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Objective: Total cavo-pulmonary connection (TCPC) is a palliative treatment for single ventricular malformations. For high-risk patients (preoperative mean pulmonary arterial pressure, mPAP > 15 mmHg), between the inhaled and oral targeted medications, the application of intravenous treprostinil as a bridge therapy to achieve "seamless" management is core postoperative treatment. This study intends to explore the effect of different administration regimens on early postoperative recovery. Methods: This was a retrospective cohort study. High-risk pediatric patients (age ≤ 14 years) who underwent TCPC procedure in Fu Wai Hospital from 2015 to 2022 were included. Since the regimen of treprostinil was standardized in our center in 2021, the patients in 2020 and before were included in group 1, patients in 2021 and 2022 were included in group 2. The hemodynamic parameters were compared before and after the maintenance dose of treprostinil. The differences of demographic characteristics, surgical data and postoperative recovery were compared between the two groups. Results: A total of 51 pediatric patients were included. Group 1 included 35 patients who received treprostinil at 1–3 postoperative days and an average dose of 12 ± 4 ng/(kg·min). Group 2 included 16 patients who received treprostinil within postoperative 1 day and an average dose of 22 ± 7 ng/(kg·min). There were no significant differences between the two groups in terms of age, weight, preoperative percutaneous oxygen saturation and mPAP, heterotaxy syndrome, TCPC procedure type, other concurrent procedure, cardiopulmonary bypass time and aortic cross-clamp proportion (p > 0.05). After 24 h of treprostinil treatment, the mPAP in group 1 reduced from 17 ± 3 mmHg to 15 ± 2 mmHg (p < 0.001), and in group 2 from 17 ± 2 mmHg to 14 ± 2 mmHg (p < 0.001), with no difference between groups. In the postoperative recovery, patients in Group 2 exhibited a reduced duration of mechanical ventilation, 19 (11, 25) hours vs 69 (23, 189) hours, p = 0.001; a shorter stay in the ICU, 8 (6, 12) days vs 16 (9,26) days, p = 0.006; and a shorter postoperative length of stay, 27 (17,55) days vs 39 (29,58) days, p = 0.032. Patients in Group 2 also exhibited a lower incidence of thromboembolic events, 0 (0/26) vs 26% (9/35), p = 0.043; and the need for renal replacement therapy, 0 (0/26) vs 31% (11/35), p = 0.011. Conclusion: Treprostinil reduces pulmonary artery pressure after TCPC procedure. The standardized application of treprostinil may improve the postoperative recovery which should be proven by randomized controlled trials or matched cohort studies in the future. [ABSTRACT FROM AUTHOR]

Abstract Objective Total cavo-pulmonary connection (TCPC) is a palliative treatment for single ventricular malformations. For high-risk patients (preoperative mean pulmonary arterial pressure, mPAP > 15 mmHg), between the inhaled and oral targeted medications, the application of intravenous treprostinil as a bridge therapy to achieve “seamless” management is core postoperative treatment. This study intends to explore the effect of different administration regimens on early postoperative recovery. Methods This was a retrospective cohort study. High-risk pediatric patients (age ≤ 14 years) who underwent TCPC procedure in Fu Wai Hospital from 2015 to 2022 were included. Since the regimen of treprostinil was standardized in our center in 2021, the patients in 2020 and before were included in group 1, patients in 2021 and 2022 were included in group 2. The hemodynamic parameters were compared before and after the maintenance dose of treprostinil. The differences of demographic characteristics, surgical data and postoperative recovery were compared between the two groups. Results A total of 51 pediatric patients were included. Group 1 included 35 patients who received treprostinil at 1–3 postoperative days and an average dose of 12 ± 4 ng/(kg·min). Group 2 included 16 patients who received treprostinil within postoperative 1 day and an average dose of 22 ± 7 ng/(kg·min). There were no significant differences between the two groups in terms of age, weight, preoperative percutaneous oxygen saturation and mPAP, heterotaxy syndrome, TCPC procedure type, other concurrent procedure, cardiopulmonary bypass time and aortic cross-clamp proportion (p > 0.05). After 24 h of treprostinil treatment, the mPAP in group 1 reduced from 17 ± 3 mmHg to 15 ± 2 mmHg (p

Objective: Limited data exists regarding prostanoid (PGI2) use in critically ill patients with pulmonary hypertension. (PH) in the pediatric cardiac intensive care unit (CICU) setting. Materials and Methods: Single center, retrospective study of patients with diagnosis of PH who received continuous PGI2 and were admitted to CICU from January/2015 to April/2022. Data collected included patient demographics and clinical characteristics including diagnosis, etiology of PH, vasoactive and ventilatory support, length of stay, and survival. Type, initial, maximum, and final dose of PGI2 as well as hemodynamic data was obtained. Data reported as mean ± standard deviation. Significance taken p value < 0.05. Results: 24 patients received PGI2 therapy at a mean age of 3.1 years, range (0–16.6 years). PGI2 was in the form of IV epoprostenol in 12 patients, IV treprostinil in 6, and SQ treprostinil in 6 patients. Mean initial dose was 2.79 ng/kg/min, max dose 18.75 ng/kg/min, and mean duration of therapy was 38.5 days. At PGI2 initiation, 21 (87.5%) were on vasoactive infusions, 19 (79.2%) mechanically ventilated (MV), and 6 (25%) were on extracorporeal membrane oxygenation (ECMO). The in-hospital mortality rate was 37.5% (n = 9). Patients MV and on ECMO support had higher risk of death (p = 0.04, and < 0.01, respectively). Conclusion: PGI2 therapy was tolerated in approximately 50% of patients with the most common side effect being hypotension leading to discontinuation in 1/3rd of patients. Ongoing evaluation of the benefits of PGI2 for patients in the CICU setting will help better identify patient selection, type, and dosing of PGI2. [ABSTRACT FROM AUTHOR]

