The use of treprostinil for bronchopulmonary dysplasia associated pulmonary hypertension

Treprostinil for the treatment of bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) has previously been described in small cohort studies, often used later in the course after failure to improve on other therapies. We retrospectively describe the clinical course and outcomes of 18 infants (gestational age 26.3±2.6 weeks) who received parenteral treprostinil to treat BPD-PH, including changes in echocardiographic and cardiac catheterization parameters. All patients had moderate-to-severe BPD and PH, with a mean pulmonary arterial pressure of 45.6 ± 12.7 mm Hg at cardiac catheterization prior to treprostinil. Treprostinil was initiated at a median postmenstrual age of 53.5 (IQR 45.7, 62.6) weeks. Echocardiograms after 3 months of treatment showed preserved right ventricular function (tricuspid annular plane systolic excursion (TAPSE) average 1.40 ± 0.32) and improvement of PH severity. At repeat catheterization, mean pulmonary arterial pressure (delta -16.4 ± 12.2, p < 0.01) and indexed pulmonary vascular resistance (delta -4.2 ± 3.3, p < 0.01) significantly improved. Ten of 18 infants (55.6%) survived to discharge. Our study shows a potential benefit of treprostinil use in moderate-to-severe BPD-PH; larger studies are needed to validate our findings and guide decision-making around treprostinil initiation and duration. The use of treprostinil for bronchopulmonary dysplasia associated pulmonary hypertension Stephanie M Tsoi, MD 1, Claire Parker, PNP 2, Elizabeth Colglazier, PNP 2, Shannon Cheung 1, Mariam Taleb, MD 3, Hythem Nawaytou, MD 3, Elena Amin, MD 3, Jeffrey R Fineman, MD 1,4, Roberta L Keller, MD 5 1. Division of Critical Care Medicine, Department of Pediatrics, University of California San Francisco, San Francisco, CA. 2. Division of Pediatric Pulmonary Hypertension, Department of Pediatrics, University of California, San Francisco, California, United States. 3. Division of Cardiology, Department of Pediatrics, University of California, San Francisco, San Francisco, CA. 4. Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA. 5. Division of Neonatology, Department of Pediatrics, University of California San Francisco, San Francisco, CA Corresponding author: [email protected] (ORCID-ID: 0000-0002-0115-5843) Address: 550 16 th Street, Mission Hall 5 th Floor, San Francisco, CA 94158 Telephone: 415-713-7054 Fax: 415-353-4485 Other authors: [email protected], [email protected], [email protected], [email protected], [email protected], [email protected], [email protected] , [email protected] Author contribution form attached.

bronchopulmonary dysplasia, prematurity, pulmonary hypertension, prostacyclin, treprostinil Funding: Supported by the National Institutes of Health (T32HL160508-01A1 [SMT], P01 HL146369 [JRF]) Conflict of Interest: none Ethical Statement: This study was approved by the University of California, San Francisco IRB (23-39071), which approved waiver of consent. Previous Presentations: Western Society for Pediatric Research, Carmel-by-the-Sea CA (January 16-18, 2025) Abbreviated Title: Treprostinil for BPD-PH

Treprostinil for the treatment of bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) has previously been described in small cohort studies, often used later in the course after failure to improve on other therapies. We retrospectively describe the clinical course and outcomes of 18 infants (gestational age 26.3±2.6 weeks) who received parenteral treprostinil to treat BPD-PH, including changes in echocardiographic and cardiac catheterization parameters. All patients had moderate-to-severe BPD and PH, with a mean pulmonary arterial pressure of 45.6 ± 12.7 mm Hg at cardiac catheterization prior to treprostinil. Treprostinil was initiated at a median postmenstrual age of 53.5 (IQR 45.7, 62.6) weeks. Echocardiograms after 3 months of treatment showed preserved right ventricular function (tricuspid annular plane systolic excursion (TAPSE) average 1.40 ± 0.32) and improvement of PH severity. At repeat catheterization, mean pulmonary arterial pressure (delta -16.4 ± 12.2, p < 0.01) and indexed pulmonary vascular resistance (delta -4.2 ± 3.3, p < 0.01) significantly improved. Ten of 18 infants (55.6%) survived to discharge. Our study shows a potential benefit of treprostinil use in moderate-to-severe BPD-PH; larger studies are needed to validate our findings and guide decision-making around treprostinil initiation and duration.

