at 15 years was 18% after replacement versus 52% after repair. Nomograms from the multivariable equation revealed that in 94% of cases, 10-year survival was calculated to be higher after repair than after replacement. In patients with coexisting degenerative mitral valve and coronary artery diseases, mitral valve repair is expected to confer a long-term survival advantage over replacement despite some recurrence of MR. When feasible, it is the procedure of choice for these patients. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Comparative hemodynamics in an aorta with bicuspid and trileaflet valves

NASA Astrophysics Data System (ADS)

Gilmanov, Anvar; Sotiropoulos, Fotis

2016-04-01

Bicuspid aortic valve (BAV) is a congenital heart defect that has been associated with serious aortopathies, such as aortic stenosis, aortic regurgitation, infective endocarditis, aortic dissection, calcific aortic valve and dilatation of ascending aorta. There are two main hypotheses to explain the increase prevalence of aortopathies in patients with BAV: the genetic and the hemodynamic. In this study, we seek to investigate the possible role of hemodynamic factors as causes of BAV-associated aortopathy. We employ the curvilinear immersed boundary method coupled with an efficient thin-shell finite-element formulation for tissues to carry out fluid-structure interaction simulations of a healthy trileaflet aortic valve (TAV) and a BAV placed in the same anatomic aorta. The computed results reveal major differences between the TAV and BAV flow patterns. These include: the dynamics of the aortic valve vortex ring formation and break up; the large-scale flow patterns in the ascending aorta; the shear stress magnitude, directions, and dynamics on the heart valve surfaces. The computed results are in qualitative agreement with in vivo magnetic resonance imaging data and suggest that the linkages between BAV aortopathy and hemodynamics deserve further investigation.

A unique case of "double-orifice aortic valve"-comprehensive assessment by 2-, 3-dimensional, and color Doppler echocardiography.

PubMed

Stirrup, James E; Cowburn, Peter J; Pousios, Dimitrios; Ohri, Sunil K; Shah, Benoy N

2016-09-01

Transesophageal echocardiography (TEE) is a powerful imaging tool for the comprehensive assessment of valvular structure and function. TEE may be of added benefit when anatomy is difficult to delineate accurately by transthoracic echocardiography. In this article, we present 2-, 3-dimensional, and color Doppler TEE images from a male patient with aortic stenosis. A highly unusual and complex pattern of valvular calcification created a functionally "double-orifice" valve. Such an abnormality may have implications for the accuracy of continuous-wave Doppler echocardiography, which assumes a single orifice valve in native aortic valves. © 2016, Wiley Periodicals, Inc.

The Double-Orifice Valve Technique to Treat Tricuspid Valve Incompetence.

PubMed

Hetzer, Roland; Javier, Mariano; Delmo Walter, Eva Maria

2016-01-01

reoperations for TV insufficiency or stenosis. Reoperations on three patients (mean age 42.5 ± 8.7 years) were indicated for aortic valve replacement at 14 months postoperatively (n = 1) and for assist device implantation (n = 2) who eventually underwent heart transplant at 18 and 20 months after TV repair, respectively. The cumulative 12-year survival rate was 86.9%. This double-orifice technique is technically a straightforward repair to abolish TV incompetence with highly satisfactory results, particularly in patients with severe annular dilatation or with leaflet and chordal tethering. In the present series, the technique provided no pitfalls (if the location of the conduction system was borne in mind), requiring only a gentle placement of sutures. It also led to no residual regurgitation or reoperation during the follow up period.

Biological Niches within Human Calcified Aortic Valves: Towards Understanding of the Pathological Biomineralization Process

PubMed Central

Cottignoli, Valentina; Agrosì, Giovanna; Familiari, Giuseppe; Salvador, Loris

2015-01-01

Despite recent advances, mineralization site, its microarchitecture, and composition in calcific heart valve remain poorly understood. A multiscale investigation, using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy dispersive X-ray spectrometry (EDS), from micrometre up to nanometre, was conducted on human severely calcified aortic and mitral valves, to provide new insights into calcification process. Our aim was to evaluate the spatial relationship existing between bioapatite crystals, their local growing microenvironment, and the presence of a hierarchical architecture. Here we detected the presence of bioapatite crystals in two different mineralization sites that suggest the action of two different growth processes: a pathological crystallization process that occurs in biological niches and is ascribed to a purely physicochemical process and a matrix-mediated mineralized process in which the extracellular matrix acts as the template for a site-directed nanocrystals nucleation. Different shapes of bioapatite crystallization were observed at micrometer scale in each microenvironment but at the nanoscale level crystals appear to be made up by the same subunits. PMID:26509159

Bicuspid aortic valve hemodynamics: a fluid-structure interaction study

NASA Astrophysics Data System (ADS)

Chandra, Santanu; Seaman, Clara; Sucosky, Philippe

2011-11-01

The bicuspid aortic valve (BAV) is a congenital defect in which the aortic valve forms with two leaflets instead of three. While calcific aortic valve disease (CAVD) also develops in the normal tricuspid aortic valve (TAV), its progression in the BAV is more rapid. Although studies have suggested a mechano-potential root for the disease, the native BAV hemodynamics remains largely unknown. This study aimed at characterizing BAV hemodynamics and quantifying the degree of wall-shear stress (WSS) abnormality on BAV leaflets. Fluid-structure interaction models validated with particle-image velocimetry were designed to predict the flow and leaflet dynamics in idealized TAV and BAV anatomies. Valvular function was quantified in terms of the effective orifice area. The regional leaflet WSS was characterized in terms of oscillatory shear index, temporal shear magnitude and temporal shear gradient. The predictions indicate the intrinsic degree of stenosis of the BAV anatomy, reveal drastic differences in shear stress magnitude and pulsatility on BAV and TAV leaflets and confirm the side- and site-specificity of the leaflet WSS. Given the ability of abnormal fluid shear stress to trigger valvular inflammation, these results support the existence of a mechano-etiology of CAVD in the BAV.

Transcatheter aortic valve-in-valve implantation for severe bioprosthetic stenosis after Bentall operation using a homograft in a patient with Behçet's disease.

PubMed

Joo, Hyung Joon; Hong, Soon Jun; Yu, Cheol Woong

2015-03-01

A 43-year-old man presented with severe aortic stenosis. Eight years previously, he had undergone primary surgical aortic valve replacement (AVR) for severe aortic regurgitation, but one year later developed cardiac arrest and complete atrioventricular block as a result of non-bacterial thrombotic endocarditis with severe valvular dehiscence. Following the diagnosis of prosthetic valve failure caused by Behçet's disease, the patient underwent a Bentall operation using 23 mm aortic homograft with permanent pacemaker implantation and coronary artery bypass grafting. Subsequently, he was stable with steroid administration and azathioprine for seven years after the second operation, but recently suffered from severe dyspnea and chest pain. Echocardiography revealed the development of severe aortic stenosis. A preprocedural evaluation demonstrated a porcelain aorta with severe calcification in the previous homograft valve on computed tomography, and critical stenosis at the ostium of the left circumflex artery on coronary angiography. After percutaneous coronary intervention for the ostium of the left circumflex artery, a transcatheter AVR was successfully performed using a 26 mm Edwards SAPIEN XT valve. The patient recovered without any complications after the procedure. This is the first report of a successful transcatheter aortic valve-in valve implantation for severe homograft aortic stenosis after a Bentall operation, using a homograft, in a patient with Behçet's disease.

Heart valve scaffold fabrication: Bioinspired control of macro-scale morphology, mechanics and micro-structure.

PubMed

D'Amore, Antonio; Luketich, Samuel K; Raffa, Giuseppe M; Olia, Salim; Menallo, Giorgio; Mazzola, Antonino; D'Accardi, Flavio; Grunberg, Tamir; Gu, Xinzhu; Pilato, Michele; Kameneva, Marina V; Badhwar, Vinay; Wagner, William R

2018-01-01

Valvular heart disease is currently treated with mechanical valves, which benefit from longevity, but are burdened by chronic anticoagulation therapy, or with bioprosthetic valves, which have reduced thromboembolic risk, but limited durability. Tissue engineered heart valves have been proposed to resolve these issues by implanting a scaffold that is replaced by endogenous growth, leaving autologous, functional leaflets that would putatively eliminate the need for anticoagulation and avoid calcification. Despite the diversity in fabrication strategies and encouraging results in large animal models, control over engineered valve structure-function remains at best partial. This study aimed to overcome these limitations by introducing double component deposition (DCD), an electrodeposition technique that employs multi-phase electrodes to dictate valve macro and microstructure and resultant function. Results in this report demonstrate the capacity of the DCD method to simultaneously control scaffold macro-scale morphology, mechanics and microstructure while producing fully assembled stent-less multi-leaflet valves composed of microscopic fibers. DCD engineered valve characterization included: leaflet thickness, biaxial properties, bending properties, and quantitative structural analysis of multi-photon and scanning electron micrographs. Quasi-static ex-vivo valve coaptation testing and dynamic organ level functional assessment in a pressure pulse duplicating device demonstrated appropriate acute valve functionality. Copyright © 2017. Published by Elsevier Ltd.

Relation of aortic valve calcium to chronic kidney disease (from the Chronic Renal Insufficiency Cohort Study).

PubMed

Guerraty, Marie A; Chai, Boyang; Hsu, Jesse Y; Ojo, Akinlolu O; Gao, Yanlin; Yang, Wei; Keane, Martin G; Budoff, Matthew J; Mohler, Emile R

2015-05-01

Although subjects with chronic kidney disease (CKD) are at markedly increased risk for cardiovascular mortality, the relation between CKD and aortic valve calcification has not been fully elucidated. Also, few data are available on the relation of aortic valve calcification and earlier stages of CKD. We sought to assess the relation of aortic valve calcium (AVC) with estimated glomerular filtration rate (eGFR), traditional and novel cardiovascular risk factors, and markers of bone metabolism in the Chronic Renal Insufficiency Cohort (CRIC) Study. All patients who underwent aortic valve scanning in the CRIC study were included. The relation between AVC and eGFR, traditional and novel cardiovascular risk factors, and markers of calcium metabolism were analyzed using both unadjusted and adjusted regression models. A total of 1,964 CRIC participants underwent computed tomography for AVC quantification. Decreased renal function was independently associated with increased levels of AVC (eGFR 47.11, 44.17, and 39 ml/min/1.73 m2, respectively, p<0.001). This association persisted after adjusting for traditional, but not novel, AVC risk factors. Adjusted regression models identified several traditional and novel risk factors for AVC in patients with CKD. There was a difference in AVC risk factors between black and nonblack patients. In conclusion, our study shows that eGFR is associated in a dose-dependent manner with AVC in patients with CKD, and this association is independent of traditional cardiovascular risk factors. Copyright © 2015 Elsevier Inc. All rights reserved.

Pineal Calcification Among Black Patients

PubMed Central

Fan, Kuang-Jaw

1983-01-01

A postmortem histopathological study was done in 233 pineal glands of black patients. Among them, 70 percent showed microscopic evidence of calcification in the pineal parenchyma. The frequency of calcification increased with age. However, the severity of calcification reached the peak in the 60 to 69 year old age group and then gradually declined. As compared to males, females had slightly higher frequency and reached the peak of severity in younger age groups. When pineal calcification was compared among patients with various malignancies, a higher frequency and more severe calcification were observed in patients with carcinoma of the prostate and the pancreas. A lower frequency and less severe calcification were observed in patients with carcinoma of the breast and the cervix. The results of this study emphasize the important role of sex hormone in genesis of pineal calcification. PMID:6631985

MALDI-Imaging Mass Spectrometry: a step forward in the anatomopathological characterization of stenotic aortic valve tissue.

PubMed

Mourino-Alvarez, Laura; Iloro, Ibon; de la Cuesta, Fernando; Azkargorta, Mikel; Sastre-Oliva, Tamara; Escobes, Iraide; Lopez-Almodovar, Luis F; Sanchez, Pedro L; Urreta, Harkaitz; Fernandez-Aviles, Francisco; Pinto, Angel; Padial, Luis R; Akerström, Finn; Elortza, Felix; Barderas, Maria G

2016-06-03

Aortic stenosis (AS) is the most common form of valve disease. Once symptoms develop, there is an inexorable deterioration with a poor prognosis; currently there are no therapies capable of modifying disease progression, and aortic valve replacement is the only available treatment. Our goal is to study the progression of calcification by matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS) and get new insights at molecular level that could help in the understanding of this disease. In this work, we analyzed consecutive slices from aortic valve tissue by MALDI-IMS, to establish the spatial distribution of proteins and peptides directly from the surface of the histological sections. The analysis showed different structures corresponding to regions observed in conventional histology, including large calcification areas and zones rich in collagen and elastic fibers. Peptide extraction from the tissue, followed by liquid chromatography mass spectrometry analysis, provided the identification of collagen VI α-3 and NDRG2 proteins which correlated with the masses obtained by MALDI-IMS and were confirmed by immunohistochemistry. These results highlighted the molecular mechanism implied in AS using MALDI-IMS, a novel technique never used before in this pathology. In addition, we can define specific regions proving a complementary resolution of the molecular histology.

Transapical aortic valve implantation – a rescue procedure for patients with aortic stenosis and “porcelain aorta”

PubMed Central

Czerwinska, Katarzyna; Orłowska-Baranowska, Ewa; Witkowski, Adam; Demkow, Marcin; Abramczuk, Elżbieta; Michałek, Piotr; Greszata, Lidia; Stoklosa, Patrycjusz; Kuśmierski, Krzysztof; Kowal, Jaroslaw; Stepinska, Janina

2011-01-01

Surgical aortic valve replacement (AVR) still remains the treatment of choice in symptomatic significant aortic stenosis (AS). Due to technical problems, extensive calcification of the ascending aorta (“porcelain aorta”) is an additional risk factor for surgery and transapical aortic valve implantation (TAAVI) is likely to be the only rescue procedure for this group of patients. We describe the case of an 81-year-old woman with severe AS and “porcelain aorta”, in whom the only available life-saving intervention was TAAVI. PMID:22295040

Automated coronary artery calcification detection on low-dose chest CT images

NASA Astrophysics Data System (ADS)

Xie, Yiting; Cham, Matthew D.; Henschke, Claudia; Yankelevitz, David; Reeves, Anthony P.

2014-03-01

Coronary artery calcification (CAC) measurement from low-dose CT images can be used to assess the risk of coronary artery disease. A fully automatic algorithm to detect and measure CAC from low-dose non-contrast, non-ECG-gated chest CT scans is presented. Based on the automatically detected CAC, the Agatston score (AS), mass score and volume score were computed. These were compared with scores obtained manually from standard-dose ECG-gated scans and low-dose un-gated scans of the same patient. The automatic algorithm segments the heart region based on other pre-segmented organs to provide a coronary region mask. The mitral valve and aortic valve calcification is identified and excluded. All remaining voxels greater than 180HU within the mask region are considered as CAC candidates. The heart segmentation algorithm was evaluated on 400 non-contrast cases with both low-dose and regular dose CT scans. By visual inspection, 371 (92.8%) of the segmentations were acceptable. The automated CAC detection algorithm was evaluated on 41 low-dose non-contrast CT scans. Manual markings were performed on both low-dose and standard-dose scans for these cases. Using linear regression, the correlation of the automatic AS with the standard-dose manual scores was 0.86; with the low-dose manual scores the correlation was 0.91. Standard risk categories were also computed. The automated method risk category agreed with manual markings of gated scans for 24 cases while 15 cases were 1 category off. For low-dose scans, the automatic method agreed with 33 cases while 7 cases were 1 category off.

Incremental prognostic value of cardiac computed tomography angiography in asymptomatic aortic stenosis: significance of aortic valve calcium score.

PubMed

Utsunomiya, Hiroto; Yamamoto, Hideya; Kitagawa, Toshiro; Kunita, Eiji; Urabe, Yoji; Tsushima, Hiroshi; Hidaka, Takayuki; Awai, Kazuo; Kihara, Yasuki

2013-10-15

Cardiac computed tomography angiography (CCTA) provides the simultaneous evaluation of the aortic valve, myocardium, and coronary arteries. In particular, aortic valve calcium score (AVCS) can be accurately measured on the same scanning sequence used to measure coronary artery calcification, with no additional cost or radiation exposure. We sought to evaluate the prognostic value of CCTA measures, including AVCS, in asymptomatic aortic stenosis (AS). Sixty-four initially asymptomatic patients with AS with a normal ejection fraction were prospectively enrolled and followed for median 29 (IQR=18-50) months. During follow-up, 27 (42%) patients experienced cardiac events, including five cardiac deaths, eleven aortic valve replacements. Multivariate Cox proportional hazards analysis identified three CCTA measures as significant predictors of cardiac events: aortic valve area (per 0.1cm(2) decrease; hazard ratio [HR]: 1.19, 95% confidence interval [CI]: 1.05-1.34); multi-vessel obstructive coronary artery disease (HR: 2.84, 95% CI: 1.10-7.32); and AVCS (per 100; HR: 1.09, 95% CI: 1.04-1.15). Kaplan-Meier analysis showed that patients with AVCS greater than or equal to the median value of 723 had significantly worse outcomes than those with AVCS less than 723 (p<0.0001). The C-statistic value for cardiac events substantially increased when these CCTA measures were added to clinical characteristics plus echocardiographic peak transaortic velocity (0.913 vs. 0.702, p<0.001). In patients with asymptomatic AS, CCTA measures of valve area, coronary stenosis, and calcification severity provide independent and incremental prognostic value after accounting for the echocardiographic severity of stenosis. © 2013.

Preoperative planning of left-sided valve surgery with 3D computed tomography reconstruction models: sternotomy or a minimally invasive approach?

PubMed

Heuts, Samuel; Maessen, Jos G; Sardari Nia, Peyman

2016-05-01

With the emergence of a new concept aimed at individualization of patient care, the focus will shift from whether a minimally invasive procedure is better than conventional treatment, to the question of which patients will benefit most from which technique? The superiority of minimally invasive valve surgery (MIVS) has not yet been proved. We believe that through better patient selection advantages of this technique can become more pronounced. In our current study, we evaluate the feasibility of 3D computed tomography (CT) imaging reconstruction in the preoperative planning of patients referred for MIVS. We retrospectively analysed all consecutive patients who were referred for minimally invasive mitral valve surgery (MIMVS) and minimally invasive aortic valve replacement (MIAVR) to a single surgeon in a tertiary referral centre for MIVS between March 2014 and 2015. Prospective preoperative planning was done for all patients and was based on evaluations by a multidisciplinary heart-team, an echocardiography, conventional CT images and 3D CT reconstruction models. A total of 39 patients were included in our study; 16 for mitral valve surgery (MVS) and 23 patients for aortic valve replacement (AVR). Eleven patients (69%) within the MVS group underwent MIMVS. Five patients (31%) underwent conventional MVS. Findings leading to exclusion for MIMVS were a tortuous or slender femoro-iliac tract, calcification of the aortic bifurcation, aortic elongation and pericardial calcifications. Furthermore, 2 patients had a change of operative strategy based on preoperative planning. Seventeen (74%) patients in the AVR group underwent MIAVR. Six patients (26%) underwent conventional AVR. Indications for conventional AVR instead of MIAVR were an elongated ascending aorta, ascending aortic calcification and ascending aortic dilatation. One patient (6%) in the MIAVR group was converted to a sternotomy due to excessive intraoperative bleeding. Two mortalities were reported during

Aortic valve calcification as a predictor of location and severity of paravalvular regurgitation after transcatheter aortic valve implantation.

PubMed

Koh, Ezra Y; Lam, Kayan Y; Bindraban, Navin R; Cocchieri, Riccardo; Planken, R Nils; Koch, Karel T; Baan, Jan; de Mol, Bas A; Marquering, Henk A

2015-03-01

To determine whether the location of aortic valve calcium (AVC) influences the location of paravalvular regurgitation (PR). PR is an adverse effect of transcatheter aortic valve implantation (TAVI) with a negative effect on long-term patient survival. The relationship between AVC and the occurrence of PR has been documented. However, the relationship between the distribution of AVC and the location of PR is still sparsely studied. The purpose of this study was to correlate severity and location of AVC with PR in patients treated with TAVI. Fifty-six consecutive patients who underwent transaortic or transapical TAVI and had preoperative computed tomography scans were included in this retrospective study. The volume, mass and location of AVC was determined and compared between patients with and without PR using a non-parametric t-test. Postoperative echocardiography was performed to determine the presence and location of PR, which was associated with the cusp with highest AVC using a χ(2) test. Valve deployment was successful in all 56 patients. PR was present in 38 patients (68%) after TAVI. There was a non-significantly higher volume of AVC in the PR group [214 (70-418) vs 371 (254-606) cm(3), P = 0.15]. AVC mass was significantly higher in patients with PR than in patients without PR [282 (188-421) vs 142 (48-259) mg, respectively, P = 0.043]. The location of PR was determined in 36 of these patients. Of these 36 patients, PR occurred at the cusp with the highest AVC in 20 patients (56%, χ(2) P = 0.030). In our population, PR was associated with greater AVC mass. Moreover, the location of PR was associated with the cusp with the highest amount of AVC. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Measurement of aortic valve calcification using multislice computed tomography: correlation with haemodynamic severity of aortic stenosis and clinical implication for patients with low ejection fraction.

PubMed

Cueff, Caroline; Serfaty, Jean-Michel; Cimadevilla, Claire; Laissy, Jean-Pierre; Himbert, Dominique; Tubach, Florence; Duval, Xavier; Iung, Bernard; Enriquez-Sarano, Maurice; Vahanian, Alec; Messika-Zeitoun, David

2011-05-01

Measurement of the degree of aortic valve calcification (AVC) using electron beam computed tomography (EBCT) is an accurate and complementary method to transthoracic echocardiography (TTE) for assessment of the severity of aortic stenosis (AS). Whether threshold values of AVC obtained with EBCT could be extrapolated to multislice computed tomography (MSCT) was unclear and AVC diagnostic value in patients with low ejection fraction (EF) has never been specifically evaluated. Patients with mild to severe AS underwent prospectively within 1 week MSCT and TTE. Severe AS was defined as an aortic valve area (AVA) of less than 1 cm(2). In 179 patients with EF greater than 40% (validation set), the relationship between AVC and AVA was evaluated. The best threshold of AVC for the diagnosis of severe AS was then evaluated in a second subset (testing set) of 49 patients with low EF (≤40%). In this subgroup, AS severity was defined based on mean gradient, natural history or dobutamine stress echocardiography. Correlation between AVC and AVA was good (r=-0.63, p<0.0001). A threshold of 1651 arbitrary units (AU) provided 82% sensitivity, 80% specificity, 88% negative-predictive value and 70% positive-predictive value. In the testing set (patients with low EF), this threshold correctly differentiated patients with severe AS from non-severe AS in all but three cases. These three patients had an AVC score close to the threshold (1206, 1436 and 1797 AU). In this large series of patients with a wide range of AS, AVC was shown to be well correlated to AVA and may be a useful adjunct for the evaluation of AS severity especially in difficult cases such as patients with low EF.

The influence of aortic valve calcification on the risk of periprocedural myocardial injury after elective coronary intervention.

PubMed

Chen, Zhang-Wei; Yang, Hong-Bo; Chen, Ying-Hua; Qian, Ju-Ying; Shu, Xian-Hong; Ge, Jun-Bo

2015-10-01

Aortic valve calcification (AVC) is a common progressive condition that involves several inflammatory and atherosclerotic mediators. However, it is unclear whether the occurrence of periprocedural myocardial injury (PMI) after elective coronary intervention is associated with AVC in stable coronary artery disease (CAD) patients. A total of 530 stable CAD patients who underwent elective coronary intervention were enrolled in this clinical study. High sensitive cardiac troponin T (hs-cTnT) was detected before and after the procedure. PMI was defined as hs-cTnT after coronary intervention higher than 99th percentile upper reference limit (URL). All patients underwent echocardiography to detect the occurrence of AVC. Univariate and multivariate analyses were applied to analyze risk factors of PMI. A total of 210 patients (39.6 %) were diagnosed with PMI after elective coronary intervention. Compared with non-AVC patients (n = 386), AVC patients (n = 144) had higher rate of PMI (64.6 vs. 30.3 %, P < 0.01). CAD patients with AVC had higher Gensini score (39.9 ± 26.6 vs. 34.2 ± 22.1, P < 0.05) and more number of implanted stents (1.7 ± 0.8 vs. 1.5 ± 0.7, P < 0.05). After stratification by classic risk factors of CAD (such as age, male gender and diabetes) in subgroup analyses, we found that AVC patients had increased risk of PMI compared with non-AVC patients. Importantly, even after being adjusted by multivariate analysis, AVC still independently increased the risk of PMI (OR = 3.329, 95 % CI = 2.087-5.308, P < 0.01). AVC significantly increased the risk of PMI after elective coronary intervention. It could be one of the independent predictors for PMI in stable CAD patients.

CorMatrix valved conduit in a porcine model: long-term remodelling and biomechanical characterization.

PubMed

Mosala Nezhad, Zahra; Poncelet, Alain; de Kerchove, Laurent; Fervaille, Caroline; Banse, Xavier; Bollen, Xavier; Dehoux, Jean-Paul; El Khoury, Gebrine; Gianello, Pierre

2017-01-01

Porcine small intestinal submucosa extracellular matrix (CorMatrix; CorMatrix Cardiovascular, Rosewell, GA) is a relatively novel tissue substitute used in cardiovascular applications. We investigated the biological reaction and remodelling of CorMatrix as a tri-leaflet valved conduit in a pig model. We hypothesized that CorMatrix maintains a durable architecture as a valved conduit and remodels to resemble surrounding tissues. We fashioned the valved conduit using a 7 × 10 cm 4-ply CorMatrix sheet and placed it in the thoracic aorta of seven landrace pigs for 3, 4, 5 and 6 months. Biodegradation, replacement by native tissue, strength and durability were examined by histology, immunohistochemistry and mechanical testing. Four pigs, one per time frame, completed the study. The conduit lost its original architecture as a tri-leaflet valve due to cusp immobility, subsequent attachment to the wall segment and consequent maintenance of a thick arterial wall-like structure. Scaffold resorption was incomplete, with disorganized inconsistent spatial and temporal degradation even at 6 months. Fibrosis, scarring and calcification started at 4 months and chronic inflammation persisted. The partially remodelled scaffold did not resemble the aortic wall, suggesting impaired remodelling. Mechanical testing showed progressive weakening of the tissues over time, which were liable to breakage. CorMatrix is biodegradable; however, it failed to remodel in a structured and anatomical fashion in an arterial environment. Progressive mechanical and remodelling failure in this scenario might be explained by the complexity of the conduit design and the host's chronic inflammatory response, leading to early fibrosis and calcification. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Dialysis Amyloid Deposition in the Aortic Valve and Its Association with Aortic Stenosis.

PubMed

Kurita, Noriaki; Fujii, Akiko; Kotera, Nagaaki; Tanaka, Mototsugu; Tanaka, Shinji; Miyairi, Takeshi; Sugimoto, Tokuichiro; Mori, Masaya; Fukuhara, Shunichi; Mise, Naobumi

2015-01-01

The relationship between dialysis amyloid (DA) deposition in the aortic valve (AV) and aortic stenosis (AS) is unknown. This was a cross-sectional study. AV specimens of dialysis patients (median vintage: 8.8 years) consecutively collected from cardiac surgeries (n = 56) or autopsies (n = 13) were examined by a board-certified pathologist blinded to clinical data. DAs were considered to be present if deposits were stained both by Congo red with apple-green birefringence under polarized light and by anti-β2-microblobulin antibody. Degree of deposition was graded as follows: Amyloid (-), no deposit; Amyloid (1+), occasional small deposits; Amyloid (2+), multiple small to large deposits or a single large deposit. Calcification was defined as a calcified deposit with a diameter >1 mm in the specimen. Severe AS (sAS) was defined as a mean gradient >50 mm Hg by echocardiogram. We examined the proportion of DAs and the association between DAs and the sAS. DAs were present in 71% (n = 49) of specimens and primarily co-localized with calcification. Non-dialysis related amyloid was found in one specimen. After excluding this specimen, sAS was associated with ‘Amyloid (1+) and Calcification >1 mm' and ‘Amyloid (2+) and Calcification >1 mm' (vs. ‘Amyloid (-) and Calcification ≤1 mm', odds ratios (ORs): 13.5 and 34.2, respectively). Furthermore, after adjustment for covariates, sAS was found to be associated with ‘Amyloid (2+) and Calcification >1 mm' (OR: 24.3). DA deposition in the AV was prevalent among dialysis patients. DA deposition with accompanying calcification might contribute to the severity of AS.

CD133 antibody conjugation to decellularized human heart valves intended for circulating cell capture.

PubMed

Vossler, John D; Min Ju, Young; Williams, J Koudy; Goldstein, Steven; Hamlin, James; Lee, Sang Jin; Yoo, James J; Atala, Anthony

2015-09-03

The long term efficacy of tissue based heart valve grafts may be limited by progressive degeneration characterized by immune mediated inflammation and calcification. To avoid this degeneration, decellularized heart valves with functionalized surfaces capable of rapid in vivo endothelialization have been developed. The aim of this study is to examine the capacity of CD133 antibody-conjugated valve tissue to capture circulating endothelial progenitor cells (EPCs). Decellularized human pulmonary valve tissue was conjugated with CD133 antibody at varying concentrations and exposed to CD133 expressing NTERA-2 cl.D1 (NT2) cells in a microflow chamber. The amount of CD133 antibody conjugated on the valve tissue surface and the number of NT2 cells captured in the presence of shear stress was measured. Both the amount of CD133 antibody conjugated to the valve leaflet surface and the number of adherent NT2 cells increased as the concentration of CD133 antibody present in the surface immobilization procedure increased. The data presented in this study support the hypothesis that the rate of CD133(+) cell adhesion in the presence of shear stress to decellularized heart valve tissue functionalized by CD133 antibody conjugation increases as the quantity of CD133 antibody conjugated to the tissue surface increases.

Novel self-expandable, stent-based transcatheter pulmonic valve: a preclinical animal study.

PubMed

Kim, Gi Beom; Lim, Hong-Gook; Kim, Yong Jin; Choi, Eun Young; Kwon, Bo Sang; Jeong, Saeromi

2014-04-15

Because transcatheter implantation of pulmonary valve is indicated for limited-size dysfunctional right ventricular outflow tract only as a balloon-expandable stent, we investigated the feasibility of a large-diameter self-expandable valved stent and the durability of the valve after >6 months. We made a nitinol-wire-based, self-expandable valved stent with leaflets made from porcine pericardium. The porcine pericardium was treated with α-galactosidase, glutaraldehyde, and glycine after decellularization. After cutting the inguinal or cervical area, we implanted a valved stent in 12 sheep through the femoral or jugular vein by using an 18-Fr delivery catheter, controlling the catheter handles and hook block under fluoroscopic and echocardiographic guidance. The mean body weight of sheep was 43.9 kg. We successfully implanted valved stents (diameter: 24 mm in 7 sheep, 26 mm in 5 sheep) in good position in 8 sheep, in the main pulmonary artery (PA) in 2 sheep, and in the right ventricular outlet tract (RVOT) in 2 sheep. We sacrificed 8 sheep (6 sheep in good position, 1 sheep in the main PA, and 1 sheep in the RVOT) after >6 months. Five of the 6 sheep implanted in good position showed well-preserved valve morphology at the time of sacrifice. Histologic findings after routine sacrifice showed well-maintained collagen wave structure and no visible calcification in all explanted valve leaflets. Transcatheter implantation of a nitinol-wire-based, self-expandable valved stent in the pulmonic valve was feasible, and stents implanted in good position showed well-preserved valve leaflets with functional competence in the mid-term results. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Exogenous BMP7 in aortae of rats with chronic uremia ameliorates expression of profibrotic genes, but does not reverse established vascular calcification

PubMed Central

Gravesen, Eva; Lerche Mace, Maria; Nordholm, Anders; Hofman-Bang, Jacob; Hruska, Keith; Haagen Nielsen, Carsten; Kjær, Andreas; Olgaard, Klaus

2018-01-01

results highlight the importance of preventing the development of vascular calcification in chronic kidney disease. Once established, vascular calcification persists even in the setting when hyperphosphatemia or the uremic milieu is abolished. PMID:29304096

Relation of Aortic Valve Calcium to Chronic Kidney Disease (from the Chronic Renal Insufficiency Cohort [CRIC] Study)

PubMed Central

Guerraty, Marie A.; Chai, Boyang; Hsu, Jesse Yenchih; Ojo, Akinlolu O.; Gao, Yanlin; Yang, Wei; Keane, Martin G.; Budoff, Matthew J.; Mohler, Emile R.

2015-01-01

Although subjects with chronic kidney disease (CKD) are at markedly increased risk for cardiovascular mortality, the relationship between CKD and aortic valve calcification has not been fully elucidated. Also, few data are available on the relationship of aortic valve calcification and earlier stages of CKD. We sought to assess the relationship of aortic valve calcium (AVC) with estimated glomerular filtration rate (eGFR), traditional and novel cardiovascular risk factors, and markers of bone metabolism in the Chronic Renal Insufficiency Cohort (CRIC) Study. All patients who underwent aortic valve scanning in the CRIC study were included. The relationship between AVC and eGFR, traditional and novel cardiovascular risk factors, and markers of calcium metabolism were analyzed using both unadjusted and adjusted regression models. A total of 1964 CRIC participants underwent computed tomography for AVC quantification. Decreased renal function was independently associated with increased levels of AVC (eGFR 47.11 ml/min/1.73m2, 44.17 ml/min/1.73m2, and 39 ml/min/1.73m2, respectively, p< 0.001). This association persisted after adjusting for traditional, but not novel, AVC risk factors. Adjusted regression models identified several traditional and novel risk factors for AVC in patients with CKD. There was a difference in AVC risk factors between black and non-black patients. In conclusion, our study shows that eGFR is associated in a dose-dependent manner with AVC in patients with CKD, and this association is independent of traditional cardiovascular risk factors. PMID:25791240

Long-Term Results of Mitral Valve Repair

PubMed Central

da Costa, Francisco Diniz Affonso; Colatusso, Daniele de Fátima Fornazari; Martin, Gustavo Luis do Santos; Parra, Kallyne Carolina Silva; Botta, Mariana Cozer; Balbi Filho, Eduardo Mendel; Veloso, Myrian; Miotto, Gabriela; Ferreira, Andreia Dumsch de Aragon; Colatusso, Claudinei

2018-01-01

Introduction Current guidelines state that patients with severe mitral regurgitation should be treated in reference centers with a high reparability rate, low mortality rate, and durable results. Objective To analyze our global experience with the treatment of organic mitral regurgitation from various etiologies operated in a single center. Methods We evaluated all surgically treated patients with organic mitral regurgitation from 2004-2017. Patients were evaluated clinically and by echocardiography every year. We determined early and late survival rates, valve related events and freedom from recurrent mitral regurgitation and tricuspid regurgitation. Valve failure was defined as any mitral regurgitation ≥ moderate degree or the need for reoperation for any reason. Results Out of 133 patients with organic mitral regurgitation, 125 (93.9%) were submitted to valve repair. Mean age was 57±15 years and 52 patients were males. The most common etiologies were degenerative disease (73 patients) and rheumatic disease (34 patients). Early mortality was 2.4% and late survival was 84.3% at 10 years, which are similar to the age- and gender-matched general population. Only two patients developed severe mitral regurgitation, and both were reoperated (95.6% at 10 years). Freedom from mitral valve failure was 84.5% at 10 years, with no difference between degenerative and rheumatic valves. Overall, late ≥ moderate tricuspid regurgitation was present in 34% of the patients, being more common in the rheumatic ones. The use of tricuspid annuloplasty abolished this complication. Conclusion We have demonstrated that mitral regurgitation due to organic mitral valve disease from various etiologies can be surgically treated with a high repair rate, low early mortality and long-term survival that are comparable to the matched general population. Concomitant treatment of atrial fibrillation and tricuspid valve may be important adjuncts to optimize long-term results. PMID:29617498

Transcatheter aortic valve implantation using anatomically oriented, marrow stromal cell-based, stented, tissue-engineered heart valves: technical considerations and implications for translational cell-based heart valve concepts.

PubMed

Emmert, Maximilian Y; Weber, Benedikt; Behr, Luc; Sammut, Sebastien; Frauenfelder, Thomas; Wolint, Petra; Scherman, Jacques; Bettex, Dominique; Grünenfelder, Jürg; Falk, Volkmar; Hoerstrup, Simon P

2014-01-01

While transcatheter aortic valve implantation (TAVI) has rapidly evolved for the treatment of aortic valve disease, the currently used bioprostheses are prone to continuous calcific degeneration. Thus, autologous, cell-based, living, tissue-engineered heart valves (TEHVs) with regeneration potential have been suggested to overcome these limitations. We investigate the technical feasibility of combining the concept of TEHV with transapical implantation technology using a state-of-the-art transcatheter delivery system facilitating the exact anatomical position in the systemic circulation. Trileaflet TEHVs fabricated from biodegradable synthetic scaffolds were sewn onto self-expanding Nitinol stents seeded with autologous marrow stromal cells, crimped and transapically delivered into the orthotopic aortic valve position of adult sheep (n = 4) using the JenaValve transapical TAVI System (JenaValve, Munich, Germany). Delivery, positioning and functionality were assessed by angiography and echocardiography before the TEHV underwent post-mortem gross examination. For three-dimensional reconstruction of the stent position of the anatomically oriented system, a computed tomography analysis was performed post-mortem. Anatomically oriented, transapical delivery of marrow stromal cell-based TEHV into the orthotopic aortic valve position was successful in all animals (n = 4), with a duration from cell harvest to TEHV implantation of 101 ± 6 min. Fluoroscopy and echocardiography displayed sufficient positioning, thereby entirely excluding the native leaflets. There were no signs of coronary obstruction. All TEHV tolerated the loading pressure of the systemic circulation and no acute ruptures occurred. Animals displayed intact and mobile leaflets with an adequate functionality. The mean transvalvular gradient was 7.8 ± 0.9 mmHg, and the mean effective orifice area was 1.73 ± 0.02 cm(2). Paravalvular leakage was present in two animals, and central aortic regurgitation due to a

Acute Renal Infarction Secondary to Calcific Embolus from Mitral Annular Calcification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bande, Dinesh; Abbara, Suhny; Kalva, Sanjeeva P., E-mail: skalva@partners.org

2011-06-15

We report a case of a 62-year-old man who presented with right groin pain who subsequently was found to have a renal infarct secondary to calcific embolus from mitral annular calcification on CT and angiography. We briefly review the literature and discuss the importance of this entity in clinical practice.

Comparison of tricuspid and bicuspid aortic valve hemodynamics under steady flow conditions

NASA Astrophysics Data System (ADS)

Seaman, Clara; Ward, James; Sucosky, Philippe

2011-11-01

The bicuspid aortic valve (BAV), a congenital valvular defect consisting of two leaflets instead of three, is associated with a high prevalence of calcific aortic valve disease (CAVD). CAVD also develops in the normal tricuspid aortic valve (TAV) but its progression in the BAV is more severe and rapid. Although hemodynamic abnormalities are increasingly considered potential pathogenic contributor, the native BAV hemodynamics remain largely unknown. Therefore, this study aims at comparing experimentally the hemodynamic environments in TAV and BAV anatomies. Particle-image velocimetry was used to characterize the flow downstream of a native TAV and a model BAV mounted in a left-heart simulator and subjected to three steady flow rates characterizing different phases of the cardiac cycle. While the TAV developed a jet aligned along the valve axis, the BAV was shown to develop a skewed systolic jet with skewness decreasing with increasing flow rate. Measurement of the transvalvular pressure revealed a valvular resistance up to 50% larger in the BAV than in the TAV. The increase in velocity between the TAV and BAV leads to an increase in shear stress downstream of the valve. This study reveals strong hemodynamic abnormalities in the BAV, which may contribute to CAVD pathogenesis.

Acute Calcific Bursitis After Ultrasound-Guided Percutaneous Barbotage of Rotator Cuff Calcific Tendinopathy: A Case Report.

PubMed

Kang, Bo-Sung; Lee, Seung Hak; Cho, Yung; Chung, Sun Gun

2016-08-01

Ultrasound-guided percutaneous barbotage is an effective treatment for rotator cuff calcific tendinopathy, providing rapid and substantial pain relief. We present the case of a 49-year-old woman with aggravated pain early after ultrasound-guided barbotage of a large calcific deposit in the supraspinatus tendon. Subsequent examination revealed a thick calcification spreading along the subacromial-subdeltoid bursa space, suggesting acute calcific bursitis complicated by barbotage. Additional barbotage alleviated her pain completely. Therefore, a high index of suspicion for acute calcific bursitis is required in patients with unresolved or aggravated pain after barbotage. Repeated barbotage could be effective for this condition. Copyright © 2016 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Relationship of aortic annular eccentricity and paravalvular regurgitation post transcatheter aortic valve implantation with CoreValve.

