Parenteral Prostacyclin Therapy Research Articles

Effect of a short course of parenteral treprostinil therapy on right heart structure and function in pulmonary arterial hypertension

Abstract Background Pulmonary arterial hypertension (PAH) is characterized by an increase in pulmonary vascular resistance, leading to increased afterload and right-sided heart failure. It is important to routinely assess disease progression and treatment response, with echocardiography an increasingly recognized important component of risk assessment. Parenteral prostacyclin therapy has been shown to be associated with improvements in right-sided cardiac structure and function, which are prognostic in PAH. Purpose To describe changes in right-sided cardiac structural and functional parameters after a short course of parenteral treprostinil. Methods The EXPEDITE trial (NCT03497689) was a 16-week open-label study of WHO Functional Class (FC) II or III patients with PAH designed to assess short-term (expedited) induction therapy with parenteral treprostinil over 2-8 weeks, to facilitate transition to comparable doses of oral treprostinil. The subset of patients in the per-protocol population that had clinical and/or echocardiographic data available at both baseline (prior to initiation of parenteral treprostinil) and end of induction (2-8 weeks) were included for analysis. Changes in each parameter were analyzed using the non-parametric Wilcoxon signed-rank test. Results In the per-protocol population of EXPEDITE (n=29), the median age was 56 years, 62% were female, and 79% were white. At baseline, 52% were classified as WHO FC II and 48% WHO FC III. Patients were on either no (n=6, 21%), 1 (n=11, 38%), or 2 (n=12, 41%) background PAH therapies. The end of the parenteral treprostinil induction period occurred at Week 2 (n=1), Week 4 (n=5), or Week 8 (n=23); the median (interquartile range) parenteral treprostinil dose achieved was 23.8 (20, 39.3) ng/kg/min. Median changes from baseline to the end of the parenteral treprostinil induction period for this analysis are shown in Table 1. There were directional changes for most measures of right-sided cardiac structure and function that reflected overall improvement; two key markers of cardiac function, cardiac output and NT-proBNP significantly improved. Conclusions In this trial of expedited parenteral treprostinil induction, we saw favorable directional trends in changes in right heart structure and function that were achieved in 8 weeks or less, including some statistically-significant parameters known to have prognostic value in PAH. The relatively rapid improvements we observed in this small cohort may signal important changes in risk status, and support treatment guidelines emphasizing importance of early improvement in the first 3-6 months following treatment. Furthermore, changes in cardiac structure and function often occur before other clinically-evident indicators of disease progression, and early response to treatment has been shown to impact long-term outcomes in patients with PAH. Larger studies with short-term serial right heart imaging assessment to confirm findings are warranted.Table 1

Prognosis of pulmonary arterial hypertension patients with pericardial effusion before and after initiation of parenteral prostacyclin therapy.

Few studies have evaluated the effects of pulmonary arterial hypertension therapies on pericardial effusion. We evaluated hemodynamics, echocardiograms, and outcomes for 119 parenteral prostanoid-treated patients. We discoveredan increased frequency of pericardial effusions posttreatment, and that a moderate-large pericardial effusion at initiation, but not at 1st follow-up, was significantly associated with mortality.

PORTOPULMONARY HYPERTENSION PRACTICE PATTERNS AFTER LIVER TRANSPLANTATION

PORTOPULMONARY HYPERTENSION PRACTICE PATTERNS AFTER LIVER TRANSPLANTATION

Prognostic Value of Echocardiographic Variables Prior to and Following Initiation of Parenteral Prostacyclin Therapy: An Observational Study

Echocardiographic parameters are used as prognostic markers in patients with pulmonary arterial hypertension (PAH) receiving parenteral (IV or subcutaneous [IV/SC]) prostacyclin therapy. However, data on how posttreatment echocardiographic results associate with outcomes are limited. Are echocardiographic parameters pre- and post-parenteral prostacyclin therapy in patients with PAH associated with long-term outcomes? In this retrospective cohort study, patients with PAH initiated on IV epoprostenol or IV/SC treprostinil therapy between 2007 and 2016 were included and followed up through May 31, 2020. Survival free from transplant was assessed from the time of IV/SC prostacyclin therapy initiation and from first follow-up echocardiogram following at least 90days of therapy. Patients with PAH initiated on IV/SC prostacyclin therapy (N= 118) were followed up for a median of 7.3 years. Survival was 86%, 79%, and 69%at 1, 2, and 3 years, respectively. Follow-up echocardiogram in 101 patients (median, 178days; interquartile range, 140-273days) showed improvement in five echocardiographic measures: right ventricular function, right ventricular systolic pressure, right ventricular diastolic diameter, left ventricular diastolic diameter, and tricuspid regurgitation (TR) severity. TR severity and pericardial effusion were associated with survival from IV/SC therapy initiation, whereas right ventricular diastolic diameter, right atrial (RA) size, TR severity, and inferior vena cava characteristics were associated with survival from first follow-up. In a multivariable analysis incorporating other prognostic measures at first follow-up, walk distance, functional class, N-terminal pro-B-type natriuretic peptide, and RA size resulted in the best fit model for survival. Echocardiographic variables improved following IV/SC therapy, and multiple echocardiographic measures associated significantly with survival, particularly when reassessed after at least 90days of therapy. RA size in particular may be useful in prognostication in follow-up of patients with PAH on IV/SC therapy.

