Treatment effects of pulmonary artery denervation for pulmonary arterial hypertension stratified by REVEAL risk score: Results from PADN-CFDA trial

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Background

The differential treatment effect of pulmonary artery denervation (PADN) in pulmonary arterial hypertension (PAH) patients with different risk burdens remains unclear. This study aimed to determine the effectiveness of PADN in low vs intermediate-high-risk PAH patients.

Methods

In total, 128 patients with treatment naive PAH included in the PADN-CFDA trial were categorized into low-risk and intermediate-high-risk patients. The primary endpoint was the between-group difference in the change in 6-min walk distance (6 MWD) from baseline to 6 months.

Results

In the intermediate-high-risk group, those treated with PADN and PDE-5i had a greater improvement in 6 MWD from baseline to 6 months as compared to those treated with sham plus PDE-5i. From baseline to 6 months, pulmonary vascular resistance (PVR) was reduced by –6.1 ± 0.6 and –2.0 ± 0.7 Wood units following PADN plus PDE-5i and sham plus PDE-5i, respectively, along with the significant reduction of NT-proBNP in the intermediate-high-risk group. However, there were no significant differences in 6 MWD, PVR, and NT-proBNP between the PADN plus PDE-5i and sham plus PDE-5i groups among low-risk patients. Moreover, the right ventricular function was equally improved by PADN treatment across the low-, intermediate-, and high-risk groups. Clinical worsening was less with PADN plus PDE-5i treatment during the 6-month follow-up.

Conclusions

In patients with pulmonary arterial hypertension, pulmonary artery denervation plus PDE-5i improved exercise capacity, NT-proBNP, hemodynamic, and clinical outcomes during the 6-month follow-up among intermediate-high risk patients.

Section snippets

Study design and patient population

Patients eligible for PADN plus PDE-5i or sham PADN plus PDE-5i were randomized in a 1:1 ratio following right heart catheterization (RHC).16 Sample size calculation, randomization, and masking have been described previously.16 The study protocol was approved by the ethics committee of each participating site, and all patients or their legal representatives signed an informed consent form before enrolling in the trial. In addition, this study was registered at ClinicalTrials.gov (under the

Results

Among 128 PAH patients randomly assigned to PADN plus PDE-5i (n=63) or a sham procedure plus PDE-5i (n=65), 57 (44.5%) patients were at low risk and 71 (55.5%) were in the intermediate or high-risk groups (Supplemental Table 1 and Supplemental Figure 1). Patients in the intermediate- or high-risk group were generally characterized by 1) lower SBP, 2) frequent functional class III or IV, 3) common idiopathic PAH, 4) less 6 MWD, and 5) higher plasma concentration of NT-proBNP before

Discussion

PAH is an incurable chronic disease with high mortality resulting from progressive pulmonary arterial remodeling and subsequent RHF.17 The goal of PAH treatment is to achieve a low-risk status. Consequently, robust risk stratification is a key tool for guiding the treatment approach and predicting 1-year mortality.3, 4, 5, 6, 7, 8, 9, 10 One of these assessment tools, REVEAL Lite 2.010 involves six non-invasive parameters and is in good agreement with its previous versions. In this analysis

Authors contribution

Study design (Shao-Liang Chen, Gregg W. Stone, Xiaoyan Yan, Cheng Yao); patient enrollment (Juan Zhang, Caojin Zhang, Zhenwen Yang, Heping Gu, Fenling Fan, Hong Gu, Qiguang Wang, Dujiang Xie, Gangcheng Zhang, Xiaomei Guo, Yuehui Yin, Bowen Jin, Hongmei Zhou, Ziyang Yang, Zhouming Wang, Chen Zhang, Lili Meng, Xiaoyu Wang, Chunxia Zhao, Hang Zhang, Yu Xin); coordinator (Jing Kan); independent statisticians (Yongyue Wei, Feng Chen).

Disclosure statement

This trial was granted by the National Scientific Foundation of China (grant numbers: NSFC 91639303, NSFC 81770441, and NSFC 82121001). Nanjing First Hospital funded this trial, and Pulnovo provided all PADN catheters throughout the study period.

Dr. Stone has received speaker honoraria from Medtronic, Pulnovo, and Infraredx and has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow,

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