Легочная гипертензия. Диагностика и лечение. Европейские клинические рекомендации (2015) (часть 3-я)

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Аннотация

Легочная гипертензия (ЛГ) – это патофизиологическое состояние, которое может развиваться при многих заболеваниях и осложнять большинство сердечно-сосудистых и бронхолегочных заболеваний. Целью создания рекомендаций Европейского общества кардиологов (European Society of Cardiology (ESC)) и Европейского респираторного общества (European Respiratory Society (ERS)) явилось не только объединение большинства исследований последних лет, но и разработка образовательного инструмента и программ внедрения данных рекомендаций в клиническую практику. Данный документ продолжает 2 предшествующих варианта клинических рекомендаций ESC и ERS (2004, 2009) и концентрируется на клиническом ведении больных с ЛГ, однако при этом отмечены значительные отличия от версии 2009 г., суммированы все существующие на сегодняшний день доказательства по диагностике и лечению ЛГ для оказания помощи врачам при повседневном выборе оптимальной стратегии ведения конкретного пациента с учетом желаемого исхода и соотношения риск / польза конкретных диагностических и терапевтических мероприятий. Систематический обзор литературы выполнен по публикациям базы MEDLINE, в которой искали новые исследования по соответствующей теме, опубликованные после 2009 г. При создании рекомендаций тщательно обсуждалась вся научная и медицинская информация и доступные доказательства. Ожидаемые исходы заболевания оценены для больших популяций, насколько позволяли существующие данные. Подчеркивается, что ESC поддерживает национальные кардиологические общества в переводе всех рекомендаций ESC на национальные языки и внедрении их в практику этих стран, поскольку показано, что исход ЛГ напрямую зависит от выполнения действующих клинических рекомендаций. Окончательный вариант данных рекомендаций утвержден Комитетом ESC и ERS и опубликован в журналах EuropeanHeartJournal и EuropeanRespiratoryJournal.


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Редакционная статья

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Список литературы

1. Hoeper M.M., Bogaard H.J., Condliffe R. et al. Definitions and diagnosis of pulmonary hypertension. J. Am. Coll. Cardiol. 2013; 62 (Suppl.): D42–D50. DOI: 10.1016/j.jacc.2013.10.032.

2. Kovacs G., Berghold A., Scheidl S. et al. Pulmonary arterial pressure during rest and exercise in healthy subjects: A systematic review. Eur. Respir. J. 2009; 34 (4): 888–894. DOI: 10.1183/09031936.00145608.

3. Herve P., Lau E., Sitbon O. et al. Criteria for diagnosis of exercise pulmonary hypertension. Eur. Respir. J. 2015; 46 (3): 728–737. DOI: 10.1183/09031936.00021915.

4. Vachiery J.L., Adir Y., Barbera J.A. et al. Pulmonary hypertension due to left heart disease. J. Am. Coll. Cardiol. 2013; 62 (25, Suppl.): D100–D108. DOI: 10.1016/j.jacc.2013.10.033.

5. Simonneau G., Galiè N., Rubin L.J. et al. Clinical classification of pulmonary hypertension. J. Am. Coll. Cardiol. 2004; 43 (Suppl. 1): S5–S12.

6. Simonneau G., Gatzoulis M.A., Adatia I. et al. Updated clinical classification of pulmonary hypertension. J. Am. Coll. Cardiol. 2013; 62 (25, Suppl.): D34–D41. DOI: 10.1016/j.jacc.2013.10.029.

7. Dhillon R. The management of neonatal pulmonary hypertension. Arch. Dis. Child Fetal. Neonatal. Ed. 2012; 97 (3): F223–F228. DOI: 10.1136/adc.2009.180091.

8. Porta N.F., Steinhorn R.H. Pulmonary vasodilator therapy in the NICU: inhaled nitric oxide, sildenafil, and other pulmonary vasodilating agents. Clin. Perinatol. 2012; 39 (1): 149–164. DOI: 10.1016/j.clp.2011.12.006.

9. Ivy D.D., Abman S.H., Barst R.J. et al. Pediatric pulmonary hypertension. J. Am. Coll. Cardiol. 2013; 62 (25, Suppl.): D117–D126. DOI: 10.1016/j.jacc.2013.10.028.

10. 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): 1023–1030. DOI: 10.1164/rccm.200510-1668OC.

11. Peacock A.J., Murphy N.F., McMurray J.J.V. et al. An epidemiological study of pulmonary arterial hypertension. Eur. Respir. J. 2007; 30 (1): 104–109. DOI: 10.1183/09031936.00092306.

12. McGoon M.D., Benza R.L., Escribano-Subias P. et al. Pulmonary arterial hypertension: epidemiology and registries. J. Am. Coll. Cardiol. 2013; 62 (25, Suppl.): D51–D59.

13. Simonneau G., Robbins I., Beghetti M., et al. Updated clinical classification of pulmonary hypertension. J. Am. Coll. Cardiol. 2009; 54 (Suppl.): S43–S54.

14. Montani D., Bergot E., Günther S. et al. Pulmonary arterial hypertension in patients treated by dasatinib. Circulation. 2012; 125 (17): 2128–2137. DOI: 10.1161/CIRCULATIONAHA.111.079921.

15. Savale L., Chaumais M.C., Cottin V. et al. Pulmonary hypertension associated with benfluorex exposure. Eur. Respir. J. 2012; 40 (5): 1164–1172. DOI: 10.1183/09031936.00188611.

16. Savale L., Sattler C., Gunther S. et al. Pulmonary arterial hypertension in patients treated with interferon. Eur. Respir. J. 2014; 44 (6): 1627–1634. DOI: 10.1183/09031936.00057914.

17. Badesch B.D., Champion H.C., Gomez-Sanchez M.A. et al. Diagnosis and assessment of pulmonary arterial hypertension. J. Am. Coll. Cardiol. 2009; 54 (Suppl.): S55–S56.

18. Oudiz R.J. Pulmonary hypertension associated with left-sided heart disease. Clin. Chest Med. 2007; 28 (1): 233–241. DOI: 10.1016/j.ccm.2006.12.001.

19. Vahanian A., Alfieri O., Andreotti F. et al. Guidelines on the management of valvular heart disease (version 2012). Eur. Heart J. 2012; 33 (19): 2451–2496. DOI: 10.1093/eurheartj/ehs109.

20. Seeger W., Adir Y., Barberà J.A. et al. Pulmonary hypertension in chronic lung diseases. J. Am. Coll. Cardiol. 2013; 62 (25, Suppl.): D109–D116.

21. Hurdman J., Condliffe R., Elliot C.A. et al. Pulmonary hypertension in COPD: results from the ASPIRE registry. Eur. Respir. J. 2013; 41 (6): 1292–1301. DOI: 10.1183/09031936.00079512.

22. Cottin V., Nunes H., Brillet P.Y. et al. Combined pulmonary fibrosis and emphysema: a distinct underrecognised entity. Eur. Respir. J. 2005; 26 (4): 586–593. DOI: 10.1183/09031936.05.00021005.

23. Escribano-Subias P., Blanco I., Lopez-Meseguer M. et al. Survival in pulmonary hypertension in Spain: insights from the Spanish registry. Eur. Respir. J. 2012; 40 (3): 596–603. DOI: 10.1183/09031936.00101211.

24. Pengo V., Lensing A.W., Prins M.H. et al. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N. Engl. J. Med. 2004; 350 (22): 2257–2264. DOI: 10.1056/NEJMoa032274.

25. Pepke-Zaba J., Delcroix M., Lang I. et al. Chronic thromboembolic pulmonary hypertension (CTEPH): results from an international prospective registry. Circulation. 2011; 124 (18): 1973–1981. DOI: 10.1161/CIRCULATIONAHA.110.015008.

26. Soubrier F., Chung W.K., Machado R. et al. Genetics and genomics of pulmonary arterial hypertension. J. Am. Coll. Cardiol. 2013; 62 (25, Suppl.): D13–D21.

27. Ma L., Roman-Campos D., Austin E.D. et al. A novel channelopathy in pulmonary arterial hypertension. N. Engl. J. Med. 2013; 369 (4): 351–361. DOI: 10.1056/NEJMoa1211097.

28. Eyries M., Montani D., Girerd B. et al. EIF2AK4 mutations cause pulmonary veno-occlusive disease, a recessive form of pulmonary hypertension. Nat. Genet. 2014; 46 (1): 65–69. DOI: 10.1038/ng.2844.

29. Eddahibi S., Chaouat A., Morrell N. et al. Polymorphism of the serotonin transporter gene and pulmonary hypertension in chronic obstructive pulmonary disease. Circulation. 2003; 108 (15): 1839–1844. DOI: 10.1161/01.CIR.0000091409.53101.E8.

30. Bonderman D., Wexberg P., Martischnig A.M. et al. A noninvasive algorithm to exclude pre-capillary pulmonary hypertension. Eur. Respir. J. 2011; 37 (5): 1096–1103. DOI: 10.1183/09031936.00089610.

31. Rich J.D., Thenappan T., Freed B. et al. QTc prolongation is associated with impaired right ventricular function and predicts mortality in pulmonary hypertension. Int. J. Cardiol. 2013; 167 (3): 669–676. DOI: 10.1016/j.ijcard.2012.03.071.

32. Sun P.Y., Jiang X., Gomberg-Maitland M. et al. Prolonged QRS duration: a new predictor of adverse outcome in idiopathic pulmonary arterial hypertension. Chest. 2012; 141: 374–380.

33. Olsson K.M., Nickel N.P., Tongers J. et al. Atrial flutter and fibrillation in patients with pulmonary hypertension. Int. J. Cardiol. 2013; 167 (5): 2300–2305. DOI: 10.1016/j.ijcard.2012.06.024.

34. Rich S., Dantzker D.R., Ayres S.M. et al. Primary pulmonary hypertension: a national prospective study. Ann. Intern. Med. 1987; 107 (2): 216–223.

35. Milne E.N. Forgotten gold in diagnosing pulmonary hypertension: the plain chest radiograph. Radiographics. 2012; 32 (4): 1085–1087. DOI: 10.1148/rg.324125021.

36. Trip P., Nossent E.J., de Man F.S. et al. Severely reduced diffusion capacity in idiopathic pulmonary arterial hypertension: patient characteristics and treatment responses. Eur. Respir. J. 2013; 42 (6): 1575–1585. DOI: 10.1183/09031936.00184412.

37. Sun X.G., Hansen J.E., Oudiz R.J. et al. Pulmonary function in primary pulmonary hypertension. J. Am. Coll. Cardiol. 2003; 41 (6): 1028–1035.

38. Hoeper M.M., Pletz M.W., Golpon H. et al. Prognostic value of blood gas analyses in patients with idiopathic pulmonary arterial hypertension. Eur. Respir. J. 2007; 29 (5): 944–950. DOI: 10.1183/09031936.00134506.

39. Pellegrino R., Viegi G., Brusasco V. et al. Interpretative strategies for lung function tests. Eur. Respir. J. 2005; 26 (5): 948–968. DOI: 10.1183/09031936.05.00035205.

40. Holverda S., Bogaard H.J., Groepenhoff H. et al. Cardiopulmonary exercise test characteristics in patients with chronic obstructive pulmonary disease and associated pulmonary hypertension. Respiration. 2008; 76 (2): 160–167. DOI: 10.1159/000110207.

41. Jilwan F.N., Escourrou P., Garcia G. et al. High occurrence of hypoxemic sleep respiratory disorders in precapillary pulmonary hypertension and mechanisms. Chest. 2013; 143 (1): 47–55. DOI: 10.1378/chest.11-3124.

42. Rafanan A.L., Golish J.A., Dinner D.S. et al. Nocturnal hypoxemia is common in primary pulmonary hypertension. Chest. 2001; 120 (3): 894–899.

43. Rudski L.G., Lai W.W., Afilalo J. et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J. Am. Soc. Echocardiogr. 2010; 23 (7): 685–713. DOI: 10.1016/j.echo.2010.05.010.

44. Lang R.M., Badano L.P., Mor-Avi V. et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur. Heart J. Cardiovasc. Imaging. 2015; 16 (3): 233–270. DOI: 10.1093/ehjci/jev014.

45. Foale R., Nihoyannopoulos P., McKenna W. et al. Echocardiographic measurement of the normal adult right ventricle. Br. Heart J. 1986; 56 (1): 33–44.

46. Hachulla E., Gressin V., Guillevin L. et al. Early detection of pulmonary arterial hypertension in systemic sclerosis: a French nationwide prospective multicenter study. Arthritis Rheum. 2005; 52 (12): 3792–3800. DOI: 10.1002/art.21433.

47. Tunariu N., Gibbs S.J.R., Win Z. et al. Ventilation-perfusion scintigraphy is more sensitive than multidetector CTPA in detecting chronic thromboembolic pulmonary disease as a treatable cause of pulmonary hypertension. J. Nucl. Med. 2007; 48 (5): 680–684. DOI: 10.2967/jnumed.106.039438.

48. Meng J.J., Zhang L.J., Wang Q. et al. A comparison of ventilation/perfusion single photon emission CT and CT pulmonary angiography for diagnosis of pulmonary embolism. Zhonghua Jie He He Hu Xi Za Zhi. 2013; 36 (3): 177–181.

49. Rajaram S., Swift A.J., Telfer A. et al. 3D contrast-enhanced lung perfusion MRI is an effective screening tool for chronic thromboembolic pulmonary hypertension: results from the ASPIRE Registry. Thorax. 2013; 68 (7): 677–678. DOI: 10.1136/thoraxjnl-2012-203020.

50. Rajaram S., Swift A.J., Condliffe R. et al. CT features of pulmonary arterial hypertension and its major subtypes: a systematic CT evaluation of 292 patients from the ASPIRE Registry. Thorax. 2015; 70 (4): 382–387. DOI: 10.1136/thoraxjnl-2014-206088.

51. Shen Y., Wan C., Tian P. et al. CT-base pulmonary artery measurement in the detection of pulmonary hypertension: a meta-analysis and systematic review. Medicine (Baltimore). 2014; 93 (27): e256. DOI: 10.1097/MD.0000000000000256.

52. Tan R.T., Kuzo R., Goodman L.R. et al. Utility of CT scan evaluation for predicting pulmonary hypertension in patients with parenchymal lung disease. Chest. 1998; 113 (5): 1250–1256.

53. Resten A., Maitre S., Humbert M. et al. Pulmonary hypertension: CT of the chest in pulmonary venoocclusive disease. Am. J. Roentgenol. 2004; 183 (1): 65–70. DOI: 10.2214/ajr.183.1.1830065.

54. Dartevelle P., Fadel E., Mussot S. et al. Chronic thromboembolic pulmonary hypertension. Eur. Respir. J. 2004; 23 (4): 637–648.

55. Reichelt A., Hoeper M.M., Galanski M. et al. Chronic thromboembolic pulmonary hypertension: evaluation with 64-detector row CT versus digital substraction angiography. Eur. J. Radiol. 2008; 71 (1): 49–54. DOI: 10.1016/j.ejrad.2008.03.016.

