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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 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 The Regulation of Pulmonary Vascular Tone by Neuropeptides and the Implications for Pulmonary Hypertension 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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