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Healing response to the Clamshell device for closure of intracardiac defects in humans.

The healing response to intracardiac devices in humans is largely unknown. During regulatory trials using the Clamshell device in over 800 patients, attempts were made to perform histopathological evaluation of all explanted devices. We reviewed all those with complete histopathological examination (n = 12) from Fontan baffles (n = 4), ventricular septal defects (n = 2), and atrial septal defects (ASD; n = 6), explanted at 2.7 months to 3.6 years (median, 1.6 years), at autopsy (n = 1) or surgery (n = 11), performed for residual defects (n = 5), atrial masses (n = 3), or Fontan revision (n = 3). All but one were nearly (n = 3) or completely (n = 8) covered by pseudointima, composed of fibroelastic tissue, predominantly collagen, with focal foreign body reaction in contact with fabric, without acute inflammation or infection. Atrial masses of granulation tissue were present in three cases (ASD), opposite to protruding fractured arms. No associations were identified between coverage and closure status, position, arm fractures, or implant period. In conclusion, the healing response to transcatheter Clamshell implantation in humans is characterized by a relatively rapid development of a nonthrombotic pseudointima composed of fibroelastic tissue with minimal foreign body reaction. Cathet Cardiovasc Intervent 2001;54:101-111.

Adolescent↗

Acquired Lutembacher syndrome or mitral stenosis and acquired atrial septal defect after transseptal mitral valvuloplasty.

Critical mitral stenosis in selected patients may be treated successfully with percutaneous mitral valvuloplasty. Complications of this procedure, particularly an atrial septal defect following transseptal approach, are generally of minor clinical significance. We describe a woman who initially underwent a successful percutaneous double-balloon mitral valvuloplasty via the transseptal approach. Three months later she presented with right-sided heart failure. Color Doppler echocardiography and cardiac catheterization demonstrated an atrial septal defect (ASD) as well as restenosis of the mitral valve. We conclude that significant ASDs may occur following transseptal mitral valvuloplasty with appearance of right ventricular failure and that color Doppler imaging aids in the diagnosis of this new variant of the classical Lutembacher syndrome.

Aged↗

Echocardiographic predictors of candidacy for successful transcatheter atrial septal defect closure.

We reviewed pre-closure echocardiograms on all patients undergoing transcatheter atrial septal defect (ASD) closure with the Bard double-umbrella occluder device aided by simultaneous transesophageal echocardiography to determine precatheterization predictors of outcome. Transesophageal echocardiograms were performed on 28 of 132 patients (22%) undergoing device closure (age = 3-72 years, mean = 14 years; weight = 15-68 kg, mean = 35 kg). Three devices were removed because of unstable position. Of the remaining 25 patients, 21 had effective closure (residual flow diameter < or = 3 mm) and 18 had favorable arm position (device arm on proper side of the septum and not in contact with an atrioventricular valve leaflet). Only ASD size predicted effective closure. All patients with a maximum defect size of < 13 mm had effective closure. Among the 17 patients with defects > or = 13 mm, 10 had effective closure, 4 had significant residual flow, and 3 had devices removed for unstable position. Atrial dimensions and rim size did not predict effective closure. There were no pre-closure predictors of favorable arm position which was associated only with the size of the device implanted.

Adolescent↗

Transcatheter closure of large atrial septal defects with the Babic system.

An improved 10 Fr version of the atrial septal defect (ASD) occlusion system consisting of two umbrellas for transvenous introduction over the long veno-arterial guide-wire was used to attempt closure in five adult patients with large defects (26-35 mm). The umbrellas are made of nitinol wire frame and a thin membrane of microporous polyurethane. Supported by the metal cannula and guided by selective left atriography, the umbrellas of 45-60 mm were placed individually into the atria and screwed together at the septum level by means of a torquer catheter. Positioning and screwing on, unscrewing, separating, and repositioning the umbrellas up to 17 times were needed to anchor the prosthesis correctly in a patient. The prosthesis could be implanted primarily in all patients (in one at second session). Dislodgement of a 60 mm prosthesis and left atrial perforation with a 55 mm prosthesis required surgery in two patients 8 hours and 2 weeks post procedure, respectively. A single umbrella-arm fracture was noticed in one patient 4 months after the implantation. All five patients were free of symptoms at follow-up after 7-10 months. Transcatheter closure of large ASDs is technically feasible with this system. The morbidity is mainly associated with the implantation of very large umbrellas.

Adult↗

Assessment of patient radiation doses during transcatheter closure of ventricular and atrial septal defects with Amplatzer devices.