Background: Patients with pulmonary arterial hypertension (PAH) and additional cardiac or pulmonary comorbidities have a poor prognosis and are frequently excluded from clinical trials. The purpose of this study was to evaluate outcomes of patients with pulmonary hypertension (PH) secondary to a range of World Symposium on PH (WSPH) groups treated with inhaled treprostinil (iTRE) in a real-world setting. Methods: Patients with PH who were started on treatment with iTRE at Duke University were classified by WSPH Group and included patients with Groups 1, 2, 3, combined Groups 2 and 3 (PH in the setting of left heart failure and chronic lung disease), Group 4, and Group 5 PH. Time to disease worsening, a composite of death, lung transplantation, or transition to intravenous prostacyclin was compared by WSPH Group, and iTRE treatment status using a multivariable Cox proportional hazards model adjusted for age, sex, and Registry to Evaluate Early and Long-Term PAH Disease Management Lite 2 risk score. Treatment with iTRE was defined as a time-varying covariate. Results: The cohort included 270 patients with PH: 30.6% Group 1; 10% Group 2; 32.2% Group 3; 11.1% combined Groups 2 and 3; and 15.9% with either Group 4 or 5 PH. At 3 and 6 months of follow-up, 24.8% and 38.9% of patients, respectively, were no longer treated with iTRE. Patients who discontinued treatment with iTRE had a significantly higher risk of disease worsening (adjusted hazard ratio: 5.02, 95% confidence interval: 3.44-7.31). There was no significant difference in disease worsening among WSPH Groups. Conclusions: In a real-world setting, many patients with PH secondary to a range of WSPH Groups tolerated treatment with iTRE. Future studies should phenotype patients with PH based on both comorbidities and therapeutic responsiveness.

Charles D Burger,1 Yuen Tsang,2 Marie Chivers,3 Riya Vijay Vekaria,3 Gurinderpal Doad,2,4 Nikki Atkins,3 Sumeet Panjabi2,4 1Division of Pulmonary Medicine, Mayo Clinic Florida, Jacksonville, FL, USA; 2Janssen Scientific Affiars, Titusville, NJ, USA; 3Avalere Health, Fleet, UK; 4Actelion Pharmaceuticals US, Inc, A Johnson and Johnson Co., Titusville, NJ, USACorrespondence: Marie Chivers, Avalere Health, Fleet, UK, Email MarieChivers@facilipharma.comPurpose: Pulmonary arterial hypertension (PAH) is a rare and progressive pulmonary vascular disease that can result in right heart failure and death. Oral prostacyclins play an important role in the management of intermediate-low risk PAH. This targeted literature review (TLR) aimed to identify and compare evidence supporting use of oral prostacyclin pathway agents (PPAs: selexipag and oral treprostinil) in intermediate-low risk PAH.Methods: A targeted literature review was conducted. Literature databases (MEDLINE, Embase, and Cochrane reviews) were searched for studies describing clinical practice and treatment outcomes for oral treprostinil and selexipag globally, published in English (2012 to 2022). Electronic searches were supplemented by manual-searches of targeted conferences (2020 to 2022), and reference lists of identified publications were reviewed. One reviewer assessed studies for eligibility.Results: In total, 95 publications met inclusion criteria: 47 full-text articles (selexipag n = 22; oral treprostinil n = 16; selexipag and oral treprostinil n = 9) and 48 conference materials. Selexipag and oral treprostinil target the prostacyclin pathway differently; their label-supporting trials had different primary endpoints (disease progression and hospitalization vs exercise capacity and disease progression), differing baseline therapy (0, 1 or 2 vs 0 or 1 baseline treatments), titration duration and dosing (personalized dose capped at 1600 ug twice daily (BID) vs increasing doses over time with no maximum dose), respectively. While both oral PPAs have demonstrated reduced risk of disease progression, only selexipag showed reduction in hospitalization rates. Oral PPAs have been shown to reduce healthcare costs in real-world clinical practice. This difference is reflected in labeled indications.Conclusion: Given differences in trial- and real-world outcomes, number of prior therapies, and dosing, personalizing the choice of oral PPA is critical to maximizing the benefit for individual patients.Plain Language Summary: PAH is a condition that causes heart failure. It is important to take medicines to slow down this process. For people with early disease, there are some medicines that can be taken as a tablet rather than as an injection to slow down disease progression. The differences between two of the tablet options – selexipag and oral treprostinil, are unclear. We reviewed publications describing how, when and why these medicines are used and how well they work, to improve our understanding of the value of these medicines to people with PAH.Keywords: treprostinil, selexipag, pulmonary hypertension, outcomes