Prostacyclin Therapy Research Articles

Severe bronchospasm and acute respiratory failure associated with inhaled prostacyclin therapy

AbstractProstacyclin therapy is a mainstay of the management of pulmonary arterial hypertension (PAH). Inhaled prostacyclins present safe and effective options for the management of PAH that limit systemic side effects. We describe the first reported case of life‐threatening bronchospasm and acute respiratory failure associated with inhaled prostacyclin administration.

Severe pulmonary hypertension-interstitial lung disease presenting as right ventricular failure: stabilisation with intravenous prostacyclin and maintenance with inhaled prostacyclin.

Pulmonary hypertension (PH) leads to increased morbidity and mortality in interstitial lung disease (ILD). While the INCREASE trial highlighted the use of inhaled prostacyclin in PH-ILD patients, such therapy may be inadequate when right ventricular failure (RVF) is also present. In this study, we report the use of intravenous prostacyclin in three PH-ILD patients to stabilise right ventricular (RV) function, with a subsequent transition to maintenance therapy with inhaled prostacyclin. We evaluated three consecutive PH-ILD patients with RVF. RV afterload and pulmonary vascular resistance (PVR) were treated with intravenous prostacyclin during the induction phase of the therapy. Patients transitioned from intravenous prostacyclin to the maintenance phase of the treatment with inhaled prostacyclin once three transition criteria were met: cardiac index (CI) >2 L·min-1·m-2, PVR <7 Wood units (WU) and tricuspid annular plane systolic excursion (TAPSE) change >1 mm or TAPSE >1.6 cm. Pre-treatment parameters for the three patients were a mean PVR of 14.3 WU, a mean Fick CI of 1.8 L·min-1·m-2 and a mean TAPSE of 1.4 cm. The average intravenous prostacyclin dose at the time of transition to maintenance therapy was 20.7 ng·kg-1·m-2 of treprostinil. At 3-months follow-up, the mean PVR was 6.3 WU, Fick CI 2.2 L·min-1·m-2 and TAPSE 1.7 cm. This case series of three PH-ILD patients with RVF introduces the concept of an initial intravenous prostacyclin induction phase, followed by a transition to maintenance therapy with inhaled prostacyclin. Further development of this treatment algorithm with a refinement of the transition criteria, potential testing in a clinical trial and a longer-term follow-up period is warranted to improve the outcomes of advanced PH-ILD patients with concomitant RVF.

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

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.

Association Between Early Prostacyclin Therapy and Extracorporeal Life Support Use in Patients With Congenital Diaphragmatic Hernia

Prostacyclin (PGI2) is a therapeutic option to treat congenital diaphragmatic hernia (CDH)-associated pulmonary hypertension in neonates. Its use may decrease the need for extracorporeal life support (ECLS). To evaluate the association of early PGI2 therapy with ECLS use and outcomes among patients with CDH. This was a cohort study from the CDH Study Group (CDHSG) registry of patients born from January 2007 to December 2019. Patients were from 88 different tertiary pediatric referral centers worldwide that contributed data to the CDHSG. Patients were included in the study if they were admitted within the first week of life. Propensity score matching was performed using estimated gestational age, birth weight, transfer status, 1-minute and 5-minute Apgar scores, highest and lowest partial pressure of arterial carbon dioxide in the first 24 hours of life, and degree of pulmonary hypertension as covariates to generate a matched cohort of exposed and unexposed patients. Data were analyzed from January 2021 to December 2022. Early PGI2 therapy was defined as initiation of PGI2 within the first week of life. Patients who received ECLS were included in the early PGI2 group if PGI2 was started prior to ECLS. The primary outcome of the study was the proportion of patients receiving ECLS in the exposed and unexposed groups. Of 6227 patients who met inclusion criteria (mean [SD] gestational age, 37.4 [2.36] weeks; 2618 [42%] female), 206 (3.3%) received early PGI2 therapy. ECLS was used in 46 of 206 patients who received PGI2 (22.2%) and 1682 of 6021 who did not (27.9%). After propensity score matching, there were 147 patients in the treatment and control groups. Thirty-four patients who received PGI2 (23.3%) and 63 who did not (42.9%) received ECLS. Those who received PGI2 were less likely to receive ECLS (adjusted odds ratio, 0.39; 95% CI, 0.22-0.68) and had shorter mean (SD) duration of ECLS (8.6 [3.73] days vs 12.6 [6.61] days; P < .001), although there was no significant difference in in-hospital mortality. In this study, there was decreased use of ECLS and decreased ECLS duration among patients with CDH who started PGI2 therapy during the first week of life. These results identify a potential advantage of early prostacyclin therapy in this population.

