Skip to main content
SpringerLink
Log in

Current Management of Primary Pulmonary Hypertension

  • Therapy in Practice
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Primary pulmonary hypertension (PPH) is a rare disorder with an annual incidence of 1 to 2 per million people. The aetiology of this disorder is unknown, but it appears to result from an abnormal interaction of environmental and genetic factors leading to a vasculopathy. The pulmonary arteries in these patients exhibit a spectrum of pathological lesions ranging from the early medial hypertrophy to the end-stage fibrotic plexiform lesions. This characteristic pathology is also observed in pulmonary hypertension resulting from connective tissue disease (particularly systemic sclerosis), HIV infection, portal hypertension and certain toxins.

PPH is a condition that is difficult to diagnose and treat, with a median survival of 2.8 years in historical studies. One of the difficulties in treating patients with PHH is that the subacute nature of disease presentation often prevents an accurate diagnosis during the early stages of the illness. Progressive dyspnoea on exertion is the most common presenting symptom. Diagnostic evaluation should include electrocardiography, chest radiograph and echocardiography, and laboratory and other studies to evaluate for secondary causes (e.g. pulmonary function tests, chest computed tomography and ventilation/perfusion scans, pulmonary arteriogram, cardiopulmonary testing, right heart catherisation).

PHH is a disorder for which there is no known cure. Current medical and surgical treatment options for patients with PHH include anticoagulation, vasodilators and transplantation. Calcium channel antagonists are currently the oral drugs of choice for the treatment of patients with New York Heart Association (NYHA) Class II disease. These agents, in particular the dihydropyridine compounds, have beneficial effects on haemodynamics and right ventricular function, and possibly increased survival. Epoprostenol is administered by intravenous infusion, and studies have demonstrated short- and long-term improvements in symptoms, haemodynamics and survival. It is well tolerated and has become the treatment of choice for patients with NYHA Class III and IV disease.

Inotropic agents are used as a bridge to transplant, which is indicated in patients who do not respond to maximal medical therapy. Experience has shown that single lung, double lung and heart-lung transplantation are approximately of equal efficacy. Currently, single lung transplant appears to be the procedure of choice.

Newer agents, such as sildenafil, beraprost and bosentan, are presently being evaluated for the treatment of this disorder. Future study should include elucidation of the pathogenic mechanisms in the development of this vasculopathy, which will hopefully lead to the development of improved treatment options for patients with PHH.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Table I
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Peacock AJ. Primary pulmonary hypertension. Thorax 1999; 54: 1107–18

    Article  PubMed  CAS  Google Scholar 

  2. Rubin LJ. Primary pulmonary hypertension. N Engl J Med 1997; 336: 111–7

    Article  PubMed  CAS  Google Scholar 

  3. Rubin LJ. Primary pulmonary hypertension. Chest 1993; 104: 236–50

    Article  PubMed  CAS  Google Scholar 

  4. Rich S, editor. Primary pulmonary hypertension. Executive Summary from the World Symposium. Primary Pulmonary Hypertension. World Health Organization, 1998

  5. Langleben D. Familial primary pulmonary hypertension. Chest 1994; 105: 13–6S

    Article  Google Scholar 

  6. Grunig E, Janssen B, Mereles D, et al. Abnormal pulmonary artery pressure response in asymptomatic carriers of primary pulmonary hypertension gene. Circulation 2000; 102: 1145–50

    Article  PubMed  CAS  Google Scholar 

  7. Deng Z, Morse JH, Slager SL, et al. Familial primary pulmonary hypertension (gene PPH1)iscausedby mutations in the bone morphogenetic protein receptor-II gene. Am J Hum Genetics 2000; 67: 737–44

    Article  CAS  Google Scholar 

  8. Silver RM. Clinical problems: the lungs. Rheum Dis Clin North Am 1996; 22: 825–40

    Article  PubMed  CAS  Google Scholar 

  9. Bolster MB, Silver RM. Lung disease in systemic Sclerosis (Scleroderma). Baillieres Clin Rheumatol 1993; 7: 79–97

    Article  PubMed  CAS  Google Scholar 

  10. Battle RW, Davitt MA, Cooper SM, et al. Prevalence of pulmonary hypertension in limited and diffuse scleroderma. Chest 1996; 110: 1515–9

