Christoph Fink

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.

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.

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.

Secondary embolization of a Helex occluder implanted into a secundum atrial septal defect

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 manufacturers suggestion due to a mechanism not yet understood. Cathet Cardiovasc Intervent 2003;59:77–82.

Anterograde balloon valvuloplasty for the treatment of neonatal critical valvar aortic stenosis.

We report our experience with anterograde balloon valvuloplasty in 17 neonates treated between November 1996 and June 2001 for critical aortic stenosis. Patients with hypoplastic left heart syndrome were excluded. Anterograde balloon valvoplasty of the aortic valve was possible in all 17 patients. The mean peak systolic gradient prior to cardiac catheterization was 73 mm Hg (range, 30–117 mm Hg) and decreased to 37 mm Hg (range, 21–60 mm Hg) after the dilation. Aortic regurgitation after balloon valvoplasty was absent or mild in 14/17 patients, moderate in 2 patients, and severe in 1 patient. There was no mortality or echocardiographic evidence for aortic cusp perforation or mitral regurgitation associated with the procedure. Redilation was necessary in 3/17 patients. Two patients are awaiting elective Ross operation. One patient with endocardial fibroelastosis died at 11 months of age. Anterograde balloon valvoplasty can be safely and effectively performed to palliate neonates with critical aortic valve stenosis. Cathet Cardiovasc Intervent 2002;56:516–520.

Assessment of subacute inflammatory and proliferative response to coronary stenting in a porcine model by local gene expression studies and histomorphometry.

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.

Interventioneller Verschluss von großlumigen veno-venösen Kollateralen nach univentrikulärer Palliation angeborener Herzfehler mittels Starflex- und Amplatzer-PDA-Occluder

Arterial hypoxemia is frequently observed after Fontan-like palliation of congenital heart defects. Whereas small systemic-to-pulmonary venous collaterals can easily be occluded by use of metal spirals, large collateral vessels may be therapeutically challenging. We report on two patients with arterial hypoxemia (transcutaneous oxygen saturations 72% and 82%, respectively) after Fontan-like operation. One patient was diagnosed with double inlet left ventricle, malposition of the great arteries and subaortic obstruction; another patient was diagnosed with mitral atresia, double-outlet right ventricle, malposition of the great arteries and hemiazygos continuity. In the first patient, a large venous collateral (measuring 16 mm in diameter) was observed connecting the superior vena cava and the right upper pulmonary vein. In the latter patient, hepatic fistulas drained systemic venous blood into an excluded hepatic vein. There was an associated patent fenestration of the conduit connecting the hepatic veins to the pulmonary artery. After occlusion of the supracardiac venous collateral with a 33 mm Starflex device, arterial oxxgen saturation rose to levels above 95%. The excluded hepatic vein was occluded with of an 10/8 mm Amplatzer PDA occluder and the fenestration was closed with a 17 mm Starflex device. Arterial oxygen saturations rose to 98%. Conclusion: Occlusion of large collateral vessels after Fontan-like palliation of congenital heart defects can be effectively performed using the Amplatzer PDA device and the Starflex device. Different occlusion devices are needed to address the morphological differences of the collateral vessels. Arterielle Hypoxämien nach Fontan-ähnlicher Palliation angeborener Herzfehler sind ätiologisch vielfältig. Während kleinlumige veno-venöse Kollateralgefäße technisch einfach mittels ablösbarer Coils verschlossen werden können stellt die Therapie großkalibriger Kollateralgefäße häufig eine technische Herausforderung dar. Wir berichten über 2 Patienten mit arterieller Hypoxämie (transkutane Sauerstoffsättigungen: 72% bzw. 82%) nach Fontan-Operation. Bei einer Patientin konnte eine großkalibrige (16mm) Kollaterale aus der oberen Hohlvene in die rechte obere Lungenvene ursächlich identifiziert werden, bei dem anderen Patienten bestanden hepatische Fistelgefäße in eine exkludierte Lebervene (8mm). Durch die Implantation eines 33mm Starflex-Occluders in die Kollaterale aus der oberen Hohlvene bzw. die Implantation eines 10/8mm Amplatzer-PDA-Occluders in die exkludierte Lebervene und Fenestrationsocclusion mit einem 17mm Starflex-Occluder konnten die arteriellen Sauerstoffsättigungen auf Werte von 95–98% gesteigert werden. Schlussfolgerung: Der Verschluss großkalibriger unerwünschter Kollateralgefäße nach univentrikulärer Palliation angeborener Herzfehler mittels Amplatzer PDA-Occluder und Starflex-Occludern ist technisch möglich. Zur Berücksichtigung unterschiedlicher Morphologien der Kollateralgefäße sind für die interventionelle Therapie verschiedene Schirmsysteme von Vorteil.

[Interventional therapy of large veno-venous collaterals after univentricular palliation for congenital heart disease using the Starflex- and Amplatzer- PDA occluder].

