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Objective: To assess the effect of treating pulmonary hypertension (PH) in infants younger than 1 year of age with systemic glucocorticoids while using echocardiographic and diagnostic biomarkers as measures of efficacy., Study Design: A retrospective chart review was performed on 17 hospitalized infants younger than 1 year of age at St Louis Children's Hospital who received a 5- to 7-day course of systemic glucocorticoid treatment followed by a 3-week taper with no significant intracardiac shunts from January 1, 2017, to December 31, 2021. Quantitative echocardiographic indices for PH, N-terminal pro b-type natriuretic peptide, and/or b-type natriuretic peptide levels were collected before glucocorticoid treatment, after the glucocorticoid burst, and after the 21-day taper., Results: Mean (±SD) gestational age was 32.1 (±5.8) weeks, 5 infants were (29%) concomitantly treated with sildenafil, and 8 were male. Twelve were classified as World Health Organization group 3 PH (71%) and 5 as World Health Organization group 1 PH. There were significant improvements 30 days after glucocorticoid initiation in b-type natriuretic peptide levels (P = .008), PCO 2 (P = .03), eccentricity index (P = .005), right ventricular ejection time (P = .04), pulmonary artery acceleration time (P = .002), and pulmonary artery acceleration time-to-right ventricular ejection time ratio (P = .02). Tricuspid regurgitation velocity was not able to be assessed. There were no mortalities during the study timeline., Conclusions: In our retrospective study, systemic glucocorticoid therapy was well tolerated and appeared to be associated with significant improvement in cardiopulmonary function in infants with PH. Further prospective study in a larger sample is warranted., Competing Interests: Declaration of Competing Interest This study was funded in part by a generous gift from the family of Ollie Tschudin and the St Louis Children’s Hospital Foundation. The authors have no conflicts of interest relevant to this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To describe the safety and effectiveness of treating pediatric patients who have pulmonary arterial hypertension (PAH) with selexipag in a real-world, multicenter cohort, given that data supporting its use in pediatric PAH are sparse., Study Design: We report a multicenter, retrospective, cohort study of children with PAH treated with selexipag. Demographic and clinical variables were extracted from the medical records. Clinical parameters were analyzed at 3 timepoints: before selexipag, 3-12 months after selexipag, and >12 months follow-up., Results: Eighty-seven patients were included, 32 received selexipag as add-on to background therapy, and 55 transitioned from another prostanoid. The median starting and final doses were 4.7 and 28.5 μg/kg/dose twice daily, respectively. Add-on patients demonstrated improved indexed pulmonary to systemic vascular resistance ratio after selexipag initiation (PVRi/SVRi, 0.62v0.53; P = .034) with a lower average mean pulmonary artery pressure (46 vs 39 mm Hg; P = NS), and oxygen consumption (maximal oxygen consumption during cardiopulmonary exercise testing [VO 2 max] 27.8 mL/kg/min vs 30.9 mL/kg/min; P = NS). Transition patients demonstrated stable mean pulmonary artery pressure (47 mm Hg vs 45 mm Hg; P = NS) and a lower mean indexed pulmonary vascular resistance (10.9 Wood units∗m 2 vs 8.2 Wood units∗m 2 ; P = NS) but late functional worsening in some with VO 2 max decreased at follow-up (26.0 mL/kg/min vs 19.5 mL/kg/min). Side effects were noted in 40% of the cohort, but prompted discontinuation in only 2%., Conclusions: In a large, multicenter cohort, the oral prostacyclin agonist selexipag demonstrates favorable tolerability and effectiveness. Add-on patients demonstrated early hemodynamic improvement. Transition patients demonstrated early stability with risk of late functional worsening, highlighting the importance of ongoing monitoring., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The efficacy of iloprost in treating pulmonary arterial hypertension (PAH) is controversial. Adverse reactions such as hypotension may occur during treatment., Objectives: Aim to evaluate the efficacy and safety of iloprost for PAH., Methods: Studies were obtained from an electronic search of the CNKI, Wanfang, VIP, SinoMed, PubMed, Medline, Embase, and Cochrane Library databases up to May 18, 2023. A meta-analysis of each study was performed using RevMan 5.4 with a 95 % confidence interval (CI). A randomized or fixed-effects model was applied according to a heterogeneity test., Results: Twelve trials involving 718 participants were selected, including 433 in five randomized controlled trials (RCTs) and 285 in seven prospective clinical trials. All the patients received iloprost inhalation. The short- and prolonged treatment groups significantly improved the 6-minute walking distance (6 MWD). The mortality and clinical deterioration incidences in the iloprost group were not significantly different from those in the control group. The mean pulmonary arterial pressure (mPAP) was reduced after 3 months of iloprost RCTs and 12 months of prospective treatment. Iloprost decreased pulmonary vascular resistance (PVR) by approximately 231.29 units, significantly increased cardiac output (CO), and improved the quality of life (QoL). The main adverse reactions to iloprost treatment were cough (17 %), headache (16.4 %), and flushing (12.4 %)., Conclusion: Iloprost, either used alone or as adjuvant therapy, can enhance exercise capacity, lower hemodynamic parameters, and improve long-term outcomes. However, the risk of mortality and clinical deterioration remains unknown., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To describe current treatment practices of preterm infants with early hypoxemic respiratory failure (HRF) and pulmonary hypertension (PH) and their association with patient outcomes., Study Design: We developed a prospective, observational, multicenter clinical registry of preterm newborns <34 weeks' gestation with HRF and PH, based on either clinical or echocardiographic evidence during the first 72 hours of life, from 28 neonatal intensive care units in the US from 2017 through 2022. The primary end point was mortality among those who did or did not receive PH-targeted treatment, and the secondary end points included comparisons of major morbidities. Variables were compared using t tests, Wilcoxon rank-sum tests, Fisher exact tests, and χ² tests., Results: We analyzed the results of 224 preterm infants enrolled in the registry. Of which, 84% (188/224) received PH-targeted treatment, most commonly inhaled nitric oxide (iNO). Early mortality in this cohort was high, as 33% (71/224) of this sample died in the first month of life, and 77% of survivors (105/137) developed bronchopulmonary dysplasia. Infants who received PH-targeted treatment had higher oxygenation indices at the time of enrollment (28.16 [IQR: 13.94, 42.5] vs 15.46 [IQR: 11.94, 26.15]; P = .0064). Patient outcomes did not differ between those who did or did not receive PH-targeted therapy., Conclusions: Early-onset HRF with PH in preterm infants is associated with a high early mortality and a high risk of developing bronchopulmonary dysplasia. iNO is commonly used to treat early-onset PH in preterm infants with HRF. In comparison with untreated infants with lower