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.

Failure to tolerate continuous subcutaneous treprostinil in pediatric pulmonary hypertension patients.

Continuous subcutaneous (SubQ) treprostinil is an effective therapy for pediatric patients diagnosed with pulmonary hypertension (PH). To date, the clinical characteristics and factors associated with failure to tolerate this therapy have not been described. The purpose was to describe patient-reported factors contributing to SubQ treprostinil intolerance in pediatric patients with PH. A retrospective descriptive study was performed at 11 participating sites in the United States and Canada for patients younger than 21 years of age diagnosed with PH who failed treatment to tolerate SubQ treprostinil between January 1, 2009, and December 31, 2019. All data were summarized using descriptive statistics. Forty-one patients met the inclusion criteria. The average age at SQ treprostinil initiation, and length of treatment, was 8.6 years and 22.6 months, respectively. The average maximum dose, concentration, and rate were 95.8 ng/kg/min, 6.06 mg/mL, and 0.040 mL/h, respectively. The reasons for failure to tolerate SubQ treprostinil included intractable site pain (73.2%), frequent site changes (56.1%), severe site reactions (53.7%), infections (26.8%), and noncompliance/depression/anxiety (17.1%). Thirty-nine (95.1%) patients transitioned to a prostacyclin therapy with 23 patients transitioning to intravenous prostacyclin, 5 to inhaled prostacyclin, 5 to oral prostacyclin, and 7 to a prostacyclin receptor agonist. A subset of pediatric PH patients failed to tolerate SubQ treprostinil infusions despite advances in SubQ site maintenance and pain management strategies. Intractable site pain, frequent SubQ site changes, and severe localized skin reactions were the most common reasons for failure.

Inhaled prostacyclin therapy in the acute respiratory distress syndrome: a randomized controlled multicenter trial

BackgroundAcute respiratory distress syndrome (ARDS) results in significant hypoxia, and ARDS is the central pathology of COVID-19. Inhaled prostacyclin has been proposed as a therapy for ARDS, but data regarding its role in this syndrome are unavailable. Therefore, we investigated whether inhaled prostacyclin would affect the oxygenation and survival of patients suffering from ARDS.MethodsWe performed a prospective randomized controlled single-blind multicenter trial across Germany. The trial was conducted from March 2019 with final follow-up on 12th of August 2021. Patients with moderate to severe ARDS were included and randomized to receive either inhaled prostacyclin (3 times/day for 5 days) or sodium chloride (Placebo). The primary outcome was the oxygenation index in the intervention and control groups on Day 5 of therapy. Secondary outcomes were mortality, secondary organ failure, disease severity and adverse events.ResultsOf 707 patients approached 150 patients were randomized to receive inhaled prostacyclin (n = 73) or sodium chloride (n = 77). Data from 144 patients were analyzed. The baseline PaO2/FiO2 ratio did not differ between groups. The primary analysis of the study was negative, and prostacyclin improved oxygenation by 20 mmHg more than Placebo (p = 0.17). Secondary analysis showed that the oxygenation was significantly improved in patients with ARDS who were COVID-19-positive (34 mmHg, p = 0.04). Mortality did not differ between groups. Secondary organ failure and adverse events were similar in the intervention and control groups.ConclusionsThe primary result of our study was negative. Our data suggest that inhaled prostacyclin might be beneficial treatment in patients with COVID-19 induced ARDS.Trial registration: The study was approved by the Institutional Review Board of the Research Ethics Committee of the University of Tübingen (899/2018AMG1) and the corresponding ethical review boards of all participating centers. The trial was also approved by the Federal Institute for Drugs and Medical Devices (BfArM, EudraCT No. 2016003168-37) and registered at clinicaltrials.gov (NCT03111212) on April 6th 2017.