56. Fedullo P.F., Auger W.R., Kerr K.M. et al. Chronic thromboembolic pulmonary hypertension. N. Engl. J. Med. 2001; 345 (20): 1465–1472. DOI: 10.1056/NEJMra010902.

57. Fukui S., Ogo T., Morita Y. et al. Right ventricular reverse remodelling after balloon pulmonary angioplasty. Eur. Respir. J. 2014; 43 (5): 1394–1402. DOI: 10.1183/09031936.00012914.

58. Castaner E., Alguersuari A., Andreu M. et al. Imaging findings in pulmonary vasculitis. Semin. Ultrasound. CT MR. 2012; 33 (6): 567–579. DOI: 10.1053/j.sult.2012.05.001.

59. Nawaz A., Litt H.I., Stavropoulos S.W. et al. Digital subtraction pulmonary arteriography versus multidetector CT in the detection of pulmonary arteriovenous malformations. J. Vasc. Interv. Radiol. 2008; 19 (11): 1582–1588. DOI: 10.1016/j.jvir.2008.07.011.

60. Peacock A.J., Vonk Noordegraaf A. Cardiac magnetic resonance imaging in pulmonary arterial hypertension. Eur. Respir. Rev. 2013; 22 (130): 526–534. DOI: 10.1183/09059180.00006313.

61. Swift A.J., Rajaram S., Condliffe R. et al. Diagnostic accuracy of cardiovascular magnetic resonance imaging of right ventricular morphology and function in the assessment of suspected pulmonary hypertension results from the ASPIRE registry. J. Cardiovasc. Magn. Reson. 2012; 14: 40–50. DOI: 10.1186/1532-429X-14-40.

62. Swift A.J., Rajaram S., Hurdman J. et al. Noninvasive estimation of PA pressure, flow, and resistance with CMR imaging: derivation and prospective validation study from the ASPIRE registry. JACC Cardiovasc. Imaging. 2013; 6 (10): 1036–1047. DOI: 10.1016/j.jcmg.2013.01.013.

63. Ley S., Kauczor H.U., Heussel C.P. et al. Value of contrast-enhanced MR angiography and helical CT angiography in chronic thromboembolic pulmonary hypertension. Eur. Radiol. 2003; 13 (10): 2365–2371. DOI: 10.1007/s00330-003-1878-8.

64. van Wolferen S.A., Marcus J.T., Boonstra A. et al. Prognostic value of right ventricular mass, volume, and function in idiopathic pulmonary arterial hypertension. Eur. Heart J. 2007; 28 (10): 1250–1257. DOI: 10.1093/eurheartj/ehl477.

65. Peacock A.J., Crawley S., McLure L. et al. Changes in right ventricular function measured by cardiac magnetic resonance imaging in patients receiving pulmonary arterial hypertension–targeted therapy: the EURO-MR Study. Circ. Cardiovasc. Imaging. 2014; 7 (1): 107–114. DOI: 10.1161/CIRCIMAGING.113.000629.

66. van de Veerdonk M.C., Kind T., Marcus J.T. et al. Progressive right ventricular dysfunction in patients with pulmonary arterial hypertension responding to therapy. J. Am. Coll. Cardiol. 2011; 58 (24): 2511–2519. DOI: 10.1016/j.jacc.2011.06.068.

67. Albrecht T., Blomley M.J., Cosgrove D.O. et al. Non-invasive diagnosis of hepatic cirrhosis by transit-time analysis of an ultrasound contrast agent. Lancet. 1999; 353 (9164): 1579–1583. DOI: 10.1016/S0140-6736(98)06373-9.

68. Naeije R. Hepatopulmonary syndrome and portopulmonary hypertension. Swiss. Med. Wkly. 2003; 133 (11-12): 163–169. DOI: 2003/11/smw-10016.

69. Hoeper M.M., Lee S.H., Voswinckel R. et al. Complications of right heart catheterization procedures in patients with pulmonary hypertension in experienced centers. J. Am. Coll. Cardiol. 2006; 48 (12): 2546–2552. DOI: 10.1016/j.jacc.2006.07.061.

70. Kovacs G., Avian A., Pienn M. et al. Reading pulmonary vascular pressure tracings. How to handle the problems of zero leveling and respiratory swings. Am. J. Respir. Crit. Care Med. 2014; 190: 252–257.

71. Hoeper M.M., Maier R., Tongers J. et al. Determination of cardiac output by the Fick method, thermodilution, and acetylene rebreathing in pulmonary hypertension. Am. J. Respir. Crit. Care Med. 1999; 160 (2): 535–541. DOI: 10.1164/ajrccm.160.2.9811062.

72. Frost A.E., Farber H.W., Barst R.J. et al. Demographics and outcomes of patients diagnosed with pulmonary hypertension with pulmonary capillary wedge pressures 16 to 18 mm Hg: insights from the REVEAL Registry. Chest. 2013; 143 (1): 185–195. DOI: 10.1378/chest.11-1387.

73. Abraham W.T., Adamson P.B., Bourge R.C. et al. Wireless pulmonary artery haemodynamic monitoring in chronic heart failure: a randomised controlled trial. Lancet. 2011; 377 (9766): 658–666. DOI: 10.1016/S0140-6736(11)60101-3.

74. Prasad A., Hastings J.L., Shibata S. et al. Characterization of static and dynamic left ventricular diastolic function in patients with heart failure with a preserved ejection fraction. Circ. Heart Fail. 2010; 3 (5): 617–626. DOI: 10.1161/CIRCHEARTFAILURE.109.867044.

75. Fujimoto N., Borlaug B.A., Lewis G.D. et al. Hemodynamic responses to rapid saline loading: the impact of age, sex, and heart failure. Circulation. 2013; 127 (1): 55–62. DOI: 10.1161/CIRCULATIONAHA.112.111302.

76. Fox B.D., Shimony A., Langleben D. et al. High prevalence of occult left heart disease in scleroderma-pulmonary hypertension. Eur. Respir. J. 2013; 42 (4): 1083–1091. DOI: 10.1183/09031936.00091212.

77. Robbins I.M., Hemnes A.R., Pugh M.E. et al. High prevalence of occult pulmonary venous hypertension revealed by fluid challenge in pulmonary hypertension. Circ. Heart Fail. 2014; 7 (1): 116–122. DOI: 10.1161/CIRCHEARTFAILURE.113.000468.

78. Borlaug B.A., Nishimura R.A., Sorajja P. et al. Exercise hemodynamics enhance diagnosis of early heart failure with preserved ejection fraction. Circ. Heart Fail. 2010; 3 (5): 588–595. DOI: 10.1161/CIRCHEARTFAILURE.109.930701.

79. Hager W.D., Collins I., Tate J.P. et al. Exercise during cardiac catheterization distinguishes between pulmonary and left ventricular causes of dyspnea in systemic sclerosis patients. Clin. Respir. J. 2013; 7 (3): 227–236. DOI: 10.1111/j.1752-699X.2012.00310.x.

80. Halpern S.D., Taichman D.B. Misclassification of pulmonary hypertension due to reliance on pulmonary capillary wedge pressure rather than left ventricular end-diastolic pressure. Chest. 2009; 136 (1): 37–43. DOI: 10.1378/chest.08-2784.

81. Naeije R., Vachiery J.L., Yerly P. et al. The transpulmonary pressure gradient for the diagnosis of pulmonary vascular disease. Eur. Respir. J. 2013; 41 (1): 217–223. DOI: 10.1183/09031936.00074312.

82. Provencher S., Herve P., Sitbon O. et al. Changes in exercise haemodynamics during treatment in pulmonary arterial hypertension. Eur. Respir. J. 2008; 32 (2): 393–398. DOI: 10.1183/09031936.00009008.

83. Tedford R.J., Beaty C.A., Mathai S.C. et al. Prognostic value of the pre-transplant diastolic pulmonary artery pressure-to-pulmonary capillary wedge pressure gradient in cardiac transplant recipients with pulmonary hypertension. J. Heart Lung Transplant. 2014; 33: 289–297. DOI: 10.1056/NEJM199207093270203.

84. Rich S., Kaufmann E., Levy P.S. The effect of high doses of calcium-channel blockers on survival in primary pulmonary hypertension [see comments]. N. Engl. J. Med. 1992; 327 (2): 76–81.

85. Sitbon O., Humbert M., Jaïs X., et al. Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation. 2005; 111 (23): 3105–3111. DOI: 10.1161/CIRCULATIONAHA.104.488486.

86. Barst R., McGoon M., Torbicki A. et al. Diagnosis and differential assessment of pulmonary arterial hypertension. J. Am. Coll. Cardiol. 2004; 43 (Suppl. 1): S40–S47.

87. Morgan J.M., McCormack D.G., Griffiths M.J. et al. Adenosine as a vasodilator in primary pulmonary hypertension [see comments]. Circulation. 1991; 84 (83): 1145–1149.

88. Nootens M., Schrader B., Kaufmann E. et al. Comparative acute effects of adenosine and prostacyclin in primary pulmonary hypertension. Chest. 1995; 107 (1): 54–57.

89. Hoeper M.M., Olschewski H., Ghofrani H.A. et al. A comparison of the acute hemodynamic effects of inhaled nitric oxide and aerosolized iloprost in primary pulmonary hypertension. J. Am. Coll. Cardiol. 2000; 35 (1): 176–182.

90. Opitz C.F., Wensel R., Bettmann M. et al. Assessment of the vasodilator response in primary pulmonary hypertension. Comparing prostacyclin and iloprost administered by either infusion or inhalation. Eur. Heart J. 2003; 24: 356–365.

91. Kim N.H., Delcroix M., Jenkins D.P. et al. Chronic thromboembolic pulmonary hypertension. J. Am. Coll. Cardiol. 2013; 62 (25, Suppl.): D92–D99. DOI: 10.1016/j.jacc.2013.10.024.

92. Montani D., Price L.C., Dorfmuller P. et al. Pulmonary veno-occlusive disease. Eur. Respir. J. 2009; 33 (1): 189–200. DOI: 10.1183/09031936.00090608.

93. He J., Fang W., Lv B. et al. Diagnosis of chronic thromboembolic pulmonary hypertension: comparison of ventilation/perfusion scanning and multidetector computed tomography pulmonary angiography with pulmonary angiography. Nucl. Med. Commun. 2012; 33 (5): 459–463. DOI: 10.1097/MNM.0b013e32835085d9.

94. Cottin V., Le Pavec J., Prevot G. et al. Pulmonary hypertension in patients with combined pulmonary fibrosis and emphysema syndrome. Eur. Respir. J. 2010; 35 (1): 105–111. DOI: 10.1183/09031936.00038709.

95. Taichman D.B., McGoon M.D., Harhay M.O. et al. Wide variation in clinicians’ assessment of New York Heart Association/World Health Organization functional class in patients with pulmonary arterial hypertension. Mayo Clin. Proc. 2009; 84 (7): 586–592. DOI: 10.1016/S0025-6196(11)60747-7.

96. Sitbon O., Humbert M., Nunes H. et al. Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: prognostic factors and survival. J. Am. Coll. Cardiol. 2002; 40 (4): 780–788.

97. Nickel N., Golpon H., Greer M. et al. The prognostic impact of follow-up assessments in patients with idiopathic pulmonary arterial hypertension. Eur. Respir. J. 2012; 39 (3): 589–596. DOI: 10.1183/09031936.00092311.

98. Barst R.J., Chung L., Zamanian R.T. et al. Functional class improvement and 3-year survival outcomes in patients with pulmonary arterial hypertension in the REVEAL Registry. Chest. 2013; 144 (1): 160–168. DOI: 10.1378/chest.12-2417.

99. Benza R.L., Miller D.P., Gomberg-Maitland M. et al. Predicting survival in pulmonary arterial hypertension: insights from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL). Circulation. 2010; 122 (2): 164–172. DOI: 10.1161/CIRCULATIONAHA.109.898122.

100. McLaughlin V.V., Sitbon O., Badesch D.B. et al. Survival with first-line bosentan in patients with primary pulmonary hypertension. Eur. Respir. J. 2005; 25 (2): 244–249. DOI: 10.1183/09031936.05.00054804.

101. Sachdev A., Villarraga H.R., Frantz R.P. et al. Right ventricular strain for prediction of survival in patients with pulmonary arterial hypertension. Chest. 2011; 139 (6): 1299–1309. DOI: 10.1378/chest.10-2015.

102. Raymond R.J., Hinderliter A.L., Willis P.W. et al. Echocardiographic predictors of adverse outcomes in primary pulmonary hypertension. J. Am. Coll. Cardiol. 2002; 39 (7): 1214–1219.

103. Bustamante-Labarta M., Perrone S., De La Fuente R.L. et al. Right atrial size and tricuspid regurgitation severity predict mortality or transplantation in primary pulmonary hypertension. J. Am. Soc. Echocardiogr. 2002; 15 (10, Pt 2): 1160–1164.

104. Forfia P.R., Fisher M.R., Mathai S.C. et al. Tricuspid annular displacement predicts survival in pulmonary hypertension. Am. J. Respir. Crit. Care Med. 2006; 174 (9): 1034–1041. DOI: 10.1164/rccm.200604-547OC.

105. Thenappan T., Shah S.J., Rich S. et al. Survival in pulmonary arterial hypertension: a reappraisal of the NIH risk stratification equation. Eur. Respir. J. 2010; 35 (5): 1079–1087. DOI: 10.1183/09031936.00072709.

106. Wensel R., Opitz C.F., Anker S.D. et al. Assessment of survival in patients with primary pulmonary hypertension: importance of cardiopulmonary exercise testing. Circulation. 2002; 106 (3): 319–324.

107. McLaughlin V.V., Shillington A., Rich S. Survival in primary pulmonary hypertension: the impact of epoprostenol therapy. Circulation. 2002; 106 (12): 1477–1482.

108. Fine N.M., Chen L., Bastiansen P.M. et al. Outcome prediction by quantitative right ventricular function assessment in 575 subjects evaluated for pulmonary hypertension. Circ. Cardiovasc. Imaging. 2013; 6 (5): 711–721. DOI: 10.1161/CIRCIMAGING.113.000640.

109. Shimada Y.J., Shiota M., Siegel R.J. et al. Accuracy of right ventricular volumes and function determined by three-dimensional echocardiography in comparison with magnetic resonance imaging: a meta-analysis study. J. Am. Soc. Echocardiogr. 2010; 23 (9): 943–953. DOI: 10.1016/j.echo.2010.06.029.

110. Smith B.C., Dobson G., Dawson D. et al. Three-dimensional speckle tracking of the right ventricle: toward optimal quantification of right ventricular dysfunction in pulmonary hypertension. J. Am. Coll. Cardiol. 2014; 64 (1): 41–51. DOI: 10.1016/j.jacc.2014.01.084.

111. Grunig E., Tiede H., Enyimayew E.O. et al. Assessment and prognostic relevance of right ventricular contractile reserve in patients with severe pulmonary hypertension. Circulation. 2013; 128 (18): 2005–2015. DOI: 10.1161/CIRCULATIONAHA.113.001573.

