Children with Pulmonary Arterial Hypertension and Prostanoid Therapy: Long-term Hemodynamics

Overview

Journal J Heart Lung Transplant

Publisher Elsevier

Specialties Cardiology & Vascular Diseases
General Surgery
Pulmonary Medicine

Date 2013 Mar 5

PMID 23453572

Citations 27

Authors

Stephanie L Siehr

D Dunbar Ivy

Kathleen Miller-Reed

Michelle Ogawa

David N Rosenthal

Jeffrey A Feinstein

Affiliations

Soon will be listed here.

Abstract

Background: Pediatric patients with severe pulmonary arterial hypertension (PAH) are treated with intravenous epoprostenol or intravenous or subcutaneous treprostinil. Little is known about longitudinal hemodynamics and outcomes of epoprostenol, treprostinil, and transitions from epoprostenol to treprostinil.

Methods: This was retrospective study of 77 pediatric patients (47 idiopathic PAH, 24 congenital heart disease-PAH) receiving epoprostenol or treprostinil from 1992 to 2010 at 2 centers. Outcomes were defined as living vs dead/transplant.

Results: Mean age at baseline was 7.7 ± 5.2 years, with follow-up of 4.3 ± 3.4 years. Thirty-seven patients were treated with epoprostenol, 20 with treprostinil, and 20 were transitioned from epoprostenol to treprostinil. Mean pulmonary-to-systemic vascular resistance ratio (Rp/Rs) for epoprostenol was 1.0 ± 0.4, 0.8 ± 0.4, 0.8 ± 0.4, 1.0 ± 0.4, and 1.2 ± 0.4, respectively, at baseline, 1, 2, 3, and 4 years. For treprostinil, Rp/Rs was 0.9 ± 0.3, 0.7 ± 0.3, 0.5 ± 0.2, (p < 0.01 vs baseline), and 1.1 ± 0.2, respectively, at baseline, 1, 2, and 3 to 4 years, respectively. There were similar changes in mean pulmonary artery pressure and pulmonary vascular resistance index. The Rp/Rs 1 year after epoprostenol to treprostinil transition increased from 0.6 to 0.8 (n = 7). Changes not statistically significant unless noted. Eight patients died or received a transplant within 2 years of baseline; compared with the rest of the cohort, mean baseline Rp/Rs, right atrial pressure, and pulmonary vascular resistance index were significantly worse in this group. Thirty-nine patients remain on prostanoids, 17 are off, 16 died, and 5 received heart-lung transplant. Kaplan-Meier 5-year transplant-free survival was 70% (95% confidence interval, 56%-80%).

Conclusion: There was improvement in Rp/Rs on both therapies at 1 to 2 years that was not sustained. The 5-year transplant-free survival was better than in similar adult studies.

Citing Articles

Younger age at initiation of subcutaneous treprostinil is associated with better response in pediatric Group 1 pulmonary arterial hypertension.

Kochanski J, Feinstein J, Ogawa M, Ritter V, Hopper R, Adamson G Pulm Circ. 2024; 14(1):e12328.

PMID: 38348195 PMC: 10860541. DOI: 10.1002/pul2.12328.

Factors leading to supranormal cardiac index in pediatric pulmonary hypertension patients treated with parenteral prostanoid therapy.

Miles K, Critser P, Evers P, Cash M, Magness M, Geers E Pulm Circ. 2023; 13(3):e12264.

PMID: 37427091 PMC: 10323166. DOI: 10.1002/pul2.12264.

Failure to tolerate continuous subcutaneous treprostinil in pediatric pulmonary hypertension patients.

McSweeney J, Colglazier E, Becerra J, Leary B, Miller-Reed K, Walker S Pulm Circ. 2023; 13(2):e12224.

PMID: 37143765 PMC: 10151594. DOI: 10.1002/pul2.12224.

Hemodynamic assessment of transitioning from parenteral prostacyclin to selexipag in pediatric pulmonary hypertension.

Colglazier E, Stevens L, Parker C, Nawaytou H, Amin E, Becerra J Pulm Circ. 2022; 12(4):e12159.

PMID: 36514390 PMC: 9732384. DOI: 10.1002/pul2.12159.

Critical Care Management of Decompensated Right Heart Failure in Pulmonary Arterial Hypertension Patients - An Ongoing Approach.

Tilea I, Varga A, Georgescu A, Grigorescu B J Crit Care Med (Targu Mures). 2021; 7(3):170-183.

PMID: 34722920 PMC: 8519386. DOI: 10.2478/jccm-2021-0020.