    Article  PubMed  CAS  Google Scholar 

  11. Speich R, Jenni R, Opravil M, et al. Primary pulmonary hypertension in HIV infection. Chest 1991; 100: 1268–71

    Article  PubMed  CAS  Google Scholar 

  12. Gertner HP. Pulmonary hypertension ‘Plexogenic pulmonary arteriopathy’ and the appetite suppressant drug aminorex: post or proctor. Bull Eur Physiopathol Respir 1979; 15: 897–923

    Google Scholar 

  13. Abenheim L, Moride Y, Breno F, et al. Appetite suppressant use and the risk of primary pulmonary hypertension. N Engl J Med 1996; 335: 609–16

    Article  Google Scholar 

  14. Rich S, Rubin LJ, Walker AM, et al. Anorexigens and pulmonary hypertension in the United States: results from the surveillance of North American pulmonary hypertension. Chest 2000; 117: 870–4

    Article  PubMed  CAS  Google Scholar 

  15. Hadengue A, Behayoun MK, Lebrec D, et al. Pulmonary hypertension complicating portal hypertension: prevalence and relation to splanchnic hemodynamics. Gastroenterology 1991; 100: 520–8

    PubMed  CAS  Google Scholar 

  16. Rich S, Dantzker DR, Ayres SM, et al. Primary pulmonary hypertension: a national prospective study. Ann Intern Med 1987; 107: 216–23

    PubMed  CAS  Google Scholar 

  17. Kanemoto N. Electrocardiogram in primary pulmonary hypertension. Eur J Cardiol 1980; 12: 181–93

    Google Scholar 

  18. Goodman J, Harrison DC, Popp RL. Echocardiographic features of primary pulmonary hypertension. Am J Cardiol 1974; 33: 438–43

    Article  PubMed  CAS  Google Scholar 

  19. Barst RJ, Rubin LJ, Long WA, et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension: the Primary Pulmonary Hypertension study group. N Engl J Med 1996; 334: 296–302

    Article  PubMed  CAS  Google Scholar 

  20. 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

    PubMed  Google Scholar 

  21. Packer M. Vasodilator therapy for primary pulmonary hypertension. Ann Inter Med 1985; 103: 258–70

    CAS  Google Scholar 

  22. Fuster V, Steele PM, Edwards WD, et al. Primary pulmonary hypertension: natural history and the importance of thrombosis. Circulation 1984; 70: 580–7

    Article  PubMed  CAS  Google Scholar 

  23. Rich S, Kaufmann E, Levy PS. The effect of high doses of calcium channel blockers on survival in primary pulmonary hypertension. N Engl J Med 1992; 327: 76–81

    Article  PubMed  CAS  Google Scholar 

  24. Rubin LJ, Mendoza J, Hood M, et al. Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol). Ann Intern Med 1990; 112: 485–91

    PubMed  CAS  Google Scholar 

  25. Barst RJ, Rubin LJ, McGoon M, et al. Survival in primary pulmonary hypertension with long-term continuous intravenous prostacyclin. Ann Intern Med 1994; 121: 409–15

    PubMed  CAS  Google Scholar 

  26. Sitbon O, Brenot F, Denjean A, et al. Inhaled nitric oxide as a screening vasodilator agent in primary pulmonary hypertension. Am J Respir Crit Care Med 1995; 151: 384–9

    PubMed  CAS  Google Scholar 

  27. Channick RN, Rubin LJ. Combination therapy for pulmonary hypertension: a glimpse into the future. Crit Care Med 2000; 28: 896–7

    Article  PubMed  CAS  Google Scholar 

  28. Morgan JM, McCormack DG, Griffiths MJD, et al. Adenosine as a vasodilator in primary pulmonary hypertension. Circulation 1991; 84: 1145–9

    Article  PubMed  CAS  Google Scholar 

  29. Weir EK, Rubin LJ, Ayres SM, et al. The acute administration of vasodilators in primary pulmonary hypertension: experience from the National Institutes of Health Registry on Primary Pulmonary Hypertension. Am Rev Respir Dis 1989; 140: 1623–30