112. Swift A.J., Rajaram S., Marshall H. et al. Black blood MRI has diagnostic and prognostic value in the assessment of patients with pulmonary hypertension. Eur. Radiol. 2012; 22 (3): 695–702. DOI: 10.1007/s00330-011-2306-0.

113. Swift A.J., Rajaram S., Campbell M.J. et al. Prognostic value of cardiovascular magnetic resonance imaging measurements corrected for age and sex in idiopathic pulmonary arterial hypertension. Circ. Cardiovasc. Imaging. 2014; 7 (1): 100–106. DOI: 10.1161/CIRCIMAGING.113.000338.

114. Sitbon O., McLaughlin V.V., Badesch D.B. et al. Survival in patients with class III idiopathic pulmonary arterial hypertension treated with first line oral bosentan compared with an historical cohort of patients started on intravenous epoprostenol. Thorax. 2005; 60 (12): 1025–1030. DOI: 10.1136/thx.2005.040618.

115. Rich J.D., Archer S.L., Rich S. Noninvasive cardiac output measurements in patients with pulmonary hypertension. Eur. Respir. J. 2013; 42 (1): 125–133. DOI: 10.1183/09031936.00102212.

116. Savarese G., Paolillo S., Costanzo P. et al. Do changes of 6-minute walk distance predict clinical events in patients with pulmonary arterial hypertension?: a meta-analysis of 22 randomized trials. J. Am. Coll. Cardiol. 2012; 60 (13): 1192–1201. DOI: 10.1016/j.jacc.2012.01.083.

117. Gabler N.B., French B., Strom B.L. et al. Validation of 6-minute walk distance as a surrogate end point in pulmonary arterial hypertension trials. Circulation. 2012; 126 (3): 349–356. DOI: 10.1161/CIRCULATIONAHA.112.105890.

118. Fritz J.S., Blair C., Oudiz R.J. et al. Baseline and follow-up 6-min walk distance and brain natriuretic peptide predict 2-year mortality in pulmonary arterial hypertension. Chest. 2013; 143 (2): 315–323. DOI: 10.1378/chest.12-0270.

119. Paciocco G., Martinez F., Bossone E. et al. Oxygen desaturation on the six-minute walk test and mortality in untreated primary pulmonary hypertension. Eur. Respir. J. 2001; 17 (4): 647–652.

120. Provencher S., Chemla D., Herve P. et al. Heart rate responses during the 6-minute walk test in pulmonary arterial hypertension. Eur. Respir. J. 2006; 27 (1): 114–120. DOI: 10.1183/09031936.06.00042705.

121. Sun X.G., Hansen J.E., Oudiz R.J. et al. Exercise pathophysiology in patients with primary pulmonary hypertension. Circulation. 2001; 104 (4): 429–435.

122. Wensel R., Francis D.P., Meyer F.J. et al. Incremental prognostic value of cardiopulmonary exercise testing and resting haemodynamics in pulmonary arterial hypertension. Int. J. Cardiol. 2013; 167 (4): 1193–1198. DOI: 10.1016/j.ijcard.2012.03.135.

123. Blumberg F.C., Arzt M., Lange T. et al. Impact of right ventricular reserve on exercise capacity and survival in patients with pulmonary hypertension. Eur. J. Heart Fail. 2013; 15 (7): 771–775. DOI: 10.1093/eurjhf/hft044.

124. Diller G.P., Dimopoulos K., Okonko D. et al. Exercise intolerance in adult congenital heart disease: comparative severity, correlates, and prognostic implication. Circulation. 2005; 112 (6): 828–835. DOI: 10.1161/CIRCULATIONAHA.104.529800.

125. Arena R., Lavie C.J., Milani R.V. et al. Cardiopulmonary exercise testing in patients with pulmonary arterial hypertension: an evidence-based review. J. Heart Lung Transplant. 2010; 29 (2): 159–173. DOI: 10.1016/j.healun.2009.09.003.

126. Pullamsetti S., Kiss L., Ghofrani H.A. et al. Increased levels and reduced catabolism of asymmetric and symmetric dimethylarginines in pulmonary hypertension. FASEB J. 2005; 19 (9): 1175–1177. DOI: 10.1096/fj.04-3223fje.

127. Kielstein J.T., Bode-Boger S.M., Hesse G. et al. Asymmetrical dimethylarginine in idiopathic pulmonary arterial hypertension. Arterioscler. Thromb. Vasc. Biol. 2005; 25 (7): 1414–1418. DOI: 10.1161/01.ATV.0000168414.06853.f0.

128. Kielstein J.T., Impraim B., Simmel S. et al. Cardiovascular effects of systemic nitric oxide synthase inhibition with asymmetrical dimethylarginine in humans. Circulation. 2004; 109 (2): 172–177. DOI: 10.1161/01.CIR.0000105764.22626.B1.

129. Kawut S.M., Horn E.M., Berekashvili K.K. et al. von Willebrand factor independently predicts long-term survival in patients with pulmonary arterial hypertension. Chest. 2005; 128 (4): 2355–2362. DOI: 10.1378/chest.128.4.2355.

130. Kümpers P., Nickel N., Lukasz A. et al. Circulating angiopoietins in idiopathic pulmonary arterial hypertension. Eur. Heart J. 2010; 31 (18): 2291–2300. DOI: 10.1093/eurheartj/ehq226.

131. Rubens C., Ewert R., Halank M. et al. Big endothelin-1 and endothelin-1 plasma levels are correlated with the severity of primary pulmonary hypertension. Chest. 2001; 120 (5): 1562–1569.

132. Quarck R., Nawrot T., Meyns B. et al. C-reactive protein: a new predictor of adverse outcome in pulmonary arterial hypertension. J. Am. Coll. Cardiol. 2009; 53 (14): 1211–1218. DOI: 10.1016/j.jacc.2008.12.038.

133. Balabanian K., Foussat A., Dorfmuller P. et al. CX(3)C chemokine fractalkine in pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. 2002; 165 (10): 1419–1425. DOI: 10.1164/rccm.2106007.

134. Dorfmuller P., Zarka V., Durand-Gasselin I, et al. Chemokine RANTES in severe pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. 2002; 165 (4): 534–539. DOI: 10.1164/ajrccm.165.4.2012112.

135. Humbert M., Monti G., Brenot F. et al. Increased interleukin-1 and interleukin-6 serum concentrations in severe primary pulmonary hypertension. Am. J. Respir. Crit. Care Med. 1995; 151 (5): 1628–1631. DOI: 10.1164/ajrccm.151.5.7735624.

136. Nagaya N., Nishikimi T., Uematsu M. et al. Plasma brain natriuretic peptide as a prognostic indicator in patients with primary pulmonary hypertension. Circulation. 2000; 102 (8): 865–870.

137. Leuchte H.H., El Nounou M., Tuerpe J.C. et al. N-terminal pro-brain natriuretic peptide and renal insufficiency as predictors of mortality in pulmonary hypertension. Chest. 2007; 131 (2): 402–409. DOI: 10.1378/chest.06-1758.

138. Fijalkowska A., Kurzyna M., Torbicki A. et al. Serum N-terminal brain natriuretic peptide as a prognostic parameter in patients with pulmonary hypertension. Chest. 2006; 129 (5): 1313–1321. DOI: 10.1378/chest.129.5.1313.

139. Torbicki A., Kurzyna M., Kuca P. et al. Detectable serum cardiac troponin T as a marker of poor prognosis among patients with chronic precapillary pulmonary hypertension. Circulation. 2003; 108 (7): 844–848. DOI: 10.1161/01.CIR.0000084544.54513.E2.

140. Nickel N., Kempf T., Tapken H. et al. Growth differentiation factor-15 in idiopathic pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. 2008; 178 (5): 534–541. DOI: 10.1164/rccm.200802-235OC.

141. Nagaya N., Uematsu M., Satoh T. et al. Serum uric acid levels correlate with the severity and the mortality of primary pulmonary hypertension. Am. J. Respir. Crit. Care Med. 1999; 160 (2): 487–492. DOI: 10.1164/ajrccm.160.2.9812078.

142. Lorenzen J.M., Nickel N., Kramer R. et al. Osteopontin in patients with idiopathic pulmonary hypertension. Chest. 2011; 139 (5): 1010–1017. DOI: 10.1378/chest.10-1146.

143. Warwick G., Thomas P.S., Yates D.H. Biomarkers in pulmonary hypertension. Eur. Respir. J. 2008; 32 (2): 503–512. DOI: 10.1183/09031936.00160307.

144. Hoeper M.M., Markevych I., Spiekerkoetter E. et al. Goal-oriented treatment and combination therapy for pulmonary arterial hypertension. Eur. Respir. J. 2005; 26 (5): 858–863. DOI: 10.1183/09031936.05.00075305.

145. McLaughlin V.V., Gaine S.P., Howard L.S. et al. Treatment goals of pulmonary hypertension. J. Am. Coll. Cardiol. 2013; 62 (25, Suppl.): D73–D81.

146. Galiè N., Manes A., Negro L. et al. A meta-analysis of randomized controlled trials in pulmonary arterial hypertension. Eur. Heart J. 2009; 30 (4): 394–403. DOI: 10.1093/eurheartj/ehp022.

147. Bai Y., Sun L., Hu S. et al. Combination therapy in pulmonary arterial hypertension: a meta-analysis. Cardiology. 2011; 120 (3): 157–165. DOI: 10.1159/000334431.

148. Galie N., Simonneau G. The Fifth World Symposium on Pulmonary Arterial Hypertension. J. Am. Coll. Cardiol. 2013; 62 (Suppl.): D1–D3.

149. Galie N., Corris P., Frost A. et al. Updated treatment algorithm of pulmonary hypertension. J. Am. Coll. Cardiol. 2013; 62 (Suppl.): D60–D72.

150. Lowe B., Grafe K., Ufer C. et al. Anxiety and depression in patients with pulmonary hypertension. Psychosom. Med. 2004; 66 (6): 831–836. DOI: 10.1097/01.psy.0000145593.37594.39.

151. Galie N., Hoeper M., Humbert M. et al. Guidelines on diagnosis and treatment of pulmonary hypertension: the Task Force on Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology and of the European Respiratory Society. Eur. Heart J. 2009; 30 (20): 2493–2537. DOI: 10.1093/eurheartj/ehp297.

152. Mereles D., Ehlken N., Kreuscher S. et al. Exercise and respiratory training improve exercise capacity and quality of life in patients with severe chronic pulmonary hypertension. Circulation. 2006; 114 (14): 1482–1489. DOI: 10.1161/CIRCULATIONAHA.106.618397.

153. de Man F.S., Handoko M.L., Groepenhoff H. et al. Effects of exercise training in patients with idiopathic pulmonary arterial hypertension. Eur. Respir. J. 2009; 34 (3): 669–675. DOI: 10.1183/09031936.00027909.

154. Grunig E., Ehlken N., Ghofrani A. et al. Effect of exercise and respiratory training on clinical progression and survival in patients with severe chronic pulmonary hypertension. Respiration. 2011; 81 (5): 394–401. DOI: 10.1159/000322475.

155. Grunig E., Maier F., Ehlken N. et al. Exercise training in pulmonary arterial hypertension associated with connective tissue diseases. Arthritis Res. Ther. 2012; 14 (3): R148. DOI: 10.1186/ar3883.

156. Grunig E., Lichtblau M., Ehlken N. et al. Safety and efficacy of exercise training in various forms of pulmonary hypertension. Eur. Respir. J. 2012; 40 (1): 84–92. DOI: 10.1183/09031936.00123711.

157. Becker-Grunig T., Klose H., Ehlken N. et al. Efficacy of exercise training in pulmonary arterial hypertension associated with congenital heart disease. Int. J. Cardiol. 2013; 168 (1): 375–381. DOI: 10.1016/j.ijcard.2012.09.036.

158. Weinstein A.A., Chin L.M.K., Keyser R.E. et al. Effect of aerobic exercise training on fatigue and physical activity in patients with pulmonary arterial hypertension. Respir. Med. 2013; 107 (5): 778–784. DOI: 10.1016/j.rmed.2013.02.006.

159. Chan L., Chin L.M., Kennedy M. et al. Benefits of intensive treadmill exercise training on cardiorespiratory function and quality of life in patients with pulmonary hypertension. Chest. 2013; 143 (2): 333–343. DOI: 10.1378/chest.12-0993.

160. Jais X., Olsson K.M., Barbera J.A. et al. Pregnancy outcomes in pulmonary arterial hypertension in the modern management era. Eur. Respir. J. 2012; 40 (4): 881–885. DOI: 10.1183/09031936.00141211.

161. Duarte A.G., Thomas S., Safdar Z. et al. Management of pulmonary arterial hypertension during pregnancy: a retrospective, multicenter experience. Chest. 2013; 143 (5): 1330–1336. DOI: 10.1378/chest.12-0528.

162. Thorne S., Nelson-Piercy C., MacGregor A.J. et al. Pregnancy and contraception in heart disease and pulmonary arterial hypertension. J. Fam. Plann. Reprod. Health Care. 2006; 32 (2): 75–81. DOI: 10.1783/147118906776276486.

163. Bendayan D., Hod M., Oron G. et al. Pregnancy outcome in patients with pulmonary arterial hypertension receiving prostacyclin therapy. Obstet. Gynecol. 2005; 106 (5, Pt 2): 1206–1210. DOI: 10.1097/01.AOG.0000164074.64137.f1.

164. Bonnin M., Mercier F.J., Sitbon O. et al. Severe pulmonary hypertension during pregnancy: mode of delivery and anesthetic management of 15 consecutive cases. Anesthesiology. 2005; 102 (6): 1133–1137.

165. Meyer S., McLaughlin V.V., Seyfarth H.J. et al. Outcomes of noncardiac, nonobstetric surgery in patients with PAH: an international prospective survey. Eur. Respir. J. 2013; 41 (6): 1302–1307. DOI: 10.1183/09031936.00089212.

166. Olofsson C., Bremme K., Forssell G. et al. Cesarean section under epidural ropivacaine 0.75% in a parturient with severe pulmonary hypertension. Acta. Anaesthesiol. Scand. 2001; 45 (2): 258–260.

167. Raines D.E., Liberthson R.R., Murray J.R. Anesthetic management and outcome following noncardiac surgery in nonparturients with Eisenmenger’s physiology. J. Clin. Anesth.1996; 8 (5): 341–347.

168. Guillevin L., Armstrong I., Aldrighetti R. et al. Understanding the impact of pulmonary arterial hypertension on patients’ and carers’ lives. Eur. Respir. Rev. 2013; 22 (130): 535–542. DOI: 10.1183/09059180.00005713.

169. Weitzenblum E., Sautegeau A., Ehrhart M. et al. Long-term oxygen therapy can reverse the progression of pulmonary hypertension in patients with chronic obstructive pulmonary disease. Am. Rev. Respir. Dis. 1985; 131 (4): 493–498. DOI: 10.1164/arrd.1985.131.4.493.