Bronchopulmonary dysplasia (BPD) is a form of chronic lung disease that affects premature infants 1 . Twenty percent of infants with BPD will develop pulmonary hypertension (PH), and have a 4.7-fold increased risk of mortality 2 . The pathogenesis of BPD-associated PH (BPD-PH) is characterized by exposure of the immature lung to prenatal and postnatal injurious conditions, such as infection, prolonged mechanical ventilation, and supplemental oxygen exposure, ultimately leading to impaired growth, structural remodeling of the pulmonary vasculature and increased pulmonary vascular resistance (PVR) 3,4 . Without appropriate monitoring and treatment, BPD-PH can lead to right ventricular failure and death 5 . Current strategies to diagnose and treat BPD-PH are limited and based on expert opinions 6,7 . Recommendations for the initial approach include involvement of a multidisciplinary team, screening echocardiograms for patients with a diagnosis of BPD, and optimization and treatment of comorbid cardiopulmonary conditions. Severity of BPD-PH should be assessed via cardiac catheterization when it is safe and feasible to guide a targeted treatment approach. Treatment can range from judicious use of supplemental oxygen, inhaled nitric oxide (iNO), and/or PH-targeted medications 7–9 . PH-targeted drug use in this population is off-label and highly dependent on institutional experience 8 . After supplemental oxygen, sildenafil and iNO remain the most widely used pulmonary vasodilator therapies for BPD-PH, while neonatal data from randomized studies of these medications are in persistent pulmonary hypertension of the newborn (PPHN), within hours or days of birth 7,9,10 . Endothelin receptor antagonists, like bosentan, and prostacyclin analogues, such as treprostinil, target alternative pathways for pulmonary vasodilator therapy and have been used with limited evidence as adjunctive therapies when BPD-PH persists, is severe, or life-threatening. Parenteral treprostinil requires specialty care to initiate and monitor, and stable access for continuous delivery. Three small cohort studies describe treprostinil as well-tolerated and associated with improved echocardiographic markers of right ventricular function and PH in infants with BPD, without increased mortality 11–13 . These publications show the feasibility of treprostinil use in BPD-PH, but larger cohort studies are needed to validate the findings and expand outcomes, including cardiac catheterization data. We describe our institution’s experience using parenteral treprostinil to treat infants with BPD-PH, and report baseline condition and clinical outcomes after treprostinil initiation, including hemodynamics at cardiac catheterization, echocardiographic parameters, and B-type natriuretic peptide (BNP) levels (as a predictor of outcome).

This is a single-center, retrospective cohort study from the University of California San Francisco, an academic institution with a quaternary children’s hospital that provides specialized referral-based care in BPD and PH. Infants were included if they had PH secondary to BPD, had treprostinil initiated during their initial neonatal admission (including following transfer to our center), and were either discharged or deceased at the time of data collection in June, 2025 (birth dates 2012-2023). The primary outcome was survival to discharge. Secondary outcomes included duration of treprostinil use, cardiac catheterization hemodynamics, echocardiographic findings, and BNP levels. BPD severity was classified per Jensen et al criteria 1 . PH was clinically evaluated by echocardiography, with diagnosis confirmed by cardiac catheterization. All echocardiograms were overread for the purposes of the study (HN, MT) using previously established echocardiographic