CONTEMPORARY STRATEGY OF PULMONARY HYPERTENSION MANAGEMENT IN PEDIATRICS

Pulmonary hypertension (PH) in pediatrics is a polygenic multifactorial condition with extremely adverse prognosis. Selection of optimal management is a severe task. In absence of treatment the mean life duration in children is not higher one year. Last two decades, revolution in approaches to treatment improved the survival of this patients group. Recently, pediatricians and pediatric cardiologists have three drugs groups that act on the main pathogenetic chains of PH: endothelin pathway, nitric oxide pathway and prostacyclin pathway. At the moment, approaches to pediatric PH are based on the data obtained in the trials on adult patients. However, not long ago there were first randomized trials on children performed. The group of authors of current article presents a modern view on the problem of PH in children, and expert recommendations on children management. Class of recommendations and evidence level were set by the data obtained in pediatric population or on adult population with at least 10% of children included. To the strategy, developed by the Russian clinicians, laid the analysis of experience of the pathology treatment in Russian Federation, as the current practics and clinical guidelines on pediatric PH in Europe, and the recent trials published.

1. Bockeria LA, Gorbachev SV, Shkol’nikova MA. Pulmonary hypertension in children. Moscow, 2013. 416 p. (In Russ.)

2. Galie N, Humbert M, Vachiery J, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. European Heart Journal 2016; 37:67–119. DOI: 10.1093/eurheartj/ehv317

3. Ivy DD, Abman SH, Barst RJ, et al. Paediatric pulmonary hypertension. J Am Coll Cardiol 2013;62(25 Suppl): D117–26. DOI: 10.1016/j.jacc.2013.10.028

4. Abman S, Hansmann G, Archer S, et al. Pediatric Pulmonary Hypertension. Guidelines From the American Heart Association and American Thoracic Society. Circulation 2015;132:2037­99.

5. Hansmann G, Apitz C, Abdul­Khaliq H, et al. Executive summary. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK. Heart 2016; 102: ii86–ii100. DOI: 10.1136/heartjnl­2015­309132

6. Lammers AE, Apitz C, Zartner P, et al. Diagnostics, monitoring and outpatient care in children with suspected pulmonary hypertension/paediatric pulmonary hypertensive vascular disease. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. Heart 2016; 102: ii1–13. DOI: 10.1136/heartjnl­2015­307792

7. Bockeria LA, Gorbachev SV, Schmalz AA, et al. Pediatric hypertensive vascular disease associated with congenital heart defects. Clinical guidelines. M.: A. N. Bakulev center. 2015. (In Russ.)

8. Gorbachevsky SV, Shmalts AA. Hypertension vascular lung disease associated with congenital heart disease. In the book.: Pediatric cardiac surgery. Manual for doctors. M, 2016: 833­50. (In Russ.)

9. Schmaltz AA, Belkin MV, Gorbachev SV. Specific pulmonary vasodilators after the surgery, Fontaine. Children’s diseases of the heart and blood vessels. 2017; 14 (1): 16­25. (In Russ.). DOI: 10.24022/1810­0686­2017­14­1­16­24

10. Humbert M, Morrell N, Archer S, et al. Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol. 2004;43:13S­24S.

11. Rabinovitch M. Molecular pathogenesis of pulmonary arterial hypertension. J Clin Invest.2008;118(7):2372­9.

12. Zijlstra W, Douwes J, Rosenzweig E, et al. Survival differences in pediatric pulmonary arterial hypertension: clues to a better understanding of outcome and optimal treatment strategies. J Am Coll Cardiol. 2014;63(20):2159–69. DOI: 10.1016/j.jacc.2014.02.575

13. D’Alonzo G, Barst R, Ayres S, et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med 1991;115:343–9.

14. Haworth S, Hislop A. Treatment and survival in children with pulmonary arterial hypertension: The UK pulmonary hypertension service for children 2001­2006. Heart. 2009;95(4):312­7.

15. Barst R, McGoon M, Elliott C, et al. Survival in childhood pulmonary arterial hypertension: Insights from the registry to evaluate early and long­term pulmonary arterial hypertension disease management. Circulation. 2012;125(1):113­22. DOI: 10.1161/CIRCULATIONAHA.111.026591

16. Hilgendorff A, Apitz C, Bonnet D, Hansmann G. Pulmonary hypertension associated with acute or chronic lung diseases in the preterm and term neonate and infant. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK. Heart. 2016 May;102 Suppl 2:ii49­56. DOI: 10.1136/heartjnl­2015­308591.