PORTOPULMONARY HYPERTENSION PRACTICE PATTERNS AFTER LIVER TRANSPLANTATION

PORTOPULMONARY HYPERTENSION PRACTICE PATTERNS AFTER LIVER TRANSPLANTATION

Trends in use of prostacyclin analogs for management of CDH-associated pulmonary hypertension.

Off-label use of prostacyclins to manage congenital diaphragmatic hernia-associated pulmonary hypertension (CDH-PHTN) has been described over recent years, but use is not standardized across institutions. This study aims to describe trends in use of these medications in the CDH Study Group (CDHSG) patients. The CDHSG was queried for all patients born from 2007 to 2019. Records were reviewed to describe the number of patients receiving prostacyclins, the day of life on which the agent was started, start time relative to ECLS, the duration of medication use, and continuation of the medication at the time of discharge. Finally, trends in use by year of birth were evaluated to assess for changes in use over time. There were 6439 patients identified from the registry who were born during the study period. 4372 (68%) patients received medications to treat pulmonary hypertension. Of these, 604 (14%) received a prostacyclin at some point during their care. The median start time for prostacyclins was 7.5days of life (mean 16.9days, SD 32.5days), and the median duration was 12.5days (mean 25.1days, SD 49.1days). Among patients who received prostacyclins, 340 patients required ECLS during care, 53 (15.5%) of whom started the prostacyclin prior to ECLS, and 159 (46.8%) of whom started prostacyclin therapy during their ECLS run. Only a small cohort (26/604, 4.3%) required continuation of the prostacyclin at the time of discharge. The proportion of patients receiving a prostacyclin remained relatively stable over the study period. While the proportion of patients receiving a prostacyclin for management of CDH-PHTN has remained relatively stable over the last 13years, there is significant variation in timing of initiation and duration of use especially in the pre-ECLS period that warrants further investigation to describe optimal use in these patients.

INSPIRE: Safety and tolerability of inhaled Yutrepia (treprostinil) in pulmonary arterial hypertension (PAH).

The INSPIRE trial was a Phase 3, open‐label, multicenter trial (LTI‐301) that enrolled patients with pulmonary arterial hypertension (PAH) ≥ 18 years of age who transitioned to Yutrepia from nebulized treprostinil (Transition) or added Yutrepia to prostacyclin naïve patients on ≤2 nonprostacyclin oral therapies. The objectives of the trial were to evaluate the safety and tolerability of Yutrepia (dry‐powder formulation of treprostinil) in patients with PAH. The primary safety measures were the incidence of adverse events (AEs) and serious AEs. Exploratory efficacy measures were also assessed during the trial. Transition patients initiated Yutrepia at a dose comparable to their nebulized treprostinil dose while prostacyclin naïve patients received 26.5‐mcg QID; up‐titration in 26.5‐mcg increments was permitted for both groups. A total of 121 patients were enrolled, of which 29 patients discontinued from the trial, with the most common reason being AEs. Eighty percent of the Transition group and 96% of the prostacyclin naïve group titrated to a dose ≥79.5 mcg QID at Day 360, respectively, with one patient achieving a dose of 212‐mcg QID. The most common AEs were cough, headache, upper respiratory tract infection, dyspnea, dizziness, throat irritation, diarrhea, chest discomfort, fatigue, and nasopharyngitis. Most of these events were considered treatment‐related though mild to moderate in severity and expected for prostacyclin therapy administered by inhalation. In an evaluation of exploratory efficacy measures, patients remained stable or improved over the 1 year of treatment. Yutrepia was found to be a convenient, safe, and well‐tolerated inhaled prostacyclin treatment option for PAH patients.