Arterial hypoxemia is frequently observed after Fontan-like palliation of congenital heart defects. Whereas small systemic-to-pulmonary venous collaterals can easily be occluded by use of metal spirals, large collateral vessels may be therapeutically challenging. We report on two patients with arterial hypoxemia (transcutaneous oxygen saturations 72% and 82%, respectively) after Fontan-like operation. One patient was diagnosed with double inlet left ventricle, malposition of the great arteries and subaortic obstruction; another patient was diagnosed with mitral atresia, double-outlet right ventricle, malposition of the great arteries and hemiazygos continuity. In the first patient, a large venous collateral (measuring 16 mm in diameter) was observed connecting the superior vena cava and the right upper pulmonary vein. In the latter patient, hepatic fistulas drained systemic venous blood into an excluded hepatic vein. There was an associated patent fenestration of the conduit connecting the hepatic veins to the pulmonary artery. After occlusion of the supracardiac venous collateral with a 33 mm Starflex device, arterial oxxgen saturation rose to levels above 95%. The excluded hepatic vein was occluded with of an 10/8 mm Amplatzer PDA occluder and the fenestration was closed with a 17 mm Starflex device. Arterial oxygen saturations rose to 98%. Conclusion: Occlusion of large collateral vessels after Fontan-like palliation of congenital heart defects can be effectively performed using the Amplatzer PDA device and the Starflex device. Different occlusion devices are needed to address the morphological differences of the collateral vessels. Arterielle Hypoxämien nach Fontan-ähnlicher Palliation angeborener Herzfehler sind ätiologisch vielfältig. Während kleinlumige veno-venöse Kollateralgefäße technisch einfach mittels ablösbarer Coils verschlossen werden können stellt die Therapie großkalibriger Kollateralgefäße häufig eine technische Herausforderung dar. Wir berichten über 2 Patienten mit arterieller Hypoxämie (transkutane Sauerstoffsättigungen: 72% bzw. 82%) nach Fontan-Operation. Bei einer Patientin konnte eine großkalibrige (16mm) Kollaterale aus der oberen Hohlvene in die rechte obere Lungenvene ursächlich identifiziert werden, bei dem anderen Patienten bestanden hepatische Fistelgefäße in eine exkludierte Lebervene (8mm). Durch die Implantation eines 33mm Starflex-Occluders in die Kollaterale aus der oberen Hohlvene bzw. die Implantation eines 10/8mm Amplatzer-PDA-Occluders in die exkludierte Lebervene und Fenestrationsocclusion mit einem 17mm Starflex-Occluder konnten die arteriellen Sauerstoffsättigungen auf Werte von 95–98% gesteigert werden. Schlussfolgerung: Der Verschluss großkalibriger unerwünschter Kollateralgefäße nach univentrikulärer Palliation angeborener Herzfehler mittels Amplatzer PDA-Occluder und Starflex-Occludern ist technisch möglich. Zur Berücksichtigung unterschiedlicher Morphologien der Kollateralgefäße sind für die interventionelle Therapie verschiedene Schirmsysteme von Vorteil.

Influence of two perfusion strategies on oxygen metabolism in paediatric cardiac surgery. Evaluation of the high-flow, low-resistance technique §

OBJECTIVE Paediatric cardiac surgery is often performed under hypothermic conditions, that is, with a reduced core body temperature. Certain interventions even require the circulation to be stopped. This can only be done at a body temperature of 18 degrees C, with no risk of neurological damage and harm to the brain and other organs. Vasoconstriction is a natural reaction of the body to cold, causing the blood vessels to contract. Such a reaction would lead to a clear rise in blood pressure on cardiopulmonary bypass (CPB). Since the blood pressure is regulated in the arteriolar loop of the capillary system, there is a marked increase in blood pressure and a suppression of free water into the surrounding tissue, which, in turn, may lead to the intra-operative development of oedemas. This study aimed to investigate whether the high-flow, low-resistance (HFLR) technique offers any benefits over conventional methods. METHOD This open, prospective, randomised study was to recruit 48 children scheduled to undergo surgery for congenital heart disease. To investigate the two different perfusion strategies, we have measured intestinal perfusion as well as skin perfusion with laser Doppler spectroscopy. To identify the effects on the immune system, selected immunologic parameters of systemic inflammation were additionally measured. Laser Doppler spectroscopy is a method that uses a glass fibre probe to determine the parameters of oxygen saturation of haemoglobin and relative haemoglobin quantity in an illuminated tissue volume, as well as the perfusion parameters of relative blood flow and blood flow velocity in the sample volume of the probe. RESULTS During the study period, the change in oxygen saturation over time was comparable in both groups. At the end of surgery, the patients of the high-flow group had significantly higher saturation levels in the intestinal mucosa (p<0.05). Over the course of intensive care, the groups did not differ in terms of fluid supply, administration of packed red blood cells, platelet concentrates or fresh frozen plasma. Analysis of urinary output revealed significant group differences. It was higher in the patients of the high-flow group than the normal-flow group (p<0.03), without differences in diuretic administration. CONCLUSION Laser Doppler spectroscopy is highly suited to the detection even of the slightest changes in flow characteristics and oxygenation of the skin, musculature and intestinal mucosa during surgery with extracorporeal circulation using CPB. At the same time, the technique of HFLR perfusion was found to have benefits over conventional bypass methods.

Transcatheter closure of a multiperforated atrial septal defect extending from the oval fossa to the mouth of the inferior caval vein.

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.