Respiratory Medicine
Volume 104, Issue 4 , Pages 481-496 , April 2010

Pulmonary vasodilator testing and use of calcium channel blockers in pulmonary arterial hypertension

Received 5 June 2009 ,Accepted 21 November 2009.

References 

  1. Rubin LJ. American College of Chest Physicians. Diagnosis and management of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest. 2004;126:7S–10S
  2. Simonneau G, Galiè N, Rubin LJ, et al. Clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2004;43:5S–12S
  3. Simonneau G, Robbins IM, Beghetti M, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2009;54:S43–S54
  4. McGoon M, Gutterman D, Steen V, et al. American College of Chest Physicians. Screening, early detection, and diagnosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest. 2004;126:14S–34S
  5. Badesch DB, Abman SH, Simonneau G, Rubin LJ, McLaughlin VV. Medical therapy for pulmonary arterial hypertension: updated ACCP evidence-based clinical practice guidelines. Chest. 2007;131:1917–1928
  6. McLaughlin VV, Archer SL, Badesch DB, 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 and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. J Am Coll Cardiol. 2009;53:1573–1619
  7. Badesch DB, Champion HC, Sanchez MA, et al. Diagnosis and assessment of pulmonary arterial hypertension. J Am Coll Cardiol. 2009;54:S55–S66
  8. Galiè N, Torbicki A, Barst R, et al. Task Force. Guidelines on diagnosis and treatment of pulmonary arterial hypertension. The Task Force on Diagnosis and Treatment of Pulmonary Arterial Hypertension of the European Society of Cardiology. Eur Heart J. 2004;25:2243–2278
  9. 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;115:343–349
  10. Chin KM, Rubin LJ. Pulmonary arterial hypertension. J Am Coll Cardiol. 2008;51:1527–1538
  11. 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;140:1623–1630
  12. Hoeper MM, Lee SH, Voswinckel R, et al. Complications of right heart catheterization procedures in patients with pulmonary hypertension in experienced centers. J Am Coll Cardiol. 2006;48:2546–2552
  13. Oliveira EC, Amaral CF, Moura MA, Campos FT, Pauperio HM. Testing pulmonary vasoreactivity. J Bras Pneumol. 2008;34:838–844
  14. Groves BM, Badesch DB, Turkevich D, et al. Correlation of acute prostacyclin response in primary (unexplained) pulmonary hypertension with efficacy of treatment with calcium channel blockers and survival. In:  Weir K editors. In flux in pulmonary vascular control. New York: Plenum Press; 1993;
  15. Sitbon O, Humbert M, Jagot JL, et al. Inhaled nitric oxide as a screening agent for safely identifying responders to oral calcium-channel blockers in primary pulmonary hypertension. Eur Respir J. 1998;12:265–270
  16. Badesch DB, Abman SH, Ahearn GS, et al. American College of Chest Physicians. Medical therapy for pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest. 2004;126:35S–62S
  17. 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
  18. Partanen J, Nieminen MS, Luomanmäki K. Death in a patient with primary pulmonary hypertension after 20 mg of nifedipine. N Engl J Med. 1993;329:812
  19. Barst RJ, Gibbs JS, Ghofrani HA, et al. Updated evidence-based treatment algorithm in pulmonary arterial hypertension. J Am Coll Cardiol. 2009;54:S78–S84
  20. Packer M. Pathophysiological mechanisms underlying the adverse effects of calcium channel-blocking drugs in patients with chronic heart failure. Circulation. 1989;80:IV59–IV67
  21. Hill NS, Klings ES. General therapeutic approach and traditional therapies. In:  Hill NS,  Farber HW editor. Contemporary cardiology: pulmonary hypertension. New Jersey: Humama Press; 2008;
  22. Sitbon O, Humbert M, Jaïs X, et al. Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation. 2005;111:3105–3111
  23. Naeije R, Vachiéry JL. Medical therapy of pulmonary hypertension. Conventional therapies. Clin Chest Med. 2001;22:517–527
  24. Morales-Blanhir J, Santos S, de Jover L, et al. Clinical value of vasodilator test with inhaled nitric oxide for predicting long-term response to oral vasodilators in pulmonary hypertension. Respir Med. 2004;98:225–234
