Sotatercept for Pulmonary Arterial Hypertension in the Inpatient Setting.

Patients with pulmonary arterial hypertension (PAH) who are admitted to the hospital pose a challenge to the multidisciplinary healthcare team due to the complexity of the pathophysiology of their disease state and PAH-specific medication considerations. Pulmonary arterial hypertension is a progressive disease that may lead to death as a result of right ventricular (RV) failure. During acute on chronic RV failure it is critical to decrease the pulmonary vascular resistance with the goal of improving RV function and prognosis; therefore, aggressive PAH-treatment based on disease risk stratification is essential. Pulmonary arterial hypertension treatment for acute on chronic RV failure can be impacted by end-organ damage, hemodynamic instability, drug interactions, and PAH medications dosage and delivery. Sotatercept, a first in class activin signaling inhibitor that works on the bone morphogenetic protein/activin pathway is on track for Food and Drug Administration approval for the treatment of PAH based on results of recent trials in where the medication led to clinical and hemodynamic improvements, even when added to traditional PAH-specific therapies. The purpose of this review is to highlight important considerations when starting or continuing sotatercept in patients admitted to the hospital with PAH.

Impact of body position on hemodynamic measurements during exercise: A tale of two bikes.

The addition of exercise testing during right heart catheterization (RHC) is often required to accurately diagnose causes of exercise intolerance like early pulmonary vascular disease, occult left heart disease, and preload insufficiency. We tested the influence of body position (supine vs. seated) on hemodynamic classification both at rest and during exercise. We enrolled patients with exercise intolerance due to dyspnea who were referred for exercise RHC at the Cleveland Clinic. Patients were randomized (1:1) to exercise in seated or supine position to a goal of 60 W followed by maximal exercise in the alternate position. We analyzed 17 patients aged 60.3 ± 10.9 years, including 13 females. At rest in the sitting position, patients had significantly lower right atrial pressure (RAP), mean pulmonary artery pressure (mPAP), pulmonary artery wedge pressure (PAWP) and cardiac index (CI). In every stage of exercise (20, 40, and 60 W), the RAP, mPAP, and PAWP were lower in the sitting position. Exercise in the sitting position allowed the identification of preload insufficiency in nine patients. Exercise in either position increased the identification of postcapillary pulmonary hypertension (PH). Body position significantly influences hemodynamics at rest and with exercise; however, mPAP/CO and PAWP/CO were not positionally affected. Hemodynamic measurements in the seated position allowed the detection of preload insufficiency, a condition that was predominantly identified as no PH during supine exercise.

Fluid loading during the hemodynamic evaluation of pulmonary hypertension: a cross-sectional study.

Background: Compensated pulmonary hypertension due to left heart disease (PH-LHD) may be difficult to identify based on resting hemodynamics. Fluid challenge is commonly used to unmask occult PH-LHD. We sought to determine the hemodynamic effect of fluid loading and its association with the clinical pretest probability of PH-LHD. Methods: We included consecutive patients evaluated for PH who underwent right heart catheterization (RHC) with fluid challenge at Cleveland Clinic between April 2013 and January 2019. We obtained hemodynamic measurements at rest and after intravenous rapid fluid challenge (500 mL of normal saline). We calculated the pretest probability of PH-LHD based on the 6th World Symposium on PH proceedings. For statistical analyses we used t-test, analysis of variance (ANOVA), Chi-square, paired t-test, Wilcoxon signed-rank test and linear regression as indicated. Results: We included 174 patients with mean ± standard deviation (SD) age of 63.7±13.0 years and 123 (71%) of female sex. Baseline pulmonary artery wedge pressure (PAWP) was 11±5 mmHg, with a PAWP/cardiac output (CO) ratio of 2.1±1.1 Wood units (WU). The absolute increase in PAWP and PAWP/CO was 6.9±3.6 mmHg and 1.06±0.91 WU, respectively. The change in PAWP was inversely associated with baseline PAWP (P<0.001). The PAWP with fluids was >18 mmHg in 81% of the patients with baseline PAWP 13-15 mmHg. We found no strong associations between the change in PAWP, PAWP/CO or right atrial pressure to pulmonary arterial wedge pressure ratio (RAP/PAWP) and the pretest probability of PH-LHD. Conclusions: The absolute change in PAWP, PAWP/CO, or achieving a PAWP >18 mmHg with rapid fluid loading was not robustly associated with the pretest probability of PH-LHD. Patients with PAWP between 13-15 mmHg commonly had a positive fluid challenge, questioning the utility of this intervention in these patients.

