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J Am Coll Cardiol, 2002; 40:780-788
© 2002 by the American College of Cardiology Foundation
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CLINICAL STUDY: PULMONARY HYPERTENSION

Long-term intravenous epoprostenol infusion in primary pulmonary hypertension

Prognostic factors and survival

Olivier Sitbon, MD*,*, Marc Humbert, MD*, Hilario Nunes, MD*, Florence Parent, MD*, Gilles Garcia, MD*, Philippe Hervé, MD*, Maurizio Rainisio, PhD* and G.érald Simonneau, MD*

* Service de Pneumologie et Réanimation, UPRES EA 2705 on Pulmonary Vascular Diseases, Hôpital Antoine Béclère, Université Paris-Sud, Clamart, France

Manuscript received December 18, 2001; revised manuscript received April 11, 2002, accepted May 15, 2002.

* Reprint requests and correspondence: Dr. Olivier Sitbon, Service de Pneumologie et Réanimation, Hôpital Antoine Béclère, 157 rue de la Porte de Trivaux, 92141 Clamart, France.
olivier.sitbon{at}abc.ap-hop-paris.fr

OBJECTIVES: We sought to determine the factors associated with long-term survival in patients with primary pulmonary hypertension (PPH) treated with continuous epoprostenol infusion.

BACKGROUND: Epoprostenol improves survival in patients with PPH in New York Heart Association (NYHA) functional class III or IV. However, some patients do not benefit from epoprostenol and must be considered for lung transplantation. The best timing for listing these patients on a lung transplantation program is currently unknown.

METHODS: Between December 1992 and January 2001, 178 patients with PPH in NYHA functional class III or IV were treated with epoprostenol. The 6-min walk test (WT) and right-sided heart catheterization were performed at baseline, after three months on epoprostenol and thereafter once a year.

RESULTS: Overall survival rates at one, two, three, and five years were 85%, 70%, 63%, and 55%, respectively. On univariate analysis, the baseline variables associated with a poor outcome were a history of right-sided heart failure, NYHA functional class IV, 6-min WT ≤250 m (median value), right atrial pressure ≥12 mm Hg, and mean pulmonary artery pressure <65 mm Hg. On multivariate analysis, including both baseline variables and those measured after three months on epoprostenol, a history of right-sided heart failure, persistence of NYHA functional class III or IV at three months, and the absence of a fall in total pulmonary resistance of >30%, relative to baseline, were associated with poor survival.

CONCLUSIONS: Survival of patients with PPH treated with epoprostenol depends on the severity at baseline, as well as the three-month response to therapy. These findings suggest that lung transplantation should be considered in a subset of patients who remain in NYHA functional class III or IV or in those who cannot achieve a significant hemodynamic improvement after three months of epoprostenol therapy, or both.

Abbreviations and Acronyms
  CI
  cardiac index
  PAP
  pulmonary artery pressure
  NYHA
  New York Heart Association
  PGI2
  epoprostenol (prostacyclin)
  PPH
  primary pulmonary hypertension
  RAP
  right atrial pressure
  Svo2
  mixed venous oxygen saturation
  TPR
  total pulmonary resistance
  WT
  walk test




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R. N. Channick, H. Olschewski, W. Seeger, T. Staub, R. Voswinckel, and L. J. Rubin
Safety and Efficacy of Inhaled Treprostinil as Add-On Therapy to Bosentan in Pulmonary Arterial Hypertension
J. Am. Coll. Cardiol., October 3, 2006; 48(7): 1433 - 1437.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
M. Gomberg-Maitland
Learning to pair therapies and the expanding matrix for pulmonary arterial hypertension: is more better?
Eur. Respir. J., October 1, 2006; 28(4): 683 - 686.
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 Eur Respir JHome page
E. Cenedese, R. Speich, L. Dorschner, S. Ulrich, M. Maggiorini, R. Jenni, and M. Fischler
Measurement of quality of life in pulmonary hypertension and its significance
Eur. Respir. J., October 1, 2006; 28(4): 808 - 815.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. I. Said
Mediators and modulators of pulmonary arterial hypertension
Am J Physiol Lung Cell Mol Physiol, October 1, 2006; 291(4): L547 - L558.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
V. V. McLaughlin and M. D. McGoon
Pulmonary Arterial Hypertension
Circulation, September 26, 2006; 114(13): 1417 - 1431.
[Full Text] [PDF]

