Interventional treatment of pulmonary hypertension: percutaneous pulmonary artery denervation_West China Medical Journal

Authors：

ZHAO Ji , GUO Jiajun ,  CHEN Yucheng

Department of Cardiology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

CHEN Yucheng, Email: chenyucheng2003@126.com

Keywords：

Pulmonary hypertension; percutaneous pulmonary artery denervation; clinical application; combined therpay

DOI：

10.7507/1002-0179.202412287

Video：

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Abstract Full text Figures/Tables Video References Cited by

Pulmonary hypertension (PH), characterized by diverse etiologies and intricate pathological mechanisms, is a complex cardiopulmonary vascular disorder featuring high morbidity and mortality. Percutaneous pulmonary artery denervation (PADN) represents an emerging interventional treatment method, which shows good prospects in the clinical practice of PH. The PADN has attained preliminary achievements in terms of safety and efficacy. Nevertheless, its long-term prognosis, the characteristics of the appropriate patient populations, and the optimization strategies combined with targeted pharmacotherapy remain to be further explored. This article reviews the current clinical applications of PADN as well as the challenges it confronts.

Citation： ZHAO Ji, GUO Jiajun, CHEN Yucheng. Interventional treatment of pulmonary hypertension: percutaneous pulmonary artery denervation. West China Medical Journal, 2025, 40(1): 87-91. doi: 10.7507/1002-0179.202412287 Copy