parameters: tricuspid regurgitant (TR) jet velocity, pulmonary regurgitant (PR) jet velocity, ventricular septal defect (VSD) and patent ductus arteriosus (PDA) shunt direction and flow velocity (if present), interventricular septal (IVS) wall motion and systolic eccentricity index (EI), and tricuspid annular plane systolic excursion (TAPSE, a marker of systolic right ventricular function, with normal values for age corrected for prematurity 14,15 ). We classified infants into three categories of PH based on the degree of elevation of the estimated right ventricular pressure (RVP): mild (< 50% systemic RVP), moderate (≥ 50% systemic RVP, but less than systemic RVP), and severe (≥ systemic RVP) 16 . Cardiac catheterization parameters for PH diagnosis included mean pulmonary arterial pressure (mPAP) equal to or greater than 20 mmHg or indexed PVRi greater than 3.0 WU/m 2 . Treprostinil initiation is guided by a multidisciplinary PH team who use a comprehensive evaluation of each patient, including echocardiogram, cardiac catheterization, BPD disease severity and course, functional class and current therapies to determine treatment approach 17 . Respiratory support, diuretics, and adjunctive pulmonary vasodilatory therapy (i.e. modest provision of supplemental oxygen, iNO, and sildenafil or bosentan if started at prior institutions) were optimized before treprostinil initiation. Descriptive data are reported as means with standard deviations, medians with interquartile range, or counts and frequencies. Comparisons across survivors and non-survivors were performed for categorical data via chi-squared or Fisher’s Exact test, as appropriate. Continuous parametric data were compared using t-test and paired t-test, and non-parametric data were compared using Wilcoxon Rank Sum test and Wilcoxon Signed-Rank test. Patients with missing values for a particular variable were retained in the cohort, but excluded for that particular analysis. We modeled the relationship between BNP and mortality using a receiver operating characteristic (ROC) curve and the area under the curve (AUC) to report discrimination. For all analyses, statistical significance was set at a p-value ≤ 0.05. All analyses were performed using Stata SE (Statacorp. 2021. Stata Statistical Software: Release 17. College Station, TX: Statacorp LLC). The study protocol was approved by the institutional review board of University of California, San Francisco (IRB Protocol #23-39071), which waived requirement for informed consent due to the retrospective nature of the study.

Eighteen infants with BPD-PH used treprostinil, with an average gestational age of 26.3 ± 2.6 weeks and average birth weight of 718 ± 300 grams. Seventeen (94.4%) infants were transferred from an outside hospital at an average postmenstrual age (PMA) of 52.3 ± 13.9 weeks. Seven (38.9%) infants were small-for-gestational age and 5 (27.8%) were products of multiple gestation. Ten (55.6%) had moderate (Grade 2) BPD and 8 (44.4%) had severe (Grade 3) BPD. PH was diagnosed by echocardiography at an average PMA of 43.0 ± 14.3 weeks. A total of 12 (72.2%) patients had a PDA and 5 (27.8%) had pulmonary vein stenosis ( Table 1 ). Ten (55.6%) infants survived to discharge. Of survivors, the average PMA at discharge was 95.8 ± 30.8 weeks ( Table 1 ). For non-survivors, average PMA at death was 72.2 ± 17.1 weeks. Of the eight deaths, 2 (25%) were due to sepsis, 1 (12.5%) due to pulmonary vein stenosis, 2 (25%) due to acute cardiac events, 1 (12.5%) due to a PH crisis, and 3 (37.5%) had redirection of care ( Table 2 ). When categorized by treatment approach, 14 infants were treated with upfront treprostinil therapy based on diagnosis of significant pulmonary hypertension by cardiac catheterization and 4 (mortality rate of 