MP36-19 PROSTACYCLIN (TREPROSTINIL) THERAPY IMPROVES RENAL HEMODYNAMICS DURING RAT RENAL ISCHEMIA-REPERFUSION INJURY

You have accessJournal of UrologyCME1 May 2022MP36-19 PROSTACYCLIN (TREPROSTINIL) THERAPY IMPROVES RENAL HEMODYNAMICS DURING RAT RENAL ISCHEMIA-REPERFUSION INJURY Frances Kazal, Meiwen Ding, Dicken Ko, Reginald Gohh, and Nisanne Ghonem Frances KazalFrances Kazal More articles by this author , Meiwen DingMeiwen Ding More articles by this author , Dicken KoDicken Ko More articles by this author , Reginald GohhReginald Gohh More articles by this author , and Nisanne GhonemNisanne Ghonem More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002590.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Renal ischemia-reperfusion injury (IRI) is a crucial factor causing acute kidney injury (AKI). To date, no pharmacological treatments are available for the prevention of I/R-induced renal injury. Here, we investigate the renal hemodynamics and reno-protective effects of the prostacyclin analog, treprostinil, against renal IRI in vivo. METHODS: Male Sprague Dawley rats were subjected to bilateral renal ischemia (45 minutes) followed by reperfusion (1–48 hour). Treprostinil (100 ng/kg/min) was administered subcutaneously either (A) at the time of ischemia (IRI-immT) or (B) approximately 18-24 hours before renal IRI (IRI-preT). RESULTS: Serum and urine creatinine were elevated at 24 hours post-reperfusion in the IRI group vs. sham (P <0.001), which both the IRI-immT and IRI-preT reduced the peak of serum creatinine at 24 hours after renal IRI (P <0.001). Also, medullary and cortical renal blood flow (RBF) were significantly reduced in the IRI group vs. sham (P <0.001), whereas the IRI-immT (P <0.01) and IRI-preT (P <0.05) groups improved RBF at 90 minutes post-reperfusion and maintained throughout 120 minutes. In parallel, animals in the IRI injury group experienced a decreased eGFR, increased urinary sodium (UNa 2+) excretion and proteinuria during the first 24 hours post-reperfusion vs. sham (P <0.01). Meanwhile, treprostinil reduced the UNa 2+ and proteinuria and completely restored the eGRF to baseline by 48 hours post-reperfusion and, compared to the IRI group (P <0.01). CONCLUSIONS: This study demonstrates the efficacy of treprostinil in improving renal hemodynamics and kidney function early post-IRI in a clinically relevant rat model of AKI. Specifically, our data show that treprostinil remarkably increased renal blood flow and GFR, and reduced sodium excretion and proteinuria post-reperfusion. Importantly, these data suggest that treprostinil has the potential to serve as a therapeutic agent to protect the kidney against renal IRI. Source of Funding: Funding support for this project was provided in part by the Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health, which funds the University of Rhode Island Core Lab (P20GM103430). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e605 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Frances Kazal More articles by this author Meiwen Ding More articles by this author Dicken Ko More articles by this author Reginald Gohh More articles by this author Nisanne Ghonem More articles by this author Expand All Advertisement PDF DownloadLoading ...

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.

Right Heart Reverse Remodeling Correlates with NT-proBNP Outcomes Among Pulmonary Arterial Hypertension Patients on Combination Therapy

