Методы стратификации рисков и их значение при легочной артериальной гипертензии
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Avdeev S.N., Tsareva N.A. Risk stratification methods and their significance in pulmonary arterial hypertension. Therapeutic Archive. 2019; 91 (9): 150–157. DOI: 10.26442/00403660.2019.09.000192
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Ключевые слова: легочная артериальная гипертензия, стратификация рисков, ЛАГ-специфическая терапия, комбинированная терапия.
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Despite significant advances in therapy, pulmonary arterial hypertension (PAH) remains a progressive disease with a poor prognosis. Immediately after establishing the diagnosis of PAH, urgent treatment with PAH-specific therapy is required. Due to the progressive nature of the disease, all patients should be closely monitored and their treatment regimen should be promptly changed according to clinical need. Risk stratification is an important method for informing the clinician and the patient about the prognosis of disease and the choice of therapy methods. The REVEAL scale and the ESC/ERS 2015 risk assessment table are important multifactorial tools for making decisions about the prescription and correction of PAH therapy, as well as for assessment of patients' response to therapy. Current guidelines for PAH indicate that the most important task of treatment of PAH is to achieve the low-risk status.
Keywords: pulmonary arterial hypertension, risk stratification, PAH-specific therapy, combination therapy.
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3. Simonneau G, Hoeper MM, McLaughlin V, et al. Future perspectives in pulmonary arterial hypertension. Eur Respir Rev. 2016;25:381-9.
4. Weatherald J, Boucly A, Sitbon O. Risk stratification in pulmonary arterial hypertension. Curr Opin Pulm Med. 2018;24:407-15.
5. Weatherald J, Sitbon O, Humbert M. Validation of a risk assessment instrument for pulmonary arterial hypertension. Eur Heart J. 2018;39:4182-5.
6. Humbert M, Sitbon O, Chaouat A, et al. Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation. 2010;122:156-63.
7. Benza RL, Miller DP, 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;122:164-72.
8. Condliffe R, Kiely DG, Peacock AJ, et al. Connective tissue disease-associated pulmonary arterial hypertension in the modern treatment era. Am J Respir Crit Care Med. 2009;179:151-7.
9. Chung L, Farber HW, Benza R, et al. Unique predictors of mortality in patients with pulmonary arterial hypertension associated with systemic sclerosis in the REVEAL registry. Chest. 2014;146:1494-504.
10. Rubenfire M, Huffman MD, Krishnan S, et al. Survival in systemic sclerosis with pulmonary arterial hypertension has not improved in the modern era. Chest. 2013;144:1282-90.
11. Evans JDW, Girerd B, Montani D, et al. BMPR2 mutations and survival in pulmonary arterial hypertension: an individual participant data meta-analysis. Lancet Respir Med. 2016;4:129-37.
12. McLaughlin VV, Gaine SP, Howard LS, et al. Treatment goals of pulmonary hypertension. J Am Coll Cardiol. 2013;62:73-81.
13. 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;40:780-8.
14. Savarese G, Paolillo S, Costanzo P, et al. Do changes of 6-min walk distance predict clinical events in patients with pulmonary arterial hypertension? A meta-analysis of 22 randomized trials. J Am Coll Cardiol. 2012;60:1192-201.
15. Wensel R, Opitz CF, Anker SD, et al. Assessment of survival in patients with primary pulmonary hypertension: importance of cardiopulmonary exercise testing. Circulation. 2002;106:319-24.
16. Wensel R, Francis DP, Meyer FJ, et al. Incremental prognostic value of cardiopulmonary exercise testing and resting haemodynamics in pulmonaryarterial hypertension. Int J Cardiol. 2013;167:1193-8.
17. Badagliacca R, Papa S, Valli G, et al. Echocardiography combined with cardiopulmonary exercise testing for the prediction of outcome in idiopathic pulmonary arterial hypertension. Chest. 2016;150:1313-22.
18. Groepenhoff H, Vonk-Noordegraaf A, Boonstra A, et al. Exercise testing to estimate survival in pulmonary hypertension. Med Sci Sports Exerc. 2008;40:1725-32.
19. Schwaiblmair M, Faul C, von Scheidt W, Berghaus TM. Ventilatory efficiency testing as prognostic value in patients with pulmonary hypertension. BMC Pulm Med. 2012;12:23.
20. Benza RL, Gomberg-Maitland M, Miller DP, et al. The REVEAL Registry risk score calculator in patients newly diagnosed with pulmonary arterial hypertension. Chest. 2012;141:354-62.
