Intravenous Treprostinil Research Articles

The effects of standardized intravenous treprostinil in pulmonary arterial hypertension patients after total cavo-pulmonary connection procedure

ObjectiveTotal 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.MethodsThis 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.ResultsA 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.ConclusionTreprostinil 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.

Short term effect of intravenous treprostinil in term and preterm infants with pulmonary hypertension

BackgroundPulmonary hypertension (PH) is a life-threatening condition in newborns. We aimed to assess the clinical and echocardiographic responses of term and preterm infants to treprostinil.MethodsThis retrospective study included newborns diagnosed with PH and treated with treprostinil as additional therapy after inhaled nitric oxide administration in the neonatal intensive care unit of a tertiary center. Term and preterm infants were compared in terms of echocardiographic findings and clinical findings 4 weeks after treprostinil treatment.ResultsDuring the study period, 11 term and 18 preterm infants were diagnosed with PH and received treprostinil. There were no differences in the echocardiographic findings of interventricular septal deviation, direction of shunt, and ratio of estimated pulmonary artery pressure over systolic blood pressure. Congenital diaphragmatic hernia was the most common condition occurring upon PH diagnosis among term infants, while severe bronchopulmonary dysplasia was the most common in preterm infants. Improvements in echocardiographic findings were more pronounced in term infants than in preterm infants (100% vs. 55.6%, P = 0.012). The inhaled nitric oxide dose was gradually tapered for term infants and was lower than that for preterm infants at 1, 2, and 3 weeks after treprostinil.ConclusionIntravenous treprostinil could be an adjuvant therapy option for term and preterm infants with PH, especially for those who cannot receive oral medication. The efficacy and safety of treprostinil in this population with PH should be investigated further.

Comparison of treprostinil and oral sildenafil for the treatment of persistent pulmonary hypertension of the newborn: a retrospective cohort study.

This study aims to evaluate the effectiveness of treprostinil and oral sildenafil in managing persistent pulmonary hypertension of newborns (PPHN). We conducted a retrospective cohort study of 42 neonates with PPHN treated with continuous intravenous treprostinil or oral sildenafil from January 2020 to October 2022 in China. Outcomes assessed included echocardiographic pulmonary artery systolic pressure (PASP), shunt direction, and arterial blood gas measures. Treprostinil lowered PASP and improved oxygenation significantly better than sildenafil on days 1, 2, and 3 of treatment (P < 0.05). Treprostinil also corrected shunt direction faster than sildenafil (P < 0.05). The duration of mechanical ventilation, length of NICU stay, and overall hospital stay did not significantly differ between the two groups (P > 0.05). Treprostinil effectively lowers pulmonary artery pressure and improves oxygenation in neonates with PPHN, without being associated with severe complications. It may serve as a beneficial adjunct therapy for neonates with PPHN.

Transition from Intravenous Epoprostenol to Treprostinil Due to Intolerable Side Effects in Patients With Pulmonary Arterial Hypertension

Intravenous epoprostenol improves exercise capacity and survival in patients with pulmonary arterial hypertension (PAH); however, it has side effects. Reviewing the side effects associated with epoprostenol and treprostinil is essential for improving the long-term treatment strategies for PAH. This retrospective review included patients with PAH who transitioned from intravenous epoprostenol to intravenous treprostinil owing to intolerable side effects, including high cardiac output symptoms, ascites, and thrombocytopenia. Of the 85 patients who received epoprostenol at our hospital between 2013 and 2021, 16 (11 women), with a median age of 33 (range 26 to 40) years (including 12 with idiopathic PAH, 3 with hereditary PAH, and 1 with connective tissue disease pulmonary hypertension), had to switch from intravenous epoprostenol to treprostinil owing to the side effects. After transitioning, epoprostenol-associated intolerable side effects, such as high cardiac output symptoms, ascites, and thrombocytopenia, were ameliorated. In conclusion, for patients with PAHwho have intolerable side effects fromepoprostenol and have difficulty in continuing treatment, switching from epoprostenol to treprostinil may be an option. Switching treatment leads to better adherence and improved long-term prostacyclin therapy.

Pulmonary Vasodilator Therapy in Pediatric Patients on Ventricular Assist Device Support: A Single-Center Experience and Proposal for Use.

