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Charles D Burger,1 Yuen Tsang,2 Marie Chivers,3 Riya Vijay Vekaria,3 Gurinderpal Doad,2,4 Nikki Atkins,3 Sumeet Panjabi2,4 1Division of Pulmonary Medicine, Mayo Clinic Florida, Jacksonville, FL, USA; 2Janssen Scientific Affiars, Titusville, NJ, USA; 3Avalere Health, Fleet, UK; 4Actelion Pharmaceuticals US, Inc, A Johnson and Johnson Co., Titusville, NJ, USACorrespondence: Marie Chivers, Avalere Health, Fleet, UK, Email MarieChivers@facilipharma.comPurpose: Pulmonary arterial hypertension (PAH) is a rare and progressive pulmonary vascular disease that can result in right heart failure and death. Oral prostacyclins play an important role in the management of intermediate-low risk PAH. This targeted literature review (TLR) aimed to identify and compare evidence supporting use of oral prostacyclin pathway agents (PPAs: selexipag and oral treprostinil) in intermediate-low risk PAH.Methods: A targeted literature review was conducted. Literature databases (MEDLINE, Embase, and Cochrane reviews) were searched for studies describing clinical practice and treatment outcomes for oral treprostinil and selexipag globally, published in English (2012 to 2022). Electronic searches were supplemented by manual-searches of targeted conferences (2020 to 2022), and reference lists of identified publications were reviewed. One reviewer assessed studies for eligibility.Results: In total, 95 publications met inclusion criteria: 47 full-text articles (selexipag n = 22; oral treprostinil n = 16; selexipag and oral treprostinil n = 9) and 48 conference materials. Selexipag and oral treprostinil target the prostacyclin pathway differently; their label-supporting trials had different primary endpoints (disease progression and hospitalization vs exercise capacity and disease progression), differing baseline therapy (0, 1 or 2 vs 0 or 1 baseline treatments), titration duration and dosing (personalized dose capped at 1600 ug twice daily (BID) vs increasing doses over time with no maximum dose), respectively. While both oral PPAs have demonstrated reduced risk of disease progression, only selexipag showed reduction in hospitalization rates. Oral PPAs have been shown to reduce healthcare costs in real-world clinical practice. This difference is reflected in labeled indications.Conclusion: Given differences in trial- and real-world outcomes, number of prior therapies, and dosing, personalizing the choice of oral PPA is critical to maximizing the benefit for individual patients.Plain Language Summary: PAH is a condition that causes heart failure. It is important to take medicines to slow down this process. For people with early disease, there are some medicines that can be taken as a tablet rather than as an injection to slow down disease progression. The differences between two of the tablet options – selexipag and oral treprostinil, are unclear. We reviewed publications describing how, when and why these medicines are used and how well they work, to improve our understanding of the value of these medicines to people with PAH.Keywords: treprostinil, selexipag, pulmonary hypertension, outcomes

Charles D Burger,1 Mohamedanwar Ghandour,1 Divya Padmanabhan Menon,2 Haytham Helmi,3 Raymond L Benza4 1Division of Pulmonary, Allergy and Sleep Medicine, Mayo Clinic, 2Department of Internal Medicine, Mayo Clinic, 3Division of Transplant Medicine and Research Administration, Mayo Clinic, Jacksonville, FL, USA; 4Advanced Heart Failure, Transplant, Mechanical Circulatory Support and Pulmonary Hypertension, Allegheny Health Network, Pittsburg, PA, USA Abstract: Pulmonary arterial hypertension (PAH) has a high morbidity rate and is fatal if left untreated. Increasing evidence supports early intervention, possibly with initial combination therapy. PAH-specific pharmaceuticals, however, are expensive and may have serious adverse effects, particularly when used in combination. The currently dynamic health care economy reinforces the need for a review of early intervention from both outcomes and economic perspectives. We aimed to review the clinical and economic impact of PAH therapy, particularly examining drug cost, hospitalization burden, and health care economics impact, and the effect of early intervention on clinical outcomes. We searched PubMed, Scopus, Ovid, and MEDLINE databases from 2005 to 2017 for studies comparing drug cost, clinical outcomes, and hospitalization burden associated with therapy for PAH. Emerging