<h3>Purpose</h3> Combination therapy is the current standard for severe pulmonary arterial hypertension (PAH). Few studies have characterized reverse remodeling achievable with therapy, and in particular, how it correlates with prognostic trends in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. We evaluated the longitudinal impact of PAH combination therapy on echocardiographic right heart parameters and observed how reverse remodeling correlates with a prognostic indicator of treatment response. <h3>Methods</h3> Thirty-two adults (age, 32±9years) with newly diagnosed PAH were initiated on combination therapy and had transthoracic echocardiograms performed prior to, and at least 3 months after, starting therapy. Pre- and follow-up NT-proBNP values were collected and speckle-tracking strain analysis was applied to echocardiogram images. Paired samples t-test was used to evaluate the statistical difference between baseline and follow-up measurements. <h3>Results</h3> After a mean 2.7 years, there was a significant decrease in mean RV basal diameter from 4.6cm to 4.2cm (p=0.03) and mean right atrial area from 23.6cm² to 19.8cm² (p<0.01). RV fractional area change (RVFAC) increased from 21% to 31% (p<0.01) and mean RV free wall strain (RVFWS) improved from -11.4% to -15.8% (p<0.01). Prior to therapy, 63% of patients had elevated NT-proBNP levels (>900pg/mL). By follow-up, there was a greater improvement in RVFAC among patients who maintained or achieved a normal NT-proBNP level with therapy compared to those whose biomarker level increased or remained elevated (+0.10% vs +0.003%, p=0.03). RVFWS improved to a greater extent in the former group compared to the latter, though this did not reach statistical significance (-5.32% vs. -0.86%, p=0.07). Five out of the 6 patients who died during follow-up maintained elevated NT-proBNP levels despite therapy. Half were on aggressive regimens including intravenous prostacyclin therapy. <h3>Conclusion</h3> While combination PAH therapy was associated with improved RV structure and function parameters among our cohort; patients with persistently elevated or deteriorated NT-proBNP levels demonstrated less reverse remodeling and had increased mortality. These findings highlight a need for novel future therapies that target right heart-specific remodeling pathways in high-risk PAH patients.

Prostacyclin for Pulmonary Arterial Hypertension

Prostacyclin for Pulmonary Arterial Hypertension

A Review of Pulmonary Arterial Hypertension Treatment in Extracorporeal Membrane Oxygenation: A Case Series of Adult Patients.

Little data is published describing the use of medications prescribed for pulmonary arterial hypertension (PAH) in patients receiving extracorporeal membrane oxygenation (ECMO). Even though many patients with PAH may require ECMO as a bridge to transplant or recovery, little is reported regarding the use of PAH medications in this setting. This retrospective case series summarizes the clinical experience of 8 patients with PAH receiving ECMO and reviews medication management in the setting of ECMO. Eight PAH patients, 5 of whom were female, ranging in age from 21 to 61 years old, were initiated on ECMO. Veno-arterial (VA) ECMO was used in 4 patients, veno-venous (VV) ECMO and hybrid ECMO configurations in 2 patients respectively. Common indications for ECMO included cardiogenic shock, bridge to transplant, and cardiac arrest. All patients were on intravenous (IV) prostacyclin therapy at baseline. Refractory hypotension was noted in 7 patients of whom 5 patients required downtitration or discontinuation of baseline PAH therapies. Three patients had continuous inhaled epoprostenol added during their time on ECMO. In patients who were decannulated from ECMO, PAH therapies were typically resumed or titrated back to baseline dosages. One patient required no adjustment in PAH therapy while on ECMO. Two patients were not able to be decannulated from ECMO. The treatment of critically ill PAH patients is challenging given a variety of factors that could affect PAH drug concentrations. In particular, PAH patients on prostacyclin analogues placed on VA ECMO appear to have pronounced systemic vasodilation requiring vasopressors which is alleviated by temporarily reducing the intravenous prostacyclin dose. Patients should be closely monitored for potential need for rapid titrations in prostacyclin therapy to maintain hemodynamic stability.

PH Roundtable: Transitions in Pulmonary Hypertension

PH Roundtable: Transitions in Pulmonary Hypertension

Abstract 9677: Therapeutic Improvements in Pulmonary Arterial Hypertension Are Related to Cardiopulmonary Function but Not Skeletal Muscle Oxygen Extraction