Pediatric precapillary pulmonary hypertension can develop in response to systemic atrial hypertension. Systemic atrial decompression following ventricular assist device (VAD) implantation may not sufficiently lower pulmonary vascular resistance (PVR) to consider heart transplant candidacy. Prostacyclins have been used in adult VAD patients with success, but pediatric data on safety and efficacy in this population are limited. We sought to describe our center's experience to show its safety and to present our current protocol for perioperative use. We reviewed our use of prostacyclin therapy in pediatric patients on VAD support with high PVR from 2016 to 2021. Of the 17 patients who met inclusion, 12 survived to transplant and 1 is alive with VAD in situ. All patients survived posttransplant. With continuous intravenous (IV) epoprostenol or treprostinil therapy, there were no bleeding complications or worsening of end-organ function. A significant reduction was observed in vasoactive inotropic scores by 49% in the first 24 hours post-prostacyclin initiation. The proportion of patients surviving to transplant in this high-risk cohort is favorable. In conclusion, prostacyclins may be safe to use in patients with elevated PVR as part of their VAD and transplant course and may provide a transplant option in those otherwise not candidates.

Long-Term Safety, Outcome, and Clinical Effects of Subcutaneous and Intravenous Treprostinil Treatment in Patients with Severe Chronic Pulmonary Arterial Hypertension

Background: Current guidelines recommend treatment with parenteral prostacyclin analogs in patients with severe pulmonary arterial hypertension (PAH), who have insufficient response to treatment. Real-life data are sought to help physicians in treatment decisions and clinical care of patients. Objective: This study analyzed safety, clinical effects, and long-term outcomes of subcutaneous (sc) and/or intravenous (iv) treprostinil via different pump systems in consecutive patients with PAH. Methods: Thirty-seven patients with severe progressive PAH despite dual combination therapy (20 female, mean age: 52.3 ± 15 years, mean pulmonary vascular resistance: 12.1 ± 5.1 WU) were initiated with add-on treprostinil sc and were routinely clinically assessed. Changes in clinical parameters, adverse events, and outcome were analyzed retrospectively. Results: In 24 of 37 patients, treprostinil administration was continued iv via implantation of LENUS Pro® pump after 3 ± 1.3 months, 6 patients continued with sc therapy, and 7 discontinued treatment. After 3, 6, 9, and 12 months of treprostinil treatment, patients showed a significant improvement in mean 6-min walk distance and tricuspid annular plane systolic excursion compared to baseline. In 8 of the 24 patients, iv pumps required surgical revision. During a mean follow-up of 2.82 ± 1.95 years, 12 patients died, four received lung transplantation. Transplant-free survival after 1, 2, and 3 years was 85.7%, 69.2%, and 65.3%, respectively. Conclusion: sc treprostinil as add-on to double combination treatment significantly improved exercise capacity and right heart function. In most patients, treprostinil could be continued via more tolerable iv administration approach (LENUS Pro® pump), showing reasonable overall survival with respect to the severity of PAH.

Quantitative Measures of Right Ventricular Size and Function by Echocardiogram Correlate with Cardiac Catheterization Hemodynamics in Congenital Diaphragmatic Hernia

To evaluate associations between cardiac catheterization (cath) hemodynamics, quantitative measures of right ventricular (RV) function by echocardiogram, and survival in patients with congenital diaphragmatic hernia (CDH). This single-center retrospective cohort study enrolled patients with CDH who underwent index cath from 2003 to 2022. Tricuspid annular plane systolic excursion z score, RV fractional area change, RV free wall and global longitudinal strain, left ventricular (LV) eccentricity index, RV/LV ratio, and pulmonary artery acceleration time were measured from preprocedure echocardiograms. Associations between hemodynamic values, echocardiographic measures, and survival were evaluated by Spearman correlation and Wilcoxon rank sum test, respectively. Fifty-three patients (68% left-sided, 74% liver herniation, 57% extracorporeal membrane oxygenation, 93% survival) underwent cath (39 during index hospitalization, 14 later) including device closure of a patent ductus arteriosus in 5. Most patients (n=31, 58%) were on pulmonary hypertension treatment at cath, most commonly sildenafil (n=24, 45%) and/or intravenous treprostinil (n=16, 30%). Overall, hemodynamics were consistent with precapillary pulmonary hypertension. Pulmonary capillary wedge pressure was >15mm Hg in 2 patients (4%). Lower fractional area change and worse ventricular strain were associated with higher pulmonary artery pressure while higher LV eccentricity index and higher RV/LV ratio were associated with both higher pulmonary artery pressure and higher pulmonary vascular resistance. Hemodynamics did not differ based on survival status. Worse RV dilation and dysfunction by echocardiogram correlate with higher pulmonary artery pressure and pulmonary vascular resistance on cath in this CDH cohort. These measures may represent novel, noninvasive clinical trial targets in this population.

