Children with pulmonary arterial hypertension and prostanoid therapy: long-term hemodynamics

J Heart Lung Transplant. 2013 May;32(5):546-52. doi: 10.1016/j.healun.2013.01.1055. Epub 2013 Feb 28.

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.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous
  • Adolescent
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use*
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Child
  • Child, Preschool
  • Epoprostenol / administration & dosage
  • Epoprostenol / analogs & derivatives*
  • Epoprostenol / pharmacology
  • Epoprostenol / therapeutic use*
  • Familial Primary Pulmonary Hypertension
  • Female
  • Follow-Up Studies
  • Hemodynamics / drug effects
  • Hemodynamics / physiology*
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / mortality
  • Hypertension, Pulmonary / physiopathology
  • Infusions, Subcutaneous
  • Longitudinal Studies
  • Male
  • Prostaglandins / administration & dosage
  • Prostaglandins / pharmacology
  • Prostaglandins / therapeutic use*
  • Retrospective Studies
  • Survival Rate
  • Treatment Outcome
  • Vascular Resistance / drug effects
  • Vascular Resistance / physiology

Substances

  • Antihypertensive Agents
  • Prostaglandins
  • Epoprostenol
  • treprostinil