Portopulmonary hypertension: A focused review for the internist.

Portopulmonary hypertension, ie, pulmonary arterial hypertension in a patient with portal hypertension, affects transplant eligibility and has a poor prognosis. The pathogenesis remains an area of active research, with various mechanisms proposed. Diagnosing it requires a detailed history, physical examination, laboratory tests, and echocardiographic evaluation, followed by a careful hemodynamic assessment.

Lung ultrasonography derived B-line scores as predictors of left ventricular end-diastolic pressure and pulmonary artery wedge pressure.

BACKGROUND: Non-invasive assessment of elevated left ventricular end-diastolic pressure (LVEDP) and pulmonary artery wedge pressure (PAWP) in patients with heart diseases is challenging. Lung ultrasonography (LUS) is a promising modality for predicting LVEDP and PAWP. METHODS: Fifty-seven stable ambulatory patients who underwent right and left heart catheterization were included. Following the procedures, LUS was performed in twenty-eight ultrasonographic zones, and the correlation between five different LUS derived B-line scores with LVEDP and PAWP was examined. RESULTS: The B-line index correlated with LVEDP and PAWP, with coefficients of 0.45 (p = 0.006) and 0.30 (p = 0.03), respectively. B-line index showed an AUC of 0.76 for identifying LVEDP > 15 mmHg (p = 0.01) and an AUC of 0.73 for identifying PAWP > 15 mmHg (p = 0.008). Overall, scores performances were similar in predicting LVEDP or PAWP > 15 mmHg. A B-line index ≥ 28 was significantly associated with LVEDP > 15 mmHg (OR: 9.97) and PAWP > 15 mmHg (OR: 6.61), adjusted for age and indication for heart catheterization. CONCLUSIONS: LUS derived B-line scores are moderately correlated with PAWP and LVEDP in patients with heart diseases. A B-line index ≥ 28 can be used to predict elevated LVEDP and PAWP with high specificity.

Impact on Pulmonary Hypertension Hemodynamic Classification Based on the Methodology Used to Measure Pulmonary Artery Wedge Pressure and Cardiac Output.

Rationale: Guidelines recommend using end-expiration pulmonary pressure measurements to determine the hemodynamic subgroups in pulmonary hypertension. Pulmonary artery wedge pressure (PAWP) determinations averaged across the respiratory cycle (PAWPav) instead of PAWP at end-expiration (PAWPee) and cardiac output (CO) measured by Fick (COFick) instead of thermodilution (COTD) may affect the hemodynamic classification of pulmonary hypertension. Objectives: To assess the impact on the pulmonary hypertension hemodynamic classification of the use of PAWPee versus PAWPav as well as COFick versus COTD. Methods: This was a single-center retrospective study of consecutive patients (n = 151) who underwent right heart catheterization with COTD, COFick, PAWPee, and PAWPav. A secondary cohort consisted of consecutive patients (n = 71) who had mean pulmonary artery pressure at end-expiration (mPAPee) and mPAP averaged across the respiratory cycle (mPAPav) measured, as well as PAWPee and PAWPav. Results: The PAWPee and PAWPav were 16.8 ± 6.4 and 15.1 ± 6.8 mm Hg, respectively, with a mean difference of 1.7 ± 2.1 mm Hg. The COTD and COFick determinations were 5.0 ± 2.4 and 5.3 ± 2.5 L/min, respectively, with a mean difference of -0.4 ± 1.3 L/min. The hemodynamic group distribution was significantly different when using PAWPee versus PAWPav, when using either COTD or COFick (P < 0.001 for both comparisons), and these results were consistent in our secondary cohort. The pulmonary hypertension hemodynamic group distribution was not significantly different between COTD and COFick when using either PAWPee or PAWPav. Conclusions: The methodology used to measure PAWP, either at end-expiration or averaged across the respiratory cycle, significantly impacts the hemodynamic classification of pulmonary hypertension.