    Article  PubMed  CAS  Google Scholar 

  30. Rich S, Brundage BH. High-dose calcium channel-blocking therapy for primary pulmonary hypertension: evidence of long-term reduction in pulmonary arterial pressure and regression of right ventricular hypertrophy. Circulation 1987; 76: 135–41

    Article  PubMed  CAS  Google Scholar 

  31. Rubin LJ. Calcium channel blockers in primary pulmonary hypertension. Chest 1985; 88 Suppl. 4: 257S–60S

    Article  PubMed  CAS  Google Scholar 

  32. Higenbottam T, Wheeldon D, Wells F. Long-term treatment of primary pulmonary hypertension with continuous intravenous epoprostenol. Lancet 1984: 46–7

  33. McLaughlin VV, Genthner DE, Panella MM, et al. Reduction in pulmonary vascular resistance with long-term epoprostenol (prostacyclin) therapy in primary pulmonary hypertension. N Engl J Med 1998; 338: 273–7

    Article  PubMed  CAS  Google Scholar 

  34. Shapiro SM, Oudiz RJ, Cao T, et al. Primary pulmonary hypertension: improved long-term effects and survival with continuous intravenous epoprostenol infusion. J Am Coll Cardiol 1997; 30: 343–9

    Article  PubMed  CAS  Google Scholar 

  35. Vane JR, Botting RM. Pharmacodynamic profile of prostacyclin. Am J Cardiol 1995; 75: 3A–10A

    Article  PubMed  CAS  Google Scholar 

  36. Farber HW, Loscalzo J. Prothrombotic mechanisms in primary pulmonary hypertension. J Lab Clin Med 1999; 134: 561–6

    Article  PubMed  CAS  Google Scholar 

  37. Hinderliter AL, Willis PW, Barst RJ, et al. Effects of long-term infusion of prostacyclin (epoprostenol) on echocardiographic measures of right ventricular structure and function in primary pulmonary hypertension. Circulation 1997; 95: 1479–86

    Article  PubMed  CAS  Google Scholar 

  38. Barst RJ, Horn EM, Widlitz AC, et al. Efficacy of long-term subcutaneous infusion of UT-15 in primary pulmonary hypertension [abstract]. Eur Heart J 2000; 21: 315

    Article  Google Scholar 

  39. Olschewski H, Ghofrani HA, Schmehl T, et al. Inhaled iloprost to treat severe pulmonary hypertension. Ann Intern Med 2000; 132: 435–43

    PubMed  CAS  Google Scholar 

  40. Hoeper MM, Schwarze M, Ehlerding S, et al. Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analogue. N Engl J Med 2000; 342: 1866–70

    Article  PubMed  CAS  Google Scholar 

  41. Honey M, Cotter L, Davies N, et al. Clinical and hemodynamic effects of diazoxide in primary pulmonary hypertension. Thorax 1980; 35: 269–76

    Article  PubMed  CAS  Google Scholar 

  42. Leier CV, Bambach D, Nelson S, et al. Captopril and primary pulmonary hypertension. Circulation 1983; 67: 155–61

    Article  PubMed  CAS  Google Scholar 

  43. Packer M, Greenberg B, Massie BH. Deleterious effects of hydralazine in patients with pulmonary hypertension. N Engl J Med 1982; 306: 1326–31

    Article  PubMed  CAS  Google Scholar 

  44. Abrams D, Schulze-Neick I, Magee AG. Sildefanil as a selective pulmonary vasodilator in childhood primary pulmonary hypertension. Heart 2000; 84: E4

    Article  PubMed  CAS  Google Scholar 

  45. Lodato RF. Viagra for impotence of pulmonary vasodilator therapy [editorial]. Am J Respir Crit Care Med 2001; 163: 312–3

    PubMed  CAS  Google Scholar 

  46. Bigatello LM, Hess DR, Dennehy KC, et al. Sildefanil can increase the response to inhaled nitric oxide. Anesthesia 2000; 92: 1827

    Article  CAS  Google Scholar 

  47. Saji T, Ozawa Y, Ishikita T, et al. Short term effect of a new PGI2 analogue, beraprost, in primary and secondary pulmonary hypertension. Am J Cardiol 1996; 78: 244–7