PH Roundtable: Transitions in Pulmonary Hypertension

PH Roundtable: Transitions in Pulmonary Hypertension

TRANSITIONING FROM PARENTERAL PROSTACYCLIN THERAPY TO ORAL SELEXIPAG IN PULMONARY ARTERIAL HYPERTENSION

TOPIC: Pulmonary Vascular Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Pulmonary arterial hypertension (PAH) is a serious condition that confers a poor prognosis if not promptly diagnosed and treated. Although parenteral medications targeting the prostacyclin pathway are often prescribed for high-risk patients, the transition to a more convenient and tolerable medication acting on the same pathophysiologic pathway may provide significant benefit in patients with stable disease who are burdened by the multiple complications inherent to parenteral therapy. CASE PRESENTATION: Three patients were successfully transitioned from parenteral prostacyclin therapy to selexipag at a single tertiary-care, expert pulmonary hypertension centre. Prior to transition, two patients were prescribed subcutaneous treprostinil and one intravenous epoprostenol. Reasons for transition included severe site pain with subcutaneous therapy, recurrent line infections, and patient preference. All patients were functional class II at time of transition. Right heart catheterization pre-transition demonstrated pre-capillary pulmonary hypertension in two patients (mPAP of 33mmHg with PVR of 5.2WU in the first, and mPAP of 32mmHg with PVR of 6.3WU in the second), with normal hemodynamics in the third. Transitions were performed in the outpatient setting over the course of 4-8 weeks. All patients achieved maximum daily dosing of selexipag (3200mcg) at the end of transition, with each patient experiencing temporary side effects during transition, e.g. headache, jaw pain, diarrhea, nausea, myalgias, limb pain, and peri-orbital edema. Following transition, there was no incidence of mortality (PAH or otherwise), PAH-related hospitalizations, re-initiation of parenteral therapy, or worsening of functional class or 6-minute walk distance in any of the three patients within 36 months of follow-up (in 6-, 12-, 24-, and 36- months intervals). Echocardiographic and right heart catheterization parameters were stable post-transition. DISCUSSION: All three patients were successfully transitioned from parenteral prostacyclin therapies to selexipag as evidenced by a lack of death, hospitalizations, and/or failure of oral therapy, as well as stability in various functional, echocardiographic, and hemodynamic outcomes with up to 36-months of follow-up. While parental prostacyclin analogues are still required for patients with high-risk or refractory disease, the patients in this study were those who were clinically and hemodynamically stable pre-transition with infusion-related morbidity. This may reflect the phenotype of patient where transition could be considered. CONCLUSIONS: In a carefully selected patient population with PAH on parenteral prostacyclin therapy, transition to selexipag may be a safe and viable option. Further studies are required to better delineate baseline predictors of long-term therapeutic efficacy and safety in a real-world PAH population. REFERENCE #1: Chin KM, McLaughlin V, Kim NH, et al. Clinical Course of Patients Transitioned from Another Prostacyclin Pathway Agent (PPA) to Selexipag in SPHERE. J Hear Lung Transplant. 2019;38(4, Supplement):S486. doi:https://doi.org/10.1016/j.healun.2019.01.1236 REFERENCE #2: Parikh KS, Doerfler S, Shelburne N, et al. Experience in Transitioning From Parenteral Prostacyclins to Selexipag in Pulmonary Arterial Hypertension. J Cardiovasc Pharmacol. 2020;75(4):299-304. doi:10.1097/FJC.0000000000000800 REFERENCE #3: Sargent T, Hansen L, Hohsfield R. Transitions between infused and oral prostacyclin pathway agents in pulmonary arterial hypertension: key considerations. Pulm Circ. 2020;10(3):2045894020931324. doi:10.1177/2045894020931324 DISCLOSURES: No relevant relationships by Brandon Budhram, source=Web Response No relevant relationships by Andrea Gardner, source=Web Response Speaker/Speaker's Bureau relationship with Janssen Please note: 2016-2021 Added 05/01/2021 by Nathan Hambly, source=Web Response, value=Honoraria Advisory Committee Member relationship with Janssen Please note: 2016-2021 Added 05/01/2021 by Nathan Hambly, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: 2016-2021 Added 04/30/2021 by Nathan Hambly, source=Web Response, value=Honoraria Advisory Committee Member relationship with Boehringer Ingelheim Please note: 2016-2021 Added 04/30/2021 by Nathan Hambly, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Roche Please note: 2016-2021 Added 04/30/2021 by Nathan Hambly, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with Roche Please note: 2016-2021 Added 04/30/2021 by Nathan Hambly, source=Web Response, value=Honoraria

PH Roundtable: Conundrums and Controversies in PH-ILD: To Treat or Not to Treat—Identifying Optimal Treatment Candidates

PH Roundtable: Conundrums and Controversies in PH-ILD: To Treat or Not to Treat—Identifying Optimal Treatment Candidates