21. Mauritz G-J, Rizopoulos D, Groepenhoff H, et al. Usefulness of serial Nterminal pro-B-type natriuretic peptide measurements for determining prognosis in patients with pulmonary arterial hypertension. Am J Cardiol. 2011;108:1645-50.
22. Frantz RP, Farber HW, Badesch DB, et al. Baseline and serial brain natriuretic peptide level predicts 5-year overall survival in patients with pulmonary arterial hypertension: data from the REVEAL registry. Chest. 2018;154:126-35.
23. 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;39:589-96.
24. Mathai SC, Bueso M, Hummers LK, et al. Disproportionate elevation of Nterminal pro-brain natriuretic peptide in scleroderma-related pulmonary hypertension. Eur Respir J. 2010;35:95-104.
25. Bourji KI, Hassoun PM. Right ventricle dysfunction in pulmonary hypertension: mechanisms and modes of detection. Curr Opin Pulm Med. 2015;21:446-53.
26. Weatherald J, Boucly A, Chemla D, et al. Prognostic value of follow-up hemodynamic variables after initial management in pulmonary arterial hypertension. Circulation. 2018;137:693-704.
27. van Wolferen SA, Marcus JT, Boonstra A, et al. Prognostic value of right ventricular mass, volume, and function in idiopathic pulmonary arterial hypertension. Eur Heart J. 2007;28:1250-7.
28. Fine NM, Chen L, Bastiansen PM, et al. Outcome prediction by quantitative right ventricular function assessment in 575 subjects evaluated for pulmonary hypertension. Circ Cardiovasc Imaging. 2013;6:711-21.
29. Mazurek JA, Vaidya A, Mathai SC, et al. Follow-up tricuspid annular plane systolic excursion predicts survival in pulmonary arterial hypertension. Pulm Circ. 2017;7:361-71.
30. Forfia PR, Fisher MR, Mathai SC, et al. Tricuspid annular displacement predicts survival in pulmonary hypertension. Am J Respir Crit Care Med. 2006;174:1034-41.
31. Austin C, Alassas K, Burger C, et al. Echocardiographic assessment of estimated right atrial pressure and size predicts mortality in pulmonary arterial hypertension. Chest. 2015;147:198-208.
32. Swift AJ, Capener D, Johns C, et al. Magnetic resonance imaging in the prognostic evaluation of patients with pulmonary arterial hypertension. Am J Respir Crit Care Med. 2017;196:228-39.
33. Baggen VJM, Leiner T, Post MC, et al. Cardiac magnetic resonance findings predicting mortality in patients with pulmonary arterial hypertension: a systematic review and meta-analysis. Eur Radiol. 2016;26:3771-80.
34. Courand P-Y, Pina Jomir G, Khouatra C, et al. Prognostic value of right ventricular ejection fraction in pulmonary arterial hypertension. Eur Respir J. 2015;45:139-49.
35. Van de Veerdonk MC, Marcus JT, Westerhof N, et al. Signs of right ventricular deterioration in clinically stable patients with pulmonary arterial hypertension. Chest. 2015;147:1063-71.
36. D’Alonzo GE, Barst RJ, Ayres SM, et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med. 1991;115:343-9.
37. Humbert M, Sitbon O, Yaıci A, et al. French Pulmonary Arterial Hypertension Network. Survival in incident and prevalent cohorts of patients with pulmonary arterial hypertension. Eur Respir J. 2010;36:549-55.
38. Thenappan T, Shah SJ, Rich S, et al. Survival in pulmonary arterial hypertension: a reappraisal of the NIH risk stratification equation. Eur Respir J. 2010;35:1079-87.
39. Thenappan T, Glassner C, Gomberg-Maitland M. Validation of the pulmonary hypertension connection equation for survival prediction in pulmonary arterial hypertension. Chest. 2012;141:642-50.
40. Weatherald J, Boucly A, Sahay S, et al. The low-risk profile in pulmonary arterial hypertension. Time for a paradigm shift to goal-oriented clinical trial endpoints? Am J Respir Crit Care Med. 2018;197:860-8.
41. Kane GC, Maradit-Kremers H, Slusser JP, et al. Integration of clinical and hemodynamic parameters in the prediction of long-term survival in patients with pulmonary arterial hypertension. Chest. 2011;139:1285-93.
42. Benza RL, Miller DP, Foreman AJ, et al. Prognostic implications of serial risk score assessments in patients with pulmonary arterial hypertension: a Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) analysis. J Heart Lung Transplant. 2015;34:356-61.
