{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T04:58:10Z","timestamp":1777697890531,"version":"3.51.4"},"reference-count":33,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T00:00:00Z","timestamp":1722988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cardiawave, Levallois-Perret, France","award":["829492"],"award-info":[{"award-number":["829492"]}]},{"name":"Cardiawave, Levallois-Perret, France","award":["ANR-16-RHUS-0003_STOP-AS"],"award-info":[{"award-number":["ANR-16-RHUS-0003_STOP-AS"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation program","award":["829492"],"award-info":[{"award-number":["829492"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation program","award":["ANR-16-RHUS-0003_STOP-AS"],"award-info":[{"award-number":["ANR-16-RHUS-0003_STOP-AS"]}]},{"name":"National Research Agency (ANR)","award":["829492"],"award-info":[{"award-number":["829492"]}]},{"name":"National Research Agency (ANR)","award":["ANR-16-RHUS-0003_STOP-AS"],"award-info":[{"award-number":["ANR-16-RHUS-0003_STOP-AS"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Transcatheter aortic valve replacement (TAVR) was developed for inoperable patients with severe aortic stenosis. However, despite TAVR advancements, some patients remain untreated due to complex comorbidities, necessitating less-invasive approaches. Non-invasive ultrasound therapy (NIUT), a new treatment modality, has the potential to address this treatment gap, delivering short ultrasound pulses that create cavitation bubble clouds, aimed at softening embedded calcification in stiffened valve tissue. Methods: In the prospective Valvosoft\u00ae Serbian first-in-human study, we assessed the safety and efficacy of NIUT and its impact on aortic valve hemodynamics, on the left ventricle, and on systemic inflammation in patients with severe symptomatic aortic stenosis not eligible for TAVR or surgery. Results: Ten patients were included. Significant improvements were observed in hemodynamic parameters from baseline to one month, including a 39% increase in the aortic valve area (from 0.5 cm2 to 0.7 cm2, p = 0.001) and a 23% decrease in the mean transvalvular gradient (from 54 mmHg to 38 mmHg, p = 0.01). Additionally, left ventricular global longitudinal strain significantly rose, while global wasted work significantly declined at one month. A dose\u2013response relationship was observed between treatment parameters (peak acoustic power, intensity spatial-peak pulse-average, and mean acoustic energy) and hemodynamic outcomes. NIUT was safely applied, with no clinically relevant changes in high-sensitivity troponin T or C-reactive protein and with a numerical, but not statistically significant, reduction in brain natriuretic peptide (from 471 pg\/mL at baseline to 251 pg\/mL at one month). Conclusions: This first-in-human study demonstrates that NIUT is safe and confers statistically significant hemodynamic benefits both on the valve and ventricle.<\/jats:p>","DOI":"10.3390\/jcm13164607","type":"journal-article","created":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T08:42:28Z","timestamp":1723020148000},"page":"4607","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Non-Invasive Ultrasound Therapy for Severe Aortic Stenosis: Early Effects on the Valve, Ventricle, and Cardiac Biomarkers (A Case Series)"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2923-4145","authenticated-orcid":false,"given":"Danijela","family":"Trifunovi\u0107-Zamaklar","sequence":"first","affiliation":[{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"},{"name":"Clinic for Cardiology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Radmila","family":"Karan","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"},{"name":"Department for Anesthesia and Intensive Care at Clinic for Cardiac Surgery, Centre for Anesthesiology and Reanimatology, University Clinical Centre of Serbia, Pasterova 2, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nata\u0161a","family":"Kova\u010devi\u0107-Kosti\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"},{"name":"Department for Anesthesia and Intensive Care at Clinic for Cardiac Surgery, Centre for Anesthesiology and Reanimatology, University Clinical Centre of Serbia, Pasterova 2, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Du\u0161ko","family":"Terzi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"},{"name":"Cardiosurgery Department, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir","family":"Mili\u0107evi\u0107","sequence":"additional","affiliation":[{"name":"Cardiosurgery Department, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6631-6353","authenticated-orcid":false,"given":"Olga","family":"Petrovi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"},{"name":"Clinic for Cardiology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivana","family":"Cani\u0107","sequence":"additional","affiliation":[{"name":"Centre for Medical Biochemistry, University Clinical Centre of Serbia, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathieu","family":"Pernot","sequence":"additional","affiliation":[{"name":"Physic for Medicine, Inserm, ESPCI, CRNS, PSL Research University, 75015 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mickael","family":"Tanter","sequence":"additional","affiliation":[{"name":"Physic for Medicine, Inserm, ESPCI, CRNS, PSL Research University, 75015 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise Z.","family":"Wang","sequence":"additional","affiliation":[{"name":"Cardiovascular Department, H\u00f4pital Europ\u00e9en Georges-Pompidou, Universit\u00e9 Paris-Cit\u00e9, 75015 Paris, France"},{"name":"RHU STOP-AS Research Consortium, 76031 Rouen, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillaume","family":"Goudot","sequence":"additional","affiliation":[{"name":"Cardiovascular Department, H\u00f4pital Europ\u00e9en Georges-Pompidou, Universit\u00e9 Paris-Cit\u00e9, 75015 Paris, France"},{"name":"RHU STOP-AS Research Consortium, 76031 Rouen, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milo\u0161","family":"Velinovi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"},{"name":"Cardiosurgery Department, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuel","family":"Messas","sequence":"additional","affiliation":[{"name":"Cardiovascular Department, H\u00f4pital Europ\u00e9en Georges-Pompidou, Universit\u00e9 Paris-Cit\u00e9, 75015 Paris, France"},{"name":"RHU STOP-AS Research Consortium, 76031 Rouen, France"},{"name":"Paris Cardiovascular Research Center, INSERM UMR U970, 75015 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e1126","DOI":"10.4244\/EIJ-E-21-00009","article-title":"2021 ESC\/EACTS Guidelines for the management of valvular heart disease","volume":"17","author":"Vahanian","year":"2022","journal-title":"EuroIntervention"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1056\/NEJMoa1008232","article-title":"Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery","volume":"363","author":"Leon","year":"2010","journal-title":"N. 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