170. Frydman N., Steffann J., Girerd B., et al. Pre-implantation genetic diagnosis in pulmonary arterial hypertension due to BMPR2 mutation. Eur. Respir. J. 2012; 39 (6): 1534–1535. DOI: 10.1183/09031936.00185011.

171. Fuster V., Steele P.M., Edwards W.D. et al. Primary pulmonary hypertension: natural history and the importance of thrombosis. Circulation. 1984; 70 (4): 580–587.

172. Herve P., Humbert M., Sitbon O. et al. Pathobiology of pulmonary hypertension: the role of platelets and thrombosis. Clin. Chest Med. 2001 (3); 22: 451–458.

173. Hoeper M.M., Sosada M., Fabel H. Plasma coagulation profiles in patients with severe primary pulmonary hypertension. Eur. Respir. J. 1998; 12 (6): 1446–1449.

174. Huber K., Beckmann R., Frank H. et al. Fibrinogen, t-PA, and PAI-1 plasma levels in patients with pulmonary hypertension. Am. J. Respir. Crit. Care Med. 1994; 150 (4): 929–933. DOI: 10.1164/ajrccm.150.4.7921465.

175. Olsson K.M., Delcroix M., Ghofrani H.A. et al. Anticoagulation and survival in pulmonary arterial hypertension: results from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA). Circulation. 2014; 129 (1): 57–65. DOI: 10.1161/CIRCULATIONAHA.113.004526.

176. Galie N., Delcroix M., Ghofrani A. et al. Anticoagulant therapy does not influence long-term outcomes in patients with pulmonary arterial hypertension (PAH): insights from the randomised controlled SERAPHIN trial of macitentan. Eur. Heart J. 2014; 35: 10–12.

177. Preston R.J., Roberts K.E., Miller D.P. et al. Effect of warfarin treatment on survival of patients with pulmonary arterial hypertension (PAH) in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL). Am. J. Respir. Crit. Care Med. 2014; 189: A2464.

178. Cohn J.N. Optimal diuretic therapy for heart failure. Am. J. Med. 2001; 111 (7): 577.

179. Sandoval J., Aguirre J.S., Pulido T. et al. Nocturnal oxygen therapy in patients with the Eisenmenger syndrome. Am. J. Respir. Crit. Care Med. 2001; 164 (9): 1682–1687. DOI: 10.1164/ajrccm.164.9.2106076.

180. Rich S., Seidlitz M., Dodin E. et al. The short-term effects of digoxin in patients with right ventricular dysfunction from pulmonary hypertension. Chest. 1998; 114 (3): 787–792.

181. Ruiter G., Lankhorst S., Boonstra A. et al. Iron deficiency is common in idiopathic pulmonary arterial hypertension. Eur. Respir. J. 2011; 37: 1386–1391.

182. Ruiter G., Lanser I.J., de Man F.S. et al. Iron deficiency in systemic sclerosis patients with and without pulmonary hypertension. Rheumatology (Oxford). 2014; 53 (2): 285–292. DOI: 10.1093/rheumatology/ket331.

183. Broberg C.S., Bax B.E., Okonko D.O. et al. Blood viscosity and its relationship to iron deficiency, symptoms, and exercise capacity in adults with cyanotic congenital heart disease. J. Am. Coll. Cardiol. 2006; 48 (2): 356–365. DOI: 10.1016/j.jacc.2006.03.040.

184. Rhodes C.J., Howard L.S., Busbridge M. et al. Iron deficiency and raised hepcidin in idiopathic pulmonary arterial hypertension clinical prevalence, outcomes, and mechanistic insights. J. Am. Coll. Cardiol. 2011; 58 (3): 300–309. DOI: 10.1016/j.jacc.2011.02.057.

185. Van De Bruaene A., Delcroix M., Pasquet A. et al. Iron deficiency is associated with adverse outcome in Eisenmenger patients. Eur. Heart J. 2011; 32 (22): 2790–2799. DOI: 10.1093/eurheartj/ehr130.

186. Viethen T., Gerhardt F., Dumitrescu D. et al. Ferric carboxymaltose improves exercise capacity and quality of life in patients with pulmonary arterial hypertension and iron deficiency: a pilot study. Int. J. Cardiol. 2014; 175 (2): 233–239. DOI: 10.1016/j.ijcard.2014.04.233.

187. Galie N., Ussia G., Passarelli P. et al. Role of pharmacologic tests in the treatment of primary pulmonary hypertension. Am. J. Cardiol. 1995; 75 (3): 55A–62A.

188. Mukerjee D., St. George D., Coleiro B. et al. Prevalence and outcome in systemic sclerosis associated pulmonary arterial hypertension: application of a registry approach. Ann. Rheum. Dis. 2003; 62 (11): 1088–1093.

189. Montani D., Savale L., Natali D. et al. Long-term response to calcium-channel blockers in non-idiopathic pulmonary arterial hypertension. Eur. Heart J. 2010; 31 (15): 1898–1907. DOI: 10.1093/eurheartj/ehq170.

190. Giaid A., Yanagisawa M., Langleben D. et al. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N. Engl. J. Med. 1993; 328 (4): 1732–1739. DOI: 10.1056/NEJM199306173282402.

191. Stewart D.J., Levy R.D., Cernacek P. et al. Increased plasma endothelin-1 in pulmonary hypertension: marker or mediator of disease? Ann. Intern. Med. 1991; 114 (6): 464–469.

192. Galie N., Manes A., Branzi A. The endothelin system in pulmonary arterial hypertension. Cardiovasc. Res. 2004; 61 (2): 227–237.

193. Galie N., Badesch B.D., Oudiz R. et al. Ambrisentan therapy for pulmonary arterial hypertension. J. Am. Coll. Cardiol. 2005; 46 (3): 529–535. DOI: 10.1016/j.jacc.2005.04.050.

194. Galie N., Olschewski H., Oudiz R.J. et al. Ambrisentan for the treatment of pulmonary arterial hypertension. Results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2. Circulation. 2008; 117 (23): 3010–3019. DOI: 10.1161/CIRCULATIONAHA.107.742510.

195. McGoon M., Frost A., Oudiz R. et al. Ambrisentan therapy in patients with pulmonary arterial hypertension who discontinued bosentan or sitaxsentan due to liver function test abnormalities. Chest. 2009; 135 (1): 122–129. DOI: 10.1378/chest.08-1028.

196. Channick R.N., Simonneau G., Sitbon O. et al. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet. 2001; 358 (9288): 1119–1123. DOI: 10.1016/S0140-6736(01)06250-X.

197. Rubin L.J., Badesch D.B., Barst R.J. et al. Bosentan therapy for pulmonary arterial hypertension. N. Engl. J. Med. 2002; 346 (12): 896–903. DOI: 10.1056/NEJMoa012212.

198. Humbert M., Barst R.J., Robbins I.M. et al. Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2. Eur. Respir. J. 2004; 24 (3): 353–359. DOI: 10.1183/09031936.04.00028404.

199. Galie N., Rubin L.J., Hoeper M. et al. Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind, randomised controlled trial. Lancet. 2008; 371 (9630): 2093–2100. DOI: 10.1016/S0140-6736(08)60919-8.

200. Galie N., Beghetti M., Gatzoulis M.A. et al. Bosentan therapy in patients with Eisenmenger syndrome: a multicenter, double-blind, randomized, placebo-controlled study. Circulation. 2006; 114 (1): 48–54. DOI: 10.1161/CIRCULATIONAHA.106.630715.

201. Pulido T., Adzerikho I., Channick R.N. et al. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N. Engl. J. Med. 2013; 369 (9): 809–818. DOI: 10.1056/NEJMoa1213917.

202. Wharton J., Strange J.W., Moller G.M.O. et al. Antiproliferative effects of phosphodiesterase type 5 inhibition in human pulmonary artery cells. Am. J. Respir. Crit. Care Med. 2005; 172 (1): 105–113. DOI: 10.1164/rccm.200411-1587OC.

203. Tantini B., Manes A., Fiumana E. et al. Antiproliferative effect of sildenafil on human pulmonary artery smooth muscle cells. Basic. Res. Cardiol. 2005; 100 (2): 131–138. DOI: 10.1007/s00395-004-0504-5.

204. Ghofrani H.A., Voswinckel R., Reichenberger F. et al. Differences in hemodynamic and oxygenation responses to three different phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension: a randomized prospective study. J. Am. Coll. Cardiol. 2004; 44 (7): 1488–1496. DOI: 10.1016/j.jacc.2004.06.060.

205. Galie N., Ghofrani H.A., Torbicki A. et al. the Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group. Sildenafil citrate therapy for pulmonary arterial hypertension. N. Engl. J. Med. 2005; 353 (20): 2148–2157. DOI: 10.1056/NEJMoa050010.

206. Sastry B.K.S., Narasimhan C., Reddy N.K. et al. Clinical efficacy of sildenafil in primary pulmonary hypertension: a randomized, placebo-controlled, double-blind, crossover study. J. Am. Coll. Cardiol. 2004; 43 (7): 1149–1153. DOI: 10.1016/j.jacc.2003.10.056.

207. Iversen K., Jensen A.S., Jensen T.V. et al. Combination therapy with bosentan and sildenafil in Eisenmenger syndrome: a randomized, placebo-controlled, double-blinded trial. Eur. Heart J. 2010; 31 (9): 1124–1131. DOI: 10.1093/eurheartj/ehq011.

208. Singh T., Rohit M., Grover A. et al. A randomized, placebo-controlled, double-blind, crossover study to evaluate the efficacy of oral sildenafil therapy in severe pulmonary artery hypertension. Am. Heart J. 2006; 151 (4): 851.e1–851.e5. DOI: 10.1016/j.ahj.2005.09.006.

209. Simonneau G., Rubin L., Galie N. et al. Addition of sildenafil to long-term intravenous epoprostenol therapy in patients with pulmonary arterial hypertension. Ann. Intern. Med. 2008; 149 (8): 521–530.

210. Vachiery J.L., Huez S., Gillies H. et al. Safety, tolerability and pharmacokinetics of an intravenous bolus of sildenafil in patients with pulmonary arterial hypertension. Br. J. Clin. Pharmacol. 2011; 71 (2): 289–292. DOI: 10.1111/j.1365-2125.2010.03831.x.

211. Galie N., Brundage B.H., Ghofrani H.A. et al. Tadalafil therapy for pulmonary arterial hypertension. Circulation. 2009; 119 (22): 2894–2903. DOI: 10.1161/CIRCULATIONAHA.108.839274.

212. Jing Z.C., Yu Z.X., Shen J.Y. et al. Vardenafil in pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled study. Am. J. Respir. Crit. Care Med. 2011; 183 (12): 1723–1729. DOI: 10.1164/rccm.201101-0093OC.

213. Giaid A., Saleh D. Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension. N. Engl. J. Med. 1995; 333 (4): 214–221. DOI: 10.1056/NEJM199507273330403.

214. Ghofrani H.A., Galie N., Grimminger F. et al. Riociguat for the treatment of pulmonary arterial hypertension. N. Engl. J. Med. 2013; 369 (4): 330–340. DOI: 10.1056/NEJMoa1209655.

215. Galie N., Muller K., Scalise A.V. et al. PATENT PLUS: a blinded, randomised and extension study of riociguat plus sildenafil in PAH. Eur. Respir. J. 2015; 45 (5): 1314–1322. DOI: 10.1183/09031936.00105914.

216. Jones D.A., Benjamin C.W., Linseman D.A. Activation of thromboxane and prostacyclin receptors elicits opposing effects on vascular smooth muscle cell growth and mitogen-activated protein kinase signaling cascades. Mol. Pharmacol. 1995; 48 (5): 890–896.

217. Galie N., Manes A., Branzi A. Prostanoids for pulmonary arterial hypertension. Am. J. Respir. Med. 2003; 2 (2): 123–137.

218. Galie N., Humbert M., Vachiery J.L. et al. Effects of beraprost sodium, an oral prostacyclin analogue, in patients with pulmonary arterial hypertension: a randomised, double-blind placebo-controlled trial. J. Am. Coll. Cardiol. 2002; 39 (9): 1496–1502.

219. Barst R.J., McGoon M., McLaughlin V.V. et al. Beraprost therapy for pulmonary arterial hypertension. J. Am. Coll. Cardiol. 2003; 41 (12): 2119–2125.

220. Rubin L.J., Mendoza J., Hood M. et al. Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol). Results of a randomized trial. Ann. Intern. Med. 1990; 112 (7): 485–491. DOI: 10.7326/0003-4819-112-7-485.

221. Barst R.J., Rubin L.J., Long W.A. et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N. Engl. J. Med. 1996; 334 (5): 296–302. DOI: 10.1056/NEJM199602013340504.

222. Badesch D.B., Tapson V.F., McGoon M.D. et al. Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial. Ann. Intern. Med. 2000; 132 (6): 425–434.

223. Rosenzweig E.B., Kerstein D., Barst R.J. Long-term prostacyclin for pulmonary hypertension with associated congenital heart defects. Circulation. 1999; 99 (14): 1858–1865.

224. Krowka M.J., Frantz R.P., McGoon M.D. et al. Improvement in pulmonary hemodynamics during intravenous epoprostenol (prostacyclin): a study of 15 patients with moderate to severe portopulmonary hypertension. Hepatology. 1999; 30 (3): 641–648. DOI: 10.1002/hep.510300307.

225. Nunes H., Humbert M., Sitbon O. et al. Prognostic factors for survival in human immunodeficiency virus-associated pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. 2003; 167 (10): 1433–1439. DOI: 10.1164/rccm.200204-330OC.

226. Cabrol S., Souza R., Jais X. et al. Intravenous epoprostenol in inoperable chronic thromboembolic pulmonary hypertension. J. Heart Lung. Transplant. 2007; 26 (4): 357–362. DOI: 10.1016/j.healun.2006.12.014.

227. Doran A.K., Ivy D.D., Barst R.J. et al. Guidelines for the prevention of central venous catheter-related blood stream infections with prostanoid therapy for pulmonary arterial hypertension. Int. J. Clin. Pract. Suppl. 2008; 62 (160): 5–9. DOI: 10.1111/j.1742-1241.2008.01811.x.

228. Sitbon O., Delcroix M., Bergot E. et al. EPITOME-2: an open-label study assessing the transition to a new formulation of intravenous epoprostenol in patients with pulmonary arterial hypertension. Am. Heart J. 2014; 167 (2): 210–217. DOI: 10.1016/j.ahj.2013.08.007.

229. Olschewski H., Simonneau G., Galie N. et al. Inhaled iloprost in severe pulmonary hypertension. N. Engl. J. Med. 2002; 347 (5): 322–329. DOI: 10.1056/NEJMoa020204.

230. McLaughlin V.V., Oudiz R.J., Frost A. et al. Randomized study of adding inhaled iloprost to existing bosentan in pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. 2006; 174 (11): 1257–1263. DOI: 10.1164/rccm.200603-358OC.

231. Hoeper M., Leuchte H., Halank M. et al. Combining inhaled iloprost with bosentan in patients with idiopathic pulmonary arterial hypertension. Eur. Respir. J. 2006; 28 (4): 691–694. DOI: 10.1183/09031936.06.00057906.