43. Sitbon O, Benza RL, Badesch DB, et al. Validation of two predictive models for survival in pulmonary arterial hypertension. Eur Respir J. 2015;46:152-64.
44. Cogswell R, Pritzker M, De Marco T. Performance of the REVEAL pulmonary arterial hypertension prediction model using noninvasive and routinely measured parameters. J Heart Lung Transplant. 2014;33:382-7.
45. Benza RL, Elliott CG, Farber HW, et al. Updated risk score calculator for pulmonary arterial hypertension patients. J Heart Lung Transplant. 2017;36:S19.
46. Kylhammar D, Kjellstrom B, Hjalmarsson C, et al. A comprehensive risk stratification at early follow-up determines prognosis in pulmonary arterial hypertension. Eur Heart J. 2018;39:4175-81.
47. Hoeper MM, Kramer T, Pan Z, et al. Mortality in pulmonary arterial hypertension: prediction by the 2015 European pulmonary hypertension guidelines risk stratification model. Eur Respir J. 2017;50:1700740.
48. Boucly A, Weatherald J, Savale L, et al. Risk assessment, prognosis and guideline implementation in pulmonary arterial hypertension. Eur Respir J. 2017;50:1700889.
49. Hoeper MM, Pittrow D, Opitz C, et al. Risk assessment in pulmonary arterial hypertension. Eur Respir J. 2018;51:1702606.
50. Bartenstein P, Saxer S, Appenzeller P, et al. Risk factor profiles achieved with medical therapy in prevalent patients with pulmonary arterial and distal chronic thromboembolic pulmonary hypertension. Respiration. 2018;96:127-37.
51. Gaine S, McLaughlin V. Pulmonary arterial hypertension: tailoring treatment to risk in the current era. Eur Respir Rev. 2017;26:170095.
52. Sitbon O, Gaine S. Beyond a single pathway: combination therapy in pulmonary arterial hypertension. Eur Respir Rev. 2016;25:408-17.
53. Pulido T, Adzerikho I, Channick R, et al. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med. 2013;369:809-18.
54. Sitbon O, Channick R, Chin KM, et al. Selexipag for the treatment of pulmonary arterial hypertension. N Engl J Med. 2015;373:2522-33.
55. Galiè N, Barberà JA, Frost AE, et al. Initial use of ambrisentan plus tadalafil in pulmonary arterial hypertension. N Engl J Med. 2015;373:834-44.
56. Sitbon O, Vonk Noordegraaf A. Epoprostenol and pulmonary arterial hypertension: 20 years of clinical experience. Eur Respir Rev. 2017;26:160055.
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1. Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS). Eur Respir J. 2015;46:903-75.
2. [Chazova IE, Avdeev SN, Tsareva NA, Volkov AV, Martynyuk TV, Nakonechnikov SN. Clinical guidelines for the diagnosis and treatment of pulmonary hypertension. Therapeutic Archive. 2014;86(9):4-23 (In Russ.)].
3. Simonneau G, Hoeper MM, McLaughlin V, et al. Future perspectives in pulmonary arterial hypertension. Eur Respir Rev. 2016;25:381-9.
4. Weatherald J, Boucly A, Sitbon O. Risk stratification in pulmonary arterial hypertension. Curr Opin Pulm Med. 2018;24:407-15.
5. Weatherald J, Sitbon O, Humbert M. Validation of a risk assessment instrument for pulmonary arterial hypertension. Eur Heart J. 2018;39:4182-5.
6. Humbert M, Sitbon O, Chaouat A, et al. Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation. 2010;122:156-63.
7. Benza RL, Miller DP, 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;122:164-72.
8. Condliffe R, Kiely DG, Peacock AJ, et al. Connective tissue disease-associated pulmonary arterial hypertension in the modern treatment era. Am J Respir Crit Care Med. 2009;179:151-7.
9. Chung L, Farber HW, Benza R, et al. Unique predictors of mortality in patients with pulmonary arterial hypertension associated with systemic sclerosis in the REVEAL registry. Chest. 2014;146:1494-504.
10. Rubenfire M, Huffman MD, Krishnan S, et al. Survival in systemic sclerosis with pulmonary arterial hypertension has not improved in the modern era. Chest. 2013;144:1282-90.
11. Evans JDW, Girerd B, Montani D, et al. BMPR2 mutations and survival in pulmonary arterial hypertension: an individual participant data meta-analysis. Lancet Respir Med. 2016;4:129-37.
12. McLaughlin VV, Gaine SP, Howard LS, et al. Treatment goals of pulmonary hypertension. J Am Coll Cardiol. 2013;62:73-81.