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 ChestHome page
O. Sanchez, O. Sitbon, X. Jais, G. Simonneau, and M. Humbert
Immunosuppressive therapy in connective tissue diseases-associated pulmonary arterial hypertension.
Chest, July 1, 2006; 130(1): 182 - 189.
[Abstract] [Full Text] [PDF]

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 Eur Heart JHome page
T. Adriaenssens, M. Delcroix, K. Van Deyk, and W. Budts
Advanced therapy may delay the need for transplantation in patients with the Eisenmenger syndrome
Eur. Heart J., June 2, 2006; 27(12): 1472 - 1477.
[Abstract] [Full Text] [PDF]

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 ChestHome page
I. Lang, M. Gomez-Sanchez, M. Kneussl, R. Naeije, P. Escribano, N. Skoro-Sajer, and J.-L. Vachiery
Efficacy of Long-term Subcutaneous Treprostinil Sodium Therapy in Pulmonary Hypertension
Chest, June 1, 2006; 129(6): 1636 - 1643.
[Abstract] [Full Text] [PDF]

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 ChestHome page
A. Fijalkowska, M. Kurzyna, A. Torbicki, G. Szewczyk, M. Florczyk, P. Pruszczyk, and M. Szturmowicz
Serum N-Terminal Brain Natriuretic Peptide as a Prognostic Parameter in Patients With Pulmonary Hypertension
Chest, May 1, 2006; 129(5): 1313 - 1321.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
M. Humbert, O. Sitbon, A. Chaouat, M. Bertocchi, G. Habib, V. Gressin, A. Yaici, E. Weitzenblum, J.-F. Cordier, F. Chabot, et al.
Pulmonary Arterial Hypertension in France: Results from a National Registry
Am. J. Respir. Crit. Care Med., May 1, 2006; 173(9): 1023 - 1030.
[Abstract] [Full Text] [PDF]

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 NEJMHome page
M. M. Hoeper, T. Welte, G. Izbicki, D. Rosengarten, E. Picard, W. G. Kuschner, N. Galie, L. J. Rubin, and G. Simonneau
Sildenafil citrate therapy for pulmonary arterial hypertension.
N. Engl. J. Med., March 9, 2006; 354(10): 1091 - 1093.
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 ChestHome page
V. F. Tapson, M. Gomberg-Maitland, V. V. McLaughlin, R. L. Benza, A. C. Widlitz, A. Krichman, and R. J. Barst
Safety and Efficacy of IV Treprostinil for Pulmonary Arterial Hypertension: A Prospective, Multicenter, Open-Label, 12-Week Trial
Chest, March 1, 2006; 129(3): 683 - 688.
[Abstract] [Full Text] [PDF]

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 Eur Heart JHome page
S. Provencher, O. Sitbon, M. Humbert, S. Cabrol, X. Jais, and G. Simonneau
Long-term outcome with first-line bosentan therapy in idiopathic pulmonary arterial hypertension
Eur. Heart J., March 1, 2006; 27(5): 589 - 595.
[Abstract] [Full Text] [PDF]

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 Eur Heart JHome page
V. V. McLaughlin
'Raising the bar' for the treatment of pulmonary arterial hypertension
Eur. Heart J., March 1, 2006; 27(5): 510 - 511.
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 Proc Am Thorac SocHome page
L. J. Rubin
Pulmonary arterial hypertension.
Proceedings of the ATS, January 1, 2006; 3(1): 111 - 115.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
M. Kataoka, N. Nagaya, T. Satoh, T. Itoh, S. Murakami, T. Iwase, Y. Miyahara, S. Kyotani, Y. Sakai, K. Kangawa, et al.
A Long-Acting Prostacyclin Agonist with Thromboxane Inhibitory Activity for Pulmonary Hypertension
Am. J. Respir. Crit. Care Med., December 15, 2005; 172(12): 1575 - 1580.
[Abstract] [Full Text] [PDF]