1.	Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J, 2023, 61(1): 2200879.
2.	中华医学会心血管病学分会. 经皮肺动脉去神经术治疗肺动脉高压的中国专家建议. 中华心血管病杂志, 2024, 52(6): 647-658.
3.	Mocumbi A, Humbert M, Saxena A, et al. Pulmonary hypertension. Nat Rev Dis Primers, 2024, 10(1): 1.
4.	Hoeper MM, Humbert M, Souza R, et al. A global view of pulmonary hypertension. Lancet Respir Med, 2016, 4(4): 306-322.
5.	国家心血管病中心肺动脉高压专科联盟, 国家心血管病专家委员会右心与肺血管病专业委员会. 中国肺动脉高压诊治临床路径. 中国循环杂志, 2023, 38(7): 691-703.
6.	李晓晨, 黄玉臣, 刘先胜. 肺动脉高压的治疗进展. 内科急危重症杂志, 2024, 30(5): 385-390.
7.	Taichman DB, Leopold JA, Elliott G. Continued progress in therapy for pulmonary arterial hypertension. N Engl J Med, 2023, 388(16): 1524-1526.
8.	Hoeper MM, Badesch DB, Ghofrani HA, et al. Phase 3 Trial of sotatercept for treatment of pulmonary arterial hypertension. N Engl J Med, 2023, 388(16): 1478-1490.
9.	Chiu JS, Zuckerman WA, Turner ME, et al. Balloon atrial septostomy in pulmonary arterial hypertension: effect on survival and associated outcomes. J Heart Lung Transplant, 2015, 34(3): 376-380.
10.	Hoeper MM, Pittrow D, Opitz C, et al. Risk assessment in pulmonary arterial hypertension. Eur Respir J, 2018, 51(3): 1702606.
11.	Farber HW, Miller DP, Poms AD, et al. Five-year outcomes of patients enrolled in the REVEAL registry. Chest, 2015, 148(4): 1043-1054.
12.	Zhang J, Kan J, Wei Y, et al. Treatment effects of pulmonary artery denervation for pulmonary arterial hypertension stratified by REVEAL risk score: results from PADN-CFDA trial. J Heart Lung Transplant, 2023, 42(8): 1140-1151.
13.	Rothman AMK, Vachiery JL, 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.
14.	Vaillancourt M, Chia P, Sarji S, et al. Autonomic nervous system involvement in pulmonary arterial hypertension. Respir Res, 2017, 18(1): 201.
15.	Barnes PJ, Liu SF. Regulation of pulmonary vascular tone. Pharmacol Rev, 1995, 47(1): 87-131.
16.	Verity MA, Bevan JA. Fine structural study of the terminal effecror plexus, neuromuscular and intermuscular relationships in the pulmonary artery. J Anat, 1968, 103(Pt 1): 49-63.
17.	Juratsch CE, Jengo JA, Castagna J, et al. Experimental pulmonary hypertension produced by surgical and chemical denervation of the pulmonary vasculature. Chest, 1980, 77(4): 525-530.
18.	Ciarka A, Doan V, Velez-Roa S, et al. Prognostic significance of sympathetic nervous system activation in pulmonary arterial hypertension. Am J Respir Crit Care Med, 2010, 181(11): 1269-1275.
19.	Velez-Roa S, Ciarka A, Najem B, et al. Increased sympathetic nerve activity in pulmonary artery hypertension. Circulation, 2004, 110(10): 1308-1312.
20.	McMahon TJ, Hood JS, Kadowitz PJ. Pulmonary vasodilator response to vagal stimulation is blocked by N omega-nitro-L-arginine methyl ester in the cat. Circ Res, 1992, 70(2): 364-369.
21.	Rey-García J, Townsend RR. Renal denervation: a review. Am J Kidney Dis, 2022, 80(4): 527-535.
22.	Bradford JR. The Innervation of the renal blood vessels. J Physiol, 1889, 10(5): 358-432.18.
23.	Chen SL, Zhang YJ, Zhou L, et al. Percutaneous pulmonary artery denervation completely abolishes experimental pulmonary arterial hypertension in vivo. EuroIntervention, 2013, 9(2): 269-276.
