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Pulmonary Medicine
Volume 2011, Article ID 845864, 13 pages
http://dx.doi.org/10.1155/2011/845864
Review Article

Diagnosis and Management of Pulmonary Arterial Hypertension

Division of Pulmonary, Sleep and Critical Care Medicine, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI 02903, USA

Received 16 January 2011; Accepted 6 June 2011

Academic Editor: Aldo T. Iacono

Copyright © 2011 Jeanne Houtchens et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. R. M. Tuder, S. H. Abman, T. Braun et al., “Development and pathology of pulmonary hypertension,” Journal of the American College of Cardiology, vol. 54, supplement 1, no. 1, pp. S3–S9, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  2. G. E. D'Alonzo, R. J. Barst, S. M. Ayres et al., “Survival in patients with primary pulmonary hypertension: results from a national prospective registry,” Annals of Internal Medicine, vol. 115, no. 5, pp. 343–349, 1991. View at Google Scholar · View at Scopus
  3. Z. Deng, J. H. Morse, S. L. Slager et al., “Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene,” American Journal of Human Genetics, vol. 67, no. 3, pp. 737–744, 2000. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  4. K. B. Lane, R. D. Machado, M. W. Pauciulo et al., “Heterozygous germline mutations in BMPR2, encoding a TGF-β receptor, cause familial primary pulmonary hypertension. The International PPH consortium,” Nature Genetics, vol. 26, no. 1, pp. 81–84, 2000. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  5. B. W. Christman, C. D. McPherson, J. H. Newman et al., “An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension,” The New England Journal of Medicine, vol. 327, no. 2, pp. 70–75, 1992. View at Google Scholar · View at Scopus
  6. A. Giaid, M. Yanagisawa, D. Langleben et al., “Expression of endothelin-1 in the lungs of patients with pulmonary hypertension,” The New England Journal of Medicine, vol. 328, no. 24, pp. 1732–1739, 1993. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  7. C. Rubens, R. Ewert, M. Halank et al., “Big endothelin-1 and endothelin-1 plasma levels are correlated with the severity of primary pulmonary hypertension,” Chest, vol. 120, no. 5, pp. 1562–1569, 2001. View at Publisher · View at Google Scholar · View at Scopus
  8. A. Giaid and D. Saleh, “Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension,” The New England Journal of Medicine, vol. 333, no. 4, pp. 214–221, 1995. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  9. S. A. Kharitonov, J. B. Cailes, C. M. Black, R. M. du Bois, and P. J. Barnes, “Decreased nitric oxide in the exhaled air of patients with systemic sclerosis with pulmonary hypertension,” Thorax, vol. 52, no. 12, pp. 1051–1055, 1997. View at Google Scholar · View at Scopus
  10. K. A. Hanson, J. W. Ziegler, S. D. Rybalkin, J. W. Miller, S. H. Abman, and W. R. Clarke, “Chronic pulmonary hypertension increases fetal lung cGMP phosphodiesterase activity,” American Journal of Physiology, vol. 275, no. 5, pp. L931–L941, 1998. View at Google Scholar · View at Scopus
  11. G. Simonneau, I. M. Robbins, M. Beghetti et al., “Updated clinical classification of pulmonary hypertension,” Journal of the American College of Cardiology, vol. 54, supplement 1, no. 1, pp. S43–S54, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  12. M. Humbert, O. Sitbon, A. Chaouat et al., “Pulmonary arterial hypertension in France: results from a national registry,” American Journal of Respiratory and Critical Care Medicine, vol. 173, no. 9, pp. 1023–1030, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  13. A. J. Peacock, N. F. Murphy, J. J. McMurrey, L. Caballero, and