Matthias Peuster

A novel approach to temporary stenting: degradable cardiovascular stents produced from corrodible metal—results 6–18 months after implantation into New Zealand white rabbits

OBJECTIVE To determine whether corrodible materials may be safely used as biodegradable cardiovascular implants. DESIGN Corrodible iron stents (> 99.8% iron) were produced from pure iron and laser cut with a stent design similar to a commercially available permanent stent (PUVA-AS16). A total of 16 NOR-I stents were implanted into the native descending aorta of 16 New Zealand white rabbits (mean luminal diameter at the implantation site 3.4 mm, balloon diameter to vessel diameter ratio 1.13). RESULTS No thromboembolic complications and no adverse events occurred during the follow up of 6–18 months. All stents were patent at repeat angiography after 6 (n = 9), 12 (n = 5), and 18 months (n = 2) with no significant neointimal proliferation, no pronounced inflammatory response, and no systemic toxicity. CONCLUSIONS This initial in vivo experience suggests that degradable iron stents can be safely implanted without significant obstruction of the stented vessel caused by inflammation, neointimal proliferation, or thrombotic events.

Coronary Artery Stenosis After Radiofrequency Catheter Ablation of Accessory Atrioventricular Pathways in Children With Ebstein’s Malformation

Background —Complications concerning the coronary arteries that are directly related to radiofrequency catheter ablation procedures have not been reported in children. Coronary artery lesions, however, have been demonstrated after the endocardial application of radiofrequency current in young animals. Methods and Results —Two boys with Ebstein’s anomaly of the tricuspid valve developed clinically asymptomatic coronary artery stenosis after radiofrequency catheter ablation of right-sided accessory atrioventricular pathways with standard catheter technology. Conclusions —The complication of coronary artery stenosis demonstrates a substantial risk after right atrial free wall radiofrequency current application in children. The risk of late coronary alterations should be considered when the use of catheter ablation procedures to young patients is proposed.

Rare earth metals used in biodegradable magnesium-based stents do not interfere with proliferation of smooth muscle cells but do induce the upregulation of inflammatory genes

Rare earth metals are added to corrodible magnesium-based alloys in low amounts (up to 10%) to improve their mechanical properties and to decrease the degradation rate. Cerium (Ce), neodymium (Nd), yttrium (Y), and ytterbium (Yb) are already used for degradable cardiovascular stents. Little is known about the biocompatibility of rare earth metals released during the degradation process of the implant. Therefore the biocompatibility of rare earth metals was assessed with regard to metabolic activity of human vascular smooth muscle cells (SMCs). After coincubation with the trivalent chlorides (0.5-100 microg/mL) of rare earth metals for 24, 72, 144, and 240 h metabolic activity was determined at each time point using the colometric WST-1 test. The tested rare earth metals did not lead to significant changes in metabolic activity over a wide concentration range. However, at high concentrations a decrease was observed. Apoptotic or necrotic effects were not observed. Furthermore, we analyzed the effects of Ce, Nd, Y, and Yb on the expression of genes involved in inflammatory processes. The expression of IL-6, IL-8, and ICAM-1 in SMCs after exposure to Ce, Nd, Y, and Yb (5 and 50 microg/mL) was measured using quantitative real-time PCR. Significant up-regulation of IL-6, IL-8, and ICAM-1 genes were only found after 24 h, mainly for a concentration of 50 microg/mL. Our cell culture data indicate that rare earth metals influence cellular processes of vascular cells. Whether adverse effects occur also in in vivo is the topic of further investigations.

Biocompatibility of corroding tungsten coils: in vitro assessment of degradation kinetics and cytotoxicity on human cells.

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 Ringers 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.

Development and biocompatibility of a novel corrodible fluoride-coated magnesium-calcium alloy with improved degradation kinetics and adequate mechanical properties for cardiovascular applications.

Recently, corrodible magnesium-based alloys have been introduced for use as cardiovascular stents and orthopedic implants. However, rapid corrosion rates have raised questions about their biocompatibility. Therefore, we developed a binary fluoride-coated magnesium-calcium alloy with improved degradation kinetics. Biocompatibility of the alloys was evaluated with metabolic assays (colorimetric WST-1 test). Furthermore, five different probes of magnesium-calcium alloys (MgCa 0.4, 0.6, 0.8, 1.2, and 2.0 wt %) were cocultivated with human smooth muscle cells and endothelial cells. To investigate the decomposition kinetics in a physiological environment the alloys were used untreated and fluoride coated (MgF(2)). Mg and Ca decreased the metabolic activity in vascular cells dose-dependently, with cytotoxic effects only at unphysiological concentrations. Uncoated magnesium alloys showed signs of decomposition after a short incubation time of 24 h in contrast to MgF(2) coated alloys. After 10 days smooth muscle and endothelial cells around the alloys were still alive, whereas colonization of the surfaces was only observed for smooth muscle cells. The fluoride-coated MgCa alloys exhibited good results concerning mechanical properties, degradation kinetics, and biocompatibility in vitro. We conclude that a binary fluoride magnesium-calcium alloy is a promising candidate for the production of cardiovascular stents.

