Pathology of explanted ASD occluder.
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Biomedical subjects
Publications and source records attributed to Matthias Peuster.
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Currently there are no biodegradable stents available for treatment of vascular obstructions in patients with congenital heart defects. This study was performed to evaluate the safety of a corrodible stent produced from pure iron in a peripheral stent design (6-12mm diameter) in a slotted tube design similar to a commercially available 316-L stent which served as control. Both stents were implanted into the descending aorta of 29 minipigs with an overstretch injury without technical problems. Two animals died after the implantation not related to the iron stent. The remaining 27 minipigs were followed for 1-360 days. Histomorphometry and quantitative angiography showed no difference with regard to the amount of neointimal proliferation between 316-L and iron stents. Histopathological examination of heart, lung, spleen, liver, kidney and para-aortic lymphatic nodes demonstrated no signs of iron overload or iron-related organ toxicity. Adjacent to the iron stent struts, there was no evidence for local toxicity due to corrosion products. We conclude that iron is a suitable metal for the production of a large-size degradable stent with no local or systemic toxicity. A faster degradation rate, however, is desirable and further studies have to focus on the modification of the composition and design of the stent to expedite the degradation process.
The application of radiofrequency (RF) technologies in the treatment of congenital heart defects has provided a safe and effective alternative to conventional therapies in the restoration of vascular patency for a variety of arterial and venous occlusions. This report concerns an 8-year old girl that developed protein-losing enteropathy and elevated central venous pressure after occlusion of a surgically redirected anomalous draining left superior vena cava (SVC). Cardiac catheterization revealed complete obstruction of the anastomosis of the SVC into the coronary sinus. Transcatheter recanalization by RF perforation and subsequent stent implantation led to the restoration of upper venous blood flow and the resolution of her symptoms.
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Cardiotoxicity is a well-known consequence of anthracycline chemotherapy. We report CMR findings not previously described in two patients with anthracycline cardiotoxicity following treatment for Ewing's sarcoma. Subendocardial enhancement on late gadolinium contrast-enhanced CMR was present in both cases, with histological correlation in one case.
This study was conducted to determine the interaction of individual corrosion products from biodegradable iron stents with cells from the adjacent tissue. The response of human umbilical venous smooth muscle cells (SMCs) to an excess of ferrous ions was investigated in a cell culture model at the phenotypic and at the molecular level. When soluble ferrous ions were added to the cell culture medium the cell growth rate was reduced. Gene expression profiling indicated a reduction in the amounts of mRNA from genes that are required for cell proliferation. In addition, mRNA was regulated from multiple genes involved in iron homeostasis, DNA replication and lipid metabolism. In conclusion, ions released from iron stents could reduce the vascular SMC proliferation rate by influencing growth-related gene expression and may therefore play a beneficial role in antagonizing restenosis in vivo.
A 3-year-old boy underwent interventional closure of an atrial septal defect using an Amplatzer septal occluder. After 4 weeks, an aortic sinus-to-left atrial fistula was detected by echocardiography in an asymptomatic child. The device was surgically explanted with fistula and atrial septal defect closure. Follow-up was uneventful.
PURPOSE: To evaluate the feasibility of rapid free-breathing phase-contrast MRI (PC-MRI) at different in-plane resolutions combined with sensitivity encoding (SENSE) for flow quantification in the great arteries in healthy adult volunteers. METHODS: In 13 volunteers (mean age 33.0 +/- 7.4 years), blood flow rates in the pulmonary artery (Qp), ascending aorta (Qs), and flow ratio Qp/Qs were determined by PC-MRI with SENSE reduction-factor 2 and 3 (SF-2, SF-3). Additionally, we used PC-MRI with higher spatial in-plane resolution (1.6 x 2.1 mm vs. 2.3 x 3.1 mm) with/without SF-3. Standard (= reference) PC-MRI, which used two excitations (NEX=2), was compared with PC-MRI sequences with NEX=1. RESULTS: Reduction of signal averages and application of SENSE accelerated flow measurements by a factor of 3.8 (5.5) using PC-MRI with SF-2 (SF-3): Scan time was 36 sec (SF-2) and 25 sec (SF-3) at average heart rate of 69/min. The mean Qp/Qs by reference PC-MRI was 1.03 +/- 0.07 (range, 0.89-1.16), and 1.0 +/- 0.11 (range, 0.86-1.24) by PC-MRI + SF-3, respectively. For blood flow rate through the pulmonary artery and aorta, and for Qp/Qs ratio, we found differences of -3% to +4%. The lower limits of agreement (mean - 2 SD) ranged between -14% and -21%, and upper limits (mean + 2 SD) between +9% and +30%, demonstrating clinically acceptable agreement with standard PC-MRI (Bland-Altman analysis). PC-MRI at higher in-plane resolution both with/without SENSE yielded slightly smaller aortic and pulmonary flows (mean differences 5% to 7%, p < 0.05). CONCLUSIONS. In adults, PC-MRI may be safely combined with SENSE to reduce scan time for a quantitative flow measurement in the great arteries to "30 seconds. High in-plane resolution was not advantageous.
