IF03 - First-in-human study of non-invasive, robot-assisted high intensity focused ultrasound treatment of femoral atherosclerosis: a safety and feasibility study

Objectives: Open or endovascular revascularization options currently available for peripheral arterial disease (PAD) have limited long-term patency rates and a relatively high risk of perioperative wound healing complications. Robot-assisted high-intensity focused ultrasound (HIFU) enables precise targeting of atherosclerotic plaques, creating thermal lesions with submillimetre resolution. As a non-invasive alternative, HIFU may be associated with fewer perioperative risks. Preclinical studies in healthy and atherosclerotic animals have demonstrated the safety of HIFU treatment. This first-in-human study aims to investigate the safety and feasibility of HIFU therapy for PAD.

Methods: This first-in-human, non-randomized pilot study included symptomatic PAD patients (Fontaine 2B or 3) with a primary stenosis of the common femoral and/or proximal superficial femoral artery. Lesions with a calcified volume >80% or localized at a depth of >35 millimetres from the skin were excluded. Included patients were treated under sedation with a dual-mode ultrasound array (DMUA) system connected to a robotic arm to precisely deliver imaging-guided HIFU to the atherosclerotic plaque. Primary outcomes were the major complication rate, defined as the composite of any complication requiring reintervention, amputation, or mortality and adjudicated by two independent medical monitors, and technical feasibility, defined as successful targeting of the complete lesion. Secondary outcomes included clinical endpoints, such as the ankle-brachial index, and imaging parameters.

Results: Between June 2019 and April 2024, 232 limbs in 205 patients were screened. 12 patients with unilateral lesions underwent HIFU treatment by the same team. Mean treatment time was 113 ± 28.2 minutes and technical success was achieved in all patients. No major complications occurred within 30 days postprocedural, or during the 3-month study follow-up.
Throughout a median clinical follow-up of 19.8 months (IQR 6.9-48.9 months), one patient underwent endovascular target lesion reintervention (TLR), while the other patients remained free from TLR. Eight patients (66.7%) underwent additional ipsilateral imaging after the study follow-up, after a median 25.9 months (IQR 10.9-39.7). Of these, four (50%) no longer had significant (>50%) stenosis of the target artery, as judged by independent radiologists.

Conclusions: DMUA/HIFU therapy appears safe and feasible for the treatment of peripheral arterial disease localized in the femoral artery.