Safety and quality of life assessment at 6 months follow-up of the valvosoft pivotal study

Abstract Background Calcific Aortic stenosis (CAS) is currently the most common heart valve disease. Patients suffering from severe CAS are treated with invasive surgeries based on valve replacement. Symptoms heavily impact quality of life, including chest pain, shortness of breath, dizziness, fatigue, and major risks as heart failure or sudden death, and daily activities might also be strongly impacted. Purpose A prospective, multi-centre, single-arm, pivotal study (NCT05235568) was initiated in 2021 to treat severe CAS patients with Valvosoft, a medical device based on Non-Invasive Ultrasound Therapy (NIUT) intended to treat CAS in patients not eligible for immediate aortic valve replacement (SAVR/TAVR) or refusing such a treatment, to confirm safety and performance at 1-, 3-, 6- and 12 months. We present here the safety and quality of life results at 6M follow-up. Methods Valvosoft NIUT procedure is based on a trans-thoracic delivery of focused, high intensity short therapeutic ultrasound pulses, to precisely generate a cavitation bubble cloud on the aortic valve. Echocardiographic imaging enables to monitor the valve in real-time while cavitation causes both non-thermal tissue softening and calcification fractionation of the diseased valve. 60 planned subjects, suffering from severe calcific aortic stenosis, not recommended for aortic valve replacement or refusing such a procedure, were enrolled in 11 centres in Europe. Patients were awake or lightly sedated, NIUT was delivered during up to 70 minutes per patient per procedure. DSMB and CEC were installed to monitor safety, performance and effectiveness of Valvosoft device, and safety related to participation in the clinical investigation. Results Sixty high-risk patients advanced in age (85.2 ± 9.1) with multiple severe comorbidities were included. Primary safety endpoint (less than 25% MACE) was met at 30D (p=0.002). Furthermore patients experienced an overall quality of life improved. 6 minutes’ walk test increases from baseline towards 6 months with 10 %. At 6M follow-up, no stroke was reported, an average KCCQ score improvement of 17% was noticed, and NYHA class improved or stabilized for 78% of patients. The calcium score or volume on the aortic did not change pre- and post-procedure. Conclusion Valvosoft NIUT safety and quality of life improvement are proven at 6MFU, and the technology is presented as potentially disruptive, in the treatment of severe calcific aortic stenosis.