232. Higenbottam T., Butt A.Y., McMahon A. et al. Long-term intravenous prostaglandin (epoprostenol or iloprost) for treatment of severe pulmonary hypertension. Heart. 1998; 80 (2): 151–155.

233. Simonneau G., Barst R.J., Galie N. et al. Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension. A double-blind, randomized, placebo-controlled trial. Am. J. Respir. Crit. Care Med. 2002; 165 (6): 800–804. DOI: 10.1164/ajrccm.165.6.2106079.

234. Hiremath J., Thanikachalam S., Parikh K. et al. Exercise improvement and plasma biomarker changes with intravenous treprostinil therapy for pulmonary arterial hypertension: a placebo-controlled trial. J. Heart Lung Transplant. 2010; 29 (2): 137–149. DOI: 10.1016/j.healun.2009.09.005.

235. Tapson V.F., Gomberg-Maitland M., McLaughlin V.V. et al. Safety and efficacy of IV treprostinil for pulmonary arterial hypertension: a prospective, multicenter, open-label, 12-week trial. Chest. 2006; 129 (3): 683–688. DOI: 10.1378/chest.129.3.683.

236. Sitbon O., Manes A., Jais X. et al. Rapid switch from intravenous epoprostenol to intravenous treprostinil in patients with pulmonary arterial hypertension. J. Cardiovasc. Pharmacol. 2007; 49 (1): 1–5. DOI: 10.1097/FJC.0b013e31802b3184.

237. McLaughlin V., Rubin L., Benza R.L. et al. Addition of inhaled treprostinil to oral therapy for pulmonary arterial hypertension: a randomized controlled clinical trial. J. Am. Coll. Cardiol. 2010; 55 (18): 1915–1922. DOI: 10.1016/j.jacc.2010.01.027.

238. Tapson V.F., Torres F., Kermeen F. et al. Oral treprostinil for the treatment of pulmonary arterial hypertension in patients on background endothelin receptor antagonist and/or phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C study): a randomized controlled trial. Chest. 2012; 142 (6): 1383–1390. DOI: 10.1378/chest.11-2212.

239. Tapson V.F., Jing Z.C., Xu K.F. et al. Oral treprostinil for the treatment of pulmonary arterial hypertension in patients on background endothelin receptor antagonist and/or phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C2 study): a randomized controlled trial. Chest. 2012;142 (6): 1383-1390. DOI: 10.1378/chest.11-2212.

240. Jing Z.C., Parikh K., Pulido T. et al. Efficacy and safety of oral treprostinil monotherapy for the treatment of pulmonary arterial hypertension: a randomized, controlled trial. Circulation. 2013; 127 (5): 624–633. DOI: 10.1161/CIRCULATIONAHA.112.124388.

241. Simonneau G., Torbicki A., Hoeper M.M. et al. Selexipag, an oral, selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension. Eur. Respir. J. 2012; 40 (4): 874–880. DOI: 10.1183/09031936.00137511.

242. Chen S.L., Zhang F.F., 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. DOI: 10.1016/j.jacc.2013.05.075.

243. Galie N., Manes A. New treatment strategies for pulmonary arterial hypertension: hopes or hypes? J. Am. Coll. Cardiol. 2013; 62 (12): 1101–1102. DOI: 10.1016/j.jacc.2013.06.032.

244. Galie N., Palazzini M., Manes A. Pulmonary arterial hypertension: from the kingdom of the near-dead to multiple clinical trial meta-analyses. Eur. Heart J. 2010; 31 (17): 2080–2086. DOI: 10.1093/eurheartj/ehq152.

245. Kemp K., Savale L., O’Callaghan D.S. et al. Usefulness of first-line combination therapy with epoprostenol and bosentan in pulmonary arterial hypertension: an observational study. J. Heart Lung Transplant. 2012; 31 (2): 150–158. DOI: 10.1016/j.healun.2011.11.002.

246. Sitbon O., Jais X., Savale L. et al. Upfront triple combination therapy in pulmonary arterial hypertension: a pilot study. Eur. Respir. J. 2014; 43 (6): 1691–1697. DOI: 10.1183/09031936.00116313.

247. Galie N., Barbera J.A., Frost A. et al. Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension. N. Engl. J. Med. 2015; 379: 834–844. DOI: 10.1056/NEJMoa1413687.

248. McLaughlin V.V., Channick R., Chin K.M. et al. Effect of selexipag on morbidity/mortality in pulmonary arterial hypertension: results of the GRIPHON study. J. Am. Coll. Cardiol. 2015; 65 (Suppl. A): A380.

249. Badesch B.D., Feldman J., Keogh A. et al. ARIES-3: ambrisentan therapy in a diverse population of patients with pulmonary hypertension. Cardiovasc. Ther. 2012; 30 (2): 93–99. DOI: 10.1111/j.1755-5922.2011.00279.x.

250. Provencher S., Sitbon O., Humbert M. et al. Long-term outcome with first-line bosentan therapy in idiopathic pulmonary arterial hypertension. Eur. Heart J. 2006; 27 (5): 589–595. DOI: 10.1093/eurheartj/ehi728.

251. McLaughlin V., Channick R.N., Ghofrani H.A. et al. Bosentan added to sildenafil therapy in patients with pulmonary arterial hypertension. Eur. Respir. J. 2015; 46 (2): 405–413. DOI: 10.1183/13993003.02044-2014.

252. Dardi F., Manes A., Palazzini M. et al. Combining bosentan and sildenafil in pulmonary arterial hypertension patients failing monotherapy: real-world insights. Eur. Respir. J. 2015; 46 (2): 414–421. DOI: 10.1183/09031936.00209914.

253. Sandoval J., Gaspar J., Pulido T. et al. Graded balloon dilation atrial septostomy in severe primary pulmonary hypertension. A therapeutic alternative for patients nonresponsive to vasodilator treatment. J. Am. Coll. Cardiol. 1998; 32: 297–304.

254. Kurzyna M., Dabrowski M., Bielecki D. et al. Atrial septostomy in treatment of end-stage right heart failure in Patients with pulmonary hypertension. Chest. 2007; 131 (4): 977–983. DOI: 10.1378/chest.06-1227.

255. Althoff T.F., Knebel F., Panda A. et al. Long-term follow-up of a fenestrated Amplatzer atrial septal occluder in pulmonary arterial hypertension. Chest. 2008; 133 (1): 283–285. DOI: 10.1378/chest.07-1222.

256. Keogh A., Benza R.L., Corris P. et al. Interventional and surgical modalities of treatment in pulmonary arterial hypertension. J. Am. Coll. Cardiol. 2009; 54 (Suppl.): S67–S77.

257. Sztrymf B., Souza R., Bertoletti I. et al. Prognostic factors of acute heart failure in patients with pulmonary arterial hypertension. Eur. Respir. J. 2010; 35 (6): 1286–1293. DOI: 10.1183/09031936.00070209.

258. Zamanian R.T., Haddad F., Doyle R.L. et al. Management strategies for patients with pulmonary hypertension in the intensive care unit. Crit. Care Med. 2007; 35 (9): 2037–2050.

259. Price L.C., Wort S.J., Finney S.J. et al. Pulmonary vascular and right ventricular dysfunction in adult critical care: current and emerging options for management: a systematic literature review. Crit. Care. 2010; 14 (5): R169. DOI: 10.1186/cc9264.

260. Hoeper M.M., Granton J. Intensive care unit management of patients with severe pulmonary hypertension and right heart failure. Am. J. Respir. Crit. Care Med. 2011; 184 (10): 1114–1124. DOI: 10.1164/rccm.201104-0662CI.

261. Rosenzweig E.B., Brodie D., Abrams D.C. et al. Extracorporeal membrane oxygenation as a novel bridging strategy for acute right heart failure in group 1 pulmonary arterial hypertension. ASAIO J. 2014; 60 (1): 129–133. DOI: 10.1097/MAT.0000000000000021.

262. Olsson K.M., Simon A., Strueber M. et al. Extracorporeal membrane oxygenation in nonintubated patients as bridge to lung transplantation. Am. J. Transplant. 2010; 10 (9): 2173–2178. DOI: 10.1111/j.1600-6143.2010.03192.x.

263. Fuehner T., Kuehn C., Hadem J. et al. Extracorporeal membrane oxygenation in awake patients as bridge to lung transplantation. Am. J. Respir. Crit. Care Med. 2012; 185 (7): 763–768. DOI: 10.1164/rccm.201109-1599OC.

264. de Perrot M., Granton J.T., McRae K. et al. Impact of extracorporeal life support on outcome in patients with idiopathic pulmonary arterial hypertension awaiting lung transplantation. J. Heart Lung Transplant. 2011; 30 (9): 997–1002. DOI: 10.1016/j.healun.2011.03.002.

265. Strueber M., Hoeper M.M., Fischer S. et al. Bridge to thoracic organ transplantation in patients with pulmonary arterial hypertension using a pumpless lung assist device. Am. J. Transplant. 2009; 9 (4): 853–857. DOI: 10.1111/j.1600-6143.2009.02549.x.

266. Trulock E.P., Edwards L.B., Taylor D.O. et al. Registry of the International Society for Heart and Lung Transplantation: twenty-third official adult lung and heart lung transplantation report-2006. J. Heart Lung Transplant. 2006; 25: 880–892.

267. Toyoda Y., Thacker J., Santos R. et al. Long-term outcome of lung and heart-lung transplantation for idiopathic pulmonary arterial hypertension. Ann. Thorac. Surg. 2008; 86: 1116–1122.

268. Fadel E., Mercier O., Mussot S. et al. Long-term outcome of double-lung and heart−lung transplantation for pulmonary hypertension: a comparative retrospective study of 219 patients. Eur. J. Cardiothorac. Surg. 2010; 38 (4): 277–284. DOI: 10.1016/j.athoracsur.2008.05.049.

269. de Perrot M., Granton J.T., McRae K. et al. Outcome of patients with pulmonary arterial hypertension referred for lung transplantation: a 14-year single-center experience. J. Thorac. Cardiovasc. Surg. 2012; 143 (4): 910–918. DOI: 10.1016/j.jtcvs.2011.08.055.

270. Christie J.D., Edwards L.B., Kucheryavaya A.Y. et al. The Registry of the International Society for Heart and Lung Transplantation: 29th adult lung and heart-lung transplant report–2012. J. Heart Lung Transplant. 2012; 31: 1073–1086.

271. Waddell T.K., Bennett L., Kennedy R. et al. Heart-lung or lung transplantation for Eisenmenger syndrome. J. Heart Lung Transplant. 2002; 21 (7): 731–737.

272. Choong C.K., Sweet S.C., Guthrie T.J. et al. Repair of congenital heart lesions combined with lung transplantation for the treatment of severe pulmonary hypertension: a 13-year experience. J. Thorac. Cardiovasc. Surg. 2005; 129 (3): 661–669. DOI: 10.1016/j.jtcvs.2004.07.058.

273. Fleming T.R., Powers J.H. Biomarkers and surrogate endpoints in clinical trials. Statistic. Med. 2012; 31 (25): 2973–2984.

274. Fleming T.R. Surrogate endpoints and FDA accelerated approval process. Health Affairs. 2005; 24 (1): 67–78. DOI: 10.1377/hlthaff.24.1.67.

275. Tongers J., Schwerdtfeger B., Klein G. et al. Incidence and clinical relevance of supraventricular tachyarrhythmias in pulmonary hypertension. Am. Heart J. 2007; 153 (1): 127–132.

276. Hoeper M.M., Galie N., Murali S. et al. Outcome after cardiopulmonary resuscitation in patients with pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. 2002; 165 (3): 341–344. DOI: 10.1164/ajrccm.165.3.200109-0130c.

277. Showkathali R., Tayebjee M.H., Grapsa J. et al. Right atrial flutter isthmus ablation is feasible and results in acute clinical improvement in patients with persistent atrial flutter and severe pulmonary arterial hypertension. Int. J. Cardiol. 2011; 139 (3): 279–280. DOI: 10.1378/chest.10-1134.

278. Zylkowska J., Kurzyna M., Pietura R. et al. Recurrent hemoptysis: an emerging life-threatening complication in idiopathic pulmonary arterial hypertension. Chest. 2011; 139 (3): 690–693. DOI: 10.1378/chest.10-1134.

279. Zylkowska J., Kurzyna M., Florczyk M. et al. Pulmonary artery dilatation correlates with the risk of unexpected death in chronic arterial or thromboembolic pulmonary hypertension. Chest. 2012; 142 (6): 1406–1416. DOI: 10.1378/chest.11-2794.

280. Russo V., Zompatori M., Galie N. Extensive right pulmonary artery dissection in a young patient with chronic pulmonary hypertension. Heart. 2012; 98 (3): 265–266. DOI: 10.1136/heartjnl-2011-301132.

281. Demerouti E.A., Manginas A.N., Athanassopoulos G.D. et al. Complications leading to sudden cardiac death in pulmonary arterial hypertension. Respir. Care. 2013; 58 (7): 1246–1254. DOI: 10.4187/respcare.02252.

282. Lee M.S., Oyama J., Bhatia R. et al. Left main coronary artery compression from pulmonary artery enlargement due to pulmonary hypertension: a contemporary review and argument for percutaneous revascularization. Catheter. Cardiovasc. Interv. 2010; 76 (4): 543–550. DOI: 10.1002/ccd.22592.

283. Barst R.J., Ertel S.I., Beghetti M. et al. Pulmonary arterial hypertension: a comparison between children and adults. Eur. Respir. J. 2011; 37 (3): 665–677. DOI: 10.1183/09031936.00056110.

284. Barst R.J., McGoon M.D., Elliott C.G. et al. Survival in childhood pulmonary arterial hypertension. Circulation. 2012; 125 (1): 113–122. DOI: 10.1161/CIRCULATIONAHA.111.026591.

285. van Loon R.L., Roofthooft M.T.R., Hillege H.L. et al. Pediatric pulmonary hypertension in the Netherlands: epidemiology and characterization during the period 1991 to 2005. Circulation. 2011; 124 (16): 1755–1764. DOI: 10.1161/CIRCULATIONAHA.110.969584.

286. Moledina S., Hislop A.A., Foster H. et al. Childhood idiopathic pulmonary arterial hypertension: a national cohort study. Heart. 2010; 96 (17): 1401–1406. DOI: 10.1136/hrt.2009.182378.

287. Berger R.M., Beghetti M., Humpl T. et al. Clinical features of paediatric pulmonary hypertension: a registry study. Lancet. 2012; 379 (9815): 537–546. DOI: 10.1016/S0140-6736(11)61621-8.

288. Hansmann G., Hoeper M.M. Registries for paediatric pulmonary hypertension. Eur. Respir. J. 2013; 42 (3): 580–583. DOI: 10.1183/09031936.00065713.

289. Cerro M.J., 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 (2): 286–298. DOI: 10.4103/2045-8932.83456.

290. Beghetti M., Berger R.M., Schulze-Neick I. et al. Diagnostic evaluation of paediatric pulmonary hypertension in current clinical practice. Eur. Respir. J. 2013; 42 (3): 689–700. DOI: 10.1183/09031936.00140112.