The purpose of this study was to estimate the radiation dose to which children are exposed during cardiac catheterizations for the treatment of ventricular and atrial septal defects. Radiation doses were estimated for 46 children aged 1-18 years. These children were treated for secundum atrial septal defects (ASD group) for perimembranous ventricular septal defects (VSD group) or underwent a routine diagnostic catheterization (diagnostic group). Thermoluminescent dosimeters (TLDs) were attached in locations, representing the lateral entrance dose, the posterior entrance dose, the thyroid dose, and the gonad dose, respectively. A dose area product (DAP) meter was also attached externally on the posterior-anterior (PA) tube to give a direct value in cGy cm(2) for each procedure. The patient's entrance dose from the PA field ranged from 1.5 to 185.0 mGy for all patients, while the lateral entrance dose varied from 0.9 to 204 mGy. Radiation exposure to the thyroid and the gonads was found to vary from 0.4 to 8.3 and 0.1 to 2.1 mGy, respectively. The DAP meter recorded DAP values for the posterior tube, between 46 and 3,700 cGy cm(2). The mean effective dose was found to be 7.7, 16.2, and 33.3 mSv for the diagnostic, the ASD, and the VSD group, respectively. Very strong correlation was found between the DAP values and the entrance radiation dose measured with TLDs. The mean entrance dose received from therapeutic cardiac catheterizations using the Amplatzer devices was found approximately twice the dose received from a diagnostic one. Even for the most complex procedures, the maximum entrance dose was at least 10 times lower than the threshold, associated with skin erythema.

Adolescent↗

Electron beam angiography for the evaluation of percutaneous atrial septal defect closure.

Electron beam angiography (EBA) provides excellent anatomic imaging in patients with congenital heart disease and may be useful in the assessment of atrial septal defects (ASDs). We present four patients with an ASD who were considered for percutaneous closure and underwent EBA for measurement of defect size and assessment of rim adequacy, adjacent cardiac structures, and associated congenital anomalies.

Adult↗

Initial clinical experience with intracardiac echocardiography in guiding transcatheter closure of perimembranous ventricular septal defects: feasibility and comparison with transesophageal echocardiography.

Over the last several years, intracardiac echocardiography (ICE) has been employed successfully in guiding transcatheter device closure of a secundum atrial septal defect (ASD) or patent foramen ovale (PFO). Nothing is known regarding the use of ICE to guide catheter device closure of a perimembranous ventricular septal defect (PMVSD). Twelve patients (seven female/five male) who had a PMVSD (among them, three patients with associated atrial communications: two with an ASD and one with a PFO) underwent attempts at transcatheter device closure using the Amplatzer membranous VSD device of their defects, using sequential transesophageal echocardiography (TEE) and ICE guidance with general endotracheal anesthesia (five patients) and using ICE alone with conscious sedation (seven patients). The mean age of patients was 16.9 +/- 3.7, and their mean weight was 42.4 +/- 6.6. Their mean left ventricular end-diastolic dimension preclosure was 45.7 +/- 2.5. The Qp/Qs ratio ranged from 1.0 to 1.8:1. During the procedure, the ICE catheter was positioned in the right atrium (RA) in all 12 patients and the ICE catheter was advanced to the left atrium to obtain a view of the ventricular septum in 3. Both TEE and ICE provided similar anatomical views of the position of the PMVSD. Furthermore, the relationship of the defect to the aortic valve and tricuspid valves, the measured size of defect, and the guidance of various stages of device deployment were comparable by TEE and ICE. There were no complications encountered during or after closure. We conclude that ICE provides unique images of the PMVSD and measurements similar to those obtained by TEE. ICE potentially could replace TEE in most patients as a guiding imaging tool for PMVSD device closure, thus eliminating the need for general endotracheal anesthesia.

Adolescent↗

The impact of interventional cardiology for the management of adults with congenital heart defects.