Subcutaneous use of treprostinil in pediatric pulmonary hypertension patients: A report of three cases.

Treprostinil was approved by the United States Food and Drug Administration for use in the treatment of pulmonary arterial hypertension in 2002. Intravenous or subcutaneous treprostinil is used in pulmonary arterial hypertension patients in the functional classes of II-IV to alleviate exercise-related symptoms, or in cases where epoprostenol treatment should be reduced due to side effects. In this article, we describe three pediatric cases of pulmonary arterial hypertension in whom subcutaneous treprostinil was used.

Assessment of Inhaled Treprostinil Palmitil, Inhaled and Intravenous Treprostinil, and Oral Selexipag in a Sugen/Hypoxia Rat Model of Pulmonary Arterial Hypertension.

Treprostinil palmitil (TP), a long-acting inhaled pulmonary vasodilator prodrug of treprostinil (TRE), has beneficial effects in a Sugen5416/hypoxia (Su/Hx) rat model of pulmonary arterial hypertension (PAH) that compare favorably to the oral phosphodiesterase 5 inhibitor (PDE5) sildenafil. In this study in male Sprague-Dawley rats, a dry powder formulation of TP (TPIP) was compared with inhaled and intravenous TRE and oral selexipag to evaluate inhibition of hemodynamic and pathologic changes in the lungs and heart induced by Su/Hx challenge. Su (20 mg/kg) was injected subcutaneously followed by 3 weeks of Hx (10% O2/balance N2) and then initiation of test article administration over 5 weeks with room air breathing. Hemodynamics and histopathology were measured at the end of the study. Su/Hx challenge approximately doubled the mean pulmonary arterial blood pressure (mPAP) and the Fulton index, decreased cardiac output (CO), doubled the wall thickness and muscularization of the small (10-50 μm) and medium (51-100 μm) sized pulmonary arteries, and increased the percentage of obliterated pulmonary blood vessels. Even though inhaled TRE (65 μg/kg, 4× daily), intravenous TRE (810 ng/kg/min), and oral selexipag (30 mg/kg, twice daily) provided some beneficial effects against the Su/Hx challenge, the overall benefit was generally greater with TPIP at high dose (117 μg/kg, once daily). These results demonstrate that TPIP compares favorably to inhaled and intravenous TRE and oral selexipag with respect to inhibition of the pathophysiological changes induced by Su/Hx challenge in rats. SIGNIFICANCE STATEMENT: Treprostinil palmitil (TP) is a long-acting pulmonary vasodilator prodrug of treprostinil (TRE) formulated for inhaled administration by dry powder [treprostinil palmitil inhalation powder (TPIP)]. Comparison of the activity of TPIP, inhaled and intravenous TRE, and oral selexipag in a Sugen5416/hypoxia (Su/Hx) rat model of pulmonary arterial hypertension demonstrated that each of these drugs exert protection against the hemodynamic and histopathological changes induced by the Su/Hx challenge, with the greatest effect on these changes produced by TPIP.

Comparison of Healthcare Encounters and Drug Persistence in Patients With Pulmonary Arterial Hypertension Receiving Oral Selexipag, Inhaled Iloprost, or Parenteral Treprostinil: A Retrospective Database Analysis