Introduction: World Symposium Group 1 pulmonary arterial hypertension (PAH) patients have impaired function from both central oxygen delivery and skeletal muscle oxygen extraction. The effect of PH-directed therapy on skeletal muscle oxygen extraction is unknown. The aim of this study is to determine if therapy associated changes in muscle extraction parallel changes in cardiopulmonary function. Methods: Retrospective analysis was performed on twenty-nine PAH patients (24 female, mean age 54±11.4 years) receiving prostacyclin therapy (18 on monotherapy). Subjects underwent invasive cardiopulmonary exercise testing (iCPET) for treatment response evaluation followed by repeat surveillance iCPET with mean follow-up of 10.4±5.2 months. Skeletal muscle oxygen extraction was quantified by arterio-venous difference indexed to hemoglobin (Ca-vO 2 /Hgb) and systemic oxygen extraction ratio (SER) (Ca-vO 2 /CaO 2 ). Central oxygen delivery (DO 2 ) was calculated as peak cardiac output X CaO2 at peak exercise. Functional capacity was semi-quantified by six-minute walk test (6MWT) distances between assessments (n=20). Subjects were stratified into two groups: those with improvement (n=10) vs unimproved (n=19) in currently accepted ERS/COMPERA score ( Figure ). Results: Improvements in ERS/COMPERA score were related to DO 2 (318.3±273.1 vs -38.3±684.9 mL/min, P=.016 ) and PVR (-4.8±3.0 vs -0.6±3.2 WU, P=.002 ) (Figure A &amp; B). However, there was not a detectible difference between assessments in Ca-vO 2 /hgb (-0.01±0.14 vs 0.00±0.27 mL/g, P=.573 ), SER (-0.01±0.10 vs 0.00±0.20, P=.573 ), or 6MWT (7 improved, 13 unimproved) (77±115 vs 25±104 meters, P=.877 ) ( Figure C &amp; D ). Conclusions: Although PH-directed therapy improves both PVR and oxygen delivery, its effects on skeletal muscle extraction are questionable. Clinicians should consider that oxygen extraction may influence functional capacity when evaluating therapeutic improvement.

Abstract 11614: Investigating Outcomes in Patients with Pulmonary Hypertension Diagnosed with Covid-19 in a Tertiary Pulmonary Hypertension Referral Center

Introduction: Preexisting endothelial dysfunction and effects of selective pulmonary vasodilator therapy are postulated to prevent vascular remodeling and decrease morbidity and mortality in pulmonary arterial hypertension (PAH) patients with COVID-19. However, research on outcomes in PAH patients with COVID-19 is limited. We studied morbidity and mortality from COVID-19 in a tertiary PAH referral center. Methods: Of 596 clinic patients on at least one PAH specific medication, 27 patients were diagnosed with COVID-19 between March 2020 and January 2021. Retrospectively evaluated outcomes included mortality, hospitalization, intensive care unit admission (ICU), mechanical ventilation (MV), extracorporeal membrane oxygenation (ECMO), lung transplant, and hospital readmission within 30 days. Results: Of 27 PAH patients with COVID-19 (mean age=60 years; 74% female; 96% non-Hispanic; 74% White), 15 (56%) were hospitalized, 7 (26%) died, and 1 (4%) underwent ECMO followed by lung transplant. Hospitalized patients, compared to non-hospitalized patients, had higher mean age (64 vs 56 years), number of patients on IV prostacyclin (20% vs 0%), mean REVEAL 2.0 score (8.4 vs 6.5), and moderate-severe RV dysfunction (6, 40% vs 3, 25%). There was no difference in NYHA FC and mean pulmonary arterial pressure (45 mm Hg vs 43.7 mm Hg) between hospitalized and non-hospitalized patients. Complications during hospitalization included worsened hypoxemia (13, 87%), cardiac ischemia (4, 15%), new or worsening arrhythmias (3, 11%), and acute kidney injury (AKI) (6, 22%). Four patients (27%) required ICU admission and MV. Of these, 2 (50%) had new or worsening arrhythmias and all 4 (100%) had AKI. Of 15 patients hospitalized, 5 (19%) were readmitted to the hospital within 30 days. The 7 patients who died during hospitalization, compared to 8 who survived, had increased rates of ICU admission and MV (43% vs 12.5%) and higher REVEAL 2.0 scores (10.1 vs 6.9). Conclusion: COVID-19 in hospitalized PAH patients was associated with high rates of multi-organ complications, mortality, ICU admission, and hospital re-admission. Advanced age, IV prostacyclin therapy, higher REVEAL score, moderate to severe RV dysfunction, and AKI were associated with adverse outcomes.