Retrospective on global pulmonary hypertension clinical trials: 1999-2021.

Background: Data are quite sparse on the comprehensive analyses of pulmonary hypertension (PH) clinical trials worldwide. Methods: Information including participating countries (developed or developing), intervention type, trial size, PH categories, sponsorship, study phase, design strategies, and participants' demographic characteristics was extracted from PH trials registered on ClinicalTrials.gov from 1999 to 2021. Results: A total of 203 eligible clinical PH trials were screened, involving 23,402 participants, 67.8% of whom were females. Major clinical trials were designed to test drug interventions (95.6%), sponsored solely by industries in 59.5%, and targeting Group 1 PH patients in 76.3%. A large number of countries participated in PH clinical trials; however, most clinical trials were conducted in developed countries (84.2%). Developing countries were involved in clinical trials with larger sample sizes (P<0.01). Additionally, the differences between developed and developing countries centered on interventions, sponsors, PH groups, and design strategies. Furthermore, developing countries participated in multinational clinical trials with good quality, homogeneity, reliability, and data authenticity. All pediatric participants were diagnosed with Group 1 PH and were only involved in drug intervention trials. Children participated in far fewer clinical trials than adults (P<0.01), and most were enrolled in PH clinical trials in developed countries. Among the entire clinical trial population, younger patients with Group 1 PH had a much higher participation to prevalence ratio (PPR). There was no difference in women's PPRs between developed and developing countries. However, developing countries had higher PPRs for PH Groups I and IV (1.28 vs. 1.22, P<0.01), while developed countries had a lower PPR for Group III (P=0.02). Conclusions: PH is attracting increasing global attention, which is not at the same level of progress in developed and developing countries. Women and children with this disease have unique characteristics and require more attention.

Right ventricle-specific therapies in acute respiratory distress syndrome: a scoping review.

OBJECTIVE: To summarize knowledge and identify gaps in evidence regarding treatment of right ventricular dysfunction (RVD) in acute respiratory distress syndrome (ARDS). DATA SOURCES: We conducted a comprehensive search of MEDLINE, Embase, CINAHL, Web of Science, and the Cochrane Central Register of Controlled Trials. STUDY SELECTION: Studies were included if they reported effects of treatments on right ventricular function, whether or not the intent was to modify right ventricular function. DATA EXTRACTION: Data extraction was performed independently and in duplicate by two authors. Data items included the study design, patient population, type of intervention, comparison group, and RV-specific outcomes. DATA SYNTHESIS: Of 1,430 studies screened, 51 studies reporting on 1,526 patients were included. By frequency, the included studies examined the following interventions: ventilator settings (29.4%), inhaled medications (33.3%), extracorporeal life support (13.7%), intravenous or oral medications (13.7%), and prone positioning (9.8%). The majority of the studies were non-randomized experimental studies (53%), with the next most common being case reports (16%). Only 5.9% of studies were RCTs. In total, 27% of studies were conducted with the goal of modifying RV function. CONCLUSIONS: Given the prevalence of RVD in ARDS and its association with mortality, the dearth of research on this topic is concerning. This review highlights the need for prospective trials aimed at treating RV dysfunction in ARDS.

Pulmonary hypertension due to high cardiac output.

Pulmonary hypertension (PH) is usually associated with a normal or decreased cardiac output (CO). Less commonly, PH can occur in the context of a hyperdynamic circulation, characterized by high CO (>8 L/min) and/or cardiac index ≥4 L/min/m2 in the setting of a decreased systemic vascular resistance. PH due to high CO can occur due to multiple conditions and in general remains understudied. In this review article we describe the pathophysiology, etiology, diagnosis, hemodynamic characteristics, and management of PH in the setting of high CO. It is important to recognize this distinct entity as PH tends to improve with treatment of the underlying etiology and PH specific therapies may worsen the hemodynamic state.

Does veno-arterial carbon dioxide gradient provide an adequate estimation of cardiac index in pulmonary hypertension?