HEALTH OUTCOMES AND COSTS ASSOCIATED WITH ORAL TREPROSTINIL AND SELEXIPAG ONE YEAR INTO TREATMENT: A UNITED STATES CLAIMS DATABASE ANALYSIS IN PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION

TOPIC: Pulmonary Vascular Disease TYPE: Original Investigations PURPOSE: Previous comparisons of oral treprostinil (TRE) and selexipag (SLX) using real-world data have been limited to short duration follow-up periods or have used models to estimate healthcare costs. This analysis aims to characterize various outcomes and direct healthcare costs for pulmonary arterial hypertension (PAH) patients being treated with TRE or SLX 1-year into treatment. METHODS: A retrospective analysis was completed using the IBM® MarketScan® Research Databases from January 2014 to June 2019. Patients were required to have a pulmonary hypertension inpatient or outpatient medical claim identified by International Classification of Disease Codes (ICD-9-CM: 416.0, 416.8, 416.9; ICD-10-CM: I27.0, I27.20, I27.21, I27.29, I27.81, I27.83, I27.89, I27.9) plus a prescription claim for TRE or SLX. The index date was defined as the day of the first claim for TRE or SLX. Patients were ≥18 years old and required to have a PH medical claim in the 6-month pre-index, continuous health insurance enrollment 6 months pre-index and 12 months post-index. Adherence was defined as having a medication possession ratio (MPR) ≥80% and persistence was defined by continuous therapy in the 1-year follow-up period without a medication gap of ≥60 days. RESULTS: 120 patients in the TRE cohort and 155 patients in the SLX cohort met inclusion criteria. Patients were of similar age (TRE: mean [SD] = 57.0 [16.1] vs. SLX: 57.2 [13.5]), similar sex (TRE: 70% female vs. SLX: 77.4%) and had a similar Charlson Comorbidity Index (CCI) score (TRE: mean [SD] 3.5 [2.6] vs. SLX: 3.1 [2.0]). Concomitant PAH therapies received during the pre-index period were generally similar between cohorts, however, more patients on TRE compared to SLX (11.7% vs. 2.6%, p=0.003) transitioned from parenteral PAH treatment. In the 1-year following treatment, adherence and persistence were comparable: adherence was 83% for TRE and 81% for SLX (p=0.567) and persistence was 53% for TRE and 59% for SLX (p=0.373). Among the patients persistent on therapy at 1-year, median (IQR) annual pharmacy costs were $232,071 ($211,039-$256,402) for SLX compared with $107,511 ($45,647-$186,622) for TRE (p<0.01) representing 116% higher median annual pharmacy costs for SLX. A similar proportion within each group switched to parenteral prostacyclin therapy (TRE: 6.7% vs SLX: 5.2%, p=0.794) or inhaled prostacyclin therapy (TRE: 3.3% vs SLX: 3.2%, p=1.0) in the 1-year follow-up period. After adjusting for baseline differences between cohorts, total mean PAH-related healthcare costs (pharmacy + medical) in the 1-year follow-up period were $350,782 ($307,873-$394,849) for SLX compared to $229,564 ($198,791-$264,944) for TRE (p<0.05). CONCLUSIONS: Real-world claims data show similar utilization and outcomes for TRE and SLX in patients with PAH with notable differences in costs in the 1-year following treatment initiation. CLINICAL IMPLICATIONS: Cost differences between TRE and SLX should be considered when selecting oral prostacyclin therapies given the broader economic impact on the U.S. healthcare system as well as potential costs specific to health insurers, pharmacy-benefit managers, employers, and patients. DISCLOSURES: Employee relationship with United Therapeutics Please note: >$100000 by Peter Classi, source=Web Response, value=Salary Consultant relationship with United Therapeutics Please note: 2020-current Added 04/27/2021 by Bonnie Dean, source=Web Response, value=Grant/Research Support Employee relationship with United Therapeutics Please note: 2017 to Present Added 04/27/2021 by Alex DeRuiter, source=Web Response, value=Salary Employee relationship with Xcenda, LLC Please note: 01/04/2020 Added 04/30/2021 by Henry Lee, source=Web Response, value=Salary Employee relationship with United Therapeutics Corporation Please note: >$100000 by Kellie Morland, source=Web Response, value=Salary Employee relationship with Xcenda LLC Please note: Jan 1, 2020 Added 04/27/2021 by Dana Stafkey-Mailey, source=Web Response, value=UT provided Xcenda Fin Support Employee relationship with United Therapeutics Corporation Please note: 11 Months Added 04/27/2021 by Benjamin Wu, source=Web Response, value=Salary

Reasons for refusing parenteral therapy: a qualitative study of patients with pulmonary arterial hypertension