oxygenation indices, iNO treatment in severe PH may prevent poorer outcomes., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest. This study was sponsored by an investigator-initiated research grant from Mallinckrodt Pharmaceuticals (grant number IIR-USA-003947 to J.P.K.). The study was also supported by NIH/NCATS Colorado CTSA Grant Number UL1 TR002535. The manuscript's contents are the authors' sole responsibility and do not necessarily represent the sponsors' views. The sponsors had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To describe our experience with treprostinil, evaluate correlations with cardiac function, and assess for adverse effects in neonates with congenital diaphragmatic hernia-related pulmonary hypertension (CDH-PH)., Study Design: A retrospective review of a single-center prospective registry at a quaternary care children's hospital. Patients included in the study had CDH-PH treated with treprostinil between April 2013 and September 2021. Assessed outcomes were brain-type natriuretic peptide levels and quantitative echocardiographic parameters collected at baseline, 1 week, 2 weeks, and 1 month after treprostinil initiation. Right ventricular (RV) function was assessed by tricuspid annular plane systolic excursion Z-score and speckle tracking echocardiography (global longitudinal and free wall strain). Septal position and left ventricular (LV) compression were assessed by eccentricity index and M-mode Z-scores., Results: Fifty-one patients were included, with an average expected/observed lung-to-head ratio of 28.4 ± 9.0%. Most patients required extra-corporeal membrane oxygenation (n = 45, 88%). Survival to hospital discharge was 31/49 (63%). Treprostinil was initiated at a median age of 19 days with a median effective dose of 34 ng/kg/minute. Median baseline brain-type natriuretic peptide level decreased from 416.9 pg/mL to 120.5 pg/mL after 1 month. Treprostinil was associated with improved tricuspid annular plane systolic excursion Z-score, RV global longitudinal strain, RV free wall strain, LV eccentricity index, and LV diastolic and systolic dimensions, reflecting less compression by the RV, regardless of ultimate patient survival. No serious adverse effects were recorded., Conclusions: In neonates with CDH-PH, treprostinil administration is well tolerated and is associated with improved RV size and function., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To evaluate the cost-utility of catheterization-obligate treatment in preterm infants with pulmonary hypertension, as compared with empiric initiation of sildenafil based on echocardiographic findings alone., Study Design: A Markov state transition model was constructed to simulate the clinical scenario of a preterm infant with echocardiographic evidence of pulmonary hypertension associated with bronchopulmonary dysplasia (BPD) and without congenital heart disease under consideration for the initiation of pulmonary vasodilator therapy via one of two modeled treatment strategies-empiric or catheterization-obligate. Transitional probabilities, costs and utilities were extracted from the literature. Forecast quality-adjusted life-years was the metric for strategy effectiveness. Sensitivity analyses for each variable were performed. A 1000-patient Monte Carlo microsimulation was used to test the durability of our findings., Results: The catheterization-obligate strategy resulted in an increased cost of $10 778 and 0.02 fewer quality-adjusted life-years compared with the empiric treatment strategy. Empiric treatment remained the more cost-effective paradigm across all scenarios modeled through one-way sensitivity analyses and the Monte Carlo microsimulation (cost-effective in 98% of cases)., Conclusions: Empiric treatment with sildenafil in infants with pulmonary hypertension associated with BPD is a superior strategy with both decreased costs and increased effectiveness when compared with catheterization-obligate treatment. These findings suggest that foregoing catheterization before the initiation of sildenafil is a reasonable strategy in preterm infants with uncomplicated pulmonary hypertension associated with BPD., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Mortality of pulmonary hypertension associated with congenital heart disease (PAH-CHD) in adults remains high., Objectives: To identify predictors of death and to assess the impact of treatment on outcome., Methods: Retrospective, multicenter cohort study of 103 adults with PAH-CHD followed-up for 8.6 ± 4.6 years. Patients were grouped according to underlying shunt type into pre-tricuspid, post-tricuspid and complex. Survival rates were analyzed and predictors of death were investigated with Cox regression models., Results: In the post-tricuspid and complex groups (38 and 37 patients, respectively), the most common clinical PAH-CHD subgroup was Eisenmenger syndrome (76.3% and 59.5%, respectively) whereas, in the pre-tricuspid group (28 patients), 46.5% of patients had small or corrected defects. Overall, 88 patients received vasodilators; 39% required combination-therapy. Overall survival at 10 years was 65%. Mortality was highest in the pre-tricuspid group, FC-III-IV and amongst patients receiving monotherapy (p < 0.050). On multivariate analysis, predictors of poor outcome were pericardial effusion (HR: 4,520 [1,470-13,890]; p = 0,008), oxygen saturation(HR: 0.940 [0,900 - 0,990]; p = 0,018) and genetic syndromes(HR: 3,280 [1,098-9,780]; p = 0,033)., Conclusions: Patients in advanced stages at initiation of treatment were at high risk of death and strong consideration should be given for more aggressive therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Combined post- and precapillary pulmonary hypertension (CpcPH) portends poor outcomes in pulmonary hypertension related to left heart disease (PH-LHD). While recent evidence does not support the use of targeted pulmonary arterial hypertension (PAH) therapy in PH-LHD, there is a lack of clinical data on their use in CpcPH. We evaluated the outcomes in patients with CpcPH treated with PAH therapies., Methods: Retrospectively, 50 patients meeting hemodynamic criteria of CpcPH and started on PAH-targeted drugs were identified. Fifty age- and gender-matched PAH patients were chosen as controls. We evaluated the change in 6-minute walk distance, World Health Organization functional class (FC), tricuspid annular plane systolic excursion, BNP or NT-proBNP, and pulmonary artery systolic pressure at 3, 6, 12, and 24 months of follow-up., Results: After adjusting for age and gender, there was no improvement in World Health Organization FC in CpcPH over 2 years (odds ratio of change to FC I/II 1.01, 95% CI: 0.98-1.04). There was no significant improvement in 6-minute walk distance (β coefficient 0.21, 95% CI: -0.98 to 1.4), reduction in BNP/NT-proBNP (β coefficient -12.16, 95% CI: -30.68 to 6.37), increase in tricuspid annular plane systolic excursion (β coefficient 0.074, 95% CI: 0.010-0.139), or decrease in pulmonary artery systolic pressure (0.996, 95% CI: 0.991-1.011) in CpcPH with therapy. There was higher mortality in CpcPH compared to PAH on treatment (24% vs 4%, P = .003)., Conclusions: There were no improvements in symptoms, exercise capacity, or echocardiographic parameters with PAH-targeted therapy in CpcPH. Further studies into potential treatments benefiting this population are needed., (Copyright © 2021. Published by Elsevier Inc.)