AIMS: Pulmonary hypertension (PH) management is dependent on cardiac output (CO) assessment. The gold standard Fick method for CO and cardiac index (CI) measurement is not widely available. An accessible and reliable method for CO/CI estimation is needed not only in catheterization labs but also in other environments such as the intensive care unit, where pulmonary artery catheters are less likely to be used. We hypothesized that veno-arterial carbon dioxide gradient (PvaCO2) is a reliable surrogate for Fick CI in patients with PH. METHODS AND RESULTS: A single-centre retrospective analysis of patients with PH who underwent direct Fick CI (DFCI) measurement during right heart catheterization. The primary outcome was correlation between PvaCO2 and DFCI. To assess the agreement between central and mixed venous CO2 values, a separate prospective cohort of patients was analysed. Data from 186 patients with all haemodynamic types of PH were analysed. PvaCO2 moderately correlated with Fick CI, R = -0.51 [95% confidence interval (CI): -0.61, -0.39]. A higher PvaCO2 was associated with an increased risk of CI < 2.5 L/min/m2 (odds ratio: 1.88, 95% CI: 1.55, 2.35). Low thermodilution CI with normal veno-arterial carbon dioxide gradient values was associated with a thermodilution underestimation of Fick CI. In the prospective analysis of 32 patients, central venous CO2 overestimated mixed venous values (mean difference 3.3, 95% CI: 2.5, 4.0) and there was poor agreement overall (limits of agreement -1.10, 7.59). CONCLUSION: Veno-arterial carbon dioxide gradient moderately correlates with Fick CI and may be useful to identify patients with low CI. Central and mixed venous CO2 values should not be used interchangeably in PH.

Hemodynamic indices in pulmonary hypertension: a narrative review.

Background and Objective: Pulmonary hypertension (PH) is defined as a mean pulmonary artery pressure (mPAP) >20 mmHg and its presence is associated with worse outcomes. A comprehensive hemodynamic evaluation of the pulmonary circulation is essential for diagnosis, hemodynamic classification, and prognostication. A multitude of indices assess different aspects of the pulmonary circulation but there are no reviews that describe their specific value in PH. Methods: We performed a thorough literature search of relevant articles in English from 1970-2021 using PubMed. Key Content and Findings: In this article, we present both static and dynamic indices used for the hemodynamic assessment of PH. While some of these indices are routinely used in clinical practice, including cardiac index (CI), stroke volume (SV), and pulmonary vascular resistance (PVR); others such as pulmonary artery compliance (PAC), pulmonary effective arterial elastance (Ea), and pulmonary artery pulsatility index (PAPi) are gaining popularity by enhancing the understanding of different aspects of the pulmonary circulation. We described the advantages and pitfalls of various indices, including when to use them in the hemodynamic evaluation of patients with PH. Conclusions: A variety of indices measuring different aspects of the right ventricle (RV)-pulmonary arteries (PA) system provide valuable information in patients with PH. However, it remains important to develop and validate indices that provide a comprehensive hemodynamic evaluation to improve outcomes in patients with PH.

Liver Transplant Outcomes in Patients With Postcapillary Pulmonary Hypertension.

Postcapillary pulmonary hypertension (PH) can be seen in cirrhosis. Research and treatment goals exist for patients with portopulmonary hypertension but not for postcapillary PH. The aim of this study was to investigate outcomes after liver transplant (LT) for patients with postcapillary PH. Methods: This was a retrospective cohort study of 1173 patients who underwent LT at our center between 2010 and 2020. Using a propensity score matched analysis followed by multivariable Cox modeling on matched patients, we compared post-LT survival between patients with and without postcapillary PH. We also compared several post-LT outcomes between patient with different types of PH. Results: Sixty-eight patients had PH, and 50 had postcapillary PH. The median age was 59 y and the sample was 54% male. There was no significant difference in mortality between patients with postcapillary PH and patients without PH (hazard ratio, 1.72; 95% confidence interval, 0.90-3.31; P = 0.10). There was no significant difference in survival between patients with any type of PH and those without PH. There was no significance difference in post-LT survival, acute kidney injury, or pulmonary edema between patients with different types of PH. Patients with postcapillary PH who survived had a higher cardiac output than those who died (11 L/min in patients who lived, as compared with 8 L/min in patients who died; P = 0.03). Conclusions: Postcapillary PH does not appear to convey a negative impact on post-LT survival. A higher cardiac output may be protective against mortality in patients with postcapillary PH.

