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

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.

Figure 1

Length of prostanoid therapy for the entire cohort by drug treatment group.

Figure 2

Change in pulmonary-to-systemic vascular resistance ratio (Rp/Rs) over time on epoprostenol or treprostinil. There was an initial improvement in Rp/Rs at 1 to 2 years on therapy that was not sustained long-term.

Figure 3

(A) Change in pulmonary vascular resistance (PVR) index over time on epoprostenol or treprostinil. (B) Change in mean pulmonary artery pressure (mPAP) over time on epoprostenol and treprostinil. There was an initial improvement in both parameters at 1 to 2 years on therapy that was not sustained long-term.

Figure 4

Change in pulmonary-to-systemic vascular resistance ratio (Rp/Rs) from baseline catheterization on epoprostenol to follow-up catheterizations over time on treprostinil for 10 patients who transitioned from epoprostenol to treprostinil. Mean Rp/Rs at 9 to 15 months after transition increased from 0.6 to 0.8 (n = 7), which was similar to the increase in Rp/Rs in the entire cohort several years into therapy.

Figure 5

Kaplan-Meier survival curve for the entire cohort, comprising patients on epoprostenol, treprostinil, and those who transitioned, with 95% confidence intervals (CI) depicted. Transplant-free 5-year survival was 70% (95% CI, 56%–80%).

Figure 6

Survival curve by drug treatment group. Sub-groups were too small to permit meaningful statistical comparison of the curves. Transition occurred on average at 3.3 years into therapy.