PubMed

Wong, Dennis T L; Bertaso, Angela G; Liew, Gary Y H; Thomson, Viji S; Cunnington, Michael S; Richardson, James D; Gooley, Robert; Lockwood, Siobhan; Meredith, Ian T; Worthley, Matthew I; Worthley, Stephen G

2013-04-01

Significant paravalvular aortic regurgitation (PAR) after transcatheter aortic valve implantation (TAVI) is associated with negative clinical consequences. We hypothesize that increased eccentricity of the aortic annulus is associated with greater PAR. Patients with severe aortic stenosis underwent multidetector computed tomography (MDCT) before successful TAVI with the Medtronic CoreValve bioprosthesis. The smallest (D(min)) and largest (D(max)) orthogonal diameters in the basal ring of the aortic annulus were determined. We defined circularity of aortic annulus using the eccentricity index (1 - D(min)/D(max)). The primary endpoint was early occurrence of significant PAR, defined as > grade II PAR by postprocedural aortography. Eighty-four patients, mean age 83 ± 4 years with a mean aortic valve area of 0.7 ± 0.2 cm² were included. Twenty patients had postprocedural PAR > grade II. Using a receiver operating characteristic (ROC) analysis, eccentricity index correlated with significant PAR (AUC = 0.834; P=.034). A retrospectively determined eccentricity index cut-off of >0.25 was related to significant PAR with a sensitivity of 80%, specificity of 86%, and negative predictive value of 95% (P<.001). On univariate logistic regression, eccentricity index of >0.25 (P<.001) and device implantation depth (P=.015) correlated with significant PAR, while other parameters such as annular calcification and cover index did not. On multivariate analysis including only parameters with P<.1 on univariate analysis, eccentricity index >0.25 was the sole independent predictor of significant PAR. Eccentricity index is related to significant PAR after TAVI with Medtronic CoreValve. Further larger studies are required to determine the utility of this novel index in screening suitable patients for this procedure.

Cardiovascular Event Prediction and Risk Reclassification by Coronary, Aortic, and Valvular Calcification in the Framingham Heart Study.

PubMed

Hoffmann, Udo; Massaro, Joseph M; D'Agostino, Ralph B; Kathiresan, Sekar; Fox, Caroline S; O'Donnell, Christopher J

2016-02-22

We determined whether vascular and valvular calcification predicted incident major coronary heart disease, cardiovascular disease (CVD), and all-cause mortality independent of Framingham risk factors in the community-based Framingham Heart Study. Coronary artery calcium (CAC), thoracic and abdominal aortic calcium, and mitral or aortic valve calcium were measured by cardiac computed tomography in participants free of CVD. Participants were followed for a median of 8 years. Multivariate Cox proportional hazards models were used to determine association of CAC, thoracic and abdominal aortic calcium, and mitral and aortic valve calcium with end points. Improvement in discrimination beyond risk factors was tested via the C-statistic and net reclassification index. In this cohort of 3486 participants (mean age 50±10 years; 51% female), CAC was most strongly associated with major coronary heart disease, followed by major CVD, and all-cause mortality independent of Framingham risk factors. Among noncoronary calcifications, mitral valve calcium was associated with major CVD and all-cause mortality independent of Framingham risk factors and CAC. CAC significantly improved discriminatory value beyond risk factors for coronary heart disease (area under the curve 0.78-0.82; net reclassification index 32%, 95% CI 11-53) but not for CVD. CAC accurately reclassified 85% of the 261 patients who were at intermediate (5-10%) 10-year risk for coronary heart disease based on Framingham risk factors to either low risk (n=172; no events observed) or high risk (n=53; observed event rate 8%). CAC improves discrimination and risk reclassification for major coronary heart disease and CVD beyond risk factors in asymptomatic community-dwelling persons and accurately reclassifies two-thirds of the intermediate-risk population. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Hemodynamics in an Aorta with Bicuspid and Trileaflet Valves

NASA Astrophysics Data System (ADS)

Gilmanov, Anvar; Sotiropoulos, Fotis

2015-11-01

Bicuspid aortic valve (BAV) is a congenital heart defect that has been associated with serious aortopathies, such as ascending aortic aneurysm, aortic stenosis, aortic regurgitation, infective endocarditis, aortic dissection, calcific aortic valve and dilatation of ascending aorta. Two main hypotheses - the genetic and the hemodynamic are discussed in literature to explain the development and progression of aortopathies in patients with BAV. In this study we seek to investigate the possible role of hemodynamic factors as causes of BAV-associated aortopathy. We employ the Curvilinear Immersed Boundary (CURVIB) method coupled with an efficient thin-shell finite element (TS-FE) formulation for tissues to carry out fluid-structure interaction simulations of a healthy tri-leaflet aortic valve (TAV) and a BAV placed in the same anatomic aorta. The computed results reveal major differences between the TAV and BAV flow patterns. These include: the dynamics of the aortic valve vortex ring formation and break up; the large scale flow patterns in the ascending aorta; and the shear stress magnitude on the aortic wall. The computed results are in qualitative agreement with in vivo Magnetic Resonance Imaging (MRI) data and suggest that the linkages between BAV aortopathy and hemodynamics deserve further investigation. This work is supported by the Lillehei Heart Institute at the University of Minnesota and the Minnesota Supercomputing Institute.

Improvement of aortic valve stenosis by ApoA-I mimetic therapy is associated with decreased aortic root and valve remodelling in mice

PubMed Central

Trapeaux, J; Busseuil, D; Shi, Y; Nobari, S; Shustik, D; Mecteau, M; El-Hamamsy, I; Lebel, M; Mongrain, R; Rhéaume, E; Tardif, J-C

2013-01-01

Background and Purpose We have shown that infusions of apolipoprotein A-I (ApoA-I) mimetic peptide induced regression of aortic valve stenosis (AVS) in rabbits. This study aimed at determining the effects of ApoA-I mimetic therapy in mice with calcific or fibrotic AVS. Experimental Approach Apolipoprotein E-deficient (ApoE−/−) mice and mice with Werner progeria gene deletion (WrnΔhel/Δhel) received high-fat diets for 20 weeks. After developing AVS, mice were randomized to receive saline (placebo group) or ApoA-I mimetic peptide infusions (ApoA-I treated groups, 100 mg·kg−1 for ApoE−/− mice; 50 mg·kg−1 for Wrn mice), three times per week for 4 weeks. We evaluated effects on AVS using serial echocardiograms and valve histology. Key Results Aortic valve area (AVA) increased in both ApoE−/− and Wrn mice treated with the ApoA-I mimetic compared with placebo. Maximal sinus wall thickness was lower in ApoA-I treated ApoE−/− mice. The type I/III collagen ratio was lower in the sinus wall of ApoA-I treated ApoE−/− mice compared with placebo. Total collagen content was reduced in aortic valves of ApoA-I treated Wrn mice. Our 3D computer model and numerical simulations confirmed that the reduction in aortic root wall thickness resulted in improved AVA. Conclusions and Implications ApoA-I mimetic treatment reduced AVS by decreasing remodelling and fibrosis of the aortic root and valve in mice. PMID:23638718

Brain calcifications and PCDH12 variants

PubMed Central

Nicolas, Gaël; Sanchez-Contreras, Monica; Ramos, Eliana Marisa; Lemos, Roberta R.; Ferreira, Joana; Moura, Denis; Sobrido, Maria J.; Richard, Anne-Claire; Lopez, Alma Rosa; Legati, Andrea; Deleuze, Jean-François; Boland, Anne; Quenez, Olivier; Krystkowiak, Pierre; Favrole, Pascal; Geschwind, Daniel H.; Aran, Adi; Segel, Reeval; Levy-Lahad, Ephrat; Dickson, Dennis W.; Coppola, Giovanni; Rademakers, Rosa

2017-01-01

Objective: To assess the potential connection between PCDH12 and brain calcifications in a patient carrying a homozygous nonsense variant in PCDH12 and in adult patients with brain calcifications. Methods: We performed a CT scan in 1 child with a homozygous PCDH12 nonsense variant. We screened DNA samples from 53 patients with primary familial brain calcification (PFBC) and 26 patients with brain calcification of unknown cause (BCUC). Results: We identified brain calcifications in subcortical and perithalamic regions in the patient with a homozygous PCDH12 nonsense variant. The calcification pattern was different from what has been observed in PFBC and more similar to what is described in in utero infections. In patients with PFBC or BCUC, we found no protein-truncating variant and 3 rare (minor allele frequency <0.001) PCDH12 predicted damaging missense heterozygous variants in 3 unrelated patients, albeit with no segregation data available. Conclusions: Brain calcifications should be added to the phenotypic spectrum associated with PCDH12 biallelic loss of function, in the context of severe cerebral developmental abnormalities. A putative role for PCDH12 variants remains to be determined in PFBC. PMID:28804758

Tremolite whitewashing and pleural calcifications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Constantopoulos, S.H.; Saratzis, N.A.; Kontogiannis, D.

1987-10-01

Radiologic screening of 688 inhabitants of the Metsovo area in Northwest Greece revealed that 323 (46.9 percent) had pleural calcifications. The percentage of positive examinations rose with age. Calcifications were observed in all four villages of the area where a material (luto soil) had been extensively used for whitewashing until 1940 to 1950. In four other villages in the immediate vicinity, where luto had never been used, pleural calcifications were not observed. Results suggest that Metsovo tremolite may have caused pleural calcifications to all individuals born in Metsovo before 1940. This is the first study indicating that environmental asbestos exposuremore » can cause abnormalities in everyone exposed to it.« less

Recombinant apolipoprotein A-I Milano rapidly reverses aortic valve stenosis and decreases leaflet inflammation in an experimental rabbit model.

PubMed

Speidl, Walter S; Cimmino, Giovanni; Ibanez, Borja; Elmariah, Sammy; Hutter, Randolph; Garcia, Mario J; Fuster, Valentin; Goldman, Martin E; Badimon, Juan J

2010-08-01

Aortic stenosis (AS) is associated with significant morbidity and mortality. Recombinant apolipoprotein A-I Milano (rApoA-I(M)) induces atherosclerotic plaque regression. The aims of this study were to determine the effects of rApoA-I(M) on experimental aortic valve degeneration and its mechanisms of action. New Zealand White rabbits (n = 20) were fed an atherogenic diet for 9 months and then randomized to either placebo or rApoA-I(M). Echocardiography was used to assess the effect of the treatments on AS. Porcine aortic valve myofibroblasts (PAVMF) treated with oxidized low-density lipoprotein served to define the effects of rApoA-I(M) on the expression of monocyte chemoattractant protein-1 (MCP-1), nuclear factor (NF)-kappaB, and alkaline phosphatase (AP). Recombinant apolipoprotein A-I Milano increased aortic valve area (AVA) by 32% (0.25 +/- 0.05 to 0.34 +/- 0.07 cm(2), P < 0.01); whereas AVA remained unchanged in the placebo group (0.24 +/- 0.05 to 0.26 +/- 0.04 cm(2), P = 0.58). Histopathological examination of aortic valves in the rApoA-I(M) animals showed significantly less leaflet thickening, inflammation, and calcification vs. the placebo group. In vitro, rApoA-I(M) significantly inhibited MCP-1, AP, and NF-kappaB and decreased intracellular cholesterol content in PAVMF. Recombinant apolipoprotein A-I Milano treatment reverses AS in this experimental rabbit model. The beneficial effects seem to be mediated by enhanced cholesterol removal and by reduced inflammation and calcification.

In Vitro Evaluation of a Novel Hemodynamically Optimized Trileaflet Polymeric Prosthetic Heart Valve

PubMed Central

Claiborne, Thomas E.; Sheriff, Jawaad; Kuetting, Maximilian; Steinseifer, Ulrich; Slepian, Marvin J.; Bluestein, Danny

2013-01-01

Calcific aortic valve disease is the most common and life threatening form of valvular heart disease, characterized by stenosis and regurgitation, which is currently treated at the symptomatic end-stages via open-heart surgical replacement of the diseased valve with, typically, either a xenograft tissue valve or a pyrolytic carbon mechanical heart valve. These options offer the clinician a choice between structural valve deterioration and chronic anticoagulant therapy, respectively, effectively replacing one disease with another. Polymeric prosthetic heart valves (PHV) offer the promise of reducing or eliminating these complications, and they may be better suited for the new transcatheter aortic valve replacement (TAVR) procedure, which currently utilizes tissue valves. New evidence indicates that the latter may incur damage during implantation. Polymer PHVs may also be incorporated into pulsatile circulatory support devices such as total artificial heart and ventricular assist devices that currently employ mechanical PHVs. Development of polymer PHVs, however, has been slow due to the lack of sufficiently durable and biocompatible polymers. We have designed a new trileaflet polymer PHV for surgical implantation employing a novel polymer—xSIBS—that offers superior bio-stability and durability. The design of this polymer PHV was optimized for reduced stresses, improved hemodynamic performance, and reduced thrombogenicity using our device thrombogenicity emulation (DTE) methodology, the results of which have been published separately. Here we present our new design, prototype fabrication methods, hydrodynamics performance testing, and platelet activation measurements performed in the optimized valve prototype and compare it to the performance of a gold standard tissue valve. The hydrodynamic performance of the two valves was comparable in all measures, with a certain advantage to our valve during regurgitation. There was no significant difference between the

Direct transcatheter aortic valve implantation with self-expandable bioprosthesis: feasibility and safety.

PubMed

Fiorina, Claudia; Maffeo, Diego; Curello, Salvatore; Lipartiti, Felicia; Chizzola, Giuliano; D'Aloia, Antonio; Adamo, Marianna; Mastropierro, Rosy; Gavazzi, Emanuele; Ciccarese, Camilla; Chiari, Ermanna; Ettori, Federica

2014-06-01

Balloon valvuloplasty has been considered a mandatory step of the transcatheter aortic valve implantation (TAVI), although it is not without risk. The aim of this work was to evaluate the feasibility and safety of TAVI performed without pre-dilation (direct TAVI) of the stenosed aortic valve. Between June 2012 and June 2013, 55 consecutive TAVI performed without pre-dilation at our institution using the self-expandable CoreValve prosthesis (Medtronic, Minneapolis, MN) were analyzed and compared with 45 pre-dilated TAVI performed the previous year. Inclusion criteria were a symptomatic and severe aortic stenosis. Exclusion criteria were defined as presence of pure aortic regurgitation, degenerated surgical bioprosthesis or bicuspid aortic valve and prior procedure of balloon aortic valvuloplasty performed as a bridge to TAVI. High-burden calcification in the device landing zone, assessed by CT scan, was found in most of the patients. The valve size implanted was similar in both groups. Device success was higher in direct TAVI (85%vs.64%,p=0.014), mostly driven by a significant lower incidence of paravalvular leak (PVL≥2;9%vs.33%,p=0.02). Safety combined end point at 30 days was similar in both groups. Compared to TAVI with pre-dilation, direct TAVI is feasible regardless of the presence of bulky calcified aortic valve and the valve size implanted. Device success was higher in direct TAVI, mostly driven by a lower incidence of paravalvular leak. Safety at 30 days was similar in two groups. Copyright © 2014 Elsevier Inc. All rights reserved.

The JUPITER registry: 1-year results of transapical aortic valve implantation using a second-generation transcatheter heart valve in patients with aortic stenosis.

PubMed

Silaschi, Miriam; Treede, Hendrik; Rastan, Ardawan J; Baumbach, Hardy; Beyersdorf, Friedhelm; Kappert, Utz; Eichinger, Walter; Rüter, Florian; de Kroon, Thomas L; Lange, Rüdiger; Ensminger, Stephan; Wendler, Olaf

2016-11-01

obstruction, annular rupture or with limited aortic valve calcification, the JenaValve might be preferable for implantation due to its clipping-mechanism engaging native aortic valve cusps for fixation with reduced radial forces of the self-expanding stent. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

TexMi: Development of Tissue-Engineered Textile-Reinforced Mitral Valve Prosthesis

PubMed Central

Moreira, Ricardo; Gesche, Valentine N.; Hurtado-Aguilar, Luis G.; Schmitz-Rode, Thomas; Frese, Julia

2014-01-01

Mitral valve regurgitation together with aortic stenosis is the most common valvular heart disease in Europe and North America. Mechanical and biological prostheses available for mitral valve replacement have significant limitations such as the need of a long-term anticoagulation therapy and failure by calcifications. Both types are unable to remodel, self-repair, and adapt to the changing hemodynamic conditions. Moreover, they are mostly designed for the aortic position and do not reproduce the native annular-ventricular continuity, resulting in suboptimal hemodynamics, limited durability, and gradually decreasing ventricular pumping efficiency. A tissue-engineered heart valve specifically designed for the mitral position has the potential to overcome the limitations of the commercially available substitutes. For this purpose, we developed the TexMi, a living textile-reinforced mitral valve, which recapitulates the key elements of the native one: annulus, asymmetric leaflets (anterior and posterior), and chordae tendineae to maintain the native annular-ventricular continuity. The tissue-engineered valve is based on a composite scaffold consisting of the fibrin gel as a cell carrier and a textile tubular structure with the twofold task of defining the gross three-dimensional (3D) geometry of the valve and conferring mechanical stability. The TexMi valves were molded with ovine umbilical vein cells and stimulated under dynamic conditions for 21 days in a custom-made bioreactor. Histological and immunohistological stainings showed remarkable tissue development with abundant aligned collagen fibers and elastin deposition. No cell-mediated tissue contraction occurred. This study presents the proof-of-principle for the realization of a tissue-engineered mitral valve with a simple and reliable injection molding process readily adaptable to the patient's anatomy and pathological situation by producing a patient-specific rapid prototyped mold. PMID:24665896

Clinical and hemodynamic results after direct transcatheter aortic valve replacement versus pre-implantation balloon aortic valvuloplasty: A case-matched analysis.

PubMed

Ferrera, Carlos; Nombela-Franco, Luis; Garcia, Eulogio; Jimenez-Quevedo, Pilar; Biagioni, Corina; Gonzalo, Nieves; Nuñez-Gil, Ivan; Viana-Tejedor, Ana; Salinas, Pablo; Alberto de Agustin, Jose; Almeria, Carlos; Islas, Fabian; Perez de Isla, Leopoldo; Fernandez-Perez, Cristina; Escaned, Javier; Fernández-Ortiz, Antonio; Macaya, Carlos

2017-11-01

To evaluate the safety and midterm hemodynamic results of direct transcatheter aortic valve replacement (TAVR) without pre-implantation balloon aortic valvuloplasty (BAV). BAV was considered a mandatory previous step in TAVR procedures. A total of 339 consecutive patients who underwent transfemoral TAVR were prospectively selected. A 1:1 matching was conducted, pairing age, prosthesis type (self-expandable or balloon expandable) and size, and valve calcification grade (48% with moderate to severe valve calcification). Finally, 102 pairs (102 patients with previous BAV and 102 without BAV) were obtained. Direct TAVR was feasible in all patients without any crossover to BAV group. Device success was achieved in 91.2% and 90.2% of cases in direct TAVR and pre-BAV groups (P = 0.810), respectively, without any differences in balloon postdilation rate and residual aortic regurgitation. The amount of contrast agent, acute kidney injury and myocardial injury was significantly lower in the direct implantation group (P < 0.05). No differences were found in 30-day and 1-year mortality between both groups (4.9% vs. 9.8%, P = 0.177 and 14.0% vs. 23.8%, P = 0.771, respectively). Hemodynamic parameters remained stable after 1-year follow-up in both groups. Direct transfemoral TAVR without prior BAV was safe in patients with calcified severe aortic stenosis. Pre-implantation BAV could be omitted in patients undergoing TAVR, without influence in procedure success rate, and subsequent patients' clinical course and valve hemodynamic performance. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

49 CFR 236.383 - Valve locks, valves, and valve magnets.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Valve locks, valves, and valve magnets. 236.383... Inspection and Tests § 236.383 Valve locks, valves, and valve magnets. Valve locks on valves of the non-cut-off type shall be tested at least once every three months, and valves and valve magnets shall be...

Transapical implantation of a second-generation transcatheter heart valve in patients with noncalcified aortic regurgitation.

PubMed

Seiffert, Moritz; Diemert, Patrick; Koschyk, Dietmar; Schirmer, Johannes; Conradi, Lenard; Schnabel, Renate; Blankenberg, Stefan; Reichenspurner, Hermann; Baldus, Stephan; Treede, Hendrik

2013-06-01

This study sought to report on the feasibility and early results of transcatheter aortic valve implantation employing a second-generation device in a series of patients with pure aortic regurgitation. Efficacy and safety of transcatheter aortic valve implantation in patients with calcific aortic stenosis and high surgical risk has been demonstrated. However, experience with implantation for severe noncalcified aortic regurgitation has been limited due to increased risk for valve dislocation or annular rupture. Five patients (mean age: 66.6 ± 7 years) underwent transapical implantation of a JenaValve (JenaValve Technology GmbH, Munich, Germany) transcatheter heart valve for moderate to severe, noncalcified aortic regurgitation. All patients were considered high risk for surgical aortic valve replacement after evaluation by an interdisciplinary heart team (logistic EuroSCORE [European System for Cardiac Operative Risk Evaluation] range 3.1% to 38.9%). Procedural and acute clinical outcomes were analyzed. Implantation was successful in all cases without relevant remaining aortic regurgitation or signs of stenosis in any of the patients. No major device- or procedure-related adverse events occurred and all 5 patients were alive with improved exercise tolerance at 3-month follow-up. Noncalcified aortic regurgitation continues to be a challenging pathology for transcatheter aortic valve implantation due to the risk for insufficient anchoring of the valve stent within the aortic annulus. This report provides first evidence that the JenaValve prosthesis may be a reasonable option in these specific patients due to its unique stent design, clipping the native aortic valve leaflets, and offering promising early results. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The effects of the covalent attachment of 3-(4-hydroxy-3,5-di-tert-butylphenyl)propyl amine to glutaraldehyde pre-treated bovine pericardium on structural degeneration, oxidative modification and calcification of rat subdermal implants

PubMed Central

Christian, Abigail J.; Alferiev, Ivan S.; Connolly, Jeanne M.; Ischiropoulos, Harry; Levy, Robert J.

2014-01-01

Bioprosthetic heart valves (BHV) fabricated from glutaraldehyde pretreated heterograft materials, porcine aortic valves or bovine pericardium (BP), are widely used in cardiac surgery. BHV progressively fail in clinical use due to structural degeneration. Previously we reported that dityrosine, an oxidized amino acid, was present in failed clinical BP-BHV explants; unimplanted BP had no detectable dityrosine. In the same studies BP were demonstrated in vitro to be susceptible to oxidative damage, that could be mitigated with BP covalently modified with the antioxidant, 3-(4-hydroxy-3,5-di-tert-butylphenyl)propyl amine (DBP). The present studies compared in rat subdermal implants glutaraldehyde pretreated BP to BP modified with either DBP or the chemical reactions used to link DBP. All BP explants regardless of DBP demonstrated reduced hydroxyproline and increased digestibility by collagenase. However, the DBP-BP explants showed significant inhibition of reduced explant shrink temperatures (an index of crosslinking) compared to control BP. Significant mitigation of calcification was observed in both the BP-DBP and chemically modified explants compared to BP. Dityrosine was not detectable in the 90 day explants. It is concluded that rat subdermal BP implants undergo both calcific and non-calcific structural degeneration, but without the formation of dityrosine, unlike clinical BP explants. PMID:25546235

Durability of Aortic Valve Cusp Repair With and Without Annular Support.

PubMed

Zeeshan, Ahmad; Idrees, Jay J; Johnston, Douglas R; Rajeswaran, Jeevanantham; Roselli, Eric E; Soltesz, Edward G; Gillinov, A Marc; Griffin, Brian; Grimm, Richard; Hammer, Donald F; Pettersson, Gösta B; Blackstone, Eugene H; Sabik, Joseph F; Svensson, Lars G

2018-03-01

To determine the value of aortic valve repair rather than replacement for valve dysfunction, we assessed late outcomes of various repair techniques in the contemporary era. From January 2001 to January 2011, aortic valve repair was planned in 1,124 patients. Techniques involved commissural figure-of-8 suspension sutures (n = 63 [6.2%]), cusp repair with commissuroplasty (n = 481 [48%]), debridement (n = 174 [17%]), free-margin plication (n = 271 [27%]) or resection (n = 75) or both, or annulus repair with resuspension (n = 230 [23%]), root reimplantation (n = 252 [25%]), or remodeling (n = 35 [3.5%]). Planned repair was aborted for replacement in 115 patients (10%); risk factors included greater severity of aortic regurgitation (AR; p = 0.0002) and valve calcification (p < 0.0001). In-hospital outcomes for the remaining 1,009 patients included death (12 [1.2%]), stroke (13 [1.3%]), and reoperation for valve dysfunction (14 [1.4%]). Freedom from aortic valve reoperation at 1, 5, and 10 years was 97%, 93%, and 90%, respectively. Figure-of-8 suspension sutures, valve resuspension, and root repair and replacement were least likely to require reoperation; cusp repair with commissural sutures, plication, and commissuroplasty was most likely (p < 0.05). Survival at 1, 5, and 10 years was 96%, 92%, and 83%. Immediate postoperative AR grade was none-mild (94%), moderate (5%), and severe (1%). At 10 years after repair, AR grade was none (20%), mild (33%), moderate (26%), and severe (21%). Patients undergoing root procedures were less likely to have higher-grade postoperative AR (p < 0.0001). Valve repair is effective and durable for treating aortic valve dysfunction. Greater severity of AR preoperatively is associated with higher likelihood of repair failure. Commissural figure-of-8 suspension sutures and repair with annular support have the best long-term durability. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights

Bioprosthetic Valve Fracture to Facilitate Transcatheter Valve-in-Valve Implantation.

PubMed

Allen, Keith B; Chhatriwalla, Adnan K; Cohen, David J; Saxon, John T; Aggarwal, Sanjeev; Hart, Anthony; Baron, Suzanne; Davis, J Russell; Pak, Alex F; Dvir, Danny; Borkon, A Michael

2017-11-01

Valve-in-valve transcatheter aortic valve replacement is less effective in small surgical bioprostheses. We evaluated the feasibility of bioprosthetic valve fracture with a high-pressure balloon to facilitate valve-in-valve transcatheter aortic valve replacement. In vitro bench testing on aortic tissue valves was performed on 19-mm and 21-mm Mitroflow (Sorin, Milan, Italy), Magna and Magna Ease (Edwards Lifesciences, Irvine, CA), Trifecta and Biocor Epic (St. Jude Medical, Minneapolis, MN), and Hancock II and Mosaic (Medtronic, Minneapolis, MN). High-pressure balloons Tru Dilation, Atlas Gold, and Dorado (C.R. Bard, Murray Hill, NJ) were used to determine which valves could be fractured and at what pressure fracture occurred. Mitroflow, Magna, Magna Ease, Mosaic, and Biocor Epic surgical valves were successfully fractured using high-pressures balloon 1 mm larger than the labeled valve size whereas Trifecta and Hancock II surgical valves could not be fractured. Only the internal valve frame was fractured, and the sewing cuff was never disrupted. Manufacturer's rated burst pressures for balloons were exceeded, with fracture pressures ranging from 8 to 24 atmospheres depending on the surgical valve. Testing further demonstrated that fracture facilitated the expansion of previously constrained, underexpanded transcatheter valves (both balloon and self-expanding) to the manufacturer's recommended size. Bench testing demonstrates that the frame of most, but not all, bioprosthetic surgical aortic valves can be fractured using high-pressure balloons. The safety of bioprosthetic valve fracture to optimize valve-in-valve transcatheter aortic valve replacement in small surgical valves requires further clinical investigation. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

CT of schistosomal calcification of the intestine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fataar, S.; Bassiony, H.; Satyanath, S.

1985-01-01

The spectrum of schistosomal colonic calcification on abdominal radiographs has been described. The appearance on computed tomography (CT) is equally distinctive and occurs with varying degrees of genitourinary calcification. The authors have experience in three cases with the appearance on CT of intestinal calcification due to schistosomiasis.

[Selection of patients for transcatheter aortic valve implantation].

PubMed

Tron, Christophe; Godin, Matthieu; Litzler, Pierre-Yves; Bauer, Fabrice; Caudron, Jérome; Dacher, Jean-Nicolas; Borz, Bogdan; Canville, Alexandre; Kurtz, Baptiste; Bessou, Jean-Paul; Cribier, Alain; Eltchaninoff, Hélène

2012-06-01

A good selection of patients is a crucial step before transcatheter aortic valve implantation (TAVI) in order to select the good indications and choose the access route. TAVI should be considered only in patients with symptomatic severe aortic stenosis and either contraindication or high surgical risk. Indication for TAVI should be discussed in a multidisciplinary team meeting. Echocardiography and/or CT scan are mandatory to evaluate the aortic annulus size and select the good prosthesis size. The possibility of transfemoral implantation is evaluated by angiography and CT scan, and based on the arterial diameters, but also on the presence of tortuosities and arterial calcifications. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Quantification of Aortic Valve Calcifications Detected During Lung Cancer-Screening CT Helps Stratify Subjects Necessitating Echocardiography for Aortic Stenosis Diagnosis.

PubMed

Lee, Hee Young; Kim, Sung Mok; Lee, Kyung Soo; Park, Seung Woo; Chung, Myung Jin; Cho, Hyoun; Jung, Jung Im; Jang, Hye Won; Jung, Sin-Ho; Goo, Juna

2016-05-01

No study has been published on aortic valve calcification (AVC) extent at lung cancer screening low-dose CT (LDCT) and its relationship with aortic stenosis (AS). The purpose of this study was to estimate the cutoff value of AVC on LDCT for detecting AS in asymptomatic Asian subjects. Six thousand three hundred thirty-eight subjects (mean age, 55.9 years ± 8.6) self-referred to health-promotion center underwent LDCT, coronary calcium scoring CT (CSCT), and echocardiography. AVC was quantified using Agatston methods on CT. AVC extent on LDCT was compared with that on CSCT, and AVC threshold for diagnosing AS was calculated. Clinical factors associated with AS and AVC were sought.AVC was observed in 403 subjects (64.9 years ± 8.7) on LDCT (6.4%), and AVC score measured from LDCT showed strong positive correlation with that from CSCT (r = 0.83, P < 0.0001). Of 403 subjects, 40 (10%) were identified to have AS on echocardiography. Cutoff value of AVC score for detecting AS was 138.37 with sensitivity of 90.0% and specificity 83.2%. On multivariate analysis, age (odds ratio [OR] = 1.10, 95% CI: 1.09-1.12) and hypertension (OR = 1.39, 95% CI: 1.10-1.76) were associated with the presence of AVC, whereas AVC extent at LDCT (OR = 104.32, 95% CI: 16.16-673.70) was the only significant clinical factor associated with AS; AVC extent on LDCT (OR = 104.32, 95% CI: 16.16-673.70) was the significant clinical factor associated with AS.The AVC extent on LDCT is significantly related to the presence of AS, and we recommend echocardiography for screening AS based on quantified AVC values on LDCT.

Quantification of Aortic Valve Calcifications Detected During Lung Cancer-Screening CT Helps Stratify Subjects Necessitating Echocardiography for Aortic Stenosis Diagnosis

PubMed Central

Lee, Hee Young; Kim, Sung Mok; Lee, Kyung Soo; Park, Seung Woo; Chung, Myung Jin; Cho, Hyoun; Jung, Jung Im; Jang, Hye Won; Jung, Sin-Ho; Goo, Juna

2016-01-01

Abstract No study has been published on aortic valve calcification (AVC) extent at lung cancer screening low-dose CT (LDCT) and its relationship with aortic stenosis (AS). The purpose of this study was to estimate the cutoff value of AVC on LDCT for detecting AS in asymptomatic Asian subjects. Six thousand three hundred thirty-eight subjects (mean age, 55.9 years ± 8.6) self-referred to health-promotion center underwent LDCT, coronary calcium scoring CT (CSCT), and echocardiography. AVC was quantified using Agatston methods on CT. AVC extent on LDCT was compared with that on CSCT, and AVC threshold for diagnosing AS was calculated. Clinical factors associated with AS and AVC were sought. AVC was observed in 403 subjects (64.9 years ± 8.7) on LDCT (6.4%), and AVC score measured from LDCT showed strong positive correlation with that from CSCT (r = 0.83, P < 0.0001). Of 403 subjects, 40 (10%) were identified to have AS on echocardiography. Cutoff value of AVC score for detecting AS was 138.37 with sensitivity of 90.0% and specificity 83.2%. On multivariate analysis, age (odds ratio [OR] = 1.10, 95% CI: 1.09–1.12) and hypertension (OR = 1.39, 95% CI: 1.10–1.76) were associated with the presence of AVC, whereas AVC extent at LDCT (OR = 104.32, 95% CI: 16.16–673.70) was the only significant clinical factor associated with AS; AVC extent on LDCT (OR = 104.32, 95% CI: 16.16–673.70) was the significant clinical factor associated with AS. The AVC extent on LDCT is significantly related to the presence of AS, and we recommend echocardiography for screening AS based on quantified AVC values on LDCT. PMID:27175713

Etidronate prevents dystrophic cardiac calcification by inhibiting macrophage aggregation.

PubMed

Bauer, Carolin; le Saux, Olivier; Pomozi, Viola; Aherrahrou, Redouane; Kriesen, Rene; Stölting, Stephanie; Liebers, Annett; Kessler, Thorsten; Schunkert, Heribert; Erdmann, Jeanette; Aherrahrou, Zouhair

2018-04-11

Cardiovascular calcification is associated with high risk of vascular disease. This involves macrophage infiltration of injured vascular tissue and osteoclast-related processes. Splenic monocytes from mice, that are predisposed (C3H) or resistant (B6) to calcification, were isolated and differentiated in vitro with M-CSF to generate macrophages, which aggregate to form multinucleated (MN) cells in the presence of RANKL. MN cell formation was significantly decreased in monocytes from resistant compared with calcifying mice. Conditioned media from C3H macrophages strongly induced calcification in vitro. However, medium from B6 macrophages inhibited calcification. An increase in ICAM-1 was detected in conditioned media from C3H macrophages compared with B6, suggesting a key role for this molecule in calcification processes. Due to natural genetic loss of Abcc6, the causal gene for cardiac calcification, C3H mice have reduced plasma levels of inorganic pyrophosphate (PPi), a potential calcification inhibitor. Supplementation of C3H mice with PPi or Etidronate prevented but did not completely reverse cardiac calcification. Our data provide strong evidence of the pathogenesis of macrophages and MNs during tissue calcification and suggest PPi or its analogue Etidronate as a potential inhibitor of MN formation and calcification. Furthermore, the adhesion molecule ICAM-1 was shown to play a key role in calcification.

Inhibition of FOXO1/3 promotes vascular calcification.

PubMed

Deng, Liang; Huang, Lu; Sun, Yong; Heath, Jack M; Wu, Hui; Chen, Yabing

2015-01-01

Vascular calcification is a characteristic feature of atherosclerosis, diabetes mellitus, and end-stage renal disease. We have demonstrated that activation of protein kinase B (AKT) upregulates runt-related transcription factor 2 (Runx2), a key osteogenic transcription factor that is crucial for calcification of vascular smooth muscle cells (VSMC). Using mice with SMC-specific deletion of phosphatase and tensin homolog (PTEN), a major negative regulator of AKT, the present studies uncovered a novel molecular mechanism underlying PTEN/AKT/FOXO (forkhead box O)-mediated Runx2 upregulation and VSMC calcification. SMC-specific PTEN deletion mice were generated by crossing PTEN floxed mice with SM22α-Cre transgenic mice. The PTEN deletion resulted in sustained activation of AKT that upregulated Runx2 and promoted VSMC calcification in vitro and arterial calcification ex vivo. Runx2 knockdown did not affect proliferation but blocked calcification of the PTEN-deficient VSMC, suggesting that PTEN deletion promotes Runx2-depedent VSMC calcification that is independent of proliferation. At the molecular level, PTEN deficiency increased the amount of Runx2 post-transcriptionally by inhibiting Runx2 ubiquitination. AKT activation increased phosphorylation of FOXO1/3 that led to nuclear exclusion of FOXO1/3. FOXO1/3 knockdown in VSMC phenocopied the PTEN deficiency, demonstrating a novel function of FOXO1/3, as a downstream signaling of PTEN/AKT, in regulating Runx2 ubiquitination and VSMC calcification. Using heterozygous SMC-specific PTEN-deficient mice and atherogenic ApoE(-/-) mice, we further demonstrated AKT activation, FOXO phosphorylation, and Runx2 ubiquitination in vascular calcification in vivo. Our studies have determined a new causative effect of SMC-specific PTEN deficiency on vascular calcification and demonstrated that FOXO1/3 plays a crucial role in PTEN/AKT-modulated Runx2 ubiquitination and VSMC calcification. © 2014 American Heart Association, Inc.

After Superficial Ablation for Superficial Reflux Associated with Primary Deep Axial Reflux, Can Variable Outcomes be Caused by Deep Venous Valve Anomalies?

PubMed

Maleti, O; Lugli, M; Perrin, M

2017-02-01

To identify which deep anatomical anomalies can explain variable hemodynamic outcomes in patients with superficial reflux associated with primary deep axial reflux who underwent isolated superficial vein ablation without improvement. This is a retrospective study of deep venous valve anomalies in patients who underwent superficial vein ablation for superficial and associated deep reflux. A group of 21 patients who were diagnosed with saphenous reflux associated with primary deep axial reflux, were submitted to great saphenous vein ablation. In 17 patients the deep reflux was not abolished. In this subgroup, surgical exploration of the deep valve was carried out using venotomy for possible valve repair. Among the 17 subgroup patients, four post-thrombotic lesions were discovered intra-operatively in four patients; they underwent different surgical procedures. In 13 of the subgroup patients, primary valve incompetence was confirmed intra-operatively. In 11 cases the leaflets were asymmetrical and in only two were they symmetrical. After valvuloplasty, deep reflux was abolished in all 13 patients. Clinical improvement was obtained in 12/13 patients (92%). It is noteworthy that abolition of deep reflux was associated with significant improvement in air plethysmography data as well as with improvement in clinical status measured on CEAP class, VCSS and the SF-36 questionnaire. Failure to correct deep axial reflux by superficial ablation in patients with superficial and associated primary deep axial reflux may be related to asymmetry in the leaflets of the incompetent deep venous valve. Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Impact of aortic valve calcification, as measured by MDCT, on survival in patients with aortic stenosis: results of an international registry study.

PubMed

Clavel, Marie-Annick; Pibarot, Philippe; Messika-Zeitoun, David; Capoulade, Romain; Malouf, Joseph; Aggarval, Shivani; Araoz, Phillip A; Michelena, Hector I; Cueff, Caroline; Larose, Eric; Miller, Jordan D; Vahanian, Alec; Enriquez-Sarano, Maurice

2014-09-23

Aortic valve calcification (AVC) load measures lesion severity in aortic stenosis (AS) and is useful for diagnostic purposes. Whether AVC predicts survival after diagnosis, independent of clinical and Doppler echocardiographic AS characteristics, has not been studied. This study evaluated the impact of AVC load, absolute and relative to aortic annulus size (AVCdensity), on overall mortality in patients with AS under conservative treatment and without regard to treatment. In 3 academic centers, we enrolled 794 patients (mean age, 73 ± 12 years; 274 women) diagnosed with AS by Doppler echocardiography who underwent multidetector computed tomography (MDCT) within the same episode of care. Absolute AVC load and AVCdensity (ratio of absolute AVC to cross-sectional area of aortic annulus) were measured, and severe AVC was separately defined in men and women. During follow-up, there were 440 aortic valve implantations (AVIs) and 194 deaths (115 under medical treatment). Univariate analysis showed strong association of absolute AVC and AVCdensity with survival (both, p < 0.0001) with a spline curve analysis pattern of threshold and plateau of risk. After adjustment for age, sex, coronary artery disease, diabetes, symptoms, AS severity on hemodynamic assessment, and LV ejection fraction, severe absolute AVC (adjusted hazard ratio [HR]: 1.75; 95% confidence interval [CI]: 1.04 to 2.92; p = 0.03) or severe AVCdensity (adjusted HR: 2.44; 95% CI: 1.37 to 4.37; p = 0.002) independently predicted mortality under medical treatment, with additive model predictive value (all, p ≤ 0.04) and a net reclassification index of 12.5% (p = 0.04). Severe absolute AVC (adjusted HR: 1.71; 95% CI: 1.12 to 2.62; p = 0.01) and severe AVCdensity (adjusted HR: 2.22; 95% CI: 1.40 to 3.52; p = 0.001) also independently predicted overall mortality, even with adjustment for time-dependent AVI. This large-scale, multicenter outcomes study of quantitative Doppler echocardiographic and MDCT

Evaluation of prosthetic valve thrombosis by 64-row multi-detector computed tomography. .