291. Schulze-Neick I., Beghetti M. Issues related to the management and therapy of paediatric pulmonary hypertension. Eur. Respir. Rev. 2010; 19 (118): 331–339. DOI: 10.1183/09059180.00008510.

292. Adatia I., Haworth S.G., Wegner M. et al. Clinical trials in neonates and children: report of the Pulmonary Hypertension Academic Research Consortium Pediatric Advisory Committee. Pulm. Circ. 2013; 3 (1): 252–266. DOI: 10.4103/2045-8932.109931.

293. Lammers A.E., Hislop A.A., Flynn Y. et al. Epoprostenol treatment in children with severe pulmonary hypertension. Heart. 2007; 93 (6): 739–743. DOI: 10.1136/hrt.2006.096412.

294. Barst R.J., Maislin G., Fishman A.P. Vasodilator therapy for primary pulmonary hypertension in children. Circulation. 1999; 99 (9): 1197–1208. DOI: 10.1161/01.CIR.99.9.1197.

295. Levy M., Celermajer D.S., Bourges-Petit E. et al. Add-on therapy with subcutaneous treprostinil for refractory pediatric pulmonary hypertension. J. Pediatr. 2011; 158 (4): 584–588. DOI: 10.1016/j.jpeds.2010.09.025.

296. Ivy D.D., Doran A.K., Smith K.J. et al. Short- and long-term effects of inhaled iloprost therapy in children with pulmonary arterial hypertension. J. Am. Coll. Cardiol. 2008; 51 (2): 161–169. DOI: 10.1016/j.jacc.2007.09.031.

297. Barst R., Ivy D., Widlitz A.C. et al. Pharmacokinetics, safety, and efficacy of bosentan in pediatric patients with pulmonary arterial hypertension. Clin. Pharmacol. Therl. 2003; 73 (4): 372–382. DOI: 10.1016/S0009-9236(03)00005-5.

298. Rosenzweig E.B., Ivy D.D., Widlitz A. et al. Effects of long-term bosentan in children with pulmonary arterial hypertension. J. Am. Coll. Cardiol. 2005; 46 (4): 697–704. DOI: 10.1016/j.jacc.2005.01.066.

299. Beghetti M., Haworth S.G., Bonnet D. et al. Pharmacokinetic and clinical profile of a novel formulation of bosentan in children with pulmonary arterial hypertension: the FUTURE-1 study. Br. J. Clin. Pharmacol. 2009; 68 (6): 948–955. DOI: 10.1111/j.1365-2125.2009.03532.x.

300. Barst R.J., Ivy D.D., Gaitan G. et al. A randomized, double-blind, placebo-controlled, dose-ranging study of oral sildenafil citrate in treatment-naive children with pulmonary arterial hypertension. Circulation. 2012; 125 (2): 324–334. DOI: 10.1161/CIRCULATIONAHA.110.016667.

301. Barst R.J., Beghetti M., Pulido T. et al. STARTS-2: long-term survival with oral sildenafil monotherapy in treatment-naive pediatric pulmonary arterial hypertension. Circulation. 2014; 129 (19): 1914–1923. DOI: 10.1161/CIRCULATIONAHA.113.005698.

302. Takatsuki S., Calderbank M., Ivy D.D. Initial experience with tadalafil in pediatric pulmonary arterial hypertension. Pediatr. Cardiol. 2012; 33 (5): 683–688. DOI: 10.1007/s00246-012-0180-4.

303. Douwes J.M., Roofthooft M.T., Van Loon R.L. et al. Sildenafil add-on therapy in paediatric pulmonary arterial hypertension, experiences of a national referral centre. Heart. 2014; 100 (3): 224–230. DOI: 10.1136/heartjnl-2013-304895.

304. Micheletti A., Hislop A.A., Lammers A. et al. Role of atrial septostomy in the treatment of children with pulmonary arterial hypertension. Heart. 2006; 92 (7): 969–972. DOI: 10.1136/hrt.2005.077669.

305. Boudjemline Y., Patel M., Malekzadeh-Milani 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 (2): e18–20. DOI: 10.1161/CIRCINTERVENTIONS.112.000091.

306. Baruteau A.E., Belli E., Boudjemline Y. et al. Palliative Potts shunt for the treatment of children with drug-refractory pulmonary arterial hypertension: updated data from the first 24 patients. Eur. J. Cardiothorac. Surg. 2015; 47 (3): e105–110. DOI: 10.1093/ejcts/ezu445.

307. Esch J.J., Shah P.B., Cockrill B.A. et al. Transcatheter Potts shunt creation in patients with severe pulmonary arterial hypertension: initial clinical experience. J. Heart. Lung Transplant. 2013; 32 (4): 381–387. DOI: 10.1016/j.healun.2013.01.1049.

308. Ploegstra M.J., Douwes J.M., Roofthooft M.T. et al. Identification of treatment goals in paediatric pulmonary arterial hypertension. Eur. Respir. J. 2014; 44 (6): 1616–1626. DOI: 10.1183/09031936.00030414.

309. Galiè N., Manes A., Palazzini M. et al. Management of pulmonary arterial hypertension associated with congenital systemic-to-pulmonary shunts and Eisenmenger’s syndrome. Drugs. 2008; 68 (8): 1049–1066.

310. Engelfriet P.M., Duffels M.G.J., Moller T. et al. Pulmonary arterial hypertension in adults born with a Heart septal defect: the Euro Heart Survey on adult congenital Heart disease. Heart. 2007; 93 (6): 682–687. DOI: 10.1136/hrt.2006.098848.

311. Beghetti M., Galie N. Eisenmenger syndrome: a clinical perspective in a new therapeutic era of pulmonary arterial hypertension. J. Am. Coll. Cardiol. 2009; 53 (9): 733–740. DOI: 10.1016/j.jacc.2008.11.025.

312. Daliento L., Somerville J., Presbitero P. et al. Eisenmenger syndrome. Factors relating to deterioration and death. Eur. Heart J. 1998; 19 (12): 1845–1855.

313. Hopkins W.E., Ochoa L.L., Richardson G.W. et al. Comparison of the hemodynamics and survival of adults with severe primary pulmonary hypertension or Eisenmenger syndrome. J. Heart Lung Transplant. 1996; 15 (1, Pt 1): 100–105.

314. Manes A., Palazzini M., Leci E. et al. Current era survival of patients with pulmonary arterial hypertension associated with congenital heart disease: a comparison between clinical subgroups. Eur. Heart J. 2014; 35 (11): 716–724. DOI: 10.1093/eurheartj/eht072.

315. Hopkins W.E. The remarkable right ventricle of patients with Eisenmenger syndrome. Coron. Artery Dis. 2005; 16 (1): 19–25.

316. Diller G.P., Gatzoulis M.A. Pulmonary vascular disease in adults with congenital heart disease. Circulation. 2007; 115 (8): 1039–1050. DOI: 10.1161/CIRCULATIONAHA.105.592386.

317. Moller J.H., Patton C., Varco R.L. et al. Late results (30 to 35 years) after operative closure of isolated ventricular septal defect from 1954 to 1960. Am. J. Cardiol. 1991; 68 (15): 1491–1497. DOI: 10.1016/0002-9149(91)90284-R.

318. van Albada M.E., Berger R.M. Pulmonary arterial hypertension in congenital cardiac disease–the need for refinement of the Evian-Venice classification. Cardiol. Young. 2008; 18 (1): 10–17. DOI: 10.1017/S1047951107001849.

319. Schulze-Neick I., Beghetti M. Classifying pulmonary hypertension in the setting of the congenitally malformed heart-cleaning up a dog’s dinner. Cardiol. Young. 2008; 18 (1): 22–25. DOI: 10.1017/S1047951107001850.

320. Lopes A.A., Leary P.W. Measurement, interpretation and use of hemodynamic parameters. Cardiol. Young. 2009; 19 (Suppl. 1): 8–12. DOI: 10.1017/S1047951109003886.

321. Broberg C.S., Ujita M., Prasad S. et al. Pulmonary arterial thrombosis in Eisenmenger syndrome is associated with biventricular dysfunction and decreased pulmonary flow velocity. J. Am. Coll. Cardiol. 2007; 50 (7): 634–642. DOI: 10.1016/j.jacc.2007.04.056.

322. Gatzoulis M.A., Beghetti M., Galie N. et al. Longer-term bosentan therapy improves functional capacity in Eisenmenger syndrome: results of the BREATHE-5 open-label extension study. Int. J. Cardiol. 2007; 127 (1): 27–32. DOI: 10.1016/j.ijcard.2007.04.078.

323. Zuckerman W.A., Leaderer D., Rowan C.A. et al. Ambrisentan for pulmonary arterial hypertension due to congenital heart disease. J. Am. Coll. Cardiol. 2011; 107 (9): 1381–1385. DOI: 10.1016/j.amjcard.2010.12.051.

324. Mukhopadhyay S., Sharma M., Ramakrishnan S. et al. Phosphodiesterase-5 inhibitor in Eisenmenger syndrome: a preliminary observational study. Circulation. 2006; 114 (17): 1807–1810. DOI: 10.1161/CIRCULATIONAHA.105.603001.

325. Khanna D., Gladue H., Channick R. et al. Recommendations for screening and detection of connective tissue disease-associated pulmonary arterial hypertension. Arthritis Rheum. 2013; 65 (12): 3194–3201. DOI: 10.1002/art.38172.

326. Gashouta M.A., Humbert M., Hassoun P.M. Update in systemic sclerosis-associated pulmonary arterial hypertension. Presse Med. 2014; 43 (10, Pt 2): e293–304. DOI: 10.1016/j.lpm.2014.06.007.

327. Coghlan J.G., Denton C.P., Gruenig E. et al. Evidence-based detection of pulmonary arterial hypertension in systemic sclerosis: the DETECT study. Ann. Rheum. Dis. 2014; 73 (7): 1340–1349. DOI: 10.1136/annrheumdis-2013-203301.

328. Humbert M., Yaici A., de Groote P. et al. Screening for pulmonary arterial hypertension in patients with systemic sclerosis: clinical characteristics at diagnosis and long-term survival. Arthritis Rheum. 2011; 63 (11): 3522–3530. DOI: 10.1002/art.30541.

329. Hao Y.J., Jiang X., Zhou W. et al. Connective tissue disease-associated pulmonary arterial hypertension in Chinese patients. Eur. Respir. J. 2014; 44 (4): 963–972. DOI: 10.1183/09031936.00182813.

330. Hachulla E., Carpentier P., Gressin V. et al. Risk factors for death and the 3-year survival of patients with systemic sclerosis: the French ItinerAIR-Sclerodermie study. Rheumatology. 2009; 48 (3): 304–308. DOI: 10.1093/rheumatology/ken488.

331. Avouac J., Airo P., Meune C. et al. Prevalence of pulmonary hypertension in systemic sclerosis in European Caucasians and metaanalysis of 5 studies. J. Rheumatol. 2010; 37 (11): 2290–2298. DOI: 10.3899/jrheum.100245.

332. Gunther S., Jaïs X., Maitre S. et al. Computed tomography findings of pulmonary venoocclusive disease in scleroderma patients presenting with precapillary pulmonary hypertension. Arthritis Rheum. 2012; 64 (9): 2995–3005. DOI: 10.1002/art.34501.

333. Coghlan G. Does left Heart disease cause most systemic sclerosis associated pulmonary hypertension? Eur. Respir. J. 2013; 42 (4): 888–890. DOI: 10.1183/09031936.00025413.

334. Humbert M., Sitbon O., Yaïci A, et al. Survival in incident and prevalent cohorts of patients with pulmonary arterial hypertension. Eur. Respir. J. 2010; 36 (3): 549–555. DOI: 10.1183/09031936.00057010.

335. Fisher M.R., Mathai S.C., Champion H.C. et al. Clinical differences between idiopathic and scleroderma-related pulmonary hypertension. Arthritis Rheum. 2006; 54 (9): 3043–3050. DOI: 10.1002/art.22069.

336. Launay D., Sitbon O., Hachulla E. et al. Survival in systemic sclerosis-associated pulmonary arterial hypertension in the modern management era. Ann. Rheum. Dis. 2013; 72 (12): 1940–1946. DOI: 10.1136/annrheumdis-2012-202489.

337. O’Callaghan D.S., Dorfmuller P, Jaïs X, et al. Pulmonary veno-occlusive disease: the bete noire of pulmonary hypertension in connective tissue diseases? Presse Med. 2011; 40 (1, Pt 2): e65–78. DOI: 10.1016/j.lpm.2010.10.017.

338. Demling R.H., Smith M., Gunther R. et al. Pulmonary injury and prostaglandin production during endotoxemia in conscious sheep. Am. J. Physiol. 1981; 240 (3): H348–353.

339. Jaïs X., Launay D., Yaici A. et al. Immunosuppressive therapy in lupus- and mixed connective tissue disease-associated pulmonary arterial hypertension: a retrospective analysis of twenty-three cases. Arthritis Rheum. 2008; 58 (2): 521–531. DOI: 10.1002/art.23303.

340. Avouac J., Wipff J., Kahan A. et al. Effects of oral treatments on exercise capacity in systemic sclerosis related pulmonary arterial hypertension: a meta-analysis of randomised controlled trials. Ann. Rheum. Dis. 2008; 67 (6): 808–814. DOI: 10.1136/ard.2007.077149.

341. Launay D., Savale L., Berezne A. et al. Lung and heart-lung transplantation for systemic sclerosis patients. A monocentric experience of 13 patients, review of the literature and position paper of a multidisciplinary working group. Presse Med. 2014; 43 (10, Pt 2): e345–363. DOI: 10.1016/j.lpm.2014.01.020.

342. Hoeper M.M., Krowka M.J., Strassburg C.P. Portopulmonary hypertension and hepatopulmonary syndrome. Lancet. 2004; 363 (9419): 1461–1468. DOI: 10.1016/S0140-6736(04)16107-2.

343. Zopey R., Susanto I., Barjaktarevic I. et al. Transition from hepatopulmonary syndrome to portopulmonary hypertension: a case series of 3 patients. Case Rep. Pulmonol. 2013; 2013: 561870. DOI: 10.1155/2013/561870.

344. Krowka M.J., Swanson K.L., Frantz R.P. et al. Portopulmonary hypertension: results from a 10-year screening algorithm. Hepatology. 2006; 44 (6): 1502–1510. DOI: 10.1002/hep.21431.

345. Kawut S.M., Krowka M.J., Trotter J.F. et al. Clinical risk factors for portopulmonary hypertension. Hepatology. 2008; 48 (1): 196–203. DOI: 10.1002/hep.22275.

346. Roberts K.E., Fallon M.B., Krowka M.J. et al. Genetic risk factors for portopulmonary hypertension in patients with advanced liver disease. Am. J. Respir. Crit. Care Med. 2009; 179 (9): 835–842. DOI: 10.1164/rccm.200809-1472OC.