Objectives: To determine which patients with congenital diaphragmatic hernia (CDH) and pulmonary hypertension (PH) benefit from inhaled nitric oxide (iNO) treatment by comparing characteristics and outcomes of iNO responders to nonresponders., Study Design: We performed a retrospective chart review of infants with CDH treated at our center between 2011 and 2016. In a subset of patients, iNO was initiated for hypoxemia or echocardiographic evidence of extrapulmonary right to left shunting. Initial post-treatment blood gases were reviewed, and patients were classified as responders (increased PaO 2 >20 mm Hg) or nonresponders. Baseline characteristics, echocardiograms and outcomes were compared between groups with Fisher exact tests and Mann-Whitney t tests, as appropriate., Results: During the study period, 95 of 131 patients with CDH (73%) were treated with iNO. All patients with pretreatment echocardiograms (n = 90) had echocardiographic evidence of PH. Thirty-eight (40%) patients met treatment response criteria. Responders had significant improvements in PaO 2 (51 ± 3 vs 123 ± 7 mm Hg, P < .01), alveolar-arterial gradient (422 ± 30 vs 327 ± 27 mm Hg, P < .01), and PaO 2 to FiO 2 ratio (82 ± 10 vs 199 ± 15 mm Hg, P < .01). Nonresponders were more likely to have left ventricular systolic dysfunction (27% vs 8%, P = .03) on echocardiogram. Responders were less likely to require extracorporeal membrane support (50 vs 24%, P = .02)., Conclusions: iNO treatment is associated with improved oxygenation and reduced need for ECMO in a subpopulation of patients with CDH with PH and normal left ventricular systolic function., (Published by Elsevier Inc.)

Objective: To assess the demographics, treatment algorithm, and outcomes in a large cohort of children treated with sildenafil., Study Design: A retrospective cohort study of children with pulmonary hypertension (PH) treated with sildenafil at a single institution between 2004 and 2015. Baseline and follow-up data collected by chart review., Results: There were 269 children included in this study: 47 with idiopathic pulmonary arterial hypertension, 53 with congenital heart disease, 135 with bronchopulmonary dysplasia, 24 with congenital diaphragmatic hernia, and 7 with other causes. Sildenafil was initial monotherapy in 84.8% and add-on therapy in 15.2%. Median follow-up time was 3.1 years (2  weeks-12.4 years). On follow-up, 99 (37%) remained on sildenafil or transitioned to tadalafil, 93 (35%) stopped sildenafil for improvement in PH, 54 (20%) died, and 20 (7%) were lost to follow-up. PH was most likely to improve in those with bronchopulmonary dysplasia, allowing for the discontinuation of sildenafil in 45%. Eighteen deaths were related to PH and 36 from other systemic causes. Two patients stopped sildenafil owing to airway spasm with desaturation. Overall survival was significantly lower in World Health Organization group 3 PH (bronchopulmonary dysplasia and congenital diaphragmatic hernia) vs group 1 (idiopathic pulmonary arterial hypertension and congenital heart disease), P = .02., Conclusions: In this retrospective experience in children with mainly World Health Organization groups 1 and 3 PH, low-dose sildenafil was well-tolerated, safe, and had an acceptable side effect profile. Although patients with group 3 PH have high mortality, survivors have a high likelihood of PH improving., (Published by Elsevier Inc.)

Objective: To evaluate the effect of continuous treprostinil in infants with severe pulmonary hypertension associated with congenital diaphragmatic hernia (CDH) on specific markers of pulmonary hypertension severity and to report the safety and tolerability of treprostinil., Study Design: We conducted a retrospective cohort study of infants with CDH-associated pulmonary hypertension treated with treprostinil from January 2011 to September 2016. Severity of pulmonary hypertension was assessed by echocardiogram and serum B-type natriuretic peptide (BNP) by using time points before initiation and 24 hours, 1 week, and 1 month after treprostinil initiation. Fisher exact tests, Wilcoxon-rank sum tests, and mixed-effects models were used for analysis., Results: Seventeen patients were treated with treprostinil for a median of 54.5 days (IQR 44.3-110 days). Compared with the concurrent CDH population (n = 147), infants treated with treprostinil were more likely to require extracorporeal support (76.5% vs 25.2%, P < .0001), to have a longer hospital stay (144 vs 60 days, P < .0001), and to need longer mechanical ventilator support (76.5 vs 30.9 days, P < .0001). Following treprostinil initiation, there was a significant reduction in BNP at 1 week (1439 vs 393 pg/mL, P < .01) and 1 month (1439 vs 242 pg/mL, P = .01). Severity of pulmonary hypertension by echocardiogram improved at 1 month (OR 0.14, CI 95% 0.04-0.48, P = .002). Despite these improvements, overall mortality remained high (35%). There were no adverse events related to treprostinil, including no hypotension, hypoxia, or thrombocytopenia., Conclusions: In this cohort, treprostinil use was associated with improved severity of pulmonary hypertension assessed by echocardiogram and decreased BNP, with no significant side effects., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: Systemic left-to-right shunting causes pulmonary arteriopathy, leading to progressive cardiopulmonary failure and a poor prognosis. In this study, we examined the extraglycemic effect of a synthetic glucagon-like peptide, exendin-4, on pulmonary arteriopathy regression and cardiopulmonary function in nondiabetic rats., Methods: Pulmonary hypertension (PH) was induced by monocrotaline (60 mg/kg, subcutaneous) injection followed by the creation of an aortocaval fistula. After 4 weeks, exendin-4 (1 μg/kg/day) was administered intraperitoneally for 3 consecutive weeks, followed by an assessment of cardiopulmonary function, pulmonary artery vasoreactivity, tissue and blood biochemistry, and lung histology., Results: Exendin-4 significantly reduced right ventricle mass and pulmonary artery pressure, which improved right ventricle function and the survival rate in rats with PH. Tissue and blood interleukin-1β levels decreased, whereas pulmonary artery cyclic adenosine monophosphate levels were restored by exendin-4. Smooth muscle-myosin heavy chain-II and α-smooth muscle actin protein levels increased in the pulmonary arteries of exendin-4-treated rats. Histology showed that exendin-4 decreased the main