Study: Non-invasive Ultrasound Therapy Improves Cardiac Valve Function

Cardiawave SA is sharing First-In-Human (FIH) study results on the efficacy of its Non-Invasive focused Ultrasound Therapy (NIUT) device for treating calcific aortic stenosis (CAS).

The company also said it has completed enrollment in its “Valvosoft pivotal study,” signing up 60 patients.
 
These clinical studies’ series, titled “Prospective, controlled, single-arm clinical investigation for the treatment of subjects with severe symptomatic aortic valve stenosis using Valvosoft Pulsed Cavitational Ultrasound Therapy (PCUT) – First-In-Man” (Coordinating Investigator: Prof. Emmanuel Messas, M.D., Ph.D., cardiologist at Hôpital Georges Pompidou AP-HP in Paris, France) enrolled 40 patients with severe symptomatic aortic valve stenosis at three clinical sites in France (Hôpital Européen Georges Pompidou, AP-HP, Paris), the Netherlands (Amphia Hospital, Breda), and Serbia (University Clinical Center of Serbia, Belgrade). The patients were treated with Cardiawave’s NIUT investigational device in one session. Follow-ups were scheduled at one, three, six, 12, and 24 months. 
 
The primary endpoints were met with no procedure-related mortality through 30 days and improved valve function. No procedure-related mortality occurred; furthermore, no life-threatening or cerebrovascular events were reported. Improved valve function was confirmed at six months, reflected by a 10% increase in mean aortic valve area and by quality-of-life improvements.
 
The New York Heart Association (NYHA) score improved or stabilized in 96% of patients (n=24), and the mean Kansas City Cardiomyopathy Questionnaire (KCCQ) score improved by 33%.
 
“Results from this FIH series with a cohort of very frail patients suggest that the use of Non-Invasive Ultrasound Therapy is feasible and safe, and efficient with statistically significant improvements of hemodynamic and clinical parameters in high-risk patients with calcific aortic stenosis (CAS).” said Professor Roxana Mehran, M.D., Ph.D., cardiologist at Mount Sinai in New York, N.Y., and member of Cardiawave’s scientific advisory board. “Clinically, the patients experienced a considerable improvement in their clinical status, suggesting a better quality of life. These early findings can represent a change in the paradigm of CAS treatment especially for patients who have no other options. I am encouraged by the momentum of these study results as I anticipate that this therapy potentially brings a new medical breakthrough to many patients suffering from CAS in the world.”
 
In June 2022, following the positive results of its FIH clinical studies, Cardiawave began a pivotal study on severe symptomatic aortic valve stenosis patients in Germany and Netherland who refuse or were not recommended for valve replacement. Last July, Cardiawave successfully completed patient enrolment with no procedure or device-related mortality up to 30 days. The study successfully enrolled 60 patients at 11 clinical sites in France, Germany, and the Netherlands, and marks a significant milestone in Cardiawave’s medical advancements, paving the way for the device’s CE marking.
  
After successfully treating 100 patients at 12 investigational centers in four countries, Cardiawave is preparing a Series B financing round that will enable the company to scale up, access the European market, and launch its clinical developments in the United States as part of the U.S. Food and Drug Administration pre-market approval.

Valvosoft is a non-invasive ultrasound therapy investigational medical device for treating calcific aortic stenosis. The device uses a new and unique non-invasive transthoracic ultrasound technology that delivers shockwaves on the aortic valve through the cavitation phenomenon. Ultrasound softens the tissue, restores leaflet mobility, and enables a wider opening of the valve. It has not yet received any marketing authorization and is intended exclusively for clinical investigations.
 
Calcific aortic stenosis is a degenerative and potentially life-threatening condition caused by calcium buildup that prevents the aortic valve from fully opening. Aortic stenosis (AS) evolves over time, leading to heart failure and increases the risk of sudden death during its final stage (severe and symptomatic stenosis). AS has become a public health issue as the pathology affects between 1.7% and 12.4% of patients older than 75.¹  With age, the aortic valve calcifies, becomes more rigid and narrow, and no longer opens properly leading to poor blood circulation.
 
AS can be mild, moderate, or severe. Two million people are estimated to suffer from severe AS in Europe and the United States, of whom 500,000 annually benefit from Transcatheter Aortic Valve Replacement (TAVR) or open-heart surgery. About 1.5 million patients remain untreated and face a low life expectancy of two to five years. Around 3 million further patients suffer from moderate AS for whom there is no early treatment.
 
Cardiawave has developed NIUT for treating valvular heart diseases, and in particular, CAS, the most prevalent heart valve disease in adults and one of the most common causes of cardiovascular mortality worldwide. Based near Paris, Cardiawave is a member of the national research consortium RHU Stop-AS, and has EN ISO 13485:2016 certification since 2019. Cardiawave employs 30 people and has secured more than €29 milion in funding since its 2014 creation. This project was supported by the Program “Investissements d’Avenir” as part of the World Innovation Competition. It also benefited from state aid managed by the National Research Agency under the references ANR-16-RHUS-0003_STOP-AS and ANR-17-CE19- 0019-03 and the Horizon 2020 SME instruments program of the European Commission (reference no. 829492). Cardiawave is a winner of the French Tech Health 20 programme and a member of La French Care since 2023.

Reference
¹ Durko AP, et al. Annual number of candidates for transcatheter aortic valve implantation per country: current estimates and future projections. European Heart Journal. July 01, 2018; 39(28):2635-2642. (DOI: 10.1093/eurheartj/ehy107); Lindman B, et al. Calcific Aortic Stenosis. Nature Reviews Disease Primers 2, Article number: 16006. March 03, 2016. (DOI: 10.1038/nrdp.2016.6); Osnabrugge R., et al. Aortic Stenosis in the Elderly: Disease Prevalence and Number of Candidates for Transcatheter Aortic Valve Replacement: A Meta-Analysis and Modeling Study. Journal of American College of Cardiology, Volume 62, Issue 11, Pages 1013-1014. September 2013. (DOI: 10.1016/j.jacc.2013.05.015).