28.6%) of those infants died. In contrast, 4 infants were treated with treprostinil after signs and symptoms of worsening cardiopulmonary disease and all of these infants died. Prior to treprostinil initiation, 6 (35.3%) infants were treated with bosentan and 10 (58.8%) patients were treated with sildenafil (5 were on dual therapy). Treprostinil was initiated at average 55.8 ± 12.1 weeks’ PMA and 15.2 ± 15.7 days after cardiac catheterization, with 14 (77.8%) infants receiving initial subcutaneous administration and 3 infants transitioning from intravenous to subcutaneous administration during their hospital course (16.7%). The average peak treprostinil dose was 60.4 ± 13.2 ng/kg/min amongst survivors. Treprostinil discontinuation in survivors was at average 136.0 ± 38.1 weeks’ PMA, with total duration of treprostinil 81.1 ± 33.7 weeks ( Table 3 ). There was no significant mortality difference seen in patients who had treprostinil started before 50 weeks’ PMA (4/8, 50%) compared to at or after 50 weeks’ PMA (4/10, 40%, p-value 0.67). Cardiac catheterization was performed in 17 (94.4%) infants before treprostinil initiation. Of these infants, 11 (61.1%) underwent a second catheterization at an average of 42.4 ± 43.0 weeks after treprostinil initiation; only 2 of the 11 were non-survivors. The change in mPAP with treprostinil was -16.4 ± 12.2 mmHg (p<0.01) and change in PVRi was -4.2 ± 3.3 WUi (p<0.01). All infants (n=18) had an echocardiogram prior to starting treprostinil, and 13 had repeat echocardiogram within 3 months of treprostinil initiation ( Table 5) . All patients had moderate (66.7%) or severe (33.3%) PH by echocardiogram, and by 3 months, only 15.4% of patients remained with severe PH. Baseline EI (normal 2.0) with a median of 1.42 (IQR 1.35, 1.53; n=16) and at 3 months, a median of 1.38 (IQR 1.19, 1.49; n=12) 18 . Only 1 non-survivor had paradoxical motion at baseline, and none at 3 months. Using repeated measures analysis, this change was not significant (p-value 0.46). Average TAPSE at baseline was 1.12 ± 0.26 cm (n=14) and at 3-months 1.40 ± 0.32 cm (n=8); 3 survivors and 1 non-survivor had a baseline TAPSE below the normal range for age, which normalized for the 1 survivor and 1 non-survivor that had follow-up echocardiograms at 3 months. TAPSE non-significantly increased for those with measurements at both time points (0.29 ± 0.36 cm, p-value 0.08). Infants who survived tended to have less severe PH at baseline, with only 20% severe PH compared to 50% severe PH for non-survivors and a somewhat lower EI [median 1.42 (IQR 1.34, 1.53) versus 1.49 (IQR 1.36, 1.65)]. Average BNP before initiation of treprostinil was 55.9 ± 79.0 pg/ml (n=15). BNP level was predictive of mortality at a threshold value ≥ 35 pg/ml with 71.4% sensitivity and 100.0% specificity (AUC 0.87 ± 0.10, 95% CI 0.67-1.00, Figure 1 ). At time of repeat catheterization, average BNP had decreased to 14.0 ± 9.3 pg/ml (n=7, p-value 0.26).

To date, this study describes the largest cohort of premature infants with BPD-PH treated with treprostinil that includes echocardiographic and cardiac catheterization data. All infants had moderate or severe BPD and PH by echocardiography and cardiac catheterization, with a baseline median PVRi of 8.2 (6.5, 9.8). Treprostinil was typically started at 6 – 7 months chronological age (PMA 53.5 weeks (45.7, 62.6)) via subcutaneous administration. Repeat echocardiograms 3 months after initiation of treprostinil showed improvement in PH severity, with 85% of echoes with mild-to-moderate PH, and normal RV function by TAPSE. Repeat cardiac catheterization data showed substantial improvement in mPAP (11.5 mmHg (10, 18)) and PVRi (3.7 WUi (2.4, 5.7)). Although average duration of treprostinil therapy in survivors was 81.1 ± 33.7 