347. Krowka M.J., Miller D.P., Barst R.J. et al. Portopulmonary hypertension: a report from the US-based REVEAL Registry. Chest. 2012; 141 (4): 906–915. DOI: 10.1378/chest.11-0160.

348. Le Pavec J., Souza R., Herve P. et al. Portopulmonary hypertension: survival and prognostic factors. Am. J. Respir. Crit. Care Med. 2008; 178 (6): 637–643. DOI: 10.1164/rccm.200804-613OC.

349. Provencher S., Herve P., Jaïs X. et al. Deleterious effects of beta-blockers on exercise capacity and hemodynamics in patients with portopulmonary hypertension. Gastroenterology. 2006; 130 (1): 120–126. DOI: 10.1053/j.gastro.2005.10.013.

350. Hoeper M.M., Seyfarth H.J., Hoeffken G. et al. Experience with inhaled iloprost and bosentan in portopulmonary hypertension. Eur. Respir. J. 2007; 30 (6): 1096–1102. DOI: 10.1183/09031936.00032407.

351. Halank M., Knudsen L., Seyfarth H.J. et al. Ambrisentan improves exercise capacity and symptoms in patients with portopulmonary hypertension. Z. Gastroenterol. 2011; 49 (9): 1258–1262. DOI: 10.1055/s-0031-1273393.

352. Reichenberger F., Voswinckel R., Steveling E. et al. Sildenafil treatment for portopulmonary hypertension. Eur. Respir. J. 2006; 28 (3): 563–567. DOI: 10.1183/09031936.06.00030206.

353. Kuo P.C., Johnson L.B., Plotkin J.S. et al. Continuous intravenous infusion of epoprostenol for the treatment of portopulmonary hypertension. Transplantation. 1997; 63 (4): 604–606.

354. Swanson K.L., Wiesner R.H., Nyberg S.L. et al. Survival in portopulmonary hypertension: Mayo Clinic experience categorized by treatment subgroups. Am. J. Transplant. 2008; 8 (11): 2445–2453. DOI: 10.1111/j.1600-6143.2008.02384.x.

355. Sakai T., Planinsic R.M., Mathier M.A. et al. Initial experience using continuous intravenous treprostinil to manage pulmonary arterial hypertension in patients with end-stage liver disease. Transpl. Int. 2009; 22 (5): 554–561. DOI: 10.1111/j.1432-2277.2008.00830.x.

356. Savale L., Magnier R., Le Pavec J. et al. Efficacy, safety and pharmacokinetics of bosentan in portopulmonary hypertension. Eur. Respir. J. 2013; 41 (1): 96–103. DOI: 10.1183/09031936.00117511.

357. Humbert M., Segal E.S., Kiely D.G. et al. Results of European post-marketing surveillance of bosentan in pulmonary hypertension. Eur. Respir. J. 2007; 30 (2): 338–344. DOI: 10.1183/09031936.00138706.

358. Kia L., Shah S.J., Wang E. et al. Role of pretransplant echocardiographic evaluation in predicting outcomes following liver transplantation. Am. J. Transplant. 2013; 13 (9): 2395–2401. DOI: 10.1111/ajt.12385.

359. Krowka M.J., Plevak D.J., Findlay J.Y. et al. Pulmonary hemodynamics and perioperative cardiopulmonary-related mortality in patients with portopulmonary hypertension undergoing liver transplantation. Liver. Transplant. 2000; 6 (4): 443–450. DOI: 10.1053/jlts.2000.6356.

360. Ashfaq M., Chinnakotla S., Rogers L. et al. The impact of treatment of portopulmonary hypertension on survival following liver transplantation. Am. J. Transplant. 2007; 7 (5): 1258–1264. DOI: 10.1111/j.1600-6143.2006.01701.x.

361. Raevens S., De Pauw M., Reyntjens K. et al. Oral vasodilator therapy in patients with moderate to severe portopulmonary hypertension as a bridge to liver transplantation. Eur. J. Gastroenterol. Hepatol. 2013; 25 (4): 495–502. DOI: 10.1097/MEG.0b013e32835c504b.

362. Plotkin J.S., Kuo P.C., Rubin L.J. et al. Successful use of chronic epoprostenol as a bridge to liver transplantation in severe portopulmonary hypertension. Transplantation. 1998; 65 (4): 457–459.

363. Austin M.J., McDougall N.I., Wendon J.A. et al. Safety and efficacy of combined use of sildenafil, bosentan, and iloprost before and after liver transplantation in severe portopulmonary hypertension. Liver. Transplant. 2008; 14 (3): 287–291. DOI: 10.1002/lt.21310.

364. Grannas G., Neipp M., Hoeper M.M. et al. Indications for and outcomes after combined lung and liver transplantation: a single-center experience on 13 consecutive cases. Transplantation. 2008; 85 (4): 524–531. DOI: 10.1097/TP.0b013e3181636f3f.

365. Robalino B.D., Moodie D.S. Association between primary pulmonary hypertension and portal hypertension: analysis of its pathophysiology and clinical, laboratory and hemodynamic manifestations. J. Am. Coll. Cardiol.1991; 17 (2): 492–498. DOI: 10.1016/S0735-1097(10)80121-4.

366. Barbaro G., Lucchini A., Pellicelli A.M. et al. Highly active antiretroviral therapy compared with HAART and bosentan in combination in patients with HIV-associated pulmonary hypertension. Heart. 2006; 92 (8): 1164–1166. DOI: 10.1136/hrt.2005.076794.

367. Degano B. HIV-associated pulmonary arterial hypertension: survival and prognostic factors in the modern therapeutic era. AIDS. 2010; 24 (1): 67–75. DOI: 10.1097/QAD.0b013e328331c65e.

368. Opravil M., Pechere M., Speich R. et al. HIV-associated primary pulmonary hypertension. A case control study. Swiss HIV Cohort Study. Am. J. Respir. Crit. Care Med. 1997; 155 (3): 990–995. DOI: 10.1164/ajrccm.155.3.9117037.

369. Sitbon O., Lascoux-Combe C., Delfraissy J.F. et al. Prevalence of HIV-related pulmonary arterial hypertension in the current antiretroviral therapy era. Am. J. Respir. Crit. Care Med. 2008; 177 (1): 108–113. DOI: 10.1164/rccm.200704-541OC.

370. Sitbon O., Gressin V., Speich R. et al. Bosentan for the treatment of human immunodeficiency virus-associated pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. 2004; 170 (11): 1212–1217. DOI: 10.1164/rccm.200404-445OC.

371. Montani D., Achouh L., Dorfmuller P. et al. Pulmonary veno-occlusive disease: clinical, functional, radiologic, and hemodynamic characteristics and outcome of 24 cases confirmed by histology. Medicine (Baltimore) 2008; 87 (4): 220–233. DOI: 10.1097/MD.0b013e31818193bb.

372. Lantuejoul S., Sheppard M.N., Corrin B. et al. Pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis: a clinicopathologic study of 35 cases. Am. J. Surg. Pathol. 2006; 30 (7): 850–857. DOI: 10.1097/01.pas.0000209834.69972.e5.

373. Humbert M., Maître S, Capron F, et al. Pulmonary edema complicating continuous intravenous prostacyclin in pulmonary capillary hemangiomatosis. Am. J. Respir. Crit. Care Med. 1998; 157 (5, Pt 1): 1681–1685. DOI: 10.1164/ajrccm.157.5.9708065.

374. Mandel J., Mark E.J., Hales C.A. Pulmonary veno-occlusive disease. Am. J. Respir. Crit. Care Med. 2000; 162 (5): 1964–1973. DOI: 10.1164/ajrccm.162.5.9912045.

375. Langleben D., Heneghan J.M., Batten A.P. et al. Familial pulmonary capillary hemangiomatosis resulting in primary pulmonary hypertension. Ann. Intern. Med. 1988; 109 (2): 106–109 [published erratum appears in Ann. Intern. Med. 1988; 109 (5): 439].

376. Best D.H., Sumner K.L., Austin E.D. et al. EIF2AK4 mutations in pulmonary capillary hemangiomatosis. Chest. 2014; 145 (2): 231–236. DOI: 10.1378/chest.13-2366.

377. Seferian A., Helal B., Jaïs X. et al. Ventilation/perfusion lung scan in pulmonary veno-occlusive disease. Eur. Respir. J. 2012; 40 (1): 75–83. DOI: 10.1183/09031936.00097911.

378. Rabiller A., Jaïs X., Hamid A. et al. Occult alveolar haemorrhage in pulmonary veno-occlusive disease. Eur. Respir. J. 2006; 27 (1): 108–113. DOI: 10.1183/09031936.06.00054105.

379. Montani D., Jaïs X., Price L.C.et al. Cautious epoprostenol therapy is a safe bridge to lung transplantation in pulmonary veno-occlusive disease. Eur. Respir. J. 2009; 34 (6): 1348–1356. DOI: 10.1183/09031936.00017809.

380. Fang J.C., DeMarco T., Givertz M.M. et al. World Health Organization Pulmonary Hypertension Group 2: pulmonary hypertension due to left heart disease in the adult – a summary statement from the Pulmonary Hypertension Council of the International Society for Heart and Lung Transplantation. J. Heart Lung Transplant. 2012; 31 (9): 913–933. DOI: 10.1016/j.healun.2012.06.002.

381. Ghio S., Gavazzi A., Campana C. et al. Independent and additive prognostic value of right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure. J. Am. Coll. Cardiol. 2001; 37 (1): 183–188.

382. Thenappan T., Shah S.J., Gomberg-Maitland M. et al. Clinical characteristics of pulmonary hypertension in patients with heart failure and preserved ejection fraction. Circ. Heart Fail. 2011; 4 (3): 257–265. DOI: 10.1161/CIRCHEARTFAILURE.110.958801.

383. Robbins I.M., Newman J.H., Johnson R.F. et al. Association of the metabolic syndrome with pulmonary venous hypertension. Chest. 2009; 136 (1): 31–36. DOI: 10.1378/chest.08-2008.

384. Bursi F., McNallan S.M., Redfield M.M. et al. Pulmonary pressures and death in heart failure: a community study. J. Am. Coll. Cardiol. 2012; 59 (3): 222–231. DOI: 10.1016/j.jacc.2011.06.076.

385. Gerges C., Gerges M., Lang M.B. et al. Diastolic pulmonary vascular pressure gradient: a predictor of prognosis in “out-of-proportion” pulmonary hypertension. Chest. 2013; 143 (3): 758–766. DOI: 10.1378/chest.12-1653.

386. Moraes D.L., Colucci W.S., Givertz M.M. Secondary pulmonary hypertension in chronic heart failure: the role of the endothelium in pathophysiology and management. Circulation. 2000; 102 (14): 1718–1723. DOI: 10.1161/01.CIR.102.14.1718.

387. Rapp A.H., Lange R.A., Cigarroa J.E. et al. Relation of pulmonary arterial diastolic and mean pulmonary arterial wedge pressures in patients with and without pulmonary hypertension. Am. J. Cardiol. 2001; 88 (7): 823–824.

388. Miller W.L., Grill D.E., Borlaug B.A. Clinical features, hemodynamics, and outcomes of pulmonary hypertension due to chronic heart failure with reduced ejection fraction: pulmonary hypertension and heart failure. JACC Heart Fail. 2013; 1 (4): 290–299. DOI: 10.1016/j.jchf.2013.05.001.

389. Tampakakis E., Leary P.J., Selby V.N. et al. The diastolic pulmonary gradient does not predict survival in patients with pulmonary hypertension due to left heart disease. JACC Heart Fail. 2015; 3 (1): 9–16. DOI: 10.1016/j.jchf.2014.07.010.

390. Pellegrini P., Rossi A., Pasotti M. et al. Prognostic relevance of pulmonary arterial compliance in patients with chronic heart failure. Chest. 2014; 145 (5): 1064–1070. DOI: 10.1378/chest.13-1510.

391. Chatterjee N.A., Lewis G.D. Characterization of pulmonary hypertension in heart failure using the diastolic pressure gradient: limitations of a solitary measurement. JACC Heart Fail. 2015; 3 (1): 17–21. DOI: 10.1016/j.jchf.2014.09.002.

392. McMurray J.J., Adamopoulos S., Anker S.D. et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur. Heart J. 2012; 14 (8): 1787–1847. [published erratum appears in Eur. J. Heart Fail. 2013; 15 (3): 361–362]. DOI: 10.1093/eurjhf/hfs105.

393. Khush K.K., Tasissa G., Butler J. et al. Effect of pulmonary hypertension on clinical outcomes in advanced heart failure: analysis of the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) database. Am. Heart J. 2009; 157 (6): 1026–1034. DOI: 10.1016/j.ahj.2009.02.022.

394. Patel N.D., Weiss E.S., Schaffer J. et al. Right heart dysfunction after left ventricular assist device implantation: a comparison of the pulsatile Heart Mate I and axial-flow Heart Mate II devices. Ann. Thorac. Surg. 2008; 86 (3): 832–840. DOI: 10.1016/j.athoracsur.2008.05.016.

395. Torre-Amione G., Southard R.E., Loebe M.M. et al. Reversal of secondary pulmonary hypertension by axial and pulsatile mechanical circulatory support. J. Heart Lung Transplant. 2010; 29 (2): 195–200. DOI: 10.1016/j.healun.2009.05.030.

396. Barnett C.F., DeMarco T. Pulmonary hypertension associated with left-sided heart disease. Heart Fail. Clin. 2012; 8 (3): 447–459. DOI: 10.1016/j.hfc.2012.04.009.

397. Bonderman D., Ghio S., Felix S.B. et al. Riociguat for patients with pulmonary hypertension caused by systolic left ventricular dysfunction: a phase IIb double-blind, randomized, placebo-controlled, dose-ranging hemodynamic study. Circulation. 2013; 128 (5): 502–511. DOI: 10.1161/CIRCULATIONAHA.113.001458.

398. Oswald-Mammosser M., Weitzenblum E., Quoix E. et al. Prognostic factors in COPD patients receiving long-term oxygen therapy. Importance of pulmonary artery pressure. Chest. 1995; 107 (5): 1193–1198.

399. Kessler R., Faller M., Weitzenblum E. et al. “Natural history” of pulmonary hypertension in a series of 131 patients with chronic obstructive lung disease. Am. J. Respir. Crit. Care Med. 2001; 164 (2): 219–224. DOI: 10.1164/ajrccm.164.2.2006129.

400. Lettieri C.J., Nathan S.D., Barnett S.D. et al. Prevalence and outcomes of pulmonary arterial hypertension in advanced idiopathic pulmonary fibrosis. Chest. 2006; 129 (3): 746–752. DOI: 10.1378/chest.129.3.746.

401. Thabut G., Dauriat G., Stern J.B. et al. Pulmonary hemodynamics in advanced COPD candidates for lung volume reduction surgery or lung transplantation. Chest. 2005; 127 (5): 1531–1536. DOI: 10.1378/chest.127.5.1531.

402. Chaouat A., Bugnet A.S., Kadaoui N. et al. Severe pulmonary hypertension and chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2005; 172 (2): 189–194. DOI: 10.1164/rccm.200401-006OC.