While parenteral prostacyclin (pPCY) therapy, delivered either subcutaneously or intravenously, is recommended for pulmonary arterial hypertension patients with severe or rapidly developing disease, some patients refuse this treatment. This study aimed to understand, directly from patients with pulmonary arterial hypertension, why pPCY was refused and, in some cases, later accepted. Interviews were conducted with 25 pulmonary arterial hypertension patients who previously refused pPCY therapy (Group A: Refused/Never initiated (n = 9) and Group B: Refused/Initiated (n = 16)). Patients in both groups believed that pPCY could improve their symptoms, slow disease progression, and provide them a greater ability to perform activities. Reasons for refusal included concern over side effects and the perceived limitations of pPCY on daily activities. Group A perceived their decision as a balance between quality of life and prolonging life and most acknowledged they would reconsider pPCY if other treatment options were exhausted. Group B cited they initiated therapy due to a worsening of symptoms, disease progression, to improve quality of life, to be there for their family, or a desire to live. Following initiation, Group B indicated their experience met expectations with reduced symptoms, slowed disease progression, and perception of improved survival; concerns related to pPCY were described as manageable. Given the efficacy of pPCY therapy, clinicians should apply knowledge of these findings in clinical practice. Patients noted improvements to parenteral pump technologies to include smaller size, water resistance, and implantability may increase their acceptance of this modality. Development efforts should focus on technologies that increase the acceptance of pPCY when indicated.

Significance of autoimmune disease in severe pulmonary hypertension complicating extensive pulmonary fibrosis: a prospective cohort study.

The association of autoimmune disease (AI) with transplant-free survival in the setting of severe Group 3 pulmonary hypertension and extensive pulmonary fibrosis remains unclear. We report cases of severe pulmonary hypertension (mean pulmonary artery pressure ≥35 mmHg and right ventricular dysfunction) and extensive pulmonary fibrosis after pulmonary arterial hypertension-specific therapy. We used multivariate regression to determine the clinical variables associated with transplant-free survival. Of 286 screened patients, 55 demonstrated severe pulmonary hypertension and extensive pulmonary fibrosis and were treated with parenteral prostacyclin therapy. The (+)AI subgroup (n = 34), when compared to the (–)AI subgroup (n = 21), was more likely to be female (77% versus 19%) and younger (58.7 ± 12.1 versus 66.0 ± 10.7 years), and revealed lower forced vital capacity (absolute) (1.9 ± 0.7 versus 2.9 ± 1.1 L), higher DLCO (% predicted) (31.1 ± 15.2 versus 23.2 ± 8.0), and increased unadjusted transplant-free survival (1 year (84.6 ± 6.3% versus 45 ± 11.1%)), 3 years (71 ± 8.2% versus 28.6 ± 11.9%), and 5 years (47.6 ± 9.6% versus 6.4 ± 8.2%); (p = 0.01)). Transplant-free survival was unchanged after adjusting for age and gender. The pulmonary hemodynamic profiles improved after parenteral prostacyclin therapy, independent of AI status. The baseline variables associated with mortality included age at pulmonary hypertension diagnosis (heart rate (HR) 1.23 (confidence interval (CI) 1.03–1.47); p = 0.02) and presence of AI (HR 0.26 (confidence interval (CI) 0.10–0.70); p < 0.01). Gas exchange was not adversely affected by parenteral prostacyclin therapy. In the setting of severe Group 3 pulmonary hypertension and extensive pulmonary fibrosis treated with pulmonary arterial hypertension-specific therapy, AI is independently associated with increased transplant-free survival. Pulmonary hypertension/pulmonary fibrosis associated with AI should be considered in future clinical trials of pulmonary arterial hypertension-specific therapy in Group 3 pulmonary hypertension.

Effects of Parenteral Prostacyclin Therapy on Echocardiographic Variables

<h3>Purpose</h3> To evaluate the effects of treating patients with pulmonary arterial hypertension (PAH) with parenteral prostacyclin (IV/SC PGI₂) therapy on echocardiographic parameters. <h3>Methods</h3> We retrospectively assessed echocardiograms of patients diagnosed with PAH by right heart catherization between 2007 and 2020. Patients were included if they had group 1 PAH with a baseline echocardiogram performed 0 - 12 months prior to starting PGI₂ therapy and follow up echocardiogram performed 3 - 18 months post therapy. Comparison between the two studies was done using paired Student t-tests or Wilcoxon signed rank tests, and categorical variables were reported as percentages. <h3>Results</h3> Out of 166 patients with PAH, 122 met study criteria. Mean age was 47 ± 13, 79% were female and IPAH/HPAH (52%) and CTD-PAH (32%) were the most common diagnoses. At baseline, severe right heart abnormalities were seen. Mean RVSP was 83 ± 21, and most patients had a moderately (33%) or severely (43%) dilated RA and a moderately (32%) or severely (40%) dilated RV. Echocardiogram was performed a mean 202 ± 105 days after IV/SC PGI2 therapy was initiated. Significant improvement in most echocardiographic parameters was seen, as shown in table 1. This included improvements in RVSP, RV size, RV function and tricuspid regurgitation severity. Of note, individuals with severely diminished RV function went down from 40% to 23% (p < 0.001), and patients with a severely dilated RV decreased from 55% to 23% (p < 0.001). Notably, however, there was no significant change in RA size, and while only 34% patients had a pericardial effusion at baseline, this increased to 44% (p = 0.047) at follow-up. In addition to the RV changes, LA size (p = 0.024) and LV diastolic diameter (p < 0.001) both increased. <h3>Conclusion</h3> Given the significant changes in key echocardiographic variables after prostacyclin therapy and the non-invasive nature of these studies, echocardiograms may be useful in monitoring patient responses to prostacyclin therapies.