Hemodynamic Responses to Provocative Maneuvers during Right Heart Catheterization.

Rationale: Current guidelines recognize the utility of provocative maneuvers during right heart catheterization to aid the diagnosis of pulmonary hypertension. Few studies have compared the performance of different provocation maneuvers. Objectives: To assess the hemodynamic correlation among three provocative maneuvers, including their effect on pulmonary hypertension classification. Methods: This prospective trial was conducted between October 2016 and May 2018. Adult patients underwent three provocative maneuvers during right heart catheterization: passive leg raise (PLR), load-targeted supine bicycle exercise, and rapid crystalloid fluid infusion. Patients were classified as follows: no pulmonary hypertension, precapillary pulmonary hypertension, isolated postcapillary pulmonary hypertension, combined pre- and postcapillary pulmonary hypertension, and uncategorized pulmonary hypertension. We assessed the hemodynamic changes associated with each maneuver. We also assessed whether provocative maneuvers led to hemodynamic reclassification of the patient to either postcapillary pulmonary hypertension with provocation or exercise pulmonary hypertension. Results: Eighty-five patients (mean age 62 ± 12 years, 53% women) were included. Correlation between exercise and fluid challenge was moderate to strong (0.49-0.82; P < 0.001) for changes in right atrial pressure, mean pulmonary arterial pressure, pulmonary arterial wedge pressure, and cardiac index from baseline. Correlation between PLR and exercise (0.4-0.65; P < 0.001) and between PLR and fluid challenge (0.45-0.6; P < 0.001) was moderate for changes in right atrial pressure, mean pulmonary arterial pressure, pulmonary arterial wedge pressure, pulmonary vascular resistance, and cardiac index. Hemodynamic correlation between other provocative maneuvers was poor. Depending on provocative maneuver and classification criteria, there was significant variation in the number of patients reclassified as having exercise pulmonary hypertension (3-50%) or postcapillary pulmonary hypertension with provocation (11-48%). Conclusions: Hemodynamic determinations during exercise and fluid challenge showed moderate to strong hemodynamic correlation. Moderate hemodynamic correlation was seen between PLR and exercise or fluid challenge. Although some provocative maneuvers demonstrate good hemodynamic correlation, there is inconsistency when using these maneuvers to identify patients with postcapillary or exercise pulmonary hypertension.

Mechanistic Insights into Tricuspid Regurgitation Secondary to Pulmonary Arterial Hypertension.

The simultaneous presence of pulmonary arterial hypertension (PAH) and secondary tricuspid regurgitation (STR) portends particularly poor outcomes. However, not all patients with PAH develop significant STR, and the mechanisms and clinical implications underlying this phenomenon remain unclear. We sought to describe the functional, anatomic, hemodynamic, and clinical characteristics of patients with PAH with and without STR. Patients diagnosed with PAH between 2007 and 2013 were included. STR, defined by absent primary tricuspid valve disease on transthoracic echocardiogram, was considered significant if ≥ moderate in severity. The characteristics of right-sided chambers and tricuspid valve annuli and leaflets were compared between patients with significant versus nonsignificant STR using a transthoracic echocardiogram, cardiac computed tomography, and right-sided cardiac catheterization. These features were then correlated with the composite outcome of all-cause mortality and PAH hospitalization. Of 88 included patients, 52 had significant STR. No baseline clinical differences, including atrial fibrillation, were observed. Patients with significant STR had worse right ventricular dysfunction (tricuspid annular planar systolic excursion = 1.5 vs 2.1 cm; p = 0.02) and increased right ventricular sphericity (sphericity index = 1.8 vs 2; p = 0.004), with similar annular dimensions/shape, lengths/angles of the mural and septal leaflets, and tenting height. After a median of 54 months, right atrial mean pressure was independently associated with the composite outcome on multivariable analysis (hazard ratio = 1.07, p = 0.02). In conclusion, anatomic and functional alterations in the right ventricle rather than the tricuspid valve are implicated in developing significant STR in PAH. Multimodality imaging provides mechanistic insight, and hemodynamic assessment may offer prognostic guidance in this population.