13. 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;40:780-8.
14. Savarese G, Paolillo S, Costanzo P, et al. Do changes of 6-min walk distance predict clinical events in patients with pulmonary arterial hypertension? A meta-analysis of 22 randomized trials. J Am Coll Cardiol. 2012;60:1192-201.
15. Wensel R, Opitz CF, Anker SD, et al. Assessment of survival in patients with primary pulmonary hypertension: importance of cardiopulmonary exercise testing. Circulation. 2002;106:319-24.
16. Wensel R, Francis DP, Meyer FJ, et al. Incremental prognostic value of cardiopulmonary exercise testing and resting haemodynamics in pulmonaryarterial hypertension. Int J Cardiol. 2013;167:1193-8.
17. Badagliacca R, Papa S, Valli G, et al. Echocardiography combined with cardiopulmonary exercise testing for the prediction of outcome in idiopathic pulmonary arterial hypertension. Chest. 2016;150:1313-22.
18. Groepenhoff H, Vonk-Noordegraaf A, Boonstra A, et al. Exercise testing to estimate survival in pulmonary hypertension. Med Sci Sports Exerc. 2008;40:1725-32.
19. Schwaiblmair M, Faul C, von Scheidt W, Berghaus TM. Ventilatory efficiency testing as prognostic value in patients with pulmonary hypertension. BMC Pulm Med. 2012;12:23.
20. Benza RL, Gomberg-Maitland M, Miller DP, et al. The REVEAL Registry risk score calculator in patients newly diagnosed with pulmonary arterial hypertension. Chest. 2012;141:354-62.
21. Mauritz G-J, Rizopoulos D, Groepenhoff H, et al. Usefulness of serial Nterminal pro-B-type natriuretic peptide measurements for determining prognosis in patients with pulmonary arterial hypertension. Am J Cardiol. 2011;108:1645-50.
22. Frantz RP, Farber HW, Badesch DB, et al. Baseline and serial brain natriuretic peptide level predicts 5-year overall survival in patients with pulmonary arterial hypertension: data from the REVEAL registry. Chest. 2018;154:126-35.
23. 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;39:589-96.
24. Mathai SC, Bueso M, Hummers LK, et al. Disproportionate elevation of Nterminal pro-brain natriuretic peptide in scleroderma-related pulmonary hypertension. Eur Respir J. 2010;35:95-104.
25. Bourji KI, Hassoun PM. Right ventricle dysfunction in pulmonary hypertension: mechanisms and modes of detection. Curr Opin Pulm Med. 2015;21:446-53.
26. Weatherald J, Boucly A, Chemla D, et al. Prognostic value of follow-up hemodynamic variables after initial management in pulmonary arterial hypertension. Circulation. 2018;137:693-704.
27. van Wolferen SA, Marcus JT, Boonstra A, et al. Prognostic value of right ventricular mass, volume, and function in idiopathic pulmonary arterial hypertension. Eur Heart J. 2007;28:1250-7.
28. Fine NM, Chen L, Bastiansen PM, et al. Outcome prediction by quantitative right ventricular function assessment in 575 subjects evaluated for pulmonary hypertension. Circ Cardiovasc Imaging. 2013;6:711-21.
29. Mazurek JA, Vaidya A, Mathai SC, et al. Follow-up tricuspid annular plane systolic excursion predicts survival in pulmonary arterial hypertension. Pulm Circ. 2017;7:361-71.
30. Forfia PR, Fisher MR, Mathai SC, et al. Tricuspid annular displacement predicts survival in pulmonary hypertension. Am J Respir Crit Care Med. 2006;174:1034-41.
31. Austin C, Alassas K, Burger C, et al. Echocardiographic assessment of estimated right atrial pressure and size predicts mortality in pulmonary arterial hypertension. Chest. 2015;147:198-208.
32. Swift AJ, Capener D, Johns C, et al. Magnetic resonance imaging in the prognostic evaluation of patients with pulmonary arterial hypertension. Am J Respir Crit Care Med. 2017;196:228-39.
33. Baggen VJM, Leiner T, Post MC, et al. Cardiac magnetic resonance findings predicting mortality in patients with pulmonary arterial hypertension: a systematic review and meta-analysis. Eur Radiol. 2016;26:3771-80.
34. Courand P-Y, Pina Jomir G, Khouatra C, et al. Prognostic value of right ventricular ejection fraction in pulmonary arterial hypertension. Eur Respir J. 2015;45:139-49.
