Treatment of severe symptomatic aortic valve stenosis using non-invasive ultrasound therapy: a cohort study

Emmanuel Messas; Alexander Ijsselmuiden; Danijela Trifunović-Zamaklar; Bernard Cholley; Etienne Puymirat; Jonathan Halim; Radmila Karan; Menno van Gameren; Duško Terzić; Vladimir Milićević; Mickael Tanter; Mathieu Pernot; Guillaume Goudot

doi:10.1016/S0140-6736(23)01518-0

Treatment of severe symptomatic aortic valve stenosis using non-invasive ultrasound therapy: a cohort study

Lancet. 2023 Dec 16;402(10419):2317-2325. doi: 10.1016/S0140-6736(23)01518-0. Epub 2023 Nov 14.

Affiliations

¹ Cardiovascular Department, Hôpital Européen Georges-Pompidou, Université Paris-Cité, Paris, France; Paris Cardiovascular Research Center, Inserm UMR_U970, Université Paris-Cité, Paris, France; STOP-AS Research Consortium, Recherche Hospitalo-Universitaire, Rouen, France. Electronic address: emmanuel.messas@aphp.fr.
² Cardiology Department, Amphia Hospital, Breda, Netherlands.
³ Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Clinic for Cardiology, University Clinical Centre of Serbia, Belgrade, Serbia.
⁴ Department of Anaesthesiology and Intensive Care Medicine, Hôpital Européen Georges-Pompidou, Université Paris-Cité, Paris, France; Innovative Therapies in Haemostasis, Inserm UMR_S1140, Université Paris-Cité, Paris, France.
⁵ Cardiovascular Department, Hôpital Européen Georges-Pompidou, Université Paris-Cité, Paris, France; Paris Cardiovascular Research Center, Inserm UMR_U970, Université Paris-Cité, Paris, France.
⁶ Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Department of Anaesthesiology and Intensive Care at Clinic for Cardiac Surgery, University Clinical Centre of Serbia, Belgrade, Serbia.
⁷ Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Clinic for Cardiac Surgery, University Clinical Centre of Serbia, Belgrade, Serbia.
⁸ Clinic for Cardiac Surgery, University Clinical Centre of Serbia, Belgrade, Serbia.
⁹ Physics for Medicine Paris, Inserm/ESPCI Paris-PSL/CRNS, Paris, France.
¹⁰ Cardiovascular Department, Hôpital Européen Georges-Pompidou, Université Paris-Cité, Paris, France.

PMID: 37972628
DOI: 10.1016/S0140-6736(23)01518-0

Abstract

Background: Calcific aortic stenosis is commonly treated using surgical or transcatheter aortic valve replacement; however, many patients are not considered suitable candidates for these interventions due to severe comorbidities and limited life expectancy. As such, non-invasive therapies might offer alternative therapeutic possibilities in these patients. This study aimed to assess the safety of non-invasive ultrasound therapy and its ability to improve valvular function by softening calcified valve tissue.

Methods: This prospective, multicentre, single-arm series enrolled 40 adult patients with severe symptomatic aortic valve stenosis at three hospitals in France, the Netherlands, and Serbia between March 13, 2019, and May 8, 2022. Patients were treated with transthoracically delivered non-invasive ultrasound therapy. Follow-ups were scheduled at 1, 3, 6, 12, and 24 months. The primary endpoints were procedure-related deaths within 30 days and improved valve function. We report the 6-month data. This study is registered at ClinicalTrials.gov, NCT03779620 and NCT04665596.

Findings: 40 high-risk patients with a mean Society of Thoracic Surgeons score of 5·6% (SD 4·4) and multiple severe comorbidities were included. The primary endpoint, procedure-related mortality, did not occur; furthermore, no life-threatening or cerebrovascular events were reported. Improved valve function was confirmed up to 6 months, reflected by a 10% increase in mean aortic valve area from 0·58 cm² (SD 0·19) at baseline to 0·64 cm² (0·21) at follow-up (p=0·0088), and a 7% decrease in mean pressure gradient from 41·9 mm Hg (20·1) to 38·8 mm Hg (17·8; p=0·024). At 6 months, the New York Heart Association score had improved or stabilised in 24 (96%) of 25 patients, and the mean Kansas City Cardiomyopathy Questionnaire score had improved by 33%, from 48·5 (SD 22·6) to 64·5 (21·0). One serious procedure-related adverse event occurred in a patient who presented with a transient decrease in peripheral oxygen saturation. Non-serious adverse events included pain, discomfort during treatment, and transient arrhythmias.

Interpretation: This novel, non-invasive ultrasound therapy for calcified aortic stenosis proved to be safe and feasible.

Funding: Cardiawave.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Aortic Valve / diagnostic imaging
Aortic Valve / surgery
Aortic Valve Stenosis* / diagnostic imaging
Aortic Valve Stenosis* / surgery
Cohort Studies
Heart Valve Prosthesis*
Humans
Prospective Studies
Risk Factors
Severity of Illness Index
Transcatheter Aortic Valve Replacement* / adverse effects
Treatment Outcome
Ultrasonic Therapy*

Supplementary concepts

Aortic Valve, Calcification of

Associated data

ClinicalTrials.gov/NCT03779620
ClinicalTrials.gov/NCT04665596