and intra-acinar pulmonary artery medial thickness., Conclusions: Exendin-4 treatment improved pulmonary artery function in flow-induced PH via its direct vasoactive properties, anti-inflammatory effects, and vascular smooth muscle cell phenotypic modulation. Mitigation of pulmonary arteriopathy further potentiated right ventricle performance and reduced overall mortality. These responses were associated with suppressed expression and activity of interleukin-1β and its downstream signaling molecules. Glucagon-like peptide analogs may possess pleiotropic therapeutic potential in flow-induced PH., (Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Pulmonary arterial hypertension (PAH) is progressive disorder characterized by elevated pulmonary vascular resistance that can lead to right heart failure and death. One of the main therapeutic options for PAH are medications targeting the prostacyclin pathway. Treprostinil is a prostacyclin analogue and selexipag is a selective IP receptor agonist. Treprostinil can be delivered by a variety of routes including oral, inhaled, subcutaneous and intravenous. Selexipag is currently approved as an oral formulation. The impact of the route of delivery and the optimal dosing for transitioning inhaled treprostinil to oral treprostinil or selexipag is unknown. More importantly, given the different selectivity for prostacyclin receptors, it is uncertain whether treprostinil and selexipag can be substituted. We present two patients with PAH who received medications targeting the prostacyclin pathway and were transitioned from inhaled treprostinil to either oral treprostinil or selexipag. In both cases, we noted clinical, functional and hemodynamic deterioration. These cases highlight that the route of delivery (inhaled versus oral) and/or the specific PH medication (treprostinil versus selexipag) matter; therefore close monitoring during transitions is imperative., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Pulmonary hypertension (PH) is a life-threatening complication in patients with chronic kidney disease on hemodialysis (CKD-HD)., Objectives: To determine whether subcutaneous infusion of treprostinil was effective and tolerable CKD-PH., Methods and Results: A 57-year-old man was admitted to our hospital due to presyncope and dyspnea during exercise with a history of CKD-HD. Cardiac catheterization revealed high pulmonary arterial pressure (PAP) of 53/24/32 mmHg and pulmonary vascular resistance (PVR) of 11.2 w.u. Upfront combination therapy with bosentan and sildenafil was started. However, 6-month therapy did not attenuate his symptoms, probably due to the high PAP and PVR (60/19/30 mmHg and 5.9 w.u.). We added subcutaneous treprostinil. Surprisingly, 9-month treprostinil (50 ng/kg/min) normalized hemodynamics (PAP: 25/4/13 mmHg and PVR: 1.9 w.u.). His symptoms during excise disappeared without any adverse effects., Conclusion: This is the first report that subcutaneous treprostinil was very effective and tolerable in a PH patient with CKD-HD., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Pulmonary hypertension is a hemodynamic condition, defined as a mean pulmonary artery pressure by right-sided heart catheterization of at least 25 mm Hg at rest. It is classified into 5 general groups based on the underlying cause, with left ventricular failure and chronic obstructive pulmonary disease being 2 of the most common causes in the United States. Although the specifics of the pathophysiology will vary with the cause, appreciating the risks of pulmonary hypertension and right ventricular failure is critical to appropriately evaluating and resuscitating pulmonary hypertension patients in the emergency department (ED). Patients may present to the ED with complaints related to pulmonary hypertension or unrelated ones, but this condition will affect all aspects of care. Exertional dyspnea is the most common symptom attributable to pulmonary hypertension, but the latter should be considered in any ED patient with unexplained dyspnea on exertion, syncope, or signs of right ventricular dysfunction. Patients with right ventricular failure are often volume overloaded, and careful volume management is imperative, especially in the setting of hypotension. Vasopressors and inotropes, rather than fluid boluses, are often required in shock to augment cardiac output and reduce the risk of exacerbating right ventricular ischemia. Intubation should be avoided if possible, although hypoxemia and hypercapnia may also worsen right-sided heart function. Emergency physicians should appreciate the role of pulmonary vasodilators in the treatment of pulmonary arterial hypertension and recognize that patients receiving these medications may rapidly develop right ventricular failure and even death without these therapies. Patients may require interventions not readily available in the ED, such as a pulmonary artery catheter, inhaled pulmonary vasodilators, and mechanical support with a right ventricular assist device or extracorporeal membrane oxygenation. Therefore, early consultation with a pulmonary hypertension specialist and transfer to a tertiary care center with invasive monitoring and mechanical support capabilities is advised., (Copyright © 2015 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

A diffuse patchy pattern in the perfusion scan of the lung is a hallmark of severe pulmonary arterial hypertension (PAH). However, the mechanisms of this unique pattern remain uncertain. We here present the case of a 19-year-old woman with severe PAH who demonstrated reversal of the diffuse patchy pattern with improvement of pulmonary blood flow within a month after upfront triple combination therapy. Our case is a first report showing reversibility of diffuse patchy pattern by a short-term treatment in severe PAH. These findings suggest the possibility that the mechanisms underlying the diffuse patchy pattern may involve reversible vasoconstriction in addition to remodeling of small pulmonary arteries., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We describe 2 infants with congenital diaphragmatic hernia with severe pulmonary hypertension at 6 weeks. Treprostinil was used with rapid clinical improvement. Repeat cardiac catheterization showed dramatic improvement. Both infants were weaned off the drug, representing the first reports of successful short-term treprostinil use in neonates with congenital diaphragmatic hernia., (Published by Elsevier Inc.)