  25. Rubenfire M, Krishnan S, Montgomery D. Reponse to inhaled nitric oxide (iNO) does not predict long term mortality in pulmonary arterial hypertension (PAH). Am J Respir Crit Care Med. 2009;179:A2668
  26. Raffy O, Azarian R, Brenot F, et al. Clinical significance of the pulmonary vasodilator response during short-term infusion of prostacyclin in primary pulmonary hypertension. Circulation. 1996;93:484–488
  27. Barst RJ, Maislin G, Fishman AP. Vasodilator therapy for primary pulmonary hypertension in children. Circulation. 1999;99:1197–1208
  28. Ricciardi MJ, Knight BP, Martinez FJ, Rubenfire M. Inhaled nitric oxide in primary pulmonary hypertension: a safe and effective agent for predicting response to nifedipine. J Am Coll Cardiol. 1998;32:1068–1073
  29. Sitbon O, Brenot F, Denjean A, et al. Inhaled nitric oxide as a screening vasodilator agent in primary pulmonary hypertension. A dose–response study and comparison with prostacyclin. Am J Respir Crit Care Med. 1995;151:384–389
  30. Rich S, Brundage BH. High-dose calcium channel-blocking therapy for primary pulmonary hypertension: evidence for long-term reduction in pulmonary arterial pressure and regression of right ventricular hypertrophy. Circulation. 1987;76:135–141
  31. Rich S, D'Alonzo GE, Dantzker DR, Levy PS. Magnitude and implications of spontaneous hemodynamic variability in primary pulmonary hypertension. Am J Cardiol. 1985;55:159–163
  32. Rich S, Brundage BH, Levy PS. The effect of vasodilator therapy on the clinical outcome of patients with primary pulmonary hypertension. Circulation. 1985;71:1191–1196
  33. Costa EL, Jardim C, Bogossian HB, Amato MB, Carvalho CR, Souza R. Acute vasodilator test in pulmonary arterial hypertension: evaluation of two response criteria. Vascul Pharmacol. 2005;43:143–147
  34. Rich S, Dantzker DR, Ayres SM, et al. Primary pulmonary hypertension. A national prospective study. Ann Intern Med. 1987;107:216–223
  35. Pietra GG, Edwards WD, Kay JM, et al. Histopathology of primary pulmonary hypertension. A qualitative and quantitative study of pulmonary blood vessels from 58 patients in the National Heart, Lung, and Blood Institute, Primary Pulmonary Hypertension Registry. Circulation. 1989;80:1198–1206
  36. Bjornsson J, Edwards WD. Primary pulmonary hypertension: a histopathologic study of 80 cases. Mayo Clin Proc. 1985;60:16–25
  37. Wagenvoort CA, Wagenvoort N. Primary pulmonary hypertension: a pathologic study of the lung vessels in 156 clinically diagnosed cases. Circulation. 1970;42:1163–1184
  38. Rich S, Kaufmann E. High dose titration of calcium channel blocking agents for primary pulmonary hypertension: guidelines for short-term drug testing. J Am Coll Cardiol. 1991;18:1323–1327
  39. Schrader BJ, Inbar S, Kaufmann L, Vestal RE, Rich S. Comparison of the effects of adenosine and nifedipine in pulmonary hypertension. J Am Coll Cardiol. 1992;19:1060–1064
  40. McLaughlin VV, Genthner DE, Panella MM, Rich S. Reduction in pulmonary vascular resistance with long-term epoprostenol (prostacyclin) therapy in primary pulmonary hypertension. N Engl J Med. 1998;338:273–277
  41. Thenappan T, Shah SJ, Rich S, Gomberg-Maitland M. A USA-based registry for pulmonary arterial hypertension: 1982–2006. Eur Respir J. 2007;30:1103–1110
  42. Jing ZC, Jiang X, Han ZY, et al. Iloprost for pulmonary vasodilator testing in idiopathic pulmonary arterial hypertension. Eur Respir J. 2009;33:1354–1360
  43. Galiè N, Ussia G, Passarelli P, Parlangeli R, Branzi A, Magnani B. Role of pharmacologic tests in the treatment of primary pulmonary hypertension. Am J Cardiol. 1995;75:55A–62A
  44. Ghofrani HA, Wilkins MW, Rich S. Uncertainties in the diagnosis and treatment of pulmonary arterial hypertension. Circulation. 2008;118:1195–1201
  45. Zimmerman P, Brown L, Schmidt J, et al. Pulmonary arterial hypertension: is there a vasoreactive phenotype?. Am J Respir Crit Care Med. 2009;179:A2650