Background: Agents targeting the prostacyclin (PGI2) pathway are important in managing pulmonary arterial hypertension (PAH). No head-to-head clinical trials have compared outcomes between the 3 different PGI2-pathway drugs most commonly available in countries with advanced healthcare: oral selexipag, inhaled iloprost, and parenteral (subcutaneous or intravenous) treprostinil. Objectives: To conduct retrospective database analyses to describe characteristics of patients with PAH initiating therapy with these agents and compare the rate and risk of healthcare facility encounters and drug persistence. Methods: Data were obtained from the Optum™ Clinformatics® Data Mart and Truven™ Health Analytics® MarketScan® Commercial Claims and Encounters databases from July 1, 2008, to September 30, 2020 (Optum™), or October 31, 2020 (Truven™). Patients were categorized into index-drug cohorts based on first pharmacy claims for selexipag, inhaled iloprost, or parenteral treprostinil. Eligible patients were ≥18 years of age with ≥1 ICD-9-CM or ICD-10-CM diagnosis code indicating pulmonary hypertension and no diagnosis code suggesting Group 3–5 pulmonary hypertension. Rates of hospitalization (inpatient admissions), emergency room visits, or outpatient visits per person-year were calculated. Drug persistence was measured as time to discontinuation of index drug. Multivariable analyses were performed to compare outcomes with selexipag vs inhaled iloprost and parenteral treprostinil, adjusting for baseline characteristics using inverse probability of treatment weighting. Results: Overall, 583 patients were included in the Optum™ sample and 482 in the Truven™ sample. Mean (SD) age was 61.7 (14.5) and 49.3 (11.3) years, respectively; 74.4% and 75.7% of patients, respectively, were women. In the pooled samples, after adjustment for baseline characteristics, selexipag had a lower risk than inhaled iloprost or parenteral treprostinil for hospitalization (relative rate ratio [95% CI], 0.40 [0.22, 0.75], and 0.26 [0.17, 0.39]) and outpatient visits (0.66 [0.56, 0.78] and 0.76 [0.66, 0.88]). Trends toward lower risk of emergency room visits did not attain statistical significance. Drug discontinuation risk was 16% and 36% lower with selexipag vs parenteral treprostinil and inhaled iloprost, respectively. Conclusions: In real-world use, selexipag appears to be associated with lower rates of hospitalization and outpatient visits than inhaled iloprost or parenteral treprostinil. Further research is required to identify factors underlying these differences.

Comparison of Healthcare Encounters and Drug Persistence in Patients With Pulmonary Arterial Hypertension Receiving Oral Selexipag, Inhaled Iloprost, or Parenteral Treprostinil: A Retrospective Database Analysis.

Background: Agents targeting the prostacyclin (PGI2) pathway are important in managing pulmonary arterial hypertension (PAH). No head-to-head clinical trials have compared outcomes between the 3 different PGI2-pathway drugs most commonly available in countries with advanced healthcare: oral selexipag, inhaled iloprost, and parenteral (subcutaneous or intravenous) treprostinil.Objectives: To conduct retrospective database analyses to describe characteristics of patients with PAH initiating therapy with these agents and compare the rate and risk of healthcare facility encounters and drug persistence.Methods: Data were obtained from the Optum™ Clinformatics® Data Mart and Truven™ Health Analytics® MarketScan® Commercial Claims and Encounters databases from July 1, 2008, to September 30, 2020 (Optum™), or October 31, 2020 (Truven™). Patients were categorized into index-drug cohorts based on first pharmacy claims for selexipag, inhaled iloprost, or parenteral treprostinil. Eligible patients were ≥18 years of age with ≥1 ICD-9-CM or ICD-10-CM diagnosis code indicating pulmonary hypertension and no diagnosis code suggesting Group 3–5 pulmonary hypertension. Rates of hospitalization (inpatient admissions), emergency room visits, or outpatient visits per person-year were calculated. Drug persistence was measured as time to discontinuation of index drug. Multivariable analyses were performed to compare outcomes with selexipag vs inhaled iloprost and parenteral treprostinil, adjusting for baseline characteristics using inverse probability of treatment weighting.Results: Overall, 583 patients were included in the Optum™ sample and 482 in the Truven™ sample. Mean (SD) age was 61.7 (14.5) and 49.3 (11.3) years, respectively; 74.4% and 75.7% of patients, respectively, were women. In the pooled samples, after adjustment for baseline characteristics, selexipag had a lower risk than inhaled iloprost or parenteral treprostinil for hospitalization (relative rate ratio [95% CI], 0.40 [0.22, 0.75], and 0.26 [0.17, 0.39]) and outpatient visits (0.66 [0.56, 0.78] and 0.76 [0.66, 0.88]). Trends toward lower risk of emergency room visits did not attain statistical significance. Drug discontinuation risk was 16% and 36% lower with selexipag vs parenteral treprostinil and inhaled iloprost, respectively.Conclusions: In real-world use, selexipag appears to be associated with lower rates of hospitalization and outpatient visits than inhaled iloprost or parenteral treprostinil. Further research is required to identify factors underlying these differences.