403. Arcasoy S.M., Christie J.D., Ferrari V.A. et al. Echocardiographic assessment of pulmonary hypertension in patients with advance lung disease. Am. J. Respir. Crit. Care Med. 2003; 167 (5): 735–740. DOI: 10.1164/rccm.200210-1130OC.

404. Fisher M.R., Forfia P.R., Chamera E. et al. Accuracy of Doppler echocardiography in the hemodynamic assessment of pulmonary hypertension. Am. J. Respir. Crit. Care Med. 2009; 179 (7): 615–621. DOI: 10.1164/rccm.200811-1691OC.

405. Nathan S.D., Shlobin O.A., Barnett S.D. et al. Right ventricular systolic pressure by echocardiography as a predictor of pulmonary hypertension in idiopathic pulmonary fibrosis. Respir. Med. 2008; 102 (9): 1305–1310. DOI: 10.1016/j.rmed.2008.03.022.

406. Agusti A.G., Barbera J.A., Roca J. et al. Hypoxic pulmonary vasoconstriction and gas exchange during exercise in chronic obstructive pulmonary disease. Chest. 1990; 97 (2): 268–275. DOI: 10.1378/chest.97.2.268.

407. Barbera J.A., Roger N., Roca J. et al. Worsening of pulmonary gas exchange with nitric oxide inhalation in chronic obstructive pulmonary disease. Lancet. 1996; 347 (8999): 436–440.

408. Simonneau G., Escourrou P., Duroux P. et al. Inhibition of hypoxic pulmonary vasoconstriction by nifedipine. N. Engl. J. Med. 1981; 304 (26): 1582–1585. DOI: 10.1056/NEJM198106253042606.

409. Morrell N.W., Higham M.A., Phillips P.G. et al. Pilot study of losartan for pulmonary hypertension in chronic obstructive pulmonary disease. Respir. Res. 2005; 6: 88–95. DOI: 10.1186/1465-9921-6-88.

410. Saadjian A., Philip-Joet F., Paganelli F. et al. Long-term effects of cicletanine on secondary pulmonary hypertension. J. Cardiovasc. Pharmacol. 1998; 31 (3): 364–371.

411. Stolz D., Rasch H., Linka A. et al. A randomised, controlled trial of bosentan in severe COPD. Eur. Respir. J. 2008; 32 (3): 619–628. DOI: 10.1183/09031936.00011308.

412. Blanco I., Gimeno E., Munoz P.A. et al. Hemodynamic and gas exchange effects of sildenafil in patients with chronic obstructive pulmonary disease and pulmonary hypertension. Am. J. Respir. Crit. Care Med. 2010; 181 (3): 270–278. DOI: 10.1164/rccm.200907-0988OC.

413. Zisman D.A., Schwarz M., Anstrom K.J. et al. A controlled trial of sildenafil in advanced idiopathic pulmonary fibrosis. N. Engl. J. Med. 2010; 363 (7): 620–628. DOI: 10.1056/NEJMoa1002110.

414. Blanco I., Santos S., Gea J. et al. Sildenafil to improve respiratory rehabilitation outcomes in COPD: a controlled trial. Eur. Respir. J. 2013; 42 (4): 982–992. DOI: 10.1183/09031936.00176312.

415. Lederer D.J., Bartels M.N., Schluger N.W. et al. Sildenafil for chronic obstructive pulmonary disease: a randomized crossover trial. COPD. 2012; 9 (3): 268–275. DOI: 10.3109/15412555.2011.651180.

416. Goudie A.R., Lipworth B.J., Hopkinson P.J. et al. Tadalafil in patients with chronic obstructive pulmonary disease: a randomised, double-blind, parallel-group, placebo-controlled trial. Lancet. Respir. Med. 2014; 2 (4): 293–300. DOI: 10.1016/S2213-2600(14)70013-X.

417. Lang I.M., Pesavento R., Bonderman D. et al. Risk factors and basic mechanisms of chronic thromboembolic pulmonary hypertension: a current understanding. Eur. Respir. J. 2013; 41 (2): 462–468. DOI: 10.1183/09031936.00049312.

418. Guerin L., Couturaud F., Parent F. et al. Prevalence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism. Prevalence of CTEPH after pulmonary embolism. Thromb. Haemost. 2014; 112 (3): 598–605. Doi: 10.1160/TH13-07-0538.

419. Pepke-Zaba J., Jansa P., Kim N.H. et al. Chronic thromboembolic pulmonary hypertension: role of medical therapy. Eur. Respir. J. 2013; 41 (4): 985–990. DOI: 10.1183/09031936.00201612.

420. Madani M.M., Wittine L.M., Auger W.R. et al. Chronic thromboembolic pulmonary hypertension in pediatric patients. J. Thorac. Cardiovasc. Surg. 2011; 141 (3): 624–630. DOI: 10.1016/j.jtcvs.2010.07.010.

421. Pepke-Zaba J., Hoeper M.M., Humbert M. Chronic thromboembolic pulmonary hypertension: advances from bench to patient management. Eur. Respir. J. 2013; 41 (1): 8–9. DOI: 10.1183/09031936.00181212.

422. Lang I.M., Simonneau G., Pepke-Zaba J.W. et al. Factors associated with diagnosis and operability of chronic thromboembolic pulmonary hypertension. A case-control study. Thromb. Haemost. 2013; 110 (1): 83–91. DOI: 10.1160/TH13-02-0097

423. Lang I.M., Plank C., Sadushi-Kolici R. et al. Imaging in pulmonary hypertension. JACC Cardiovasc. Imaging. 2010; 3 (12): 1287–1295. DOI: 10.1016/j.jcmg.2010.09.013.

424. Hoeper M.M., Mayer E., Simonneau G. et al. Chronic thromboembolic pulmonary hypertension. Circulation. 2006; 113 (16): 2011–2020. DOI: 10.1161/CIRCULATIONAHA.105.602565.

425. Sherrick A.D., Swensen S.J., Hartman T.E. Mosaic pattern of lung attenuation on CT scans: frequency among patients with pulmonary artery hypertension of different causes. Am. J. Roentgenol. 1997; 169 (1): 79–82. DOI: 10.2214/ajr.169.1.9207504.

426. Ley S., Ley-Zaporozhan J., Pitton M.B. et al. Diagnostic performance of state-of-the-art imaging techniques for morphological assessment of vascular abnormalities in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Eur. Radiol. 2012; 22 (3): 607–616. DOI: 10.1007/s00330-011-2290-4.

427. Sugiyama M., Fukuda T., Sanda Y. et al. Organized thrombus in pulmonary arteries in patients with chronic thromboembolic pulmonary hypertension; imaging with cone beam computed tomography. Jpn. J. Radiol. 2014; 32 (7): 375–382. DOI: 10.1007/s11604-014-0319-8.

428. Shure D., Gregoratos G., Moser K.M. Fiberoptic angioscopy: role in the diagnosis of chronic pulmonary arterial obstruction. Ann. Intern. Med. 1985; 103 (6, Pt 1): 844–850. DOI: 10.7326/0003-4819-103-6-844.

429. Skoro-Sajer N., Marta G., Gerges C. et al. Surgical specimens, haemodynamics and long-term outcomes after pulmonary endarterectomy. Thorax. 2014; 69 (2): 116–122. DOI: 10.1136/thoraxjnl-2013-203746.

430. Mayer E., Jenkins D., Lindner J. et al. Surgical management and outcome of patients with chronic thromboembolic pulmonary hypertension: results from an international prospective registry. J. Thorac. Cardiovasc. Surg. 2011; 141 (3): 702–710. DOI: 10.1016/j.jtcvs.2010.11.024.

431. Madani M.M., Auger W.R., Pretorius V. et al. Pulmonary endarterectomy: recent changes in a single institution’s experience of more than 2,700 patients. Ann. Thorac. Surg. 2012; 94 (1): 97–103. DOI: 10.1016/j.athoracsur.2012.04.004.

432. Jenkins D., Mayer E., Screaton N. et al. State-of-the-art chronic thromboembolic pulmonary hypertension diagnosis and management. Eur. Respir. Rev. 2012; 21 (123): 32–39. DOI: 10.1183/09059180.00009211.

433. Vuylsteke A., Sharples L., Charman G. et al. Circulatory arrest versus cerebral perfusion during pulmonary endarterectomy surgery (PEACOG): a randomised controlled trial. Lancet. 2011; 378 (9800): 1379–1387. DOI: 10.1016/S0140-6736(11)61144-6.

434. Thistlethwaite P.A., Madani M.M., Kemp A.D. et al. Venovenous extracorporeal life support after pulmonary endarterectomy: indications, techniques, and outcomes. Ann. Thorac. Surg. 2006; 82 (6): 2139–2145. DOI: 10.1016/j.athoracsur.2006.07.020.

435. Berman M., Tsui S., Vuylsteke A. et al. Successful extracorporeal membrane oxygenation support after pulmonary thromboendarterectomy. Ann. Thorac. Surg. 2008; 86 (4): 1261–1267. DOI: 10.1016/j.athoracsur.2008.06.037.

436. Mydin M., Berman M., Klein A. et al. Extracorporeal membrane oxygenation as a bridge to pulmonary endarterectomy. Ann. Thorac. Surg. 2011; 92 (5): e101–e103. DOI: 10.1016/j.athoracsur.2011.05.035.

437. Hughes R.J., Jaïs X., Bonderman D. et al. The efficacy of bosentan in inoperable chronic thromboembolic pulmonary hypertension: a 1-year follow-up study. Eur. Respir. J. 2006; 28 (1): 138–143. DOI: 10.1183/09031936.06.00135905.

438. Skoro-Sajer N., Bonderman D., Wiesbauer F. et al. Treprostinil for severe inoperable chronic thromboembolic pulmonary hypertension. Thromb. Haemost. 2007; 5 (3): 483–489. DOI: 10.1111/j.1538-7836.2007.02394.x.

439. Reichenberger F., Voswinckel R., Enke B. et al. Long-term treatment with sildenafil in chronic thromboembolic pulmonary hypertension. Eur. Respir. J. 2007; 30 (5): 922–927. DOI: 10.1183/09031936.00039007.

440. Jaïs X., D’Armini A.M., Jansa P. et al. Bosentan for treatment of inoperable chronic thromboembolic pulmonary hypertension: BENEFiT (Bosentan Effects in iNopErable Forms of chronIc Thromboembolic pulmonary hypertension), a randomized, placebo-controlled trial. J. Am. Coll. Cardiol. 2008; 52 (25): 2127–2134. DOI: 10.1016/j.jacc.2008.08.059.

441. Ghofrani H.A., D’Armini A.M., Grimminger F. et al. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N. Engl. J. Med. 2013; 369 (4): 319–329. DOI: 10.1056/NEJMoa1209657.

442. Reesink H.J., Surie S., Kloek J.J. et al. Bosentan as a bridge to pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension. J. Thorac. Cardiovasc. Surg. 2010; 139 (1): 85–91. DOI: 10.1016/j.jtcvs.2009.03.053.

443. Feinstein J.A., Goldhaber S.Z., Lock J.E. et al. Balloon pulmonary angioplasty for treatment of chronic thromboembolic pulmonary hypertension. Circulation. 2001; 103 (1): 10–13. DOI: 10.1161/01.CIR.103.1.10.

444. Kataoka M., Inami T., Hayashida K. et al. Percutaneous transluminal pulmonary angioplasty for the treatment of chronic thromboembolic pulmonary hypertension. Circ. Cardiovasc. Interv. 2012; 5 (6): 756–762. DOI: 10.1161/CIRCINTERVENTIONS.112.971390.

445. Mizoguchi H., Ogawa A., Munemasa M. et al. Refined balloon pulmonary angioplasty for inoperable patients with chronic thromboembolic pulmonary hypertension. Circ. Cardiovasc. Interv. 2012; 5 (6): 748–755. DOI: 10.1161/CIRCINTERVENTIONS.112.971077.

446. Sugimura K., Fukumoto Y., Satoh K. et al. Percutaneous transluminal pulmonary angioplasty markedly improves pulmonary hemodynamics and long-term prognosis in patients with chronic thromboembolic pulmonary hypertension. Circ. J. 2012; 76 (2): 485–488. DOI: 10.1253/circj.CJ-11-1217.

447. Inami T., Kataoka M., Shimura N. et al. Pulmonary edema predictive scoring index (PEPSI), a new index to predict risk of reperfusion pulmonary edema and improvement of hemodynamics in percutaneous transluminal pulmonary angioplasty. JACC Cardiovasc. Interv. 2013; 6 (7): 725–736. DOI: 10.1016/j.jcin.2013.03.009.

448. Andreassen A.K., Ragnarsson A., Gude E. et al. Balloon pulmonary angioplasty in patients with inoperable chronic thromboembolic pulmonary hypertension. Heart. 2013; 99 (19): 1415–1420. DOI: 10.1136/heartjnl-2012-303549.

449. Rubin L.J., Hoeper M.M., Klepetko W. et al. Current and future management of chronic thromboembolic pulmonary hypertension: from diagnosis to treatment responses. Proc. Am. Thorac. Soc. 2006; 3 (7): 601–607. DOI: 10.1513/pats.200605-111LR.

450. Peacock A. Pulmonary hypertension due to chronic hypoxia. Br. Med. J. 1990; 300 (6727): 763. DOI: 10.1136/bmj.300.6727.763.

451. Recommendations on the management of pulmonary hypertension in clinical practice. Heart. 2001; 86 (Suppl. 1): I1–I13.

452. Consensus statement on the management of pulmonary hypertension in clinical practice in the UK and Ireland. Thorax. 2008; 63 (Suppl. 2): ii1–ii41.

453. Barbera J.A., Escribano P., Morales P. et al. [Standards of care in pulmonary hypertension. Consensus statement of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) and the Spanish Society of Cardiology (SEC)]. Rev. Esp. Cardiol. 2008; 61: 170–184.

454. Armstrong I., Rochnia N., Harries C. et al. The trajectory to diagnosis with pulmonary arterial hypertension: a qualitative study. BMJ Open 2012; 2 (2): e000806. DOI: 10.1136/bmjopen-2011-000806.

455. Ghofrani H.A., Distler O., Gerhardt F. et al. Treatment of pulmonary arterial hypertension (PAH): updated Recommendations of the Cologne Consensus Conference 2011. Int. J. Cardiol. 2011; 154 (Suppl. 1): S20–S33.

456. Vachiery J.L., Gaine S. Challenges in the diagnosis and treatment of pulmonary arterial hypertension. Eur. Respir. Rev. 2012; 21 (126): 313–320. DOI: 10.1183/09059180.00005412.


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Для цитирования: статья Р. Легочная гипертензия. Диагностика и лечение. Европейские клинические рекомендации (2015) (часть 3-я).  Пульмонология. 2017;27(5):573-606.

For citation: article E. Pulmonary hypertension. Diagnosis and therapy. European guidelines, 2015 (Part 3). Russian Pulmonology. 2017;27(5):573-606. (In Russ.)

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