References

Gomberg-Maitland M, Tapson V, Benza R, McLaughlin V, Krichman A, Widlitz A . Transition from intravenous epoprostenol to intravenous treprostinil in pulmonary hypertension. Am J Respir Crit Care Med. 2005; 172(12):1586-9. DOI: 10.1164/rccm.200505-766OC. View

Yung D, Widlitz A, Rosenzweig E, Kerstein D, Maislin G, Barst R . Outcomes in children with idiopathic pulmonary arterial hypertension. Circulation. 2004; 110(6):660-5. DOI: 10.1161/01.CIR.0000138104.83366.E9. View

McLaughlin V, Shillington A, Rich S . Survival in primary pulmonary hypertension: the impact of epoprostenol therapy. Circulation. 2002; 106(12):1477-82. DOI: 10.1161/01.cir.0000029100.82385.58. View

Barst R, Rubin L, Long W, McGoon M, Rich S, Badesch D . A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med. 1996; 334(5):296-301. DOI: 10.1056/NEJM199602013340504. View

Melnick L, Barst R, Rowan C, Kerstein D, Rosenzweig E . Effectiveness of transition from intravenous epoprostenol to oral/inhaled targeted pulmonary arterial hypertension therapy in pediatric idiopathic and familial pulmonary arterial hypertension. Am J Cardiol. 2010; 105(10):1485-9. DOI: 10.1016/j.amjcard.2009.12.075. View

Lammers A, Hislop A, Flynn Y, Haworth S . Epoprostenol treatment in children with severe pulmonary hypertension. Heart. 2006; 93(6):739-43. PMC: 1955199. DOI: 10.1136/hrt.2006.096412. View

Sitbon O, Humbert M, Nunes H, Parent F, Garcia G, Herve P . Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: prognostic factors and survival. J Am Coll Cardiol. 2002; 40(4):780-8. DOI: 10.1016/s0735-1097(02)02012-0. View

Barst R, Ivy D, Dingemanse J, Widlitz A, Schmitt K, Doran A . Pharmacokinetics, safety, and efficacy of bosentan in pediatric patients with pulmonary arterial hypertension. Clin Pharmacol Ther. 2003; 73(4):372-82. DOI: 10.1016/s0009-9236(03)00005-5. View

Bergstra A, van Dijk R, Hillege H, Lie K, Mook G . Assumed oxygen consumption based on calculation from dye dilution cardiac output: an improved formula. Eur Heart J. 1995; 16(5):698-703. DOI: 10.1093/oxfordjournals.eurheartj.a060976. View

10.

Rosenzweig E, Ivy D, Widlitz A, Doran A, Claussen L, Yung D . Effects of long-term bosentan in children with pulmonary arterial hypertension. J Am Coll Cardiol. 2005; 46(4):697-704. DOI: 10.1016/j.jacc.2005.01.066. View

11.

Mourani P, Sontag M, Ivy D, Abman S . Effects of long-term sildenafil treatment for pulmonary hypertension in infants with chronic lung disease. J Pediatr. 2008; 154(3):379-84, 384.e1-2. PMC: 2783835. DOI: 10.1016/j.jpeds.2008.09.021. View

12.

Levy M, Celermajer D, Bourges-Petit E, Del Cerro M, Bajolle F, Bonnet D . Add-on therapy with subcutaneous treprostinil for refractory pediatric pulmonary hypertension. J Pediatr. 2010; 158(4):584-8. DOI: 10.1016/j.jpeds.2010.09.025. View

13.

Humpl T, Reyes J, Holtby H, Stephens D, Adatia I . 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(24):3274-80. DOI: 10.1161/CIRCULATIONAHA.104.473371. View

14.

van Loon R, Roofthooft M, Delhaas T, van Osch-Gevers M, Ten Harkel A, Strengers J . Outcome of pediatric patients with pulmonary arterial hypertension in the era of new medical therapies. Am J Cardiol. 2010; 106(1):117-24. DOI: 10.1016/j.amjcard.2010.02.023. View

15.

DAlonzo G, Barst R, Ayres S, Bergofsky E, Brundage B, Detre K . Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med. 1991; 115(5):343-9. DOI: 10.7326/0003-4819-115-5-343. View

16.

Rubin L, GROVES B, Reeves J, Frosolono M, HANDEL F, Cato A . Prostacyclin-induced acute pulmonary vasodilation in primary pulmonary hypertension. Circulation. 1982; 66(2):334-8. DOI: 10.1161/01.cir.66.2.334. View

17.

Ivy D, Doran A, Smith K, Mallory Jr G, Beghetti M, Barst R . Short- and long-term effects of inhaled iloprost therapy in children with pulmonary arterial hypertension. J Am Coll Cardiol. 2008; 51(2):161-9. PMC: 3125969. DOI: 10.1016/j.jacc.2007.09.031. View

18.

Balzer D, Kort H, Day R, Corneli H, Kovalchin J, Cannon B . Inhaled Nitric Oxide as a Preoperative Test (INOP Test I): the INOP Test Study Group. Circulation. 2002; 106(12 Suppl 1):I76-81. View

19.

McLaughlin V, Gaine S, Barst R, Oudiz R, Bourge R, Frost A . Efficacy and safety of treprostinil: an epoprostenol analog for primary pulmonary hypertension. J Cardiovasc Pharmacol. 2003; 41(2):293-9. DOI: 10.1097/00005344-200302000-00019. View

20.

Rosenzweig E, Kerstein D, Barst R . Long-term prostacyclin for pulmonary hypertension with associated congenital heart defects. Circulation. 1999; 99(14):1858-65. DOI: 10.1161/01.cir.99.14.1858. View