PubMed

Tarzia, Vincenzo; Bortolussi, Giacomo; Rubino, Maurizio; Gallo, Michele; Bottio, Tomaso; Gerosa, Gino

2015-03-01

Multi-detector computed tomography (MDCT), combined with retrospective electrocardiographic gating, permits cardiac imaging with high accuracy. Recent advances in MDCT have seemed to respond adequately to the need for a non-invasive and reliable assessment of the coronary artery lumen. Two patients with prosthetic aortic valves (one bioprosthetic, one mechanical) presented at the authors' institution with dyspnea and syncopal episodes. MDCT was performed to evaluate thrombus characteristics and exclude coronary artery disease (CAD). Based on the MDCT coronary artery assessment, neither patient underwent preoperative invasive coronary angiography, abolishing the risk of any iatrogenic thrombus fragmentation and subsequent embolization. One patient underwent surgical treatment without complications, while medical therapy was successful in the other case. MDCT can be used for the accurate imaging of thrombi on prosthetic aortic valves, and to correctly assess possible CAD.

Beneficial Effects of Galectin-3 Blockade in Vascular and Aortic Valve Alterations in an Experimental Pressure Overload Model

PubMed Central

Ibarrola, Jaime; Martínez-Martínez, Ernesto; Sádaba, J. Rafael; Arrieta, Vanessa; García-Peña, Amaia; Álvarez, Virginia; Fernández-Celis, Amaya; Gainza, Alicia; Rossignol, Patrick; Cachofeiro Ramos, Victoria; López-Andrés, Natalia

2017-01-01

Galectin-3 (Gal-3) is involved in cardiovascular fibrosis and aortic valve (AV) calcification. We hypothesized that Gal-3 pharmacological inhibition with modified citrus pectin (MCP) could reduce aortic and AV remodeling in normotensive rats with pressure overload (PO). Six weeks after aortic constriction, vascular Gal-3 expression was up-regulated in male Wistar rats. Gal-3 overexpression was accompanied by an increase in the aortic media layer thickness, enhanced total collagen, and augmented expression of fibrotic mediators. Further, vascular inflammatory markers as well as inflammatory cells content were greater in aorta from PO rats. MCP treatment (100 mg/kg/day) prevented the increase in Gal-3, media thickness, fibrosis, and inflammation in the aorta of PO rats. Gal-3 levels were higher in AVs from PO rats. This paralleled enhanced AV fibrosis, inflammation, as well as greater expression of calcification markers. MCP treatment prevented the increase in Gal-3 as well as fibrosis, inflammation, and calcification in AVs. Overall, Gal-3 is overexpressed in aorta and AVs from PO rats. Gal-3 pharmacological inhibition blocks aortic and AV remodeling in experimental PO. Gal-3 could be a new therapeutic approach to delay the progression and the development of aortic remodeling and AV calcification in PO. PMID:28758988

Bicuspid aortic valves are associated with increased wall and turbulence shear stress levels compared to trileaflet aortic valves.

PubMed

Saikrishnan, Neelakantan; Mirabella, Lucia; Yoganathan, Ajit P

2015-06-01

Congenital bicuspid aortic valves (BAVs) are associated with accelerated disease progression, such as leaflet calcification and ascending aorta dilatation. Although common underlying genetic factors have been implicated in accelerated disease in BAV patients, several studies have suggested that altered hemodynamics also play a role in this disease process. The present study compares turbulence and wall shear stress (WSS) measurements between various BAV and trileaflet aortic valve (TAV) models to provide information for mechanobiological models of BAV disease. BAV and TAV models were constructed from excised porcine aortic valves to simulate parametric variations in BAV stenosis, hemodynamics and geometry. Particle image velocimetry experiments were conducted at physiological pressure conditions to characterize velocity fields in the ascending aorta. The velocity fields were post-processed to calculate turbulence, viscous and wall shear stresses in the ascending aorta. Stenosed BAV models showed the presence of eccentric systolic jets, causing increased WSS. Lower cardiac output resulted in a narrower jet, lower turbulence and lower viscous shear stress (VSS). The specific severe stenosis BAV model studied here showed reduced WSS due to reduction in non-fused leaflet mobility. Dilation of the aorta did not affect any turbulence or VSS, but reduced the WSS. In comparison with BAVs, TAVs have similar VSS values, but much smaller WSS and turbulence levels. These increased turbulence  and WSS levels in BAVs may play a key role in amplifying the biological responses of the ascending aorta wall and valvular leaflets, and support the hemodynamic underpinnings of BAV disease processes.

Rectus Femoris Tendon Calcification

PubMed Central

Zini, Raul; Panascì, Manlio; Papalia, Rocco; Franceschi, Francesco; Vasta, Sebastiano; Denaro, Vincenzo

2014-01-01

Background: Since it was developed, hip arthroscopy has become the favored treatment for femoroacetabular impingement. Due to recent considerable improvements, the indications for this technique have been widely extended. Injuries of the rectus femoris tendon origin, after an acute phase, could result in a chronic tendinopathy with calcium hydroxyapatite crystal deposition, leading to pain and loss of function. Traditionally, this condition is addressed by local injection of anesthetic and corticosteroids or, when conservative measures fail, by open excision of the calcific lesion by an anterior approach. Purpose: To assess whether arthroscopic excision of calcification of the proximal rectus is a safe and effective treatment. Study Design: Case series; Level of evidence, 4. Methods: Outcomes were studied from 6 top amateur athletes (age range, 30-43 years; mean, 32.6 years) affected by calcification of the proximal rectus who underwent arthroscopic excision of the calcification. Patients were preoperatively assessed radiographically, and diagnosis was confirmed by a 3-dimensional computed tomography scan. To evaluate the outcome, standardized hip rating scores were used pre- and postoperatively (at 6 and 12 months): the Hip disability and Osteoarthritis Outcome Score, Oxford Hip Score, and Modified Harris Hip Score. Moreover, visual analog scales (VAS) for pain, sport activity level (SAL), and activities of daily living (ADL) were also used. Results: One year after surgery, all patients reported satisfactory outcomes, with 3 of 6 rating their return-to-sport level as high as preinjury level, and the remaining 3 with a percentage higher than 80%. Five patients ranked their ability to carry on daily activities at 100%. Statistical analysis showed significant improvement of the Oxford Hip Score, the Modified Harris Hip Score, and all 3 VAS subscales (pain, SAL, and ADL) from pre- to latest postoperative assessment (P < .05). Conclusion: Arthroscopic excision of

Transaortic edge-to-edge mitral valve repair for moderate secondary/functional mitral regurgitation in patients undergoing aortic root/valve intervention.

PubMed

Choudhary, Shiv Kumar; Abraham, Atul; Bhoje, Amol; Gharde, Parag; Sahu, Manoj; Talwar, Sachin; Airan, Balram

2017-11-01

The present study evaluates the feasibility, safety, and efficacy of edge-to-edge repair for moderate secondary/functional mitral regurgitation in patients undergoing aortic valve/root interventions. Sixteen patients underwent transaortic edge-to-edge mitral valve repair. Mitral regurgitation was 2+ in 8 patients and 3+ in 6 patients. Two patients in whom cardiac arrest developed preoperatively had severe (4+) mitral regurgitation. Patients underwent operation for severe aortic regurgitation ± aortic root lesions. The mean left ventricular systolic and diastolic diameters were 51.5 ± 12.8 mm and 70.7 ± 10.7 mm, respectively. Left ventricular ejection fraction ranged from 20% to 60%. Primary surgical procedure included Bentall's ± hemiarch replacement in 10 patients, aortic valve replacement in 5 patients, and noncoronary sinus replacement with aortic valve repair in 1 patient. Severity of mitral regurgitation decreased to trivial or zero in 13 patients, 1+ in 2 patients, and 2+ in 1 patient. There were no gradients across the mitral valve in 9 patients, less than 5 mm Hg in 6 patients, and 9 mm Hg in 1 patient. There was no operative mortality. Follow-up ranged from 2 weeks to 54 months. Echocardiography showed trivial or no mitral regurgitation in 12 patients, 1+ in 2 patients, and 2+ in 2 patients. None of the patients had significant mitral stenosis. The mean left ventricular systolic and diastolic diameters decreased to 40.5 ± 10.3 mm and 58.7 ± 11.6 mm, respectively. Ejection fraction also improved slightly (22%-65%). Transaortic edge-to-edge mitral valve repair is a safe and effective technique to abolish secondary/functional mitral regurgitation. However, its impact on overall survival needs to be studied. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Transcatheter aortic-valve implantation with one single minimal contrast media injection.

PubMed

Arrigo, Mattia; Maisano, Francesco; Haueis, Sabine; Binder, Ronald K; Taramasso, Maurizio; Nietlispach, Fabian

2015-06-01

Performing transcatheter aortic valve implantation (TAVI) with the use of minimal contrast in patients at high-risk for acute kidney injury (AKI). Contrast-induced nephropathy (CIN) is a major cause of AKI following TAVI and is associated with increased morbidity and mortality. The amount of contrast media used increases the risk for CIN. Computed tomography was omitted during the screening process. For the procedure transfemoral access was default. The self-expanding CoreValve prosthesis was chosen in all patients to minimize the risk of annular rupture in case of oversizing. Valve sizing was based on echocardiography, aortography, calcification on fluoroscopy, as well as weight and height of the patient. A single contrast injection was performed to confirm correct position of the pigtail catheter at the level of the annulus. The pigtail then served as the marker for the device landing zone. Intraprocedural assessment of the implantation result relied on echocardiography and hemodynamics. Five patients with severe aortic stenosis and at high risk for developing CIN were included. Device success was achieved in all patients and no major complications occurred. The median dose of injected contrast media was 8 ml (4-9). All but one patient had improved renal function after the intervention compared to baseline. Our study shows feasibility of performing TAVI with a single minimal contrast media injection, using a self-expandable valve. This technique has the potential to reduce the incidence of CIN. © 2015 Wiley Periodicals, Inc.

Breast Calcifications

MedlinePlus

... al. Diagnostic evaluation of women with suspected breast cancer. http://www.uptodate.com/home. Accessed Dec. 9, 2015. Lai KC, et al. Linear breast calcifications. American Journal of Roentgenology. 2012;199:W151. Demetri-Lewis A, ...

Polymeric heart valves for surgical implantation, catheter-based technologies and heart assist devices.

PubMed

Bezuidenhout, Deon; Williams, David F; Zilla, Peter

2015-01-01

Efficient function and long-term durability without the need for anticoagulation, coupled with the ability to be accommodated in many different types of patient, are the principal requirements of replacement heart valves. Although the clinical use of valves appeared to have remained steady for several decades, the evolving demands for the elderly and frail patients typically encountered in the developed world, and the needs of much younger and poorer rheumatic heart disease patients in the developing world have now necessitated new paradigms for heart valve technologies and associated materials. This includes further consideration of durable elastomeric materials. The use of polymers to produce flexible leaflet valves that have the benefits of current commercial bioprosthetic and mechanical valves without any of their deficiencies has been held desirable since the mid 1950s. Much attention has been focused on thermoplastic polyurethanes in view of their generally good physico-chemical properties and versatility in processing, coupled with the improving biocompatibility and stability of recent formulations. Accelerated in vitro durability of between 600 and 1000 million cycles has been achieved using polycarbonate urethanes, and good resistance to degradation, calcification and thrombosis in vivo has been shown with some polysiloxane-based polyurethanes. Nevertheless, polymeric valves have remained relegated to use in temporary ventricular assist devices for bridging heart failure patients to transplantation. Some recent studies suggest that there is a greater degree of instability in thermoplastic materials than hitherto believed so that significant challenges remain in the search for the combination of durability and biocompatibility that would allow polymeric valves to become a clinical reality for surgical implantation. Perhaps more importantly, they could become candidates for use in situations where minimally invasive transcatheter procedures are used to

[Experimental studies of original valved conduit using glutaraldehyde-preserved equine pericardium (Xenomedica)].

PubMed

Murakami, T

1989-05-01

Extracardiac conduits, such as Dacron or homo-graft, have been utilized for the operative management of many patients with congenital right ventricular outflow obstruction. However, they have been recognized to become obstructed or calcified with time. As a new material for extracardiac conduit, an original valved conduit using glutaraldehyde-preserved equine pericardium (Xenomedica) was investigated. Various types of valved conduit were evaluated for the hydrodynamics by a circulation system. A flow-pressure gradient Lissajous was used for the evaluation. The conduit of 10 mm in diameter had a high resistance to flow. The monocusp-valved conduit had a diastolic regurgitation (DR) at any given pressures and heart rates. The bicusp-valved conduit had a DR at higher heart rates (greater than 153/min). In this experiment, the tricusp-valved conduit with a valvular vertical versus horizontal length ratio of 2:3 had utmost favorable results under any given conditions. The valved conduits were also evaluated using sixteen mongrel dogs in which the conduit were used for the reconstruction of continuity between right ventricle and pulmonary artery. Five dogs died of bacterial infection or thrombotic obstruction. Following hemodynamic studies, which were performed in eleven dogs 1, 6, and 12 months after the operation, the dogs were sacrificed to evaluate the histological changes in the conduits. The valvular function had been satisfactory until one month, however, it was lost in 6 months because the valvular leaflets were covered with neointimae grown over them. Thin neointimae were observed both at the sites of anastomosis and at the base of the valves in dogs sacrificed at one month. They spread from the proximal anastomotic site to distal one. They were organized and it was hard to remove them manually. Thrombi were found in six dogs at the proximal anastomotic site with intimal hyperplasia. There was no calcification in Xenomedica and its degenerative change was

Bioprosthetic Valve Fracture Improves the Hemodynamic Results of Valve-in-Valve Transcatheter Aortic Valve Replacement.

PubMed

Chhatriwalla, Adnan K; Allen, Keith B; Saxon, John T; Cohen, David J; Aggarwal, Sanjeev; Hart, Anthony J; Baron, Suzanne J; Dvir, Danny; Borkon, A Michael

2017-07-01

Valve-in-valve (VIV) transcatheter aortic valve replacement (TAVR) may be less effective in small surgical valves because of patient/prosthesis mismatch. Bioprosthetic valve fracture (BVF) using a high-pressure balloon can be performed to facilitate VIV TAVR. We report data from 20 consecutive clinical cases in which BVF was successfully performed before or after VIV TAVR by inflation of a high-pressure balloon positioned across the valve ring during rapid ventricular pacing. Hemodynamic measurements and calculation of the valve effective orifice area were performed at baseline, immediately after VIV TAVR, and after BVF. BVF was successfully performed in 20 patients undergoing VIV TAVR with balloon-expandable (n=8) or self-expanding (n=12) transcatheter valves in Mitroflow, Carpentier-Edwards Perimount, Magna and Magna Ease, Biocor Epic and Biocor Epic Supra, and Mosaic surgical valves. Successful fracture was noted fluoroscopically when the waist of the balloon released and by a sudden drop in inflation pressure, often accompanied by an audible snap. BVF resulted in a reduction in the mean transvalvular gradient (from 20.5±7.4 to 6.7±3.7 mm Hg, P <0.001) and an increase in valve effective orifice area (from 1.0±0.4 to 1.8±0.6 cm 2 , P <0.001). No procedural complications were reported. BVF can be performed safely in small surgical valves to facilitate VIV TAVR with either balloon-expandable or self-expanding transcatheter valves and results in reduced residual transvalvular gradients and increased valve effective orifice area. © 2017 American Heart Association, Inc.

Proton pumping accompanies calcification in foraminifera.

PubMed

Toyofuku, Takashi; Matsuo, Miki Y; de Nooijer, Lennart Jan; Nagai, Yukiko; Kawada, Sachiko; Fujita, Kazuhiko; Reichart, Gert-Jan; Nomaki, Hidetaka; Tsuchiya, Masashi; Sakaguchi, Hide; Kitazato, Hiroshi

2017-01-27

Ongoing ocean acidification is widely reported to reduce the ability of calcifying marine organisms to produce their shells and skeletons. Whereas increased dissolution due to acidification is a largely inorganic process, strong organismal control over biomineralization influences calcification and hence complicates predicting the response of marine calcifyers. Here we show that calcification is driven by rapid transformation of bicarbonate into carbonate inside the cytoplasm, achieved by active outward proton pumping. Moreover, this proton flux is maintained over a wide range of pCO 2 levels. We furthermore show that a V-type H + ATPase is responsible for the proton flux and thereby calcification. External transformation of bicarbonate into CO 2 due to the proton pumping implies that biomineralization does not rely on availability of carbonate ions, but total dissolved CO 2 may not reduce calcification, thereby potentially maintaining the current global marine carbonate production.

Proton pumping accompanies calcification in foraminifera

NASA Astrophysics Data System (ADS)

Toyofuku, Takashi; Matsuo, Miki Y.; de Nooijer, Lennart Jan; Nagai, Yukiko; Kawada, Sachiko; Fujita, Kazuhiko; Reichart, Gert-Jan; Nomaki, Hidetaka; Tsuchiya, Masashi; Sakaguchi, Hide; Kitazato, Hiroshi

2017-01-01

Ongoing ocean acidification is widely reported to reduce the ability of calcifying marine organisms to produce their shells and skeletons. Whereas increased dissolution due to acidification is a largely inorganic process, strong organismal control over biomineralization influences calcification and hence complicates predicting the response of marine calcifyers. Here we show that calcification is driven by rapid transformation of bicarbonate into carbonate inside the cytoplasm, achieved by active outward proton pumping. Moreover, this proton flux is maintained over a wide range of pCO2 levels. We furthermore show that a V-type H+ ATPase is responsible for the proton flux and thereby calcification. External transformation of bicarbonate into CO2 due to the proton pumping implies that biomineralization does not rely on availability of carbonate ions, but total dissolved CO2 may not reduce calcification, thereby potentially maintaining the current global marine carbonate production.

Treatment with pyrophosphate inhibits uremic vascular calcification

PubMed Central

O’Neill, W. Charles; Lomashvili, Koba A.; Malluche, Hartmut H.; Faugere, Marie-Claude; Riser, Bruce L.

2011-01-01

Pyrophosphate, which may be deficient in advanced renal failure, is a potent inhibitor of vascular calcification. To explore its use as a potential therapeutic, we injected exogenous pyrophosphate subcutaneously or intraperitoneally in normal rats and found that their plasma pyrophosphate concentrations peaked within 15 min. There was a single exponential decay with a half-life of 33 min. The kinetics were indistinguishable between the two routes of administration or in anephric rats. The effect of daily intraperitoneal pyrophosphate injections on uremic vascular calcification was then tested in rats fed a high-phosphate diet containing adenine for 28 days to induce uremia. Although the incidence of aortic calcification varied and was not altered by pyrophosphate, the calcium content of calcified aortas was significantly reduced by 70%. Studies were repeated in uremic rats given calcitriol to produce more consistent aortic calcification and treated with sodium pyrophosphate delivered intraperitoneally in a larger volume of glucose-containing solution to prolong plasma pyrophosphate levels. This maneuver significantly reduced both the incidence and amount of calcification. Quantitative histomorphometry of bone samples after double-labeling with calcein indicated that there was no effect of pyrophosphate on the rates of bone formation or mineralization. Thus, exogenous pyrophosphate can inhibit uremic vascular calcification without producing adverse effects on bone. PMID:21124302

Treatment with pyrophosphate inhibits uremic vascular calcification.

PubMed

O'Neill, W Charles; Lomashvili, Koba A; Malluche, Hartmut H; Faugere, Marie-Claude; Riser, Bruce L

2011-03-01

Pyrophosphate, which may be deficient in advanced renal failure, is a potent inhibitor of vascular calcification. To explore its use as a potential therapeutic, we injected exogenous pyrophosphate subcutaneously or intraperitoneally in normal rats and found that their plasma pyrophosphate concentrations peaked within 15 min. There was a single exponential decay with a half-life of 33 min. The kinetics were indistinguishable between the two routes of administration or in anephric rats. The effect of daily intraperitoneal pyrophosphate injections on uremic vascular calcification was then tested in rats fed a high-phosphate diet containing adenine for 28 days to induce uremia. Although the incidence of aortic calcification varied and was not altered by pyrophosphate, the calcium content of calcified aortas was significantly reduced by 70%. Studies were repeated in uremic rats given calcitriol to produce more consistent aortic calcification and treated with sodium pyrophosphate delivered intraperitoneally in a larger volume of glucose-containing solution to prolong plasma pyrophosphate levels. This maneuver significantly reduced both the incidence and amount of calcification. Quantitative histomorphometry of bone samples after double-labeling with calcein indicated that there was no effect of pyrophosphate on the rates of bone formation or mineralization. Thus, exogenous pyrophosphate can inhibit uremic vascular calcification without producing adverse effects on bone.

Transcatheter Aortic Valve-in-Valve Procedure in Patients with Bioprosthetic Structural Valve Deterioration

PubMed Central

Reul, Ross M.; Ramchandani, Mahesh K.; Reardon, Michael J.

2017-01-01

Surgical aortic valve replacement is the gold standard procedure to treat patients with severe, symptomatic aortic valve stenosis or insufficiency. Bioprosthetic valves are used for surgical aortic valve replacement with a much greater prevalence than mechanical valves. However, bioprosthetic valves may fail over time because of structural valve deterioration; this often requires intervention due to severe bioprosthetic valve stenosis or regurgitation or a combination of both. In select patients, transcatheter aortic valve replacement is an alternative to surgical aortic valve replacement. Transcatheter valve-in-valve (ViV) replacement is performed by implanting a transcatheter heart valve within a failing bioprosthetic valve. The transcatheter ViV operation is a less invasive procedure compared with reoperative surgical aortic valve replacement, but it has been associated with specific complications and requires extensive preoperative work-up and planning by the heart team. Data from experimental studies and analyses of results from clinical procedures have led to strategies to improve outcomes of these procedures. The type, size, and implant position of the transcatheter valve can be optimized for individual patients with knowledge of detailed dimensions of the surgical valve and radiographic and echocardiographic measurements of the patient's anatomy. Understanding the complexities of the ViV procedure can lead surgeons to make choices during the original surgical valve implantation that can make a future ViV operation more technically feasible years before it is required. PMID:29743998

Calcification by Reef-Building Sclerobionts

PubMed Central

Mallela, Jennie

2013-01-01

It is widely accepted that deteriorating water quality associated with increased sediment stress has reduced calcification rates on coral reefs. However, there is limited information regarding the growth and development of reef building organisms, aside from the corals themselves. This study investigated encruster calcification on five fore-reefs in Tobago subjected to a range of sedimentation rates (1.2 to 15.9 mg cm−2 d−1). Experimental substrates were used to assess rates of calcification in sclerobionts (e.g. crustose coralline algae, bryozoans and barnacles) across key reef microhabitats: cryptic (low-light), exposed (open-horizontal) and vertical topographic settings. Sedimentation negatively impacted calcification by photosynthesising crustose coralline algae in exposed microhabitats and encrusting foram cover (%) in exposed and cryptic substrates. Heterotrophs were not affected by sedimentation. Fore-reef, turbid water encruster assemblages calcified at a mean rate of 757 (SD ±317) g m−2 y−1. Different microhabitats were characterised by distinct calcareous encruster assemblages with different rates of calcification. Taxa with rapid lateral growth dominated areal cover but were not responsible for the majority of CaCO3 production. Cryptobiont assemblages were composed of a suite of calcifying taxa which included sciaphilic cheilostome bryozoans and suspension feeding barnacles. These calcified at mean rates of 20.1 (SD ±27) and 4.0 (SD ±3.6) g m−2 y−1 respectively. Encruster cover (%) on exposed and vertical substrates was dominated by crustose coralline algae which calcified at rates of 105.3 (SD ±67.7) g m−2 y−1 and 56.3 (SD ±8.3) g m−2 y−1 respectively. Globally, encrusting organisms contribute significant amounts of carbonate to the reef framework. These results provide experimental evidence that calcification rates, and the importance of different encrusting organisms, vary significantly according to topography and sediment

Secondary calcification and dissolution respond differently to future ocean conditions

NASA Astrophysics Data System (ADS)

Silbiger, N. J.; Donahue, M. J.

2014-09-01

Climate change threatens both the accretion and erosion processes that sustain coral reefs. Secondary calcification, bioerosion, and reef dissolution are integral to the structural complexity and long-term persistence of coral reefs, yet these processes have received less research attention than reef accretion by corals. In this study, we use climate scenarios from RCP8.5 to examine the combined effects of rising ocean acidity and SST on both secondary calcification and dissolution rates of a natural coral rubble community using a flow-through aquarium system. We found that secondary reef calcification and dissolution responded differently to the combined effect of pCO2 and temperature. Calcification had a non-linear response to the combined effect of pCO2-temperature: the highest calcification rate occurred slightly above ambient conditions and the lowest calcification rate was in the highest pCO2-temperature condition. In contrast, dissolution increased linearly with pCO2-temperature. The rubble community switched from net calcification to net dissolution at +272 μatm pCO2 and 0.84 °C above ambient conditions, suggesting that rubble reefs may shift from net calcification to net dissolution before the end of the century. Our results indicate that dissolution may be more sensitive to climate change than calcification, and that calcification and dissolution have different functional responses to climate stressors, highlighting the need to study the effects of climate stressors on both calcification and dissolution to predict future changes in coral reefs.

Smoking and morphology of calcific deposits affect the outcome of needle aspiration of calcific deposits (NACD) for calcific tendinitis of the rotator cuff.

PubMed

Oudelaar, Bart W; Ooms, Edwin M; Huis In 't Veld, Rianne M H A; Schepers-Bok, Relinde; Vochteloo, Anne J

2015-11-01

Although NACD has proven to be an effective minimal invasive treatment for calcific tendinitis of the rotator cuff, little is known about the factors associated with treatment failure or the need for multiple procedures. Patients with symptomatic calcific tendinitis who were treated by NACD were evaluated in a retrospective cohort study. Demographic details, medical history, sonographic and radiographic findings were collected from patient files. Failure of NACD was defined as the persistence of symptoms after a follow-up of at least six months. NACD procedures performed within six months after a previous NACD procedure were considered repeated procedures. Multivariate logistic regression analysis was used to determine factors associated with treatment failure and multiple procedures. 431 patients (277 female; mean age 51.4±9.9 years) were included. Smoking (adjusted odds ratio (AOR): 1.7, 95% CI 1.0-2.7, p=0.04) was significantly associated with failure of NACD. Patients with Gärtner and Heyer (GH) type I calcific deposits were more likely to need multiple NACD procedures (AOR: 3.4, 95% CI 1.6-7.5, p<0.01) compared to patients with type III calcific deposits. Partial thickness rotator cuff tears were of no influence on the outcome of NACD or the number of treatments necessary. Smoking almost doubled the chance of failure of NACD and the presence of GH type I calcific deposits significantly increased the chance of multiple procedures. Partial thickness rotator cuff tears did not seem to affect the outcome of NACD. Based on the findings in this study, the importance of quitting smoking should be emphasized prior to NACD and partial thickness rotator cuff tears should not be a reason to withhold patients NACD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Calcification and photosynthesis of the coral acropora cervicornis under calcium limited conditions

NASA Technical Reports Server (NTRS)

Rathfon, Megan; Brewer, Debbie

1997-01-01

Differing hypothesis about the function of calcification are based on an interesting dilemma. Is the purpose of calcification mainly a structural and protective one or does calcification serve other functions? Does photosynthesis increase carbonate ion activity and cause calcification or does calcification increase CO2 levels and stimulate photsynthesis? It is proposed that calcification in corals is not dependent upon photosynthesis but upon calcium levels in the water. Under normal ocean conditions, corals convert a certain percentage of energy to photosynthesis and respiration and another percentage to calcification. As corals become nutrient stressed, particularly calcium limited, the ratio of photosynthesis to calcification shifts towards calcification in order to generate protons. The protons generated during calcification may stimulate photosynthesis and aid in the uptake of nutrients and biocarbonates. The results of the calcification experiment show a trend towards increased calcification and decreased photosynthesis when the coral Acropora cervicornis is calcium limited, but the data are inconclusive and further research is needed.

Secondary calcification and dissolution respond differently to future ocean conditions

NASA Astrophysics Data System (ADS)

Silbiger, N. J.; Donahue, M. J.

2015-01-01

Climate change threatens both the accretion and erosion processes that sustain coral reefs. Secondary calcification, bioerosion, and reef dissolution are integral to the structural complexity and long-term persistence of coral reefs, yet these processes have received less research attention than reef accretion by corals. In this study, we use climate scenarios from RCP 8.5 to examine the combined effects of rising ocean acidity and sea surface temperature (SST) on both secondary calcification and dissolution rates of a natural coral rubble community using a flow-through aquarium system. We found that secondary reef calcification and dissolution responded differently to the combined effect of pCO2 and temperature. Calcification had a non-linear response to the combined effect of pCO2 and temperature: the highest calcification rate occurred slightly above ambient conditions and the lowest calcification rate was in the highest temperature-pCO2 condition. In contrast, dissolution increased linearly with temperature-pCO2 . The rubble community switched from net calcification to net dissolution at +271 μatm pCO2 and 0.75 °C above ambient conditions, suggesting that rubble reefs may shift from net calcification to net dissolution before the end of the century. Our results indicate that (i) dissolution may be more sensitive to climate change than calcification and (ii) that calcification and dissolution have different functional responses to climate stressors; this highlights the need to study the effects of climate stressors on both calcification and dissolution to predict future changes in coral reefs.

Feasibility of pig and human-derived aortic valve interstitial cells seeding on fixative-free decellularized animal pericardium.

PubMed

Santoro, Rosaria; Consolo, Filippo; Spiccia, Marco; Piola, Marco; Kassem, Samer; Prandi, Francesca; Vinci, Maria Cristina; Forti, Elisa; Polvani, Gianluca; Fiore, Gianfranco Beniamino; Soncini, Monica; Pesce, Maurizio

2016-02-01

Glutaraldehyde-fixed pericardium of animal origin is the elective material for the fabrication of bio-prosthetic valves for surgical replacement of insufficient/stenotic cardiac valves. However, the pericardial tissue employed to this aim undergoes severe calcification due to chronic inflammation resulting from a non-complete immunological compatibility of the animal-derived pericardial tissue resulting from failure to remove animal-derived xeno-antigens. In the mid/long-term, this leads to structural deterioration, mechanical failure, and prosthesis leaflets rupture, with consequent need for re-intervention. In the search for novel procedures to maximize biological compatibility of the pericardial tissue into immunocompetent background, we have recently devised a procedure to decellularize the human pericardium as an alternative to fixation with aldehydes. In the present contribution, we used this procedure to derive sheets of decellularized pig pericardium. The decellularized tissue was first tested for the presence of 1,3 α-galactose (αGal), one of the main xenoantigens involved in prosthetic valve rejection, as well as for mechanical tensile behavior and distensibility, and finally seeded with pig- and human-derived aortic valve interstitial cells. We demonstrate that the decellularization procedure removed the αGAL antigen, maintained the mechanical characteristics of the native pig pericardium, and ensured an efficient surface colonization of the tissue by animal- and human-derived aortic valve interstitial cells. This establishes, for the first time, the feasibility of fixative-free pericardial tissue seeding with valve competent cells for derivation of tissue engineered heart valve leaflets. © 2015 Wiley Periodicals, Inc.

Hepatic steatosis is associated with aortic valve sclerosis in the general population: the Study of Health in Pomerania (SHIP).

PubMed

Markus, Marcello Ricardo Paulista; Baumeister, Sebastian Edgar; Stritzke, Jan; Dörr, Marcus; Wallaschofski, Henri; Völzke, Henry; Lieb, Wolfgang

2013-07-01

We aimed to analyze the association between hepatic steatosis and aortic valve sclerosis in the general population. Cross-sectional data of 2212 men and women, aged 45 to 81 years, from the baseline examination of the population-based Study of Health in Pomerania (SHIP-0) were analyzed. Hepatic steatosis was primarily defined as the presence of a hyperechogenic ultrasound pattern of the liver. Aortic valve sclerosis was determined by echocardiography. In our sample, hepatic steatosis was present in 877 (39.7%) individuals. Among participants with hepatic steatosis, aortic valve sclerosis was more common (n=323; 36.8%) compared with participants without hepatic steatosis (n=379; 28.4%; P<0.001). After adjustment for potential confounders, individuals with hepatic steatosis had 33% higher odds of aortic valve sclerosis compared with those without hepatic steatosis (95% confidence interval, 6%-66%; P=0.014). Additional adjustment for high-sensitive C-reactive protein, serum ferritin levels, and white blood cells slightly reduced the association to 32% (95% confidence interval, 4%-66%; P=0.021). Our findings add evidence that hepatic steatosis and aortic valve sclerosis are interrelated after adjustment for major confounders. The release of proatherogenic substances by the steatotic liver or its contribution to insulin resistance and dyslipidemia may contribute to the development of calcification and sclerosis of the aortic valve.

Chronic parotitis with multiple calcifications: Clinical and sialendoscopic findings.

PubMed

Jáuregui, Emmanuel; Kiringoda, Ruwan; Ryan, William R; Eisele, David W; Chang, Jolie L

2017-07-01

To characterize clinical, imaging, and sialendoscopy findings in patients with chronic parotitis and multiple parotid calcifications. Retrospective review. Clinical history, radiographic images and reports, lab tests, and operative reports were reviewed for adult patients with chronic parotitis and multiple parotid calcifications who underwent parotid sialendoscopy. Thirteen of 133 (10%) patients undergoing parotid sialendoscopy for chronic sialadenitis had more than one calcification in the region of the parotid gland. Seven patients (54%) were diagnosed with immune-mediated disease from autoimmune parotitis (positive Sjögren's antibodies or antinuclear antibodies) or human immunodeficiency virus (HIV) disease. The six patients (46%) who did not have an immune-mediated disorder had most calcifications located anterior or along the masseter muscle. Eight of 13 patients (61%) had at least one calculus found in the parotid duct on sialendoscopy. Four patients (38%) had multiple punctate calcifications within the parotid gland, all of whom had either autoimmune parotitis or HIV. None of the proximal or punctate parotid calcifications posterior to the masseter were visualized on sialendoscopy. Chronic parotitis in conjunction with multiple parotid calcifications is uncommon and was identified in 10% of our cohort. We contrast two classifications of parotid calcifications: 1) intraductal stones that cause recurrent duct obstruction and are often located within the main parotid duct along or anterior to the masseter and 2) punctate intraparenchymal parotid gland calcifications that are not visualized on sialendoscopy and may represent underlying inflammatory disease. 4 Laryngoscope, 127:1565-1570, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Predictors of temporary epicardial pacing wires use after valve surgery

PubMed Central

2014-01-01

Background Although temporary cardiac pacing is infrequently needed, temporary epicardial pacing wires are routinely inserted after valve surgery. As they are associated with infrequent, but life threatening complications, and the decreased need for postoperative pacing in a group of low risk patients; this study aims to identify the predictors of temporary cardiac pacing after valve surgery. Methods A retrospective analysis of data collected prospectively on 400 consecutive valve surgery patients between May 2002 and December 2012 was performed. Patients were grouped according to avoidance or insertion of temporary pacing wires, and were further subdivided according to temporary cardiac pacing need. Multiple logistic regression was used to determine the predictors of temporary cardiac pacing. Results 170 (42.5%) patients did not have insertion of temporary pacing wires and none of them needed temporary pacing. 230 (57.5%) patients had insertion of temporary pacing wires and among these, only 55 (23.9%) required temporary pacing who were compared with the remaining 175 (76.1%) patients in the main analysis. The determinants of temporary cardiac pacing (adjusted odds ratios; 95% confidence interval) were as follows: increased age (1.1; 1.1, 1.3, p = 0.002), New York Heart Association class III- IV (5.6; 1.6, 20.2, p = 0.008) , pulmonary artery pressure ≥ 50 mmHg (22.0; 3.4, 142.7, p = 0.01), digoxin use (8.0; 1.3, 48.8, p = 0.024), multiple valve surgery (13.5; 1.5, 124.0, p = 0.021), aorta cross clamp time ≥ 60 minutes (7.8; 1.6, 37.2, p = 0.010), and valve annulus calcification (7.9; 2.0, 31.7, p = 0.003). Conclusion Although limited by sample size, the present results suggest that routine use of temporary epicardial pacing wires after valve surgery is only necessary for high risk patients. Preoperative identification and aggressive management of predictors of temporary cardiac pacing and the possible modulation of

The incidence of renal calcification in preterm infants.

PubMed Central

Short, A; Cooke, R W

1991-01-01

A total of 79 infants born at less than 32 weeks' gestation were studied with serial renal ultrasound scans to assess the incidence of nephrocalcinosis. Twenty one infants developed renal calcification giving an overall incidence of 26.6% in the study group. Affected infants were significantly smaller (mean (SD) birth weight 940 (323) g) and significantly less mature (mean (SD) gestation 26.9 (1.9) weeks). In 17 patients the calcification was represented by hyperechogenic renal pyramids alone, and in four patients renal calculi were demonstrated. Factors associated with renal calcification included hypophosphataemia, hypercalcaemia, hypercreatininaemia, and prolonged oxygen requirement during the first month of life. Multivariate analysis showed that the strongest clinical indicator of calcification was duration of oxygen treatment. Infants who still required oxygen treatment at 28 days had a 62% chance of developing renal calcification. Images Figure 4 Figure 5 PMID:2025034

[Arterial media calcification in patients with type 2 diabetes mellitus].

PubMed

Belovici, Maria Isabela; Pandele, G I

2008-01-01

Arterial calcification was previously viewed as an inevitable, passive, and degenerative process that occurred at the end stages of atherosclerosis. Recent studies, however, have demonstrated that calcification of arteries is a complex and regulated process. It may occur in conjunction with atherosclerosis or in an isolated form that is commonly associated with diabetes and renal failure. Higher artery calcium scores are associated with increased cardiovascular events, and some aspects of arterial calcification are similar to the biology of forming bone. Arterial calcification can thus be viewed as a distinct inflammatory arteriopathy, much like atherosclerosis and aneurysms, with its own contribution to cardiovascular morbidity and mortality. Current research involves efforts to define the complex interactions between cellular and molecular mediators of arterial calcification and, in particular, the role of endogenous calcification inhibitors. This review discusses the clinical relevance, cellular events, and suspected molecular pathways that control arterial calcification.

Periodontal disease is an independent predictor of intracardiac calcification.

PubMed

Pressman, Gregg S; Qasim, Atif; Verma, Nitin; Miyamae, Masami; Arishiro, Kumiko; Notohara, Yasuhiro; Crudu, Vitalie; Figueredo, Vincent M

2013-01-01

Periodontitis is the most common chronic inflammatory condition worldwide and is associated with incident coronary disease. We hypothesized that periodontal disease would also be associated with cardiac calcification, a condition which shares many risk factors with atherosclerosis and is considered a marker of subclinical atherosclerosis. Cross-sectional study at two sites (USA and Japan) involving subjects with both clinical echocardiograms and detailed dental examinations. Semiquantitative scoring systems were used to assess severity of periodontal disease and echocardiographic calcification. Fifty-six of 73 subjects (77%) had cardiac calcifications, and 51% had moderate to severe periodontal disease (score > 2). In unadjusted analysis, a significant relationship between periodontal score and cardiac calcification (Spearman rho = 0.4, P = 0.001) was noted, with increases in mean calcification score seen across increasing levels of periodontal disease. On multivariate logistic regression, adjusted for age, gender, race, glomerular filtration rate, and traditional risk factors, this association remained significant (P = 0.024). There was no significant interaction by study site, race, or gender. In a multiracial population, we found a significant association between the degree of periodontal disease, a chronic inflammatory condition, and cardiac calcification. Further, higher periodontal scores were associated with greater degrees of calcification.

Early graft failure of small-sized porcine valved conduits in reconstruction of the right ventricular outflow tract.

PubMed

Schreiber, Christian; Sassen, Stefanie; Kostolny, Martin; Hörer, Jürgen; Cleuziou, Julie; Wottke, Michael; Holper, Klaus; Fend, Falko; Eicken, Andreas; Lange, Rüdiger

2006-07-01

The quest for an alternative to homografts for reconstruction of the right ventricular outflow tract is ongoing. The Shelhigh No-React (NR-4000PA series) treated porcine pulmonic valve conduit (SPVC) was developed as a potential alternative. During a 12-month period from May 2004 to May 2005, the SPVC was implanted in 34 patients, of whom 62% were younger than 1 year. Median age at operation was 7 months (range, 5 days to 12 years). Thirteen SPCV conduits size 10, 11 size 12, 8 size 14, and 2 size 16 were initially implanted. Since May 2005, however, we have temporarily abandoned its implantation as we were concerned about a number of early failures. Until November 2005, 1 early and 1 late death have occurred. Both were not conduit related. Fifteen conduits were replaced in 13 patients. Of these, 10 were size 10, 3 size 12, 2 size 14, and none size 16. Mean time to replacement of the SPVC was 313 +/- 116 days. A pseudointimal peel formation and chronic inflammation with foreign-body reaction was found in all explanted conduits at all levels. The maximum of the inflammatory reaction occurred at the valvular level around the porcine tissues, with shrinkage of the valve and hemodynamic compromise. At valvular level, small punctuate calcifications were observed in 2 cases. In 6 patients an acute inflammatory component was observed. At late follow-up (mean follow-up 366 +/- 102 days, 34 patient-years), echocardiography showed a mean graft gradient of 39.8 +/- 29.7 mm Hg, with mild to moderate insufficiency in 4 patients. Although the No-React treated valve largely resists calcification, pseudointimal peel formation was found in all explanted conduits and led to multilevel conduit stenoses. The small-sized SPVC can not be regarded as an ideal conduit for right ventricular outflow tract reconstruction.