24.	Chen SL, Zhang FF, Xu J, et al. Pulmonary artery denervation to treat pulmonary arterial hypertension: the single-center, prospective, first-in-man PADN-1 study (first-in-man pulmonary artery denervation for treatment of pulmonary artery hypertension). J Am Coll Cardiol, 2013, 62(12): 1092-1100.
25.	Huang Y, Liu YW, Pan HZ, et al. Transthoracic pulmonary artery denervation for pulmonary arterial hypertension. Arterioscler Thromb Vasc Biol, 2019, 39(4): 704-718.
26.	Maas ET, Ostelo RW, Niemisto L, et al. Radiofrequency denervation for chronic low back pain. Cochrane Database Syst Rev, 2015, 2015(10): CD008572.
27.	Chin KJ, Lirk P, Hollmann MW, et al. Mechanisms of action of fascial plane blocks: a narrative review. Reg Anesth Pain Med, 2021, 46(7): 618-628.
28.	Schwartz PJ, Ackerman MJ. Cardiac sympathetic denervation in the prevention of genetically mediated life-threatening ventricular arrhythmias. Eur Heart J, 2022, 43(22): 2096-2102.
29.	Sharp TE 3rd, Lefer DJ. Renal denervation to treat heart failure. Annu Rev Physiol, 2021, 83: 39-58.
30.	Zhang H, Wei Y, Zhang C, et al. Pulmonary artery denervation for pulmonary arterial hypertension: a sham-controlled randomized PADN-CFDA trial. JACC Cardiovasc Interv, 2022, 15(23): 2412-2423.
31.	Kan J, Zhang H, Xie D, et al. A sham-controlled randomised trial of pulmonary artery denervation for group 1 pulmonary arterial hypertension: one-year outcomes of the PADN-CFDA trial. EuroIntervention, 2023, 19(8): 684-694.
32.	Zhang H, Kan J, Zhang C, et al. Long-term mortality after pulmonary artery denervation stratified by baseline functional class in patients with pulmonary arterial hypertension: long-term mortality after PADN stratified by functional class. AsiaIntervention, 2022, 8(1): 58-68.
33.	Zhang H, Zhang J, Chen M, et al. Pulmonary artery denervation significantly increases 6-min walk distance for patients with combined pre- and post-capillary pulmonary hypertension associated with left heart failure: the PADN-5 study. JACC Cardiovasc Interv, 2019, 12(3): 274-284.
34.	Romanov A, Cherniavskiy A, Novikova N, et al. Pulmonary artery denervation for patients with residual pulmonary hypertension after pulmonary endarterectomy. J Am Coll Cardiol, 2020, 76(8): 916-926.
35.	Zhang H, Kan J, Zhang J, et al. 3-year outcome in patients with combined precapillary and postcapillary pulmonary hypertension: results from PADN-5 trial. JACC Heart Fail, 2023, 11(8 Pt 2): 1135-1146.
36.	Chernyavskiy AM, Edemskiy AG, Novikova NV, et al. Radiofrequency pulmonary artery ablation for treatment of residual pulmonary hypertension after pulmonary endarterectomy. Kardiologiia, 2018, 58(4): 15-21.
37.	Gradient Denervation Technologies. Pulmonary artery denervation clinical study using the Gradient Denervation System in heart failure patients with pulmonary hypertension group 2 (PreVail-PH2 OUS Study). Gradient Denervation Technologies, 2024.
38.	Pulnovo Medical (Wuxi) Co. , Ltd. A trial to evaluate the safety and efficacy of pulmonary artery denervation for the treatment of pulmonary hypertension associated with left heart failure (PADN-HF-PH). Pulnovo Medical (Wuxi) Co. , Ltd, 2024.
39.	侯池, 温冬梅, 王健. 肺动脉高压神经调控机制研究进展. 中华结核和呼吸杂志, 2023, 46(9): 936-940.
40.	Nanjing Medical University. Pulmonary artery denervation for HF without PH. Nanjing Medical University, 2024.

1. Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J, 2023, 61(1): 2200879.
2. 中华医学会心血管病学分会. 经皮肺动脉去神经术治疗肺动脉高压的中国专家建议. 中华心血管病杂志, 2024, 52(6): 647-658.
3. Mocumbi A, Humbert M, Saxena A, et al. Pulmonary hypertension. Nat Rev Dis Primers, 2024, 10(1): 1.
4. Hoeper MM, Humbert M, Souza R, et al. A global view of pulmonary hypertension. Lancet Respir Med, 2016, 4(4): 306-322.
5. 国家心血管病中心肺动脉高压专科联盟, 国家心血管病专家委员会右心与肺血管病专业委员会. 中国肺动脉高压诊治临床路径. 中国循环杂志, 2023, 38(7): 691-703.
6. 李晓晨, 黄玉臣, 刘先胜. 肺动脉高压的治疗进展. 内科急危重症杂志, 2024, 30(5): 385-390.
7. Taichman DB, Leopold JA, Elliott G. Continued progress in therapy for pulmonary arterial hypertension. N Engl J Med, 2023, 388(16): 1524-1526.
8. Hoeper MM, Badesch DB, Ghofrani HA, et al. Phase 3 Trial of sotatercept for treatment of pulmonary arterial hypertension. N Engl J Med, 2023, 388(16): 1478-1490.
9. Chiu JS, Zuckerman WA, Turner ME, et al. Balloon atrial septostomy in pulmonary arterial hypertension: effect on survival and associated outcomes. J Heart Lung Transplant, 2015, 34(3): 376-380.
10. Hoeper MM, Pittrow D, Opitz C, et al. Risk assessment in pulmonary arterial hypertension. Eur Respir J, 2018, 51(3): 1702606.
11. Farber HW, Miller DP, Poms AD, et al. Five-year outcomes of patients enrolled in the REVEAL registry. Chest, 2015, 148(4): 1043-1054.
12. Zhang J, Kan J, Wei Y, et al. Treatment effects of pulmonary artery denervation for pulmonary arterial hypertension stratified by REVEAL risk score: results from PADN-CFDA trial. J Heart Lung Transplant, 2023, 42(8): 1140-1151.
13. Rothman AMK, Vachiery JL, 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.
14. Vaillancourt M, Chia P, Sarji S, et al. Autonomic nervous system involvement in pulmonary arterial hypertension. Respir Res, 2017, 18(1): 201.
15. Barnes PJ, Liu SF. Regulation of pulmonary vascular tone. Pharmacol Rev, 1995, 47(1): 87-131.
16. Verity MA, Bevan JA. Fine structural study of the terminal effecror plexus, neuromuscular and intermuscular relationships in the pulmonary artery. J Anat, 1968, 103(Pt 1): 49-63.
17. Juratsch CE, Jengo JA, Castagna J, et al. Experimental pulmonary hypertension produced by surgical and chemical denervation of the pulmonary vasculature. Chest, 1980, 77(4): 525-530.
18. Ciarka A, Doan V, Velez-Roa S, et al. Prognostic significance of sympathetic nervous system activation in pulmonary arterial hypertension. Am J Respir Crit Care Med, 2010, 181(11): 1269-1275.
19. Velez-Roa S, Ciarka A, Najem B, et al. Increased sympathetic nerve activity in pulmonary artery hypertension. Circulation, 2004, 110(10): 1308-1312.
20. McMahon TJ, Hood JS, Kadowitz PJ. Pulmonary vasodilator response to vagal stimulation is blocked by N omega-nitro-L-arginine methyl ester in the cat. Circ Res, 1992, 70(2): 364-369.
21. Rey-García J, Townsend RR. Renal denervation: a review. Am J Kidney Dis, 2022, 80(4): 527-535.
22. Bradford JR. The Innervation of the renal blood vessels. J Physiol, 1889, 10(5): 358-432.18.
23. Chen SL, Zhang YJ, Zhou L, et al. Percutaneous pulmonary artery denervation completely abolishes experimental pulmonary arterial hypertension in vivo. EuroIntervention, 2013, 9(2): 269-276.
24. Chen SL, Zhang FF, Xu J, et al. Pulmonary artery denervation to treat pulmonary arterial hypertension: the single-center, prospective, first-in-man PADN-1 study (first-in-man pulmonary artery denervation for treatment of pulmonary artery hypertension). J Am Coll Cardiol, 2013, 62(12): 1092-1100.
25. Huang Y, Liu YW, Pan HZ, et al. Transthoracic pulmonary artery denervation for pulmonary arterial hypertension. Arterioscler Thromb Vasc Biol, 2019, 39(4): 704-718.
26. Maas ET, Ostelo RW, Niemisto L, et al. Radiofrequency denervation for chronic low back pain. Cochrane Database Syst Rev, 2015, 2015(10): CD008572.
27. Chin KJ, Lirk P, Hollmann MW, et al. Mechanisms of action of fascial plane blocks: a narrative review. Reg Anesth Pain Med, 2021, 46(7): 618-628.
28. Schwartz PJ, Ackerman MJ. Cardiac sympathetic denervation in the prevention of genetically mediated life-threatening ventricular arrhythmias. Eur Heart J, 2022, 43(22): 2096-2102.
29. Sharp TE 3rd, Lefer DJ. Renal denervation to treat heart failure. Annu Rev Physiol, 2021, 83: 39-58.
30. Zhang H, Wei Y, Zhang C, et al. Pulmonary artery denervation for pulmonary arterial hypertension: a sham-controlled randomized PADN-CFDA trial. JACC Cardiovasc Interv, 2022, 15(23): 2412-2423.
31. Kan J, Zhang H, Xie D, et al. A sham-controlled randomised trial of pulmonary artery denervation for group 1 pulmonary arterial hypertension: one-year outcomes of the PADN-CFDA trial. EuroIntervention, 2023, 19(8): 684-694.
32. Zhang H, Kan J, Zhang C, et al. Long-term mortality after pulmonary artery denervation stratified by baseline functional class in patients with pulmonary arterial hypertension: long-term mortality after PADN stratified by functional class. AsiaIntervention, 2022, 8(1): 58-68.
33. Zhang H, Zhang J, Chen M, et al. Pulmonary artery denervation significantly increases 6-min walk distance for patients with combined pre- and post-capillary pulmonary hypertension associated with left heart failure: the PADN-5 study. JACC Cardiovasc Interv, 2019, 12(3): 274-284.
34. Romanov A, Cherniavskiy A, Novikova N, et al. Pulmonary artery denervation for patients with residual pulmonary hypertension after pulmonary endarterectomy. J Am Coll Cardiol, 2020, 76(8): 916-926.
35. Zhang H, Kan J, Zhang J, et al. 3-year outcome in patients with combined precapillary and postcapillary pulmonary hypertension: results from PADN-5 trial. JACC Heart Fail, 2023, 11(8 Pt 2): 1135-1146.
36. Chernyavskiy AM, Edemskiy AG, Novikova NV, et al. Radiofrequency pulmonary artery ablation for treatment of residual pulmonary hypertension after pulmonary endarterectomy. Kardiologiia, 2018, 58(4): 15-21.
37. Gradient Denervation Technologies. Pulmonary artery denervation clinical study using the Gradient Denervation System in heart failure patients with pulmonary hypertension group 2 (PreVail-PH2 OUS Study). Gradient Denervation Technologies, 2024.
38. Pulnovo Medical (Wuxi) Co. , Ltd. A trial to evaluate the safety and efficacy of pulmonary artery denervation for the treatment of pulmonary hypertension associated with left heart failure (PADN-HF-PH). Pulnovo Medical (Wuxi) Co. , Ltd, 2024.
39. 侯池, 温冬梅, 王健. 肺动脉高压神经调控机制研究进展. 中华结核和呼吸杂志, 2023, 46(9): 936-940.
40. Nanjing Medical University. Pulmonary artery denervation for HF without PH. Nanjing Medical University, 2024.

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