weeks, median age at discontinuation (137.9 weeks’ PMA) among survivors was less than 2 years corrected age. The mortality rate of our cohort was 44.4%, which is similar to a prior “natural history” study of infants with PH and severe BPD 19 . We found no significant differences in co-morbidities between survivors and non-survivors. Our sample includes both infants who were treated with treprostinil as part of aggressive upfront therapy following cardiac catheterization (n = 14, 28.6% mortality rate), and infants who received treprostinil as salvage therapy after signs and symptoms of worsening disease (n=4, 100% mortality rate). As BNP greater than 35 pg/ml prior to treprostinil initiation was predictive of mortality, it may serve as clinical useful biomarker for grading BPD-PH severity. Although this cutoff is lower than previously reported BNP levels associated with survival in this population 20, it should aid in decision-making regarding treprostinil initiation. Of patients who received upfront therapy with a BNP measured prior to treatment, only 1 had a BNP greater than 35 and that patient did not survive. The value of BNP in this setting is significant when also considering TAPSE at baseline, which was low in three survivors and one non-survivor. Overall, our data suggest that treprostinil has more potential to improve outcomes when initiated as upfront therapy in infants with severe pulmonary vascular disease who are not in crisis, rather than as rescue during acute decompensation. Our data were collected over 13 years, during which there was an evolution in our approach to infants with severe Grade 3 BPD. In 2018, our institution’s ventilator management for these infants changed to align with best practices toward achieving stability and limiting hyperoxia exposure in infants receiving chronic ventilation 21 ; mortality of infants with treprostinil initiated after 2017 (n=11) is 27.3%. In fact, our data compare favorably to that of Arjaans et al. in this respect as among their cohort of infants on CPAP (none on mechanical ventilation), 6/8 (75%) expired 19 . Overall, in the setting of significant lung disease, our approach emphasizes the importance of optimizing lung recruitment, oxygenation, and ventilation in the management of BPD-PH. A multidisciplinary team is the foundation of our institutional approach to treatment of BPD-PH, including the importance of early recognition and multi-pronged management of PH. We recommend transferring infants with echocardiographic evidence or signs and symptoms of PH to a specialized center of excellence with the ability to perform cardiac catheterization and initiate treprostinil, if indicated by the evaluation. As this patient population is heterogeneous, careful individualized assessment of clinical status, lab values (i.e. BNP), echocardiographic and cardiac catheterization data, cardiac co-morbidities, respiratory support needs, and prior pulmonary vasodilator therapies should be considered by a team of neonatologists, pulmonologists, cardiologists and pulmonary hypertension specialists before treprostinil initiation. Once our team has decided to initiate treprostinil, we place a subcutaneous site, if size and condition of the patient allow, in order to avoid the need for long-term secure intravenous access and consequent risk of central line infection. A typical starting dose is 1-2 ng/kg/min, with initial increase by 1 ng/kg/min every 6-12 hours with uptitration slowed if there are side effects (i.e. hypotension, emesis, diarrhea). We monitor clinical progress (i.e. ability to tolerate intercurrent illness and recovery from respiratory events, PH crises, and successful weaning of other vasoactive medications, including inhaled nitric oxide) as well as interval echocardiograms (typically monthly) and BNP to assess RV pressure estimate and function. Initial target dose of treprostinil is usually 50 -80 ng/kg/min. The single-centered nature of this study at an academic institution, accredited as a pulmonary hypertension care center by the Pulmonary Hypertension Association with a multidisciplinary team of experts in PH and BPD serves as a strength that enabled us to be the first to describe the cardiac catheterization data and changes with therapy in this patient cohort. The small sample size of 18 patients, although the largest currently described in the literature, is a limitation to this study. It is too small to power significant differences between the survivor and non-survivor group to inform optimal timing or other criteria that might inform the decision to initiate treprostinil. Further, our cohort spans 10 years which includes practice variation across the years, as noted. In conclusion, we described the clinical course and outcomes of 18 infants with moderate to severe BPD-PH treated with treprostinil via a multidisciplinary approach. Treprostinil administration was associated with improved grade of PH by echocardiography, and maintained TAPSE, while significantly decreasing mean pulmonary arterial pressure and PVRi on cardiac catheterization. Future studies are needed to create data-driven clinical practice guidelines that utilize treprostinil. Table 1: Demographics, neonatal characteristics, co-morbidities, and outcomes of cohort | Gestational Age (wk) | 26.3 ± 2.6 | 26.0 ± 2.5 | 26.8 ± 2.7 | 0.55 | | Female | 7 (38.9%) | 4 (40.0%) | 3 (37.5%) | 0.91 | | Birth Weight (g) | 717.8 ± 299.5 | 770.0 ± 313.7 | 652.5 ± 287.2 | 0.42 | | Transferred | 17 (94.4%) | 9 (90.0%) | 8 (100%) | 0.85 | | PMA at Transfer (wk) | 52.3 ± 13.9 | 49.5 ± 7.6 | 55.4 ± 18.8 | 0.40 | | Birth History: | |||| | Pre-Eclampsia | 1 (5.9%) | 1 (10.0%) | 0 | 1.00 | | Chorioamnionitis | 0 | 0 | 0 | - | | Small for Gestational Age | 7 (38.9%) | 4 (40.0%) | 3 (37.5%) | 1.00 | | Multiple Gestation | 5 (27.8%) | 3 (30.0%) | 2 (25.0%) | 1.00 | | Steroids Before Birth | 14 (82.4%) | 6 (67.0%) | 8 (100.0%) | 0.21 | | Surfactant After Birth | 16 (100%) | 9 (100%) | 7 (100%) | - | | Oligohydramnios | 5 (38.5%) | 4 (44.4%) | 1 (25.0%) | 1.00 | | Comorbidities: | |||| | ASD | 4 (22.2%) | 2 (20.0%) | 2 (25.0%) | 1.00 | | VSD | 4 (22.2%) | 1 (10.0%) | 3 (37.5%) | 0.28 | | PDA | 13 (72.2%) | 7 (70.0%) | 6 (75.0%) | 1.00 | | Pulmonary Vein Stenosis None Single vein Multiple veins | 13 (72.2%) 2 (11.1%) 3 (16.7%) | 7 (70.0%) 2 (20.0%) 1 (10.0%) | 6 (75.0%) 0 2 (25.0%) | 0.59 | | Sepsis | 10 (58.8%) | 5 (50.0%) | 5 (71.4%) | 0.62 | | Necrotizing Enterocolitis | 6 (35.3%) | 3 (30.0%) | 3 (42.9%) | 0.64 | | Retinopathy of Prematurity | 8 (53.3%) | 4 (40.0%) | 4 (80.0%) | 0.28 | | Intracranial Pathology | 7 (38.9%) | 4 (40.0%) | 3 (37.5%) | 1.00 | | Outcomes: | |||| | BPD Severity: Grade 1 Grade 2 Grade 3 | 0 10 (55.6%) 8 (44.4%) | 0 7 (70.0%) 3 (30.0%) | 0 3 (37.5%) 5 (62.5%) | 0.18 | | PMA at PH Diagnosis (wk) | 43.0 ± 14.3 | 44.8 ± 18.9 | 40.8 ± 5.3 | 0.57 | | Tracheostomy | 11 (61.1%) | 7 (70.0%) | 4 (50.0%) | 0.35 | | G-Tube | 16 (88.9%) | 10 (100%) | 6 (75.0%) | 0.18 | | PMA at Discharge (wk) | 95.8 ± 30.8 | ||| | PMA at Death (wk) | 72.2 ± 17.1 | Table 2: Cause of death and timing for non-survivors | 2012 | 2013 | 78 | 2013 | 82 | Adrenal insufficiency | PH crisis with DNR in place | | 2013 | 2014 | 67 | 2014 | 69 | Intrauterine growth restriction, ASD, pulmonary vein stenosis (x2), retinopathy of prematurity, pyloric stenosis | Intracranial hemorrhages, poor neurologic prognosis, redirection of care | | 2015 | 2015 | 47 | 2017 | 105 | Retinopathy of prematurity, airway malacia, adrenal insufficiency | Sepsis | | 2016 | 2016 | 57 | 2017 | 77 | Necrotizing enterocolitis, retinopathy of prematurity | Bradycardic event with DNR in place | | 2016 | 2017 | 46 | 2017 | 52 | Intrauterine growth restriction, necrotizing enterocolitis, retinopathy of prematurity, intraventricular hemorrhage, ASD, VSD | Pulmonary vein stenosis (x3), redirection of care | | 2018 | 2019 | 44 | 2019 | 73 | Intraventricular hemorrhage, severe brain atrophy | Cardiac arrest with DNR in place | | 2019 | 2019 | 49 | 2019 | 55 | Trisomy 21, VSD | Redirection of care | | 2021 | 2021 | 57 | 2021 | 61 | Intrauterine growth restriction, VSD, necrotizing enterocolitis | Sepsis | Table 3: Treprostinil Course | PMA at Initiation (wk) | 53.5 (45.7, 62.6) | 53.5 (45.1, 62.6) | 53.2 (46.8, 62.2) | 0.97 | | PMA at Discontinuation (wk) | 90.6 (71.6, 137.9) | 137.9 (104.1, 170.6) | 71.6 (58.0, 80.1) | < 0.01 | | Total duration (wk) | 48.7 ± 42.7 | 81.1 ± 33.7 | 16.3 ± 19.4 | < 0.01 | | Highest dose (ng/kg/min) | 58.4 ± 18.1 | 60.4 ± 13.2 | 56.0 ± 23.6 | 0.62 | | Subcutaneous Administration | 17 (94.4%) | 10 (100%) | 7 (87.5%) | 0.25 | | Time between catheterization and treprostinil initiation (d) | 9 (5, 19) | 6 (4, 15) | 17 (6, 34) | 0.14 | Table 4: Cardiac catheterization data before and after treprostinil initiation | PMA at Cath (wk) | 48.9 (44.1, 61.4) | 65.1 (59.7, 154.9) | 21.6 (10.7, 93.4) | - | | Mean PAP (mm Hg) | 45.6 ± 12.7 | 27.8 ± 8.1 | -16.4 ± 12.2 | < 0.01 | | Systolic PAP (mm Hg) | 63.4 ± 16.4 | 36.7 ± 10.5 | -23.7 ± 16.0 | < 0.01 | | Diastolic PAP (mm Hg) | 32.4 ± 10.0 | 20.8 ± 7.1 | -11.7 ± 9.4 | < 0.01 | | PVRi (WUi) | 8.7 ± 2.9 | 3.8 ± 2.2 | -4.2 ± 3.3 | 1.2 | 5 (35.7%) N=14 | 3 (42.9%) N=7 | || | Therapy at Time of Catheterization | |||| | ERA | 6 (35.3%) | 7 (63.6%) | || | PDE5i | 10 (58.8%) | 7 (63.6%) | || | Remodulin | - | 9 (81.8%) | || | iNO | 5 (31.3%) | 1 (10.0%) | || | Clinical Data at Time of Catheterization | |||| | Non-invasive Positive Pressure Ventilation | 1 (5.9%) | 1 (9.1%) | || | Mechanical Ventilation | 16 (94.1%) | 10 (90.9%) | a. analysis from paired t-test on repeated measures only. Table 5: Echocardiogram parameters before treprostinil and 3 months after treprostinil initiation | Baseline | 3 months | Baseline | 3 months | Baseline | 3 months | | | Echo Grading of PH Mild (< 50% systemic) Moderate (≥50%) Severe (≥ systemic) | 0 12 (66.7%) 6 (33.3%) | 3 (23.1%) 8 (61.5%) 2 (15.4%) | 0 8 (80.0%) 2 (20.0%) | 3 (30.0%) 6 (60.0%) 1 (10.0%) | 0 4 (50.0%) 4 (50.0%) | 0 2 (66.7%) 1 (33.3%) | | PDA Shunt Direction Closed/None Left to Right Bidirectional | 12 (66.7%) 3 (16.7%) 3 (16.7%) | 11 (84.6%) 0 2 (15.4%) | 7 (70.0%) 2 (20.0%) 1 (10.0%) | 9 (90.0%) 0 1 (10.0%) | 5 (62.5%) 1 (12.5%) 2 (25.0%) | 2 (66.7%) 0 1 (33.3%) | | Septal Position Normal Flat D-shaped | 0 16 (94.1%) 1 (5.9%) | 3 (23.1%) 10 (76.9%) 0 | 0 10 (100%) 0 | 3 (30.0%) 7 (70.0%) 0 | 0 6 (85.7%) 1 (14.3%) | 0 3 (100%) 0 | | Eccentricity Index | 1.44 (1.35, 1.59) N=16 | 1.38 (1.19, 1.49) N=12 | 1.42 (1.34, 1.53) N=10 | 1.35 (1.14, 1.45) N=10 | 1.46 (1.36, 1.65) N=6 | 1.6 (1.39, 1.9) N=2 | | TAPSE (cm) | 1.12 ± 0.26 N=14 | 1.40 ± 0.32 N=8 | 1.06 ± 0.19 N=9 | 1.33 ± 0.20 N=6 | 1.25 ± 0.36 N=5 | 1.63 ± 0.61 N=2 | Figure 1: Receiver operating characteristic curve for prediction of mortality based on BNP levels prior to treprostinil initiation

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Authors Metrics & Citations Metrics Article Usage 296views 169downloads Citations Download citation Stephanie Tsoi M, Claire Parker, Elizabeth Colglazier, et al. The use of treprostinil for bronchopulmonary dysplasia associated pulmonary hypertension. Authorea. 30 July 2025. DOI: https://doi.org/10.22541/au.175390400.01348466/v1 DOI: https://doi.org/10.22541/au.175390400.01348466/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu.