Abstract
A large proportion of patients with congenital heart disease (CHD), in particular those with relevant systemic-to-pulmonary shunts, will develop pulmonary arterial hypertension (PAH) if left untreated. Persistent exposure of the pulmonary vasculature to increased blood flow, as well as increased pressure, may result in pulmonary obstructive arteriopathy, which leads to increased pulmonary vascular resistance that, if it approaches or exceeds systemic resistance, will result in shunt reversal. Eisenmenger’s syndrome, the most advanced form of PAH associated with CHD, is defined as CHD with an initial large systemic-to-pulmonary shunt that induces severe pulmonary vascular disease and PAH, with resultant reversal of the shunt and central cyanosis.
The histopathological and pathobiological changes seen in patients with PAH associated with congenital systemic-to-pulmonary shunts, such as endothelial dysfunction of the pulmonary vasculature, are considered similar to those observed in idiopathic or other associated forms of PAH. A pathological and pathophysiological classification of CHD with systemic-to-pulmonary shunt leading to PAH has been developed that includes specific characteristics, such as the type, dimensions and direction of the shunt, extracardiac abnormalities and repair status. A clinically oriented classification has also been proposed.
The prevalence of PAH associated with congenital systemic-to-pulmonary shunts in Western countries has been estimated to range between 1.6 and 12.5 cases per million adults, with 25–50% of this population affected by Eisenmenger’s syndrome.
Clinically, Eisenmenger’s syndrome presents with multiple organ involvement, with progressive deterioration of function over time. The signs and symptoms of Eisenmenger’s syndrome in the advanced stages include central cyanosis, dyspnoea, fatigue, haemoptysis, syncope and right-sided heart failure. Survival of patients with Eisenmenger’s syndrome is clearly less than that of the general population, but appears to be better than that of patients with idiopathic PAH in a comparable functional class.
The treatment strategy for patients with PAH associated with congenital systemic-to-pulmonary shunts and, in particular, those with Eisenmenger’s syndrome is based mainly on clinical experience rather than being evidence based. General measures include recommendations for physical activity, pregnancy, infections, air travel, exposure to high altitudes and elective surgery, and that psychological assistance be provided as necessary. Phlebotomies are required only when hyperviscosity of the blood is evident, usually when the haematocrit is >65%. The use of supplemental oxygen therapy is controversial and it should be used only in patients in whom it produces a consistent increase in arterial oxygen saturation. Oral anticoagulant treatment with warfarin can be initiated in patients with pulmonary artery thrombosis and absent, or only mild, haemoptysis.
The following three classes of drugs targeting the correction of abnormalities in endothelial dysfunction have been approved recently for the treatment of PAH: (i) prostanoids; (ii) endothelin receptor antagonists; and (iii) phosphodiesterase-5 inhibitors. The efficacy and safety of these compounds have been confirmed in uncontrolled studies in patients with PAH associated with corrected and uncorrected congenital systemic-to-pulmonary shunts, as well as in patients with Eisenmenger’s syndrome. One randomized controlled trial reported favourable short- and long-term outcomes of treatment with the orally active dual endothelin receptor antagonist bosentan in patients with Eisenmenger’s syndrome. Lung transplantation with repair of the cardiac defect or combined heart-lung transplantation are options for Eisenmenger’s syndrome patients with a poor prognosis. A treatment algorithm based on the one used in the treatment of PAH patients is proposed for patients with PAH associated with corrected and uncorrected congenital systemic-to-pulmonary shunts and Eisenmenger’s syndrome.