    Article  PubMed  CAS  Google Scholar 

  48. Ichida F, Uese K, Tsubata S, et al. Additive effect of beraprost on pulmonary vasodilation by inhaled nitric oxide in children with pulmonary hypertension. Am J Cardiol 1997; 80: 662–4

    Article  PubMed  CAS  Google Scholar 

  49. Williamson DJ, Wallman LL, Jones R, et al. Hemodynamic effects of bosentan, an endothelin receptor antagonist, in patients with pulmonary hypertension. Circulation 2000; 102: 411–8

    Article  PubMed  CAS  Google Scholar 

  50. Rich S, Lamb W. Atrial septostomy as palliative therapy for refractory primary pulmonary hypertension. Am J Cardiol 1983; 51: 1560–1

    Article  PubMed  CAS  Google Scholar 

  51. Rich S, Dodin E, McLaughlin VV. Usefulness of atrial septostomy as a treatment for primary pulmonary hypertension and guidelines for its application. Am J Cardiol 1997; 80: 369–71

    Article  PubMed  CAS  Google Scholar 

  52. Kerstein D, Levy PS, Hesu DT, et al. Balloon atrial septostomy in patients with severe primary pulmonary hypertension. Circulation 1995; 91: 2028–35

    Article  PubMed  CAS  Google Scholar 

  53. Pasque MK, Trulock EP, Cooper JD, et al. Single lung transplantation for pulmonary hypertension: single institution experience in 34 patients. Circulation 1995; 92: 2252–8

    Article  PubMed  CAS  Google Scholar 

  54. Moulton MJ, Creswell LL, Ungacta FF, et al. Magnetic Resonance Imaging provides evidence for remodeling of the right ventricle after single-lung transplantation for pulmonary hypertension. Circulation 1996; 94 Suppl II: II312–II9

    PubMed  CAS  Google Scholar 

  55. Williamson DJ, Hayward C, Rogers P, et al. Acute hemodynamic response to inhaled nitric oxide in patients with limited scleroderma and isolated pulmonary hypertension. Circulation 1996; 94: 477–82

    Article  PubMed  CAS  Google Scholar 

  56. Klings ES, Hill NS, Ieong MH, et al. Systemic sclerosis-associated pulmonary hypertension: short and long-term effects of epoprostenol. Arthritis Rheum 1999; 42: 2638–45

    Article  PubMed  CAS  Google Scholar 

  57. Badesch DB, Tapson VF, McGoon MD, et al. Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. Ann Intern Med 2000; 132: 425–34

    PubMed  CAS  Google Scholar 

  58. Humbert M, Sanchez O, Fartoukh M, et al. Short-term and long-term epoprostenol (prostacyclin) therapy in pulmonary hypertension secondary to connective tissue diseases: results of a pilot study. Eur Respir J 1999: 13: 1351–6

    Article  PubMed  CAS  Google Scholar 

  59. Aquilar RV, Farber HW. Long-term epoprostenol (prostacyclin) therapy in HIV-associated pulmonary hypertension. Am J Resp Crit Care Med 2000; 162: 1846–50

    Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge the physicians and nurses of the Medical Intensive Care Unit at Boston Medical Center for their assistance in the care of patients.

Dr Klings is funded by American Lung Association Research Training Fellowship RT-030-N and American Heart Association Beginning Grant In Aid 0160150T. Dr Farber is funded by American Heart Association Grant In Aid 0150155N. There are no conflicts on interest involving the authors of this manuscript.

Author information

Authors and Affiliations

  1. The Pulmonary Center, R-304, Boston University School of Medicine, 715 Albany Street, Boston, Massachusetts, 02118, USA

    Elizabeth S. Klings & Harrison W. Farber

Authors
  1. Elizabeth S. Klings
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Harrison W. Farber
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elizabeth S. Klings.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Klings, E.S., Farber, H.W. Current Management of Primary Pulmonary Hypertension. Drugs 61, 1945–1956 (2001). https://doi.org/10.2165/00003495-200161130-00005

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200161130-00005

Keywords

Search

Navigation