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Objectives We recently developed a unique transthoracic non-invasive ultrasound therapy device called Valvosoft to treat aortic stenosis. The therapy consists in delivering trans-thoracically precisely focused and controlled short ultrasound pulses (<20μsec) at a high acoustic intensity to produce non-thermal mechanical tissue softening of the calcified aortic valve with the ultimate aim of improving the valve opening. Ultrasound imaging enables to follow valve movements in real-time and thus targets the ultrasound waves on the valve with great precision. After having validated this concept in pre-clinical studies, we aimed at applying this technique in human. The primary objectives were to assess the safety and feasibility of this novel technique along with its performance by evaluation of the valve leaflets mobility and valve opening area. Methods This is a multi-center, prospective, controlled first-in-man study. Ten patients with severe symptomatic calcific aortic stenosis and not eligible for SAVR/TAVR underwent a Valvosoft ultrasound therapy. The therapy consists of 6 sessions of ultrasound therapy. The Valvosoft transducer is applied on the patient's chest and coupled at its center with an echocardiography phased array probe to allow real-time control of the therapy (cavitation bubble detection). Preselection of the region of interest is performed by echo still frame before each session. Ultrasonic evaluation was performed by an independent core lab at baseline, discharge, 30-day and 3 month follow-up along with clinical follow up. Results Enrolled patients were advanced in age (84.1±6.5 yrs) with severe comorbidities (8 with heart failure, 5 with coronary heart disease and 5 with kidney failure). All had extensive aortic valve calcification (mean calcification volume of 687.28 mm3) with mean AVA of 0.61±0.17 cm2 and mean pressure gradient of 37.5±10.5 mmHg (6 patients had SV<35ml/m2). No adverse events were recorded during the procedures other than some benign ventricular extrasystoles. The mean treatment time was 52 minutes. At 3 months follow-up, one patient had died due to end stage heart failure not linked to the procedure (9 weeks post procedure) and another got finally TAVI (45 days post procedure). Of the other 8 patients, 6 experienced an improvement of their NYHA status. No device or procedure related major adverse events nor deterioration of neurological status were observed at 3 months follow-up. Of the 7 patients that had echo follow-up at 3 months (one patient refused to get echo evaluation), 5 increased the AVA (between 14% and 46%) and 4 patients decreased the mean pressure gradient (from 6% to 44%). No AI or EF deterioration occurred during follow up. Conclusion Non-invasive ultrasound therapy is feasible and safe in patients with severe aortic valve stenosis and is able to improve AVA and pressure gradient in some patient. Larger studies with longer follow up will need to be conducted. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Cardiawave SA, Paris, France

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The prognostic value of SYNTAX score (SS), intravascular ultrasound (IVUS)-derived plaque burden (PB) and near-infrared spectroscopy (NIRS)-derived lipid core burden index(LCBI) for identification of high-risk patients for major adverse cardiovascular events (MACE) has been proven in previous studies. The majority of patients presenting in the cathlab however do not endure MACE over time, and identification of low-risk groups has remained underexposed. This study evaluates the combined prognostic value of SS, PB and LCBI in identifying patients with low MACE risk. This post-hoc analysis combines the ATHEROREMO and IBIS-3 studies and included 798 patients undergoing coronary angiography. Anatomical SS was calculated (N = 617) and ≥40mm non-stenotic segment of a non-target vessel was investigated with IVUS (N = 645) and NIRS (N = 273) to determine PB and maximum 4mm LCBI (LCBI4mm). During five-year follow-up, 191 MACE were observed. Patients with PB ≤70%, LCBI4mm ≤227 (median), or SS ≤8 (median) had lower MACE incidence than their counterparts with higher values. Combined into one model, LCBI4mm ≤227 (adjusted hazard ratio [aHR] 0.49, 95% confidence interval [CI] 0.30–0.78; p-value = 0.003) and SS ≤8 (aHR 0.67, 95%CI 0.48–0.96, p-value = 0.027) were independently associated with (lower) MACE rate, but PB was not. Additionally, negative predictive value (NPV) of this model was high (SS<8: 0.80, PB<70%: 0.77, LCBI4mm<227: 0.79). In this cohort, SS and LCBI4mm proved to be independent predictors of MACE-free survival during five-year follow-up. Combination of SS and LCBI4mm is useful to identify a low-risk population. Furthermore, NPV of SS, PB and LCBI4mm for prediction of MACE is high.

Background: Not all patients with severe aortic valve stenosis are eligible for open-heart surgery or TAVR. CARDIAWAVE (Paris, France) has developed Valvosoft, a unique non-invasive ultrasound therapy device to treat aortic stenosis. The therapy aims to improve the opening of severely calcified aortic valves by cracking the calcium and reducing the stiffness in the aortic valve tissue by delivering transthoracically local shock waves on the valve leaflets. This study assesses the safety, feasibility and performance of this novel technique. Methods: This is a multi-center, prospective, first-in-man study designed to evaluate the safety and feasibility of the Valvosoft device. Ten patients with severe symptomatic calcific aortic stenosis and not eligible for SAVR/TAVR underwent a Valvosoft ultrasound therapy. Echocardiographic evaluation was performed by an independent core lab at baseline, discharge, and at 1, 3, 6 and 12 months along with clinical follow up. Results: Enrolled patients were advanced in age (84.1±6.5 yrs) with severe comorbidities (8 with heart failure, 5 with coronary heart disease and 5 with kidney failure). All had extensive aortic valve calcification with mean AVA of 0.61±0.17 cm2 and mean pressure gradient of 37.5±10.5 mmHg. At one-month follow-up, six patients had significantly improved their AVA with increase of 27.5% (p=0.03) and mean pressure gradient decrease of 23.2 % (p=0.025). These patients also received the highest dose and longest treatment duration. During one year follow up, 4 patients died due to progression of end stage heart failure not linked to the procedure and one patient had undergone a TAVR procedure. At 12 months, the five remaining patients has no device or procedure related major adverse events nor deterioration of neurological status. Echo, brain-MRI and clinical follow up will be presented. Conclusions: Non-invasive ultrasound therapy is feasible and safe in patients with severe aortic valve stenosis and can improve AVA and hemodynamic parameters. NIUT can be an important tool complementary to TAVI in treating patients with aortic valve stenosis.