PREVALENCE AND OUTCOMES OF INHALED, ORAL, AND PARENTERAL PROSTACYCLIN THERAPY IN PULMONARY HYPERTENSION CLINIC PATIENTS: A RETROSPECTIVE COHORT STUDY

SESSION TITLE: Pulmonary Vascular Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Prostacyclin therapy has become a standard of current management for patients with severe pulmonary arterial hypertension (PAH). CurrentlY therapy may be administered via inhaled, oral, and parenteral routes, however there use is often reserved for patients with severe disease. This study aimed to assess the prevalence and effect via hemodynamic evaluation and functional outcome measurements of inhaled, oral, and parenteral prostacyclin therapy among pulmonary hypertension clinic patients. METHODS: This was a retrospective cohort study of pulmonary hypertension (PH) clinic patients at Keck Medical Center. Patients were studied from time of initial clinic visit and most recent follow up. Data ranged from 2011 to 2020. Patient demographics, hemodynamics via right heart catheterization (RHC), transthoracic echocardiography findings (TTE), and functional capacity via six-minute walk testing (6MWT) were collected. Patients were then separated by presence of prostacyclin therapy and route of administration if present. RESULTS: Data was collected on 473 PH patients, 298 of which had complete therapy data and were included in the final analysis. WHO group 1 PAH patients comprised 72% (n = 214) of all patients. The composition of prostacyclin therapy was as follows 152 (51%) no prostacyclin therapy (NP), 29 (9.7%) inhaled prostacyclin therapy (IP), 25 (8.3%) oral prostacyclin therapy (OP), 85 (28.5%) parenteral prostacyclin therapy (PP), and 7 (2.3%) combination therapy. Percentage of patients in each group with PAH was as follows NP (58.6%), IP (75.9%), OP (80%), PP (90.6%), and combination (85.7%). RHC hemodynamics revealed a significant relationship between increasing pulmonary artery pressures and pulmonary vascular resistance (PVR) and therapy in order from NP to IP to OP to PP at initial and follow up visit. TTE findings showed a significant relationship between increasing right ventricular (RV) dilation, RV dysfunction, RVSP, presence of pericardial effusion, and prostacyclin therapy from NP to IP to OP to PP. 6MWT revealed the PP group had the furthest distance walked and had an increase between at follow up while the IP group had the shortest 6MWT distance and greatest reduction in average 6MWT distance at follow up. CONCLUSIONS: The cohort of patients between types of therapy differed significantly in baseline characteristics and outcomes on cardiopulmonary hemodynamics and functional status. The PP group compared to IP and OP were shown to have more severe pulmonary hypertension. Despite that, they had greater 6MWT distances and even improved values from initial to follow up testing. The increase in distance adds to the body of literature suggesting the benefit of parenteral prostacyclin long term in comparison to other modes of drug delivery. CLINICAL IMPLICATIONS: This study may contribute to identifying subsets of patients with pulmonary hypertension who would benefit from prostacyclin therapy. DISCLOSURES: No relevant relationships by Tiffany Chang, source=Web Response No relevant relationships by Lucas Cruz, source=Web Response No relevant relationships by Jared Geibig, source=Web Response No relevant relationships by Moses Koo, source=Web Response No relevant relationships by Ashil Panchal, source=Web Response Speaker/Speaker's Bureau relationship with Actelion, United therapeutic, and Bayer Please note: $20001 - $100000 Added 05/30/2020 by Bassam Yaghmour, source=Web Response, value=Honoraria

BLOODSHED TREATED SUCCESSFULLY IN A HOUSE OF VILLAINS: A CHALLENGING AND UNUSUAL CASE OF HEMOPTYSIS IN A PATIENT WITH CONNECTIVE TISSUE DISEASE- PULMONARY ARTERIAL HYPERTENSION