S. Stewart, “An epidemiological study of pulmonary arterial hypertension,” European Respiratory Journal, vol. 30, no. 1, pp. 104–109, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  14. D. B. Badesch, G. E. Raskob, C. G. Elliott et al., “Pulmonary arterial hypertension: baseline characteristics from the REVEAL registry,” Chest, vol. 137, no. 2, pp. 376–387, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  15. T. M. Bull, “Physical exam in pulmonary arterial hypertension,” Advances in Pulmonary Hypertension, vol. 4, pp. 6–10, 2005. View at Google Scholar
  16. H. H. Leuchte, M. Holzapel, R. A. Baumgartner et al., “Clinical significance of brain natriurectic peptide in primary pulmonary hypertension,” Journal of the American College of Cardiology, vol. 43, no. 5, pp. 764–770, 2004. View at Google Scholar
  17. P. R. Forfia, S. C. Mathai, M. R. Fisher et al., “Hyponatremia predicts right heart failure and poor survival in pulmonary arterial hypertension,” American Journal of Respiratory and Critical Care Medicine, vol. 177, no. 12, pp. 1364–1369, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  18. E. Bossone, R. Citro, F. Blasi, and L. Allegra, “Echocardiography in pulmonary arterial hypertension: an essential tool,” Chest, vol. 131, no. 2, pp. 339–341, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  19. S. M. Arcasoy, J. D. Christie, V. A. Ferrare et al., “Echocardiographic assessment of pulmonary hypertension in patients with advanced lung disease,” American Journal of Respiratory and Critical Care Medicine, vol. 167, no. 5, pp. 735–740, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  20. A. L. Hinderliter, P. W. Willis IV, W. Long et al., “Frequency and prognostic significance of pericardial effusion in primary pulmonary hypertension. PPH study group. Primary pulmonary hypertension,” American Journal of Cardiology, vol. 84, no. 4, pp. 481–484, 1999. View at Google Scholar
  21. V. V. McLaughlin, S. L. Archer, D. B. Badesch et al., “ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation task force on expert consensus documents,” Journal of the American College of Cardiology, vol. 53, no. 17, pp. 1573–1619, 2009. View at Publisher · View at Google Scholar · View at PubMed
  22. S. Rich, E. Kaufmann, and P. S. Levy, “The effect of high doses of calcium-channel blockers on survival in primary pulmonary hypertension,” The New England Journal of Medicine, vol. 327, no. 2, pp. 76–81, 1992. View at Google Scholar · View at Scopus
  23. O. Sitbon, M. Humbert, X. Jaïs et al., “Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension,” Circulation, vol. 111, no. 23, pp. 3105–3111, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  24. F. Ichinose, J. Erana-Garcia, J. Hromi et al., “Nebulized sildenafil is a selective pulmonary vasodilator in lambs with acute pulmonary hypertension,” Critical Care Medicine, vol. 29, no. 5, pp. 1000–1005, 2001. View at Google Scholar
  25. H. Wilkens, A. Guth, J. König et al., “Effect of inhaled iloprost plus oral sildenafil in patients with primary pulmonary hypertension,” Circulation, vol. 104, no. 11, pp. 1218–1222, 2001. View at Google Scholar
  26. E. Michelakis, W. Tymchak, D. Lien, L. Webster, K. Hashimoto, and S. Archer, “Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: comparison with inhaled nitric oxide,” Circulation, vol. 105, no. 20, pp. 2398–2403, 2002. View at Publisher · View at Google Scholar
  27. N. Galie, H. A. Ghofrani, A. Torbicki et al., “Sildenafil citrate therapy for pulmonary arterial hypertension,” The New England Journal of Medicine, vol. 353, no. 20, pp. 2148–2157, 2005. View at Publisher · View at Google Scholar · View at PubMed