17. Stewart D, Cogan J, Kramer M, et al. Is pulmonary arterial hypertension in neurofibromatosis type 1 secondary to a plexogenic arteriopathy? Chest. 2007;132:798–808.

18. Lo S, Liu J, Chen F, et al. Pulmonary vascular disease in Gaucher disease: clinical spectrum, determinants of phenotype and long­term outcomes of therapy. J Inherit Metab Dis. 2011;34:643–50. DOI: 10.1007/s10545­011­9313­9.

19. Alghamdi M, Steinraths M, Panagiotopoulos C, et al. Primary pulmonary arterial hypertension and autoimmune polyendocrine syndrome in a pediatric patient. Pediatr Cardiol. 2010;31:872­4. DOI: 10.1007/s00246­010­9704­y.

20. Peacock A, Murphy N, McMurrey J, et al. An epidemiological study of pulmonary arterial hypertension. European Respiratory Journal 2007;30:104–9.

21. Moledina S, Hislop A, Foster H, et al. Childhood idiopathic pulmonary arterial hypertension: A national cohort study. Heart 2010;96:1401­6.

22. Soubrier F, Chung W, Machado R, et al. Genetics and Genomics of Pulmonary Arterial Hypertension. J Am Coll Cardiol. 2013 Dec 24; 62 (25 Suppl):D13­21. DOI: 10.1016/j.jacc.2013.10.035.

23. Roberts K, McElroy J, Wong W, et al. BMPR2 mutations in pulmonary arterial hypertension with congenital heart disease. Eur Respir J. 2004;24:371–4.

24. Sztrymf B, Coulet F, Girerd B, et al. Clinical outcomesof pulmonary arterial hypertension in carriers of BMPR2 mutation. Am J Respir Crit Care Med. 2008;177:1377–83.

25. Runo J, Vnencak­Jones C, Prince M, et al. Pulmonary veno­occlusive disease caused by an inherited mutation in bone morphogenetic protein receptor II. Am J Respir Crit Care Med.2003;167:889–94.

26. Ji R, Meng J, et al. Functional changes in pulmonary arterial endothelial cells associated with BMPR2 mutations. PLoS One. 2014;9(9):e106703. DOI: 10.1371/journal.pone.0106703

27. Klinger J. The nitric oxide/cGMP signaling pathway in pulmonary hypertension. Clin Chest Med 2007;28(1):143–67.

28. Sitbon O, Morrell N. Pathways in pulmonary arterial hypertension: the future is here. Eur Respir Rev 2012; 21: 126, 321–7. DOI: 10.1183/09059180.00004812

29. Galie´ N, Manes A, Branzi A. The endothelin system in pulmonary arterial hypertension. Cardiovasc Res 2004; 61: 227–37.

30. Simonneau G, Gatzoulis M, Adatia I, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2013;62:D34–D41.

31. Cerro M, Abman S, Diaz G, et al. A consensus approach to the classification of pediatric pulmonary hypertensive vascular disease: Report from the PVRI Pediatric Taskforce, Panama 2011. Pulm Circ. 2011;1:286–98.

32. Lammers A, Adatia I, Cerro MJ, et al. Functional classification of pulmonary hypertension in children: report from the PVRI Pediatric Taskforce, Panama 2011. Pulm Circ. 2011;1:280–5.

33. Humbert M, Sitbon O, Chaouat A, et al. Pulmonary arterial hypertension in France: Results from a national registry. Am J Respir Crit Care Med. 2006;173(9):1023­30.

34. Peacock A, Murphy N, McMurray J, et al. An epidemiological study of pulmonary arterial hypertension. Eur Respir J. 2007;30(1):104­9.

35. van Loon R, Roofthooft M, Hillege H, et al. Pediatric pulmonary hypertension in the Netherlands: Epidemiology and characterization during the period 1991 to 2005. Circ ulation.2011;124(16):1755­64. DOI: 10.1161/CIRCULATIONAHA.110.969584

36. Van Loon R, Roofthooft M, van Osch­Gevers M, et al. Clinical characterization of pediatric pulmonary hypertension: complex presentation and diagnosis.