  46. Widimský J, Morpurgo M, Jezek V. Haemodynamic requirements for an ideal pulmonary vasodilator. Eur Heart J. 1988;9(Suppl. J):23–28
  47. Yamaki S, Wagenvoort CA. Comparison of primary plexogenic arteriopathy in adults and children. A morphometric study in 40 patients. Br Heart J. 1985;54:428–434
  48. Rosenzweig EB, Morse JH, Knowles JA, et al. Clinical implications of determining BMPR2 mutation status in a large cohort of children and adults with pulmonary arterial hypertension. J Heart Lung Transplant. 2008;27:668–674
  49. Wood P. Pulmonary hypertension with special reference to the vasoconstrictive factor. Br Heart J. 1958;20:557–570
  50. Hoeper MM, Olschewski H, Ghofrani HA, et al. A comparison of the acute hemodynamic effects of inhaled nitric oxide and aerosolized iloprost in primary pulmonary hypertension. German PPH study group. J Am Coll Cardiol. 2000;35:176–182
  51. Packer M. Vasodilator therapy for primary pulmonary hypertension. Limitations and hazards. Ann Intern Med. 1985;103:258–270
  52. Higenbottam T, Pepke-Zaba J, Scott J, et al. Inhaled “endothelial derived-relaxing factor” (EDRF) in primary hypertension (PPH). Am Rev Resp Dis. 1988;137:A107
  53. Pepke-Zaba J, Higenbottam TW. Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension. Lancet. 1991;338:1173–1174
  54. IchNOse F, Roberts JD, Zapol WM. Inhaled nitric oxide: a selective pulmonary vasodilator: current uses and therapeutic potential. Circulation. 2004;109:3106–3111
  55. Atz AM, Adatia I, Lock JE, Wessel DL. Combined effects of nitric oxide and oxygen during acute pulmonary vasodilator testing. J Am Coll Cardiol. 1999;33:813–819
  56. Jolliet P, Bulpa P, Thorens JB, Ritz M, Chevrolet JC. Nitric oxide and prostacyclin as test agents of vasoreactivity in severe precapillary pulmonary hypertension: predictive ability and consequences on haemodynamics and gas exchange. Thorax. 1997;52:369–372
  57. Opitz CF, Wensel R, Bettmann M, et al. Assessment of the vasodilator response in primary pulmonary hypertension. Comparing prostacyclin and iloprost administered by either infusion or inhalation. Eur Heart J. 2003;24:356–365
  58. Frampton MW, Morrow PE, Cox C, Gibb FR, Speers DM, Utell MJ. Effects of nitrogen dioxide exposure on pulmonary function and airway reactivity in normal humans. Am Rev Respir Dis. 1991;143:522–527
  59. Steudel W, Hurford WE, Zapol WM. Inhaled nitric oxide: basic biology and clinical applications. Anesthesiology. 1999;91:1090–1121
  60. Pearl JM, Nelson DP, Raake JL, et al. Inhaled nitric oxide increases endothelin-1 levels: a potential cause of rebound pulmonary hypertension. Crit Care Med. 2002;30:89–93
  61. Aranda M, Pearl RG. Inhaled nitric oxide and pulmonary vasoreactivity. J Clin Monit Comput. 2000;16:393–401
  62. Gomberg-Maitland M, Olschewski H. Prostacyclin therapies for the treatment of pulmonary arterial hypertension. Eur Respir J. 2008;31:891–901
  63. Palevsky HI, Fishman AP. Comparison of acute hemodynamic responses to prostacyclin with standard vasodilators in patients with primary pulmonary hypertension. Chest. 1988;93:179S
  64. Nootens M, Schrader B, Kaufmann E, Vestal R, Long W, Rich S. Comparative acute effects of adenosine and prostacyclin in primary pulmonary hypertension. Chest. 1995;107:54–57
  65. Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med. 2004;351:1425–1436
  66. Califf RM, Adams KF, McKenna WJ, et al. A randomized controlled trial of epoprostenol therapy for severe congestive heart failure: The Flolan International Randomized Survival Trial (FIRST). Am Heart J. 1997;134:44–54
  67. Olschewski H, Simonneau G, Galiè N, et al. Aerosolized Iloprost Randomized Study Group. Inhaled iloprost for severe pulmonary hypertension. N Engl J Med. 2002;347:322–329
  68. Wilkens H, Guth A, König J, et al. Effect of inhaled iloprost plus oral sildenafil in patients with primary pulmonary hypertension. Circulation. 2001;104:1218–1222
  69. Pelleg A, Porter RS. The pharmacology of adenosine. Pharmacotherapy. 1990;10:157–174
