Treatment

Alex Rothman, PhD, on the Use of Pulmonary Artery Denervation for PAH Treatment

Previous studies have shown that pulmonary artery denervation (PDN) may reduce pulmonary vascular resistance (PVR) among patients with pulmonary artery hypertension (PAH). Now, results of the Treatment of Pulmonary Hypertension 1 (TROPHY1) early feasibility study1 appear to further support this efficacy.

According to the TROPHY1 findings, PDN with an intravascular ultrasound catheter was associated with a reduction in PVR, as well as with increases in 6-minute walk distance and daily activity among patients with PAH receiving background dual oral or triple therapy. PDN had also been performed without procedure-related adverse events.

Alex Rothman, BM BCh, PhD, a Wellcome Trust Clinical Research Career Development fellow and honorary consultant cardiologist at Sheffield Teaching Hospitals NHS Trust in the United Kingdom, was the study’s lead author. Pulmonology Consultant asked him about the TROPHY1 findings and the future of intravascular ultrasound PDN.

PULMONOLOGY CONSULTANT: How does PDN, and specifically a therapeutic intravascular ultrasonic system, fit into and reflect the current PAH management landscape?

Alex Rothman: The TROPHY study demonstrated early feasibility and safety of ultrasound PDN in patients with PAH established on best medical therapy. Following the procedure, there were improvements in hemodynamics, walk test, and daily activity.

PULM CON: What prompted you to conduct this study? What knowledge gaps were you hoping to bridge?

AR: Patients with PAH manifest signs of increase sympathetic nerve activity, and the lungs produce and metabolize approximately 40% of circulating catecholamines. It is unclear whether increased sympathetic activity contributes to disease pathology or is a secondary phenomenon. PDN provided a means to target the nerves supplying the pulmonary vasculature to examine their role in disease pathology and potential therapeutic effect. 

PULM CON: According to your findings, what may be the long-term safety and efficacy of a therapeutic intravascular ultrasonic system among patients with PAH?

AR: The primary endpoint of TROPHY was 4 or 6 months. At this point, PDN had a good safety and efficacy profile. The 12-month data from the study will be released shortly. Further studies are required to examine the long-term safety and efficacy of PDN in patients with all forms of pulmonary hypertension.

Editor’s Note: Early 12-month data2 have been released as an abstract through the American Thoracic Society. According to those results, no serious procedure-related adverse events were reported during the 12 months following PDN; and compared with baseline, mean pulmonary artery pressure was reduced and other indicators of hemodynamic and functional capacity were maintained.

References:

1. Rothman A, Vachiery J-LE, Howard LS, et al. Intravascular ultrasound pulmonary artery denervation to treat pulmonary arterial hypertension (TROPHY1): multicenter, early feasibility study. JACC Cardiovasc Interv. 2020;13(8):989-999. doi:10.1016/j.jcin.2019.12.027

2. Rothman A, Vachiery J-LE, Howard LS, et al. Percutaneous endovascular ultrasound pulmonary artery denervation for the treatment of pulmonary arterial hypertension: 12-month results of the Trophy 1 study. Am J Respir Crit Care Med. 2020;201:A7278. https://www.atsjournals.org/doi/pdf/10.1164/ajrccm-conference.2020.201.1_MeetingAbstracts.A7278.