Interventions for hypertension and stroke

Pulmonary artery denervation using catheter-based ultrasonic energy

EuroIntervention 2019;15:722-730. DOI: 10.4244/EIJ-D-18-01082

Alex Rothman
Alex Rothman1, BM, BCh, PhD; Michael Jonas2, MD; David Castel3, MD; Abraham Rami Tzafriri4, PhD; Hannes Traxler5, DM; Dalit Shav6, MD; Martin B. Leon7, PhD; Ori Ben-Yehuda8, MD; Lewis Rubin9, MD
1. Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom; 2. Department of Cardiology, Kaplan Medical Center, Hebrew University School of Medicine, Rehovot, Israel; 3. Neufeld Cardiac Research Institute, Sheba Medical Center, Tel Hashomer, Israel; 4. CBSET Inc, Lexington, MA, USA; 5. Center of Anatomy and Cell Biology, Medical University Vienna, Vienna, Austria; 6. SoniVie, Rosh Haayin, Israel; 7. Columbia University Medical Center, NY, USA; 8. Cardiovascular Research Foundation, NY, USA; 9. University of California, San Diego, CA, USA

Aims: Pulmonary arterial hypertension is a devastating disease characterised by pulmonary vascular remodelling and right heart failure. Radio-frequency pulmonary artery denervation (PDN) has improved pulmonary haemodynamics in preclinical and early clinical studies; however, denervation depth is limited. High-frequency non-focused ultrasound can deliver energy to the vessel adventitia, sparing the intima and media. We therefore aimed to investigate the feasibility, safety and efficacy of ultrasound PDN.

Methods and results: Histological examination demonstrated that innervation of human pulmonary arteries is predominantly sympathetic (71%), with >40% of nerves at a depth of >4 mm. Finite element analysis of ultrasound energy distribution and ex vivo studies demonstrated generation of temperatures >47ºC to a depth of 10 mm. In domestic swine, PDN reduced mean pulmonary artery pressure induced by thromboxane A2 in comparison to sham. No adverse events were observed up to 95 days. Histological examination identified structural and immunohistological changes of nerves in PDN-treated animals, with sparing of the intima and media and reduced tyrosine hydroxylase staining 95 days post procedure, indicating persistent alteration of the structure of sympathetic nerves.

Conclusions: Ultrasound PDN is safe and effective in the preclinical setting, with energy delivery to a depth that would permit targeting sympathetic nerves in humans.

Sign in to read and download the full article

Forgot your password?

No account yet?
Sign up for free!

Create my pcr account

Join us for free and access thousands of articles from EuroIntervention, as well as presentations, videos, cases from

innovationpreclinical researchpulmonary hypertension
Interventions for heart failureInterventions for hypertensionAcute heart failureChronic heart failureOther hypertensionOther
Read next article
Impella device use in high-risk PCI

Latest news