Meeting abstracts from the 15th international conference on neonatal and childhood pulmonary vascular disease

Meeting abstracts from the 15th international conference on neonatal and childhood pulmonary vascular disease

Transition from Parenteral to Oral Prostacyclin Agents in Pulmonary Arterial Hypertension in Ambulatory Care Setting: A Tertiary Care Institutional Experience

<h3>Purpose</h3> Prostacyclins are used to treat advanced pulmonary arterial hypertension as continuous intravenous or subcutaneous infusions. In the right clinical setting, parenteral Prostacyclins can be transitioned to newer oral Prostacyclins. There is a dearth of published guidance for this transition and is limited to inpatient setting. We present our experience with transitioning patients with WHO group 1 pulmonary arterial hypertension from parenteral Treprostinil to oral Treprostinil in the outpatient setting. <h3>Methods</h3> 6 patients with WHO group 1 pulmonary arterial hypertension on stable doses of intravenous or subcutaneous Treprostinil for at least 6 months were transitioned to oral Treprostinil as per published protocol albeit at a slower rate of transition at 6 ng/kg/min per day <h3>Results</h3> All the 6 patients were successfully transitioned from Parenteral Treprostinil to oral Treprostinil and 4 remain on oral therapy for 1- 4 years. The reasons for transition include complications of central line, side effects related to parenteral Prostacyclins and personal preference. Two patients deteriorated over 6-12 months after the transition requiring transition back to parenteral Treprostinil. No deterioration in PAH was noted during the transition. High 6 MWD, High WHO FC (1/2) and normal RV function on parenteral Prostacyclins are associated with successful results. <h3>Conclusion</h3> In the right clinical setting, patients can be successfully transitioned from parenteral Treprostinil to oral Treprostinil and this can be accomplished safely in the outpatient setting.

Management of Severe Scoliosis with Pulmonary Arterial Hypertension: A Single-Center Retrospective Case Series Study

AimsTo determine the impact of anesthesia encountered and to optimize the treatment of perioperative pulmonary arterial hypertension (PAH) in an effort to improve perioperative management and reduce complications.MethodsWe conducted a retrospective analysis of scoliosis patients with PAH who underwent scoliosis surgery.ResultsDuring this period, we identified a total of 22 patients. Their mean age was 22.18 ± 2.11 years. 16 PAH patients (72.72%) received PAH-specific treatment. Only Propofol-based TIVA was used intraoperatively. During the procedure, pulmonary artery catheters and PICCO catheters were placed in all patients to monitor intraoperative and postoperative mPAP, MAP, PRVI and SRVI. During tracheal intubation and intraoperative awake testing, mPAP generally tended to increase in all patients. 6 patients (27.27%) received intraoperative PAH-Specific therapy. All patients received oral sildenafil (75-100 mg/d orally), and 9 patients received postoperative oral sildenafil combined with nebulized iloprost (20 μg/d); intravenous treprostinil (2 ng/kg/min started and titrated to 10-17.5 ng/kg/min); or bosentan (250 mg/d) postoperatively. 7 patients (31.82%) reported postoperative complications, including 2 cases of respiratory failure requiring reintubation, 1 case of right heart failure, 2 cases of superficial surgical site infection, 1 case of fluid and electrolyte and acid-base imbalances, 2 cases of pneumonia and 1 case of pulmonary oedema with fluid overload. Two patients developed more than 1 postoperative complication. No in-hospital death occurred.ConclusionsThe anesthetic management of scoliosis patients with PAH is important task that, like its own surgery, relies on the input of the multidisciplinary team for its success. Close monitoring, optimization of systemic blood pressure, pain control, oxygenation and ventilation, avoidance of exacerbating factors, and the use of vasopressors and pulmonary vasodilators when necessary are essential elements of management.