35. Van de Veerdonk MC, Marcus JT, Westerhof N, et al. Signs of right ventricular deterioration in clinically stable patients with pulmonary arterial hypertension. Chest. 2015;147:1063-71.
36. D’Alonzo GE, Barst RJ, Ayres SM, et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med. 1991;115:343-9.
37. Humbert M, Sitbon O, Yaıci A, et al. French Pulmonary Arterial Hypertension Network. Survival in incident and prevalent cohorts of patients with pulmonary arterial hypertension. Eur Respir J. 2010;36:549-55.
38. Thenappan T, Shah SJ, Rich S, et al. Survival in pulmonary arterial hypertension: a reappraisal of the NIH risk stratification equation. Eur Respir J. 2010;35:1079-87.
39. Thenappan T, Glassner C, Gomberg-Maitland M. Validation of the pulmonary hypertension connection equation for survival prediction in pulmonary arterial hypertension. Chest. 2012;141:642-50.
40. Weatherald J, Boucly A, Sahay S, et al. The low-risk profile in pulmonary arterial hypertension. Time for a paradigm shift to goal-oriented clinical trial endpoints? Am J Respir Crit Care Med. 2018;197:860-8.
41. Kane GC, Maradit-Kremers H, Slusser JP, et al. Integration of clinical and hemodynamic parameters in the prediction of long-term survival in patients with pulmonary arterial hypertension. Chest. 2011;139:1285-93.
42. Benza RL, Miller DP, Foreman AJ, et al. Prognostic implications of serial risk score assessments in patients with pulmonary arterial hypertension: a Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) analysis. J Heart Lung Transplant. 2015;34:356-61.
43. Sitbon O, Benza RL, Badesch DB, et al. Validation of two predictive models for survival in pulmonary arterial hypertension. Eur Respir J. 2015;46:152-64.
44. Cogswell R, Pritzker M, De Marco T. Performance of the REVEAL pulmonary arterial hypertension prediction model using noninvasive and routinely measured parameters. J Heart Lung Transplant. 2014;33:382-7.
45. Benza RL, Elliott CG, Farber HW, et al. Updated risk score calculator for pulmonary arterial hypertension patients. J Heart Lung Transplant. 2017;36:S19.
46. Kylhammar D, Kjellstrom B, Hjalmarsson C, et al. A comprehensive risk stratification at early follow-up determines prognosis in pulmonary arterial hypertension. Eur Heart J. 2018;39:4175-81.
47. Hoeper MM, Kramer T, Pan Z, et al. Mortality in pulmonary arterial hypertension: prediction by the 2015 European pulmonary hypertension guidelines risk stratification model. Eur Respir J. 2017;50:1700740.
48. Boucly A, Weatherald J, Savale L, et al. Risk assessment, prognosis and guideline implementation in pulmonary arterial hypertension. Eur Respir J. 2017;50:1700889.
49. Hoeper MM, Pittrow D, Opitz C, et al. Risk assessment in pulmonary arterial hypertension. Eur Respir J. 2018;51:1702606.
50. Bartenstein P, Saxer S, Appenzeller P, et al. Risk factor profiles achieved with medical therapy in prevalent patients with pulmonary arterial and distal chronic thromboembolic pulmonary hypertension. Respiration. 2018;96:127-37.
51. Gaine S, McLaughlin V. Pulmonary arterial hypertension: tailoring treatment to risk in the current era. Eur Respir Rev. 2017;26:170095.
52. Sitbon O, Gaine S. Beyond a single pathway: combination therapy in pulmonary arterial hypertension. Eur Respir Rev. 2016;25:408-17.
53. Pulido T, Adzerikho I, Channick R, et al. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med. 2013;369:809-18.
54. Sitbon O, Channick R, Chin KM, et al. Selexipag for the treatment of pulmonary arterial hypertension. N Engl J Med. 2015;373:2522-33.
55. Galiè N, Barberà JA, Frost AE, et al. Initial use of ambrisentan plus tadalafil in pulmonary arterial hypertension. N Engl J Med. 2015;373:834-44.
56. Sitbon O, Vonk Noordegraaf A. Epoprostenol and pulmonary arterial hypertension: 20 years of clinical experience. Eur Respir Rev. 2017;26:160055.
1 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия;
2 ФГБУ «Научно-исследовательский институт пульмонологии» ФМБА России, Москва, Россия
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S.N. Avdeev 1,2, N.A. Tsareva 1,2
1 Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia;
2 Pulmonology Research Institute, Moscow, Russia