Clinical Feasibility Study Of Recyclable/Removable Drug-Coated Inferior Vena Cava Filter

Background:Pulmonary embolism (PE) is an acute cardiovascular system disease threatening human health and costing lives secondary only to coronary artery disease and hypertension. Its insidious onset and rapid progression with a variety of nonspecific clinical manifestations complicate early detection and accurate diagnosis, resulting in relatively high mortality. It has been reported that in PE patients approximately 90-95% of emboli originated from deep vein thrombosis (DVT). Despite routine anticoagulation using a combination of heparin plus warfarin PE still develops in up to 20% of patients. It is well recognized that in high risk PE patients simple anticoagulation is inadequate. Such patients include at least those with pelvic vein thrombosis, lower extremity deep vein thrombosis, and recurrent DVT/PE despite adequate anticoagulation. In these patients inferior vena cava filter (IVCF) could be a better choice of treatment to certain degree, because this device minimizes the risk or prevent PE formation so that mortality may be decreased. In general there are two different types of IVCF: permanent and recyclable/removable. Although fatal PE incidence is decreased in patients with permanent IVCF, these patients still require long-term anticoagulation. Complete occlusion of permanent IVCF with prolonged follow-up remains an important concern. Recurrent DVT is significantly higher than those without IVCF. Other complications such as device migration and vascular perforation may increase with time. As a result the case-specific and total mortalities remain unchanged in patients with permanent IVCF. For all those reasons the recyclable/removable IVCF which effectively filters out emboli but is removable in appropriate time attracts major research and clinical interests. Recyclable IVCF may be removed from patients as dictated by clinical conditions such as improved symptoms or elimination of reversible causes for DVT. Such device retains the advantage of permanent IVCF. Nevertheless in clinical practice recyclable/removable IVCF is far from being perfect. This type of device may stay in body for a limited time of approximate 12-14 days. Prolonged implantation may cause adhesion to vascular endothelial membrane because of local inflammatory stimulation by the device with contacted tissue, resulting failure of device removal. Fatal complication can occur during forceful device explantation which causes vascular wall tear and laceration. Currently the development of recyclable/removable IVCF reaches the bottle-neck stage.Hypothesis and Objectives: As interventional cardiologists we hypothesize that recyclable/removable IVCF coated with drugs that inhibit local inflammation and tissue growth just like drug-elute stent may inhibit vascular endothelial proliferation, therefore prolong the time of implantation and facilitate device removal. The overall objective of this study is to explore the clinical feasibility of drug-coated recyclable/removable IVCF. The first phase of this study is to compare the differences in local and systemic responses including retrievability in experimental animals implanted with drug elute stents (DES) and bare metal stents (BMS).Materials And Methods1. Experimental GroupsAge and weight matched 20 Japanese big-ear rabbits were randomly divided into two groups to receive either drug elute stents (experimental) or bare metal stents (control).2. MethodsAnimals were fed with warfarin at a dose of 60ng/kg/day for 7 days until plasma drug concentration was at steady-state. Under general anesthesia DES or BMS was implanted in IVC in catheterization laboratory using DSA flat plate (GE, USA). Warfarin was continued after stent implantation. Animals were euthanized by air embolization at experimental day 7, 15, 30, and 60. Stented IVC segments with 2-3 mm vessel tissue on each ends were removed and placed in 10% polyphosphate formaldehyde solution for 24 hour-fixation. Thereafter longitudinal sections were made for gross inspection of vascular endothelial proliferation. After removing the stents, the vascular tissues were further fixed, embolded, sliced and stained for quantitative measurements of the thickness of neo-endotheliolization under microscopy. Data were expressed by mean +/- standard deviation. Statistical analysis was performed using software SPSS 13.0 and paired sample one way test. Means between the two groups were analyzed using Student t-test. p value <0.05 defined as statistically significant at a pre-set standardα=0.05.Results1. Seven days after stent placement there was no gross difference in vascular neo-endothelialization between the experimental (DES) and the control (BMS) groups. Stents were easily separated and removed from vessel tissue. Endothelial coverage was incomplete in BMS group but essentially lacking in DES group at day 15. DES was still easily separated and removed from the vessel. However, longitudinal sections demonstrated semi-transparent neo-endothelium coverage in both DES and BMS groups at experimental day 30 and 60.2. Under microscopic examination there was statistically significant difference (p<0.05) in the thickness of neo-endothelialization between the DES and BMS implanted IVC segments at experimental day 30.3. There appeared to be a correlation between the pressure from the applied stent toward the vascular media layer and adventitia and the neo-endothelialization. Higher the applied pressure correlated with increased endothelial proliferation.4. Finally, the local inflammatory response from the DES group was less significant than that from the BMS group.Conclusions1. In experimental animal's body, drug-coated stents is superior to bare metal stents in preventing excessive endothelial proliferation in 30 days, but there are no gross difference between the two group in endothelial proliferation when the stents were placement for 60 days.2. The degree of endothelial proliferation in the stent section was related not only to the distribution of the stent struts, but also the compression degree of the media layer and adventitia of the vessels.3. The vascular local inflammatory reaction of drug-coated coronary stents is lighter than bare metal stents .