Skeletal maturity assessment using mandibular canine calcification stages.

PubMed

Džemidžić, Vildana; Tiro, Alisa; Zukanović, Amila; Redžić, Ismeta; Nakaš, Enita

2016-11-01

The aims of this study were: to investigate the relationship between mandibular canine calcification stages and skeletal maturity; and to evaluate whether the mandibular canine calcification stages may be used as a reliable diagnostic tool for skeletal maturity assessment. This study included 151 subjects: 81 females and 70 males, with ages ranging from 9 to 16 years (mean age: 12.29±1.86 years). The inclusion criteria for subjects were as follows: age between 9 and 16 years; good general health without any hormonal, nutritional, growth or dental development problems. Subjects who were undergoing or had previously received orthodontic treatment were not included in this study. The calcification stages of the left permanent mandibular canine were assessed according to the method of Demirjian, on panoramic radiographs. Assessment of skeletal maturity was carried out using the cervical vertebral maturation index (CVMI), as proposed by the Hassel-Farman method, on lateral cephalograms. The correlation between the calcification stages of mandibular canine and skeletal maturity was estimated separately for male and female subjects. Correlation coefficients between calcification stages of mandibular canine and skeletal maturity were 0.895 for male and 0.701 for female subjects. A significant correlation was found between the calcification stages of the mandibular canine and skeletal maturity. The calcification stages of the mandibular canine show a satisfactory diagnostic performance only for assessment of pre-pubertal growth phase. Copyright © 2016 by Academy of Sciences and Arts of Bosnia and Herzegovina.

Susceptibility weighted imaging: differentiating between calcification and hemosiderin*

PubMed Central

Barbosa, Jeam Haroldo Oliveira; Santos, Antonio Carlos; Salmon, Carlos Ernesto Garrido

2015-01-01

Objective To present a detailed explanation on the processing of magnetic susceptibility weighted imaging (SWI), demonstrating the effects of echo time and sensitive mask on the differentiation between calcification and hemosiderin. Materials and Methods Computed tomography and magnetic resonance (magnitude and phase) images of six patients (age range 41– 54 years; four men) were retrospectively selected. The SWI images processing was performed using the Matlab’s own routine. Results Four out of the six patients showed calcifications at computed tomography images and their SWI images demonstrated hyperintense signal at the calcification regions. The other patients did not show any calcifications at computed tomography, and SWI revealed the presence of hemosiderin deposits with hypointense signal. Conclusion The selection of echo time and of the mask may change all the information on SWI images, and compromise the diagnostic reliability. Amongst the possible masks, the authors highlight that the sigmoid mask allows for contrasting calcifications and hemosiderin on a single SWI image. PMID:25987750

Inverse Relationship Between Membranous Septal Length and the Risk of Atrioventricular Block in Patients Undergoing Transcatheter Aortic Valve Implantation.

PubMed

Hamdan, Ashraf; Guetta, Victor; Klempfner, Robert; Konen, Eli; Raanani, Ehud; Glikson, Michael; Goitein, Orly; Segev, Amit; Barbash, Israel; Fefer, Paul; Spiegelstein, Dan; Goldenberg, Ilan; Schwammenthal, Ehud

2015-08-17

This study sought to examine whether imaging of the atrioventricular (AV) membranous septum (MS) by computed tomography (CT) can be used to identify patient-specific anatomic risk of high-degree AV block and permanent pacemaker (PPM) implantation before transcatheter aortic valve implantation (TAVI) with self-expandable valves. MS length represents an anatomic surrogate of the distance between the aortic annulus and the bundle of His and may therefore be inversely related to the risk of conduction system abnormalities after TAVI. Seventy-three consecutive patients with severe aortic stenosis underwent contrast-enhanced CT before TAVI. The aortic annulus, aortic valve, and AV junction were assessed, and MS length was measured in the coronal view. In 13 patients (18%), high-degree AV block developed, and 21 patients (29%) received a PPM. Multivariable logistic regression analysis revealed MS length as the most powerful pre-procedural independent predictor of high-degree AV block (odds ratio [OR]: 1.35, 95% confidence interval [CI]: 1.1 to 1.7, p = 0.01) and PPM implantation (OR: 1.43, 95% CI: 1.1 to 1.8, p = 0.002). When taking into account pre- and post-procedural parameters, the difference between MS length and implantation depth emerged as the most powerful independent predictor of high-degree AV block (OR: 1.4, 95% CI: 1.2 to 1.7, p < 0.001), whereas the difference between MS length and implantation depth and calcification in the basal septum were the most powerful independent predictors of PPM implantation (OR: 1.39, 95% CI: 1.2 to 1.7, p < 0.001 and OR: 4.9, 95% CI: 1.2 to 20.5, p = 0.03; respectively). Short MS, insufficient difference between MS length and implantation depth, and the presence of calcification in the basal septum, factors that may all facilitate mechanical compression of the conduction tissue by the implanted valve, predict conduction abnormalities after TAVI with self-expandable valves. CT assessment of membranous septal anatomy provides

Concurrent Transcatheter Aortic Valve Implantation and Percutaneous Transvenous Mitral Commissurotomy for Totally Percutaneous Treatment of Combined Severe Rheumatic Aortic and Mitral Stenosis.

PubMed

Bilge, Mehmet; Alsancak, Yakup; Ali, Sina; Yasar, Ayse Saatci

2015-05-01

Transcatheter aortic valve implantation (TAVI) is a new promising therapeutic option for patients with symptomatic severe calcific aortic valve stenosis (AS) who are inoperable or at high risk for conventional cardiac surgery. Percutaneous transvenous mitral commissurotomy (PTMC) is performed routinely in patients with severe mitral stenosis (MS) having a favorable anatomy. Although concurrent TAVI and PTMC is a theoretically possible approach in the treatment of patients with severe AS and MS who are unsuitable for conventional surgery, no cases have yet been reported in which this combined technique is used. For patients with severe AS and MS, the standard therapy is replacement of both the mitral and aortic valves. Herein are presented the details of a 52-year-old woman with urethral carcinoma, in whom simultaneous TAVI and PTMC was the chosen technique to treat combined severe rheumatic AS and MS in a single procedure.

Transcatheter aortic valve-in-valve implantation of a CoreValve in a JenaValve prosthesis: a case report.

PubMed

Lotfi, Shahram; Becker, Michael; Moza, Ajay; Autschbach, Rüdiger; Marx, Nikolaus; Schröder, Jörg

2017-09-10

Transcatheter aortic valve implantation has become an accepted treatment modality for inoperable or high-risk surgical patients with symptomatic severe aortic stenosis. We report the case of a 70-year-old white man who was treated for severe symptomatic aortic regurgitation using transcatheter aortic valve implantation from the apical approach. Because of recurrent cardiac decompensation 4 weeks after implantation he underwent the implantation of a left ventricular assist device system. A year later echocardiography showed a severe transvalvular central insufficiency. Our heart team decided to choose a valve-in-valve approach while reducing the flow rate of left ventricular assist device to minimum and pacing with a frequency of 140 beats/minute. There was an excellent result and our patient is doing well with no relevant insufficiency of the aortic valve at 12-month follow-up. This is the first report about a successful treatment of a stenotic JenaValve using a CoreValve Evolut R; the use of a CoreValve Evolut R prosthesis may be an optimal option for valve-in-valve procedures.

Nanobacteria may be linked to calcification in placenta.

PubMed

Lu, He; Guo, Ya-nan; Liu, Sheng-nan; Zhang, De-chun

2012-05-01

Placental calcification is a common pathologic condition in obstetrics. To detect the bacteria infection mechanisms for calcification, an experiment was performed to isolate, culture, and identify the nanobacteria in placental calcification. Sixteen cases of placental calcification of pregnant women were collected for the purpose of the isolation of nanobacteria, cultivation, and identification of 16S rDNA sequence. Under transmission electron microscope, novel oval-shape nanobacteria-like particles (NLP) in extracellular matrix of calcified placenta tissues were found with 50-500 nm in diameter, and among hydroxyapatite crystals aggregation existed. After about 4 weeks of culturing and isolating NLP from these calcified tissues, all calcified placental tissue samples and one adjacent tissue of calcified placental tissue samples showed white granular depositions, which were firmly attached to the bottom of the culture tubes and visible to the naked eyes. In the control group they could not be seen. After PCR was amplified a 1407-bp fragment was obtained and submitted to GenBank after sequencing with accession number JN029830. The 16S rDNA sequence homology between the isolation strain and strain nanobacteria (X98418) was 92% in GenBank. For the first time isolated, cultured, and identified nanobacteria in placental calcification indicated that nanobacteria infection is related to placental calcification.

Dietary potassium regulates vascular calcification and arterial stiffness.

PubMed

Sun, Yong; Byon, Chang Hyun; Yang, Youfeng; Bradley, Wayne E; Dell'Italia, Louis J; Sanders, Paul W; Agarwal, Anupam; Wu, Hui; Chen, Yabing

2017-10-05

Vascular calcification is a risk factor that predicts adverse cardiovascular complications of several diseases including atherosclerosis. Reduced dietary potassium intake has been linked to cardiovascular diseases such as hypertension and incidental stroke, although the underlying molecular mechanisms remain largely unknown. Using the ApoE-deficient mouse model, we demonstrated for the first time to our knowledge that reduced dietary potassium (0.3%) promoted atherosclerotic vascular calcification and increased aortic stiffness, compared with normal (0.7%) potassium-fed mice. In contrast, increased dietary potassium (2.1%) attenuated vascular calcification and aortic stiffness. Mechanistically, reduction in the potassium concentration to the lower limit of the physiological range increased intracellular calcium, which activated a cAMP response element-binding protein (CREB) signal that subsequently enhanced autophagy and promoted vascular smooth muscle cell (VSMC) calcification. Inhibition of calcium signals and knockdown of either CREB or ATG7, an autophagy regulator, attenuated VSMC calcification induced by low potassium. Consistently, elevated autophagy and CREB signaling were demonstrated in the calcified arteries from low potassium diet-fed mice as well as aortic arteries exposed to low potassium ex vivo. These studies established a potentially novel causative role of dietary potassium intake in regulating atherosclerotic vascular calcification and stiffness, and uncovered mechanisms that offer opportunities to develop therapeutic strategies to control vascular disease.

Serum Fetuin-A Levels in Patients with Bilateral Basal Ganglia Calcification.

PubMed

Demiryurek, Bekir Enes; Gundogdu, Asli Aksoy

2018-02-14

The idiopathic basal ganglia calcification (Fahr syndrome) may occur due to senility. Fetuin-A is a negative acute phase reactant which inhibits calcium-phosphorus precipitation and vascular calcification. In this study, we aimed to evaluate whether serum fetuin-A levels correlate with bilateral basal ganglia calcification. Forty-five patients who had bilateral basal ganglia calcification on brain CT were selected according to the inclusion and exclusion criteria, and 45 age and gender-matched subjects without basal ganglia calcification were included for the control group. Serum fetuin-A levels were measured from venous blood samples. All participants were divided into two groups; with and without basal ganglia calcification. These groups were divided into subgroups regarding age (18-32 and 33-45 years of age) and gender (male, female). We detected lower levels of serum fetuin-A in patients with basal ganglia calcification compared with the subjects without basal ganglia calcification. In all subgroups (female, male, 18-32 years and 33-45 years), mean fetuin-A levels were significantly lower in patients with basal ganglia calcification (p = 0.017, p = 0.014, p = 0.024, p = 0.026, p = 0.01 respectively). And statistically significantly lower levels of fetuin-A was found to be correlated with the increasing densities of calcification in the calcified basal ganglia group (p-value: <0.001). Considering the role of fetuin-A in tissue calcification and inflammation, higher serum fetuin-A levels should be measured in patients with basal ganglia calcification. We believe that the measurement of serum fetuin-A may play a role in the prediction of basal ganglia calcification as a biomarker. Copyright © 2017 Elsevier B.V. All rights reserved.

Periodontal Disease Is an Independent Predictor of Intracardiac Calcification

PubMed Central

Pressman, Gregg S.; Qasim, Atif; Verma, Nitin; Arishiro, Kumiko; Notohara, Yasuhiro; Crudu, Vitalie; Figueredo, Vincent M.

2013-01-01

Background. Periodontitis is the most common chronic inflammatory condition worldwide and is associated with incident coronary disease. Hypothesis. We hypothesized that periodontal disease would also be associated with cardiac calcification, a condition which shares many risk factors with atherosclerosis and is considered a marker of subclinical atherosclerosis. Methods. Cross-sectional study at two sites (USA and Japan) involving subjects with both clinical echocardiograms and detailed dental examinations. Semiquantitative scoring systems were used to assess severity of periodontal disease and echocardiographic calcification. Results. Fifty-six of 73 subjects (77%) had cardiac calcifications, and 51% had moderate to severe periodontal disease (score > 2). In unadjusted analysis, a significant relationship between periodontal score and cardiac calcification (Spearman rho = 0.4, P = 0.001) was noted, with increases in mean calcification score seen across increasing levels of periodontal disease. On multivariate logistic regression, adjusted for age, gender, race, glomerular filtration rate, and traditional risk factors, this association remained significant (P = 0.024). There was no significant interaction by study site, race, or gender. Conclusions. In a multiracial population, we found a significant association between the degree of periodontal disease, a chronic inflammatory condition, and cardiac calcification. Further, higher periodontal scores were associated with greater degrees of calcification. PMID:24106721

The challenge of valve-in-valve procedures in degenerated Mitroflow bioprostheses and the advantage of using the JenaValve transcatheter heart valve.

PubMed

Conradi, Lenard; Kloth, Benjamin; Seiffert, Moritz; Schirmer, Johannes; Koschyk, Dietmar; Blankenberg, Stefan; Reichenspurner, Hermann; Diemert, Patrick; Treede, Hendrik

2014-12-01

Recently, the feasibility of valve-in-valve procedures using current first-generation transcatheter heart valves (THV) in cases of structural valve degeneration has been reported as an alternative to conventional open repeat valve replacement. By design, certain biological valve xenografts carry a high risk of coronary ostia occlusion due to lateral displacement of leaflets after valve-in-valve procedures. In the present report we aimed to prove feasibility and safety of transapical valve-in-valve implantation of the JenaValve THV in two cases of degenerated Mitroflow bioprostheses. We herein report two cases of successful transapical valve-in-valve procedures using a JenaValve THV implanted in Sorin Mitroflow bioprostheses for structural valve degeneration. Both patients were alive and in good clinical condition at 30 days from the procedure. However, increased transvalvular gradients were noted in both cases. Transcatheter valve-in-valve implantation of a JenaValve THV is a valid alternative for patients with degenerated Mitroflow bioprostheses of sufficient size and in the presence of short distances to the coronary ostia who are too ill for conventional repeat open heart surgery. Increased pressure gradients have to be expected and weighed against the disadvantages of other treatment options when planning such a procedure.

Computerized assessment of placental calcification post-ultrasound: a novel software tool.

PubMed

Moran, M; Higgins, M; Zombori, G; Ryan, J; McAuliffe, F M

2013-05-01

Placental calcification is associated with an increased risk of perinatal morbidity and mortality. The subjectivity of current ultrasound methods of assessment of placental calcification indicates that a more objective method is required. The aim of this study was to correlate the percentage of calcification defined by the clinician using a new software tool for calculating the extent of placental calcification with traditional ultrasound methods and with pregnancy outcome. Ninety placental images were individually assessed. An upper threshold was defined, based on high intensity, to quantify calcification within the placenta. Output metrics were then produced including the overall percentage of calcification with respect to the total number of pixels within the region of interest. The results were correlated with traditional ultrasound methods of assessment of placental calcification and with pregnancy outcome. The results demonstrate a significant correlation between placental calcification, as defined using the software, and traditional methods of Grannum grading of placental calcification. Whilst correlation with perinatal outcome and cord pH was not significant as a result of small numbers, patients with placental calcification assessed using the computerized software at the upper quartile had higher rates of poor perinatal outcome when compared with those at the lower quartile (8/22 (36%) vs 3/23 (13%); P = 0.069). These results suggest that this computerized software tool has the potential to become an alternative method of assessing placental calcification. Copyright © 2012 ISUOG. Published by John Wiley & Sons Ltd.

Bilateral intraocular calcification in necrotizing cytomegalovirus retinitis.

PubMed

Tuncer, Samuray; Oray, Merih; Yildirim, Yeliz; Camcioglu, Yildiz; Tugal-Tutkun, Ilknur

2014-10-01

We report a unique case of bilateral intraocular calcification due to necrotizing cytomegalovirus (CMV) retinitis associated with congenital CMV infection. A 7-month-old boy with a history of congenital CMV infection showed bilateral intraocular calcific plaques on computed tomography (CT) and ultrasonography. We reviewed the patient's medical files for the purpose of this report. The patient had a prior medical history of hospitalization for fever and swelling in the neck at 3 months of age. Systemic findings (anemia, neutropenia, hepatosplenomegaly, and reactive lymphadenomegaly) in association with a low CD4 count, high blood CMV viral load, and positivity for urine CMV DNA by polymerase chain reaction led to the diagnosis of bone marrow suppression and congenital CMV infection. At 7 months, he developed horizontal nystagmus and bilateral leukocoria over 20 days. Cranial CT and ultrasonography revealed bilateral intraocular calcific plaques and the patient was referred to rule out retinoblastoma. Fundoscopy was consistent with bilateral hemorrhagic, necrotizing CMV retinitis. Significant resolution of the retinal infiltrations occurred 2 weeks after initiation of systemic treatment with ganciclovir. Intraocular calcification may be a sign of active CMV retinitis. To our knowledge this is the first report of bilateral intraocular calcification serving as the presenting clinical manifestation of necrotizing CMV retinitis.

Popcorn calcification in osteogenesis imperfecta: incidence, progression, and molecular correlation.

PubMed

Obafemi, Abimbola A; Bulas, Dorothy I; Troendle, James; Marini, Joan C

2008-11-01

Osteogenesis imperfecta (OI) is a heritable disorder characterized by osteoporosis and increased susceptibility to fracture. All children with severe OI have extreme short stature and some have "popcorn" calcifications, areas of disorganized hyperdense lines in the metaphysis and epiphysis around the growth plate on lower limb radiographs. Popcorn calcifications were noted on radiographs of two children with non-lethal type VIII OI, a recessive form caused by P3H1 deficiency. To determine the incidence, progression, and molecular correlations of popcorn calcifications, we retrospectively examined serial lower limb radiographs of 45 children with type III or IV OI and known dominant mutations in type I collagen. Popcorn calcifications were present in 13 of 25 type III (52%), but only 2 of 20 type IV (10%), OI children. The mean age of onset was 7.0 years, with a range of 4-14 years. All children with popcorn calcifications had this finding in their distal femora, and most also had calcifications in proximal tibiae. While unilateral popcorn calcification contributes to femoral growth deficiency and leg length discrepancy, severe linear growth deficiency, and metaphyseal flare do not differ significantly between type III OI patients with and without popcorn calcifications. The type I collagen mutations associated with popcorn calcifications occur equally in both COL1A1 and COL1A2, and have no preferential location along the chains. These data demonstrate that popcorn calcifications are a frequent feature of severe OI, but do not distinguish cases with defects in collagen structure (primarily dominant type III OI) or modification (recessive type VIII OI). Copyright 2008 Wiley-Liss, Inc.

Identification of side- and shear-dependent microRNAs regulating porcine aortic valve pathogenesis

NASA Astrophysics Data System (ADS)

Rathan, Swetha; Ankeny, Casey J.; Arjunon, Sivakkumar; Ferdous, Zannatul; Kumar, Sandeep; Fernandez Esmerats, Joan; Heath, Jack M.; Nerem, Robert M.; Yoganathan, Ajit P.; Jo, Hanjoong

2016-05-01

Aortic valve (AV) calcification is an inflammation driven process that occurs preferentially in the fibrosa. To explore the underlying mechanisms, we investigated if key microRNAs (miRNA) in the AV are differentially expressed due to disturbed blood flow (oscillatory shear (OS)) experienced by the fibrosa compared to the ventricularis. To identify the miRNAs involved, endothelial-enriched RNA was isolated from either side of healthy porcine AVs for microarray analysis. Validation using qPCR confirmed significantly higher expression of 7 miRNAs (miR-100, -130a, -181a/b, -199a-3p, -199a-5p, and -214) in the fibrosa versus the ventricularis. Upon bioinformatics analysis, miR-214 was selected for further investigation using porcine AV leaflets in an ex vivo shear system. Fibrosa and ventricularis sides were exposed to either oscillatory or unidirectional pulsatile shear for 2 days and 3 & 7 days in regular and osteogenic media, respectively. Higher expression of miR-214, increased thickness of the fibrosa, and calcification was observed when the fibrosa was exposed to OS compared to the ventricularis. Silencing of miR-214 by anti-miR-214 in whole AV leaflets with the fibrosa exposed to OS significantly increased the protein expression of TGFβ1 and moderately increased collagen content but did not affect AV calcification. Thus, miR-214 is identified as a side- and shear-dependent miRNA that regulates key mechanosensitive gene in AV such as TGFβ1.

Cardiovascular calcifications in chronic kidney disease: Potential therapeutic implications.

PubMed

Bover, Jordi; Ureña-Torres, Pablo; Górriz, José Luis; Lloret, María Jesús; da Silva, Iara; Ruiz-García, César; Chang, Pamela; Rodríguez, Mariano; Ballarín, José

Cardiovascular (CV) calcification is a highly prevalent condition at all stages of chronic kidney disease (CKD) and is directly associated with increased CV and global morbidity and mortality. In the first part of this review, we have shown that CV calcifications represent an important part of the CKD-MBD complex and are a superior predictor of clinical outcomes in our patients. However, it is also necessary to demonstrate that CV calcification is a modifiable risk factor including the possibility of decreasing (or at least not aggravating) its progression with iatrogenic manoeuvres. Although, strictly speaking, only circumstantial evidence is available, it is known that certain drugs may modify the progression of CV calcifications, even though a direct causal link with improved survival has not been demonstrated. For example, non-calcium-based phosphate binders demonstrated the ability to attenuate the progression of CV calcification compared with the liberal use of calcium-based phosphate binders in several randomised clinical trials. Moreover, although only in experimental conditions, selective activators of the vitamin D receptor seem to have a wider therapeutic margin against CV calcification. Finally, calcimimetics seem to attenuate the progression of CV calcification in dialysis patients. While new therapeutic strategies are being developed (i.e. vitamin K, SNF472, etc.), we suggest that the evaluation of CV calcifications could be a diagnostic tool used by nephrologists to personalise their therapeutic decisions. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Impact of seawater carbonate variables on post-larval bivalve calcification

NASA Astrophysics Data System (ADS)

Li, Jiaqi; Mao, Yuze; Jiang, Zengjie; Zhang, Jihong; Bian, Dapeng; Fang, Jianguang

2017-05-01

Several studies have demonstrated that shellfish calcification rate has been impacted by ocean acidification. However, the carbonate system variables responsible for regulating calcification rate are controversial. To distinguish the key variables, we manipulated a seawater carbonate system by regulating seawater pH and dissolved inorganic carbon (DIC). Calcification rates of juvenile blue mussel (Mytilus edulis) and Zhikong scallop (Chlamys farreri) were measured in different carbonate systems. Our results demonstrated that neither [HCO{3/-}], DIC, or pH ([H+]) were determining factors for the shellfish calcification rate of blue mussel or Zhikong scallop. However, a significant correlation was detected between calcification rate and DIC/[H+] and [CO{3/2-}] in both species.

Decellularized heart valve as a scaffold for in vivo recellularization: deleterious effects of granulocyte colony-stimulating factor.

PubMed

Juthier, Francis; Vincentelli, André; Gaudric, Julien; Corseaux, Delphine; Fouquet, Olivier; Calet, Christine; Le Tourneau, Thierry; Soenen, Valérie; Zawadzki, Christophe; Fabre, Olivier; Susen, Sophie; Prat, Alain; Jude, Brigitte

2006-04-01

Autologous recellularization of decellularized heart valve scaffolds is a promising challenge in the field of tissue-engineered heart valves and could be boosted by bone marrow progenitor cell mobilization. The aim of this study was to examine the spontaneous in vivo recolonization potential of xenogeneic decellularized heart valves in a lamb model and the effects of granulocyte colony-stimulating factor mobilization of bone marrow cells on this process. Decellularized porcine aortic valves were implanted in 12 lambs. Six lambs received granulocyte colony-stimulating factor (10 microg x kg(-1) x d(-1) for 7 days, granulocyte colony-stimulating factor group), and 6 received no granulocyte colony-stimulating factor (control group). Additionally, nondecellularized porcine valves were implanted in 5 lambs (xenograft group). Angiographic and histologic evaluation was performed at 3, 6, 8, and 16 weeks. Few macroscopic modifications of leaflets and the aortic wall were observed in the control group, whereas progressive shrinkage and thickening of the leaflets appeared in the granulocyte colony-stimulating factor and xenograft groups. In the 3 groups progressive ovine cell infiltration (fluorescence in situ hybridization) was observed in the leaflets and in the adventitia and the intima of the aortic wall but not in the media. Neointimal proliferation of alpha-actin-positive cells, inflammatory infiltration, adventitial neovascularization, and calcifications were more important in the xenograft and the granulocyte colony-stimulating factor groups than in the control group. Continuous re-endothelialization appeared only in the control group. Decellularized xenogeneic heart valve scaffolds allowed partial autologous recellularization. Granulocyte colony-stimulating factor led to accelerated heart valve deterioration similar to that observed in nondecellularized xenogeneic cardiac bioprostheses.

Safety valve

DOEpatents

Bergman, Ulf C.

1984-01-01

The safety valve contains a resilient gland to be held between a valve seat and a valve member and is secured to the valve member by a sleeve surrounding the end of the valve member adjacent to the valve seat. The sleeve is movable relative to the valve member through a limited axial distance and a gap exists between said valve member and said sleeve.

Steady flow hemodynamic and energy loss measurements in normal and simulated calcified tricuspid and bicuspid aortic valves.

PubMed

Seaman, Clara; Akingba, A George; Sucosky, Philippe

2014-04-01

The bicuspid aortic valve (BAV), which forms with two leaflets instead of three as in the normal tricuspid aortic valve (TAV), is associated with a spectrum of secondary valvulopathies and aortopathies potentially triggered by hemodynamic abnormalities. While studies have demonstrated an intrinsic degree of stenosis and the existence of a skewed orifice jet in the BAV, the impact of those abnormalities on BAV hemodynamic performance and energy loss has not been examined. This steady-flow study presents the comparative in vitro assessment of the flow field and energy loss in a TAV and type-I BAV under normal and simulated calcified states. Particle-image velocimetry (PIV) measurements were performed to quantify velocity, vorticity, viscous, and Reynolds shear stress fields in normal and simulated calcified porcine TAV and BAV models at six flow rates spanning the systolic phase. The BAV model was created by suturing the two coronary leaflets of a porcine TAV. Calcification was simulated via deposition of glue beads in the base of the leaflets. Valvular performance was characterized in terms of geometric orifice area (GOA), pressure drop, effective orifice area (EOA), energy loss (EL), and energy loss index (ELI). The BAV generated an elliptical orifice and a jet skewed toward the noncoronary leaflet. In contrast, the TAV featured a circular orifice and a jet aligned along the valve long axis. While the BAV exhibited an intrinsic degree of stenosis (18% increase in maximum jet velocity and 7% decrease in EOA relative to the TAV at the maximum flow rate), it generated only a 3% increase in EL and its average ELI (2.10 cm2/m2) remained above the clinical threshold characterizing severe aortic stenosis. The presence of simulated calcific lesions normalized the alignment of the BAV jet and resulted in the loss of jet axisymmetry in the TAV. It also amplified the degree of stenosis in the TAV and BAV, as indicated by the 342% and 404% increase in EL, 70% and 51% reduction

Interleukin-24 attenuates β-glycerophosphate-induced calcification of vascular smooth muscle cells by inhibiting apoptosis, the expression of calcification and osteoblastic markers, and the Wnt/β-catenin pathway.

PubMed

Lee, Ki-Mo; Kang, Haeng-A; Park, Min; Lee, Hwa-Youn; Choi, Ha-Rim; Yun, Chul-Ho; Oh, Jae-Wook; Kang, Hyung-Sik

2012-11-09

Vascular calcification is a hallmark of cardiovascular disease. Interleukin-24 (IL-24) has been known to suppress tumor progression in a variety of human cancers. However, the role of IL-24 in the pathophysiology of diseases other than cancer is unclear. We investigated the role of IL-24 in vascular calcification. IL-24 was applied to a β-glycerophosphate (β-GP)-induced rat vascular smooth muscle cell (VSMC) calcification model. In this study, IL-24 significantly inhibited β-GP-induced VSMC calcification, as determined by von Kossa staining and calcium content. The inhibitory effect of IL-24 on VSMC calcification was due to the suppression of β-GP-induced apoptosis and expression of calcification and osteoblastic markers. In addition, IL-24 abrogated β-GP-induced activation of the Wnt/β-catenin pathway, which plays a key role in the pathogenesis of vascular calcification. The specificity of IL-24 for the inhibition of VSMC calcification was confirmed by using a neutralizing antibody to IL-24. Our results suggest that IL-24 inhibits β-GP-induced VSMC calcification by inhibiting apoptosis, the expression of calcification and osteoblastic markers, and the Wnt/ β-catenin pathway. Our study may provide a novel mechanism of action of IL-24 in cardiovascular disease and indicates that IL-24 is a potential therapeutic agent in VSMC calcification. Copyright © 2012 Elsevier Inc. All rights reserved.

NT5E Mutations and Arterial Calcifications

PubMed Central

St. Hilaire, Cynthia; Ziegler, Shira G.; Markello, Thomas C.; Brusco, Alfredo; Groden, Catherine; Gill, Fred; Carlson-Donohoe, Hannah; Lederman, Robert J.; Chen, Marcus Y.; Yang, Dan; Siegenthaler, Michael P.; Arduino, Carlo; Mancini, Cecilia; Freudenthal, Bernard; Stanescu, Horia C.; Zdebik, Anselm A.; Chaganti, R. Krishna; Nussbaum, Robert L.; Kleta, Robert; Gahl, William A.; Boehm, Manfred

2011-01-01

BACKGROUND Arterial calcifications are associated with increased cardiovascular risk, but the genetic basis of this association is unclear. METHODS We performed clinical, radiographic, and genetic studies in three families with symptomatic arterial calcifications. Single-nucleotide-polymorphism analysis, targeted gene sequencing, quantitative polymerase-chain-reaction assays, Western blotting, enzyme measurements, transduction rescue experiments, and in vitro calcification assays were performed. RESULTS We identified nine persons with calcifications of the lower-extremity arteries and hand and foot joint capsules: all five siblings in one family, three siblings in another, and one patient in a third family. Serum calcium, phosphate, and vitamin D levels were normal. Affected members of Family 1 shared a single 22.4-Mb region of homozygosity on chromosome 6 and had a homozygous nonsense mutation (c.662C→A, p.S221X) in NT5E, encoding CD73, which converts AMP to adenosine. Affected members of Family 2 had a homozygous missense mutation (c.1073G→A, p.C358Y) in NT5E. The proband of Family 3 was a compound heterozygote for c.662C→A and c.1609dupA (p.V537fsX7). All mutations found in the three families result in nonfunctional CD73. Cultured fibroblasts from affected members of Family 1 showed markedly reduced expression of NT5E messenger RNA, CD73 protein, and enzyme activity, as well as increased alkaline phosphatase levels and accumulated calcium phosphate crystals. Genetic rescue experiments normalized the CD73 and alkaline phosphatase activity in patients’ cells, and adenosine treatment reduced the levels of alkaline phosphatase and calcification. CONCLUSIONS We identified mutations in NT5E in members of three families with symptomatic arterial and joint calcifications. This gene encodes CD73, which converts AMP to adenosine, supporting a role for this metabolic pathway in inhibiting ectopic tissue calcification. (Funded by the National Human Genome Research

Design of a Cyclic Pressure Bioreactor for the Ex Vivo Study of Aortic Heart Valves

PubMed Central

Schipke, Kimberly J.; Filip To, S. D.; Warnock, James N.

2011-01-01

The aortic valve, located between the left ventricle and the aorta, allows for unidirectional blood flow, preventing backflow into the ventricle. Aortic valve leaflets are composed of interstitial cells suspended within an extracellular matrix (ECM) and are lined with an endothelial cell monolayer. The valve withstands a harsh, dynamic environment and is constantly exposed to shear, flexion, tension, and compression. Research has shown calcific lesions in diseased valves occur in areas of high mechanical stress as a result of endothelial disruption or interstitial matrix damage1-3. Hence, it is not surprising that epidemiological studies have shown high blood pressure to be a leading risk factor in the onset of aortic valve disease4. The only treatment option currently available for valve disease is surgical replacement of the diseased valve with a bioprosthetic or mechanical valve5. Improved understanding of valve biology in response to physical stresses would help elucidate the mechanisms of valve pathogenesis. In turn, this could help in the development of non-invasive therapies such as pharmaceutical intervention or prevention. Several bioreactors have been previously developed to study the mechanobiology of native or engineered heart valves6-9. Pulsatile bioreactors have also been developed to study a range of tissues including cartilage10, bone11 and bladder12. The aim of this work was to develop a cyclic pressure system that could be used to elucidate the biological response of aortic valve leaflets to increased pressure loads. The system consisted of an acrylic chamber in which to place samples and produce cyclic pressure, viton diaphragm solenoid valves to control the timing of the pressure cycle, and a computer to control electrical devices. The pressure was monitored using a pressure transducer, and the signal was conditioned using a load cell conditioner. A LabVIEW program regulated the pressure using an analog device to pump compressed air into the

Design of a cyclic pressure bioreactor for the ex vivo study of aortic heart valves.

PubMed

Schipke, Kimberly J; To, S D Filip; Warnock, James N

2011-08-23

The aortic valve, located between the left ventricle and the aorta, allows for unidirectional blood flow, preventing backflow into the ventricle. Aortic valve leaflets are composed of interstitial cells suspended within an extracellular matrix (ECM) and are lined with an endothelial cell monolayer. The valve withstands a harsh, dynamic environment and is constantly exposed to shear, flexion, tension, and compression. Research has shown calcific lesions in diseased valves occur in areas of high mechanical stress as a result of endothelial disruption or interstitial matrix damage(1-3). Hence, it is not surprising that epidemiological studies have shown high blood pressure to be a leading risk factor in the onset of aortic valve disease(4). The only treatment option currently available for valve disease is surgical replacement of the diseased valve with a bioprosthetic or mechanical valve(5). Improved understanding of valve biology in response to physical stresses would help elucidate the mechanisms of valve pathogenesis. In turn, this could help in the development of non-invasive therapies such as pharmaceutical intervention or prevention. Several bioreactors have been previously developed to study the mechanobiology of native or engineered heart valves(6-9). Pulsatile bioreactors have also been developed to study a range of tissues including cartilage(10), bone(11) and bladder(12). The aim of this work was to develop a cyclic pressure system that could be used to elucidate the biological response of aortic valve leaflets to increased pressure loads. The system consisted of an acrylic chamber in which to place samples and produce cyclic pressure, viton diaphragm solenoid valves to control the timing of the pressure cycle, and a computer to control electrical devices. The pressure was monitored using a pressure transducer, and the signal was conditioned using a load cell conditioner. A LabVIEW program regulated the pressure using an analog device to pump compressed

Dual-energy digital mammography for calcification imaging: scatter and nonuniformity corrections.

PubMed

Kappadath, S Cheenu; Shaw, Chris C

2005-11-01

Mammographic images of small calcifications, which are often the earliest signs of breast cancer, can be obscured by overlapping fibroglandular tissue. We have developed and implemented a dual-energy digital mammography (DEDM) technique for calcification imaging under full-field imaging conditions using a commercially available aSi:H/CsI:Tl flat-panel based digital mammography system. The low- and high-energy images were combined using a nonlinear mapping function to cancel the tissue structures and generate the dual-energy (DE) calcification images. The total entrance-skin exposure and mean-glandular dose from the low- and high-energy images were constrained so that they were similar to screening-examination levels. To evaluate the DE calcification image, we designed a phantom using calcium carbonate crystals to simulate calcifications of various sizes (212-425 microm) overlaid with breast-tissue-equivalent material 5 cm thick with a continuously varying glandular-tissue ratio from 0% to 100%. We report on the effects of scatter radiation and nonuniformity in x-ray intensity and detector response on the DE calcification images. The nonuniformity was corrected by normalizing the low- and high-energy images with full-field reference images. Correction of scatter in the low- and high-energy images significantly reduced the background signal in the DE calcification image. Under the current implementation of DEDM, utilizing the mammography system and dose level tested, calcifications in the 300-355 microm size range were clearly visible in DE calcification images. Calcification threshold sizes decreased to the 250-280 microm size range when the visibility criteria were lowered to barely visible. Calcifications smaller than approximately 250 microm were usually not visible in most cases. The visibility of calcifications with our DEDM imaging technique was limited by quantum noise, not system noise.

Dual-energy digital mammography for calcification imaging: Scatter and nonuniformity corrections

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kappadath, S. Cheenu; Shaw, Chris C.

Mammographic images of small calcifications, which are often the earliest signs of breast cancer, can be obscured by overlapping fibroglandular tissue. We have developed and implemented a dual-energy digital mammography (DEDM) technique for calcification imaging under full-field imaging conditions using a commercially available aSi:H/CsI:Tl flat-panel based digital mammography system. The low- and high-energy images were combined using a nonlinear mapping function to cancel the tissue structures and generate the dual-energy (DE) calcification images. The total entrance-skin exposure and mean-glandular dose from the low- and high-energy images were constrained so that they were similar to screening-examination levels. To evaluate the DEmore » calcification image, we designed a phantom using calcium carbonate crystals to simulate calcifications of various sizes (212-425 {mu}m) overlaid with breast-tissue-equivalent material 5 cm thick with a continuously varying glandular-tissue ratio from 0% to 100%. We report on the effects of scatter radiation and nonuniformity in x-ray intensity and detector response on the DE calcification images. The nonuniformity was corrected by normalizing the low- and high-energy images with full-field reference images. Correction of scatter in the low- and high-energy images significantly reduced the background signal in the DE calcification image. Under the current implementation of DEDM, utilizing the mammography system and dose level tested, calcifications in the 300-355 {mu}m size range were clearly visible in DE calcification images. Calcification threshold sizes decreased to the 250-280 {mu}m size range when the visibility criteria were lowered to barely visible. Calcifications smaller than {approx}250 {mu}m were usually not visible in most cases. The visibility of calcifications with our DEDM imaging technique was limited by quantum noise, not system noise.« less

Dietary potassium regulates vascular calcification and arterial stiffness

PubMed Central

Sun, Yong; Byon, Chang Hyun; Yang, Youfeng; Bradley, Wayne E.; Dell’Italia, Louis J.; Agarwal, Anupam; Wu, Hui

2017-01-01

Vascular calcification is a risk factor that predicts adverse cardiovascular complications of several diseases including atherosclerosis. Reduced dietary potassium intake has been linked to cardiovascular diseases such as hypertension and incidental stroke, although the underlying molecular mechanisms remain largely unknown. Using the ApoE-deficient mouse model, we demonstrated for the first time to our knowledge that reduced dietary potassium (0.3%) promoted atherosclerotic vascular calcification and increased aortic stiffness, compared with normal (0.7%) potassium–fed mice. In contrast, increased dietary potassium (2.1%) attenuated vascular calcification and aortic stiffness. Mechanistically, reduction in the potassium concentration to the lower limit of the physiological range increased intracellular calcium, which activated a cAMP response element–binding protein (CREB) signal that subsequently enhanced autophagy and promoted vascular smooth muscle cell (VSMC) calcification. Inhibition of calcium signals and knockdown of either CREB or ATG7, an autophagy regulator, attenuated VSMC calcification induced by low potassium. Consistently, elevated autophagy and CREB signaling were demonstrated in the calcified arteries from low potassium diet–fed mice as well as aortic arteries exposed to low potassium ex vivo. These studies established a potentially novel causative role of dietary potassium intake in regulating atherosclerotic vascular calcification and stiffness, and uncovered mechanisms that offer opportunities to develop therapeutic strategies to control vascular disease. PMID:28978809

Coccolithophore growth and calcification in a changing ocean

NASA Astrophysics Data System (ADS)

Krumhardt, Kristen M.; Lovenduski, Nicole S.; Iglesias-Rodriguez, M. Debora; Kleypas, Joan A.