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References
Galie N, Rubin L. Pulmonary arterial hypertension: epidemiology, pathobiology, assessment and therapy. J Am Coll Cardiol 2004; 43: S1–90
Eisenmenger V. Die angeboren Defects des Kammerscheidewand des Herzen. Z Klin Med 1897; 32: 1–28
Brickner ME, Hillis LD, Lange RA. Congenital heart disease in adults: second of two parts [published erratum appears in N Engl J Med 2000 Mar 30; 342 (13): 988]. N Engl J Med 2000; 342: 334–342
Engelfriet P, Boersma E, Oechslin E, et al. The spectrum of adult congenital heart disease in Europe: morbidity and mortality in a 5 year follow-up period: The Euro Heart Survey on adult congenital heart disease. Eur Heart J 2005; 26: 2325–33
Duffels MGJ, Engelfriet PM, Berger RMF, et al. Pulmonary arterial hypertension in congenital heart disease: an epidemiologic perspective from a Dutch registry. Int J Cardiol 2007; 120: 198–204
Engelfriet PM, Duffels MGJ, Moller T, et al. Pulmonary arterial hypertension in adults born with a heart septal defect: the Euro Heart Survey on adult congenital heart disease. Heart 2007; 93: 682–7
Simonneau G, Galie N, Rubin L, et al. Clinical classification of pulmonary hypertension. J Am Coll Cardiol 2004; 43: S5–12
Lee SD, Shroyer KR, Markham NE, et al. Monoclonal endothelial cell proliferation is present in primary but not secondary pulmonary hypertension. J Clin Invest 1998; 101: 927–34
Galie N. Classification of patients with congenital systemic-to-pulmonary shunts associated with pulmonary hypertension: current status and future directions. In: Beghetti M, Barst R, Naeije R, et al., editors. Pulmonary arterial hypertension related to congenital heart disease. Munchen: Elsevier, 2006: 11–7
Gatzoulis MA, Barst RJ, Fineman J, et al. Eisenmenger’s syndrome and pulmonary arterial hypertension in adults with congenital heart disease. Curr Med Res Opin 2007; 23 Suppl. 2: S19–25
van Albada ME, Berger RMF. Pulmonary hypertension in the setting of the congenital cardiac disease: the need for refinement of the Evian-Venice classification. Cardiol Young 2008; 18: 10–17
Schulze-Neick I, Beghetti M. Classifying pulmonary hypertension in the setting of the congenitally malformed heart: cleaning up a dog’s dinner. Cardiol Young 2008; 18: 22–25
Daliento L, Somerville J, Presbitero P, et al. Eisenmenger’s syndrome: factors relating to deterioration and death. Eur Heart J 1998; 19: 1845–55
Besterman E. Atrial septal defects with pulmonary hypertension. Br Heart J 1961; 23: 587–98
Hoffman JE, Rudolph AM. The natural history of ventricular septal defects in infancy. Am J Cardiol 1985; 16: 634–53
Steele P, Fuster V, Cohen M, et al. Isolated atrial septal defect with pulmonary vascular obstructive disease: long-term follow-up and prediction of outcome after surgical correction. Circulation 1987; 76: 1037–42
Vogel M, Berger F, Kramer A, et al. Incidence of secondary pulmonary hypertension in adults with atrial septal or sinus venosus defects. Heart 1999; 82: 30–3
Kidd L, Driscoll D, Gersony W, et al. Second natural history study of congenital heart defects: results of treatment of patients with ventricular septal defects. Circulation 1993; 87: 138–51
Neumayer U, Stone S, Somerville J. Small ventricular septal defects in adults. Eur Heart J 1988; 19: 1573–82
Task FM, Galie N, Torbicki A, et al. 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: 2243–78
Humbert M, Sitbon O, Chaouat A, et al. Pulmonary arterial hypertension in France: results from a national registry. Am J Respir Crit Care Med 2006; 173: 1023–30
Peacock AJ, Murphy NF, McMurray JJV, et al. An epidemiological study of pulmonary arterial hypertension. Eur Respir J 2007; 30: 104–9
Pietra GG, Capron F, Stewart S, et al. Pathologic assessment of vasculopathies in pulmonary hypertension. J Am Coll Cardiol 2004; 43 (12 Suppl. 1): S25–32
