Oral everolimus inhibits neointimal proliferation in prosthetic pulmonary valved stents in pigs.

BACKGROUND AND AIM OF THE STUDY: Growth factor-dependent cell proliferation can cause in-stent neointimal hyperplasia. The study aim was to evaluate whether oral everolimus inhibits the intimal proliferation associated with the implantation of prosthetic pulmonary valved stents. METHODS: Prosthetic pulmonary valves were implanted in 12 pigs (mean bodyweight 25 kg) using a transcatheter technique. Tricuspid valves were prepared from a titanium-coated polymer and sewn into a self-expanding nitinol stent (diameter 20 mm). Valved stents were implanted in the pulmonary position, where they remained for three months. In six animals, treatment with 2 mg/kg everolimus (Certican; Novartis) per day was started three days before implantation and continued throughout the course of the experiment. The other six pigs acted as controls. Adjuvant anticoagulation treatment consisted of acetylsalicylic acid and oral clopidogrel. After three months, hemodynamic valve function was investigated at catheterization and with MRI. At postmortem investigation the valved stents were explanted and subjected to macroscopic, histological and electron microscopic examination. RESULTS: There were no adverse side effects due to everolimus treatment. The overall mean everolimus plasma level during the study was 4.2 +/- 2.4 ng/ml. MRI revealed intact valve function with a regurgitation fraction of 7.3 +/- 4.2% in controls and 4.3 +/- 3.1% in the everolimus group (p <0.01). On macroscopic inspection and histological examination, the everolimus group showed only a thin tissue coverage of the stent struts. The valve cusps were free from intimal thickening, and electron microscopy showed a thin continuous cellular coating. In contrast, substantial neointimal formation was noted in controls. Tissue neogenesis was pronounced at the base of the valve, extended to the valve cusps, and caused valve thickening and foreshortening. CONCLUSION: The oral administration of everolimus effectively inhibits tissue neogenesis in pulmonary valved stents in pigs.

Magnetic resonance imaging-guided balloon angioplasty of coarctation of the aorta: a pilot study.

BACKGROUND: MRI guidance of percutaneous transluminal balloon angioplasty (PTA) of aortic coarctation (CoA) would be desirable for continuous visualization of anatomy and to eliminate x-ray exposure. The aim of this study was (1) to determine the suitability of MRI-controlled PTA using the iron oxide-based contrast medium Resovist (ferucarbotran) for catheter visualization and (2) to subsequently apply this technique in a pilot study with patients with CoA. METHODS AND RESULTS: The MRI contrast-to-noise ratio and artifact behavior of Resovist-treated balloon catheters was optimized in in vitro and animal experiments (pigs). In 5 patients, anatomy of the CoA was evaluated before and after intervention with high-resolution respiratory-navigated 3D MRI and multiphase cine MRI. Position monitoring of Resovist-treated catheters was realized with interactive real-time MRI. Aortic pressures were continuously recorded. Conventional catheterization was performed before and after MRI to confirm interventional success. During MRI, catheters filled with 25 micromol of iron particles per milliliter of Resovist produced good signal contrast between catheters and their background anatomy but no image distortion due to susceptibility artifacts. All MRI procedures were performed successfully in the patient study. There was excellent agreement between the diameters of CoA and pressure gradients as measured during MRI and conventional catheterization. In 4 patients, PTA resulted in substantial widening of the CoA and a decrease in pressure gradients. In 1 patient, PTA was ineffective. CONCLUSIONS: The MRI method described represents a potential alternative to conventional x-ray fluoroscopy for catheter-based treatment of patients with CoA.