A DOUBLE HIT: PULMONARY ARTERIAL HYPERTENSION, BMPR2 MUTATION, AND EXPOSURE TO PRESCRIPTION AMPHETAMINES

TOPIC: Pulmonary Vascular Disease TYPE: Fellow Case Reports INTRODUCTION: Pulmonary arterial hypertension (PAH) management during pregnancy is challenging. We present a case of PAH diagnosed during 3rd trimester of pregnancy, in a patient with familial history of PAH and exposure to prescription-amphetamines. CASE PRESENTATION: 30-year-old primigravid female at 30 weeks of gestation was referred to our Pulmonary Hypertension program for evaluation of rapidly progressive dyspnea, lightheadedness and echocardiogram revealing increased pulmonary pressures. She had a history of Attention-deficit/hyperactivity disorder, treated with dextroamphetamine/amphetamine (Adderall®) and lisdexamfetamine (Vyvanse®) for several years. Her mother had died of pulmonary hypertension at the age of 30. She had functional class III symptoms. An echo showed an estimated right ventricular systolic pressure of 69mm Hg, with right ventricular dilation and dysfunction, as well as interventricular septal flattening. A right heart catheterization (RHC) showed a mPAP of 34 mmHg, PAWP 10 mmHg, cardiac output 3.96 L/min, cardiac index of 2.08 L/min/m2 and PVR of 6.1 WU. She was admitted for expedited work-up and treatment of pulmonary hypertension. Investigational studies were negative for alternative etiologies of pulmonary hypertension, there was no evidence of chronic thromboembolic disease. She was started on a rapid titration with intravenous treprostinil. Once at a dose of 40 ng/kg/min, a repeated RHC showed mPAP of 28 mmHg, PAWP 6 mmHg, cardiac output 5.8 L/min, cardiac index of 3.1 L/min/m2 and PVR of 5.1 WU. A multidisciplinary discussion with high-risk OB, cardiac anesthesia, neonatology and our Pulmonary Hypertension program recommended for C-section under epidural anesthesia with VA-ECMO on stand-by, which was performed at 32 weeks of gestation. Her post-op course was uneventful and she was discharged home on triple therapy with sildenafil, ambrisentan and intravenous treprostinil. She was found to have the BMPR2 mutation. At follow-up, she is functional class II, six-minute walk distance is 530 meters and BNP values are 17 ?g/mL. DISCUSSION: Studies report 75% prevalence of BMPR2 mutations in cases of hereditary PAH, with an autosomal dominant mode of inheritance and incomplete penetrance. It is hypothesized that a "two-hit” phenomenon with environmental influencers like drugs, toxins or infection known to cause pulmonary hypertension may have a role in providing the "second hit” leading to development of the disease. We wonder if the exposure to prescription-amphetamines could have been a second hit, on top of her genetic background. PAH in pregnant females poses a very high risk of maternal and fetal mortality. Aggressive counseling focusing of avoiding pregnancy and early termination should be instituted in all patients. In cases where pregnancy is continued, care at centers with expertise in pulmonary hypertension and ECMO/transplant capability is recommended. CONCLUSIONS: . REFERENCE #1: Geraci MW, Bull TM, Tuder RM. Genomics of pulmonary arterial hypertension: implications for therapy. Heart failure clinics. 2010 Jan 1;6(1):101-14. DISCLOSURES: No relevant relationships by Roberto Bernardo, source=Web Response No relevant relationships by HUZAIFA JALIAWALA, source=Web Response No relevant relationships by Katherine Summers, source=Web Response

Safety and Tolerability of a Rapid Transition From Intravenous Treprostinil to Oral Selexipag in Three Adolescent Patients With Pulmonary Arterial Hypertension.

There is limited published experience with transitioning pediatric patients from parenteral treprostinil to oral selexipag therapy. In addition, published transitions have typically been protracted, taking several weeks to complete. We present a case series of 3 adolescent patients who were transitioned from parenteral treprostinil to oral selexipag over a 5- to 7-day period. Their clinical courses leading up to the transitions are summarized and their outcomes are described. The 3 patients were successfully rapidly transitioned during an inpatient hospitalization without any observed adverse events or prostacyclin-related side effects. We conclude that when indicated rapid transition of parenteral to oral prostacyclin therapy may be performed safely in adolescents in an inpatient setting.

Periprocedural safety and outcome after pump implantation for intravenous treprostinil administration in patients with pulmonary arterial hypertension