  70. Reeves JT, Groves BM, Weir EK. Adenosine and selective reduction of pulmonary vascular resistance in primary pulmonary hypertension. Circulation. 1991;84:1437–1439
  71. McLaughlin VV, Shillington A, Rich S. Survival in primary pulmonary hypertension: the impact of epoprostenol therapy. Circulation. 2002;106:1477–1482
  72. Morgan JM, McCormack DG, Griffiths MJ, Morgan CJ, Barnes PJ, Evans TW. Adenosine as a vasodilator in primary pulmonary hypertension. Circulation. 1991;84:1145–1149
  73. Preston IR, Klinger JR, Houtches J, Nelson D, Farber HW, Hill NS. Acute and chronic effects of sildenafil in patients with pulmonary arterial hypertension. Respir Med. 2005;99:1501–1510
  74. Stocker C, Penny DJ, Brizard CP, Cochrane AD, Soto R, Shekerdemian LS. Intravenous sildenafil and inhaled nitric oxide: a randomized trial in infants after cardiac surgery. Intensive Care Med. 2003;29:1996–2003
  75. Packer M. Is it ethical to administer vasodilator drugs to patients with primary pulmonary hypertension?. Chest. 1989;95:1173–1175
  76. Sitbon O, Humbert M, Jais X, et al. Acute vasodilator responsiveness and long-term response to calcium-channel blockers in different forms of pulmonary arterial hypertension. Am J Respir Crit Care Med. 2004;169:A210
  77. Elliott CG, Glissmeyer EW, Havlena GT, et al. Relationship of BMPR2 mutations to vasoreactivity in pulmonary arterial hypertension. Circulation. 2006;113:2509–2515
  78. Newman JH, Trembath RC, Morse JA, et al. Genetic basis of pulmonary arterial hypertension: current understanding and future directions. J Am Coll Cardiol. 2004;43:33S–39S
  79. Sztrymf B, Coulet F, Girerd B, et al. Clinical outcomes of pulmonary arterial hypertension in carriers of BMPR2 mutation. Am J Respir Crit Care Med. 2008;177:1377–1383
  80. Simonneau G, Fartoukh M, Sitbon O, et al. Primary pulmonary hypertension associated with the use of fenfluramine derivatives. Chest. 1998;114:195S–199S
  81. Klings ES, Hill NS, Ieong MH, Simms RW, Korn JH, Farber HW. Systemic sclerosis-associated pulmonary hypertension: short- and long-term effects of epoprostenol (prostacyclin). Arthritis Rheum. 1999;42:2638–2645
  82. Alpert MA, Pressly TA, Mukerji V, et al. Acute and long-term effects of nifedipine on pulmonary and systemic hemodynamics in patients with pulmonary hypertension associated with diffuse systemic sclerosis, the CREST syndrome and mixed connective tissue disease. Am J Cardiol. 1991;68:1687–1691
  83. ShNOhara S, Murata I, Yamada H, et al. Combined effects of diltiazem and oxygen in pulmonary hypertension of mixed connective tissue disease. J Rheumatol. 1994;21:1763–1765
  84. Sfikakis PP, Kyriakidis MK, Vergos CG, et al. Cardiopulmonary hemodynamics in systemic sclerosis and response to nifedipine and captopril. Am J Med. 1991;90:541–546
  85. Williamson DJ, Hayward C, Rogers P, et al. Acute hemodynamic responses to inhaled nitric oxide in patients with limited scleroderma and isolated pulmonary hypertension. Circulation. 1996;94:477–482
  86. Strange C, Bolster M, Mazur J, Taylor M, Gossage JR, Silver R. Hemodynamic effects of epoprostenol in patients with systemic sclerosis and pulmonary hypertension. Chest. 2000;118:1077–1082
  87. Jais X, Launay D, Yaici A, et al. Immunosuppressive therapy in lupus- and mixed connective tissue disease-associated pulmonary arterial hypertension: a retrospective analysis of twenty-three cases. Arthritis Rheum. 2008;58:521–531
  88. Farber HW, Graven KK, Kokolski G, Korn JH. Pulmonary edema during acute infusion of epoprostenol in a patient with pulmonary hypertension and limited scleroderma. J Rheumatol. 1999;26:1195–1196
  89. Preston IR, Klinger JR, Houtchens J, Nelson D, Mehta S, Hill NS. Pulmonary edema caused by inhaled nitric oxide therapy in two patients with pulmonary hypertension associated with the CREST syndrome. Chest. 2002;121:656–659
  90. Aguilar RV, Farber HW. Epoprostenol (prostacyclin) therapy in HIV-associated pulmonary hypertension. Am J Respir Crit Care Med. 2000;162:1846–1850