SESSION TITLE: Medical Student/Resident Chest Infections Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Pulmonary arterial hypertension (PAH) is a progressive disease caused by a remodeling of precapillary arterioles that leads to a progressive increase in pulmonary vascular resistance and right ventricular failure. PAH can complicate any connective tissue disease, most frequently SSc as discussed above, but also SLE, MCTD, RA, or other diseases such as Sjogren’s syndrome (SS) and dermatomysositis with often a poor prognosis. Our case illustrates a case of Hemoptysis under uniquely complex circumstances. CASE PRESENTATION: 53-year-old Hispanic female initially presented with features of severe Acute right heart failure, cardiogenic shock and Hypoxemia. Pulmonary arterial hypertension (PAH) diagnosis was made and was stabilized on emergent parenteral prostacyclin therapy. We also found connective tissue disease (CTD) with Sjogren’s features. She had history of recurrent Venous thromboembolism (VTE) and was on rivaroxaban. PAH therapy - SQ Treprostinil (@ 60ng/kg/min) + tadalafil 40mg qd. A few months later, she developed (CNPA). She responded well to voriconazole with clinical & radiographic improvement. A significant cutaneous allergic reaction to voriconazole led to its cessation and substitution with posaconazole. She presented with large volume hemoptysis with preceding minor episodes for several days. She was hemodynamically stable with no constitutional symptoms. CT chest revealed a stable appearing right upper lobe pulmonary mass measuring 5.5 x 3.0 cm. BNP was 67. Anticoagulation was held and an IVC filter was placed emergently. Bronchoscopy revealed necrotic debris, tan purulent mucous, and blood in the anterior segment of the right upper lobe. Interventional radiology performed bronchial and subclavian angiography with chemoembolization (small branch of the right subclavian artery & the distal portion of the right bronchial artery) of the Aspergilloma. Anticoagulation was resumed after with no further episodes of hemoptysis and she was successfully discharged. DISCUSSION: In a review of patients with SS & PAH, the mean age at diagnosis of PAH was 50 and all female with severe functional class (FC III and IV) and hemodynamic impairment (1), strikingly similar to our case. Survival rate was low (66% at 3 years) as standard therapy of PAH was typically ineffective despite an initial improvement. However, Significant clinical improvement was noted in our patient with Parenteral prostacyclin therapy and PDE5 inhibitors. CONCLUSIONS: This case illustrates a complex unique clinical situation that was challenging – Hemoptysis from CNPA with a background of the following active diagnoses: PAH, CTD (Sjogren’s features), Recurrent VTE. Chemoembolization of feeding arteries + IVC filter placement + temporary cessation of anticoagulation was used with a successful outcome. Reference #1: Sato T, Hatano M, Iwasaki Y, et al. Prevalence of primary Sjögren's syndrome in patients undergoing evaluation for pulmonary arterial hypertension. PLoS One. 2018;13(5):e0197297. Published 2018 May 15. doi:10.1371/journal.pone.0197297 DISCLOSURES: Clinical Research - PI relationship with United Therapeutics Please note: 3 years Added 05/08/2020 by Vijay Balasubramanian, source=Web Response, value=Grant/Research Support Speaker relationship with Bayer Please note: 3 years Added 05/08/2020 by Vijay Balasubramanian, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: $1001 - $5000 Added 05/08/2020 by Vijay Balasubramanian, source=Web Response, value=Honoraria No relevant relationships by Eric Reid, source=Web Response No relevant relationships by James Yang, source=Web Response

Experience in Transitioning From Parenteral Prostacyclins to Selexipag in Pulmonary Arterial Hypertension.

Parenteral prostacyclin therapies remain first-line therapy for patients with pulmonary arterial hypertension (PAH) with class IV symptoms. In selected patients who have been clinically stabilized, switching to selexipag, a chemically distinct prostacyclin receptor agonist, may alleviate risks associated with long-term parenteral therapy. We report our experience with transition of patients from parenteral prostacyclin therapy to selexipag. From January 2016 to July 2017, patients with PAH at the Duke University Pulmonary Vascular Disease Center with functional class II symptoms on stable parenteral prostacyclin therapy were offered the opportunity to transition to selexipag. A standardized protocol was developed to guide titration of therapies. Patients underwent pre- and post-transition assessments of hemodynamics, echocardiography, laboratory biomarkers, and functional status. We studied 14 patients with PAH (11 women; median age 53 years) in total. Overall, 13 patients tolerated the switch to selexipag and remained on the drug at study completion, and 1 patient passed away due to progressive liver failure. Surrogate markers including NT-proBNP, 6MWD, RV function, and TAPSE, and right heart catheterization hemodynamics were similar before and after transition. The transition from parenteral prostanoid therapy to oral selexipag was overall well-tolerated in patients with stable PAH and functional class II symptoms. Finally, doses of selexipag up to 3200 μg twice daily were well-tolerated in patients who had been treated with prior parenteral prostacyclins.

Sarcoidosis Associated Pulmonary Hypertension: Correlation of Cascular Morphologic Changes with Hemodynamic Data in Explanted Lungs

Purpose Sarcoidosis associated pulmonary hypertension (PH) is classified as WHO Group V according to the 2018 WHO classification system. Previous case series have demonstrated efficacy of pulmonary vasodilators in treating severe PH in sarcoidosis. We present a series of patients with sarcoidosis associated PH and describe correlation between the pre-transplant hemodynamic data from a right heart catheterization (RHC) and vascular morphologic changes in the native explanted lungs. Methods Patients with sarcoidosis who underwent lung transplantation at Loyola University Medical Center were analyzed from 2014-2018. We collected demographic data, RHC data, NYHA functional class data, and echocardiogram. Pathology was reviewed to assess for presence and severity of fibrosis, presence or absence of granulomas in lung parenchyma and lymph nodes, and vascular morphologic changes using Heath Edwards PH classification. We evaluated PH changes in arterioles, muscular arteries of 1mm and 3mm caliber, and elastic arteries. These findings were correlated to RHC data. Results Seven patients who had a RHC prior to lung transplantation were identified and had a mean pulmonary artery pressure greater than 25 mmHg. All of the patients had well-formed granulomas except two cases that showed ill formed granulomas. 5 of 7 cases had lymph nodes involved and 5 of 7 had fibrosis. Medial hypertrophy of 1 and 3mm arteries was observed in all cases. 3 of 4 patients with severe PH (NYHA Class IV) and RV dysfunction on echocardiogram were on parenteral prostacyclin therapy at the time of transplant and had grade 3 changes in the 1 mm arteries and grade 2 changes in the 3 mm arteries. Only 2 of 7 cases showed arteriolar changes, which correlated with higher pressures. No plexiform lesions were seen in any of the patients. Conclusion In our series of sarcoidosis patients with PH who underwent lung transplant or transplantation, vascular morphologic changes at the level of the 1 mm and arterioles correlated with the presence of severe PH (NYHA Class IV) and RV dysfunction on echocardiogram. These patients lack the plexiform lesions typically seen in idiopathic pulmonary arterial hypertension. Our study may identify a subset of sarcoid patients who have significant vascular remodeling and possibly explains the recently observed favorable response to vasodilator therapy.