37. J Pediatr.2009;155:176–82. 37. Barst R, Ertel S, Beghetti M, Ivy D. Pulmonary arterial hypertension:

38. A comparison between children and adults. Eur Respir J. 2011;37(3):665­77. DOI: 10.1183/09031936.00056110.

39. Berger R, Beghetti M, Humpl T, et al. Clinical features of paediatric pulmonary hypertension: A registry study. Lancet. 2012;379(9815):537­46. DOI: 10.1016/S0140­6736(11)61621­8.

40. Fraisse A, Jais X, Schleich J, et al. Characteristics and prospective 2­year follow­up of children with pulmonary arterial hypertension in France. Arch Cardiovasc Dis. 2010;103(2):66­74.

41. Van Albada M, Loot F, Fokkema R, et al. Biological serum markers in the management of pediatric pulmonary arterial hypertension. Pediatr Res. 2008;63(3):321­7.

42. Berger R, Bonnet D. Treatment options for paediatric pulmonary arterial hypertension. EurRespir Rev. 2010;19(118):321­30.

43. Kleinman ME, de Caen AR, Chameides L, et al. Pediatric Basic and Advanced Life Support Chapter Collaborators. Pediatric basic and advanced life support: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with treatment recommendations. Pediatrics. 2010;126:e1261–e1318.

44. Maslach­Hubbard A, Bratton S. Extracorporeal membrane oxygenation for pediatric respiratory failure: History, development and current status. World J Crit Care Med 2013; 2(4): 29­39. DOI: 10.5492/wjccm.v2.i4.29

45. Sandoval J, Aguirre JS, Pulido T, et al. Nocturnal oxygen therapy in patients with the Eisenmenger syndrome. Am. J. Respir. Crit. Care Med. 2001; 164: 1682–7.

46. Maron BA, Waxman AB, Opotowsky AR, et al. Effectiveness of spironolactone plus ambrisentan for treatment of pulmonary arterial hypertension (from the[ARIES] study 1 and 2 trials). Am J Cardiol. 2013; 112: 720–5. DOI: 10.1016/j.amjcard.2013.04.051.

47. Calvier L, Legchenko E, et al. Galectin­3 and aldosterone as potential tandem biomarkers in pulmonary arterial hypertension. Heart. 2016; 102: 390–6. DOI: 10.1136/heartjnl­2015­308365.

48. Bogaard HJ, Natarajan R, Mizuno S, et al. Adrenergic receptor blockade reverses right heart remodeling and dysfunction in pulmonary hypertensive rats. Am J Respir Crit Care Med. 2010;182(5):652–60.

49. Perros F, Ranchoux B, Izikki M, et al. Nebivolol for improving endothelial dysfunction, pulmonary vascular remodeling, and right heart function in pulmonary hypertension. J Am Coll Cardiol. 2015;65(7):668­80. DOI: 10.1016/j.jacc.2014.11.050

50. Farha S, Saygin D, Park M, et al. Pulmonary arterial hypertension treatment with carvedilol for heart failure: a randomized controlled trial. JCI Insight. 2017;2(16):e95240. DOI: 10.1172/jci.insight.95240.

51. Rich S, Seidlitz M, Dodin E, et al. The short­term effects of digoxin in patients with right ventricular dysfunction from pulmonary hypertension. Chest. 1998; 114: 787–792

52. Sandoval J, Santos LE, Córdova J, et al. Does anticoagulation in Eisenmenger syndrome impact long­term survival? Congenit. Heart Dis. 2012; 7: 268–76.

53. Barst R, Maislin G, Fishman A. Vasodilator therapy for primary pulmonary hypertension in children. Circulation. 1999;99(9):1197­208.

54. Douwes J, van Loon RL, Hoendermis ES, et al. Acute pulmonary vasodilator response in paediatric and adult pulmonary arterial hypertension: Occurrence and prognostic value when comparing three response criteria. Eur Heart J. 2011;32(24):3137­46.

55. Sitbon O, Humbert M, Jais X, et al. Long­term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation. 2005;111(23):3105­11.