Objective: The pathogenesis of pulmonary arterial hypertension (PAH) involves reactive oxygen species and inflammation. Beneficial effects of molecular hydrogen, which exerts both anti-inflammatory and antioxidative effects, have been reported for various pathologic conditions. We therefore hypothesized that molecular hydrogen would improve monocrotaline (MCT)-induced PAH in rats., Methods: Nineteen male Sprague-Dawley rats (body weight: 200-300 g) were divided into groups, receiving: (1) MCT + hydrogen-saturated water (group H); (2) MCT + dehydrogenized water (group M); or (3) saline + dehydrogenized water (group C). Sixteen days after substance administration, we evaluated hemodynamics, harvested the lungs and heart, and performed morphometric analysis of the pulmonary vasculature. Macrophage infiltration, antiproliferating cell nuclear antigen-positive cells, 8-hydroxy-deoxyguanosine (8-OHdG)-positive cells, and expressions of phosphorylated signal transducers and activators of transcription-3 (STAT3) and nuclear factor of activated T-cells (NFAT) were evaluated immunohistochemically. Stromal cell-derived factor-1 and monocyte chemoattractant protein-1 expressions were evaluated by quantitative reverse-transcription polymerase chain reaction., Results: Pulmonary arterial hypertension was significantly exacerbated in group M compared to group C, but was significantly improved in group H. Vascular density was significantly reduced in group M, but not in group H. Adventitial macrophages, antiproliferating cell nuclear antigen - and 8-OHdG-positive cells, and stromal cell-derived factor-1 and monocyte chemoattractant protein-1 expressions were significantly increased in group M, but improved in group H. Expressions of phosphorylated STAT3 and NFAT were up-regulated in group M, but improved in group H., Conclusions: Molecular hydrogen ameliorates MCT-induced PAH in rats by suppressing macrophage accumulation, reducing oxidative stress and modulating the STAT3/NFAT axis., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Many targeted therapies have been approved for pulmonary arterial hypertension (PAH), most of which are in oral forms. However, the effects of these drugs on lifesaving are unclear. Our objective was to evaluate the effects of oral treatments on clinical outcomes especially all-cause mortality in patients with PAH., Methods: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for relevant articles up to April 2014. Randomized, double-blind, parallel-group clinical trials that compared oral agents with placebo were selected. Data for populations, interventions, and outcomes were extracted independently by 2 investigators, and disagreements were resolved by consensus. Quality assessment was performed using the Cochrane risk-of-bias tool., Results: Twenty-one randomized, controlled, clinical trials involving 5105 patients were identified in the primary analysis. The overall estimated odds ratio (OR) of combined clinical worsening (CCW) events between active treatment groups and control groups was 0.55 (95% CI 0.47-0.64, P < .001). However, the effect of oral treatments on reducing all-cause mortality was not statistically significant (OR 0.82, 95% CI 0.61-1.10, P = .192), which was consistent for approved drugs (OR 0.84, 95% CI 0.61-1.18, P = .316) and drugs that were not approved (OR 0.72, 95% CI 0.36-1.44, P = .352). In the sensitivity analysis, a significant reduction was achieved in CCW events (P < .001) but not in all-cause mortality (P = .057)., Conclusions: This pooled analysis shows the benefits of oral treatments on CCW events in patients with PAH. However, these drugs seem to exhibit less favorable effects on life expectancy in the short-term follow-up, suggesting further evaluation is required., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Lung ischemia-reperfusion (IR) injury during cardiopulmonary surgery is associated with postoperative morbidity and mortality, particularly in patients with pulmonary hypertension (PH). Using a rat model for monocrotaline-induced PH, we investigated the protective effect of rosuvastatin against IR injury in lungs affected by PH and attempted to elucidate its mechanism of action., Methods: Male Sprague-Dawley monocrotaline-treated rats were divided into 4 groups (n = 8-9): sham, control + IR, statin + IR, and statin + mevalonolactone + IR. Lung ischemia was induced by left pulmonary artery occlusion (1 hour), followed by reperfusion (4 hours). Rosuvastatin (2 mg/kg) was injected 18 hours before reperfusion and mevalonolactone (1 mg/kg) was injected immediately before reperfusion. The arterial oxygen tension/inspired oxygen fraction ratio was used as a measure of lung oxygenation. Left lung tissue was analyzed for the wet-to-dry lung weight ratio and protein expression of endothelial nitric oxide synthase (eNOS) and phospho-eNOS. Macrophage recruitment was assessed by CD68 immunostaining., Results: Our results showed that rosuvastatin decreased IR lung injury (control + IR vs statin + IR) in terms of the arterial oxygen tension/inspired oxygen fraction ratio (272 ± 43 vs 442 ± 13), wet-to-dry ratio (5.7 ± 0.7 vs 4.8 ± 0.6), and macrophage infiltration (8.0 ± 0.6/field vs 4.0 ± 0.5/field) (P < .05 for all). eNOS and phospho-eNOS were downregulated by IR, which was blocked by rosuvastatin. Effects of rosuvastatin were blunted by mevalonolactone., Conclusions: Single-dose rosuvastatin decreased IR injury in lungs affected by PH via 2 anti-inflammatory mechanisms: preserving eNOS function and inhibiting macrophage infiltration., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: Pulmonary vein stenosis (PVS) is a relentless disease with a poor prognosis. Although surgical repair can effectively treat "downstream" (near left atrial junction) PVS, residual "upstream" (deep in lung parenchyma) PVS commonly dictates long-term survival. Our initial studies revealed an association between PVS and transforming growth factor-β signaling, which led us to investigate the effect of losartan on upstream pulmonary vein vasculopathy in a piglet model of PVS., Methods: Neonatal Yorkshire piglets underwent sham surgical banding (sham, n = 6), staged bilateral pulmonary vein banding of all pulmonary veins except the right middle pulmonary vein (banded, n = 6), and staged pulmonary vein banding with losartan treatment (losartan, 1 mg/kg/d, n = 7). After 7 weeks, the hemodynamic data were obtained and the piglets killed., Results: Pulmonary vein banding (compared with sham) was associated with continuous turbulent flow in banded pulmonary veins, pulmonary hypertension (pulmonary artery/systemic blood pressure ratio 0.51 ± 0.06 vs 0.23 ± 0.02, P < .001), and diffuse pulmonary vein intimal hyperplasia in the upstream pulmonary veins (P < .001). Losartan administration decreased the pulmonary artery/systemic blood pressure ratios compared with those in the banded piglets (0.36 ± 0.08 vs 0.51 ± 0.06, P = .007) but