  28. N. Galie, B. H. Brundage, H. A. Ghofrani et al., “Tadalafil therapy for pulmonary arterial hypertension,” Circulation, vol. 119, no. 22, pp. 2894–2903, 2009. View at Publisher · View at Google Scholar · View at PubMed
  29. M. Gomberg-Maitland and H. Olschewski, “Prostacyclin therapies for the treatment of pulmonary arterial hypertension,” European Respiratory Journal, vol. 31, no. 4, pp. 891–901, 2008. View at Publisher · View at Google Scholar · View at PubMed
  30. D. K. Jones, T. W. Higenbottam, and J. Wallwork, “Treatment of primary pulmonary hypertension with intravenous epoprostenol (prostacyclin),” British Heart Journal, vol. 57, no. 3, pp. 270–278, 1987. View at Google Scholar
  31. L. J. Rubin, J. Mendoza, M. Hood et al., “Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol),” Annals of Internal Medicine, vol. 112, no. 7, pp. 485–491, 1990. View at Google Scholar
  32. R. J. Barst, L. J. Rubin, W. A. Long et al., “A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension,” The New England Journal of Medicine, vol. 334, no. 5, pp. 296–301, 1996. View at Google Scholar
  33. N. Menon, L. McAlpine, A. J. Peacock, and R. Madhok, “The acute effects of prostacyclin on pulmonary hemodynamics in patients with pulmonary hypertension secondary to systemic sclerosis,” Arthritis and Rheumatism, vol. 41, no. 3, pp. 466–469, 1998. View at Publisher · View at Google Scholar
  34. M. Humbert, O. Sanchez, M. Fartoukh et al., “Treatment of severe pulmonary hypertension secondary to connective tissue diseases with continuous IV epoprostenol (prostacyclin),” Chest, vol. 114, supplement 1, pp. 80S–82S, 1998. View at Google Scholar
  35. D. B. Badesch, V. F. Tapson, M. D. McGoon et al., “Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease,” Annals of Internal Medicine, vol. 132, no. 6, pp. 425–434, 2000. View at Google Scholar
  36. V. V. McLaughlin, R. J. Barst, S. Rich et al., “Efficacy and safety of UT-15, a prostacyclin analogue for primary pulmonary hypertension,” European Heart Journal, vol. 20, p. 486, 1990. View at Google Scholar
  37. S. P. Gaine, R. Oudiz, and S. Rich, “Acute hemodynamic effects of 15AU81, a stable prostacyclin analogue, in severe primary pulmonary hypertension,” American Journal of Respiratory and Critical Care Medicine, vol. 157, p. A595, 1998. View at Google Scholar
  38. G. Simonneau, R. J. Barst, and N. Galie, “Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension,” American Journal of Respiratory and Critical Care Medicine, vol. 165, no. 6, pp. 800–804, 2002. View at Google Scholar
  39. M. Gomberg-Maitland, V. F. Tapson, R. L. Benza et al., “Transition from intravenous epoprostenol to intravenous treprostinil in pulmonary hypertension,” American Journal of Respiratory and Critical Care Medicine, vol. 172, no. 12, pp. 1586–1589, 2005. View at Publisher · View at Google Scholar · View at PubMed
  40. H. Olschewski, G. Simonneau, and N. Galie, “Inhaled iloprost for severe pulmonary hypertension,” The New England Journal of Medicine, vol. 347, no. 5, pp. 22–29, 2002. View at Publisher · View at Google Scholar · View at PubMed
  41. R. Voswinckel, B. Enke, F. Reichenberger et al., “Favorable effects of inhaled treprostinil in severe pulmonary hypertension: results from randomized controlled pilot studies,” Journal of the American College of Cardiology, vol. 48, no. 8, pp. 1672–1681, 2006. View at Publisher · View at Google Scholar · View at PubMed
  42. R. Voswinckel, H. A. Ghofrani et al., “Inhaled treprostinil for treatment of chronic pulmonary arterial hypertension,” Annals of Internal Medicine, vol. 144, no. 2, pp. 149–150, 2006. View at Google Scholar