56. Apitz C, Hansmann G, Schranz D. Hemodynamic assessment and acute pulmonary vasoreactivity testing in the evaluation of children with pulmonary vascular disease. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK. Heart 2016;102:ii23–9. DOI: 10.1136/heartjnl­2014­307340.

57. Hislop A, Moledina S, Foster H, et al. Long­term efficacy of bosentan in treatment of pulmonary arterial hypertension in children. Eur Respir J. 2011;38(1):70­7.

58. Humpl T, Reyes JT, Holtby H, et al. Beneficial effect of oral sildenafil therapy on childhood pulmonary arterial hypertension: twelvemonth clinical trial of a single­drug, open­label, pilot study. Circulation. 2005;111:3274–80.

59. Kahveci H, Yilmaz O, Avsar U, et al.. Combination therapy with bosentan and sildenafil in idiopathic pulmonary arterial hypertension. Eur Respir J.2004;24(6):1007­10.

60. D’Alto M, Romeo E, Argiento P, et al. Bosentan­sildenafil association in patients with congenital heart disease­related pulmonary arterial hypertension and eisenmenger physiology. Int J Cardiol.2012;155(3):378­82.

61. Porhownik N, Al­Sharif H, Bshouty Z. Addition of sildenafil in patients with pulmonary arterial hypertension with inadequate response to bosentan monotherapy. Can Respir J. 2008;15(8):427­30.

62. Mathai S, Girgis R, Fisher M, et al. Addition of sildenafil to bosentan monotherapy in pulmonary arterial hypertension. Eur Respir J. 2007;29(3):469­75.

63. Douwes J, Roofthooft M, Van Loon RL, et al. Sildenafil add­on therapy in paediatric pulmonary arterial hypertension, experiences of a national referral centre. Heart. 2014;100(3):224­30. DOI: 10.1136/heartjnl­2013­304895.

64. Sitbon O, Beghetti M, Petit J, et al. Bosentan for the treatment of pulmonary arterial hypertension associated with congenital heart defects. Eur J Clin Invest. 2006;36 (suppl 3):25–31.

65. van Loon R, Hoendermis E, Duffels M, et al. Long­term effect of bosentan in adults versus children with pulmonary arterial hypertension associated with systemic­topulmonary shunt: does the beneficial effect persist? AmHeart J. 2007;154:776–82.

66. Gorbachevsky SV, Belkin VM, Schmaltz AA, Aibasov RA. The Use of Bosentan in patients with a complicated course of hemodynamic correction of a functionally single ventricle and pulmonary hypertension the original. Bulletin of the A. N. Bakulev center. Russian Academy of medical Sciences of cardiovascular disease. 2015; 16 (C3): 14. (In Russ.)

67. Barst R, Ivy D, Dingemanse J, et al. Pharmacokinetics, safety, and efficacy of bosentan in pediatric patients with pulmonary arterial hypertension. Clin Pharmacol Ther. 2003;73(4):372­82.

68. Rosenzweig E, Ivy D, Widlitz A, et al. Effects of long­term bosentan in children with pulmonary arterial hypertension. J Am Coll Cardiol. 2005;46(4):697­704.

69. Beghetti M, Hoeper M, Kiely D, et al. Safety experience with bosentan in 146 children 2­11years old with pulmonary arterial hypertension: Results From The European Postmarketing Surveillance Program. Pediatr Res. 2008;64(2):200­4.

70. Ivy D, Rosenzweig E, Lemarie J, et al. Long­term outcomes in children with pulmonary arterial hypertension treated with bosentan in real­world clinical settings. Am J Cardiol. 2010;106(9):1332­8.

71. Taguchi M, Ichida F, Hirono K, et al. et al. Pharmacokinetics of bosentan in routinely treated Japanese pediatric patients with pulmonary arterial hypertension. Drug Metab Pharmacokinet. 2011;26:280–7.

72. Beghetti M, Haworth S, Bonnet D, et al. Pharmacokinetic and clinical profile of a novel formulation of bosentan in children with pulmonary arterial hypertension: The FUTURE­1 study. Br J Clin Pharmacol. 2009;68(6):948­55.

73. Berger RM, Haworth SG, Bonnet D, et al. FUTURE­2: results from an open­label, long­term safety and tolerability extension study using the paediatric FormUlation of bosenTan in pUlmonary arterial hypeRtEnsion. Int. J. Cardiol. 2016; 202: 52–8. DOI: 10.1016/j.ijcard.2015.08.080.