it remained greater than those in the sham group (P = .001). Losartan was also associated with diminished pulmonary vein intimal hyperplasia compared with that in the banded piglets (P < .001) but still remained more than that in the sham group (P = .035). Pulmonary vein banding reduced vascular endothelial-cadherin expression, indicative of diminished endothelial integrity, which was restored with losartan., Conclusions: Losartan treatment improved PVS-associated pulmonary hypertension and intimal hyperplasia and might be a beneficial prophylactic therapy for patients at high risk of developing PVS after pulmonary vein surgery., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Left main coronary artery compression syndrome (LMCS) in patients with severe pulmonary arterial hypertension (PAH) is an unusual, and often a missed cause of exertional angina. Spontaneous coronary dissection (SCD) is a rare cause of acute coronary syndrome of unknown etiology, with predilection to women in the 20s-40s. Weather the co-presence of LMCS and SCD in certain patients is a coincidence or of pathological significance is not known. The optimal management strategy of each of these conditions remains controversial. We report a case of SCD in a patient with PAH and LMCS, successfully treated with conservative medical therapy., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: To compare the therapeutic efficacy of recombinant human brain natriuretic peptide and prostaglandin E1 in the treatment of pulmonary hypertension after mitral valve replacement., Methods: Sixty patients with postoperative pulmonary hypertension were divided randomly into 3 groups that received saline, prostaglandin E1, and natriuretic peptide infusions for 12 hours each. The hemodynamics data were monitored consecutively, and the levels of thromboxane A2 and cyclic guanosine monophosphate were detected pretreatment, after treatment, and 1 week after surgery., Results: The arterial pressure, pulmonary arterial pressure, and pulmonary capillary wedge pressure decreased 1 hour after prostaglandin E1 treatment and rebounded after treatment discontinuation. The pulmonary arterial pressure and pulmonary capillary wedge pressure in the natriuretic peptide group decreased 3 hours after treatment; pulmonary arterial pressure decreased less than that of the prostaglandin group, and there was no evidence of hemodynamic rebound after treatment discontinuation. The natriuretic peptide had no significant effects on arterial pressure. In both the prostaglandin and natriuretic peptide groups, cyclic guanosine monophosphate increased after the treatment, which was even higher in the latter group. Prostaglandin E1 could lead to the decrease of thromboxane A2, which was not seen in the natriuretic peptide group., Conclusions: Both brain natriuretic peptide and prostaglandin E1 can effectively reduce pulmonary hypertension; however, natriuretic peptide has a slower and milder efficacy. The effects of these 2 drugs in reducing the pulmonary arterial pressure may be mediated through different pathways., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: Continuous infusion of epoprostenol is the treatment of choice in patients with pulmonary arterial hypertension in functional classes III to IV. However, this treatment's limitations include instability at room temperature. A new epoprostenol formulation offers improved storage conditions and patient convenience., Methods: The EPITOME-2 trial was an open-label, prospective, multicenter, single-arm, phase IIIb study. Patients with pulmonary arterial hypertension on long-term, stable epoprostenol therapy were transitioned from epoprostenol with glycine and mannitol excipients (Flolan; GlaxoSmithKline, Durham, NC) to epoprostenol with arginine and sucrose excipients (Veletri; Actelion Pharmaceuticals Ltd, Allschwil, Switzerland). Patients were followed up for 3 months, and dose adjustments were recorded. Efficacy measures included the 6-minute walk distance, hemodynamics assessed by right heart catheterization, and New York Heart Association functional class. Safety and tolerability of the transition were also evaluated. Quality of life was assessed using the Treatment Satisfaction Questionnaire for Medication., Results: Forty-two patients enrolled in the study, and 1 patient withdrew consent before treatment; thus, 41 patients received treatment and completed the study. Six patients required dose adjustments. There were no clinically relevant changes from baseline to month 3 in any of the efficacy end points. Adverse events were those previously described with intravenous prostacyclin therapy. Treatment Satisfaction Questionnaire for Medication scores showed an improvement from baseline to month 3 in the domain of treatment convenience., Conclusions: Transition from epoprostenol with glycine and mannitol excipients to epoprostenol with arginine and sucrose excipients did not affect treatment efficacy, raised no new safety or tolerability concerns, and provided patients with an increased sense of treatment convenience., (© 2014.)

Background: Epoprostenol sodium with arginine-mannitol excipients (epoprostenol AM; Veletri [Actelion Pharmaceuticals Ltd, Allschwil, Switzerland]) and epoprostenol sodium with glycine-mannitol excipients (epoprostenol GM; Flolan [GlaxoSmithKline, Triangle Park, NC]) are intravenous treatments for pulmonary arterial hypertension (PAH). Epoprostenol AM contains different inactive excipients, resulting in greater stability at room temperature compared with epoprostenol GM., Methods: In this prospective, multicenter, open-label, randomized, phase IV exploratory study, epoprostenol-naïve patients in need of injectable prostanoid therapy were randomized 2:1 to open-label epoprostenol AM or epoprostenol GM. The study period was 28 days, followed by a 30-day safety follow-up. Study aims were to descriptively compare the safety, tolerability, drug metabolite levels, and treatment effects of epoprostenol AM and epoprostenol GM in PAH. Statistical analysis was descriptive only because of the exploratory nature of the study., Results: Thirty patients with PAH (18-70 years, 24 women, 20 idiopathic PAH) were randomized to epoprostenol AM (n = 20) or epoprostenol GM (n = 10). Most frequently reported adverse events included jaw pain, headache, nausea, and flushing. Two deaths occurred during the study period, and 1 death occurred during the 30-day safety follow-up period, all in patients receiving epoprostenol AM. All deaths were classified by the treating physician as unrelated to epoprostenol AM. The median (range) change from baseline to day 28 in 6-minute walk distance was 36 m (-127 to 210 m) and 49 m (-44 to 110 m) for the epoprostenol AM and epoprostenol GM groups, respectively., Conclusions: In this randomized clinical study of epoprostenol AM in PAH, use of this novel preparation with greater room temperature stability was well tolerated., (© 2014.)