  43. V. V. McLaughlin, R. L. Benza, L. J. Rubin et al., “Addition of inhaled treprostinil to oral therapy for pulmonary arterial hypertension,” Journal of the American College of Cardiology, vol. 55, no. 18, pp. 1915–1922, 2010. View at Google Scholar
  44. K. A. Hickey, G. Rubanyi, R. J. Paul, and R. F. Highsmith, “Characterization of a coronary vasoconstrictor produced by cultured endothelial cells,” American journal of physiology, vol. 248, no. 5, pp. C550–C556, 1985. View at Google Scholar
  45. M. Yanagisawa, H. Kurihara, S. Kimura et al., “A novel potent vasoconstrictor peptide produced by vascular endothelial cells,” Nature, vol. 332, pp. 411–415, 1988. View at Publisher · View at Google Scholar · View at PubMed
  46. R. N. Channick, G. Simonneau, O. Sitbon et al., “Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study,” The Lancet, vol. 358, no. 9288, pp. 1119–1123, 2001. View at Publisher · View at Google Scholar · View at PubMed
  47. L. J. Rubin, D. B. Badesch, R. J. Barst et al., “Bosentan therapy for pulmonary arterial hypertension,” The New England Journal of Medicine, vol. 346, no. 12, pp. 896–903, 2002. View at Publisher · View at Google Scholar · View at PubMed
  48. N. Galie, H. Olschewski, R. J. Oudiz et al., “Ambrisentan for the treatment of pulmonary arterial hypertension,” Circulation, vol. 117, no. 23, pp. 3010–3019, 2008. View at Publisher · View at Google Scholar · View at PubMed
  49. M. R. Wilkins, G. A. Paul, J. W. Strange et al., “Sildenafil versus endothelin receptor antagonist for pulmonary hypertension (SERAPH) study,” American Journal of Respiratory and Critical Care Medicine, vol. 171, no. 11, pp. 1292–1297, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  50. R. J. Barst, J. S. Gibbs, H. A. Ghofrani et al., “Updated evidence-based treatment algorithm in pulmonary arterial hypertension,” Journal of the American College of Cardiology, vol. 54, supplement 1, no. 1, pp. S78–S84, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  51. G. Simonneau, L. J. Rubin, N. Galie, R. J. Barst, T. R. Fleming, A. E. Frost et al., “Addition of sildenafil to long-term intravenous epoprostenol therapy in patients with pulmonary arterial hypertension: a randomized trial,” Annals of Internal Medicine, vol. 149, no. 8, pp. 521–530, 2008. View at Google Scholar · View at Scopus
  52. M. Humbert, R. J. Barst, I. M. Robbins, R. N. Channick, N. Galie, A. Boonstra et al., “Combination of bosentan with epoprostenol in pulmonary arterial hypertension: breath-2,” European Respiratory Journal, vol. 24, no. 3, pp. 353–359, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  53. V. V. McLaughlin, R. J. Oudiz, A. Frost et al., “Randomized study of adding inhaled iloprost to existing bosentan in pulmonary arterial hypertension,” American Journal of Respiratory and Critical Care Medicine, vol. 174, no. 11, pp. 1257–1263, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  54. “A study of first line ambrisentan and tadalafil combination therapy in subjects with pulmonary arterial hypertension (PAH),” http://clinicaltrials.gov.
  55. Badesch et al., “ACCP clinical practice guidelines,” Chest, vol. 126S, pp. 35S–62S, 2004. View at Google Scholar
  56. S. Rich, M. Seidlitz, E. Dodin et al., “The short-term effects of digoxin in patients with right ventricular dysfunction from pulmonary hypertension,” Chest, vol. 114, no. 3, pp. 787–792, 1998. View at Google Scholar
  57. D. H. Roberts, J. J. Lepore, A. Maroo et al., “Oxygen therapy improves cardiac index and pulmonary vascular resistance in patients with pulmonary hypertension,” Chest, vol. 120, no. 5, pp. 1547–1555, 2001. View at Publisher · View at Google Scholar