MethodsIn this retrospective observational study, we analyzed all patients with pulmonary arterial hypertension undergoing LenusPro® pump implantation between November 2013 and October 2019 at our center. Periprocedural safety was assessed by describing all complications that occurred within 28 days after surgery; complications that occurred later were described to assess long-term safety. Clinical outcomes were measured by comparison of clinical parameters and echocardiographic measurements of right ventricular function from baseline to 6-months-follow-up.ResultsFifty-four patients underwent LenusPro® pump implantation for intravenous treprostinil treatment during the investigation period. Periprocedural complications occurred in 5 patients; the only anesthesia-related complication (right heart failure with recovery after prolonged intensive care and death in the further course) occurred in the only patient who underwent general anesthesia. All other patients underwent local anesthesia with or without short-acting (analgo-) sedation. Eighteen long-term complications occurred in 15 patients, most notably pump pocket or catheter related problems. Transplant-free survival rates at 1, 2, and 3 years were 77 %, 56 %, and 48 %, respectively.ConclusionsSubcutaneous pump implantation under local anesthesia and conscious analgosedation while avoiding intubation and mechanical ventilation is feasible in patients with advanced PAH. Controlled studies are needed to determine the safest anesthetic approach for this procedure.Background/ObjectivesIntravenous treprostinil treatment via a fully implantable pump is a treatment option for patients with advanced pulmonary arterial hypertension. However, there is no consensus on the preferred anesthetic approach for the implantation procedure. Primary objective was to assess periprocedural safety with particular attention to feasibility of local anesthesia and conscious analgosedation instead of general anesthesia. Long-term safety and clinical outcomes were secondary endpoints.

Is Inhaled Therapy Better Than IV? Challenges of PVOD

<h3>Introduction</h3> Group 1 pulmonary hypertension (PH) includes pulmonary veno-occlusive disease (PVOD). Diagnosis & management of this rare disease poses multiple challenges. Here we present 2 patients who worsened on systemic vasodilators but responded to inhaled therapy. <h3>Case Report</h3> 76 year old female with sarcoidoisis was admitted with worsening hypoxia requiring high flow nasal cannula. Cardiac sarcoidosis was ruled out by PET-CT (Fig. B, C). Right heart catheterization (RHC) showed severe PH with a negative vasodilator response & normal capillary wedge pressure. PVOD was suspected given hypoxia out of proportion to PH & her CT findings (D, E). She was started on intravenous treprostinil but developed pulmonary edema with worsening V/Q mismatch (F). She was weaned off treprostinil & transitioned to inhaled epoprostenol. She was discharged on inhaled treprostinil only needing nasal cannula. Another 76 year old lady with a recent diagnosis of limited sclerosis was evaluated as an outpatient for dyspnea. Echocardiogram (I) showed PH with a CTA negative for a PE (G). RHC confirmed the diagnosis. She was started on ambrisentan & tadalafil but her hypoxia worsened from 6 to 15 liters. She was referred to cardiology for further evaluation with concern for PVOD. CT chest showed diffuse ground glass pattern & fluid in the fissure (H). Her PFT's showed a normal FEV1, FVC & DLCO of 30%, both consistent with PVOD. She was started on inhaled treprotstinil & has improved since. <h3>Summary</h3> PH specific therapies are directed towards pre-capillary vasculature & pose a risk of causing pulmonary edema in patients with PVOD. Connective tissue disorders are known to be associated with PVOD but there is little data to support the improvement of PH by treating the underlying cause. Right ventricular myocardial biopsies have shown an inherent myocardial defect limiting the response to therapy, leading to poorer outcomes. Given our patients' improvement on inhaled vasodilator therapy we hypothesize that it may help improve V/Q mismatch, but more research is needed to help with management.

Rapid Switch From Subcutaneous to Intravenous Treprostinil in Precapillary Pulmonary Hypertension by Pump Implantation.

Limited data are available on the transition from subcutaneous to intravenous prostacyclin in precapillary pulmonary hypertension. We performed a retrospective analysis of all patients who were switched from subcutaneous to intravenous treprostinil with an implantable infusion pump. We included 85 consecutive, clinically stable patients (mean age 66 years and range 16-85), who had been treated with subcutaneous treprostinil for mean 9 months (range 1-78) before pump implantation. An interdisciplinary expert panel defined standards for this procedure before the first implantation. As the first patient experienced a significant hypotensive episode indicating treprostinil overdose postoperatively, the time span to stop subcutaneous treprostinil was reduced to 60 minutes for all following patients. No events associated with the switch from subcutaneous to intravenous treprostinil were observed during postoperative hospital stay in 84 (98.8%) patients. Taking into account a likely depot effect of subcutaneous treprostinil patients can safely be switched to the intravenous route by the implantation of an infusion pump.

Long-term experience with implantable infusion pumps for intravenous treprostinil in pulmonary arterial hypertension-procedural safety and system-related complications.

Implantable pumps for intravenous treprostinil provide a promising option to overcome drawbacks of parenteral prostanoid administration with external pumps in pulmonary hypertension. We retrospectively analyzed 85 patients undergoing implantation in a single center since 2010. In our cohort, serious complications were rare, and flow rate increase over time warrants careful monitoring.