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Pulmonary Artery Denervation Using Catheter based Ultrasonic Energy Japan-United States of America Harmonized Assessment by Randomized Multicentre Study of OrbusNEich's Combo StEnt (Japan-USA HARMONEE) study: primary results of the pivotal registration study of combined endothelial progenitor cell capture and drug-eluting stent in patients with ischaemic coronary disease and non-ST-elevation acute coronary syndrome Systematic Review and Network Meta‐Analysis Comparing Bifurcation Techniques for Percutaneous Coronary Intervention Comparison of drug-eluting stents and drug-coated balloon for the treatment of drug-eluting coronary stent restenosis: A randomized RESTORE trial The Regulation of Pulmonary Vascular Tone by Neuropeptides and the Implications for Pulmonary Hypertension Ticagrelor With or Without Aspirin in High-Risk Patients With Diabetes Mellitus Undergoing Percutaneous Coronary Intervention Validation of bifurcation DEFINITION criteria and comparison of stenting strategies in true left main bifurcation lesions Meta-Analysis of Death and Myocardial Infarction in the DEFINE-FLAIR and iFR-SWEDEHEART Trials
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Original Research2019 May 7. pii: EIJ-D-18-01082.

JOURNAL：EuroIntervention. Article Link

Pulmonary Artery Denervation Using Catheter based Ultrasonic Energy

Rothman A, Jonas M, Castel D et al. Keywords: pulmonary artery denervation; pulmonary hypertension

ABSTRACT

AIMS -  Pulmonary arterial hypertension is a devastating disease characterized by pulmonary vascular remodelling and right heart failure. Radio-frequency pulmonary artery denervation (PDN) improves pulmonary hemodynamics in pre-clinical 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 investigated the feasibility, safety and efficacy of ultrasound PDN.

 

METHODS AND RESULTS -  Histological examination demonstrated that innervation of human pulmonary arteries are predominantly sympathetic (71%), with >40% of nerves at a depth of >4mm. Finite element analysis of ultrasound energy distribution and ex-vivo studies demonstrated generation of temperatures >47ºC to a depth of 10mm. In domestic swine PDN reduced mean pulmonary artery pressure induced by thromboxane A2 in comparison to sham. No adverse events were observed to 95-days. Histological examination identified structural and immunohistological alterations 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 pre-clinical setting, with energy delivery to a depth that will permit targeting sympathetic nerves in humans.

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