Impact of Esophageal Pressure Measurement on Pulmonary Hypertension Diagnosis in Patients With Obesity.

BACKGROUND: Elevated intrathoracic pressure could affect pulmonary vascular pressure measurements and influence pulmonary hypertension (PH) diagnosis and classification. Esophageal pressure (Pes) measurement adjusts for the increase in intrathoracic pressure, better reflecting the pulmonary hemodynamics in patients with obesity. RESEARCH QUESTION: In individuals with obesity, what is the impact of adjusting pulmonary hemodynamic determinations for Pes on PH diagnosis and classification? Can Pes be estimated by positional or respiratory hemodynamic changes? STUDY DESIGN AND METHODS: In this prospective cohort study, we included patients with obesity who underwent right heart catheterization and demonstrated elevated pulmonary artery wedge pressure (PAWP; ≥ 12 mm Hg). After placement of an esophageal balloon, we performed pressure determination using an air-filled transducer connected to a regular hemodynamic monitor. We measured pulmonary pressures changes when sitting and the variations during the respiratory cycle. RESULTS: We included 53 patients (mean ± SD age, 59 ± 12 years; mean ± SD BMI, 44.4 ± 10.2 kg/m2). Supine end-expiratory pressures revealed a mean pulmonary artery pressure of > 20 mm Hg in all patients and a PAWP of >15 mm Hg in most patients (n = 50). The Pes adjustment led to a significant decrease in percentage of patients with postcapillary PH (from 60% to 8%) and combined precapillary and postcapillary PH (from 34% to 11%), at the expense of an increase in percentage of patients with no PH (0% to 23%), isolated precapillary PH (2% to 25%), and undifferentiated PH (4% to 34%). INTERPRETATION: Adjusting pulmonary hemodynamics for Pes in patients with obesity leads to a pronounced reduction in the number of patients who receive a diagnosis of postcapillary PH. Measuring Pes should be considered in patients with obesity, particularly those with elevated PAWP.

Effect of pulmonary artery catheter balloon inflation on pulmonary hemodynamics.

Background: Right heart catheterization (RHC), including a pulmonary artery wedge pressure (PAWP) determination, is necessary to categorize the hemodynamic type of pulmonary hypertension (PH). The potential hemodynamic implications of a pulmonary artery catheter (PAC) balloon inflation in PH have not been formally tested. Methods: We assessed the hemodynamic impact of the PAC balloon inflation during RHC by measuring systolic, diastolic, and mean pulmonary artery pressure (mPAP) in all patients, and cardiac output (CO) by thermodilution in a subgroup of patients. Hemodynamic measurements were obtained both with PAC balloon deflated and fully inflated (1.5 mL of air), while the PAC was free floating in the pulmonary artery before wedging. We calculated total pulmonary resistance (TPR). Results: We included 210 patients, age 58±14 years, 134 (64%) women. Patients had no PH (n: 12, 6%), PH group 1 (n: 68, 33%), 2 (n: 86, 41%), 3 (n: 11, 5%), 4 (n: 29, 14%), and 5 (n: 3, 1%). The mean ± standard deviation (SD) at end-expiration mPAP (balloon-up minus down) (n: 209) was -0.02±1.59 mmHg (range, -5.0 to 4.0 mmHg; P=0.84), while the TPR (n: 62) was -0.27±1.2 Wood units (WU) (range, -4.8 to 2.2 WU; P=0.08); without significant variation based on the type of PH group or degree of pulmonary vascular resistance (PVR). Interestingly, the change in mPAP at end-expiration with PAC balloon inflation was higher in women (mean ± SD: 0.31±1.43 mmHg) than men (mean ± SD: -0.61±1.70 mmHg) (P<0.001). Conclusions: Balloon inflation of the PAC in the main pulmonary artery had no significant impact on the mPAP or TPR, even when only including patients with group 1 PH or selecting a subgroup with a higher PVR.

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

BACKGROUND: 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. METHODS: This retrospective case series summarizes the clinical experience of 8 patients with PAH receiving ECMO and reviews medication management in the setting of ECMO. RESULTS: 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. CONCLUSION: 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.