74. Berger R, Gehin M, Beghetti M, et al. A bosentan pharmacokinetic study to investigate dosing regimens in paediatric patients with pulmonary arterial hypertension: FUTURE­3. British Journal of Clinical Pharmacology. 2017;83(8):1734­44. DOI: 10.1111/bcp.13267

75. Galie N, Olschewski H, Oudiz RJ, et al. Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double­Blind, Placebo­Controlled,Multicenter, Efficacy Studies (ARIES) Group. Ambrisentan for the treatment of pulmonary arterial hypertension: results of the Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double­Blind, Placebo­ Controlled, Multicenter, Efficacy (ARIES) study 1 and 2. Circulation. 2008;117:3010–9.

76. Zuckerman WA, Leaderer D, Rowan CA, et al. Ambrisentan for pulmonary arterial hypertension due to congenital heart disease. Am J Cardiol. 2011;107:1381–5.

77. Takatsuki S, Rosenzweig EB, Zuckerman W, et al. Clinical safety, pharmacokinetics, and efficacy of ambrisentan therapy in children with pulmonary arterial hypertension. Pediatr Pulmonol. 2012;48:27–34.

78. Souza RO, Pulido T, Channick R, et al. Long­Term Survival and Safety with Macitentan in Patients with Pulmonary Arterial Hypertension: Results from the SERAPHIN Study and Its Open­Label Extension. Pharmacological treatment of pulmonary hypertension 2017; May 1: A2294.

79. Walsh­Sukys MC, Tyson JE, Wright LL, Bauer CR, et al. Persistent pulmonary hypertension of the newborn in the era before nitric oxide: practice variation and outcomes. Pediatrics. 2000;105(pt 1):14–20.

80. Porta NF, Steinhorn RH. Pulmonary vasodilator therapy in the NICU: inhaled nitric oxide, sildenafil, and other pulmonary vasodilating agents. Clin Perinatol. 2012;39:149–64.

81. Konduri GG, Vohr B, Robertson C, et al. Neonatal Inhaled Nitric Oxide Study Group. Early inhaled nitric oxide therapy for term and near­term newborn infants with hypoxic respiratory failure: neurodevelopmental follow­up. JPediatr. 2007;150:235–40.

82. Krishnan U, Krishnan S, Gewitz M. Treatment of pulmonary hypertension in children with chronic lung disease with newer oral therapies. Pediatr Cardiol 2008;29:1082­6.

83. Mourani P, Sontag M, Ivy D, Abman SH. Effects of long­term sildenafil treatment for pulmonary hypertension in infants with chronic lung disease. J Pediatr 2009;154:379­84.

84. Xia Y, Yan W, Chen H. Efficacy and safety of sildenafil in the treatment of high altitude heart disease associated with severe pulmonary arterial hypertension in children: a preliminary evaluation. Zhongguo Dang Dai Er Ke Za Zhi. 2014;16(7):745–8

85. Vargas­Origel A, Gomez­Rodriguez G, Aldana­Valenzuela C, et al. The use of sildenafil in persistent pulmonary hypertension of the newborn. Am J Perinatol.2010;27(3):225–30.

86. Baquero H, Soliz A, Neira F, et al. Oral sildenafil in infants with persistent pulmonary hypertension of the newborn: a pilot randomized blinded study. Pediatrics. 2006;117(4):1077–83.

87. El Midany A, Mostafa E, Azab S, Hassan GA. Perioperative sildenafil therapy for pulmonary hypertension in infants undergoing congenital cardiac defect closure. Interact Cardiovasc Thorac Surg. 2013;17(6):963–8.

88. Michelakis E, Tymchak W, Noga M, et al. Long­term treatment with oral sildenafil is safe and improves functional capacity and hemodynamics in patients with pulmonary arterial hypertension. Circulation. 2003;108(17):2066–9.

89. Barst R, Ivy D, Gaitan G, et al. A randomized, double­blind, placebo­controlled, dose­ranging study of oral sildenafil citrate in treatment­naive children with pulmonary arterial hypertension. Circulation. 2012;125(2):324­34. doi: 10.1161/CIRCULATIONAHA.110.016667.

