Journal of Rare Cardiovascular Diseases

Pulmonary arterial hypertension is a disease characterized by poor prognosis despite treatment. Even in a modern era of pharmaco- therapy there is a strong need to further improve survival of patients. The current therapeutic strategies do not offer a real break-through in terms of reducing mortality. In a search for better efficacy of treatment we discuss a strategy based on lowering pulmonary artery pressure as much as possible with epoprostenol in monotherapy or in combination. Epoprostenol with bosentan is an effective tool in achieving this goal. A rapid up-titration regardless of maximum epoprostenol dose achieved gives additional long-term benefit. Practical issues related to such modality of treatment are also discussed. JRCD 2017; 3 (4): 110–115

pulmonary arterial hypertension; treatment; epoprostenol; outcome

Podolec P. Classification of Rare Cardiovascular Diseases (RCD Classification), Krakow 2013. JRCD 2013; 1: 49-60.

Kurzyna M, Żyłkowska J, Fijałkowska A, et al. Characteristics and prognosis of patients with decompensated right ventricular failure during the course of pulmonary hypertension. Kardiol Pol 2008; 66: 1033-1039.

Harvey LD, Chan SY. Emerging Metabolic Therapies in Pulmonary Arterial Hypertension J Clin Med 2017; 6: 43.

Bertero T, Oldham WM, Cottrill KA, et al. Vascular stiffness mechanoactivates yap/taz-dependent glutaminolysis to drive pulmonary hypertension. J Clin Invest 2016; 126: 3313–3335.

Vonk-Noordegraaf A, Haddad F, Chin KM, et al. Right heart adaptation to pulmonary arterial hypertension: physiology and pathobiology. J Am Coll Cardiol 2013; 62(Suppl): D22-33.

Ryan JJ, Archer SL. The right ventricle in pulmonary arterial hypertension: disorders of metabolism, angiogenesis and adrenergic signaling in right ventricular failure. Circ Res 2014; 115: 176-188.

D’Alonzo GE, Barst RJ, Ayres SM, et al. Survival in patients with primary pulmonary hyper- tension: Results from a national prospective registry. Ann Intern Med 1991; 115: 343–349.

Rich S, Dantzker DR, Ayres SM, et al. Primary pulmonary hypertension: A national pro- spective study. Ann Intern Med 1987; 107: 216–223.

Barst RJ, Rubin LJ, McGoon MD, et al. Survival in primary pulmonary hypertension with long-term continuous intravenous prostacyclin. Ann Intern Med 1994; 121: 409–415.

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.

Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J 2015; 46: 903-975.

Humbert M, Sitbon O, Yaici A, et al. Survival in incident and prevalent cohorts of patients with pulmonary arterial hypertension. Eur Respir J 2010; 36: 549 – 555.

Farber HW, Miller DP, Poms AD, et al. Five-Year outcomes of patients enrolled in the REVEAL Registry. Chest 2015; 148: 1043–1054.

Galie N, Hoeper MM, Humbert M, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension. The Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). European Heart Journal 2009; 30: 2493–2537.

Adel E, Mercier O, Mussot S, et al. Long-term outcome of double-lung and heart-lung transplantation for pulmonary hypertension: a comparative retrospective study of 219 patients. Eur J Cardiothorac Surg 2010; 38: 277–284.

Toyoda Y, Thacker J, Santos R et al. Long-term outcome of lung and heart-lung transplantation for idiopathic pulmonary arterial hypertension. Ann Thorac Surg, 2008; 86: 1116–1122.

Fadel E, Mercier O, Mussot S et al. Long-term outcome of double-lung and heart&lung transplantation for pulmonary hypertension: a comparative retrospective study of 219 patients. Eur J Cardiothorac Surg 2010; 38: 277–284.

de Perrot M, Granton JT, McRae K et al. Outcome of patients with pulmonary arterial hypertension referred for lung transplantation: a 14-year single-center experience. J Thorac Cardiovasc Surg 2012; 143: 910–918.

Yusen RD, Edwards LB, Kucheryavaya AY, et al. The Registry of the International Society for Heart and Lung Transplantation: Thirty-second Official Adult Lung and Heart-Lung Transplantation Report–2015; Focus Theme: Early Graft Failure. J Heart Lung Transplant 2015; 34: 1264-1277.

Oudiz RJ, Farber HW. Dosing considerations in the use of intravenous prostanoids in pulmonary arterial hypertension: an experience-based review. Am Heart J 2009; 157: 625-635.

Sitbon O, Jaïs X, Savale L, et al. Upfront triple combination therapy in pulmonary arterial hypertension: a pilot study. Eur Respir J 2014; 43: 1691-1697.

McLaughlin VV, McGoon MD. Pulmonary arterial hypertension. Circulation 2006; 114: 1417–1431.

: Akagi S, Nakamura K, Miyaji K, et al. Marked hemodynamic improvements by high-dose epoprostenol therapy in patients with idiopathic pulmonary arterial hypertension. Circ J 2010; 74: 2200-2205.

Rich S, McLaughlin VV. The effects of chronic prostacyclin therapy on cardiac output and symptoms in primary pulmonary hypertension. J Am Coll Cardiol 1999; 34: 1184–1187.

Akagi S, Matsubara H, Miyaji K, et al. Additional effects of bosentan in patients with idiopathic pulmonary arterial hypertension already treated with high-dose epoprostenol. Circ J 2008; 72: 1142–1146.

Ogawa A, Ejiri K, Matsubara H. Long-term patient survival with idiopathic/heritable pulmonary arterial hypertension treated at a single center in Japan. Life Sci 2014; 118: 414-419.

Tokunaga N, Ogawa A, Ito H, et al. Rapid and high-dose titration of epoprostenol improves pulmonary hemodynamics and clinical outcomes in patients with idiopathic and heritable pulmonary arterial hypertension. J Cardiol 2016; 68: 542-547.

Ogawa A, Satoh T, Tamura Y, et al. Survival of Japanese Patients With Idiopathic/Heritable Pulmonary Arterial Hypertension. Am J Cardiol 2017; 119: 1479-1484.

N. Nickel, H. Golpon, M. Greer, et al. The prognostic impact of follow-up assessments in patients with idiopathic pulmonary arterial hypertension. Eur Respir J 2012; 39: 589–596.