  91. Petitpretz P, Brenot F, Azarian R, et al. Pulmonary hypertension in patients with human immunodeficiency virus infection. Comparison with primary pulmonary hypertension. Circulation. 1994;89:2722–2727
  92. Opravil M, Pechère M, Speich R, et al. HIV-associated primary pulmonary hypertension. A case control study. Swiss HIV Cohort Study. Am J Respir Crit Care Med. 1997;155:990–995
  93. Gildein HP, Wildberg A, Mocellin R. Comparative studies of hemodynamics under prostacyclin and nifedipine in patients with Eisenmenger syndrome. Z Kardiol. 1995;84:55–63
  94. Fix OK, Bass NM, De Marco T, Merriman RB. Long-term follow-up of portopulmonary hypertension: effect of treatment with epoprostenol. Liver Transpl. 2007;13:875–885
  95. Jones DA, Benjamin CW, Linseman DA. Activation of thromboxane and prostacyclin receptors elicits opposing effects on vascular smooth muscle cell growth and mitogen-activated protein kinase signaling cascades. Mol Pharmacol. 1995;48:890–896
  96. Degano B, Yaïci1 A, Le Pavec1 J, et al. Long-term effects of bosentan in patients with HIV-associated pulmonary arterial hypertension. Eur Respir J. 2009;33:92–98
  97. Galiè N, Beghetti M, Gatzoulis MA, et al. Bosentan therapy in patients with Eisenmenger syndrome: a multicenter, double-blind, randomized, placebo-controlled study. Circulation. 2006;114:48–54
  98. Badesch DB, Tapson VF, McGoon MD, et al. Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial. Ann Intern Med. 2000;132:425–434
  99. Kuhlen R, Walbert E, Fränkel P, Thaden S, Behrendt W, Rossaint R. Combination of inhaled nitric oxide and intravenous prostacyclin for successful treatment of severe pulmonary hypertension in a patient with acute respiratory distress syndrome. Intensive Care Med. 1999;25:752–754
  100. Aranda M, Bradford KK, Pearl RG. Combined therapy with inhaled nitric oxide and intravenous vasodilators during acute and chronic experimental pulmonary hypertension. Anesth Analg. 1999;89:152–158
  101. Simonneau G, Rubin LJ, Galiè N, et al. Addition of sildenafil to long-term intravenous epoprostenol therapy in patients with pulmonary arterial hypertension: a randomized trial. Ann Intern Med. 2008;149:521–530
  102. Chan NS, McLay J, Kenmure AC. Reversibility of primary pulmonary hypertension during six years of treatment with oral diazoxide. Br Heart J. 1987;57:207–209
  103. Inbar S, Schrader BJ, Kaufmann E, Vestal RE, Rich S. Effects of adenosine in combination with calcium channel blockers in patients with primary pulmonary hypertension. J Am Coll Cardiol. 1993;21:413–418
  104. McMurtry IF, Davidson AB, Reeves JT, Grover RF. Inhibition of hypoxic pulmonary vasoconstriction by calcium antagonists in isolated rat lungs. Circ Res. 1976;38:99–104
  105. Kambara H, Fujimoto K, Wakabayashi A, Kawai C. Primary pulmonary hypertension: beneficial therapy with diltiazem. Am Heart J. 1981;101:230–231
  106. Oudiz RJ, Casanova A, Rubin LJ. Diagnostic work up of pulmonary arterial hypertension (PAH): data from the quality enhancement research initiative (QuERI). Am J Respir Crit Care Med. 2009;179:A2666
  107. McLaughlin V, Langer A, Dragomir A, et al. Treatment of pulmonary arterial hypertension (PAH): data from the quality enhancement research initiative. Am J Respir Crit Care Med. 2009;179:A1043
  108. Batra AK, Segall PH, Ahmed T. Pulmonary edema with nifedipine in primary pulmonary hypertension. Respiration. 1985;47:161–163
  109. Packer M, Medina N, Yushak M. Adverse hemodynamic and clinical effects of calcium channel blockade in pulmonary hypertension secondary to obliterative pulmonary vascular disease. J Am Coll Cardiol. 1984;4:890–901
  110. Aromatorio GJ, Uretsky BF, Reddy PS. Hypotension and sinus arrest with nifedipine in pulmonary hypertension. Chest. 1985;87:265–267
  111. Farber HW, Karlinsky JB, Faling LJ. Fatal outcome following nifedipine for pulmonary hypertension. Chest. 1983;83:708–709

PII: S0954-6111(09)00379-5

doi: 10.1016/j.rmed.2009.11.015

Respiratory Medicine
Volume 104, Issue 4 , Pages 481-496 , April 2010

Article Tools

* Image Usage & Resolution