90. Barst R, Beghetti M, Pulido T, Layton G. STARTS­2. Long­Term Survival With Oral Sildenafil Monotherapy in Treatment­Naive Pediatric Pulmonary Arterial Hypertension. Circulation. 2014;129:1914­23.

91. Ghofrani H, Galiè N, Grimminger F, et al. Riociguat for the treatment of pulmonary arterial hypertension. N. Engl. J. Med. 2013; 369: 330–40.

92. Galiè N, Muller K, Scalise AV, et al. PATENT PLUS: a blinded, randomised and extension study of riociguat plus sildenafil in pulmonary arterial hypertension. Eur. Respir. J. 2015; 45: 1314–22.

93. Rosenkranz S, Ghofrani HA, Beghetti M, et al. Riociguat for pulmonary arterial hypertension associated with congenital heart disease. Heart 2015;101:1792–9.

94. Ivy D, Doran A, Smith K, et al. Short­ and longterm effects of inhaled iloprost therapy in children with pulmonary arterialhypertension. J Am Coll Cardiol. 2008;51:161–16.

95. Simonneau G, Torbicki A, Hoeper MM, et al. Selexipag: an oral, selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension. Eur. Respir. J. 2012; 40: 874–80.

96. Sitbon O, Channick R, Chin KM, et al. Selexipag for the treatment of pulmonary arterial hypertension. N. Engl. J. Med. 2015; 373: 2522–33. 96. Gallotti R, Drogalis­Kim DE, Satou G, et al. Single­Center Experience Using Selexipag in a Pediatric Population. Pediatr Cardiol (2017). DOI: 10.1007/s00246­017­1677­7.

97. Micheletti A, Hislop A, Lammers A, et al. Role of atrial septostomy in the treatment of children with pulmonary arterial hypertension. Heart. 2006;92(7):969­72.

98. Keogh AM, Mayer E, Benza RL, et al. Interventional and surgical modalities of treatment in pulmonary hypertension. J. Am. Coll. Cardiol. 2009; 54: S67–77.

99. Gorbachevskiy S, Shmalts A, Zaets S. Potts Shunt in Patients with Suprasystemic Pulmonary Arterial Hypertension: Does the Size Matter? Anatomy & Physiology 2017;7(2): e140.

100. 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: 376–80.

101. Blanc J, Vouhe P, Bonnet D. Potts shunt in patients with pulmonary hypertension. N Engl J Med.2004;350(6):623.

102. Baruteau AE, Belli E, Boudjemline Y, et al. Palliative Potts shunt for the treatment of children with drug­refractory pulmonary arterial hypertension: updated data from the first 24 patients. Eur. J. Cardiothorac Surg. 2015; 47: e105–10.

103. Boudjemline Y, Patel M, Malekzadeh­Milani S, et al. Patent ductus arteriosus stenting (transcatheter Potts shunt) for palliation of suprasystemic pulmonary arterial hypertension: a case series. Circ. Cardiovasc. Interv. 2013; 6: e18–20.

104. Esch JJ, Shah PB, Cockrill BA, et al. Transcatheter Potts shunt creation in patients with severe pulmonary arterial hypertension: initial clinical experience. J. Heart Lung Transplant. 2013; 32: 381–7.

105. Gorbachevsky SV, Shmaltz AA, Belkina MV, et al. Potts Anastomosis in children with pulmonary hypertension: 7 operations in one clinic and a review of world experience. Children’s diseases of the heart and blood vessels. 2016; 13. 4: 189­98. (In Russ.)

106. Shmalts AA, Nishonov NA. Atrioseptostomy in patients with pulmonary hypertension. Thoracic and cardiovascular surgery. 2015; 5: 18­25. (In Russ.)

107. Chen SL, Zhang FF, Xu J, et al. Pulmonary artery denervation to treat pulmonary arterial hypertension: the single­center, prospective, first­in­man PADN­1 study (first­in­man pulmonary artery denervation for treatment of pulmonary artery hypertension). J. Am. Coll. Cardiol. 2013; 62: 1092–100.

108. Chen SL, Zhang H, Xie DJ, 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 denervation­1 study. Circ. Cardiovasc. Interv. 2015; 8: e002837.