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Children with severe Group 1 pulmonary arterial hypertension (PAH) have an unpredictable response to subcutaneous treprostinil (TRE) therapy, which may be influenced by age, disease severity, or other unknown variables at time of initiation. In this retrospective single‐center cohort study, we hypothesized that younger age at TRE initiation, early hemodynamic response (a decrease in pulmonary vascular resistance by ≥30% at follow‐up catheterization), and less severe baseline hemodynamics (Rp:Rs < 1.1) would each be associated with better clinical outcomes. In 40 pediatric patients with Group I PAH aged 17 days−18 years treated with subcutaneous TRE, younger age (cut‐off of 6‐years of age, AUC 0.824) at TRE initiation was associated with superior 5‐year freedom from adverse events (94% vs. 39%, p = 0.002), better WHO functional class (I or II: 88% vs. 39% p = 0.003), and better echocardiographic indices of right ventricular function at most recent follow‐up. Neither early hemodynamic response nor less severe baseline hemodynamics were associated with better outcomes. Patients who did not have a significant early hemodynamic response to TRE by first follow‐up catheterization were unlikely to show subsequent improvement in PVRi (1/8, 13%). These findings may help clinicians counsel families and guide clinical decision making regarding the timing of advanced therapies. [ABSTRACT FROM AUTHOR]

Continuous subcutaneous (SubQ) treprostinil is an effective therapy for pediatric patients diagnosed with pulmonary hypertension (PH). To date, the clinical characteristics and factors associated with failure to tolerate this therapy have not been described. The purpose was to describe patient-reported factors contributing to SubQ treprostinil intolerance in pediatric patients with PH. A retrospective descriptive study was performed at 11 participating sites in the United States and Canada for patients younger than 21 years of age diagnosed with PH who failed treatment to tolerate SubQ treprostinil between January 1, 2009, and December 31, 2019. All data were summarized using descriptive statistics. Forty-one patients met the inclusion criteria. The average age at SQ treprostinil initiation, and length of treatment, was 8.6 years and 22.6 months, respectively. The average maximum dose, concentration, and rate were 95.8 ng/kg/min, 6.06 mg/mL, and 0.040 mL/h, respectively. The reasons for failure to tolerate SubQ treprostinil included intractable site pain (73.2%), frequent site changes (56.1%), severe site reactions (53.7%), infections (26.8%), and noncompliance/depression/anxiety (17.1%). Thirty-nine (95.1%) patients transitioned to a prostacyclin therapy with 23 patients transitioning to intravenous prostacyclin, 5 to inhaled prostacyclin, 5 to oral prostacyclin, and 7 to a prostacyclin receptor agonist. A subset of pediatric PH patients failed to tolerate SubQ treprostinil infusions despite advances in SubQ site maintenance and pain management strategies. Intractable site pain, frequent SubQ site changes, and severe localized skin reactions were the most common reasons for failure. [ABSTRACT FROM AUTHOR]

Endogenous prostacyclin stimulates pulmonary vasodilation and inhibits platelet aggregation. For the synthetic analog treprostinil, used in the treatment of pulmonary hypertension (PH), conflicting, anecdotal evidence exists regarding its effects on clinically relevant platelet function. This study investigated whether treprostinil therapy results in inhibition of platelet aggregation in pediatric PH patients. This is a single institution, prospective, cohort study. Pediatric patients ≤18 years of age on medical therapy for PH underwent platelet function testing by light transmission aggregometry with U‐46619—a stable analog of endoperoxide prostaglandin H2, exhibiting properties similar to thromboxane A2 (TXA2). Results were compared for those on continuous treprostinil therapy (TRE) versus those on other, non‐prostacyclin therapies (non‐TRE). Thirty‐five patients were enrolled: 18 in the TRE group and 17 in the non‐TRE group. There was no difference in platelet aggregation abnormalities between the two groups: 44% (n = 8) in the TRE group and 41% (n = 7) in the non‐TRE group were abnormal. Furthermore, subgroup analysis showed no difference based on treprostinil dosing. This study demonstrated similar, moderately high rates of abnormal platelet aggregation in pediatric PH patients on continuous treprostinil therapy compared to those on other, non‐prostacyclin therapies. The high rate of abnormal platelet aggregation in the entire cohort, however, warrants follow‐up study to identify a potential inherent risk in this population. [ABSTRACT FROM AUTHOR]

Background: Treprostinil, a prostacyclin analog, is a safe and effective therapy for children with PAH; however, the use of this agent in children with mild PVR elevations related to HF, including those with SV congenital heart disease awaiting HT, is understudied. We describe the hemodynamic and symptomatic changes in pediatric patients awaiting HT treated with treprostinil. Methods: Single‐center retrospective review of all patients was listed for HT who received treprostinil during the listing period. Changes in hemodynamic and functional indices between the baseline catheterization (prior to drug initiation), and prior to HT, and patient outcomes were analyzed. Results: Among 16/17 (94%) who survived to HT, 8 (50%) were female, and 10 (63%) had SV physiology. The median age at drug initiation was 9 (IQR: 1, 14) years. The median duration of therapy prior to HT was 253 (IQR: 148, 504) days. Treprostinil significantly decreased PVR (3.8 vs 3.1 WU, P =.03), while mLA or mPCW pressure did not change (11 vs 13 mm Hg, P =.9). HF symptoms improved in 9/15 (60%) patients without VAD support prior to drug initiation, including 4/10 (40%) who did not receive a VAD any point while awaiting HT. Conclusions: Treprostinil may be used safely in patients with mild PAH awaiting HT, including those with SV disease. PVR falls without substantial increases in mLA/mPCW pressure. HF symptoms improve in some patients. [ABSTRACT FROM AUTHOR]