Background: Intravenous prostacyclin treatment is a well recognized option in patients suffering from pulmonary arterial hypertension (PAH), and remains the gold standard of treatment. However, intravenous prostacyclin treatment involves several limitations, because the available battery-driven pump systems carry the risk of line infections, catheter-related embolisms, thrombosis, and delivery system malfunctions., Case Report: We report for the first time, to the best of our knowledge, on the safe transition procedure from subcutaneous to intravenous treprostinil in a 74-year-old woman suffering from severe PAH (New York Heart Association functional class III), using a new implantable, gas-driven, intravenous pump device (LenusPro, Tricumed/OMT, Frittlingen, Germany)., Conclusions: This implantable pump system may overcome the well-known limitations and risks of commonly used delivery systems, and thus may provide a new option for continuous intravenous prostacyclin treatment in patients with PAH., (Copyright © 2012 Elsevier Inc. All rights reserved.)

We describe a 76-year-old former smoker with a diagnosis of combined pulmonary fibrosis and emphysema associated with pulmonary hypertension and rapidly progressive right heart failure, in whom combined treatment with sitaxsentan and sildenafil resulted in sustained improvement of his clinical condition and exercise performance, without any relevant adverse events. Combined pulmonary fibrosis and emphysema comprises a recently identified syndrome, probably related to tobacco use, and characterized by the coexistence of upper-lobe emphysema and fibrotic changes of the lower lobes, preserved lung volumes, significant hypoxemia, and a high prevalence of pulmonary hypertension, resulting in severe dyspnea. To date, no prospective series, to the best of our knowledge, has reported on the effects of pulmonary vasodilator therapy in such patients., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The association of pulmonary hypertensive vascular disease with nonketotic hyperglycinemia is rare. We describe 5 infants diagnosed with nonketotic hyperglycinemia, in whom pulmonary hypertensive vascular disease was the main presenting feature, and who developed severe pulmonary edema in response to pulmonary vasodilators., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Objective: To measure the circulating concentrations of nitric oxide (NO) adducts with NO bioactivity after inhaled NO (iNO) therapy in infants with pulmonary hypertension., Study Design: In this single center study, 5 sequential blood samples were collected from infants with pulmonary hypertension before, during, and after therapy with iNO (n = 17). Samples were collected from a control group of hospitalized infants without pulmonary hypertension (n = 16) and from healthy adults for comparison (n = 12)., Results: After beginning iNO (20 ppm) whole blood nitrite levels increased approximately two-fold within 2 hours (P<.01). Whole blood nitrate levels increased to 4-fold higher than baseline during treatment with 20 ppm iNO (P<.01). S-nitrosohemoglobin increased measurably after beginning iNO (P<.01), whereas iron nitrosyl hemoglobin and total hemoglobin-bound NO-species compounds did not change., Conclusion: Treatment of pulmonary hypertensive infants with iNO results in increases in levels of nitrite, nitrate, and S-nitrosohemoglobin in circulating blood. We speculate that these compounds may be carriers of NO bioactivity throughout the body and account for peripheral effects of iNO in the brain, heart, and other organs., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Objective: Little is known about the day-to-day experiences of patients and their support persons during the course of epoprostenol treatment for pulmonary arterial hypertension (PAH). The study objective was to describe the experiences of patients and their support persons adjusting to PAH and continuous intravenous epoprostenol., Methods: A qualitative descriptive design with semistructured interviews was conducted jointly with the patient and his/her support person. Seven patients and their support persons (spouse, child, friend) were included., Results: Patients demonstrated personal growth and resilience as they adapted to PAH. Four patient themes emerged: initial shock, figuring it out, giving life, and ongoing struggles. Themes specific to the support person included "their life is in my hands," pressure to perform, and continuation of my role., Conclusion: Nurses may assist these patients and support persons by teaching technical skills, problem-solving and troubleshooting strategies, mobilizing social support, and providing opportunities to reflect on lifestyle changes and long-term adjustment to PAH., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Pulmonary arterial hypertension (PAH) develops from an abnormal interaction between the endothelium and smooth muscle cells in the pulmonary vasculature and is characterized by a progressive rise in pulmonary vascular resistance resulting from vascular remodeling, vasoconstriction, and cellular proliferation. Currently, 3 classes of drugs are approved for the treatment of PAH based on results from small short-term clinical trials-prostacyclin analogues, endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors. The pharmacologic management of PAH is rapidly evolving as newer therapeutic targets that stabilize or reverse pulmonary vascular disease and target right ventricular function are being sought and as clinical practice patterns shift in favor of earlier diagnosis and aggressive treatment. This manuscript will review the practical management aspects of currently approved PAH treatments and briefly discuss combination therapy and novel pharmacologic targets. In addition, the treatment of acute right ventricular failure and evidence (or lack thereof) for therapies in non-PAH pulmonary hypertension, such as pulmonary hypertension from left side of the heart disease, are addressed., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Objectives: In patients with chronic thromboembolic pulmonary hypertension, high flow in unobstructed lung regions may induce small-vessel damage responsible for persistent pulmonary hypertension after pulmonary thromboendarterectomy. In piglets, closure of an experimental aortopulmonary shunt reverses the flow-induced vascular lesions and diminishes the elevated levels of messenger RNA (mRNA) expression for endothelin-1 and endothelin receptor A (ETA). We wanted to study the effect of the ETA antagonist TBC 3711 on reversal of flow-induced pulmonary vascular lesions., Methods: Twenty piglets were studied. In 15 piglets, pulmonary vasculopathy was induced by creating an aortopulmonary shunt. After 5 weeks of shunting, some animals were studied (n = 5); others underwent shunt closure for 1 week with (n = 5) or without (n = 5) TBC3711 treatment. Anti-ETA treatment started 1 week before and ended 1 week after the shunt closure. The controls were sham-operated animals (n = 5)., Results: High blood flow led to medial hypertrophy of the distal pulmonary arteries (54.9% +/- 1.3% vs 35.3% +/- 0.9%; P < .0001) by stimulating smooth muscle cell proliferation (proliferating cell nuclear