Pulmonary Edema Following Initiation of Parenteral Prostacyclin Therapy for Pulmonary Arterial Hypertension: A Retrospective Study

Pulmonary edema may complicate the use of pulmonary arterial hypertension (PAH)-targeted therapies. We aimed to determine the proportion of patients who develop pulmonary edema after initiation of parenteral prostacyclin therapy, to identify its risk factors, and to assess its implications for hospital length of stay and mortality. A retrospective cohort study of patients with PAH at the initiation of parenteral prostacyclin between 1997 and 2015 enrolled in the Cleveland Clinic PAH registry. Pulmonary edema was defined as at least one symptom or clinical sign and radiographic evidence of pulmonary edema.We determined patient characteristics predictive of pulmonary edema as well as the association between pulmonary edema and hospital length of stay (LOS) and 6-month mortality. One hundred and fifty-five patients were included (median age, 51 years; female, 72%; white, 85%; idiopathic, 64%; and connective tissue disease [CTD], 23%). Pulmonary edema developed in 33 of 155 patients (21%). Independent predictors of pulmonary edema were high right atrial pressure (RAP), CTD etiology, and the presence of three or more risk factors for left heart disease (LHD). Pulmonary edema was associated with a 4.5-day increase in hospital LOS (95%CI, 1.4-7.5days; P< .001) and a 4-fold increase in 6-month mortality (OR, 4.3; 95%CI, 1.28-14.36; P= .031). Pulmonary edema occurred in 21%of patients with PAH initiated on parenteral prostacyclin. Three or more risk factors for LHD, CTD-PAH, and a high baseline RAP were independent predictors of pulmonary edema. Pulmonary edema was associated with a prolonged hospital LOS and increased 6-month mortality.

Clinical and genetic associations with prostacyclin response in pulmonary arterial hypertension.

Parenteral prostacyclin therapy is the most efficacious pharmacologic treatment for pulmonary arterial hypertension (PAH), but clinical response is variable. We sought to identify clinical, hemodynamic, and genetic associations with response to prostacyclin therapy. We performed a retrospective analysis of patients within a de-identified electronic health record and associated DNA biobank. Patients with PAH and a right heart catheterization (RHC) in the six months before initiation of a parenteral prostacyclin were included. Responders were defined a priori by attainment of World Health Organization (WHO) functional class (FC) 2 or better at the time of repeat RHC within two years. We performed exploratory analyses to identify genomic associations with prostacyclin response. Of 129 patients identified, 54 met our criteria for “responders.” These patients were younger, more likely to be male, and were less likely to have connective tissue disease-related PAH. At follow-up, responders had improved hemodynamics, 6-min walk distance, and long-term survival. Baseline PA oxygen saturation (hazard ratio [HR] 0.568 [0.34–0.95]) and follow-up FC (HR = 2.57 [1.22–5.43]) were associated with survival. Prostacyclin responders were enriched in alleles related to cell development and circulatory system development and pathways related to aldosterone metabolism, cAMP signaling, and vascular smooth muscle contraction (P < 0.001). Age at treatment initiation, WHO FC at short-term follow-up, and PA O2% are associated with survival in patients with PAH exposed to parenteral prostacyclins. Exploratory genetic analysis yielded associations in biologically relevant pathways in the pathogenesis of PAH.

Use of subcutaneous treprostinil in pediatric pulmonary arterial hypertension-Bridge-to-transplant or long-term treatment?

PAH is a progressive life-threatening disease in children. While parenteral prostacyclin therapy improves survival in patients with severe PAH, central line-related complications are common. Our aim was to assess the efficacy, safety, and tolerability of subcutaneous treprostinil treatment in pediatric PAH patients. Eight patients were treated with subcutaneous treprostinil at the Pediatric Heart Center Budapest. Indications for subcutaneous treprostinil therapy were clinical worsening and/or echocardiographic progression or switch from intravenous to subcutaneous therapy. Following treprostinil initiation, clinical status improved or did not change in four of eight patients. Two patients were lost early during treprostinil therapy, parenteral treprostinil as a rescue therapy being insufficient in these cases. The final dose in long-term treated patients was between 60 and 100ng/kg/min. Aside from thrombocytopenia, other severe side effects were not observed. Potts shunt was performed as palliative treatment in two cases. Three patients had successful lung transplantation, and one died while on the waiting list. Long-term subcutaneous treprostinil could be a safe and well-tolerated therapy in children with severe PAH even at higher doses. It may serve as an alternative to intravenous prostacyclin treatment allowing to avoid the potential complications of permanent central line placement.