BACKGROUND: Sinus node dysfunction is a frequent complication of Fontan-type procedure. Epicardial pacing is considered as the standard treatment for these patients. METHODS AND RESULTS: We evaluated an endocardial approach in seven patients using a 4.1 French bipolar lumenless lead (SelectSecure) that is positioned through a steerable guiding catheter. Either a purely transvenous or an open transatrial approach can be used for lead placement. The smallest child weighed 12 kg. Individual anatomy was assessed preimplantation using magnetic resonance imaging and injection of radiographic contrast agent through the guiding catheter. A pullback pressure recording was used to confirm unimpaired blood flow into the pulmonary artery. Five of our seven patients underwent de novo transvenous atrial lead implantation for AAIR pacing. In the remaining two patients, both atrial and ventricular leads were inserted. One patient with an intraatrial tunnel underwent transvenous-lead placement. The remaining patient with an extracardiac conduit received atrial and ventricular leads implanted through a guiding catheter inserted through an atriotomy. The postoperative management included short- or long-term oral anticoagulation. CONCLUSIONS: Transvenous endocardial lead implantation avoids the problem of increasing capture thresholds typically observed with epicardial leads. Due to its high tensile strength and lumenless design, the isodiametric lead is expected to remain extractable for an extended period of time.
The aim of the study was to analyse inflammatory and proliferative response early after coronary stenting by angiography, histomorphometry and local gene expression analysis using quantitative rt-PCR. Therefore, eight German domestic pigs underwent stenting of the left coronary artery. Selective coronary angiography was performed after 14 days. Explanted coronary arteries were examined histomorphometrically after methacrylate-embedding. Snap-frozen samples were examined for local gene expression of TGF-beta, TNF-alpha, GM-CSF, VEGF, PDGF and Fas Ligand (FasL) by real-time quantitative rt-PCR normalized to the housekeeping gene GAPDH and compared to unstented coronary arteries. All stented coronaries were patent with only little neointima formation. The median vessel diameter was 2.55 mm (range 2.43-2.68 mm). Histopathology revealed little inflammatory response limited to the tissue surrounding the stent struts; luminal area ranged from 84% to 91%. Compared to unstented control arteries, no significant differences in local gene expression were detected for VEGF, PDGF, TGF-beta, TNF-alpha and GM-CSF. Expression of FasL was upregulated as little as 1.7-fold (p=0.01). We conclude that, in native coronary arteries, no significant upregulation of investigated genes regulating vascular remodelling, inflammation or fibrogenesis was demonstrated 14 days after stenting. Whether upregulation of FasL as a marker gene of apoptosis is transient and biological significant requires further investigation.
BACKGROUND: Parallel imaging by sensitivity encoding (SENSE) may considerably reduce scan time in MRI. For rapid flow quantification in children with congenital heart disease, we evaluated phase-contrast MRI (PC-MRI) techniques combined with SENSE. METHODS AND RESULTS: In 22 pediatric patients (mean age, 7.2+/-6.2 years) with cardiac left-to-right shunt, blood flow rate in the pulmonary artery (Qp) and ascending aorta (Qs) and flow ratio Qp/Qs were determined by PC-MRI with SENSE reduction-factor 2 and 3 (SF-2 and SF-3). Additionally, we used PC-MRI with higher spatial in-plane resolution (1.6x2.1 versus 2.3x3.1 mm) with and without SF-3. Results were compared with a recently validated standard PC-MRI protocol and tested in vitro using a pulsatile flow phantom. Reduction of signal averages from 2 to 1 and application of SENSE accelerated flow measurements by a factor of 3.5 (5.2) using PC-MRI with SF-2 (SF-3) compared with standard PC-MRI. For blood flow rate through the pulmonary artery and aorta, as well as for the Qp/Qs ratio we found negligible differences of +/-3%, lower limits of agreement (mean+/-2 SD) of -7% to -18%, and upper limits of agreement (mean+/-2 SD) of +3 to +24%, demonstrating good agreement with standard PC-MRI. Mean Qp/Qs ratio by standard PC-MRI was 1.69+/-0.45 (range, 1.27 to 2.79). Interobserver variability was low, and high accuracy was confirmed in vitro for all protocols. CONCLUSIONS: PC-MRI for flow quantitation may be combined with SENSE to achieve a substantive reduction of scanning time. In children with left-to-right shunt, Qp/Qs quantification is possible by PC-MRI+SF-3 in <60 seconds. Use of higher in-plane resolution did not improve measurement results.