2017-12-01

Coccolithophores are the most abundant calcifying phytoplankton in the ocean. These tiny primary producers have an important role in the global carbon cycle, substantially contributing to global ocean calcification, ballasting organic matter to the deep sea, forming part of the marine food web base, and influencing ocean-atmosphere CO2 exchange. Despite these important impacts, coccolithophores are not explicitly simulated in most marine ecosystem models and, therefore, their impacts on carbon cycling are not represented in most Earth system models. Here, we compile field and laboratory data to synthesize overarching, across-species relationships between environmental conditions and coccolithophore growth rates and relative calcification (reported as a ratio of particulate inorganic carbon to particulate organic carbon in coccolithophore biomass, PIC/POC). We apply our relationships in a generalized coccolithophore model, estimating current surface ocean coccolithophore growth rates and relative calcification, and projecting how these may change over the 21st century using output from the Community Earth System Model large ensemble. We find that average increases in sea surface temperature of ∼ 2-3 ° C lead to faster coccolithophore growth rates globally (> 10% increase) and increased calcification at high latitudes. Roughly an ubiquitous doubling of surface ocean pCO2 by the end of the century has the potential to moderately stimulate coccolithophore growth rates, but leads to reduced calcification (∼ 25% decrease). Decreasing nutrient availability (from warming-induced increases in stratification) produces increases in relative calcification, but leads to ∼ 25% slower growth rates. With all drivers combined, we observe decreases in calcification and growth in most low and mid latitude regions, with possible increases in both of these responses in most high latitude regions. Major limitations of our coccolithophore model stem from a lack of conclusive

Pulp Calcification in Traumatized Primary Teeth - Classification, Clinical And Radiographic Aspects.

PubMed

Mello-Moura, Anna Carolina Volpi; Santos, Ana Maria Antunes; Bonini, Gabriela Azevedo Vasconcelos Cunha; Zardetto, Cristina Giovannetti Del Conte; Moura-Netto, Cacio; Wanderley, Marcia Turolla

The aim of this study was to standardize the nomenclature of pulp alteration to pulp calcification (PC) and to classify it according to type, quantity and location, as well as relate it to clinical and radiographic features. The dental records of 946 patients from the Research and Clinical Center for Dental Trauma in Primary Teeth were studied. Two hundred and fifty PC-traumatized upper deciduous incisors were detected. According to radiographic analysis of the records, 62.5% showed diffuse calcification, 36.3% tube-like calcification, and 1.2% concentric calcification. According to the extension of pulp calcification, the records showed: 80% partial calcification, 17.2% total coronal calcification and partial radicular calcification, and 2.8 % total coronal and radicular calcification. As for location, only 2.4% were on the coronal pulp, 5.2% on the radicular pulp and 92.4% on both radicular and coronal pulp. Regarding coronal discoloration, 54% were yellow and 2% gray. In relation to periradicular changes, 10% showed widened periodontal ligament space, 3.1% internal resorption, 10% external resorption, 10.4% periapical bone rarefaction. Since PC is a general term, it is important to classify it and correlate it to clinical and radiographic changes, in order to establish the correct diagnosis, treatment and prognosis of each case.

Fracturing mechanics before valve-in-valve therapy of small aortic bioprosthetic heart valves.

PubMed

Johansen, Peter; Engholt, Henrik; Tang, Mariann; Nybo, Rasmus F; Rasmussen, Per D; Nielsen-Kudsk, Jens Erik

2017-10-13

Patients with degraded bioprosthetic heart valves (BHV) who are not candidates for valve replacement may benefit from transcatheter valve-in-valve (VIV) therapy. However, in smaller-sized surgical BHV the resultant orifice may become too narrow. To overcome this, the valve frame can be fractured by a high-pressure balloon prior to VIV. However, knowledge on fracture pressures and mechanics are prerequisites. The aim of this study was to identify the fracture pressures needed in BHV, and to describe the fracture mechanics. Commonly used BHV of small sizes were mounted on a high-pressure balloon situated in a biplane fluoroscopic system with a high-speed camera. The instant of fracture was captured along with the balloon pressure. The valves were inspected for material protrusion and later dissected for fracture zone investigation and description. The valves with a polymer frame fractured at a lower pressure (8-10 atm) than those with a metal stent (19-26 atm). None of the fractured valves had elements protruding. VIV procedures in small-sized BHV may be performed after prior fracture of the valve frame by high-pressure balloon dilatation. This study provides tentative guidelines for expected balloon sizes and pressures for valve fracturing.

Impact of seawater carbonate variables on post-larval bivalve calcification

NASA Astrophysics Data System (ADS)

Li, Jiaqi; Mao, Yuze; Jiang, Zengjie; Zhang, Jihong; Bian, Dapeng; Fang, Jianguang

2018-03-01

Several studies have demonstrated that shellfish calcification rate has been impacted by ocean acidification. However, the carbonate system variables responsible for regulating calcification rate are controversial. To distinguish the key variables, we manipulated a seawater carbonate system by regulating seawater pH and dissolved inorganic carbon (DIC). Calcification rates of juvenile blue mussel ( Mytilus edulis) and Zhikong scallop ( Chlamys farreri) were measured in different carbonate systems. Our results demonstrated that neither [HCOˉ3], DIC, or pH ([H+]) were determining factors for the shellfish calcification rate of blue mussel or Zhikong scallop. However, a significant correlation was detected between calcification rate and DIC/[H+] and [CO3 2ˉ] in both species.

Survival-Related Autophagic Activity Versus Procalcific Death in Cultured Aortic Valve Interstitial Cells Treated With Critical Normophosphatemic-Like Phosphate Concentrations

PubMed Central

Bonetti, Antonella; Della Mora, Alberto; Contin, Magali; Gregoraci, Giorgia; Tubaro, Franco; Marchini, Maurizio; Ortolani, Fulvia

2017-01-01

Valve dystrophic calcification is a common disorder affecting normophosphatemic subjects. Here, cultured aortic valve interstitial cells (AVICs) were treated 3 to 28 days with phosphate (Pi) concentrations spanning the normal range in humans (0.8, 1.3, and 2.0 mM) alone or supplemented with proinflammatory stimuli to assess possible priming of dystrophic-like calcification. Compared with controls, spectrophotometric analyses revealed marked increases in calcium amounts and alkaline phosphatase activity for 2.0-mM-Pi-containing cultures, with enhancing by proinflammatory mediators. Ultrastructurally, AVICs treated with low/middle Pi concentrations showed an enormous endoplasmic reticulum (ER) enclosing organelle debris, so apparently executing a survival-related atypical macroautophagocytosis, consistently with ultracytochemical demonstration of ER-associated acid phosphatase activity and decreases in autophagosomes and immunodetectable MAP1LC3. In contrast, AVICs cultured at 2.0-mM Pi underwent mineralization due to intracellular release and peripheral layering of phospholipid-rich material acting as hydroxyapatite nucleator, as revealed by Cuprolinic Blue and von Kossa ultracytochemical reactions. Lack of immunoblotted caspase-3 cleaved form indicated apoptosis absence for all cultures. In conclusion, fates of cultured AVICs were crucially driven by Pi concentration, suggesting that serum Pi levels just below the upper limit of normophosphatemia in humans may represent a critical watershed between macroautophagy-associated cell restoring and procalcific cell death. PMID:28112549

76 FR 81909 - Abolishment of Privacy Act System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-29

... AGENCY: Office of the Secretary, USDA. ACTION: Notice of abolishment of records systems. SUMMARY: In accordance with the Privacy Act of 1974, the Department of Agriculture (USDA) is abolishing an existing Forest Service Privacy Act system of records. A review of USDA/FS-35 Congressional Correspondence has...

In-vitro analysis of early calcification in aortic valvular interstitial cells using Laser-Induced Breakdown Spectroscopy (LIBS).

PubMed

Davari, Seyyed Ali; Masjedi, Shirin; Ferdous, Zannatul; Mukherjee, Dibyendu

2018-01-01

Calcific aortic valve disease (CAVD) is a major cardiovascular disorder caused by osteogenic differentiation of valvular interstitial cells (VICs) within aortic valves. Conventional methods like colorimetric assays and histology fail to detect small calcium depositions during in-vitro VIC cultures. Laser-induced breakdown spectroscopy (LIBS) is a robust analytical tool used for inorganic materials characterizations, but relatively new to biomedical applications. We employ LIBS, for the first time, for quantitative in-vitro detection of calcium depositions in VICs at various osteogenic differentiation stages. VICs isolated from porcine aortic valves were cultured in osteogenic media over various days. Colorimetric calcium assays based on arsenazo dye and Von Kossa staining measured the calcium depositions within VICs. Simultaneously, LIBS signatures for Ca I (422.67 nm) atomic emission lines were collected for estimating calcium depositions in lyophilized VIC samples. Our results indicate excellent linear correlation between the calcium assay and our LIBS measurements. Furthermore, unlike the assay results, the LIBS results could resolve calcium signals from cell samples with as early as 2 days of osteogenic culture. Quantitatively, the LIBS measurements establish the limit of detection for calcium content in VICs to be ∼0.17±0.04 μg which indicates a 5-fold improvement over calcium assay. Picture: Quantitative LIBS enables in-vitro analysis for early stage detection of calcium deposition within aortic valvular interstitial cells (VICs). © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Acute Calcific Tendinitis of the Index Finger in a Child.

PubMed

Walocko, Frances M; Sando, Ian C; Haase, Steven C; Kozlow, Jeffrey H

2017-09-01

Calcific tendinitis is characterized by calcium hydroxyapatite crystal deposition within tendons and is a common cause of musculoskeletal pain in adults. Its clinical manifestations may be acute, chronic, or asymptomatic. Acute calcific tendinitis is self-resolving condition that is rarely reported in the pediatric population and may be overlooked for more common processes, leading to unnecessary treatment. A chart reivew was performed of a single case of acute calcific tendonitis of the index finger in a child. We describe a case of calcific tendinitis of the index finger in a 9-year-old boy who was referred to us for a second opinion after surgical exploration of an acutely inflamed digit was recommended based on his initial presentation. The calcifications and symptoms resolved over time without operative management. Although rare in children, acute calcific tendinitis can present similar to an infection. However, appropriate managment is non-operative as the symptoms and radiographic findings resolve over time.

The Effect of Neonatal Gene Therapy with a Gamma Retroviral Vector on Cardiac Valve Disease in Mucopolysaccharidosis VII Dogs after a Decade

PubMed Central

Bigg, Paul W.; Sleeper, Meg M.; O’Donnell, Patricia A.; Liu, Yuli; Wu, Susan; Casal, Margret L.; Haskins, Mark E.; Ponder, Katherine P.

2013-01-01

Mucopolysaccharidosis VII (MPS VII) is due to deficient activity of the lysosomal enzyme β-glucuronidase (GUSB) and results in the accumulation of glycosaminoglycans (GAGs). This study determined the long-term effect of neonatal intravenous injection of a gamma retroviral vector (RV) on cardiac valve disease in MPS VII dogs. Transduced hepatocytes secreted GUSB into blood for up to 11 years at levels similar to or greater than those achieved with enzyme replacement therapy (ERT). Valve regurgitation and thickening were scored from 0 (normal) to +4 (severely abnormal). At 1 year, untreated MPS VII dogs had mitral regurgitation, mitral valve thickening, aortic regurgitation, and aortic valve thickening scores of 2.3±0.7, 2.3±0.6, 1.8±0.5, and 1.6±0.7, respectively, which were higher than the values of 0.6±0.1, 0.1±0.4, 0.3±0.8, and 0.1±0.4, respectively, in treated MPS VII dogs. Treated MPS VII dogs maintained low aortic regurgitation and aortic valve thickening scores for their lifetime. Although mitral regurgitation and mitral valve thickening scores increased to 2.0 at ≥8 years of age in the treated MPS VII dogs, older normal dogs from the colony had similar scores, making it difficult to assess mitral valve disease. Older treated dogs had calcification within the mitral and aortic valve annulus, while GUSB staining demonstrated enzyme activity within the mitral valve. We conclude that neonatal RV-mediated gene therapy reduced cardiac valve disease in MPS VII dogs for up to 11 years, and propose that neonatal initiation of ERT should have a similar effect. PMID:23860311

Treatment of hypophosphatemic rickets in generalized arterial calcification of infancy (GACI) without worsening of vascular calcification.

PubMed

Ferreira, Carlos R; Ziegler, Shira G; Gupta, Ashutosh; Groden, Catherine; Hsu, Kevin S; Gahl, William A

2016-05-01

Patients with generalized arterial calcification of infancy (GACI) develop vascular calcifications early in life. About half of them die within the first 6 months despite optimal medical care. A subset of those who survive eventually develop hypophosphatemic rickets. Since hypophosphatemia and hyperphosphaturia have been previously associated with increased survival in GACI patients, physicians often avoid phosphate repletion as treatment for rickets. As a consequence, GACI patients develop severe rachitic complications such as short stature and skeletal deformities. It appears that the recognition of hypophosphatemia later in life in some GACI patients is a consequence of having survived the first few months of life, and not the cause of their survival per se. Here, we report the long-term follow-up of a GACI patient who was phosphate-repleted for his rickets for more than 7 years without worsening of vascular calcification. © 2016 Wiley Periodicals, Inc.

Coral calcification and ocean acidification

USGS Publications Warehouse

Jokiel, Paul L.; Jury, Christopher P.; Kuffner, Ilsa B.

2016-01-01

Over 60 years ago, the discovery that light increased calcification in the coral plant-animal symbiosis triggered interest in explaining the phenomenon and understanding the mechanisms involved. Major findings along the way include the observation that carbon fixed by photosynthesis in the zooxanthellae is translocated to animal cells throughout the colony and that corals can therefore live as autotrophs in many situations. Recent research has focused on explaining the observed reduction in calcification rate with increasing ocean acidification (OA). Experiments have shown a direct correlation between declining ocean pH, declining aragonite saturation state (Ωarag), declining [CO32_] and coral calcification. Nearly all previous reports on OA identify Ωarag or its surrogate [CO32] as the factor driving coral calcification. However, the alternate “Proton Flux Hypothesis” stated that coral calcification is controlled by diffusion limitation of net H+ transport through the boundary layer in relation to availability of dissolved inorganic carbon (DIC). The “Two Compartment Proton Flux Model” expanded this explanation and synthesized diverse observations into a universal model that explains many paradoxes of coral metabolism, morphology and plasticity of growth form in addition to observed coral skeletal growth response to OA. It is now clear that irradiance is the main driver of net photosynthesis (Pnet), which in turn drives net calcification (Gnet), and alters pH in the bulk water surrounding the coral. Pnet controls [CO32] and thus Ωarag of the bulk water over the diel cycle. Changes in Ωarag and pH lag behind Gnet throughout the daily cycle by two or more hours. The flux rate Pnet, rather than concentration-based parameters (e.g., Ωarag, [CO3 2], pH and [DIC]:[H+] ratio) is the primary driver of Gnet. Daytime coral metabolism rapidly removes DIC from the bulk seawater. Photosynthesis increases the bulk seawater pH while providing the energy that drives

Differential Effects of Ocean Acidification on Coral Calcification: Insights from Geochemistry.

NASA Astrophysics Data System (ADS)

Holcomb, M.; Decarlo, T. M.; Venn, A.; Tambutte, E.; Gaetani, G. A.; Tambutte, S.; Allemand, D.; McCulloch, M. T.

2014-12-01

Although ocean acidification is expected to negatively impact calcifying animals due to the formation of CaCO3 becoming less favorable, experimental evidence is mixed. Corals have received considerable attention in this regard; laboratory culture experiments show there to be a wide array of calcification responses to acidification. Here we will show how relationships for the incorporation of various trace elements and boron isotopes into synthetic aragonite can be used to reconstruct carbonate chemistry at the site of calcification. In turn the chemistry at the site of calcification can be determined under different ocean acidification scenarios and differences in the chemistry at the site of calcification linked to different calcification responses to acidification. Importantly we will show that the pH of the calcifying fluid alone is insufficient to estimate calcification responses, thus a multi-proxy approach using multiple trace elements and isotopes is required to understand how the site of calcification is affected by ocean acidification.

Automated selection of BI-RADS lesion descriptors for reporting calcifications in mammograms

NASA Astrophysics Data System (ADS)

Paquerault, Sophie; Jiang, Yulei; Nishikawa, Robert M.; Schmidt, Robert A.; D'Orsi, Carl J.; Vyborny, Carl J.; Newstead, Gillian M.

2003-05-01

We are developing an automated computer technique to describe calcifications in mammograms according to the BI-RADS lexicon. We evaluated this technique by its agreement with radiologists' description of the same lesions. Three expert mammographers reviewed our database of 90 cases of digitized mammograms containing clustered microcalcifications and described the calcifications according to BI-RADS. In our study, the radiologists used only 4 of the 5 calcification distribution descriptors and 5 of the 14 calcification morphology descriptors contained in BI-RADS. Our computer technique was therefore designed specifically for these 4 calcification distribution descriptors and 5 calcification morphology descriptors. For calcification distribution, 4 linear discriminant analysis (LDA) classifiers were developed using 5 computer-extracted features to produce scores of how well each descriptor describes a cluster. Similarly, for calcification morphology, 5 LDAs were designed using 10 computer-extracted features. We trained the LDAs using only the BI-RADS data reported by the first radiologist and compared the computer output to the descriptor data reported by all 3 radiologists (for the first radiologist, the leave-one-out method was used). The computer output consisted of the best calcification distribution descriptor and the best 2 calcification morphology descriptors. The results of the comparison with the data from each radiologist, respectively, were: for calcification distribution, percent agreement, 74%, 66%, and 73%, kappa value, 0.44, 0.36, and 0.46; for calcification morphology, percent agreement, 83%, 77%, and 57%, kappa value, 0.78, 0.70, and 0.44. These results indicate that the proposed computer technique can select BI-RADS descriptors in good agreement with radiologists.

76 FR 81910 - Abolishment of Privacy Act System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-29

... AGENCY: Office of the Secretary, USDA. ACTION: Notice of abolishment of records systems. SUMMARY: In accordance with the Privacy Act of 1974, the Department of Agriculture (USDA) is abolishing an existing Forest Service Privacy Act system of records. A review of USDA/FS-9 Employee Assistance Program CONCERN...

Check valve

DOEpatents

Upton, Hubert Allen; Garcia, Pablo

1999-08-24

A check valve for use in a GDCS of a nuclear reactor and having a motor driven disk including a rotatable armature for rotating the check valve disk over its entire range of motion is described. In one embodiment, the check valve includes a valve body having a coolant flow channel extending therethrough. The coolant flow channel includes an inlet end and an outlet end. A valve body seat is located on an inner surface of the valve body. The check valve further includes a disk assembly, sometimes referred to as the motor driven disc, having a counterweight and a disk shaped valve. The disk valve includes a disk base having a seat for seating with the valve body seat. The disk assembly further includes a first hinge pin member which extends at least partially through the disk assembly and is engaged to the disk. The disk valve is rotatable relative to the first hinge pin member. The check valve also includes a motor having a stator frame with a stator bore therein. An armature is rotatably positioned within the stator bore and the armature is coupled to the disk valve to cause the disk valve to rotate about its full range of motion.

Check valve

DOEpatents

Upton, H.A.; Garcia, P.

1999-08-24

A check valve for use in a GDCS of a nuclear reactor and having a motor driven disk including a rotatable armature for rotating the check valve disk over its entire range of motion is described. In one embodiment, the check valve includes a valve body having a coolant flow channel extending therethrough. The coolant flow channel includes an inlet end and an outlet end. A valve body seat is located on an inner surface of the valve body. The check valve further includes a disk assembly, sometimes referred to as the motor driven disc, having a counterweight and a disk shaped valve. The disk valve includes a disk base having a seat for seating with the valve body seat. The disk assembly further includes a first hinge pin member which extends at least partially through the disk assembly and is engaged to the disk. The disk valve is rotatable relative to the first hinge pin member. The check valve also includes a motor having a stator frame with a stator bore therein. An armature is rotatably positioned within the stator bore and the armature is coupled to the disk valve to cause the disk valve to rotate about its full range of motion. 5 figs.

Impact of seawater carbonate chemistry on the calcification of marine bivalves

NASA Astrophysics Data System (ADS)

Thomsen, J.; Haynert, K.; Wegner, K. M.; Melzner, F.

2015-01-01

Bivalve calcification, particular of the early larval stages is highly sensitive to the change of ocean carbonate chemistry resulting from atmospheric CO2 uptake. Earlier studies suggested that declining seawater [CO32-] and thereby lowered carbonate saturation affect shell production. However, disturbances of physiological processes such as acid-base regulation by adverse seawater pCO2 and pH can affect calcification in a secondary fashion. In order to determine the exact carbonate system component by which growth and calcification are affected it is necessary to utilize more complex carbonate chemistry manipulations. As single factors, pCO2 had no and [HCO3-] and pH only limited effects on shell growth, while lowered [CO32-] strongly impacted calcification. Dissolved inorganic carbon (CT) limiting conditions led to strong reductions in calcification, despite high [CO32-], indicating that [HCO3-] rather than [CO32-] is the inorganic carbon source utilized for calcification by mytilid mussels. However, as the ratio [HCO3-] / [H+] is linearly correlated with [CO32-] it is not possible to differentiate between these under natural seawater conditions. Therefore, the availability of [HCO3-] combined with favorable environmental pH determines calcification rate and an equivalent of about 80 μmol kg-1 [CO32-] is required to saturate inorganic carbon supply for calcification in bivalves. Below this threshold biomineralization rates rapidly decline. A comparison of literature data available for larvae and juvenile mussels and oysters originating from habitats differing substantially with respect to prevailing carbonate chemistry conditions revealed similar response curves. This suggests that the mechanisms which determine sensitivity of calcification in this group are highly conserved. The higher sensitivity of larval calcification seems to primarily result from the much higher relative calcification rates in early life stages. In order to reveal and understand the

A technique of snaring method for fitting a prosthetic valve into the annulus.

PubMed

Nagasaka, Shigeo; Kawata, Tetsuji; Matsuta, Masahiro; Taniguchi, Shigeki

2005-01-01

Tourniquetting technique to fit a prosthetic valve (PV) into the annulus in valve replacement surgery has been previously reported. We modified the previously reported method and designed a simpler tying technique. We performed 11 aortic (AVR: including four cases for calcified aortic stenosis (AS) with a small annulus and one cases for infective endocarditis with intramuscular abscess cavity), eight mitral valve replacements (MVR), and one tricuspid valve replacement (TVR: for corrected transposition of the great arteries). A PV was implanted using 2-0 polyester mattress sutures with a pledget. Each of the two tourniquets held a suture at the bottom of the annulus and at the opposite position to fit a PV. The sutures between each snare were tied down from the bottom to the top. In MVR, after seating of a PV with two tourniquets, we could make sure that no native tissue of any preserved mitral apparatus disturbed PV leaflet motion. In calcific AS, a PV had a good fitting into the annulus because of tourniquets applied to unseated part during tying sutures. In AVR for infective endocarditis, mattress sutures supported by a Teflon pledget were placed to close the abscess cavity. After snaring on one of these sutures, we tied down the sutures, ensuring that they did not cut through the friable tissues. In TVR, we found that native leaflets interfered with PV motion after seating down the prosthesis and those leaflets were resected before tying down the sutures. Postoperative transesophageal echocardiography showed no paravalvular leakage in any patients and excellent PV functions.

Arterial calcification: friend or foe?

PubMed

Nicoll, Rachel; Henein, Michael Y

2013-07-31

There is a significant relationship between the presence, extent and progression of coronary artery calcification (CAC) and cardiovascular (CV) events and mortality in both CV and renal patients and CAC scoring can provide improved predictive ability over risk factor scoring alone. There is also a close relationship between CAC presence and atherosclerotic plaque burden, with angiography studies showing very high sensitivity but poor specificity of CAC score for predicting obstructive disease. Nevertheless, there are objections to CAC screening because of uncertainties and lack of studies showing improved outcome. Furthermore, histopathology studies indicate that heavily calcified plaque is unlikely to result in a CV event, while the vulnerable plaque tends to be uncalcified or 'mixed', suggesting that calcification may be protective. This scenario highlights a number of paradoxes, which may indicate that the association between CAC and CV events is spurious, following from the adoption of CAC as a surrogate for high plaque burden, which itself is a surrogate for the presence of vulnerable plaque. Since studies indicate that arterial calcification is a complex, organised and regulated process similar to bone formation, there is no particular reason why it should be a reliable indicator of either the plaque burden or the risk of a future CV event. We suggest that it is time to divorce arterial calcification from atherosclerosis and to view it as a distinct pathology in its own right, albeit one which frequently coexists with atherosclerosis and is related to it for reasons which are not yet fully understood. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The effects of the covalent attachment of 3-(4-hydroxy-3,5-di-tert-butylphenyl) propyl amine to glutaraldehyde pretreated bovine pericardium on structural degeneration, oxidative modification, and calcification of rat subdermal implants.

PubMed

Christian, Abigail J; Alferiev, Ivan S; Connolly, Jeanne M; Ischiropoulos, Harry; Levy, Robert J

2015-07-01

Bioprosthetic heart valves (BHV) fabricated from glutaraldehyde pretreated heterograft materials, porcine aortic valves or bovine pericardium (BP), are widely used in cardiac surgery. BHV progressively fail in clinical use due to structural degeneration. Previously we reported that dityrosine, an oxidized amino acid, was present in failed clinical BP-BHV explants; unimplanted BP had no detectable dityrosine. In the same studies BP were demonstrated in vitro to be susceptible to oxidative damage, that could be mitigated with BP covalently modified with the antioxidant, 3-(4-hydroxy-3,5-di-tert-butylphenyl)propyl amine (DBP). The present studies compared in rat subdermal implants glutaraldehyde pretreated BP to BP modified with either DBP or the chemical reactions used to link DBP. All BP explants regardless of DBP demonstrated reduced hydroxyproline and increased digestibility by collagenase. However, the DBP-BP explants showed significant inhibition of reduced explant shrink temperatures (an index of crosslinking) as compared with control BP. Significant mitigation of calcification was observed in both the BP-DBP and chemically modified explants as compared with BP. Dityrosine was not detectable in the 90 day explants. It is concluded that rat subdermal BP implants undergo both calcific and noncalcific structural degeneration, but without the formation of dityrosine, unlike clinical BP explants. © 2014 Wiley Periodicals, Inc.

Computed tomographic pattern of physiological intracranial calcifications in a city in central Africa.

PubMed

Uduma, Felix Uduma; Pius, Fokam; Mathieu, Motah

2011-12-29

Intracranial calcifications underlie certain brain diseases which may be de novo or systemic. But calcifications un-connected to pathologies are classified physiological. To evaluate physiological intracranial calcifications in Douala with establishment of earliest age range of detection. Prospective study of brain computed tomograms was done from April to October 2009 using Schumadzu CT Scan machine. Axial, reconstructed and bone window images as well Hounsfield unit measurements were used for final evaluations. RESULTS were analysed with SSPS 3. 132 patients with 75 males and 57 females were studied and 163 separate calcifications were identified due to co-existent calcifications. The highest calcification was in choroid plexi, constituting 56.82% of the studied population. This was followed by pineal gland. Both were commonly co-existent with advancing age. These calcifications were first seen at 10-19 years. No type of physiological intracranial calcification was seen below age 10. The least calcification of 0.76% of population was in dentate nucleus. No intra-cranial physiological calcifications started earlier than 9 years in Douala, a city in Cameroon, Central Africa.

Abolishing the Word-Length Effect

ERIC Educational Resources Information Center

Hulme, Charles; Suprenant, Aime M.; Bireta, Tamra J.; Stuart, George; Neath, Ian

2004-01-01

The authors report 2 experiments that compare the recall of long and short words in pure and mixed lists. In pure lists, long words were much more poorly remembered than short words. In mixed lists, this word-length effect was abolished and both the long and short words were recalled as well as short words in pure lists. These findings contradict…

Prevalence of Soft Tissue Calcifications in CBCT Images of Mandibular Region.

PubMed

Khojastepour, Leila; Haghnegahdar, Abdolaziz; Sayar, Hamed

2017-06-01

Most of the soft tissue calcifications within the head and neck region might not be accompanied by clinical symptoms but may indicate some pathological conditions. The aim of this research was to determine the prevalence of soft tissue calcifications in cone beam computed tomography (CBCT) images of mandibular region. In this cross sectional study the CBCT images of 602 patients including 294 men and 308 women with mean age 41.38±15.18 years were evaluated regarding the presence, anatomical location; type (single or multiple) and size of soft tissue calcification in mandibular region. All CBCT images were acquired by NewTom VGi scanner. Odds ratio and chi-square tests were used for data analysis and p < 0.05 was considered to be statistically significant. 156 out of 602 patients had at least one soft tissue calcification in their mandibular region (25.9%. of studied population with mean age 51.7±18.03 years). Men showed significantly higher rate of soft tissue calcification than women (30.3% vs. 21.8%). Soft tissue calcification was predominantly seen at posterior region of the mandible (88%) and most of them were single (60.7%). The prevalence of soft tissue calcification increased with age. Most of the detected soft tissue calcifications were smaller than 3mm (90%). Soft tissue calcifications in mandibular area were a relatively common finding especially in posterior region and more likely to happen in men and in older age group.

Pelvic artery calcification detection on CT scans using convolutional neural networks

NASA Astrophysics Data System (ADS)

Liu, Jiamin; Lu, Le; Yao, Jianhua; Bagheri, Mohammadhadi; Summers, Ronald M.

2017-03-01

Artery calcification is observed commonly in elderly patients, especially in patients with chronic kidney disease, and may affect coronary, carotid and peripheral arteries. Vascular calcification has been associated with many clinical outcomes. Manual identification of calcification in CT scans requires substantial expert interaction, which makes it time-consuming and infeasible for large-scale studies. Many works have been proposed for coronary artery calcification detection in cardiac CT scans. In these works, coronary artery extraction is commonly required for calcification detection. However, there are few works about abdominal or pelvic artery calcification detection. In this work, we present a method for automatic pelvic artery calcification detection on CT scan. This method uses the recent advanced faster region-based convolutional neural network (R-CNN) to directly identify artery calcification without a need for artery extraction since pelvic artery extraction itself is challenging. Our method first generates category-independent region proposals for each slice of the input CT scan using region proposal networks (RPN). Then, each region proposal is jointly classified and refined by softmax classifier and bounding box regressor. We applied the detection method to 500 images from 20 CT scans of patients for evaluation. The detection system achieved a 77.4% average precision and a 85% sensitivity at 1 false positive per image.

Geochemical Evidence for Calcification from the Drake Passage Time-series

NASA Astrophysics Data System (ADS)

Munro, D. R.; Lovenduski, N. S.; Takahashi, T.; Stephens, B. B.; Newberger, T.; Dierssen, H. M.; Randolph, K. L.; Freeman, N. M.; Bushinsky, S. M.; Key, R. M.; Sarmiento, J. L.; Sweeney, C.

2016-12-01

Satellite imagery suggests high particulate inorganic carbon within a circumpolar region north of the Antarctic Polar Front (APF), but in situ evidence for calcification in this region is sparse. Given the geochemical relationship between calcification and total alkalinity (TA), seasonal changes in surface concentrations of potential alkalinity (PA), which accounts for changes in TA due to variability in salinity and nitrate, can be used as a means to evaluate satellite-based calcification algorithms. Here, we use surface carbonate system measurements collected from 2002 to 2016 for the Drake Passage Time-series (DPT) to quantify rates of calcification across the Antarctic Circumpolar Current. We also use vertical PA profiles collected during two cruises across the Drake Passage in March 2006 and September 2009 to estimate the calcium carbonate to organic carbon export ratio. We find geochemical evidence for calcification both north and south of the APF with the highest rates observed north of the APF. Calcification estimates from the DPT are compared to satellite-based estimates and estimates based on hydrographic data from other regions around the Southern Ocean.

Eotaxin Augments Calcification in Vascular Smooth Muscle Cells.

PubMed

Raghuraman, Gayatri; Hsiung, Joseph; Zuniga, Mary C; Baughman, Brittanie D; Hitchner, Elizabeth; Guzman, Raul J; Zhou, Wei

2017-03-01

Calcification of atherosclerotic plaques in elderly patients represents a potent risk marker of cardiovascular events. Plasma analyses of patients with or without calcified plaques reveal significant differences in chemokines, particularly eotaxin, which escalates with increased calcification. We therefore, hypothesize that eotaxin in circulation augments calcification of vascular smooth muscle cells (VSMCs) possibly via oxidative stress in the vasculature. We observe that eotaxin increases the rate of calcification significantly in VSMCs as evidenced by increased alkaline phosphatase activity, calcium deposition, and osteogenic marker expression. In addition, eotaxin promotes proliferation in VSMCs and triggers oxidative stress in a NADPH oxidase dependent manner. These primary novel observations support our proposition that in the vasculature eotaxin augments mineralization. Our findings suggest that eotaxin may represent a potential therapeutic target for prevention of cardiovascular complications in the elderly. J. Cell. Biochem. 118: 647-654, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Automated aortic calcification detection in low-dose chest CT images

NASA Astrophysics Data System (ADS)

Xie, Yiting; Htwe, Yu Maw; Padgett, Jennifer; Henschke, Claudia; Yankelevitz, David; Reeves, Anthony P.

2014-03-01

The extent of aortic calcification has been shown to be a risk indicator for vascular events including cardiac events. We have developed a fully automated computer algorithm to segment and measure aortic calcification in low-dose noncontrast, non-ECG gated, chest CT scans. The algorithm first segments the aorta using a pre-computed Anatomy Label Map (ALM). Then based on the segmented aorta, aortic calcification is detected and measured in terms of the Agatston score, mass score, and volume score. The automated scores are compared with reference scores obtained from manual markings. For aorta segmentation, the aorta is modeled as a series of discrete overlapping cylinders and the aortic centerline is determined using a cylinder-tracking algorithm. Then the aortic surface location is detected using the centerline and a triangular mesh model. The segmented aorta is used as a mask for the detection of aortic calcification. For calcification detection, the image is first filtered, then an elevated threshold of 160 Hounsfield units (HU) is used within the aorta mask region to reduce the effect of noise in low-dose scans, and finally non-aortic calcification voxels (bony structures, calcification in other organs) are eliminated. The remaining candidates are considered as true aortic calcification. The computer algorithm was evaluated on 45 low-dose non-contrast CT scans. Using linear regression, the automated Agatston score is 98.42% correlated with the reference Agatston score. The automated mass and volume score is respectively 98.46% and 98.28% correlated with the reference mass and volume score.

Molecular structure of human aortic valve by μSR- FTIR microscopy

NASA Astrophysics Data System (ADS)

Borkowska, Anna M.; Nowakowski, Michał; Lis, Grzegorz J.; Wehbe, Katia; Cinque, Gianfelice; Kwiatek, Wojciech M.

2017-11-01

early phase of aortic valve calcific degeneration.

Cross-sectional relations of arterial stiffness, pressure pulsatility, wave reflection, and arterial calcification.

PubMed

Tsao, Connie W; Pencina, Karol M; Massaro, Joseph M; Benjamin, Emelia J; Levy, Daniel; Vasan, Ramachandran S; Hoffmann, Udo; O'Donnell, Christopher J; Mitchell, Gary F

2014-11-01

Arterial hemodynamics and vascular calcification are associated with increased risk for cardiovascular disease, but their inter-relations remain unclear. We sought to examine the associations of arterial stiffness, pressure pulsatility, and wave reflection with arterial calcification in individuals free of prevalent cardiovascular disease. Framingham Heart Study Third Generation and Offspring Cohort participants free of cardiovascular disease underwent applanation tonometry to measure arterial stiffness, pressure pulsatility, and wave reflection, including carotid-femoral pulse wave velocity, central pulse pressure, forward wave amplitude, and augmentation index. Participants in each cohort (n=1905, 45±6 years and n=1015, 65±9 years, respectively) underwent multidetector computed tomography to assess the presence and quantity of thoracic aortic calcification, abdominal aortic calcification, and coronary artery calcification. In multivariable-adjusted models, both higher carotid-femoral pulse wave velocity and central pulse pressure were associated with greater thoracic aortic calcification and abdominal aortic calcification, whereas higher augmentation index was associated with abdominal aortic calcification. Among the tonometry measures, carotid-femoral pulse wave velocity was the strongest correlate of all calcification measures in multivariable-adjusted models (odds ratio per SD for thoracic aortic calcification, 2.69 [95% confidence interval, 2.17-3.35]; abdominal aortic calcification, 1.47 [95% confidence interval, 1.26-1.73]; and coronary artery calcification, 1.48 [95% confidence interval, 1.28-1.72]; all P<0.001, respectively). We observed stronger relations of carotid-femoral pulse wave velocity, central pulse pressure, and forward wave amplitude with nearly all continuous calcification measures in the younger Third Generation Cohort as compared with the Offspring Cohort. In community-dwelling individuals without prevalent cardiovascular disease

SLC20A2 DEFICIENCY IN MICE LEADS TO ELEVATED PHOSPHATE LEVELS IN CEREBROSPINAL FLUID AND GLYMPHATIC PATHWAY-ASSOCIATED ARTERIOLAR CALCIFICATION, AND RECAPITULATES HUMAN IDIOPATHIC BASAL GANGLIA CALCIFICATION

PubMed Central

Wallingford, MC; Chia, J; Leaf, EM; Borgeia, S; Chavkin, NW; Sawangmake, C; Marro, K; Cox, TC; Speer, MY; Giachelli, CM

2016-01-01

Idiopathic basal ganglia calcification is a brain calcification disorder that has been genetically linked to autosomal dominant mutations in the sodium-dependent phosphate co-transporter, SLC20A2. The mechanisms whereby deficiency of Slc20a2 leads to basal ganglion calcification are unknown. In the mouse brain, we found that Slc20a2 was expressed in tissues that produce and/or regulate cerebrospinal fluid, including choroid plexus, ependyma and arteriolar smooth muscle cells. Haploinsufficient Slc20a2 +/− mice developed age-dependent basal ganglia calcification that formed in glymphatic pathway-associated arterioles. Slc20a2 deficiency uncovered phosphate homeostasis dysregulation characterized by abnormally high cerebrospinal fluid phosphate levels and hydrocephalus, in addition to basal ganglia calcification. Slc20a2 siRNA knockdown in smooth muscle cells revealed increased susceptibility to high phosphate-induced calcification. These data suggested that loss of Slc20a2 led to dysregulated phosphate homeostasis and enhanced susceptibility of arteriolar smooth muscle cells to elevated phosphate-induced calcification. Together, dysregulated cerebrospinal fluid phosphate and enhanced smooth muscle cell susceptibility may predispose to glymphatic pathway-associated arteriolar calcification. PMID:26822507

Histopathological and Immunohistochemical Evaluation of Pannus Tissue in Patients with Prosthetic Valve Dysfunction.

PubMed

Karakoyun, Süleyman; Ozan Gürsoy, Mustafa; Yesin, Mahmut; Kalçık, Macit; Astarcıoğlu, Mehmet Ali; Gündüz, Sabahattin; Emrah Oğuz, Ali; Çoban Kökten, Şermin; Nimet Karadayı, Ayşe; Tuncer, Altuğ; Köksal, Cengiz; Gökdeniz, Tayyar; Özkan, Mehmet

2016-01-01

Prosthetic valve dysfunction due to pannus formation is a rare but serious complication. Currently, limited data are available concerning the pathogenesis and immunohistochemical properties of pannus. The study aim was to investigate the morphological, histopathological and immunohistochemical characteristics of pannus formation in patients with prosthetic valve dysfunction. A total of 35 patients (10 males, 25 females; mean age 44 ± 16 years) who had undergone re-do valve surgery due to prosthetic valve obstruction was enrolled in the study. Immunohistochemical studies were aimed at evaluating the expression of alphasmooth muscle actin (α-SMA) and desmin in myofibroblasts and smooth muscle cells; epithelial membrane antigen (EMA) in epithelial cells; and CD34, Factor VIII and vascular endothelial growth factor (VEGF) in endothelial cells. Matrix metalloproteinases (MMPs) -2 and -9, and transforming growth factor-beta (TGF-β) were used to demonstrate cytokine release from macrophages, leukocytes, fibroblasts and myofibroblasts. Pannus appeared as a tough and thick tissue hyperplasia which began from outside the suture ring in the periannular region and extended to the inflow and outflow surfaces of the prosthetic valves. Histopathological analysis showed the pannus tissue to consist of chronic inflammatory cells (lymphocytes, plasma cells, macrophages and foreign body giant cells), spindle cells such as myofibroblasts, capillary blood vessels and endothelial cells laying down the lumens. Calcification was present in the pannus tissue of 19 explanted prostheses. Immunohistochemical studies revealed positive α-SMA expression in all patients, whereas 60.5% of patients were positive for desmin, 50% for EMA, 42.1% for VEGF, 39.5% for TBF-β, 42.1% for MMP-2, 86.8% for CD34, and 97.4% for Factor VIII. MMP-9 was negative in all patients. Pannus tissue appears to be formed as the result of a neointimal response in periannular regions of prosthetic valves that consist

Calcification Remodeling Index Characterized by Cardiac CT as a Novel Parameter to Predict the Use of Rotational Atherectomy for Coronary Intervention of Lesions with Moderate to Severe Calcification

PubMed Central

Yu, Mengmeng; Li, Yuehua; Li, Wenbin; Lu, Zhigang; Wei, Meng

2017-01-01

Objective To assess the feasibility of calcification characterization by coronary computed tomography angiography (CCTA) to predict the use of rotational atherectomy (RA) for coronary intervention of lesions with moderate to severe calcification. Materials and Methods Patients with calcified lesions treated by percutaneous coronary intervention (PCI) who underwent both CCTA and invasive coronary angiography were retrospectively included in this study. Calcification remodeling index was calculated as the ratio of the smallest vessel cross-sectional area of the lesion to the proximal reference luminal area. Other parameters such as calcium volume, regional Agatston score, calcification length, and involved calcium arc quadrant were also recorded. Results A total of 223 patients with 241 calcified lesions were finally included. Lesions with RA tended to have larger calcium volume, higher regional Agatston score, more involved calcium arc quadrants, and significantly smaller calcification remodeling index than lesions without RA. Receiver operating characteristic curve analysis revealed that the best cutoff value of calcification remodeling index was 0.84 (area under curve = 0.847, p < 0.001). Calcification remodeling index ≤ 0.84 was the strongest independent predictor (odds ratio: 251.47, p < 0.001) for using RA. Conclusion Calcification remodeling index was significantly correlated with the incidence of using RA to aid PCI. Calcification remodeling index ≤ 0.84 was the strongest independent predictor for using RA prior to stent implantation. PMID:28860893

Impact of seawater carbonate chemistry on the calcification of marine bivalves

NASA Astrophysics Data System (ADS)

Thomsen, J.; Haynert, K.; Wegner, K. M.; Melzner, F.

