Ultrasound Image-Guided Catheter-Directed Therapies to Treat Cardiovascular Disease

Peripheral arterial disease (PAD) represents a challenging clinical problem affecting 15–20% of people over 70 years of age due to the diffuse nature of atheroma deposition throughout the arterial bed. Management of PAD with angioplasty and bare metal stents is complicated by restenosis. Studies of drug eluting stents in PAD have reported disappointing long-term results. An innovative strategy using ultrasound-enhanced delivery of a catheter-directed pioglitazone (PGN) to prevent the buildup of additional plaque in the intervention area, reduce inflammation in the surrounding atheroma bed, and promote healthy blood flow will be discussed. Fibrin-targeted echogenic liposomes loaded with PGN were characterized before and after infusion through EKOS catheters (Boston Scientific, Maple Grove, MN, USA). Effervescent bubble activity (cavitation) was nucleated and sustained by DEFINITY® or fibrin-targeted, PGN-loaded echogenic liposomes infused and insonified with EKOS catheters. Though the EKOS catheter was not designed specifically for cavitation nucleation, infusion of echo contrast agents can be employed to trigger and sustain bubble activity for enhanced intravascular drug delivery. Other applications of ultrasound-enhanced drug delivery using the EKOS catheter include sonothrombolysis. Mechanisms for ultrasound enhancement of drug delivery, with a special emphasis on acoustic cavitation, will be reviewed. Further preclinical and clinical studies are needed to correlate the amount and type of cavitation with drug penetration into vascular tissue or thrombi with therapeutic effect.