Incidence of Pulmonary Edema After Initiation of Parenteral Prostacyclin Therapy for Group I Pulmonary Arterial Hypertension

SESSION TITLE: Pulmonary Hypertension - Advances in Management and Therapy SESSION TYPE: Original Investigation Slide PRESENTED ON: Tuesday, October 31, 2017 at 02:45 PM - 04:15 PM PURPOSE: To determine the incidence of pulmonary edema after initiation of parenteral prostacyclin therapy in patients with Group I PAH without suspicion of pulmonary veno-occlusive disease (PVOD) METHODS: A retrospective cohort study of Group I PAH patients without suspicion of PVOD treated with intravenous prostacyclin therapy at the Cleveland Clinic. We determined the incidence of pulmonary edema after initiation of prostacyclin therapy. New onset pulmonary edema was defined as the presence of at least one symptom of pulmonary congestion (worsening dyspnea, orthopnea) and at least one sign of pulmonary edema (new or worsening rales on pulmonary examination or signs of new or worsening pulmonary congestion on chest radiograph). Chest radiograph signs of pulmonary congestion were defined as at least one of the following: Kerley B lines, interstitial infiltrates, vascular cephalization, alveolar infiltrates or pleural effusions. We also analyzed the association between pulmonary edema and hospital LOS, as well as mortality. RESULTS: A total of 155 patients were included in the study. Median age was 50 years (IQR 38-57), females 127 (82%), Caucasian 132 (85%), etiology was predominantly idiopathic PAH 98 (63%), followed by CTD-PAH 36 (23%). Median left ventricular ejection fraction was 55% (IQR 55-60). On right heart catheterization median PAP was 54 (IQR 47-64), median PCWP 12 (IQR 8-16), median RAP 10 (IQR 5-16), median CI 1.9 (IQR 1.6-2.5) and median DLCO 58% (IQR 40-73). The predominant prostacyclin analogue used was IV epoprostenol in 134 (86%), followed by IV treprostinil in 18 (11.6%) and SQ treprostinil in 3 (2%). Median prostacyclin initiation dose of epoprostenol was 2ng/kg/min (IQR 2-3) and for treprostinil was 2ng/kg/min (IQR 1.25-3.25). Median hospital LOS was 6 days (IQR 4-8). Pulmonary edema occurred in 33 (21%) of patients after initiation of prostacyclin therapy. Median duration to onset of pulmonary edema was 2 days (IQR 1-4). 16 (48%) patients required intravenous diuretic therapy, 8 (24%) required de-escalation/discontinuation of prostacyclin therapy. Two patients required invasive mechanical ventilation. The development of pulmonary edema was associated with a longer hospital LOS with mean increase in 2.2 days, (95% CI 1.0- 3.4, p< 0.001) and increased 6-month mortality (OR 4.3, 95% CI 1.3 - 14.8, p<0.05). CONCLUSIONS: Pulmonary edema occurred in 21% of patients with group 1 PAH without suspicion of PVOD after the initiation of parenteral prostacyclin therapy. The development of pulmonary edema was associated with prolonged hospital LOS and increased 6-month mortality. CLINICAL IMPLICATIONS: Pulmonary edema occurs in 1 in 5 PAH patients treated with parenteral prostacyclin therapy. This is associated with worse outcomes and is in line with recently emerging evidence pointing at a high prevalence of microscopic vein involvement in PAH. DISCLOSURE: The following authors have nothing to disclose: Nauman Khan, Rizwan Khan, Raed Dweik, Gustavo Heresi No Product/Research Disclosure Information

Transition From Subcutaneous or Inhaled Treprostinil to Oral Treprostinil at Home in Patients With Pulmonary Arterial Hypertension: A Retrospective Case Series

Pulmonary arterial hypertension (PAH) is a progressive condition that can lead to right ventricular failure and death. Treprostinil is a prostacyclin analogue that has proven clinical efficacy in patients with PAH. Difficulties in the administration of inhaled and parenteral prostacyclins led to the development of extended-release treprostinil diolamine for oral use. Limited data exist on the transition to oral treprostinil. The purpose of this case series is to describe the transition from subcutaneous or inhaled treprostinil to oral treprostinil in the outpatient setting. With the current availability of oral prostacyclins and prostacyclins analogues, most transitions to oral therapy are done in the hospital setting resulting in increased cost and risk of hospital-acquired infections. Four patients on background phosphodiesterase type 5 therapy with baseline World Health Organization functional class (WHO FC) II PAH were transitioned at home. Three of the 4 patients were safely transitioned as outpatients and maintained WHO FC II status at 10 and 12 months. The fourth patient had worsening right heart failure and was admitted within 2 months of the transition and started back on parenteral prostacyclin therapy. The 6-minute walk distance (6MWD) increased in patients transitioning from inhaled therapy and decreased in the patient transitioning from subcutaneous therapy. The most common adverse event was nausea.