The objective of this study is to assess the impact of interventional cardiology procedures for the management of ACHD. The interventional approach to the management of CHD in the adult population is becoming increasingly recognized as the preferred treatment option for a wide number of congenital cardiac conditions. The files of all consecutive patients over 18 years of age who were hospitalized in our department from January 2000 to December 2004 were reviewed. Over the study period, 1,115 ACHD (583 women; mean age 41 +/- 13.8, years, range 18-72 years) were hospitalized in our department; 752 patients underwent cardiac catheterization and 82.4% of them had an interventional procedure carried out. ASD (329/620) and PFO (159/620) closure account for 78% of all the procedures carried out, with a 2.7% of major complications incidence (all of them closing ASDs). Other procedures such as stenting aortic coarctation (40/620), ventricular septal defect closure (33/620), patent ductus arteriosus embolization (30/620), pulmonary valvuloplasty (12/620), stenting pulmonary artery branches (8/620), etc (5/620) were carried out. The most important complication was one death, which occurred in the case of a 22-year-old woman after stent implantation for a recurrent aortic coarctation. A trivial residual shunt was detected in only 5% of the patients who had a 6-month follow-up after VSD closure; no residual shunt was found after PDA embolization during the 12-month follow-up. In conclusion, we believe that the interventional approach is a safe and successful treatment option for a wide number of congenital cardiac conditions. The increasing use of catheter interventions for these patients will be responsible for an increase of complex cases in surgery.

Adolescent↗

Interatrial septum rupture during balloon measurement of a patent foramen ovale in a young patient presenting cryptogenic stroke.

We report the case of a 36-year-old woman admitted for cryptogenic stroke, in whom the Patent Foramen Ovale (PFO) diameter measurement, with a purpose built sizing balloon, performed before the closure procedure, was complicated with the rupture of the inter-atrial septum generating an Atrial Septal Defect (ASD) with a significant left-to-right shunt. This kind of complication may not be easy to handle, changing the initial procedural strategy from PFO to ASD closure technique requiring specific material and operator's technical skill.

Adult↗

Psychologic distress after disclosure of genetic test results regarding hereditary nonpolyposis colorectal carcinoma.

BACKGROUND: To the authors' knowledge, there have been few studies of the psychologic distress after disclosure of genetic test results for hereditary nonpolyposis colorectal carcinoma (HNPCC). The objectives of this study were to identify the prevalence rates and predictors of psychologic distress and to evaluate the feelings of guilt after disclosure of the test results in Japanese probands and unaffected relatives. METHODS: Probands and unaffected relatives were interviewed immediately after the first genetic counseling session for HNPCC and again 1 month after disclosure of the genetic test results. The prevalence of major and minor depression, acute stress disorder (ASD), posttraumatic stress disorder (PTSD), and posttraumatic stress symptoms (PTSS) were assessed using the Structured Clinical Interview based on the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition revised (DSM-III-R) or the DSM-IV; feelings of guilt were investigated using a numeric scale and a semistructured interview. RESULTS: Among 47 participants who completed the baseline interview, 42 participants (89%) completed the 1-month follow-up interview. Although none of the participants met the criteria for major depression, ASD, or PTSD at the follow-up interview, 3 of 42 participants (7%) met the criteria for minor depression and 2 participants (5%) had PTSS. The only predictor of psychologic distress found was the presence of a history of major or minor depression (odds ratio, 19.41; 95% confidence interval, 1.42-264.95; P < 0.05). Five of 42 participants (12%) had feelings of guilt. CONCLUSIONS: Disclosure of genetic test results for HNPCC may not cause significant psychologic distress in Japanese probands or relatives. However, healthcare providers should not neglect to assess these individuals for psychologic responses, such as minor depression and PTSS.

Adult↗

Progressive AV-block and anomalous venous return among cardiac anomalies associated with two novel missense mutations in the CSX/NKX2-5 gene.

Non-syndromic cardiac septation defects are common, yet the causative factors remain largely uncharacterised. Septation defects are an integral part of many syndromes, some of which are associated with chromosomal alterations. For the majority, the physiopathogenesis is believed to be multi-factorial, hindering the identification of causative factors. Ten mutations in the gene encoding the transcription factor CSX/NKX2-5 have been described in individuals with ASD and/or atrioventricular conduction defects. In addition, several other cardiac abnormalities were observed, yet the mildest forms are reminiscent of non-syndromic septation defects. The CSX/NKX2-5 gene is thus a good candidate for various cardiopathies. We have collected two families with inherited predisposition to cardiac abnormalities. Some members of the families presented ASD and AV block. In both families a novel CSX/NKX2-5 mutation was identified in the homeodomain. Variable expressivity in the phenotype was observed in both families. Importantly, mutation carriers did not present any symptoms at young age. In addition, anomalous venous return, a phenotype not previously associated to CSX/NKX2-5 mutations, was observed in one of the families. We also screened the CSX/NKX2-5 gene in sporadic and familial cases of other cardiopathies. As additional mutations were not found, substitutions in CSX/NKX2-5 gene seem to be a rare cause of cardiopathies without conduction defect.

Amino Acid Sequence↗

TBX5 mutations in non-Holt-Oram syndrome (HOS) malformed hearts.