Degradation of tungsten coils implanted into the subclavian artery of New Zealand white rabbits is not associated with local or systemic toxicity

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.

Fontan-type procedures: residual lesions and late interventions

BACKGROUND The purpose of this study was to determine the type and incidence of hemodynamic and electrophysiological abnormalities requiring surgical or catheter-based interventions in a single-center long-term experience. METHODS Eighty-eight patients with a follow-up of at least 5 years (mean follow-up, 9.6 +/- 2.6 years) after Fontan-type procedures were included. All patients had undergone cardiac catheterization either as part of the regular postoperative protocol or because of symptomatic atrial tachycardia or increasing cyanosis. RESULTS Freedom from reoperation for up to 5 years was documented for 82% of patients and decreased to 76% after 8 years. Late reoperations included conversion of an atriopulmonary anastomosis to a total cavopulmonary anastomosis in 2 patients with atrial dysrhythmia and implantation of an extracardiac conduit in 1 patient with left atrial isomerism and intrapulmonary arteriovenous malformations after a Kawashima operation. Decline in sinus node function with symptomatic bradycardia required pacemaker therapy in 10 patients (11%). Transcatheter interventions included fenestration occlusion in 5 of the 11 patients with initial baffle fenestration. In 6 of 17 patients with aortopulmonary collaterals, coil occlusion was indicated to reduce future systemic ventricular volume load. Various systemic venous collaterals were documented in 11 patients and required coil occlusion in 2. One patient with symptomatic protein-losing enteropathy underwent transcatheter fenestration creation without sustained relief of symptoms. Freedom from transcatheter interventions decreased from 94% to 82% after 5 and 10 years, respectively. CONCLUSIONS During long-term follow-up, reoperations are rare and mainly involve Fontan conversion to either a lateral-tunnel or extracardiac-conduit procedure. Detailed angiographic evaluation on a routine basis allows identification of the vascular sites of origin of aortopulmonary collateral vessels and systemic venous collaterals potentially developing during long-term follow-up. Transcatheter interventions including fenestration occlusion and occlusion of venous collaterals and aortopulmonary collaterals were performed to maintain and improve the Fontan circulation in clinically symptomatic and asymptomatic patients. During long-term follow-up after Fontan-type operations, a regular postoperative cardiac catheterization protocol is recommended.

In vitro and in vivo corrosion properties of new iron–manganese alloys designed for cardiovascular applications

The principle of biodegradation for the production of temporary implant materials (e.g. stents) plays an important role in the treatment of congenital heart defects. In the last decade several attempts have been made with different alloy materials-mainly based on iron and magnesium. None of the currently available materials in this field have demonstrated satisfying results and have therefore not found entry into broad clinical practice. While magnesium or magnesium alloy systems corrode too fast, the corrosion rate of pure iron-stents is too slow for cardiovascular applications. In the last years FeMn alloy systems were developed with the idea that galvanic effects, caused by different electrochemical properties of Fe and Mn, would increase the corrosion rate. In vitro tests with alloys containing up to 30% Mn showed promising results in terms of biocompatibility. This study deals with the development of new FeMn alloy systems with lower Mn concentrations (FeMn 0.5 wt %, FeMn 2.7 wt %, FeMn 6.9 wt %) to avoid Mn toxicity. Our results show, that these alloys exhibit good mechanical features as well as suitable in vitro biocompatibility and corrosion properties. In contrast, the evaluation of these alloys in a mouse model led to unexpected results-even after 9 months no significant corrosion was detectable. Preliminary SEM investigations showed that passivation layers (FeMn phosphates) might be the reason for corrosion resistance. If this can be proved in further experiments, strategies to prevent or dissolve those layers need to be developed to expedite the in vivo corrosion of FeMn alloys.

Endocardial pacing after Fontan-type procedures.

Background: Sinus node dysfunction is a frequent complication of Fontan‐type procedure. Epicardial pacing is considered as the standard treatment for these patients.

Transcatheter recanalization and subsequent stent implantation for the treatment of early postoperative thrombosis of modified Blalock-Taussig shunts in two children

Two babies with duct-dependent cyanotic congenital heart disease were palliated with modified Blalock-Taussig shunts. One patient was diagnosed to have tetralogy of Fallot, and the other patient, tricuspid atresia type Ia. Early postoperative arterial oxygen saturations dropped significantly due to shunt thrombosis. Both patients were successfully treated with angioplasty and stent implantation.