Humbert M, Morrell N, Archer S, et al. Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol 2004; 43 (12 Suppl. 1): S13–24
Budhiraja R, Tuder RM, Hassoun PM. Endothelial dysfunction in pulmonary hypertension. Circulation 2004; 109: 159–65
Cowan KN, Heilbut A, Humpl T, et al. Complete reversal of fatal pulmonary hypertension in rats by a serine elastase inhibitor. Nat Med 2000; 6: 698–702
Du L, Sullivan CC, Chu D, et al. Signaling molecules in nonfamilial pulmonary hypertension. N Engl J Med 2003; 348: 500–9
Vongpatanasin W, Brickner ME, Hillis LD, et al. The Eisenmenger’s syndrome in adults. Ann Intern Med 1998; 128: 745–55
Diller GP, Dimopoulos K, Okonko D, et al. Exercise intolerance in adult congenital heart disease: comparative severity, correlates, and prognostic implication. Circulation 2005; 112: 828–35
Diller GP, Gatzoulis MA. Pulmonary vascular disease in adults with congenital heart disease. Circulation 2007; 115: 1039–50
Broberg C, Ujita M, Babu-Narayan S, et al. Massive pulmonary artery thrombosis with haemoptysis in adults with Eisenmenger’s syndrome: a clinical dilemma. Heart 2004; 90: e63
Broberg CS, Ujita M, Prasad S, et al. Pulmonary arterial thrombosis in eisenmenger’s syndrome is associated with biventricular dysfunction and decreased pulmonary flow velocity. J Am Coll Cardiol 2007; 50: 634–42
Diller GP, Dimopoulos K, Broberg CS, et al. Presentation, survival prospects, and predictors of death in Eisenmenger’s syndrome: a combined retrospective and case-control study. Eur Heart J 2006; 27: 1737–42
Hopkins WE, Ochoa LL, Richardson GW, et al. Comparison of the hemodynamics and survival of adults with severe primary pulmonary hypertension or Eisenmenger’s syndrome. J Heart Lung Transplant 1996; 15: 100–5
Berman EB, Barst RJ. Eisenmenger’s syndrome: current management. Prog Cardiovasc Dis 2002; 45: 129–38
Deanfield J, Thaulow E, Warnes C, et al. Management of grown up congenital heart disease. Eur Heart J 2003; 24: 1035–84
Galie N, Beghetti M, Gatzoulis MA, et al., for the Bosentan Randomized Trial of Endothelin Antagonist Therapy. Bosentan therapy in patients with eisenmenger’s syndrome: a multicenter, double-blind, randomized, placebo-controlled study. Circulation 2006; 114: 48–54
Mereles D, Ehlken N, Kreuscher S, et al. Exercise and respiratory training improve exercise capacity and quality of life in patients with severe chronic pulmonary hypertension. Circulation 2006; 114: 1482–9
Avila WS, Grinberg M, Snitcowsky R, et al. Maternal and fetal outcome in pregnant women with Eisenmenger’s syndrome. Eur Heart J 1995; 16: 460–4
Uebing A, Steer PJ, Yentis SM, et al. Pregnancy and congenital heart disease. BMJ 2006; 332: 401–6
Yentis SM, Steer PJ, Plaat F. Eisenmenger’s syndrome in pregnancy: maternal and fetal mortality in the 1990s. Br J Obstet Gynaecol 1998; 105: 921–2
Oakley C, Child A, Lung B, et al. Expert consensus document on management of cardiovascular diseases during pregnancy. Eur Heart J 2003; 24: 761–81
Kiely DG, Charles EA, Webster VJ, et al. Pregnancy and pulmonary hypertension: new approaches to the management of a lifethreatening combination. In: Steer PJ, Gatzoulis MA, Baker P, editors. Heart disease and pregnancy. London: RCOG press, 2006: 211–30
Broberg CS, Uebing A, Cuomo L, et al. Adult patients with Eisenmenger’s syndrome report flying safely on commercial airlines. Heart 2007 Dec; 93(12): 1599–603
Girgis A, Sanson-Fisher RW. Breaking bad news: consensus guidelines for medical practitioners. J Clin Oncol 1995; 13: 2449–56
Stewart M, Davidson K, Meade D, et al. Group support for couples coping with a cardiac condition. J Adv Nurs 2001; 33: 190–9
Broberg CS, Bax BE, Okonko DO, et al. Blood viscosity and its relationship to iron deficiency, symptoms, and exercise capacity in adults with cyanotic congenital heart disease. J Am Coll Cardiol 2006; 48: 356–65