2015-07-01

Bivalve calcification, particularly of the early larval stages, is highly sensitive to the change in ocean carbonate chemistry resulting from atmospheric CO2 uptake. Earlier studies suggested that declining seawater [CO32-] and thereby lowered carbonate saturation affect shell production. However, disturbances of physiological processes such as acid-base regulation by adverse seawater pCO2 and pH can affect calcification in a secondary fashion. In order to determine the exact carbonate system component by which growth and calcification are affected it is necessary to utilize more complex carbonate chemistry manipulations. As single factors, pCO2 had no effects and [HCO3-] and pH had only limited effects on shell growth, while lowered [CO32-] strongly impacted calcification. Dissolved inorganic carbon (CT) limiting conditions led to strong reductions in calcification, despite high [CO32-], indicating that [HCO3-] rather than [CO32-] is the inorganic carbon source utilized for calcification by mytilid mussels. However, as the ratio [HCO3-] / [H+] is linearly correlated with [CO32-] it is not possible to differentiate between these under natural seawater conditions. An equivalent of about 80 μmol kg-1 [CO32-] is required to saturate inorganic carbon supply for calcification in bivalves. Below this threshold biomineralization rates rapidly decline. A comparison of literature data available for larvae and juvenile mussels and oysters originating from habitats differing substantially with respect to prevailing carbonate chemistry conditions revealed similar response curves. This suggests that the mechanisms which determine sensitivity of calcification in this group are highly conserved. The higher sensitivity of larval calcification seems to primarily result from the much higher relative calcification rates in early life stages. In order to reveal and understand the mechanisms that limit or facilitate adaptation to future ocean acidification, it is necessary to better

Fast-Acting Valve

NASA Technical Reports Server (NTRS)

Wojciechowski, Bogdan V. (Inventor); Pegg, Robert J. (Inventor)

2003-01-01

A fast-acting valve includes an annular valve seat that defines an annular valve orifice between the edges of the annular valve seat, an annular valve plug sized to cover the valve orifice when the valve is closed, and a valve-plug holder for moving the annular valve plug on and off the annular valve seat. The use of an annular orifice reduces the characteristic distance between the edges of the valve seat. Rather than this distance being equal to the diameter of the orifice, as it is for a conventional circular orifice, the characteristic distance equals the distance between the inner and outer radii (for a circular annulus). The reduced characteristic distance greatly reduces the gap required between the annular valve plug and the annular valve seat for the valve to be fully open, thereby greatly reducing the required stroke and corresponding speed and acceleration of the annular valve plug. The use of a valve-plug holder that is under independent control to move the annular valve plug between its open and closed positions is important for achieving controllable fast operation of the valve.

Size-dependent response of foraminiferal calcification to seawater carbonate chemistry

NASA Astrophysics Data System (ADS)

Henehan, Michael J.; Evans, David; Shankle, Madison; Burke, Janet E.; Foster, Gavin L.; Anagnostou, Eleni; Chalk, Thomas B.; Stewart, Joseph A.; Alt, Claudia H. S.; Durrant, Joseph; Hull, Pincelli M.

2017-07-01

The response of the marine carbon cycle to changes in atmospheric CO2 concentrations will be determined, in part, by the relative response of calcifying and non-calcifying organisms to global change. Planktonic foraminifera are responsible for a quarter or more of global carbonate production, therefore understanding the sensitivity of calcification in these organisms to environmental change is critical. Despite this, there remains little consensus as to whether, or to what extent, chemical and physical factors affect foraminiferal calcification. To address this, we directly test the effect of multiple controls on calcification in culture experiments and core-top measurements of Globigerinoides ruber. We find that two factors, body size and the carbonate system, strongly influence calcification intensity in life, but that exposure to corrosive bottom waters can overprint this signal post mortem. Using a simple model for the addition of calcite through ontogeny, we show that variable body size between and within datasets could complicate studies that examine environmental controls on foraminiferal shell weight. In addition, we suggest that size could ultimately play a role in determining whether calcification will increase or decrease with acidification. Our models highlight that knowledge of the specific morphological and physiological mechanisms driving ontogenetic change in calcification in different species will be critical in predicting the response of foraminiferal calcification to future change in atmospheric pCO2.

Can dental pulp calcification predict the risk of ischemic cardiovascular disease?

PubMed

Khojastepour, Leila; Bronoosh, Pegah; Khosropanah, Shahdad; Rahimi, Elham

2013-09-01

To report the association of pulp calcification with that of cardiovascular disease (CVD) using digital panoramic dental radiographs. Digital panoramic radiographs of patients referred from the angiography department were included if the patient was under 55 years old and had non-restored or minimally restored molars and canines. An oral and maxillofacial radiologist evaluated the images for pulpal calcifications in the selected teeth. The sensitivity, specificity, positive predictive value and negative predictive value of panoramic radiography in predicting CVD were calculated. Out of 122 patients who met the criteria, 68.2% of the patients with CVD had pulp chamber calcifications. Pulp calcification in panoramic radiography had a sensitivity of 68.9% to predict CVD. This study demonstrates that patients with CVD show an increased incidence of pulp calcification compared with healthy patients. The findings suggest that pulp calcification on panoramic radiography may have possibilities for use in CVD screening.

Pyrophosphate Supplementation Prevents Chronic and Acute Calcification in ABCC6-Deficient Mice.

PubMed

Pomozi, Viola; Brampton, Christopher; van de Wetering, Koen; Zoll, Janna; Calio, Bianca; Pham, Kevin; Owens, Jesse B; Marh, Joel; Moisyadi, Stefan; Váradi, András; Martin, Ludovic; Bauer, Carolin; Erdmann, Jeanette; Aherrahrou, Zouhair; Le Saux, Olivier

2017-06-01

Soft tissue calcification occurs in several common acquired pathologies, such as diabetes and hypercholesterolemia, or can result from genetic disorders. ABCC6, a transmembrane transporter primarily expressed in liver and kidneys, initiates a molecular pathway inhibiting ectopic calcification. ABCC6 facilitates the cellular efflux of ATP, which is rapidly converted into pyrophosphate (PPi), a major calcification inhibitor. Heritable mutations in ABCC6 underlie the incurable calcification disorder pseudoxanthoma elasticum and some cases of generalized arterial calcification of infancy. Herein, we determined that the administration of PPi and the bisphosphonate etidronate to Abcc6 -/- mice fully inhibited the acute dystrophic cardiac calcification phenotype, whereas alendronate had no significant effect. We also found that daily injection of PPi to Abcc6 -/- mice over several months prevented the development of pseudoxanthoma elasticum-like spontaneous calcification, but failed to reverse already established lesions. Furthermore, we found that the expression of low amounts of the human ABCC6 in liver of transgenic Abcc6 -/- mice, resulting in only a 27% increase in plasma PPi levels, led to a major reduction in acute and chronic calcification phenotypes. This proof-of-concept study shows that the development of both acute and chronic calcification associated with ABCC6 deficiency can be prevented by compensating PPi deficits, even partially. Our work indicates that PPi substitution represents a promising strategy to treat ABCC6-dependent calcification disorders. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Prevalence of Soft Tissue Calcifications in CBCT Images of Mandibular Region

PubMed Central

Khojastepour, Leila; Haghnegahdar, Abdolaziz; Sayar, Hamed

2017-01-01

Statement of the Problem: Most of the soft tissue calcifications within the head and neck region might not be accompanied by clinical symptoms but may indicate some pathological conditions. Purpose: The aim of this research was to determine the prevalence of soft tissue calcifications in cone beam computed tomography (CBCT) images of mandibular region. Materials and Method: In this cross sectional study the CBCT images of 602 patients including 294 men and 308 women with mean age 41.38±15.18 years were evaluated regarding the presence, anatomical location; type (single or multiple) and size of soft tissue calcification in mandibular region. All CBCT images were acquired by NewTom VGi scanner. Odds ratio and chi-square tests were used for data analysis and p< 0.05 was considered to be statistically significant. Results: 156 out of 602 patients had at least one soft tissue calcification in their mandibular region (25.9%. of studied population with mean age 51.7±18.03 years). Men showed significantly higher rate of soft tissue calcification than women (30.3% vs. 21.8%). Soft tissue calcification was predominantly seen at posterior region of the mandible (88%) and most of them were single (60.7%). The prevalence of soft tissue calcification increased with age. Most of the detected soft tissue calcifications were smaller than 3mm (90%). Conclusion: Soft tissue calcifications in mandibular area were a relatively common finding especially in posterior region and more likely to happen in men and in older age group. PMID:28620632

The effect of neonatal gene therapy with a gamma retroviral vector on cardiac valve disease in mucopolysaccharidosis VII dogs after a decade.

PubMed

Bigg, Paul W; Sleeper, Meg M; O'Donnell, Patricia A; Liu, Yuli; Wu, Susan; Casal, Margret L; Haskins, Mark E; Ponder, Katherine P

2013-11-01

Mucopolysaccharidosis VII (MPS VII) is due to deficient activity of the lysosomal enzyme β-glucuronidase (GUSB) and results in the accumulation of glycosaminoglycans (GAGs). This study determined the long-term effect of neonatal intravenous injection of a gamma retroviral vector (RV) on cardiac valve disease in MPS VII dogs. Transduced hepatocytes secreted GUSB into the blood for up to 11 years at levels similar to or greater than those achieved with enzyme replacement therapy (ERT). Valve regurgitation and thickening were scored from 0 (normal) to +4 (severely abnormal). At 1 year, untreated MPS VII dogs had mitral regurgitation, mitral valve thickening, aortic regurgitation, and aortic valve thickening scores of 2.3 ± 0.7, 2.3 ± 0.6, 1.8 ± 0.5, and 1.6 ± 0.7, respectively, which were higher than the values of 0.6 ± 0.1, 0.1 ± 0.4, 0.3 ± 0.8, and 0.1 ± 0.4, respectively, in treated MPS VII dogs. Treated MPS VII dogs maintained low aortic regurgitation and aortic valve thickening scores in their lifetime. Although mitral regurgitation and mitral valve thickening scores increased to 2.0 at ≥ 8 years of age in the treated MPS VII dogs, older normal dogs from the colony had similar scores, making it difficult to assess mitral valve disease. Older treated dogs had calcification within the mitral and the aortic valve annulus, while GUSB staining demonstrated enzyme activity within the mitral valve. We conclude that neonatal RV-mediated gene therapy reduced cardiac valve disease in MPS VII dogs for up to 11 years, and propose that neonatal initiation of ERT should have a similar effect. © 2013.

Relationship between dental calcification and skeletal maturation in a Peruvian sample.

PubMed

Lecca-Morales, Rocío M; Carruitero, Marcos J

2017-01-01

the objective of the study was to determine the relationship between dental calcification stages and skeletal maturation in a Peruvian sample. panoramic, cephalometric and carpal radiographs of 78 patients (34 girls and 44 boys) between 7 and 17 years old (9.90 ± 2.5 years) were evaluated. Stages of tooth calcification of the mandibular canine, first premolar, second premolar, and second molar and the skeletal maturation with a hand-wrist and a cervical vertebrae method were assessed. The relationships between the stages were assessed using Spearman's correlation coefficient. Additionally, the associations of mandibular and pubertal growth peak stages with tooth calcification were evaluated by Fisher's exact test. all teeth showed positive and statistically significant correlations, the highest correlation was between the mandibular second molar calcification stages with hand-wrist maturation stages (r = 0.758, p < 0.001) and with vertebrae cervical maturation stages (r = 0.605, p < 0.001). The pubertal growth spurt was found in the G stage of calcification of the second mandibular molar, and the mandibular growth peak was found in the F stage of calcification of the second molar. there was a positive relationship between dental calcification stages and skeletal maturation stages by hand-wrist and cervical vertebrae methods in the sample studied. Dental calcification stages of the second mandibular molar showed the highest positive correlation with the hand-wrist and cervical vertebrae stages.

Periaortic Fat Tissue: A Predictor of Cardiac Valvular Calcification, Malnutrition, Inflammation, and Atherosclerosis Components in Hemodialysis Patients.

PubMed

Genctoy, Gultekin; Eldem, Olcay; Ergun, Tarkan; Arikan, Serap

2015-09-01

Cardiac valvular calcification (CVC) in end-stage renal disease is shown to be a component of malnutrition, inflammation, atherosclerosis, calcification (MIAC) syndrome. Thoracic periaortic fat tissue (T-PAFT) is shown to be increased in patients with end-stage renal disease (ESRD), and has positive correlation with MIAC. Negative correlation between CVC and vitamin D is shown in hemodialysis (HD) patients. In this study, we investigated a relationship between body composition, T-PAFT, metabolic and inflammatory parameters, and CVC in HD patients. Seventy-six HD patients (49M) were included. CVC is defined as bright echoes of >1 mm on one or more cusps on echocardiography. Results were expressed as the number of calcified valves (0,1,2). Calcium, phosphorus, parathyroid hormone (PTH), C-reactive protein (CRP), albumin and 25-hydroxy vitamin D levels were studied from predialysis blood samples. T-PAFT was calculated using a method with manual definition of borders on images from multislice computed tomography. Basal metabolic rate, muscle mass, total and truncal fat mass were measured by bioimpedance analysis. There were 65.8% of patients who had CVC. Patients with CVC were older (63.5 ± 14.6 ± 17, P = 0.02). T-PAFT (1599 ± 596, 739.7 ± 179 mm(2) , P = 0.001) and CRP (15.8 ± 11; 11.1 ± 13.2 mg/dL; P = 0.04) were higher in the group with CVC. T-PAFT had positive correlations with CRP, MIAC, body mass index (BMI) and number of calcified valves, negative correlation with left ventricular ejection fraction, and no correlation with albumin, calcium, phosphorus, and PTH. The logistic regression analysis revealed that T-PAFT was a significant predictor of CVC. In this study, T-PAFT showed a positive correlation with inflammation, CVC, and MIAC score in HD patients. T-PAFT was a significant predictor of CVC. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Foraminiferal calcification and CO2

NASA Astrophysics Data System (ADS)

Nooijer, L. D.; Toyofuku, T.; Reichart, G. J.

2017-12-01

Ongoing burning of fossil fuels increases atmospheric CO2, elevates marine dissolved CO2 and decreases pH and the saturation state with respect to calcium carbonate. Intuitively this should decrease the ability of CaCO3-producing organisms to build their skeletons and shells. Whereas on geological time scales weathering and carbonate deposition removes carbon from the geo-biosphere, on time scales up to thousands of years, carbonate precipitation increases pCO2 because of the associated shift in seawater carbon speciation. Hence reduced calcification provides a potentially important negative feedback on increased pCO2 levels. Here we show that foraminifera form their calcium carbonate by active proton pumping. This elevates the internal pH and acidifies the direct foraminiferal surrounding. This also creates a strong pCO2 gradient and facilitates the uptake of DIC in the form of carbon dioxide. This finding uncouples saturation state from calcification and predicts that the added carbon due to ocean acidification will promote calcification by these organisms. This unknown effect could add substantially to atmospheric pCO2 levels, and might need to be accounted for in future mitigation strategies.

The third hand--a simple but useful tool for holding the sheath during transapical transcatheter aortic valve implantation.

PubMed

Wisser, Wilfried

2010-11-01

Transapical aortic valve implantation is an evolving technology for treating high-risk patients with symptomatic aortic stenosis. The transition to a catheter based implantation technique inherits one fundamental change: the native valve stays in place and is no longer removed. The selection of the correct plane of the aortic annulus, therefore, is mandatory. In addition, exact alignment of the sheath and catheters according to axis of the ascending aorta is imperative for correct implantation. That is why any additional movements have to be avoided. To aid in better workflow, we developed an easy-to-use cheap holder for the introduction sheath. By using a rigid table mount instrument holder the sheath can easily be fixed in the desired orientation, abolishing any movement and reducing the X-ray load to the implanting surgeon.

Hydrogen peroxide prevents vascular calcification induced ROS production by regulating Nrf-2 pathway.

PubMed

Zhang, Wensong; Li, Yi; Ding, Hanlu; Du, Yaqin; Wang, Li

2016-08-01

Although vascular calcification in end-stage renal disease (ESRD) represents a ubiquitous human health problem, effective therapies with limited side effects are still lacking, and the precise mechanisms are not fully understood. The Nrf-2/ARE pathway is a pivotal to regulate anti-oxidative responses in vascular calcification upon ESRD. Although Nrf-2 plays a crucial role in atherosclerosis, pulmonary fibrosis, and brain ischemia, the effect of Nrf-2 and oxidative stress on vascular calcification in ESRD patients is still unclear. The aim of this research was to study the protective role of hydrogen peroxide in vascular calcification and the mechanism of Nrf-2 and oxidative stress on vascular calcification. Here we used the rat vascular smooth muscle cell model of β-glycerophosphate-induced calcification resembling vascular calcification in ESRD to investigate the therapeutic effect of 0.01 mM hydrogen peroxide on vascular calcification and further explores the possible underlying mechanisms. Our current report shows the in vitro role of 0.01 mM hydrogen peroxide in protecting against intracellular ROS accumulation upon vascular calcification. Both hydrogen peroxide and sulforaphane pretreatment reduced ROS production, increased the expression of Nrf-2, and decreased the expression of Runx2 following calcification. Our study demonstrates that 0.01 mM hydrogen peroxide can effectively protect rat aortic vascular smooth muscle cells against oxidative stress by preventing vascular calcification induced ROS production through Nrf-2 pathway. These data might define an antioxidant role of hydrogen peroxide in vascular calcification upon ESRD.

Pathological Calcification and Ossification in Relation to Leriche and Policard's Theory.

PubMed

Jones, W; Roberts, R E

1933-05-01

(1) Pathology of calcification and ossification.-The Leriche-Policard theories. Hyperaemia of bone causes decalcification. Reduced blood supply causes sclerosis. Diminution of vascularity of fibrous tissue causes calcification. Excess of calcium, adequate blood supply and fibroblasts give rise to bone anywhere. Subperiosteal ossification. "Myositis ossificans."(2) Radiological significance of density of bone shadows.-Decalcification of disuse, of infections, of neoplasms. Traumatic and infective scquestra. Evidence that a fragment of bone is avascular.(3) Hyperaemic decalcification of bone.-Delayed and non-union of fractures. Kummel's disease. Spontaneous hyperaemic dislocation of the atlas. Hyperaemic decalcification and nephrolithiasis.(4) Anaemic sclerosis of bone.-Syphilitic bone disease. Malignant bone disease. Fragility of sclerosed bone-Paget's, Kienboch's, Kohler's and Panner's, Albers-Schönberg's diseases.(5) Pathological calcification.-Calcification of supraspinatus tendon. Calcification of tumours-angioma, haematoma, and thrombosed vessels, lipoma, cysts, etc. Calcification of semilunar cartilages and intervertebral discs.(6) Pathological ossification.-Ossification of tendons. Ossification of semilunar cartilages.

Decrease in coccolithophore calcification and CO2 since the middle Miocene.

PubMed

Bolton, Clara T; Hernández-Sánchez, María T; Fuertes, Miguel-Ángel; González-Lemos, Saúl; Abrevaya, Lorena; Mendez-Vicente, Ana; Flores, José-Abel; Probert, Ian; Giosan, Liviu; Johnson, Joel; Stoll, Heather M

2016-01-14

Marine algae are instrumental in carbon cycling and atmospheric carbon dioxide (CO2) regulation. One group, coccolithophores, uses carbon to photosynthesize and to calcify, covering their cells with chalk platelets (coccoliths). How ocean acidification influences coccolithophore calcification is strongly debated, and the effects of carbonate chemistry changes in the geological past are poorly understood. This paper relates degree of coccolith calcification to cellular calcification, and presents the first records of size-normalized coccolith thickness spanning the last 14 Myr from tropical oceans. Degree of calcification was highest in the low-pH, high-CO2 Miocene ocean, but decreased significantly between 6 and 4 Myr ago. Based on this and concurrent trends in a new alkenone ɛp record, we propose that decreasing CO2 partly drove the observed trend via reduced cellular bicarbonate allocation to calcification. This trend reversed in the late Pleistocene despite low CO2, suggesting an additional regulator of calcification such as alkalinity.

Decrease in coccolithophore calcification and CO2 since the middle Miocene

PubMed Central

Bolton, Clara T.; Hernández-Sánchez, María T.; Fuertes, Miguel-Ángel; González-Lemos, Saúl; Abrevaya, Lorena; Mendez-Vicente, Ana; Flores, José-Abel; Probert, Ian; Giosan, Liviu; Johnson, Joel; Stoll, Heather M.

2016-01-01

Marine algae are instrumental in carbon cycling and atmospheric carbon dioxide (CO2) regulation. One group, coccolithophores, uses carbon to photosynthesize and to calcify, covering their cells with chalk platelets (coccoliths). How ocean acidification influences coccolithophore calcification is strongly debated, and the effects of carbonate chemistry changes in the geological past are poorly understood. This paper relates degree of coccolith calcification to cellular calcification, and presents the first records of size-normalized coccolith thickness spanning the last 14 Myr from tropical oceans. Degree of calcification was highest in the low-pH, high-CO2 Miocene ocean, but decreased significantly between 6 and 4 Myr ago. Based on this and concurrent trends in a new alkenone ɛp record, we propose that decreasing CO2 partly drove the observed trend via reduced cellular bicarbonate allocation to calcification. This trend reversed in the late Pleistocene despite low CO2, suggesting an additional regulator of calcification such as alkalinity. PMID:26762469

Assessing Anticalcification Treatments in Bioprosthetic Tissue by Using the New Zealand Rabbit Intramuscular Model

PubMed Central

Wright, Gregory A; Faught, Joelle M; Olin, Jane M

2009-01-01

The objective of this work was to demonstrate that the New Zealand White (NZW) rabbit intramuscular model can be used for detecting calcification in bioprosthetic tissue and to compare the calcification in the rabbit to that of native human valves. The rabbit model was compared with the commonly used Sprague–Dawley rat subcutaneous model. Eighteen rabbits and 18 rats were used to assess calcification in bioprosthetic tissue over time (7, 14, 30, and 90 d). The explanted rabbit and rat tissue discs were measured for calcium by using atomic absorption and Raman spectroscopy. Calcium deposits on the human valve explants were assessed by using Raman spectroscopy. The results showed that the NZW rabbit model is robust for detecting calcification in a shorter duration (14 d), with less infection complications, more space to implant tissue groups (thereby reducing animal use numbers), and a more metabolically and mechanically dynamic environment than the rat subcutaneous model . The human explanted valves and rabbit explanted tissue both showed Raman peaks at 960 cm−1 which is representative of hydroxyapatite. Hydroxyapatite is the final calcium and phosphate species in the calcification of bioprosthetic heart valves and rabbit intramuscular implants. The NZW rabbit intramuscular model is an effective model for assessing calcification in bioprosthetic tissue. PMID:19619417

Relationship between intracranial internal carotid artery calcification and enlarged cerebral perivascular space.

PubMed

Tao, Xiao-Xiao; Li, Ge-Fei; Wu, Yi-Lan; Liu, Yi-Sheng; Zhao, Ying; Shi, Yan-Hui; Zhuang, Mei-Ting; Hou, Tian-Yu; Zhao, Rong; Liu, Feng-Di; Wang, Xue-Mei; Shen, Ying; Cui, Guo-Hong; Su, Jing-Jing; Chen, Wei; Tang, Xue-Mei; Sun, Ji; Liu, Jian-Ren

2017-06-01

The association between intracranial internal carotid artery (IICA) calcification and lacunes, white matter hyperintensity (WMH), and cerebral microbleeds (CMBs) has been well researched. However, enlarged cerebral perivascular space (PVS) has not yet been reported to correlate with intracranial internal carotid artery calcification. Therefore, the primary aim of this study was to investigate the relationship between IICA calcification and enlarged PVS. A total of 189 patients with ischemic stroke in the middle cerebral artery territory who presented within 7 days of ictus from 2012 to 2015 were enrolled respectively. All patients were required to have undergone head computed tomography, magnetic resonance imaging, susceptibility-weighted magnetic resonance imaging, magnetic resonance angiography, or computed tomography angiography. Clinical characteristics were recorded. IICA calcification and enlarged PVS were semi-quantitatively evaluated, and the presence of lacunes, WMH, and CMBs was recorded. Of the 189 patients, 63.5% were male. Mean age of the patients was 68.6 ± 12.2 years. There were 104 patients with IICA calcification. Age, diabetes mellitus, lacunes, and white matter hyperintensity were significantly associated with IICA calcification (P < 0.05). Multivariate logistic regression analysis showed that age, diabetes mellitus, and lacunes were independent predictors of IICA calcification (P < 0.05). A lower risk of IICA calcification was found in patients with a higher enlarged PVS score (P = 0.004). Higher enlarged PVS scores were associated with a lesser degree of IICA calcification. There appears to be a relationship between reduced risk of IICA calcification and enlarged PVS.

Bioprosthetic Valve Fracture During Valve-in-valve TAVR: Bench to Bedside

PubMed Central

Saxon, John T; Allen, Keith B; Cohen, David J

2018-01-01

Valve-in-valve (VIV) transcatheter aortic valve replacement (TAVR) has been established as a safe and effective means of treating failed surgical bioprosthetic valves (BPVs) in patients at high risk for complications related to reoperation. Patients who undergo VIV TAVR are at risk of patient–prosthesis mismatch, as the transcatheter heart valve (THV) is implanted within the ring of the existing BPV, limiting full expansion and reducing the maximum achievable effective orifice area of the THV. Importantly, patient–prosthesis mismatch and high residual transvalvular gradients are associated with reduced survival following VIV TAVR. Bioprosthetic valve fracture (BVF) is as a novel technique to address this problem. During BPV, a non-compliant valvuloplasty balloon is positioned within the BPV frame, and a highpressure balloon inflation is performed to fracture the surgical sewing ring of the BPV. This allows for further expansion of the BPV as well as the implanted THV, thus increasing the maximum effective orifice area that can be achieved after VIV TAVR. This review focuses on the current evidence base for BVF to facilitate VIV TAVR, including initial bench testing, procedural technique, clinical experience and future directions. PMID:29593832

Bioprosthetic Valve Fracture During Valve-in-valve TAVR: Bench to Bedside.

PubMed

Saxon, John T; Allen, Keith B; Cohen, David J; Chhatriwalla, Adnan K

2018-01-01

Valve-in-valve (VIV) transcatheter aortic valve replacement (TAVR) has been established as a safe and effective means of treating failed surgical bioprosthetic valves (BPVs) in patients at high risk for complications related to reoperation. Patients who undergo VIV TAVR are at risk of patient-prosthesis mismatch, as the transcatheter heart valve (THV) is implanted within the ring of the existing BPV, limiting full expansion and reducing the maximum achievable effective orifice area of the THV. Importantly, patient-prosthesis mismatch and high residual transvalvular gradients are associated with reduced survival following VIV TAVR. Bioprosthetic valve fracture (BVF) is as a novel technique to address this problem. During BPV, a non-compliant valvuloplasty balloon is positioned within the BPV frame, and a highpressure balloon inflation is performed to fracture the surgical sewing ring of the BPV. This allows for further expansion of the BPV as well as the implanted THV, thus increasing the maximum effective orifice area that can be achieved after VIV TAVR. This review focuses on the current evidence base for BVF to facilitate VIV TAVR, including initial bench testing, procedural technique, clinical experience and future directions.

Relationship between dental calcification and skeletal maturation in a Peruvian sample

PubMed Central

Lecca-Morales, Rocío M.; Carruitero, Marcos J.

2017-01-01

ABSTRACT Objective: the objective of the study was to determine the relationship between dental calcification stages and skeletal maturation in a Peruvian sample. Methods: panoramic, cephalometric and carpal radiographs of 78 patients (34 girls and 44 boys) between 7 and 17 years old (9.90 ± 2.5 years) were evaluated. Stages of tooth calcification of the mandibular canine, first premolar, second premolar, and second molar and the skeletal maturation with a hand-wrist and a cervical vertebrae method were assessed. The relationships between the stages were assessed using Spearman’s correlation coefficient. Additionally, the associations of mandibular and pubertal growth peak stages with tooth calcification were evaluated by Fisher’s exact test. Results: all teeth showed positive and statistically significant correlations, the highest correlation was between the mandibular second molar calcification stages with hand-wrist maturation stages (r = 0.758, p < 0.001) and with vertebrae cervical maturation stages (r = 0.605, p < 0.001). The pubertal growth spurt was found in the G stage of calcification of the second mandibular molar, and the mandibular growth peak was found in the F stage of calcification of the second molar. Conclusion: there was a positive relationship between dental calcification stages and skeletal maturation stages by hand-wrist and cervical vertebrae methods in the sample studied. Dental calcification stages of the second mandibular molar showed the highest positive correlation with the hand-wrist and cervical vertebrae stages. PMID:28746492

Genetics in arterial calcification: pieces of a puzzle and cogs in a wheel.

PubMed

Rutsch, Frank; Nitschke, Yvonne; Terkeltaub, Robert

2011-08-19

Artery calcification reflects an admixture of factors such as ectopic osteochondral differentiation with primary host pathological conditions. We review how genetic factors, as identified by human genome-wide association studies, and incomplete correlations with various mouse studies, including knockout and strain analyses, fit into "pieces of the puzzle" in intimal calcification in human atherosclerosis, and artery tunica media calcification in aging, diabetes mellitus, and chronic kidney disease. We also describe in sharp contrast how ENPP1, CD73, and ABCC6 serve as "cogs in a wheel" of arterial calcification. Specifically, each is a minor component in the function of a much larger network of factors that exert balanced effects to promote and suppress arterial calcification. For the network to normally suppress spontaneous arterial calcification, the "cogs" ENPP1, CD73, and ABCC6 must be present and in working order. Monogenic ENPP1, CD73, and ABCC6 deficiencies each drive a molecular pathophysiology of closely related but phenotypically different diseases (generalized arterial calcification of infancy (GACI), pseudoxanthoma elasticum (PXE) and arterial calcification caused by CD73 deficiency (ACDC)), in which premature onset arterial calcification is a prominent but not the sole feature.

Computed Tomographic Pattern of Physiological Intracranial Calcifications in a City in Central Africa

PubMed Central

Uduma, Uduma Felix; Pius, Fokam; Mathieu, Motah

2012-01-01

Objective: Intracranial calcifications underlie certain brain diseases which may be de novo or systemic. But calclfications un-connected to pathologies are classified physiological. Aim: To evaluate physiological intracranial calcifications in Douala with establishment of earliest age range of detection. Materials and Methods: Prospective study of brain computed tomograms was done from April to October 2009 using Schumadzu CT Scan machine. Axial, reconstructed and bone window images as well Hounsfield unit measurements were used for final evaluations. Results were analysed with SSPS 3. Results: 132 patients with 75 males and 57 females were studied and 163 separate calcifications were identified due to co-existent calcifications. The highest calcification was in choroid plexi, constituiting 56.82% of the studied population. This was followed by pineal gland. Both were commonly co-existent with advancing age. These calcifications were first seen at 10-19years. No type of physiological intracranial calcification was seen below age 10. The least calcification of 0.76% of population was in dentate nucleus. Conclusion: No intra-cranial physiological calcifications started earlier than 9years in Douala, a city in Cameroon, Central Africa. PMID:22980109

Direct comparison of regulators of calcification between bone and vessels in humans.

PubMed

Schweighofer, N; Aigelsreiter, A; Trummer, O; Graf-Rechberger, M; Hacker, N; Kniepeiss, D; Wagner, D; Stiegler, P; Trummer, C; Pieber, T; Obermayer-Pietsch, B; Müller, H

2016-07-01

Calcification is not only physiologically present in bone but is a main pathophysiological process in vasculature, favouring cardiovascular diseases. Our aim was to investigate changes in the expression of calcification regulators during vascular calcification in bone and vasculature. Levels of gene expression of osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL), osteopontin (OPN), matrix gla protein (MGP), bone sialoprotein (BSP), SMAD6, and runt-related transcription factor 2 (RUNX2) were determined in bone, aorta, and external iliac artery tissue samples of transplant donors. Histological stages of atherosclerosis (AS) in vessels are defined as "no changes", "intima thickening", or "intima calcification". Patients' bone samples were subgrouped accordingly. We demonstrate that in vessels BSP and OPN expression significantly increased during intima thickening and decreased during intima calcification, whereas the expression of regulators of calcification did not significantly change in bone during intima thickening and intima calcification. At the stage of intima thickening, MGP, OPG, and SMAD6 expression and at stage of intima calcification only MGP expression was lower in bone than in vessel. The expression of BSP and RANKL was regulated in opposite ways in bone and vessels, whereas the expression of MGP, OC, RUNX2, and OPN was regulated in a tissue-specific manner. Our study is the first direct comparison of gene expression changes during AS progression in bone and vessels. Our results indicate that changes in the expression of regulators of calcification in the vessel wall as well as in bone occur early in the calcification process, even prior to deposition of calcium/phosphate precipitation. Copyright © 2016. Published by Elsevier Inc.

Subject-specific finite-element modeling of normal aortic valve biomechanics from 3D+t TEE images.

PubMed

Labrosse, Michel R; Beller, Carsten J; Boodhwani, Munir; Hudson, Christopher; Sohmer, Benjamin

2015-02-01

In the past decades, developments in transesophageal echocardiography (TEE) have opened new horizons in reconstructive surgery of the aortic valve (AV), whereby corrections are made to normalize the geometry and function of the valve, and effectively treat leaks. To the best of our knowledge, we propose the first integrated framework to process subject-specific 3D+t TEE AV data, determine age-matched material properties for the aortic and leaflet tissues, build a finite element model of the unpressurized AV, and simulate the AV function throughout a cardiac cycle. For geometric reconstruction purposes, dedicated software was created to acquire the 3-D coordinates of 21 anatomical landmarks of the AV apparatus in a systematic fashion. Measurements from ten 3D+t TEE datasets of normal AVs were assessed for inter- and intra-observer variability. These tests demonstrated mean measurement errors well within the acceptable range. Simulation of a complete cardiac cycle was successful for all ten valves and validated the novel schemes introduced to evaluate age-matched material properties and iteratively scale the unpressurized dimensions of the valves such that, given the determined material properties, the dimensions measured in vivo closely matched those simulated in late diastole. The leaflet coaptation area, describing the quality of the sealing of the valve, was measured directly from the medical images and was also obtained from the simulations; both approaches correlated well. The mechanical stress values obtained from the simulations may be interpreted in a comparative sense whereby higher values are indicative of higher risk of tearing and/or development of calcification. Copyright © 2014 Elsevier B.V. All rights reserved.

A new generation of high flex life polyurethane urea for polymer heart valve--studies on in vivo biocompatibility and biodurability.

PubMed

Thomas, Vinoy; Jayabalan, Muthu

2009-04-01

Development of new generation high flex life polyurethane urea (HFL18-PU) with appropriate elastic modulus, biocompatibility, blood compatibility, resistant to calcification, and biodurability for the long-term use as cardiac device is still a challenge. This study reports the development of a fully aliphatic, ether-free physically cross-linked and low elastic modulus (6.841 +/- 0.27 MPa) polyurethane urea having in vivo biostability, in vivo biocompatibility and high flex-life (721 +/- 30 million cycles) that can satisfy the requirements for the fabrication of tri-leaflet heart valve. Copyright 2008 Wiley Periodicals, Inc.

Reversible vascular calcifications associated with hypervitaminosis D.

PubMed

Cirillo, Massimo; Bilancio, Giancarlo; Cirillo, Chiara

2016-02-01

A 64-year-old man was hospitalized in 2002 with symptoms of stupor, weakness, and renal colic. The clinical examination indicated borderline hypertension, small masses in the glutei, and polyuria. Laboratory tests evidenced high serum concentrations of creatinine, calcium, and phosphate. Imaging assessments disclosed widespread vascular calcifications, gluteal calcifications, and pelvic ectasia. Subsequent lab tests indicated suppressed serum parathyroid hormone, extremely high serum 25-hydroxy vitamin D, and normal serum 1,25-dihydroxy vitamin D. Treatment was started with intravenous infusion of saline and furosemide due to the evidence of hypercalcemia. Prednisone and omeprazole were added given the evidence of hypervitaminosis D. The treatment improved serum calcium, kidney function, and consciousness. The medical history disclosed recent treatment with exceptionally high doses of slow-release intra-muscular cholecalciferol and the recent excretion of urinary stones. The patient was discharged when it was possible to stop the intravenous treatment. The post-discharge treatment included oral hydration, furosemide, prednisone and omeprazole for approximately 6 months up to complete resolution of the hypercalcemia. The patient came back 12 years later because of microhematuria. Lab tests were normal for calcium/phosphorus homeostasis and kidney function. Imaging tests indicated only minor vascular calcifications. This is the first evidence of reversible vascular calcifications secondary to hypervitaminosis D.

New engineering treatment of bovine pericardium confers outstanding resistance to calcification in mitral and pulmonary implantations in a juvenile sheep model.

PubMed

Brizard, Christian P; Brink, Johann; Horton, Steven B; Edwards, Glenn Anthony; Galati, John C; Neethling, William M L

2014-12-01

To conduct a test of noninferiority for CardioCel (Admedus, Brisbane, Australia), a chemically engineered bovine pericardium over autologous pericardium treated intraoperatively with glutaraldehyde in a chronic juvenile sheep model of pulmonary valve (PV) and mitral valve (MV) reconstruction. We replaced the posterior leaflet of the MV and of 1 PV cusp with patches in ewes aged 10 months. There were 2 groups: CardioCel (n = 6) and control (n = 4). All valves were competent. Echocardiography was performed before euthanasia. The collected data were function, macroscopy, histology, and calcium contents. The primary end points were thickening and calcium content. All animals survived until sacrifice after 7 months. The valves had normal echo. The macroscopic aspect of the valves was excellent. Examination of the slides for both groups revealed a continuous endothelium on both sides of the patch and a layer of new collagen developed on both sides between patch and endothelium and interstitial cells and smooth muscle cell in these layers. The patch had not thickened but the 2 layers of new collagen for the PV showed a median thickening of 37% in the CardioCel group and 111% in the control group (P = .01), and for the MV a thickening of 108% and 251%, respectively, was seen (P = .01). The median calcium content in the PV was 0.24 μg/mg (range, 0.19-0.30) in the CardioCel group versus 0.34 μg/mg (range, 0.24-0.62) in controls (P = .20). In the MV it was 0.46 μg/mg (range, 0.30-1.0) in the CardioCel group and 0.47 μg/mg (range, 0.29-1.9) in controls (P = 1.0). In this growing lamb model the CardioCel patch allowed accurate valve repair at both systemic and pulmonary pressure. The mechanical properties of CardioCel after 7 months were preserved with a more controlled healing than the treated autologous pericardium and without calcification. Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Pathological Calcification and Ossification in Relation to Leriche and Policard's Theory

PubMed Central

Jones, Watson; Roberts, R. E.

1933-01-01

(1) Pathology of calcification and ossification.—The Leriche-Policard theories. Hyperæmia of bone causes decalcification. Reduced blood supply causes sclerosis. Diminution of vascularity of fibrous tissue causes calcification. Excess of calcium, adequate blood supply and fibroblasts give rise to bone anywhere. Subperiosteal ossification. “Myositis ossificans.” (2) Radiological significance of density of bone shadows.—Decalcification of disuse, of infections, of neoplasms. Traumatic and infective scquestra. Evidence that a fragment of bone is avascular. (3) Hyperæmic decalcification of bone.—Delayed and non-union of fractures. Kummel's disease. Spontaneous hyperæmic dislocation of the atlas. Hyperæmic decalcification and nephrolithiasis. (4) Anæmic sclerosis of bone.—Syphilitic bone disease. Malignant bone disease. Fragility of sclerosed bone—Paget's, Kienboch's, Kohler's and Panner's, Albers-Schönberg's diseases. (5) Pathological calcification.—Calcification of supraspinatus tendon. Calcification of tumours—angioma, hæmatoma, and thrombosed vessels, lipoma, cysts, etc. Calcification of semilunar cartilages and intervertebral discs. (6) Pathological ossification.—Ossification of tendons. Ossification of semilunar cartilages. PMID:19989304

Is there a correlation between the pineal gland calcification and migraine?

