Impact of bosentan therapy on stress-induced pulmonary hypertension in patients with systemic sclerosis

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Aim. To describe hemodynamic and clinical changes in patients with elevated mean pulmonary artery pressure (MPAP) >30 mm Hg during exercise and the impact of bosentan therapy on stress-induced pulmonary hypertension (SIPH). Subjects and methods. The study included 19 patients with systemic sclerosis (SDS) in whom possible causes of pulmonary hypertension (PH) (lung and left heart injuries and thromboembolism) were excluded. All the patients underwent pulmonary artery catheterization at rest and during exercise. The hemodynamic (right atrial pressure (RAP), systolic and diastolic pressure, MPAP, pulmonary artery wedge pressure (PAWP), cardiac output (CO) by a thermodilution technique), clinical (demographic, immunological, and instrumental) parameters were analyzed and the risk of pulmonary arterial hypertension (PAH) was also calculated; 5 patients with SIPH received 16-week bosentan therapy according to the conventional regimen. Results. Ten of the 19 patients were at increased risk for PAH in accordance with the DETECT scale, but no signs of PH at resting catheterization were found in anybody. In 5 patients, MPAP, was in the range from 21 to 24 mm Hg; in 9 (47%) patients were found to have SIPH, a median MPAP of 35 (32; 41) mm Hg. Seven patients had no diagnostic changes during exercise; 3 patients could not perform an exercise test. There were correlations between MPAP and DETECT risk scores (p<0.05). The patients with SIPH had significantly higher levels of resting MPAP and exercise pulmonary vascular resistance (PVR) and PAWP. The calculated DETECT risk was significantly higher in the SIPH group. The level of uric acid was also higher in the SIPH group (p<0.05). There were no changes in NT-proBNP levels, telangiectasias and anti-centromere antibodies, and EchoCG and lung test results. During 16-week bosentan therapy, there was a significant decrease in MPAP and transpulmonary gradient during exercise, but PVR, MPAP/CO ratio and NT-proBNP levels tended to decrease. Conclusion. In the patients with SDS, SIPH may be a stage of pulmonary vasculopathy that precedes the development of clinical PAH. The use of current PAH-specific drugs used at the preclinical stage of the disease may substantially improve lifetime prognosis in patients with SDS-associated PAH.

References

  1. 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.
  2. Coghlan J.C., Denton C.P., Grünig E. et al. Evidence-based detection of pulmonary arterial hypertension in systemic sclerosis: the DETECT study. Ann Rheum Dis 2014; 73: 1340-1349.
  3. Kovacs G., Maier R., Aberer E. et al. Borderline pulmonary arterial pressure is associated with decreased exercise capacity in scleroderma. Am J Respir Crit Care Med 2009; 180: 881-886.
  4. Badesch D.B., Champion H.C., Sanchez M.A. et al. Diagnosis and assessment of pulmonary arterial hypertension. J Am Coll Cardiol 2009; 54: S55-S66.
  5. Saggar R., Khanna D., Shapiro S. et al. Brief report: effect of ambrisentan treatment on exercise-induced pulmonary hypertension in systemic sclerosis: a prospective single-center, open-label pilot study. Arthritis Rheum 2012; 64: 4072-4077.
  6. Hoeper M., Bogaard H.J., Condliffe R. et al. Definitions and Diagnosis of Pulmonary Hypertension. J Am Coll Cardiol 2013; 62 (25 Suppl): D42-50.
  7. Saggar R., Khanna D., Furst D.E. et al. Exercise-Induced Pulmonary Hypertension Associated With Systemic Sclerosis. Arthritis Rheum 2010; 62 (12): 3741-3750.
  8. Kovacs G., Maier R., Aberer E. et al. Pulmonary arterial hypertension therapy may be safe and effective in patients with systemic sclerosis and borderline pulmonary artery pressure. Arthritis Rheum 2012; 64 (4): 1257-1262.
  9. van den Hoogen F., Khanna D., Fransen J. et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum 2013; 65 (11): 2737-2747.
  10. LeRoy E.C., Black C., Fleischmajer R. et al. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol 1988; 15: 202-205.
  11. Tolle J.J., Waxman A.B., Van Horn T.L. et al. Exercise-induced pulmonary arterial hypertension. Circulation 2008; 118: 2183-2189.
  12. Ekelund L.G., Hofmagren A. Central hemodynamics during exercise. Circ Res 1967; 20-21 (Suppl 1): 33-43.
  13. West J.B. Left ventricular filling pressures during exercise: a cardiological blind spot? Chest 1998; 113: 1695-1697.
  14. Naeije R., Vanderpool R., Dhakal B.P. et al. Exercise-induced pulmonary hypertension: physiological basis and methodological concerns. Am J Respir Crit Care Med 2013; 187 (6): 576-583.
  15. Steen V. Advancements in diagnosis of pulmonary arterial hypertension in scleroderma. Arthritis Rheum 2005; 52: 3698-3700.
  16. 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: 3792-3800.
  17. Kovacs G., Berghold A., Scheidl S., Olschewski H. Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review. Eur Respir J 2009; 34: 888-894.
  18. Reeves J.T., Dempsey J.A., Grover R.F. Pulmonary circulation during exercise. In: Pulmonary vascular physiology and physiopathology. Weir E.K., Reeves J.T. (eds). New York: Marcel Dekker 1989; 107-133.
  19. Lewis G.D., Murphy R.M., Shah R.V. et al. Pulmonary vascular response patterns during exercise in left ventricular systolic dysfunction predict exercise capacity and outcomes. Circ Heart Fail 2011; 4: 276-285.
  20. Valerio C.J., Schreiber B.E., Handler C.E. et al. Borderline mean pulmonary artery pressure in patients with systemic sclerosis. Arth Rheum 2013; 65 (4): 1074-1084.
  21. Condliffe R., Kiely D.G., Peacock A.J. et al. Connective tissue disease-associated pulmonary arterial hypertension in the modern treatment era. Am J Respir Crit Care Med 2009; 179: 151-157.
  22. Proudman S.M., Stevens W.M., Sahhar J., Celermajer D. Pulmonary arterial hypertension in systemic sclerosis: the need for early detection and treatment. Intern Med J 2007; 37: 485-494.
  23. Fishman A.P. Hypoxia on the pulmonary circulation: how and where it acts. Circ Res 1976; 38: 221-231.
  24. Ahlborg G., Weitzberg E., Lundberg J. Metabolic and vascular effects of circulating endothelin-1 during moderately heavy prolonged exercise. J Appl Physiol 1995; 78: 2294-2300.
  25. Stebbins C.L., Symons J.D., McKirnan M.D., Hwang F.F. Factors associated with vasopressin release in exercising swine. Am J Physiol 1994; 266: R118-124.

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