antigen) and increased the expression of endothelin-1, ETA or endothelin receptor type A or endothelin receptor A, angiopoietin 1, and Tie2 (real-time polymerase chain reaction). One week after shunt closure, gene expression levels were normal and smooth muscle cells showed increased apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) without proliferation. However, pulmonary artery wall thickness returned to control values only in the group given TBC3711 (33.2% +/- 8% with and 50.3% +/- 1.3% without; P < .05)., Conclusions: Anti-ETA therapy accelerated the reversal of flow-induced pulmonary arterial disease after flow correction. In patients with chronic thromboembolic pulmonary hypertension and severe distal pulmonary vasculopathy, anti-ETA agents may prove useful for preventing persistent pulmonary hypertension after pulmonary thromboendarterectomy., (2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: To investigate the efficacy of bosentan in patients with single-ventricle physiology who were unable to undergo right-sided heart bypass surgery because of high pulmonary vascular resistance and pulmonary artery pressure., Methods: Eight patients with single-ventricle physiology (2 male and 6 female; aged 7 months to 5 years, median 1 year) were enrolled. Prior surgical interventions included pulmonary artery banding in 4 patients, Blalock-Taussig shunt operation in 2 patients, and bidirectional Glenn operation in 5 patients. Right-sided heart bypass surgery was contraindicated for all patients because of high pulmonary vascular resistance and pulmonary artery pressure., Results: Bosentan therapy successfully reduced pulmonary artery pressure and pulmonary vascular resistance in all patients. Mean pulmonary artery pressure at baseline and after bosentan therapy was 21.1 +/- 7.2 mm Hg and 11.9 +/- 4.1 mm Hg, respectively (P < .01). Mean pulmonary vascular resistance index at baseline and after bosentan therapy was 5.7 +/- 3.3 U/m(2) and 1.3 +/- 0.4 U/m(2), respectively (P < .01). Mean pulmonary vascular resistance/systemic vascular resistance at baseline and after bosentan therapy was 0.25 +/- 0.11 and 0.07 +/- 0.03, respectively (P < .01). All patients had improved clinical symptoms and underwent successful Fontan operations., Conclusion: Bosentan induces mid-term clinical and hemodynamic improvement in patients with single-ventricle physiology and elevated pulmonary vascular resistance and pulmonary artery pressure. Bosentan therapy may increase the surgical options and improve outcomes in candidates for right-sided heart bypass surgery., (Copyright 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: In a previous meta-analysis on the approved treatments for pulmonary hypertension, we reported that all therapies caused small changes in 6-minute walk distance over a short period, with minimal effects on hemodynamics and no effect on survival. Since that last review, 10 new clinical trials with about 1,500 patients have been published, which has increased the statistical power of our observations., Methods: A systematic review of all clinical trials in pulmonary arterial hypertension was done., Results: The pooled effect of all treatments strategies (relative risk [95% CI], P) now shows a significant reduction of 39% (2%-62%, P = .041) in all-cause mortality. The benefits were confined only to patients with advanced disease for 16 weeks, regardless of which class of drug is used. When considering the effects within each drug family, no class of drug produced a statistically significant reduction in all-cause mortality. The improved survival bore no relationship with the change in 6-minute walk, the primary end point in most of the trials., Conclusions: The impact of vasodilators on long-term survival in pulmonary arterial hypertension remains uncertain. Future trials need to (a) adopt new trial designs that can better address clinical benefits, (b) use new end points that incorporate our best understanding of the disease rather than the ones that are easy to administer, and (c) include longer durations of study and other strategies to clarify if survival is affected., (Copyright (c) 2010 Mosby, Inc. All rights reserved.)

Background: Intravenous (IV) prostanoid therapy remains arguably the most effective treatment of advanced pulmonary arterial hypertension (PAH) despite the introduction of newer molecules from different drug classes., Methods: Literature regarding the properties, efficacy, safety, dosing, and cost of IV prostanoids was reviewed. In addition, a survey of physicians who treat PAH in the United States was conducted to assess IV prostanoid use in clinical practice., Results: Clinical studies have demonstrated that the 2 prostanoids available for IV administration in the United States, epoprostenol and treprostinil, improve exercise capacity, dyspnea, and cardiopulmonary hemodynamics in patients with PAH. Furthermore, epoprostenol has been shown to improve quality of life, functional class, and survival. The safety profiles of epoprostenol and IV treprostinil during short-term therapy appear comparable. Potential differences in the biochemical properties of these 2 drugs may have clinical implications. Whereas long-term data with subcutaneous treprostinil have been published, such data for IV treprostinil are not currently available. The physician survey revealed differences in the common maintenance doses used for both drugs, with IV treprostinil dosing approximately twice that of epoprostenol. These differences in dose have a direct bearing on the cost of therapy., Conclusions: The unique properties of epoprostenol and treprostinil translate into clinical differences, which can influence the amount of drug used to achieve satisfactory patient improvement in the acute and long-term settings.

Objective: To determine the clinical course and outcomes of infants with chronic lung disease (CLD) and pulmonary hypertension (PH) who received prolonged sildenafil therapy., Study Design: We conducted a retrospective review of 25 patients <2 years of age with CLD in whom sildenafil was initiated for the treatment of PH while they were hospitalized from January 2004 to October 2007. Hemodynamic improvement was defined by a 20% decrease in the ratio of pulmonary to systemic systolic arterial pressure or improvement in the degree of ventricular septal flattening with serial echocardiograms., Results: Chronic sildenafil therapy (dose range, 1.5-8.0 mg/kg/d) was initiated at a median of 171 days of age (range, 14-673 days of age) for a median duration of 241 days (range, 28-950 days). Twenty-two patients (88%) achieved hemodynamic improvement after a median treatment duration of 40 days (range, 6-600 days). Eleven of the 13 patients with interval estimates of systolic pulmonary artery pressure with echocardiogram showed clinically significant reductions in PH. Five patients (20%) died during the follow-up period. Adverse events leading to cessation or interruption of therapy occurred in 2 patients, 1 for recurrent erections, and the other had the medication held briefly because of intestinal pneumatosis., Conclusion: These data suggest that chronic sildenafil therapy is well-tolerated, safe, and effective for infants with PH and CLD.