Purpose of Review
Sympathetic overactivity plays an important role in the progression of pulmonary arterial hypertension (PAH). The purpose of this review is to illustrate localization of pulmonary arterial sympathetic nerves, the key steps of pulmonary artery denervation (PADN) procedure, and to highlight clinical outcomes.
Sympathetic nerves mostly occurred in the posterior region of the bifurcation and pulmonary trunk. Emerging preclinical data provided the potential of PADN for PAH. PADN, produced at bifurcation area, improved a profound reduction of pulmonary arterial pressure and ameliorated clinical outcomes with an exclusive ablation catheter. The application of PADN in the patients of PAH or combined pre-capillary and post-capillary PH (CpcPH) improved the hemodynamic parameters and increased 6MWD.
Sympathetic overactivity aggravates PAH. PADN is a promising interventional treatment for PAH and CpcPH. Additional clinical trials are warranted to confirm the efficacy of PADN.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price includes VAT (USA)
Tax calculation will be finalised during checkout.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Galiè N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension the Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 2016;37:67–119. https://doi.org/10.1093/eurheartj/ehv317.
Hoeper MM, Bogaard HJ, Condliffe R, Frantz R, Khanna D, Kurzyna M, et al. Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D42–50. https://doi.org/10.1016/j.jacc.2013.10.032.
Hussain MB, Marshall I. Characterization of α1-adrenoceptor subtypes mediating contractions to phenylephrine in rat thoracic aorta, mesenteric artery and pulmonary artery. Br J Pharmacol. 1996;122:849–58. https://doi.org/10.1038/sj.bjp.0701461.
Velez-Roa S, Ciarka A, Najem B, Vachiery JL, Naeije R, van de Borne P, et al. Increased sympathetic nerve activity in pulmonary artery hypertension[J]. Circulation. 2004;110(10):1308–12. https://doi.org/10.1161/01.CIR.0000140724.90898.D3.
Ciarka A, Doan V, Velez-Roa S, Naeije R, van de Borne P, et al. Prognostic significance of sympathetic nervous system activation in pulmonary arterial hypertension[J]. Am J Respir Crit Care Med. 2010;181(11):1269–75. https://doi.org/10.1164/rccm.200912-1856OC.
Guidotti TL. The lung: scientific foundations. JAMA. 1997;278:2117.
Juratsch CE, Jengo JA, Castagna J, Laks MM. Experimental pulmonary hypertension produced by surgical and chemical denervation of the pulmonary vasculature. Chest. 1980;77(4):525–30. https://doi.org/10.1378/chest.77.4.525.
Szidon JP, Flint JF. Significance of sympathetic innervation of pulmonary vessels in response to acute hypoxia. J Appl Physiol Respir Environ Exerc Physiol. 1977;43(1):65–71. https://doi.org/10.1152/jappl.19188.8.131.52.
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):364–9.
Kylhammar D, Kjellström B, Hjalmarsson C, Jansson K, Nisell M, Söderberg S, et al. A comprehensive risk stratification at early follow-up determines prognosis in pulmonary arterial hypertension. Eur Heart J. 2018;39:4175–81. https://doi.org/10.1093/eurheartj/ehx257.
Maron BA, Leopold JA. Emerging concepts in the molecular basis of pulmonary arterial hypertension: part II: neurohormonal signaling contributes to the pulmonary vascular and right ventricular pathophenotype of pulmonary arterial hypertension. Circulation. 2015;131(23):2079–91. https://doi.org/10.1161/CIRCULATIONAHA.114.006980.
Zhang Y, Chen W, Xu Y, Liu H, Chen Y, Yang H, et al. Nerve distribution of canine pulmonary arteries and potential clinical implication. Am J Transl Res. 2016;8(2):365–74.
Zhou L, Zhang J, Jiang XM, Xie DJ, Wang JS, Li L, et al. Pulmonary artery denervation attenuates pulmonary arterial remodeling in dogs with pulmonary arterial hypertension induced by dehydrogenized monocrotaline[J]. JACC Cardiovasc Interv. 2015;8(15):2013–23. https://doi.org/10.1016/j.jcin.2015.09.015.
Juratsch CE, Jengo JA, Castagna J, Laks MM, et al. Experimental pulmonary hypertension produced by surgical and chemical denervation of the pulmonary vasculature. Chest. 1980;77(4):525–30. https://doi.org/10.1378/chest.77.4.525.
Chen SL, Zhang YJ, Zhou L, Xie DJ, Zhang FF, Jia HB, et al. Percutaneous pulmonary artery denervation completely abolishes experimental pulmonary arterial hypertension in vivo. EuroIntervention. 2013;9(2):269–76. https://doi.org/10.4244/EIJV9I2A43.
Rothman AM, Arnold ND, Chang W, Watson O, Swift AJ, Condliffe R, et al. Pulmonary artery denervation reduces pulmonary artery pressure and induces histological changes in an acute porcine model of pulmonary hypertension[J]. Circ Cardiovasc Interv. 2015;8(11):e2569. https://doi.org/10.1161/CIRCINTERVENTIONS.115.002569.