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 ThoraxHome page
O Sitbon, V V McLaughlin, D B Badesch, R J Barst, C Black, N Galie, M Humbert, M Rainisio, L J Rubin, and G Simonneau
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, December 1, 2005; 60(12): 1025 - 1030.
[Abstract] [Full Text] [PDF]

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 ChestHome page
S. Provencher, X. Jais, A. Yaici, O. Sitbon, M. Humbert, and G. Simonneau
Clinical Challenges in Pulmonary Hypertension: Roger S. Mitchell Lecture
Chest, December 1, 2005; 128(6_suppl): 622S - 628S.
[Abstract] [Full Text] [PDF]

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 ChestHome page
S. Provencher, X. Jais, A. Yaici, O. Sitbon, M. Humbert, and G. Simonneau
Clinical Challenges in Pulmonary Hypertension: Roger S. Mitchell Lecture
Chest, December 1, 2005; 128(6_suppl): 622S - 628S.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
M. M. Hoeper, I. Markevych, E. Spiekerkoetter, T. Welte, and J. Niedermeyer
Goal-oriented treatment and combination therapy for pulmonary arterial hypertension
Eur. Respir. J., November 1, 2005; 26(5): 858 - 863.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
D. Montani, L. Achouh, A. G. Marcelin, J-P. Viard, O. Hermine, D. Canioni, O. Sitbon, G. Simonneau, and M. Humbert
Reversibility of pulmonary arterial hypertension in HIV/HHV8-associated Castleman's disease
Eur. Respir. J., November 1, 2005; 26(5): 969 - 972.
[Abstract] [Full Text] [PDF]

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 Eur Heart JHome page
C. F. Opitz, R. Wensel, J. Winkler, M. Halank, L. Bruch, F.-X. Kleber, G. Hoffken, S. D. Anker, A. Negassa, S. B. Felix, et al.
Clinical efficacy and survival with first-line inhaled iloprost therapy in patients with idiopathic pulmonary arterial hypertension
Eur. Heart J., September 2, 2005; 26(18): 1895 - 1902.
[Abstract] [Full Text] [PDF]

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 ANN INTERN MEDHome page
L. J. Rubin and D. B. Badesch
Evaluation and Management of the Patient with Pulmonary Arterial Hypertension
Ann Intern Med, August 16, 2005; 143(4): 282 - 292.
[Abstract] [Full Text] [PDF]

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 J Am Coll CardiolHome page
M. Oikawa, Y. Kagaya, H. Otani, M. Sakuma, J. Demachi, J. Suzuki, T. Takahashi, J. Nawata, T. Ido, J. Watanabe, et al.
Increased [18F]Fluorodeoxyglucose Accumulation in Right Ventricular Free Wall in Patients With Pulmonary Hypertension and the Effect of Epoprostenol
J. Am. Coll. Cardiol., June 7, 2005; 45(11): 1849 - 1855.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
A. Vonk-Noordegraaf, S. A. van Wolferen, J. T. Marcus, A. Boonstra, P. E. Postmus, J. W. L. Peeters, and A. J. Peacock
Noninvasive assessment and monitoring of the pulmonary circulation
Eur. Respir. J., April 1, 2005; 25(4): 758 - 766.
[Abstract] [Full Text] [PDF]

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 ChestHome page
O. A. Minai and M. M. Budev
Referral for Lung Transplantation: A Moving Target
Chest, March 1, 2005; 127(3): 705 - 707.
[Full Text] [PDF]

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 ChestHome page
S. D. Nathan
Lung Transplantation: Disease-Specific Considerations for Referral
Chest, March 1, 2005; 127(3): 1006 - 1016.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
M. Humbert
Improving survival in pulmonary arterial hypertension
Eur. Respir. J., February 1, 2005; 25(2): 218 - 220.
[Full Text] [PDF]

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 Eur Respir JHome page
V. V. McLaughlin, O. Sitbon, D. B. Badesch, R. J. Barst, C. Black, N. Galie, M. Rainisio, G. Simonneau, and L. J. Rubin
Survival with first-line bosentan in patients with primary pulmonary hypertension
Eur. Respir. J., February 1, 2005; 25(2): 244 - 249.
[Abstract] [Full Text] [PDF]


 
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