The purpose of the article is to evaluate composition and biocompatibility of corroding mechanically detachable spirals (MDS, Balt Extrusion, Montmorency, France). Analysis of the material composition of corroding MDS coils was assessed by inductively coupled plasma atomic emission spectroscopy, inductively coupled plasma mass spectroscopy, and wavelength-dispersive x-ray spectrometry. Toxicity assays were performed with human venous endothelial cells, venous smooth muscle cells and fibroblasts. The analyses of the MDS coils demonstrated a tungsten content of the dissolving MDS spirals of > 99.9 mas%. In vitro, human endothelial, vascular smooth muscle cells and fibroblasts were not adversely affected by markedly elevated tungsten concentrations (60,500 microg/l) after 12 days in the culture medium. The examined cells showed an extensive vital growth on the coil surface. Corrosion of tungsten coils leads to markedly elevated tungsten levels in the culture medium. However, growth and vitality of endothelial cells, fibroblasts, and vascular smooth muscle cells are not adversely affected by elevated tungsten concentrations.
We report on a 2-year-old patient with atrial septal defect with a stretched diameter of 11 mm. The defect was closed uneventfully by use of a 25 mm Helex device. There was only trivial residual shunting (1 mm at the cranial margin of the device). After 36 hr, routine postinterventional echocardiography confirmed device embolization into the pulmonary artery. The child was asymptomatic. Transcatheter device retrieval with snares of different sizes, bioptomes, and retrieval forceps failed due to the mismatch of the diameter of the device and the small diameter of the pulmonary artery. Therefore, the device was retrieved surgically and the ASD closed by primary sutures. Secondary embolization of a Helex device complicated the closure of an uncomplicated atrial septal defect with a device-to-defect ratio according to the manufacturer's suggestion due to a mechanism not yet understood.
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OBJECTIVE: To assess whether corrosion of tungsten coils is related to residual shunting and to evaluate whether elevated tungsten serum levels are associated with local or systemic toxicity. METHODS: Tungsten coils (SPI, Balt, France) were implanted into the subclavian artery of New Zealand white rabbits leading to a residual high-flow shunt in 5/10 rabbits. Serial serum tungsten levels, complete blood count and clinical chemistry were analysed prior to the implantation as well as 15 min, 2 and 4 months thereafter. After 4 months the rabbits underwent repeat angiography before they were sacrificed and the internal organs were evaluated histopathologically. RESULTS: Mean tungsten levels rose from 0.48 microg/l prior to the implantation to 12.4 microg/l 4 months post-implantation. The rise in serum tungsten levels was neither associated with residual shunting present at the time of implantation nor with residual shunting at the time of explantation. One animal had to be sacrificed because of non-resolving palsy of the upper extremity. The remaining animals had an uneventful clinical course with no signs of toxicity of the elevated tungsten levels. Histological examination revealed no evidence of local or systemic toxicity of the tungsten coils. CONCLUSION: Tungsten coils corrode and lead to a steady increase in serum tungsten levels starting as early as 15 min after implantation. Residual shunting does not seem to influence the kinetics of corrosion of tungsten coils. Despite markedly elevated serum tungsten levels 4 months after implantation degradation of tungsten coils is not associated with local or systemic toxicity.
This study was performed to determine the in vitro degradation rate of tungsten coils and to evaluate the potential local toxicity of tungsten on human pulmonary arterial endothelial (EC) and smooth muscle cells (SMC) and human dermal fibroblasts (FB). Therefore, tungsten coils were immersed in Ringer's solution and loss of mass and increase in tungsten concentration in the electrolyte were assessed in relation to immersion time (maximum: 140 days). Primary cultures of EC, SMC and FB were grown on multiplates for 1-10 days with ascending concentrations (0.1-5000 microg/ml) of tungsten in the growth medium. Metabolic activity was assessed by the use of the WST-1 Test (Roche). The in vitro degradation rate of the tungsten coil was 29 microg/day. EC were most susceptible to tungsten with a LD50 of 50 microg/ml. In contrast, the LD50 for SMC was 100 and 1000 microg/ml for FB after 10 days of incubation. We conclude that, in vitro, degradation rate of tungsten coils is slow (29 microg/day). Very high (>50 microg/ml [normal serum value 0.0002 microg/ml]) tungsten concentrations are needed to result in local cytopathologic effects on human EC, SMC and FB. These results correspond to clinical observations demonstrating the absence of toxicity of degrading tungsten coils in adult and pediatric patients despite elevated serum tungsten levels.
We treated a neonate with pulmonary atresia and a ventricular septal defect complicated by straddling of the atrioventricular valves by constructing a central aorto-pulmonary shunt. The postoperative course was complicated by obstruction of the shunt, which was treated by implantation of a coronary stent. Six months after the stenting, a Glenn anastomosis was created and the stented shunt removed. Analysis showed that the shunt was completely covered by a vascularized neointima. The stent had not produced injury to the shunt, with struts of the stent covered nicely by neoendothelium, with sparse inflammation surrounding the artificial implants.
We report a novel technique using an Amplatzer atrial septal occluder to close a defect located in the inferior-posterior portion of the interatrial septum that extended into the mouth of the inferior caval vein. Because of the close relation of the defect to the inferior caval vein, the right atrial disc was opened into the inferior caval vein and pushed toward the right atrium by use of the delivery cable. There was no residual shunting immediately and 3 months after the intervention. We conclude that even defects located infero-posteriorly within the oval fossa may be successfully closed by transcatheter techniques using the Amplatzer device.