Sandoval J, Aguirre JS, Pulido T, et al. Nocturnal oxygen therapy in patients with the Eisenmenger’s syndrome. Am J Respir Crit Care Med 2001; 164: 1682–7
Sitbon O, Humbert M, Jais X, et al. Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation 2005; 111: 3105–11
Post MC, Janssens S, Van de Werf F, et al. Responsiveness to inhaled nitric oxide is a predictor for mid-term survival in adult patients with congenital heart defects and pulmonary arterial hypertension. Eur Heart J 2004; 25: 1651–6
Rubin LJ, Mendoza J, Hood M, et al. Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol): results of a randomized trial. Ann Intern Med 1990; 112: 485–91
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
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: 425–34
Channick RN, Simonneau G, Sitbon O, et al. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet 2001; 358: 1119–23
Langleben D, Christman BW, Barst RJ, et al. Effects of the thromboxane synthetase inhibitor and receptor antagonist terbogrel in patients with primary pulmonary hypertension. Am Heart J 2002; 143: E4
Simonneau G, Barst RJ, Galie N, et al. Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension. a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med 2002; 165: 800–4
Rubin LJ, Badesch DB, Barst RJ, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med 2002; 346: 896–903
Galie N, Humbert M, Vachiery JL, et al. Effects of beraprost sodium, an oral prostacyclin analogue, in patients with pulmonary arterial hypertension: a randomised, double-blind placebo-controlled trial. J Am Coll Cardiol 2002; 39: 1496–502
Olschewski H, Simonneau G, Galie N, et al., for the AIR Study Group. Inhaled iloprost in severe pulmonary hypertension. N Engl J Med 2002; 347: 322–9
Barst RJ, McGoon M, McLaughlin VV, et al. Beraprost therapy for pulmonary arterial hypertension. J Am Coll Cardiol 2003; 41(12): 2119–25
Humbert M, Barst RJ, Robbins IM, et al. Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2. Eur Respir J 2004; 24: 353–9
Barst RJ, Langleben D, Frost A, et al. Sitaxsentan therapy for pulmonary arterial hypertension. Am J Respir Crit Care Med 2004; 169: 441–7
Sastry BKS, Narasimhan C, Reddy NK, et al. Clinical efficacy of sildenafil in primary pulmonary hypertension-1: a randomized, placebo-controlled, double-blind, crossover study. J Am Coll Cardiol 2004; 43: 1149–53
Galie N, Ghofrani HA, Torbicki A, et al., and the Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med 2005; 353: 2148–57
Barst RJ, Langleben D, Badesch D, et al. Treatment of pulmonary arterial hypertension with the selective endothelin-a receptor antagonist sitaxsentan. J Am Coll Cardiol 2006; 47: 2049–56
McLaughlin VV, Oudiz RJ, Frost A, et al. Randomized study of adding inhaled iloprost to existing bosentan in pulmonary arterial hypertension. Am J Respir Crit Care Med 2006; 174: 1257–63
Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med 2004; 351: 1425–36
Rosenzweig EB, Kerstein D, Barst RJ. Long-term prostacyclin for pulmonary hypertension with associated congenital heart defects. Circulation 1999; 99: 1858–65
Barst R, Langleben D, Frost A, et al. Sitaxsentan therapy for pulmonary arterial hypertension. Am J Resp Crit Care Med 2004; 169(4): 441–7
Fernandes SM, Newburger JW, Lang P, et al. Usefulness of epoprostenol therapy in the severely ill adolescent/adult with Eisenmenger’s physiology. Am J Cardiol 2003; 91: 632–5
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
Sitbon O, Humbert M, Nunes H, et al. Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: prognostic factors and survival, J Am Coll Cardiol 2002; 40: 780–788
McLaughlin VV, Shillington A, Rich S. Survival in primary pulmonary hypertension: the impact of epoprostenol therapy. Circulation 2002; 106: 1477–82
Galie N, Manes A, Branzi A. The endothelin system in pulmonary arterial hypertension. Cardiovasc Res 2004; 61: 227–37
Cacoub P, Dorent R, Maistre G, et al. Endothelin-1 in primary pulmonary hypertension and the Eisenmenger’s syndrome. Am J Cardiol 1993; 71: 448–50
Giaid A, Yanagisawa M, Langleben D, et al. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med 1993; 328: 1732–9
Christensen DD, McConnell ME, Book WM, et al. Initial experience with bosentan therapy in patients with the Eisenmenger’s syndrome. Am J Cardiol 2004; 94: 261–3
Gatzoulis MA, Rogers P, Li W, et al. Safety and tolerability of bosentan in adults with Eisenmenger’s physiology. Int J Cardiol 2005; 98: 147–51
Apostolopoulou SC, Manginas A, Cokkinos DV, et al. Effect of the oral endothelin antagonist bosentan on the clinical, exercise, and haemodynamic status of patients with pulmonary arterial hypertension related to congenital heart disease. Heart 2005; 91(11): 1447–52
Schulze-Neick I, Gilbert N, Ewert R, et al. Adult patients with congenital heart disease and pulmonary arterial hypertension: first open prospective multicenter study of bosentan therapy. Am Heart J 2005; 150: 716-e7-12
Diller GP, Dimopoulos K, Kaya MG, et al. Long-term safety, tolerability and efficacy of bosentan in adults with pulmonary arterial hypertension associated with congenital heart disease. Heart 2007; 93: 974–6
Apostolopoulou SC, Manginas A, Cokkinos DV, et al. Long-term oral bosentan treatment in patients with pulmonary arterial hypertension related to congenital heart disease: a 2-year study. Heart 2007; 93: 350–4
Gatzoulis MA, Beghetti M, Galie N, et al. Longer-term bosentan therapy improves functional capacity in Eisenmenger’s syndrome: results of the BREATHE-5 open-label extension study. Int J Cardiol. Epub 2007. doi:10.1016/j.ijcard.2007.04.078
van Loon RLE, Hoendermis ES, Duffels MG, et al. Long-term effect of bosentan in adults versus children with pulmonary arterial hypertension associated with systemic-to-pulmonary shunt: does the beneficial effect persist? Am Heart J 2007; 154: 776–82
Corbin JD, Francis SH. Cyclic GMP phosphodiesterase-5: target of sildenafil. J Biol Chem 1999; 274: 13729–32
Tantini B, Manes A, Fiumana E, et al. Antiproliferative effect of sildenafil on human pulmonary artery smooth muscle cells. Basic Res Cardiol 2005; 100(2): 131–8
Nagendran J, Archer SL, Soliman D, et al. Phosphodiesterase type 5 is highly expressed in the hypertrophied human right ventricle, and acute inhibition of phosphodiesterase type 5 improves contractility. Circulation 2007; 116: 238–48
Ghofrani HA, Pepke-Zaba J, Barbera JA, et al. Nitric oxide pathway and phosphodiesterase inhibitors in pulmonary arterial hypertension. J Am Coll Cardiol 2004; 43: S68–72
Celermajer DS, Cullen S, Deanfild JE. Impairment of endothelium-dependent pulmonary artery relaxation in children with congenital heart disease and abnormal pulmonary hemodynamics. Circulation 1993; 87: 440–6
Singh T, Rohit M, Grover A, et al. A randomized, placebo-controlled, double-blind, crossover study to evaluate the efficacy of oral sildenafil therapy in severe pulmonary artery hypertension. Am Heart J 2006; 151: 851-el-5
Lim ZS, Salmon AP, Vettukattil JJ, et al. Sildenafil therapy for pulmonary arterial hypertension associated with atrial septal defects. Int J Cardiol 2007; 118: 178–82
Chau EMC, Fan KYY, Chow WH. Effects of chronic sildenafil in patients with Eisenmenger’s syndrome versus idiopathic pulmonary arterial hypertension. Int J Cardiol 2007; 120: 301–5
Garg N, Sharma MK, Sinha N. Role of oral sildenafil in severe pulmonary arterial hypertension: clinical efficacy and dose response relationship. Int J Cardiol 2007; 120: 306–13
Humpl T, Reyes JT, Holtby H, et al. Beneficial effect of oral sildenafil therapy on childhood pulmonary arterial hypertension: twelve-month clinical trial of a single-drug, open-label, pilot study. Circulation 2005; 111: 3274–80
Mukhopadhyay S, Sharma M, Ramakrishnan S, et al. Phosphodiesterase-5 inhibitor in Eisenmenger’s syndrome: a preliminary observational study. Circulation 2006; 114: 1807–10