The T-box transcription factor Tbx5 is important in mammalian cardiac development. Mutations in the human TBX5 gene cause Holt-Oram syndrome (HOS), a disorder characterized by heart and upper limb deformities. To determine the role of TBX5 in non-HOS patients with complex cardiac malformations, we analyzed 68 explanted hearts from unrelated patients with various cardiac abnormalities including atrial (ASD), ventricular (VSD) and atrioventricular septal defects (AVSD). Direct sequencing detected nine mutations in diseased cardiac tissues of patients, eight of which are novel. Six mutations would affect amino acids in the T-domain, and one (c.236C>T, p.Ala79Val) is within the recently identified nuclear localization signal (NLS1) region. Further, mutations were found in patients with ASD and AVSD, but not with VSD; and mutations were absent in normal heart tissue of same patients, thus indicating somatic origin. Our results suggest a possible role of somatically occurring TBX5 mutations in congenital heart disease. We show for the first time TBX5 mutations in non-HOS associated cardiac malformations and we identified a novel missense mutation that would impact nuclear localization of TBX5.

Abnormalities, Multiple↗

In vitro assessment of the osteointegrative potential of a novel multiphase anodic spark deposition coating for orthopaedic and dental implants.

Hydroxyapatite coatings have been proven to improve the osteointegration of metal implants through a tight binding to the bone mineral phase as well as through favorable osteoblast adhesion and proliferation onto the implant surface. However, hydroxyapatite coatings are not stable and they tend to delaminate from the metal surface when challenged by the mechanical stresses experienced by the implant. Recently, a new multiphase anodic spark deposition (ASD) method has been optimized where the formation of a thick oxide film is followed by the deposition of a calcium phosphate mineral phase and its etching by alkali. The data in this paper demonstrate that this novel type of coating, BioSpark, improves the material osteointegration potential when compared to conventional ASD while offering more mechanical stability. A faster mineralization was obtained by incubation in simulated body fluids and osteoblasts showed better adhesion, proliferation, differentiation, and collagen production. These performances were related to the surface morphology, to the film calcium/phosphate ratio and its surface oxygen content, as well as to a preferential binding of structural proteins such as fibronectin.

Adsorption↗

Identification and characterization of a bovine lipopolysaccharide-binding protein.

Endogenous regulatory mechanisms exist in mammals that enable a rapid response to lipopolysaccharide (LPS, endotoxin) stemming from gram-negative bacterial infections. Serum proteins and cell surface receptors exist that bind LPS, and this interaction may either aid in nonpathogenic removal of LPS from the body or potentiate the effects of LPS. We have used a photoreactive, thiol-cleavable, radiolabeled derivative of E. coli 0111:B4 LPS [LPS-(p-azidosalicylamido)-1,3'-dithiopropionamide; 125I-ASD-LPS], to identify the presence of LPS-binding proteins (LBPs) in bovine serum. Ion exchange chromatography was used to fractionate bovine serum, and eluted protein was subsequently photoaffinity labeled using 125I-ASD-LPS. LBPs were identified by autoradiography of sodium dodecyl sulfate-polyacrylamide gels. Several LBPs including three with apparent molecular masses of 65, 60, and 50 kDa were variably present within the chromatography pools. A 22-residue NH2-terminal amino acid sequence of the 60-kDa protein showed 77% homology with human LBP and 68% with rabbit LBP within this region. Further purification utilizing high-performance liquid chromatography yielded a protein fraction that contained the 60-kDa protein and was distinctly more active than whole bovine serum in LPS-dependent macrophage activation assays (up to 1600-fold on a weight/volume basis). The LPS-mediated macrophage activation in concert with chromatographically purified serum protein in tissue factor assays was inhibitable using anti-CD14 monoclonal antibodies. The results indicate that an LPS-binding protein exists in samples of pooled bovine serum and that this protein has features in common with human and rabbit LBP.

Acute-Phase Proteins↗

Mutations affecting gluconate catabolism in Escherichia coli. Genetic mapping of loci for the low affinity transport and the thermoresistant gluconokinase.

The isolation and properties of strains of Escherichia coli carrying mutations affecting either the low affinity transport for gluconate (gene gntU) or the thermoresistant gluconokinase (gene gntK) are described. A lesion of each type was genetically characterized by transduction experiments. Both mutations mapped in the asd region, and the order was malA-glpD-asd-gntU-gntK, with the last two markers at about min 75.78 and 75.86 on the map, respectively. Mutations altering specifically gntU have not been previously reported.

Biological Transport↗