PubMed

Ozlece, H K; Akyuz, O; Ilik, F; Huseyinoglu, N; Aydin, S; Can, S; Serim, V A

2015-10-01

The pineal gland calcifications have been associated with some diseases such as cerebral infarction, Alzheimer's disease and intracerebral hemorrhage while most cases are considered idiopathic and physiologic. However, there are limited data in the current literature about the association of pineal calcification and migraine. Our aim was to evaluate this association between migraine and pineal calcification by computed tomography of the brain. In our study, we assessed the computed tomography images of patients, who referred to the neurology outpatient clinic with the complaint of headache and were diagnosed with migraine without aura based according to 2004 criteria of the International Headache Society. 503 migraine patients and 500 control subjects without migraine diagnosis were included in this study. When migraine and control groups were compared by pineal calcification, the rates were determined as 80, 6% and 55% in migraine and control group, respectively. The difference was statistically significant (p < 0.001). In addition, it was seen that pineal calcifications, detected in migraine patients, did not show age-related increase. According to our data, we can point that pineal calcification may be associated with migraine.

[Severe generalized dystonia due to postradiotherapy cerebral calcifications].

PubMed

Chanson, J-B; Anheim, M; Lagha-Boukbiza, O; Fleury, M; Sellal, F; Tranchant, C

2008-05-01

Cerebral calcifications are a cause of secondary dystonia and may be an uncommon complication of radiotherapy. We report a very severe case of generalized dystonia due to postradiotherapy basal ganglia calcifications. An 8-year-old girl received 53 grays radiotherapy after surgery for craniopharyngioma. One year later she developed generalized dystonia. Computed tomography showed bilateral basal ganglia calcifications, especially of the lenticular nuclei. Pharmacological treatment with tetrabenazine, clonazepam and trihexiphenydile allowed a very limited improvement of dystonia; the course was complicated by dystonic storms and decompensations resulting from the iatrogenous panhypopituitarism. This case illustrates a severe complication of cranial irradiation which should be considered in the indications of this treatment, especially for children.

Control Valve

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moore, Wayne R.

A control valve includes a first conduit having a first inlet and a first outlet and defining a first passage; a second conduit having a second inlet and a second outlet and defining a second passage, the second conduit extending into the first passage such that the second inlet is located within the first passage; and a valve plate disposed pivotably within the first passage, the valve plate defining a valve plate surface. Pivoting of the valve plate within the first passage varies flow from the first inlet to the first outlet and the valve plate is pivotal between amore » first position and a second position such that in the first position the valve plate substantially prevents fluid communication between the first passage and the second passage and such that in the second position the valve plate permits fluid communication between the first passage and the second passage.« less

History of hot flashes and aortic calcification among postmenopausal women.

PubMed

Thurston, Rebecca C; Kuller, Lewis H; Edmundowicz, Daniel; Matthews, Karen A

2010-03-01

Menopausal hot flashes are considered largely a quality-of-life issue. However, emerging research also links hot flashes to cardiovascular risk. In some investigations, this risk is particularly apparent among women using hormone therapy. The aim of this study was to determine whether a longer history of reported hot flashes over the study period was associated with greater aortic and coronary artery calcification. Interactions with hormone therapy use were examined in an exploratory fashion. Participants included 302 women participating in the Healthy Women Study, a longitudinal study of cardiovascular risk during perimenopause and postmenopause, which was initiated in 1983. Hot flashes (any/none) were assessed when women were 1, 2, 5, and 8 years postmenopausal. Electron beam tomography measures of coronary artery calcification and aortic calcification were completed in 1997-2004. Associations between the number of visits with report of hot flashes, divided by the number of visits attended, and aortic or coronary artery calcification (transformed) were examined in linear regression models. Interactions by hormone therapy use were evaluated. Among women using hormone therapy, a longer history of reported hot flashes was associated with increased aortic calcification, controlling for traditional cardiovascular risk factors (b = 2.87, SE = 1.21, P < 0.05). There were no significant associations between history of hot flashes and coronary artery calcification. Among postmenopausal women using hormone therapy, a longer history of reported hot flashes measured prospectively was associated with increased aortic calcification, controlling for traditional cardiovascular risk factors. Hot flashes may signal adverse cardiovascular changes among certain postmenopausal women.

Association of conjunctival and corneal calcification with vascular calcification among hepatitis-C-seropositive hemodialysis patients.

PubMed

AbouSeif, Khaled; Sany, Dawlat; Elshahawy, Yasser; Seddik, Ayman; Rahman, Khedr; Gaber, Moustapha

2016-01-01

Disorders associated with the hepatitis C virus (HCV) have been reported including cardiovascular, metabolic, and central nervous system diseases. Since chronic HCV infections may be curable, their identification as causal contributors to cardiovascular risk could offer new perspectives in the prevention of cardiovascular disease. The aim of this study is to investigate the association between HCV and aortic arch calcification (AAC) and corneal and conjunctival calcification (CCC) in maintenance hemodialysis (MHD) patients; further, we assessed the correlation of CCC with vascular calcification. A total of 100 patients undergoing hemodialysis (HD) in our hospital were included in this study. Patients underwent a complete ocular examination including intraocular pressure, and CCC was looked for by slit lamp and fundoscopy. CCC was graded according to modified Porter and Crombie classification system described by Tokuyama et al. Helical computerized tomographic chest examination was used to evaluate the grading of AAC. Demographic, hematological, biochemical, and dialysis-related data were obtained. There was significant difference between seropositive (n = 51) and seronegative patients (n = 49) regarding grading of AAC and CCC (P <0.001). Significant positive correlation was found between grading of CCC, AAC, age (P <0.001), duration on HD (P <0.001), HCV-antibody positivity (P <0.001), serum calcium level (P <0.001), serum phosphorus level (P <0.001), calcium × phosphorus product (P <0.001), and i-parathormone level (P < 0.001). In addition, CCC grading positively correlated with AAC. Our results suggest that patients undergoing HD infected with the HCV have high degree of CCC, AAC, and mineral metabolism disorder. The strong correlation between CCC and AAC indicates that CCC evaluation is an easy, fast, non-invasive method, and might be used as an indirect indicator to detect vascular calcification in patients undergoing MHD.

Reversal of ocean acidification enhances net coral reef calcification.

PubMed

Albright, Rebecca; Caldeira, Lilian; Hosfelt, Jessica; Kwiatkowski, Lester; Maclaren, Jana K; Mason, Benjamin M; Nebuchina, Yana; Ninokawa, Aaron; Pongratz, Julia; Ricke, Katharine L; Rivlin, Tanya; Schneider, Kenneth; Sesboüé, Marine; Shamberger, Kathryn; Silverman, Jacob; Wolfe, Kennedy; Zhu, Kai; Caldeira, Ken

2016-03-17

Approximately one-quarter of the anthropogenic carbon dioxide released into the atmosphere each year is absorbed by the global oceans, causing measurable declines in surface ocean pH, carbonate ion concentration ([CO3(2-)]), and saturation state of carbonate minerals (Ω). This process, referred to as ocean acidification, represents a major threat to marine ecosystems, in particular marine calcifiers such as oysters, crabs, and corals. Laboratory and field studies have shown that calcification rates of many organisms decrease with declining pH, [CO3(2-)], and Ω. Coral reefs are widely regarded as one of the most vulnerable marine ecosystems to ocean acidification, in part because the very architecture of the ecosystem is reliant on carbonate-secreting organisms. Acidification-induced reductions in calcification are projected to shift coral reefs from a state of net accretion to one of net dissolution this century. While retrospective studies show large-scale declines in coral, and community, calcification over recent decades, determining the contribution of ocean acidification to these changes is difficult, if not impossible, owing to the confounding effects of other environmental factors such as temperature. Here we quantify the net calcification response of a coral reef flat to alkalinity enrichment, and show that, when ocean chemistry is restored closer to pre-industrial conditions, net community calcification increases. In providing results from the first seawater chemistry manipulation experiment of a natural coral reef community, we provide evidence that net community calcification is depressed compared with values expected for pre-industrial conditions, indicating that ocean acidification may already be impairing coral reef growth.

Reversal of ocean acidification enhances net coral reef calcification

NASA Astrophysics Data System (ADS)

Albright, Rebecca; Caldeira, Lilian; Hosfelt, Jessica; Kwiatkowski, Lester; MacLaren, Jana K.; Mason, Benjamin M.; Nebuchina, Yana; Ninokawa, Aaron; Pongratz, Julia; Ricke, Katharine L.; Rivlin, Tanya; Schneider, Kenneth; Sesboüé, Marine; Shamberger, Kathryn; Silverman, Jacob; Wolfe, Kennedy; Zhu, Kai; Caldeira, Ken

2016-03-01

Approximately one-quarter of the anthropogenic carbon dioxide released into the atmosphere each year is absorbed by the global oceans, causing measurable declines in surface ocean pH, carbonate ion concentration ([CO32-]), and saturation state of carbonate minerals (Ω). This process, referred to as ocean acidification, represents a major threat to marine ecosystems, in particular marine calcifiers such as oysters, crabs, and corals. Laboratory and field studies have shown that calcification rates of many organisms decrease with declining pH, [CO32-], and Ω. Coral reefs are widely regarded as one of the most vulnerable marine ecosystems to ocean acidification, in part because the very architecture of the ecosystem is reliant on carbonate-secreting organisms. Acidification-induced reductions in calcification are projected to shift coral reefs from a state of net accretion to one of net dissolution this century. While retrospective studies show large-scale declines in coral, and community, calcification over recent decades, determining the contribution of ocean acidification to these changes is difficult, if not impossible, owing to the confounding effects of other environmental factors such as temperature. Here we quantify the net calcification response of a coral reef flat to alkalinity enrichment, and show that, when ocean chemistry is restored closer to pre-industrial conditions, net community calcification increases. In providing results from the first seawater chemistry manipulation experiment of a natural coral reef community, we provide evidence that net community calcification is depressed compared with values expected for pre-industrial conditions, indicating that ocean acidification may already be impairing coral reef growth.

Abdominal calcifications and diagnostic imaging decision making: a topic review

PubMed Central

Bassano, John M.

2006-01-01

Abstract Objective To review commonly encountered calcifications found within the abdomen as seen on the lumbar spine radiograph and to determine which advanced imaging modality is best to thoroughly assess the patient. Methods Searches of electronic databases and textbooks were conducted to construct this narrative overview. Discussion By categorizing the type of calcification and localizing it anatomically, most often a definitive diagnosis can be reached. Two commonly encountered conditions, abdominal aortic aneurysms and urinary calculi, are used to compare the main advanced imaging modalities (diagnostic ultrasound and computed tomography) used to further assess abdominal calcifications. Conclusion In most circumstances, either diagnostic ultrasound or computed tomography will establish a definitive diagnosis and offer thorough imaging assessment for abdominal calcifications. PMID:19674671

Nuclear radiation actuated valve

DOEpatents

Christiansen, David W.; Schively, Dixon P.

1985-01-01

A nuclear radiation actuated valve for a nuclear reactor. The valve has a valve first part (such as a valve rod with piston) and a valve second part (such as a valve tube surrounding the valve rod, with the valve tube having side slots surrounding the piston). Both valve parts have known nuclear radiation swelling characteristics. The valve's first part is positioned to receive nuclear radiation from the nuclear reactor's fuel region. The valve's second part is positioned so that its nuclear radiation induced swelling is different from that of the valve's first part. The valve's second part also is positioned so that the valve's first and second parts create a valve orifice which changes in size due to the different nuclear radiation caused swelling of the valve's first part compared to the valve's second part. The valve may be used in a nuclear reactor's core coolant system.

Vitamin K status and vascular calcification: evidence from observational and clinical studies.

PubMed

Shea, M Kyla; Holden, Rachel M

2012-03-01

Vascular calcification occurs when calcium accumulates in the intima (associated with atherosclerosis) and/or media layers of the vessel wall. Coronary artery calcification (CAC) reflects the calcium burden within the intima and media of the coronary arteries. In population-based studies, CAC independently predicts cardiovascular disease (CVD) and mortality. A preventive role for vitamin K in vascular calcification has been proposed based on its role in activating matrix Gla protein (MGP), a calcification inhibitor that is expressed in vascular tissue. Although animal and in vitro data support this role of vitamin K, overall data from human studies are inconsistent. The majority of population-based studies have relied on vitamin K intake to measure status. Phylloquinone is the primary dietary form of vitamin K and available supplementation trials, albeit limited, suggest phylloquinone supplementation is relevant to CAC. Yet observational studies have found higher dietary menaquinone, but not phylloquinone, to be associated with less calcification. Vascular calcification is highly prevalent in certain patient populations, especially in those with chronic kidney disease (CKD), and it is plausible vitamin K may contribute to reducing vascular calcification in patients at higher risk. Subclinical vitamin K deficiency has been reported in CKD patients, but studies linking vitamin K status to calcification outcomes in CKD are needed to clarify whether or not improving vitamin K status is associated with improved vascular health in CKD. This review summarizes the available evidence of vitamin K and vascular calcification in population-based studies and clinic-based studies, with a specific focus on CKD patients.

[Valvuloplasty with balloon catheter in biologic prosthesis. Reality or illusion].

PubMed

Ledesma Velasco, M; Verdín Vázquez, R; Acosta Valdez, J L; Munayer Calderón, J; Salgado Escobar, J L; Arias Monroy, L; Flores Mendoza, J

1989-01-01

We performed catheter balloon valvuloplasty (CBV) on 8 stenotic operatively-excised bioprosthetic valves (2 Hancock and 6 Ionescu Shiley). Pathology of valves before CBV included degenerative changes: commissural fusion by mounds of calcific deposits (2 valves), fibrotic and focally calcified leaflets (7 valves) and stiff and thick valves (1 valve). Inflation of the balloon resulted in commissural splitting (2 valves), leaflet cracks and fractures (3 valves). Removal of the deflated balloon catheter was associated with debris dislodgement (3 valves). In one case the valve was unable to close with potential for acute regurgitation. Thus, CBV of bioprosthetic valves can split fused commissures by similar mechanisms as in native valves. CBV may fracture calcific deposits causing acute emboli. It can also disrupt the leaflets causing acute insufficiency. The findings suggest a limited role of CBV in the treatment of stenotic bioprosthetic valves in mitral and aortic position.

Study of calcification formation and disease diagnostics utilising advanced vibrational spectroscopy

NASA Astrophysics Data System (ADS)

Kerssens, Marleen Maartje

The accurate and safe diagnosis of breast cancer is a significant societal issue, with annual disease incidence of 48,000 women and around 370 men in the UK. Early diagnosis of the disease allows more conservative treatments and better patient outcomes. Microcalcifications in breast tissue are an important indicator for breast cancers, and often the only sign of their presence. Several studies have suggested that the type of calcification formed may act as a marker for malignancy and its presence may be of biological significance. In this work, breast calcifications are studied with FTIR, synchrotron FTIR, ATR FTIR, and Raman mapping to explore their disease specific composition. From a comparison between vibrational spectroscopy and routine staining procedures it becomes clear that calcium builds up prior to calcification formation. Raman and FTIR indicate the same size for calcifications and are in agreement with routine staining techniques. From the synchrotron FTIR measurements it can be proven that amide is present in the centre of the calcifications and the intensity of the bands depends on the pathology. Special attention is paid to the type of carbonate substitution in the calcifications relating to different pathology grades. In contrast to mammography, Raman spectroscopy has the capability to distinguish calcifications based on their chemical composition. The ultimate goal is to turn the acquired knowledge from the mapping studies into a clinical tool based on deep Raman spectroscopy. Deep Raman techniques have a considerable potential to reduce large numbers of normal biopsies, reduce the time delay between screening and diagnosis and therefore diminish patient anxiety. In order to achieve this, a deep Raman system is designed and after evaluation of its performance tested on buried calcification standards in porcine soft tissue and human mammary tissue. It is shown that, when the calcification is probed through tissue, the strong 960 cm-1 phosphate band

Intramural location and size of arterial calcification are associated with stenosis at carotid bifurcation.

PubMed

Yamada, Shigeki; Oshima, Marie; Watanabe, Yoshihiko; Ogata, Hideki; Hashimoto, Kenji; Miyake, Hidenori

2014-06-01

The purpose of this study was to investigate the association between internal carotid artery (ICA) stenosis and intramural location and size of calcification at the ICA origins and the origins of the cervical arteries proximal to the ICA. A total of 1139 ICAs were evaluated stenosis and calcification on the multi-detector row CT angiography. The intramural location was categorized into none, outside and inside location. The calcification size was evaluated on the 4-point grading scale. The multivariate analyses were adjusted for age, serum creatinine level, hypertension, hyperlipidemia, diabetes mellitus, smoking and alcohol habits. Outside calcification at the ICA origins showed the highest multivariate odds ratio (OR) for the presence of ICA stenosis (30.0) and severe calcification (a semicircle or more of calcification at the arterial cross-sectional surfaces) did the second (14.3). In the subgroups of >70% ICA stenosis, the multivariate OR of outside location increased to 44.8 and that of severe calcification also increased to 32.7. Four of 5 calcified carotid plaque specimens extracted by carotid endarterectomy were histologically confirmed to be calcified burdens located outside the internal elastic lamia which were defined as arterial medial calcification. ICA stenosis was strongly associated with severe calcification located mainly outside the carotid plaque. Outside calcification at the ICA origins should be evaluated separately from inside calcification, as a marker for the ICA stenosis. Additionally, we found that calcification at the origins of the cervical arteries proximal to the ICA was significantly associated with the ICA stenosis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Valve thrombosis following transcatheter aortic valve implantation: a systematic review.

PubMed

Córdoba-Soriano, Juan G; Puri, Rishi; Amat-Santos, Ignacio; Ribeiro, Henrique B; Abdul-Jawad Altisent, Omar; del Trigo, María; Paradis, Jean-Michel; Dumont, Eric; Urena, Marina; Rodés-Cabau, Josep

2015-03-01

Despite the rapid global uptake of transcatheter aortic valve implantation, valve trombosis has yet to be systematically evaluated in this field. The aim of this study was to determine the clinical characteristics, diagnostic criteria, and treatment outcomes of patients diagnosed with valve thrombosis following transcatheter aortic valve implantation through a systematic review of published data. Literature published between 2002 and 2012 on valve thrombosis as a complication of transcatheter aortic valve implantation was identified through a systematic electronic search. A total of 11 publications were identified, describing 16 patients (mean age, 80 [5] years, 65% men). All but 1 patient (94%) received a balloon-expandable valve. All patients received dual antiplatelet therapy immediately following the procedure and continued to take either mono- or dual antiplatelet therapy at the time of valve thrombosis diagnosis. Valve thrombosis was diagnosed at a median of 6 months post-procedure, with progressive dyspnea being the most common symptom. A significant increase in transvalvular gradient (from 10 [4] to 40 [12] mmHg) was the most common echocardiographic feature, in addition to leaflet thickening. Thrombus was not directly visualized with echocardiography. Three patients underwent valve explantation, and the remaining received warfarin, which effectively restored the mean transvalvular gradient to baseline within 2 months. Systemic embolism was not a feature of valve thrombosis post-transcatheter aortic valve implantation. Although a rare, yet likely under-reported complication of post-transcatheter aortic valve implantation, progressive dyspnea coupled with an increasing transvalvular gradient on echocardiography within the months following the intervention likely signifies valve thrombosis. While direct thrombus visualization appears difficult, prompt initiation of oral anticoagulation therapy effectively restores baseline valve function. Copyright © 2014

JenaValve.

PubMed

Treede, Hendrik; Rastan, Ardawan; Ferrari, Markus; Ensminger, Stephan; Figulla, Hans-Reiner; Mohr, Friedrich-Wilhelm

2012-09-01

The JenaValve is a next-generation TAVI device which consists of a well-proven porcine root valve mounted on a low-profile nitinol stent. Feeler guided positioning and clip fixation on the diseased leaflets allow for anatomically correct implantation of the device without rapid pacing. Safety and efficacy of transapical aortic valve implantation using the JenaValve were evaluated in a multicentre prospective study that showed good short and midterm results. The valve was CE-mark released in Europe in September 2011. A post-market registry ensures on-going and prospective data collection in "real-world" patients. The transfemoral JenaValve delivery system will be evaluated in a first-in-man study in the near future.

Depressurization valve

DOEpatents

Skoda, G.I.

1989-03-28

A depressurization valve for use in relieving completely the pressure in a simplified boiling water reactor is disclosed. The normally closed and sealed valve is provided with a valve body defining a conduit from an outlet of a manifold from the reactor through a valve seat. A closing valve disk is configured for fitting to the valve seat to normally close the valve. The seat below the disk is provided with a radially extending annulus extending a short distance into the aperture defined by the seat. The disk is correspondingly provided with a longitudinally extending annulus that extends downwardly through the aperture defined by the seat towards the high pressure side of the valve body. A ring shaped membrane is endlessly welded to the seat annulus and to the disk annulus. The membrane is conformed over the confronted surface of the seat and disk in a C-sectioned configuration to seal the depressurization valve against the possibility of weeping. The disk is held to the closed position by an elongate stem extending away from the high pressure side of the valve body. The stem has a flange configured integrally to the stem for bias by two springs. The first spring acts from a portion of the housing overlying the disk on the stem flange adjacent the disk. This spring urges the stem and attached disk away from the seat and thus will cause the valve to open at any pressure. A second spring-preferably of the Belleville variety-acts on a latch plate surrounding and freely moving relative to the end of the stem. This second spring overcomes the bias of the first spring and any pressure acting upon the disk. This Belleville spring maintains through its spring force the valve in the closed position. At the same time, the latch plate with its freedom of movement relative to the stem allows the stem to thermally expand during valve temperature excursion.

LncRNA MALAT1 sponges miR-204 to promote osteoblast differentiation of human aortic valve interstitial cells through up-regulating Smad4.

PubMed

Xiao, Xiaoxiong; Zhou, Tingwen; Guo, Shichao; Guo, Chao; Zhang, Qiao; Dong, Nianguo; Wang, Yongjun

2017-09-15

Emerging evidences have indicated that long non-coding RNAs (lncRNAs) play vital roles in cardiovascular physiology and pathology. The lncRNA MALAT1, a highly abundant and conserved imprinted gene, has been implicated in many cardiovascular diseases. However, the function of MALAT1 in calcific aortic valve disease (CAVD) remains unknown. This study sought to document the function and underlying mechanism of MALAT1 in regulating CAVD. Protein level was determined by immunoblotting and immunofluorescence staining. MALAT1, miR-204 and mRNA expressions were detected by qRT-PCR. Mineralized bone matrix formation was assessed by Alizarin Red staining. The interaction between MALAT1 and miR-204 was studied using luciferase reporter assay, RNA pull-down assay and RNA-binding protein immunoprecipitation assay. Ectopic expression of MALAT1 was observed in calcific valves and after osteogenic induction in human aortic valve interstitial cells (VICs). In vitro experiments revealed that MALAT1 acted as a positive regulator of osteogenic differentiation by repressing miR-204 expression and activity and thereby promoting expression of osteoblast-specific markers, including alkaline phosphatase, mineralized bone matrix formation and osteocalcin. Mechanistically, we identified Smad4 as a direct target of miR-204. Importantly, MALAT1 could directly interact with miR-204 and overexpression of miR-204 efficiently reversed the upregulation of Smad4 induced by MALAT1. Thus, MALAT1 positively regulated the expression of Smad4 through sponging miR-204, and promoted osteogenic differentiation of VICs. Our study provides novel mechanistic insights into a critical role for lncRNA MALAT1 as a miRNA sponge in CAVD and sheds new light on lncRNA-directed diagnostics and therapeutics in CAVD. Copyright © 2017. Published by Elsevier B.V.

Association between arterial calcifications and nonlacunar and lacunar ischemic strokes.

PubMed

van Dijk, Anouk C; Fonville, Susanne; Zadi, Taihra; van Hattem, Antonius M G; Saiedie, Ghesrouw; Koudstaal, Peter J; van der Lugt, Aad

2014-03-01

Nonlacunar cerebral infarcts are presumed to be caused by thromboembolism from the heart or extracranial arteries, whereas lacunar infarcts are thought to be caused by small vessel disease. We investigated to what extent arterial calcifications differ between nonlacunar and lacunar ischemic strokes. We studied 820 consecutive patients with transient ischemic attack or ischemic stroke in the anterior circulation who underwent multidetector computed tomography angiography and had no rare cause of stroke. The presence of likely cardioembolic pathogenesis was determined according to the Trial of Org 10172 in Acute Stroke Treatment criteria. The remaining 708 patients were categorized as nonlacunar or lacunar strokes, either transient ischemic attacks or strokes, based on clinical symptoms corrected by brain imaging results. We measured volume of calcifications in the aortic arch, symptomatic extracranial and intracranial carotid artery using multidetector computed tomography angiography. The difference in calcifications between nonlacunar and lacunar strokes was assessed with a multivariable logistic regression analysis. We adjusted for degree of symptomatic carotid artery stenosis and cardiovascular risk factors. We found an independent association between volume of aortic arch calcifications and nonlacunar ischemic strokes (adjusted odds ratio [95% confidence interval], 1.11 [1.02-1.21]). No independent associations between extracranial and intracranial carotid artery calcifications and nonlacunar strokes were present. The only difference we found between nonlacunar and lacunar strokes was a higher calcification volume in the aortic arch in nonlacunar strokes. Our findings only partially confirm the notion of distinct etiologies and suggest that the potential role of other plaque components, plaque morphology, and aortic arch calcifications in ischemic stroke subtypes awaits further evaluation.

Age-related incidence of pineal calcification detected by computed tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zimmerman, R.A.; Bilaniuk, L.T.

The age-related incidence of detectable pineal calcification in 725 patients (age range, newborn-20 yrs) suggests that there is a relationship between calcification and the hormonal role played by the pineal gland in the regulation of sexual development. Pineal calcification (demonstrated by computed tomography (CT) on 8-mm-thick sections) in patients less than 6 years old should be looked upon with suspicion, and follow-up CT should be considered to exclude the possible development of a pineal neoplasm.

Fast valve

DOEpatents

Van Dyke, W.J.

1992-04-07

A fast valve is disclosed that can close on the order of 7 milliseconds. It is closed by the force of a compressed air spring with the moving parts of the valve designed to be of very light weight and the valve gate being of wedge shaped with O-ring sealed faces to provide sealing contact without metal to metal contact. The combination of the O-ring seal and an air cushion create a soft final movement of the valve closure to prevent the fast air acting valve from having a harsh closing. 4 figs.

Fast valve

DOEpatents

Van Dyke, William J.

1992-01-01

A fast valve is disclosed that can close on the order of 7 milliseconds. It is closed by the force of a compressed air spring with the moving parts of the valve designed to be of very light weight and the valve gate being of wedge shaped with O-ring sealed faces to provide sealing contact without metal to metal contact. The combination of the O-ring seal and an air cushion create a soft final movement of the valve closure to prevent the fast air acting valve from having a harsh closing.

Why Grants.gov Should Be Abolished

ERIC Educational Resources Information Center

Kolmertern, Carol

2007-01-01

In this article, the author explains why Grants.gov, a web site for US Federal Government grants, should be abolished. Her recent attempt to submit a grant proposal to the National Institutes of Health is a case in point. She recounts how frustrating her experience was to the grant-submission process of Grants.gov. She points out that Grants.gov…

Early detection of ocean acidification effects on marine calcification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ilyina, T.; Zeebe, R. E.; E. Maier-Reimer

Ocean acidification is likely to impact calcification rates in many pelagic organisms, which may in turn cause significant changes in marine ecosystem structure. We examine effects of changes in marine CaCO3 production on total alkalinity (TA) in the ocean using the global biogeochemical ocean model HAMOCC. We test a variety of future calcification scenarios because experimental studies with different organisms have revealed a wide range of calcification sensitivities to CaCO3 saturation state. The model integrations start at a preindustrial steady state in the year 1800 and run until the year 2300 forced with anthropogenic CO2 emissions. Calculated trends in TAmore » are evaluated taking into account the natural variability in ocean carbonate chemistry, as derived from repeat hydrographic transects. We conclude that the data currently available does not allow discerning significant trends in TA due to changes in pelagic calcification caused by ocean acidification. Given different calcification scenarios, our model calculations indicate that the TA increase over time will start being detectable by the year 2040, increasing by 5–30 umol/kg compared to the present-day values. In a scenario of extreme reductions in calcification, large TA changes relative to preindustrial conditions would have occurred at present, which we consider very unlikely. However, the time interval of reliable TA observations is too short to disregard this scenario. The largest increase in surface ocean TA is predicted for the tropical and subtropical regions. In order to monitor and quantify possible early signs of acidification effects, we suggest to specifically target those regions during future ocean chemistry surveys.« less

Mitral Annular Calcification as a Possible Nidus for Endocarditis: A Descriptive Series with Bacteriological Differences Noted.

PubMed

Pressman, Gregg S; Rodriguez-Ziccardi, Mary; Gartman, Charles H; Obasare, Edinrin; Melendres, Emmanuel; Arguello, Vivian; Bhalla, Vikas

2017-06-01

Mitral annular calcification (MAC) is a chronic inflammatory process with similarities to atherosclerosis. It is common in elderly patients and those with renal dysfunction. Although MAC is associated with cardiovascular morbidity, its relationship to infective endocarditis is unclear. The aim of this study was to test the hypothesis that MAC would be prevalent in patients with mitral valve vegetations and that vegetations would frequently occur on calcific nodules. A secondary aim was to look for possible bacteriological differences between vegetations attached to the calcified annulus versus leaflet vegetations. We retrospectively reviewed all echocardiographic studies of patients with native mitral valve vegetations from January 2007 to August 2015 (N = 56). We searched for (1) presence of MAC, (2) location of MAC, and (3) vegetation location (on calcium deposits or distant). MAC was defined as focal echo brightness in a nodular or band-like pattern. The modified Duke criteria were used to confirm the diagnosis of infective endocarditis. Transthoracic, transesophageal, and three-dimensional echocardiograms (when available) at the time of infection were evaluated by a single reader. Twenty-eight subjects were infected with Staphylococcus aureus, 17 with a streptococcal species, and five with other organisms; blood cultures were sterile in 6. Thirty-four (61%) subjects had some degree of MAC, while 22 (39%) had none. Among those with MAC, the vegetation was located on the calcium deposits in 22 (65%), versus in 12 (35%) where it was not. Among all 56 subjects, when S. aureus was the infecting organism it was present on MAC in 16/28 (57%) versus 6/28 (21%; P = .01) for other bacterial species. By contrast, streptococcal infections more frequently involved the leaflets (16/17 [94%]) versus nonstreptococcal infections (18/39 [46%]; P = .0008). MAC may act as a nidus for infection especially with S. aureus. Differences in mechanism of attachment between

Stemless Ball Valve

NASA Technical Reports Server (NTRS)

Burgess, Robert K.; Yakos, David; Walthall, Bryan

2012-01-01

This invention utilizes a new method of opening and closing a ball valve. Instead of rotating the ball with a perpendicular stem (as is the case with standard ball valves), the ball is rotated around a fixed axis by two guide pins. This innovation eliminates the leak point that is present in all standard ball valves due to the penetration of an actuation stem through the valve body. The VOST (Venturi Off-Set-Technology) valve has been developed for commercial applications. The standard version of the valve consists of an off-set venturi flow path through the valve. This path is split at the narrowest portion of the venturi, allowing the section upstream from the venturi to be rotated. As this rotation takes place, the venturi becomes restricted as one face rotates with respect to the other, eventually closing off the flow path. A spring-loaded seal made of resilient material is embedded in the upstream face of the valve, making a leak-proof seal between the faces; thus a valve is formed. The spring-loaded lip seal is the only seal that can provide a class six, or bubble-tight, seal against the opposite face of the valve. Tearing action of the seal by high-velocity gas on this early design required relocation of the seal to the downstream face of the valve. In the stemless embodiment of this valve, inner and outer magnetic cartridges are employed to transfer mechanical torque from the outside of the valve to the inside without the use of a stem. This eliminates the leak path caused by the valve stems in standard valves because the stems penetrate through the bodies of these valves.

Impact of magnesium:calcium ratio on calcification of the aortic wall.

PubMed

Villa-Bellosta, Ricardo

2017-01-01

An inverse relationship between serum magnesium concentration and vascular calcification has been reported following observational clinical studies. Moreover, several studies have been suggesting a protective effect of magnesium on the vascular calcification. However, the exact mechanism remains elusive, and investigators have speculated among a myriad of potential actions. The effect of magnesium on calcification of the aortic wall is yet to be investigated. In the present study, the effects of magnesium and calcium on the metabolism of extracellular PPi, the main endogenous inhibitor of vascular calcification, were investigated in the rat aorta. Calcium and magnesium have antagonist effects on PPi hydrolysis in the aortic wall. Km and Ki values for PPi hydrolysis in rat aortic rings were 1.1 mmol/L magnesium and 32 μmol/L calcium, respectively, but ATP hydrolysis was not affected with calcium. Calcium deposition in the rat aortic wall dramatically increased when the magnesium concentration was increased (ratio of Mg:Ca = 1:1; 1.5 mmol/L calcium and 1.5 mmol/L magnesium) respect to low magnesium concentration (ratio Mg:Ca = 1:3, 1.5 mmol/L calcium and 0.75 mmol/L magnesium). Data from observational clinical studies showing that the serum magnesium concentration is inversely correlated with vascular calcification could be reinterpreted as a compensatory regulatory mechanism that reduces both PPi hydrolysis and vascular calcification. The impact of magnesium in vascular calcification in humans could be studied in association with calcium levels, for example, as the magnesium:calcium ratio.

Tricuspid valve and percutaneous approach: No longer the forgotten valve!

PubMed

Bouleti, Claire; Juliard, Jean-Michel; Himbert, Dominique; Iung, Bernard; Brochet, Eric; Urena, Marina; Dilly, Marie-Pierre; Ou, Phalla; Nataf, Patrick; Vahanian, Alec

2016-01-01

Tricuspid valve disease is mainly represented by tricuspid regurgitation (TR), which is a predictor of poor outcome. TR is usually secondary, caused by right ventricle pressure or volume overload, the leading cause being left-sided heart valve diseases. Tricuspid surgery for severe TR is recommended during left valve surgery, and consists of either a valve replacement or, most often, a tricuspid repair with or without prosthetic annuloplasty. When TR persists or worsens after left valvular surgery, redo isolated tricuspid surgery is associated with high mortality. In addition, a sizeable proportion of patients present with tricuspid surgery deterioration over time, and need a reintervention, which is associated with high morbi-mortality rates. In this context, and given the recent major breakthrough in the percutaneous treatment of aortic and mitral valve diseases, the tricuspid valve appears an appealing challenge, although it raises specific issues. The first applications of transcatheter techniques for tricuspid valve disease were valve-in-valve and valve-in-ring implantation for degenerated bioprosthesis or ring annuloplasty. Some concerns remain regarding prosthesis sizing, rapid ventricular pacing and the best approach, but these procedures appear to be safe and effective. More recently, bicuspidization using a transcatheter approach for the treatment of native tricuspid valve has been published, in two patients. Finally, other devices are in preclinical development. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Rare finding of Eustachian tube calcifications with cone-beam computed tomography.

PubMed

Syed, Ali Z; Hawkins, Anna; Alluri, Leela Subashini; Jadallah, Buthainah; Shahid, Kiran; Landers, Michael; Assaf, Hussein M

2017-12-01

Soft tissue calcification is a pathological condition in which calcium and phosphate salts are deposited in the soft tissue organic matrix. This study presents an unusual calcification noted in the cartilaginous portion of the Eustachian tube. A 67-year-old woman presented for dental treatment, specifically for implant placement, and cone-beam computed tomography (CBCT) was performed. The CBCT scan was reviewed by a board-certified oral and maxillofacial radiologist and revealed incidental findings of 2 distinct calcifications in the cartilaginous portion of the Eustachian tube. To the authors' knowledge, no previous study has reported the diagnosis of Eustachian tube calcification using CBCT. This report describes an uncommon variant of Eustachian tube calcification, which has a significant didactic value because such cases are seldom illustrated either in textbooks or in the literature. This case once again underscores the importance of having CBCT scans evaluated by a board-certified oral and maxillofacial radiologist.

Depressurization valve

DOEpatents

Skoda, George I.

1989-01-01

A depressurization valve for use in relieving completely the pressure in a simplified boiling water reactor is disclosed. The normally closed and sealed valve is provided with a valve body defining a conduit from an outlet of a manifold from the reactor through a valve seat. A closing valve disk is configured for fitting to the valve seat to normally close the valve. The seat below the disk is provided with a radially extending annulus extending a short distance into the aperture defined by the seat. The disk is correspondingly provided with a longitudinally extending annulus that extends downwardly through the aperture defined by the seat towards the high pressure side of the valve body. A ring shaped membrane is endlessly welded to the seat annulus and to the disk annulus. The membrane is conformed over the confronted surface of the seat and disk in a C-sectioned configuration to seal the depressurization valve against the possibility of weeping. The disk is held to the closed position by an elongate stem extending away from the high pressure side of the valve body. The stem has a flange configured integrally to the stem for bias by two springs. The first spring acts from a portion of the housing overlying the disk on the stem flange adjacent the disk. This spring urges the stem and attached disk away from the seat and thus will cause the valve to open at any pressure. A second spring--preferably of the Belleville variety--acts on a latch plate surrounding and freely moving relative to the end of the stem. This second spring overcomes the bias of the first spring and any pressure acting upon the disk. This Belleville spring maintains through its spring force the valve in the closed position. At the same time, the latch plate with its freedom of movement relative to the stem allows the stem to thermally expand during valve temperature excursion. The latch plate in surrounding the stem is limited in its outward movement by a boss attached to the stem at the end of

Relation of an Echocardiographic-Based Cardiac Calcium Score to Mitral Stenosis Severity and Coronary Artery Disease in Patients with Severe Aortic Stenosis.

PubMed

Sheng, Siyuan P; Howell, Lucius A; Caughey, Melissa C; Yeung, Michael; Vavalle, John P

2018-01-15

Patients with calcific aortic stenosis (AS) often have diffuse cardiac calcification involving the mitral valve apparatus and coronary arteries. We examined the association between global cardiac calcification quantified by a previously validated echocardiographic calcium score (eCS) with the severity of mitral stenosis (MS) and coronary artery disease (CAD) in patients with a clinical diagnosis of severe calcific AS. In this sample of 147 patients (mean age 81 ± 9 years, 50% male), 81 patients (55%) were determined by echocardiography to have some degree of MS. Higher mean eCS was observed in patients with more severe MS (r = 0.54, p < 0.0001). Higher eCS was also inversely associated with mitral valve area (r = -0.31, p = 0.001) and positively associated with mitral valve mean pressure gradient (r = 0.46, p < 0.0001) and mitral valve peak flow velocity (r = 0.55, p < 0.0001). The area under the receiver operating characteristic curve for using eCS to predict the presence of MS was 0.76. An eCS ≥ 8 predicted MS with a sensitivity of 68%, specificity of 76%, positive predictive value of 77%, and negative predictive value of 66%. High eCS, relative to low eCS, was associated with 2.70 times the adjusted odds of CAD (odds ratio = 2.70, 95% confidence interval 1.02 to 7.17). In conclusion, global cardiac calcification is associated with MS and CAD in patients with severe calcific AS, and eCS shows ability to predict the presence of MS. This study suggests that a simple eCS may be used as part of a risk-stratification tool in patients with severe calcific aortic valve stenosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Gene expression analysis in calcific tendinopathy of the rotator cuff.

PubMed

Oliva, F; Barisani, D; Grasso, A; Maffulli, N

2011-06-20

We evaluated the expression of several genes involved in tissue remodelling and bone development in patients with calcific tendinopathy of the rotator cuff. Biopsies from calcified and non-calcified areas were obtained from 10 patients (8 women and 2 men; average age: 55 years; range: 40-68) with calcific tendinopathy of the rotator cuff. To evaluate the expression of selected genes, RNA extraction, cDNA synthesis and quantitative polymerase chain reaction (PCR) were performed. A significantly increased expression of tissue transglutaminase (tTG)2 and its substrate, osteopontin, was detected in the calcific areas compared to the levels observed in the normal tissue from the same subject with calcific tendinopathy, whereas a modest increase was observed for catepsin K. There was also a significant decrease in mRNA expression of Bone Morphogenetic Protein (BMP)4 and BMP6 in the calcific area. BMP-2, collagen V and vascular endothelial growth factor (VEGF) did not show significant differences. Collagen X and matrix metalloproteinase (MMP)-9 were not detectable. A variation in expression of these genes could be characteristic of this form tendinopathy, since an increased level of these genes has not been detected in other forms of tendon lesions.

Calcific band keratopathy in an alpaca.

