This proposal is submitted in response to notice NHLBI Announces Small Business Topics of Special Interest (TOSI): HLS16-14: ?New animal models for the study of chronic venous insufficiency (CVI) and post-thrombotic syndrome (PTS), and innovative approaches for their prevention and treatment?. Post-thrombotic syndrome and chronic venous insufficiency that results from outflow obstructions places one of the largest burdens on the healthcare system of any disease condition. Conservative treatment of symptoms that originate from outflow obstructions are often ineffective and require endo-venous intervention for correction; i.e., venous stenting. Positive outcomes for venous stenting are limited to non-thrombotic disease, however, due to inadequate stent technology and poor understanding of the complexities of post-thrombotic veins. Efforts to extend principles of arterial stent delivery to veins are not without pitfalls as the compliance of veins contributes to 20-30% of venous stent recoil and can lead to residual stenosis and potential migration as supported by 25-29% of post- thrombotic stents requiring re-interventions. Further, stent under-deployment is related to several factors, including non-translatable manufacturer ex vivo to in vivo pressure/diameter compliance relations. Consequently, a point of care tool is needed to provide accurate balloon sizing, vein compliance and radial force information to the clinician in real-time during balloon inflation. To address this need, a novel peripheral reconnaissance venous balloon (PRVB) catheter system has been developed that functions as a typical venous pre-dilatation catheter, but with additional functionality for accurate measurement and real-time display of balloon size, vessel compliance and radial force. The PRVB catheter utilizes a predictive physical law (Ohm?s Law) to determine the balloon cross-sectional area which is displayed in real-time on a bed-side console to aid the physician during balloon expansion and subsequent stent selection. Preliminary results with the PRVB catheter system on the bench and in vivo in healthy swine show excellent accuracy (1.7% diameter error) and repeatability (0.9% diameter error) in addition to feasibility and application for direct pressure and radial force measurements. Additional work is needed to update the console and catheter, however, and further validate the system in a swine model of CVI and PTS (this Phase I) before translation to the clinic (future Phase II). Therefore, we propose the creation of a clinically-ready PRVB catheter system and its validation in diseased postmortem human vessels and in vivo in a relevant model of post-thrombotic syndrome (venous hypertension, reflux and thrombosis). Based on the fundamental physics of the technology, the excellent preliminary results, and the previously known safety of a related system, the PRVB catheter system is expected to provide highly accurate and repeatable real-time digital display of balloon size, compliance and radial force across the entire diseased venous segment (lesion and reference vessel diameter) with minimal physician training required.
A venous pre-dilatation device that can assess the severity of venous disease to guide stent selection and delivery is needed. The purpose of this Phase I proposal is to develop and validate a clinically relevant diagnostic balloon catheter system that provides accurate, real-time information on vein size, vein compliance and radial force to improve venous stent delivery.