Hang Z, Wande Y, Shao-Liang C. EXPRESS: pulmonary artery denervation improves hemodynamics and cardiac function in pulmonary hypertension secondary to heart failure. Pulm Circ. 2018;767731415. https://doi.org/10.1177/2045894018816297.
Chen SL, Zhang FF, Xu J, Xie DJ, Zhou L, Nguyen T, 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):1092–100. https://doi.org/10.1016/j.jacc.2013.05.075.
• Chen SL, Zhang H, Xie DJ, Zhang J, Zhou L, Rothman AM, et al. Hemodynamic, functional, and clinical responses to pulmonary artery denervation in patients with pulmonary arterial hypertension of different causes: phase II results from the Pulmonary Artery Denervation-1 study[J]. Circ Cardiovasc Interv. 2015;8(11):e2837. https://doi.org/10.1161/CIRCINTERVENTIONS.115.002837. PADN was safe and feasible for the treatment of PAH. The PADN procedure was associated with significant improvements in hemodynamic function, exercise capacity, and cardiac function and with less frequent PAH-related events and death at 1 year after PADN treatment.
Tanai E, Frantz S. Pathophysiology of heart failure. Compr Physiol. 2015;6:187–214. https://doi.org/10.1002/cphy.c140055.
Guazzi M, Borlaug BA. Pulmonary hypertension due to left heart disease. Circulation. 2012;126:975–90. https://doi.org/10.1161/CIRCULATIONAHA.111.085761.
Vachiéry JL, Adir Y, Barberà JA, Champion H, Coghlan JG, Cottin V, et al. Pulmonary hypertension due to left heart diseases. J Am Coll Cardiol. 2013;62:D100–8. https://doi.org/10.1016/j.jacc.2013.10.033.
Naeije R, Gerges M, Vachiery JL, Caravita S, Gerges C, Lang IM. Hemodynamic phenotyping of pulmonary hypertension in left heart failure. Circ Heart Fail. 2017;10:e004082. https://doi.org/10.1161/CIRCHEARTFAILURE.117.004082.
Fayyaz AU, Edwards WD, Maleszewski JJ, Konik EA, DuBrock HM, Borlaug BA, et al. Global pulmonary vascular remodeling in pulmonary hypertension associated with heart failure and preserved or reduced ejection fraction. Circulation. 2018;137(17):1796–810. https://doi.org/10.1161/CIRCULATIONAHA.117.031608.
Galiè N, Corris PA, Frost A, Girgis RE, Granton J, Jing ZC, et al. Updated treatment algorithm of pulmonary arterial hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D60–72. https://doi.org/10.1016/j.jacc.2013.10.031.
Hwang IC, Kim YJ, Park JB, Yoon YE, Lee SP, Kim HK, et al. Pulmonary hemodynamics and effects of phosphodiesterase type 5 inhibition in heart failure: a meta-analysis of randomized trials. BMC Cardiovasc Disord. 2017;17:150. https://doi.org/10.1186/s12872-017-0576-4.
•• Zhang H, Zhang J, Chen M, Xie DJ, Kan J, Yu W, 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):274–84. https://doi.org/10.1016/j.jcin.2018.09.021. The trial is the first to demonstrate the benefits of PADN for patients with CpcPH. Finding suggest that PADN is associated with significant improvements in hemodynamic, cardiac function, and clinical outcomes.
CHernyavskiy AM, Edemskiy AG, Novikova NV, Romanov AB, Artemenko SN, Rudenko BA, et al. Radiofrequency pulmonary artery ablation for treatment of residual pulmonary hypertension after pulmonary endarterectomy. Kardiologiia. 2018;58(4):15–21.
Fujisawa T, Kataoka M, Kawakami T, Isobe S, Nakajima K, Kunitomi A, et al. Pulmonary artery denervation by determining targeted ablation sites for treatment of pulmonary arterial hypertension[J]. Circ Cardiovasc Interv. 2017:10(10). https://doi.org/10.1161/CIRCINTERVENTIONS.117.005812.
Hohenforst-Schmidt W, Zarogoulidis P, Oezkan F, Mahnkopf C, Grabenbauer G, Kreczy A, et al. “Denervation” of autonomous nervous system in idiopathic pulmonary arterial hypertension by low-dose radiation: a case report with an unexpected outcome. Ther Clin Risk Manag. 2014;10:207–15. https://doi.org/10.2147/TCRM.S58705.
Conflict of Interest
Hang Zhang and Shao-Liang Chen declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This article is part of the Topical Collection on Interventional Cardiology
About this article
Cite this article
Zhang, H., Chen, SL. Pulmonary Artery Denervation: Update on Clinical Studies. Curr Cardiol Rep 21, 124 (2019). https://doi.org/10.1007/s11886-019-1203-z
- Pulmonary arterial hypertension
- Sympathetic nervous
- Pulmonary denervation
- Annular catheter with 10 electrodes
- Clinical trial