PubMed

Pucket, Jonathan D; Boileau, Melanie J; Sula, Mee Ja M

2014-07-01

A 4-year-old female Suri alpaca was presented for evaluation of acute onset weakness, lethargy, and recent development of opacities in both eyes. On ophthalmic examination, bilaterally symmetrical corneal opacities were noted along the interpalpebral fissures with a few corneal blood vessels intermingled. A presumed diagnosis of calcific band keratopathy was made based on location and appearance. The patient was euthanized a short while after diagnosis due to reasons unrelated to the eyes and histologic examination of the corneas revealed subepithelial calcium and vascularization, consistent with calcific band keratopathy. This case report is the first to document this ocular condition in an alpaca. © 2013 American College of Veterinary Ophthalmologists.

Magnesium intake is inversely associated with coronary artery calcification: the Framingham Heart Study

USDA-ARS?s Scientific Manuscript database

OBJECTIVES: The aim of this study was to examine whether magnesium intake is associated with coronary artery calcification (CAC) and abdominal aortic calcification (AAC). BACKGROUND: Animal and cell studies suggest that magnesium may prevent calcification within atherosclerotic plaques underlying c...

Vanishing calcification associated with a spontaneous ventral spinal cerebrospinal fluid leak.

PubMed

Schievink, Wouter I; Ross, Lindsey; Prasad, Ravi S; Maya, M Marcel

2016-12-01

Some patients with spontaneous intracranial hypotension have a ventral spinal cerebrospinal fluid (CSF) leak and these CSF leaks may be associated with calcified disk herniations. Identifying these calcifications is helpful in directing treatment. We report here the unusual case of a patient with a ventral CSF leak in whom the associated calcification absorbed over a five-month period. A 42-year-old woman developed orthostatic headaches and bilateral abducens nerve palsies. Magnetic resonance imaging of her brain showed typical findings of spontaneous intracranial hypotension. Magnetic resonance imaging of her spine showed an extensive cervicothoracic CSF leak. Computed tomographic myelography showed calcification at the Th1-2 disk space. Three epidural blood patches were performed, but her symptoms persisted. Digital subtraction myelography performed five months later showed an upper thoracic ventral CSF, but the calcification was no longer present. A dural tear, found at surgery at the Th1-2 level, was repaired and the patient made an uneventful recovery. The resorption of calcifications at the level of a ventral spinal CSF leak could explain the absence of any calcifications in at least some patients with such leaks and demonstrates the usefulness of reviewing previous imaging in patients with ventral CSF leaks if the exact site of the leak remains unknown. © International Headache Society 2016.

[Calcific tendinitis of the shoulder].

PubMed

Gärtner, J; Heyer, A

1995-06-01

Degenerative ossification is formed directly at the major tubercle. Like in any other gliding tendon, fibrocartilage cells lie on the articular side of the rotator tendon at the pivot of the humerus head. Typically, the calcific deposits of calcifying tendinitis are found between these two areas. At this site, hydroxyapatite is usually formed by fibrocartilage cells through an unknown stimulus. There is no ossification. This is a two-phase disease. During the chronic initial phase, a calcific deposit is formed in the tendon of the rotator cuff. In the X-ray, it is clearly circumscribed and has a dense appearance (type I). Pain is inconsistent and may exist for years. In the acute phase, the deposit undergoes spontaneous resolution. Now it takes on a translucent and cloudy appearance without clear circumscription (type III). Patients experience severe pain for 2-3 weeks. Finally, a normally functioning shoulder joint will result. The X-ray therefore allows a prognostic conclusion. In a study including 235 calcific deposits, it became clear that there are some cases where it is not possible to designate the specific X-ray morphology to a given deposit (type II). Irrespective of the phase of disease, the so-called calcific deposit is composed of poorly mineralized hydroxyapatite. For a diagnosis, we require: a typical history, clinical findings consistent with tendinitis of the rotator cuff, calcific deposits in the tendon associated with signs and symptoms of tendinitis. It is recommended that radiographs be taken at least in AP projections with the shoulder in internal and external rotation to demonstrate the deposits without super-imposition. Ultrasound shows concomitant bursitis and is useful for the differential diagnosis of rupture of the rotator cuff. Radiographic diagnosis is most difficult when there are small opacifications near the rotator attachment. In this case, allocation may become possible only later in the course of disease. Initial treatment should

Biomechanical and ultrastructural comparison of cryopreservation and a novel cellular extraction of porcine aortic valve leaflets.

PubMed

Courtman, D W; Pereira, C A; Omar, S; Langdon, S E; Lee, J M; Wilson, G J

1995-12-01

Heart valve substitutes of biological origin often fail by degenerative mechanisms. Many authors have hypothesized that mechanical fatigue and structural degradation are instrumental to in vivo failure. Since the properties of the structural matrix at implantation may predetermine failure, we have examined the ultrastructure, fracture, mechanics, and uniaxial high-strain-rate viscoelastic properties of: (1) fresh, (2) cryopreserved, and (3) cellular extracted porcine aortic valve leaflets. The cellular extraction process is being developed in order to reduce immunological attack and calcification. Cryopreservation causes cellular disruption and necrotic changes throughout the tissue, whereas extraction removes all cells and lipid membranes. Both processes leave an intact collagen and elastin structural matrix and preserve the high-strain-rate viscoelastic characteristics of the fresh leaflets. Extraction does cause a 20% reduction in the fracture tension and increases tissue extensibility, with the percent strain at fracture rising to 45.3 +/- 4 (mean +/- SEM) from 31.5 +/- 3 for fresh leaflets. However, extraction does preserve matrix structure and mechanics over the physiological loading range. Glutaraldehyde fixation produces increased extensibility, increased elastic behavior, and, when applied to extracted leaflets, it causes a marked drop in fracture tension, to 50% of that for fresh leaflets. The combination of extraction and fixation may lead to early degenerative failure. The cellular extraction technique alone may be a useful alternative to glutaraldehyde fixation in preparing bioprosthetic heart valves.

Calcific retropharyngeal tendinitis. [Radiological findings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karasick, D.; Karasick, S.

1981-12-01

Calcific retropharyngeal tendinitis is an imflammation of the longus colli muscle tendon which is located on the anterior surface of the verterbral column extending from the atlas to the third thoracic vertebra. The acute inflammatory condition is selflimiting with symptoms consisting of a gradually increasing neck pain often associated with throat pain and difficulty swallowing. The pain is aggravated by head and neck movement. Clinically the condition can be confused with retropharyngeal absecess, meningitis, infectious spondylitis, and post-traumatic muscle spasm. The radiographic features of this condition consist of pre-vertebral soft tissue swelling from C1 to C4 and amorphous calcific densitymore » in the longus colli tendon anterior to the body of C2 and inferior to the anterior arch of C1.« less

[Vascular Calcification - Pathological Mechanism and Clinical Application - . Role of vascular smooth muscle cells in vascular calcification].

PubMed

Kurabayashi, Masahiko

2015-05-01

Vascular calcification is commonly seen with aging, chronic kidney disese (CKD), diabetes, and atherosclerosis, and is closely associated with cardiovascular morbidity and mortality. Vascular calcification has long been regarded as the final stage of degeneration and necrosis of arterial wall and a passive, unregulated process. However, it is now known to be an active and tightly regulated process involved with phenotypic transition of vascular smooth muscle cells (VSMC) that resembles bone mineralization. Briefly, calcium deposits of atherosclerotic plaque consist of hydroxyapatite and may appear identical to fully formed lamellar bone. By using a genetic fate mapping strategy, VSMC of the vascular media give rise to the majority of the osteochondrogenic precursor- and chondrocyte-like cells observed in the calcified arterial media of MGP (- / -) mice. Osteogenic differentiation of VSMC is characterized by the expression of bone-related molecules including bone morphogenetic protein (BMP) -2, Msx2 and osteopontin, which are produced by osteoblasts and chondrocytes. Our recent findings are that (i) Runx2 and Notch1 induce osteogenic differentiation, and (ii) advanced glycation end-product (AGE) /receptor for AGE (RAGE) and palmitic acid promote osteogenic differentiation of VSMC. To understand of the molecular mechanisms of vascular calcification is now under intensive research area.

Excess flow shutoff valve

DOEpatents

Kiffer, Micah S.; Tentarelli, Stephen Clyde

2016-02-09

Excess flow shutoff valve comprising a valve body, a valve plug, a partition, and an activation component where the valve plug, the partition, and activation component are disposed within the valve body. A suitable flow restriction is provided to create a pressure difference between the upstream end of the valve plug and the downstream end of the valve plug when fluid flows through the valve body. The pressure difference exceeds a target pressure difference needed to activate the activation component when fluid flow through the valve body is higher than a desired rate, and thereby closes the valve.

Computed Tomographic Distinction of Intimal and Medial Calcification in the Intracranial Internal Carotid Artery.

PubMed

Kockelkoren, Remko; Vos, Annelotte; Van Hecke, Wim; Vink, Aryan; Bleys, Ronald L A W; Verdoorn, Daphne; Mali, Willem P Th M; Hendrikse, Jeroen; Koek, Huiberdina L; de Jong, Pim A; De Vis, Jill B

2017-01-01

Intracranial internal carotid artery (iICA) calcification is associated with stroke and is often seen as a proxy of atherosclerosis of the intima. However, it was recently shown that these calcifications are predominantly located in the tunica media and internal elastic lamina (medial calcification). Intimal and medial calcifications are thought to have a different pathogenesis and clinical consequences and can only be distinguished through ex vivo histological analysis. Therefore, our aim was to develop CT scoring method to distinguish intimal and medial iICA calcification in vivo. First, in both iICAs of 16 cerebral autopsy patients the intimal and/or medial calcification area was histologically assessed (142 slides). Brain CT images of these patients were matched to the corresponding histological slides to develop a CT score that determines intimal or medial calcification dominance. Second, performance of the CT score was assessed in these 16 patients. Third, reproducibility was tested in a separate cohort. First, CT features of the score were circularity (absent, dot(s), <90°, 90-270° or 270-360°), thickness (absent, ≥1.5mm, or <1.5mm), and morphology (indistinguishable, irregular/patchy or continuous). A high sum of features represented medial and a lower sum intimal calcifications. Second, in the 16 patients the concordance between the CT score and the dominant calcification type was reasonable. Third, the score showed good reproducibility (kappa: 0.72 proportion of agreement: 0.82) between the categories intimal, medial or absent/indistinguishable. The developed CT score shows good reproducibility and can differentiate reasonably well between intimal and medial calcification dominance in the iICA, allowing for further (epidemiological) studies on iICA calcification.

Impact of magnesium:calcium ratio on calcification of the aortic wall

PubMed Central

2017-01-01

Objective An inverse relationship between serum magnesium concentration and vascular calcification has been reported following observational clinical studies. Moreover, several studies have been suggesting a protective effect of magnesium on the vascular calcification. However, the exact mechanism remains elusive, and investigators have speculated among a myriad of potential actions. The effect of magnesium on calcification of the aortic wall is yet to be investigated. In the present study, the effects of magnesium and calcium on the metabolism of extracellular PPi, the main endogenous inhibitor of vascular calcification, were investigated in the rat aorta. Approach and results Calcium and magnesium have antagonist effects on PPi hydrolysis in the aortic wall. Km and Ki values for PPi hydrolysis in rat aortic rings were 1.1 mmol/L magnesium and 32 μmol/L calcium, respectively, but ATP hydrolysis was not affected with calcium. Calcium deposition in the rat aortic wall dramatically increased when the magnesium concentration was increased (ratio of Mg:Ca = 1:1; 1.5 mmol/L calcium and 1.5 mmol/L magnesium) respect to low magnesium concentration (ratio Mg:Ca = 1:3, 1.5 mmol/L calcium and 0.75 mmol/L magnesium). Conclusion Data from observational clinical studies showing that the serum magnesium concentration is inversely correlated with vascular calcification could be reinterpreted as a compensatory regulatory mechanism that reduces both PPi hydrolysis and vascular calcification. The impact of magnesium in vascular calcification in humans could be studied in association with calcium levels, for example, as the magnesium:calcium ratio. PMID:28570619

Comparison of the x-ray attenuation properties of breast calcifications, aluminium, hydroxyapatite and calcium oxalate.

PubMed

Warren, L M; Mackenzie, A; Dance, D R; Young, K C

2013-04-07

Aluminium is often used as a substitute material for calcifications in phantom measurements in mammography. Additionally, calcium oxalate, hydroxyapatite and aluminium are used in simulation studies. This assumes that these materials have similar attenuation properties to calcification, and this assumption is examined in this work. Sliced mastectomy samples containing calcification were imaged at ×5 magnification using a digital specimen cabinet. Images of the individual calcifications were extracted, and the diameter and contrast of each calculated. The thicknesses of aluminium required to achieve the same contrast as each calcification when imaged under the same conditions were calculated using measurements of the contrast of aluminium foils. As hydroxyapatite and calcium oxalate are also used to simulate calcifications, the equivalent aluminium thicknesses of these materials were also calculated using tabulated attenuation coefficients. On average the equivalent aluminium thickness was 0.85 times the calcification diameter. For calcium oxalate and hydroxyapatite, the equivalent aluminium thicknesses were 1.01 and 2.19 times the thickness of these materials respectively. Aluminium and calcium oxalate are suitable substitute materials for calcifications. Hydroxyapatite is much more attenuating than the calcifications and aluminium. Using solid hydroxyapatite as a substitute for calcification of the same size would lead to excessive contrast in the mammographic image.

[Vascular calcifications in subjects with and without chronic renal failure: types, sites and risk factors].

PubMed

Marinelli, Annibale; Di Napoli, Anteo

2017-04-01

Vascular calcifications worse outcomes in the general population and in patients on dialysis. We investigated 146 patients on chronic hemodialysis and 63 healthy controls with normal renal function under 65 years of age. All subjects underwent B-mode ultrasonography of common and internal carotid artery, abdominal aorta, common and superficial femoral artery and posterior tibial artery to assess the presence of intimal and medial calcifications. Intimal and media calcifications were present at the level of the carotid vessel, the abdominal aorta, the common femoral artery, the superficial femoral artery and the posterior tibial artery, respectively in 45%, 50%, 45%, 50%, 42% of patients on dialysis and in 5%, 15%, 24%, 5%, 2% of controls (p <0,01). On multivariate logistic analysis of regression, after adjustment for potential confounders, carotid intimal calcification, abdominal aortic calcification, medial calcification of the superficial femoral artery and posterior tibial artery calcification were associated with dialysis and with cardiovascular disease. Only intimal arterial calcification were associated with older age and smoking. Vascular calcifications are extremely common in middle-aged patients on chronic hemodialysis. Ultrasonography currently available in Nephrology, is a sensitive, reproducible, inexpensive imaging technique to identify arterial intimal and medial calcification in high-risk cardiovascular subjects. Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.

Inflammatory, metabolic, and genetic mechanisms of vascular calcification

PubMed Central

Demer, Linda L.; Tintut, Yin

2014-01-01

This review centers on updating the active research area of vascular calcification. This pathology underlies substantial cardiovascular morbidity and mortality, through adverse mechanical effects on vascular compliance, vasomotion, and, most likely, plaque stability. Biomineralization is a complex, regulated process occurring widely throughout nature. Decades ago, its presence in the vasculature was considered a mere curiosity and an unregulated, “dystrophic” process that does not involve biological mechanisms. While it remains controversial whether the process has any adaptive value or past evolutionary advantage, substantial advances have been made in understanding the biological mechanisms driving the process. Different types of calcific vasculopathy, such as inflammatory vs. metabolic, have parallel mechanisms in skeletal bone calcification, such as intramembranous and endochondral ossification. Recent work has identified important regulatory roles for inflammation, oxidized lipids, elastin, alkaline phosphatase, osteoprogenitor cells, matrix gamma-carboxyglutamic acid protein (MGP), transglutaminase, osteoclastic regulatory factors, phosphate regulatory hormones and receptors, apoptosis, prelamin A, autophagy, and microvesicles or microparticles similar to the matrix vesicles of skeletal bone. Recent work has uncovered fascinating interactions between MGP, vitamin K, warfarin and transport proteins. And, lastly, recent breakthroughs in inherited forms of calcific vasculopathy, have identified the genes responsible as well as an unexpected overlap of phenotypes. PMID:24665125

Molecular and cellular mechanisms of aortic stenosis.

PubMed

Yetkin, Ertan; Waltenberger, Johannes

2009-06-12

Calcific aortic stenosis is the most common cause of aortic valve replacement in developed countries, and this condition increases in prevalence with advancing age. The fibrotic thickening and calcification are common eventual endpoint in both non-rheumatic calcific and rheumatic aortic stenoses. New observations in human aortic valves support the hypothesis that degenerative valvular aortic stenosis is the result of active bone formation in the aortic valve, which may be mediated through a process of osteoblast-like differentiation in these tissues. Additionally histopathologic evidence suggests that early lesions in aortic valves are not just a disease process secondary to aging, but an active cellular process that follows the classical "response to injury hypothesis" similar to the situation in atherosclerosis. Although there are similarities with the risk factor and as well as with the process of atherogenesis, not all the patients with coronary artery disease or atherosclerosis have calcific aortic stenosis. This review mainly focuses on the potential vascular and molecular mechanisms involved in the pathogenesis of aortic valve stenosis. Namely extracellular matrix remodeling, angiogenesis, inflammation, and eventually osteoblast-like differentiation resulting in bone formation have been shown to play a role in the pathogenesis of calcific aortic stenosis. Several mediators related to underlying mechanisms, including growth factors especially transforming growth factor-beta1 and vascular endothelial growth factors, angiogenesis, cathepsin enzymes, adhesion molecules, bone regulatory proteins and matrix metalloproteinases have been demonstrated, however the target to be attacked is not defined yet.

Life-threatening subdural hematoma after aortic valve replacement in a patient with Heyde syndrome: a case report.

PubMed

Uchida, Tetsuro; Hamasaki, Azumi; Ohba, Eiichi; Yamashita, Atsushi; Hayashi, Jun; Sadahiro, Mitsuaki

2017-08-08

Heyde syndrome is known as a triad of calcific aortic stenosis, anemia due to gastrointestinal bleeding from angiodysplasia, and acquired type 2A von Willebrand disease. This acquired hemorrhagic disorder is characterized by the loss of the large von Willebrand factor multimers due to the shear stress across the diseased aortic valve. The most frequently observed type of bleeding in these patients is mucosal or skin bleeding, such as epistaxis, followed by gastrointestinal bleeding. On the other hand, intracranial hemorrhage complicating Heyde syndrome is extremely rare. A 77-year-old woman presented to our hospital with severe aortic stenosis and severe anemia due to gastrointestinal bleeding and was diagnosed with Heyde syndrome. Although aortic valve replacement was performed without recurrent gastrointestinal bleeding, postoperative life-threatening acute subdural hematoma occurred with a marked midline shift. Despite prompt surgical evacuation of the hematoma, she did not recover consciousness and she died 1 month after the operation. Postoperative subdural hematoma is rare, but it should be kept in mind as a devastating hemorrhagic complication, especially in patients with Heyde syndrome.

Incidence of Deflux® calcification masquerading as distal ureteric calculi on ultrasound.

PubMed

Yankovic, Francisca; Swartz, Robert; Cuckow, Peter; Hiorns, Melanie; Marks, Stephen D; Cherian, Abraham; Mushtaq, Imran; Duffy, Patrick; Smeulders, Naima

2013-12-01

Dextranomer-hyaluronic acid (Deflux(®)), the most widely used compound in the endoscopic treatment of vesico-ureteric reflux (VUR) today, is believed to provoke only minimal inflammation. Reports of calcification of Deflux(®) are increasing. We ascertain the incidence of Deflux(®) calcification appearing as distal ureteric calculi on ultrasound. Three cases (2 external patients) of ureteroscopy for calcified submucosal Deflux(®) prompted a retrospective review of the notes and imaging of all children treated with Deflux(®) for VUR between December 2000 and January 2011 at Great Ormond Street Hospital. 232 children (M:F = 5:3) received Deflux(®) for VUR at median age 2 years (range 2 months-12 years). Follow-up annual ultrasound, performed in all, identified calcification in 2. The interval between Deflux(®) injection and presentation of its calcification was 4 years. 104 of the 232 children had been followed up for 4-10 years. Considering the observed lag-period, after 4 years the incidence of calcification of Deflux(®) on ultrasound was 2% (2/104). Patients should be warned that calcification of Deflux(®) can occur. Misinterpretation as ureteric stones is common and may lead to unnecessary ureteroscopy. In this series, the incidence of calcification of Deflux(®) on ultrasound after 4 years was 2%. Copyright © 2012 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Atypical localizations of calcific deposits in the shoulder

PubMed Central

Vinanti, G.B.; Pavan, D.; Rossato, A.; Biz, Carlo

2015-01-01

Introduction Calcific tendinopathies of the shoulder are due to inflammation around deposits of calcium within periarticular tendineal structures. Presentation of cases We present three cases of atypical localization of calcium deposits in the shoulder. All of the cases have been treated with arthroscopic excision, followed by post-operative rehabilitation, regaining excellent results. Patients were evaluated 6 months after surgery using the Visual Analogue Scale (VAS), the Simple Shoulder Test (SST) and the UCLA modified shoulder rating. Discussion Calcific tendinopathy is a self-limiting condition or is successfully treated with conservative therapy especially during the early phases of the pathology. If conservative measures fail, removal of calcium deposits is recommended. Arthroscopic management showed good results in our three cases. Conclusion We suggest that arthroscopic treatment of calcific tendonitis guarantees good results even when calcium deposits are in atypical locations. PMID:25884610

Absence of posterior tricuspid valve leaflet and valve reconstruction

PubMed Central

Komoda, Takeshi; Stamm, Christof; Fleck, Eckart; Hetzer, Roland

2012-01-01

We report a rare case of the absence of a posterior tricuspid valve leaflet. A male patient, aged 46, suffering from severe tricuspid valve regurgitation (TR) of unknown aetiology and atrial septal aneurysm was referred to our hospital for surgery. On surgical inspection, the posterior tricuspid valve leaflet and its subvalvular apparatus were completely absent and only the valve annulus was seen in the corresponding position. The anterior and septal leaflets were normal. We successfully reconstructed the tricuspid valve as follows: the head of an anterior papillary muscle was approximated to the ventricular septum (Sebening stitch). After the approximation of the centre of the tricuspid annulus of the anterior leaflet to the tricuspid annulus on the opposite side, a sizer of 29 mm in diameter was easily passed through the anterior orifice. The posterior orifice was closed with running sutures (posterior annulorrhaphy after Hetzer). Before these procedures, we attempted to reconstruct the tricuspid valve with a posterior annulorrhaphy alone; however, valve competence was insufficient. A Sebening stitch was necessary to improve the valve competence. Echocardiography showed TR grade 1 at the patient's discharge from hospital and TR grade 1 to 2 at the follow-up, 10 months after the operation. PMID:22419794

Cardiac Fibroblasts Adopt Osteogenic Fates and Can Be Targeted to Attenuate Pathological Heart Calcification.

PubMed

Pillai, Indulekha C L; Li, Shen; Romay, Milagros; Lam, Larry; Lu, Yan; Huang, Jie; Dillard, Nathaniel; Zemanova, Marketa; Rubbi, Liudmilla; Wang, Yibin; Lee, Jason; Xia, Ming; Liang, Owen; Xie, Ya-Hong; Pellegrini, Matteo; Lusis, Aldons J; Deb, Arjun

2017-02-02

Mammalian tissues calcify with age and injury. Analogous to bone formation, osteogenic cells are thought to be recruited to the affected tissue and induce mineralization. In the heart, calcification of cardiac muscle leads to conduction system disturbances and is one of the most common pathologies underlying heart blocks. However the cell identity and mechanisms contributing to pathological heart muscle calcification remain unknown. Using lineage tracing, murine models of heart calcification and in vivo transplantation assays, we show that cardiac fibroblasts (CFs) adopt an osteoblast cell-like fate and contribute directly to heart muscle calcification. Small-molecule inhibition of ENPP1, an enzyme that is induced upon injury and regulates bone mineralization, significantly attenuated cardiac calcification. Inhibitors of bone mineralization completely prevented ectopic cardiac calcification and improved post injury heart function. Taken together, these findings highlight the plasticity of fibroblasts in contributing to ectopic calcification and identify pharmacological targets for therapeutic development. Copyright © 2017 Elsevier Inc. All rights reserved.

[Endomyocardial fibrosis with massive calcification of the left ventricle].

PubMed

Trigo, Joana; Camacho, Ana; Gago, Paula; Candeias, Rui; Santos, Walter; Marques, Nuno; Matos, Pedro; Brandão, Victor; Gomes, Veloso

2010-03-01

Endomyocardial fibrosis is a rare disease, endemic in tropical countries. It is characterized by fibrosis of the endocardium that can extend to myocardium. Important calcification of the endocardium is rare with only a few cases reported in the literature. We report a case of endomyocardial fibrosis in a european caucasian patient, associated with massive calcification of left ventricle.

[Percutaneously implantable aortic valve: the JenaValve concept evolution].

PubMed

Figulla, Hans R; Ferrari, Markus

2006-10-01

Due to the increasing incidence of severe aortic stenosis in old and multimorbid patients, the percutaneous implantation of aortic valve-carrying stents has become an alternative to the surgical replacement of aortic valves. Starting in 1995, the authors developed a self-expanding stent which transferred the necessary forces for anchoring up to the aorta ascendens-a conception taken over from CoreValve. The further improvement of this idea over the past 11 years has led to a self-expanding, relatively short stent-valve system that is reliably positioned in the cusps of the old aortic valve and holds the old valve like a paper clip, thus transferring the holding forces physiologically. As compared to conventional systems, the sophisticated insertion catheter requires further chronic animal tests so as to represent a true alternative to the conventional surgical procedure.

Editorial Commentary: Be on the Lookout for White Chalk! Hip Labrum Calcification.

PubMed

Konyves, Arpad

2018-04-01

Amorphous calcification of the hip labrum is a little known and relatively rare condition. Although patients with amorphous calcification have favorable post-arthroscopic surgery self-reported outcome, it is unclear how much of their improvement can be attributed to the debridement of the calcific lesion itself. Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

[Mechanism of losartan suppressing vascular calcification in rat aortic artery].

PubMed

Shao, Juan; Wu, Panfeng; Wu, Jiliang; Li, Mincai

2016-08-01

Objective To investigate the effect of the angiotensin II receptor 1 (AT1R) blocker losartan on vascular calcification in rat aortic artery and explore the underlying mechanisms. Methods SD rats were divided randomly into control group, vascular calcification model group and treatment group. Vascular calcification models were made by subcutaneous injection of warfarin plus vitamin K1 for two weeks. Rats in the treatment group were subcutaneously injected with losartan (10 mg/kg) at the end of the first week and consecutively for one week. We observed the morphological changes by HE staining and the calcium deposition by Alizarin red staining in the artery vascular wall. The mRNA expressions of bone morphogenetic protein 2 (BMP2) and Runt-related transcription factor 2 (RUNX2) were analyzed by reverse transcription PCR. The BMP2 and RUNX2 protein expressions were determined by Western blotting. The apoptosis of smooth muscle cells (SMCs) were detected by TUNEL. The AT1R expression was tested by fluorescent immunohistochemistry. Results The aortic vascular calcification was induced by warfarin and vitamin K1. Compared with the vascular calcification model group, the mRNA and protein expressions of BMP2 and RUNX2 were significantly downregulated in the aorta in the losartan treatment group. Furthermore, the apoptosis of SMCs and the AT1R expression obviously decreased. Conclusion AT1R blocker losartan inhibits the apoptosis of SMCs and reduces AT1R expression; it downregulates the BMP2 and RUNX2 expressions in the vascular calcification process.

Relation between calcium burden, echocardiographic stent frame eccentricity and paravalvular leakage after corevalve transcatheter aortic valve implantation.

PubMed

Di Martino, Luigi F M; Soliman, Osama I I; van Gils, Lennart; Vletter, Wim B; Van Mieghem, Nicolas M; Ren, Ben; Galema, Tjebbe W; Schultz, Carl; de Jaegere, Peter P T; Di Biase, Matteo; Geleijnse, Marcel L

2017-06-01

Paravalvular aortic leakage (PVL) after transcatheter aortic valve implantation (TAVI) is a complication with potentially severe consequences. The relation between native aortic root calcium burden, stent frame eccentricity and PVL was not studied before. Two-hundred-and-twenty-three consecutive patients with severe aortic stenosis who underwent TAVI with a Medtronic CoreValve System© and who had available pre-discharge transthoracic echocardiography were studied. Echocardiographic stent inflow frame eccentricity was defined as major-minor diameter in a short-axis view >2 mm. PVL was scored according to the updated Valve Academic Research Consortium (VARC-2) recommendations. In a subgroup of 162 (73%) patients, the calcium Agatston score was available. Stent frame eccentricity was seen in 77 (35%) of patients. The correlation between the Agatston score and stent frame eccentricity was significant (ρ = 0.241, P = 0.003). Paravalvular leakage was absent in 91 cases (41%), mild in 67 (30%), moderate in 51 (23%), and severe in 14 (6%) cases. The correlation between stent frame eccentricity and PVL severity was significant (ρ = 0.525, P < 0.0001). There was a relation between particular eccentric stent frame shapes and the site of PVL. Calcification of the aortic annulus is associated with a subsequent eccentric shape of the CoreValve prosthesis. This eccentric shape results in more PVL, with the localization of PVL related to the shape of stent frame eccentricity. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Towards predicting coral calcification responses to ocean acidification: A combined modeling and experimental approach

NASA Astrophysics Data System (ADS)

Mollica, N. R.; Guo, W.; Cohen, A. L.; Foster, G. L.; Barkley, H.

2016-02-01

Experiments show that ocean acidification is detrimental to coral calcification. Nevertheless, coral sensitivities to OA vary and the mechanism(s) underlying these variable responses are not fully understood. One hypothesis is that ocean acidification affects the ability of coral's to regulate the pH of fluid at the site of calcification. We developed a numerical model of coral calcification that simulates corals' pH regulation based on physiochemical principles and predicts the rate of calcification [1]. Here we apply this model to Palauan corals, and seek to test the model's efficacy by comparing the predicted coral calcification responses with experimental measurements. Four coral cores were collected from two sites of different pH (7.84 and 8.04 respectively). Their bulk annual calcification rates, quantified from average density and extension rate measurements, vary from .83 to 1.39 g cm-2 year-1 for the low pH site and from 0.75 to 1.21 g cm-2 year-1for the high pH site. The higher bulk calcification rates observed in corals from the low pH site contrasts the expected general decrease in calcification in low pH seawater, and differs from our model prediction. We suspect this apparent discrepancy arises because fast-calcifying corals in low pH water are able to modulate the pH of fluid at the site of calcification. We test this hypothesis using boron isotope measurements from each coral. In addition, a more accurate measurement of instantaneous calcification, considering the number of corallites per measured area and the exact surface area of each polyp's 3-dimensional calcification site is applied. [1] Guo, W. (2014). AGU Fall Meeting, Abstract B41B-0033.

Sensitivity of Calcification to Thermal Stress Varies among Genera of Massive Reef-Building Corals

PubMed Central

Carricart-Ganivet, Juan P.; Cabanillas-Terán, Nancy; Cruz-Ortega, Israel; Blanchon, Paul

2012-01-01

Reductions in calcification in reef-building corals occur when thermal conditions are suboptimal, but it is unclear how they vary between genera in response to the same thermal stress event. Using densitometry techniques, we investigate reductions in the calcification rate of massive Porites spp. from the Great Barrier Reef (GBR), and P. astreoides, Montastraea faveolata, and M. franksi from the Mesoamerican Barrier Reef (MBR), and correlate them to thermal stress associated with ocean warming. Results show that Porites spp. are more sensitive to increasing temperature than Montastraea, with calcification rates decreasing by 0.40 g cm−2 year−1 in Porites spp. and 0.12 g cm−2 year−1 in Montastraea spp. for each 1°C increase. Under similar warming trends, the predicted calcification rates at 2100 are close to zero in Porites spp. and reduced by 40% in Montastraea spp. However, these predictions do not account for ocean acidification. Although yearly mean aragonite saturation (Ωar) at MBR sites has recently decreased, only P. astreoides at Chinchorro showed a reduction in calcification. In corals at the other sites calcification did not change, indicating there was no widespread effect of Ωar changes on coral calcification rate in the MBR. Even in the absence of ocean acidification, differential reductions in calcification between Porites spp. and Montastraea spp. associated with warming might be expected to have significant ecological repercussions. For instance, Porites spp. invest increased calcification in extension, and under warming scenarios it may reduce their ability to compete for space. As a consequence, shifts in taxonomic composition would be expected in Indo-Pacific reefs with uncertain repercussions for biodiversity. By contrast, Montastraea spp. use their increased calcification resources to construct denser skeletons. Reductions in calcification would therefore make them more susceptible to both physical and biological breakdown, seriously

Arthroscopic Removal and Tendon Repair for Refractory Rotator Cuff Calcific Tendinitis of the Shoulder.

PubMed

Hashiguchi, Hiroshi; Iwashita, Satoshi; Okubo, Atsushi; Takai, Shinro

2017-01-01

The purpose of this study was to evaluate clinical and radiological outcomes of arthroscopic treatment for refractory rotator cuff calcific tendinitis of the shoulder. Subjects were 37 patients (35 women and 2 men; mean age, 47.8 years; age range 34-61 years) who had undergone arthroscopic treatment for calcific tendinitis of the shoulder. Despite sufficient nonsurgical treatments, all patients had residual calcific deposit with persistent or recurrent pain. Before surgery, all patients underwent 3-directional radiographs of the shoulder and three-dimensional computed tomography to determine the location and size of calcific deposit. Arthroscopic surgery was performed with the patient under general anesthesia in the lateral decubitus position. A 2-cm single longitudinal incision was made with a radiofrequency hook blade on the tendon surface above calcific deposit. Calcific deposit was removed as much as possible with a curette and a motorized shaver. The incised tendon was repaired with a side-to-side suture with strong sutures. The Japanese Orthopaedic Association shoulder score was used to evaluate clinical outcomes. The extent of calcific deposit removal was evaluated with radiographs obtained before surgery, 1 week after the surgery and at the final follow-up examination. The mean follow-up duration was 30.4 (range, 13-72) months. The mean shoulder score significantly improved from 69.7 (range, 58-80) points before surgery to 97.8 (range, 89-100) points at the final follow-up examination. Postoperative radiographs in all patients, showed that the calcific deposit was resolved or reduced and those from 1 week after surgery to the final examination showed no evidence of recurrence or enlargement of calcific deposit. The calcific deposit had completely resolved in 34 patients but remained in 3 patients. When treating calcific tendinitis of the shoulder, it is important to accurately determine the size and location of calcific deposit by radiographs and 3

Outcome of bioprosthetic valve replacement in dogs with tricuspid valve dysplasia.

PubMed

Bristow, P; Sargent, J; Luis Fuentes, V; Brockman, D

2017-04-01

To describe the short-term and long-term outcome in dogs with tricuspid valve dysplasia undergoing tricuspid valve replacement under cardiopulmonary bypass. Data were collected from the hospital records of all dogs that had undergone tricuspid valve replacement under cardiopulmonary bypass between 2006 and 2012. Dogs were considered candidates for tricuspid valve replacement if they had severe tricuspid valve regurgitation associated with clinical signs of cardiac compromise. Nine dogs of six different breeds were presented. Median age was 13 months (range 7 to 61 months), median weight 26·5 kg (range 9·7 to 59 kg). Eight bovine pericardial valves and one porcine aortic valve were used. One non-fatal intraoperative complication occurred. Complications during hospitalisation occurred in six dogs, four of which were fatal. Of the five dogs discharged, one presented dead due to haemothorax after minor trauma seven days later. The four remaining dogs survived a median of 533 days; all of these dogs received a bovine pericardial valve. Based on our results, tricuspid valve replacement with bovine or porcine prosthetic valves is associated with a high incidence of complications. © 2017 British Small Animal Veterinary Association.

Improving the imaging of calcifications in CT by histogram-based selective deblurring

NASA Astrophysics Data System (ADS)

Rollano-Hijarrubia, Empar; van der Meer, Frits; van der Lugt, Add; Weinans, Harrie; Vrooman, Henry; Vossepoel, Albert; Stokking, Rik

2005-04-01

Imaging of small high-density structures, such as calcifications, with computed tomography (CT) is limited by the spatial resolution of the system. Blur causes small calcifications to be imaged with lower contrast and overestimated volume, thereby hampering the analysis of vessels. The aim of this work is to reduce the blur of calcifications by applying three-dimensional (3D) deconvolution. Unfortunately, the high-frequency amplification of the deconvolution produces edge-related ring artifacts and enhances noise and original artifacts, which degrades the imaging of low-density structures. A method, referred to as Histogram-based Selective Deblurring (HiSD), was implemented to avoid these negative effects. HiSD uses the histogram information to generate a restored image in which the low-intensity voxel information of the observed image is combined with the high-intensity voxel information of the deconvolved image. To evaluate HiSD we scanned four in-vitro atherosclerotic plaques of carotid arteries with a multislice spiral CT and with a microfocus CT (μCT), used as reference. Restored images were generated from the observed images, and qualitatively and quantitatively compared with their corresponding μCT images. Transverse views and maximum-intensity projections of restored images show the decrease of blur of the calcifications in 3D. Measurements of the areas of 27 calcifications and total volumes of calcification of 4 plaques show that the overestimation of calcification was smaller for restored images (mean-error: 90% for area; 92% for volume) than for observed images (143%; 213%, respectively). The qualitative and quantitative analyses show that the imaging of calcifications in CT can be improved considerably by applying HiSD.

Early Outcomes for Valve-in-valve Transcatheter Aortic Valve Replacement in Degenerative Freestyle Bioprostheses.

PubMed

Sang, Stephane Leung Wai; Beute, Tyler; Heiser, John; Berkompas, Duane; Fanning, Justin; Merhi, William

2017-11-20

Transcatheter aortic valve replacement (TAVR) is used increasingly to treat bioprosthetic valve failure. A paucity of data exists regarding valve-in-valve (ViV) TAVR in degenerated Freestyle stentless bioprostheses (FSBs). This study sought to evaluate the feasibility and short-term outcomes of ViV TAVR in previously placed FSB. From October 2014 to September 2016, 22 patients at a single institution underwent ViV TAVR with a self-expanding transcatheter valve for a failing FSB. Patient baseline characteristics and clinical outcomes data were collected retrospectively and entered into a dedicated database. The mean patient age was 74 ± 9years, and the mean Society of Thoracic Surgeons' Risk score was 9.0 ± 7.4%. Ten patients presented with acute heart failure requiring urgent intervention. The most common mode of failure of the FSB was regurgitation caused by a flail or malcoapting leaflet. Seventeen (77%) patients had a modified subcoronary implantation, 3 (14%) had a full root replacement, and 2 (9%) had a root inclusion. Device success using a self-expanding transcatheter valve was 95%, all via transfemoral approach. The mean implant depth was 7 ± 3 mm. Thirty-day survival was 100%. No patient had more than mild paravalvular regurgitation at 30days, and the permanent pacemaker rate was 9%. The mean hospital stay after intervention was 5 ± 2days. ViV TAVR using a self-expanding transcatheter valve is safe, feasible, and can be used successfully to treat a failed FSB. Procedural challenges suggest referral to valve centers of excellence. Copyright © 2017 Elsevier Inc. All rights reserved.

Quickly Removable Valve

NASA Technical Reports Server (NTRS)

Robbins, John S.

1988-01-01

Unit removed with minimal disturbance. Valve inlet and outlet ports adjacent to each other on same side of valve body. Ports inserted into special manifold on fluid line. Valve body attached to manifold by four bolts or, alternatively, by toggle clamps. Electromechanical actuator moves in direction parallel to fluid line to open and close valve. When necessary to clean valve, removed simply by opening bolts or toggle clamps. No need to move or separate ports of fluid line. Valve useful where disturbance of fluid line detrimental or where fast maintenance essential - in oil and chemical industries, automotive vehicles, aircraft, and powerplants.

Ball valve extractor

DOEpatents

Herndon, Charles; Brown, Roger A.

2002-01-01

An apparatus and process for removing a ball valve is provided. The ball valve removal tool provides a handle sliding along the length of a shaft. One end of the shaft is secured within an interior cavity of a ball valve while the opposite end of the shaft defines a stop member. By providing a manual sliding force to the handle, the handle impacts the stop member and transmits the force to the ball valve. The direction of the force is along the shaft of the removal tool and disengages the ball valve from the ball valve housing.

Bellows sealed plug valve

DOEpatents

Dukas, Jr., Stephen J.

1990-01-01

A bellows sealed plug valve includes a valve body having an inlet passage and an outlet passage, a valve chamber between the inlet and outlet passages. A valve plug has substantially the same shape as the valve chamber and is rotatably disposed therein. A shaft is movable linearly in response to a signal from a valve actuator. A bellows is sealingly disposed between the valve chamber and the valve actuator and means are located between the bellows and the valve plug for converting linear movement of the shaft connected to the valve actuator to rotational movement of the plug. Various means are disclosed including helical thread mechanism, clevis mechanism and rack and pinion mechanism, all for converting linear motion to rotational motion.