PROJECT SUMMARY Pulmonary embolism (PE) is the third most common cause of cardiovascular death in the United States. Approximately 500,000-600,000 Americans are diagnosed with PE, which causes up to 180,000 death per year. According to the American Heart Association (AHA), PE is classified into three categories: massive, submassive, or low risk. Treatment with anticoagulants is the cornerstone for treatment of PE; however, suboptimal results such as a similar 30-days mortality, and an ~five-fold increase in the risk of major bleeding, and a 10-fold increase in the risk of intracranial hemorrhage, compared with placebo, in patients with submassive and massive PE, and only one-third of unstable PE patients (30%) received recommended thrombolytic therapy even when they are eligible. These suboptimal results with anticoagulants have led to the use of other treatments such as catheter-directed therapies (CDT). CDT includes catheter-directed thrombolysis (CDL) and catheter-based embolectomy. There are some limitations to the use of CDL, including the risk of hemorrhage, doses are still being investigated, and the evidence for the benefits of this technology is still lacking. Despite the compelling results of mechanical thrombectomy (MT) landmark trials, MT in PE is rarely performed. Our extensive discovery interviews among multiple KOLs have led us to identify the requirements of the new device to improve clinical outcomes and usability acceptance and establish MT as gold-standard treatment for submassive and massive PE, which include: 1) safe and smooth navigation into the PAs(<16F catheter); 2) rapid and continuous ingestion of emboli recanalizing large and medium-size branches of the pulmonary tree (efficacy equivalent to >20F catheter); 3) directional thrombectomy; 4) minimal blood loss; 5) negligible spillage of arrhythmogenic hemolysis byproducts. To address these issues, we propose to develop an entirely new class of MT devices, named Vortex Catheter Technology (V- CaTh), that augments suction catheters efficacy by a breakthrough mechanism we identified that generates a powerful whirlpool by converting the high rotational energy transmitted by a high-torque shaft into a hydrodynamic vortex. This mechanism enables the small catheter to remove large and stiff clots by progressive rotational elongation and pulling of the clot into the catheter (“a device that is small but acts big”) while preventing intravascular clot maceration and significantly reducing blood loss. We have previously completed extensive foundational research and iterative prototyping of our device in the context of MT for stroke. In this Phase 1 SBIR, we will expand the technological platform with pivotal engineering, development, and preclinical testing of a user- specified V-CaTh system for thrombectomy in PE. In order to ensure the adequate performance of the V-CaTh prototypes at key points along the development, we will carry out the following objectives: 1) user-specified design and development of the V-CaTh system and; 2) Iterative testing and optimization of the V-CaTh system in phantom PAs and human cadavers. If we achieve these Aims, E2 will be well-situated to move toward FDA submission, providing the interventional community with a specialized new tool to address the gap in PE care.

PROJECT NARRATIVE While there is a wide range of therapies used to treat pulmonary embolism (PE), many barriers to ideal outcomes remain, and a gold-standard treatment is currently undefined for intermediate to high-risk PE. In this Phase 1 SBIR program, Endovascular Engineering Inc. (E2) proposes to develop and validate the entirely new class of thrombectomy system (V-Cath system) that augments the efficacy of any suction catheter, including a small catheter, to ingest emboli by the generation of a unique and powerful whirlpool. Successful achievement of the goals of this proposal will enable E2 to be well-situated to move toward FDA submission.