Palazzini M, Manes A, Romanazzi S, et al. Effects of sildenafil treatment in patients with pulmonary hypertension associated with congenital cardiac shunts [abstract]. Eur Heart J 2007; 28: 308
Hoeper M, Taha N, Bekjarova A, et al. Bosentan treatment in patients with primary pulmonary hypertension receiving non-parenteral prostanoids. Eur Respir J 2003; 22: 339–43
Ghofrani HA, Rose F, Schermuly RT, et al. Oral sildenafil as long-term adjunct therapy to inhaled iloprost in severe pulmonary arterial hypertension. J Am Coll Cardiol 2003; 42: 158–64
Hoeper MM, Faulenbach C, Golpon H, et al. Combination therapy with bosentan and sildenafil in idiopathic pulmonary arterial hypertension. Eur Respir J 2004; 24: 1007–10
Hoeper M, Leuchte H, Halank M, et al. Combining inhaled iloprost with bosentan in patients with idiopathic pulmonary arterial hypertension. Eur Respir J 2006; 4(28): 691–4
Mathai SC, Girgis RE, Fisher MR, et al. Addition of sildenafil to bosentan monotherapy in pulmonary arterial hypertension. Eur Respir J 2007; 29: 469–75
Humbert M, Barst R, Robbins I, et al. Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2. Eur Respir J 2004; 24(3): 353–9
Simonneau G, Rubin L, Galie N, et al. Safety and efficacy of sildenafil-epoprostenol combination therapy in patients with pulmonary arterial hypertension [abstract]. Am J Respir Crit Care Med 2007; 175: A300
Therrien J, Warnes C, Daliento L, et al. Canadian Cardiovascular Society Consensus Conference 2001 update: recommendations for the management of adults with congenital heart disease part III. Can. J Cardiol 2001; 17: 1135–58
Frost AE, Quinones MA, Zoghbi WA, et al. Reversal of pulmonary hypertension and subsequent repair of atrial septal defect after treatment with continuous intravenous epoprostenol. J Heart Lung Transplant 2005; 24: 501–3
Schwerzmann M, Zafar M, McLaughlin PR, et al. Atrial septal defect closure in a patient with ‘irreversible’ pulmonary hypertensive arteriopathy. Int J Cardiol 2006; 110: 104–7
Eicken A, Balling G, Gielden HP et al. Transcatheter closure of a non-restrictive patent ductus arteriosus with an Amplatzer muscular ventricular septal defect occluder. Int J Cardiol 2007; 117: c40–2
Dimopoulos K, Peset A, Gatzouulis MA. Evaluating operability in adults with congenital heart disease and the role of pretreatment with targeted pulmonary arterial hypertension therapy. Int J Cardiol. Epub 2008. doi: 10.1016/j.ijcardio.2008.02.004
Klepetko W, Mayer E, Sandoval J, et al. Interventional and surgical modalities of treatment for pulmonary arterial hypertension. J Am Coll Cardiol 2004; 43 (12 Suppl. S): 73–80S
Badesch DB, Abman SH, Ahearn GS, et al. Medical therapy for pulmonary arterial hypertension: ACCP evidence-based guidelines for clinical practice. Chest 2004; 126: 35–62S
Galie N, Torbicki A, Barst R, et al. Pocket guidelines on the diagnosis and treatment of pulmonary arterial hypertension. Sophia Antipolis: European Society of Cardiology, 2006
Acknowledgements
Dr Galie reports having served on the advisory boards of Pfizer, Actelion, Schering, Encysive, Myogen, GlaxoSmithKline and Mondobiotec, and that the Institute of Cardiology has received grant support from Pfizer, Actelion, Schering, Encysive, United Therapeutics and Myogen. The other authors report no conflicts of interest that are directly relevant to the content of this review. No sources of funding were used to assist specifically in the preparation of this review.
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Galie, N., Manes, A., Palazzini, M. et al. Management of Pulmonary Arterial Hypertension Associated with Congenital Systemic-to-Pulmonary Shunts and Eisenmenger’s Syndrome. Drugs 68, 1049–1066 (2008). https://doi.org/10.2165/00003495-200868080-00004
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DOI: https://doi.org/10.2165/00003495-200868080-00004