Pulmonary Artery Denervation for Pulmonary Arterial Hypertension: A Sham-Controlled Randomized PADN-CFDA Trial

Hang Zhang; Yongyue Wei; Caojin Zhang; Zhenwen Yang; Jing Kan; Heping Gu; Fenling Fan; Hong Gu; Qiguang Wang; Dujiang Xie; Gangcheng Zhang; Xiaomei Guo; Yuehui Yin; Bowen Jin; Hongmei Zhou; Ziyang Yang; Zhouming Wang; Yu Xin; Chen Zhang; Lili Meng; Xiaoyu Wang; Jingping Sun; Chunxia Zhao; Juan Zhang; Xiaoyan Yan; Feng Chen; Cheng Yao; Gregg W Stone; Shao-Liang Chen

doi:10.1016/j.jcin.2022.09.013

Pulmonary Artery Denervation for Pulmonary Arterial Hypertension: A Sham-Controlled Randomized PADN-CFDA Trial

JACC Cardiovasc Interv. 2022 Dec 12;15(23):2412-2423. doi: 10.1016/j.jcin.2022.09.013. Epub 2022 Sep 18.

Authors

Hang Zhang¹, Yongyue Wei², Caojin Zhang³, Zhenwen Yang⁴, Jing Kan¹, Heping Gu⁵, Fenling Fan⁶, Hong Gu⁷, Qiguang Wang⁸, Dujiang Xie¹, Gangcheng Zhang⁹, Xiaomei Guo¹⁰, Yuehui Yin¹¹, Bowen Jin¹², Hongmei Zhou¹², Ziyang Yang³, Zhouming Wang⁴, Yu Xin⁵, Chen Zhang⁷, Lili Meng⁸, Xiaoyu Wang⁶, Jingping Sun¹³, Chunxia Zhao¹⁰, Juan Zhang¹³, Xiaoyan Yan¹⁴, Feng Chen², Cheng Yao¹⁴, Gregg W Stone¹⁵, Shao-Liang Chen¹⁶

Affiliations

¹ Division of Cardiology, Nanjing First Hospital of Nanjing Medical University, Nanjing, China.
² School of Public Health, Nanjing Medical University, Nanjing, China.
³ Division of Cardiology, Guangdong Provincial People's Hospital, Guangzhou, China.
⁴ Division of Pulmonary Vascular Disease, General Hospital of Tianjin Medical University, Tianjin, China.
⁵ Division of Cardiology, First Hospital of Zhengzhou University, Zhengzhou, China.
⁶ Division of Pulmonary Vascular Disease, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
⁷ Division of Congenital Heart Disease, Beijing Anzhen Hospital of Capital Medical University, Beijing, China.
⁸ Division of Pulmonary Vascular Disease, General Hospital of Northern Theater of Command, Shenyang, China.
⁹ Division of Pulmonary Vascular Disease, Zhongnan Hospital of Wuhan University, Wuhan, China.
¹⁰ Division of Cardiology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
¹¹ Division of Cardiology, Second Hospital of Chongqing Medical University, Chongqing, China.
¹² Division of Pulmonary Vascular Disease, Wuhan Asia Heart Hospital, Wuhan, China.
¹³ Cardiac Imaging Center of Nanjing Medical University, Nanjing, China.
¹⁴ Peking University Clinical Research Institute, Beijing, China.
¹⁵ The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
¹⁶ Division of Cardiology, Nanjing First Hospital of Nanjing Medical University, Nanjing, China. Electronic address: chmengx@126.com.

PMID: 36121246
DOI: 10.1016/j.jcin.2022.09.013

Abstract

Background: World Health Organization (WHO) group 1 pulmonary arterial hypertension (PAH) is a progressive, debilitating disease. Previous observational studies have demonstrated that pulmonary artery denervation (PADN) reduces pulmonary artery pressures in PAH. However, the safety and effectiveness of PADN have not been established in a randomized trial.

Objectives: The aim of this study was to determine the treatment effects of PADN in patients with group 1 PAH.

Methods: Patients with WHO group 1 PAH not taking PAH-specific drugs for at least 30 days were enrolled in a multicenter, sham-controlled, single-blind, randomized trial. Patients were assigned to receive PADN plus a phosphodiesterase-5 inhibitor or a sham procedure plus a phosphodiesterase-5 inhibitor. The primary endpoint was the between-group difference in the change in 6-minute walk distance from baseline to 6 months.

Results: Among 128 randomized patients, those treated with PADN compared with sham had a greater improvement in 6-minute walk distance from baseline to 6 months (mean adjusted between-group difference 33.8 m; 95% CI: 16.7-50.9 m; P < 0.001). From baseline to 6 months, pulmonary vascular resistance was reduced by -3.0 ± 0.3 WU after PADN and -1.9 ± 0.3 WU after sham (adjusted difference -1.4; 95% CI: -2.6 to -0.2). PADN also improved right ventricular function, reduced tricuspid regurgitation, and decreased N-terminal pro-brain natriuretic peptide. Clinical worsening was less (1.6% vs 13.8%; OR: 0.11; 95% CI: 0.01-0.87), and a satisfactory clinical response was greater (57.1% vs 32.3%; OR: 2.79; 95% CI: 1.37-5.82) with PADN treatment during 6-month follow-up.

Conclusions: In patients with WHO group 1 PAH, PADN improved exercise capacity, hemodynamic status, and clinical outcomes during 6-month follow-up. (Safety and Efficacy of Pulmonary Artery Denervation in Patients With Pulmonary Arterial Hypertension [PADN-CFDA]; NCT03282266).

Keywords: 6-minute walk distance; pulmonary arterial hypertension; pulmonary artery denervation; pulmonary artery pressure; pulmonary vascular resistance.

Publication types

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

MeSH terms

Denervation*
Humans
Phosphodiesterase 5 Inhibitors* / therapeutic use
Pulmonary Arterial Hypertension* / diagnosis
Pulmonary Arterial Hypertension* / drug therapy
Pulmonary Arterial Hypertension* / surgery
Pulmonary Artery
Single-Blind Method
Treatment Outcome

Substances

Phosphodiesterase 5 Inhibitors

Associated data

ClinicalTrials.gov/NCT03282266