data indicate that early therapy is effective, but drug therapy is expensive, particularly with combination therapy. Efficacy studies also generally show benefit of combination therapy for patients in World Health Organization functional class II, with a consistent decrease in hospitalization. Pharmacoeconomic studies are limited but indicate that increased pharmacy costs are at least partially offset by decreased health care utilization, particularly inpatient care. Modeling also shows a cost benefit with combination therapy at 2 years. Nonetheless, more rigorously collected health care economic data should be incorporated into future drug efficacy trials to provide a clearer understanding of the impact and the associated cost benefit of early PAH therapy. Increasing evidence in support of early intervention and combination therapy for PAH is associated with rising medication costs that are largely offset by reduced hospitalization, on the basis of the currently available literature. Nonetheless, the studies performed to date have methodologic limitations that highlight the need for prospective studies using more robust economic modeling. Keywords: combination therapy, health care costs, hospitalization, pulmonary arterial hypertension

BACKGROUND: The association between thyroid dysfunction and pulmonary hypertension (PH) has not been well characterized. METHODS: This retrospective study comprised 356 consecutive PH patients seen at Mayo Clinic Jacksonville Pulmonary Hypertension Center from 1992 to 2006 and 698 sex-matched control subjects without PH. Thyroid disease was defined as an abnormal thyroid-stimulating hormone level, with or without an abnormal free or total thyroxine level, a history of thyroid disease on replacement, or an elevated thyroperoxidase antibody level. The main outcome measure was prevalence of thyroid disease in each group. RESULTS: Median age of the 356 PH patients was 65 years; 230 patients (65%) were female. The control group of 698 patients had the same sex ratio and median age of 68 years. Most PH patients had severe PH, as categorized by World Health Organization (WHO) class (74% class 3-4) and pulmonary artery systolic pressure. Among those with PH, 85 patients (24%) had thyroid disease vs 107 control patients (15%). After adjusting for age and sex, the prevalence of thyroid disease was increased in PH patients compared with control patients. Increased prevalence was most prominent in WHO group 1, pulmonary artery hypertension confirmed by right-heart catheterization (odds ratio, 2.53; 95% confidence interval, 1.55 to 4.08; p < 0.001). Most patients had mild thyroid disease and were hypothyroid. Only 14 of 85 patients (16%) had previously undiagnosed thyroid disease. CONCLUSIONS: Patients with PH have a higher prevalence of thyroid disease than other pulmonary patients. Evaluation of thyroid function in PH patients may be warranted to detect and assess coexisting thyroid disease. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To determine the provider cost of administering intensive care unit (ICU) services, comparing 3 different staffing models for ICU coverage, and to compare the costs of using house staff vs nonphysician providers (NPPs). METHODS: Data were collected on total staff composition and number of beds In ICUs from January 1, 2004, through December 31, 2004, at the 3 Mayo Clinic sites: Rochester, Minn; Jacksonville, Fla; and Scottsdale, Ariz. Institutional or national average staff salaries were used to determine total staffing costs per ICU bed per year at each site. Medicare medical education reimbursements were also taken into account. RESULTS: Costs per ICU bed for physician staffing were $18,630 in Rochester, $37,515 in Jacksonville, and $38,010 in Scottsdale. When NPPs were substituted for house staff, the costs per bed were $72,466 in Rochester, $61,291 in Jacksonville, and $49,909 in Scottsdale. Incremental costs per ICU bed using NPPs were $53,836 in Rochester, $23,776 in Jacksonville, and $11,899 in Scottsdale. CONCLUSION: Use of residents and fellows in ICU staffing at a major tertiary health center is more cost-efficient than use of NPPs. This finding could have Implications for the cost of physician services in nonteaching community hospitals and the methods by which care is provided. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine the frequency and microbial pattern of pneumonia and its effect on survival in the current era of orthotopic liver transplantation (OLT). PATIENTS AND METHODS: At the Mayo Clinic in Jacksonville, Fla, the medical records of consecutive patients who underwent their first OLT between February 1998 and January 2001 were retrospectively reviewed through the end of the first year posttransplantation. RESULTS: Of 401 study patients, 20 developed pneumonia; estimates of incidence with corresponding 95% confidence interval (CI) at 1 and 12 months were 3% (1%-5%) and 5% (3%-7%), respectively. Pseudomonas aeruginosa was the predominant microorganism identified (in 8 of 14 patients) during the first month after transplantation. Between the second and sixth months, 2 of the 4 cases of pneumonia were due to fungal infections of Aspergillus fumigatus. Cytomegalovirus was associated with Aspergillus in 1 patient. No other viral or Pneumocystis carnil pneumonia was diagnosed. There were only 2 cases of pneumonia between 7 months and 1 year after transplantation, neither of which was fungal. Approximately 40% (95% CI, 14%-58%) of patients with pneumonia died within 1 month after diagnosis. The relative risk of mortality in the first month after onset of pneumonia was estimated to be 24 (95% CI, 10-54), which is strong evidence of increased risk of mortality with pneumonia (P<0.001). CONCLUSIONS: Pneumonia appears to occur less often after OLT than previously reported but still has a substantial negative effect on survival. In the early period after OLT, P. aeruginosa continues to be the predominant organism causing pneumonia. [ABSTRACT FROM AUTHOR]

Selexipag is an oral selective agonist of the prostacyclin receptor approved to treat adults with pulmonary arterial hypertension (PAH). Selexipag is initiated at a dose of 200 μg twice daily (bid) and usually titrated up by 200 μg bid weekly (per label) or more slowly (e.g., every other week in real-world clinical practice) to the highest tolerated individualized dose (ID) ranging from 200 to 1600 µg bid. In the Phase 3 GRIPHON trial, selexipag delayed disease progression and reduced risk of PAH-related hospitalization compared with placebo; the effect was consistent across three prespecified ID groups: low (200-400 µg bid), medium (600-1000 µg bid), and high (1200-1600 µg bid). This study evaluated patient outcomes across selexipag dose ranges in real-world practice. Data were analyzed from 1186 US adult patients with PAH on selexipag from the Komodo closed-claims database (2015‒2022). Of these, 634 (53.5%) patients completed titration and reached their selexipag ID (43.8% high ID, 29.8% medium ID, 26.3% low ID). Subsequently, 72.4% of patients in the low ID group had dose adjustments compared with 61.9% (medium ID) and 34.5% (high ID; standardized mean difference 0.63). There were no significant differences in patient outcomes, i,e, persistence (time to discontinuation) and risk of all-cause and PAH-related hospitalization across ID groups. The findings in this diverse, real-world population of patients with PAH reinforced an individualized approach to the dosing scheme to maximize benefit-risk and achieve the highest tolerated dose with selexipag similar to findings from the GRIPHON trial and other studies., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Actelion Pharmaceuticals US, Inc., a Johnson & Johnson company, sponsored this study. Wenze Tang, Yuen Tsang, and Sumeet Panjabi are employees of Actelion Pharmaceuticals US, Inc. and may own stocks. The study sponsor was involved in all aspects of the research, including the collection of data, its analysis and interpretation, and approval of the final manuscript for publication. Charles D. Burger provided consulting services to Janssen, LLC., (© 2024 Actelion Pharmaceuticals US, Inc (a Johnson & Johnson Company). Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Advanced Care at Home is a Mayo Clinic hospital-at-home (HaH) program that provides hospital-level care for patients. The study examines patient- and community-level factors that influence health outcomes. The authors performed a retrospective study using patient data from July 2020 to December 2022. The study includes 3 Mayo Clinic centers and community-level data from the Agency for Healthcare Research and Quality. The authors conducted binary logistic regression analyses to examine the relationship among the independent variables (patient- and community-level characteristics) and dependent variables (30-day readmission, mortality, and escalation of care back to the brick-and-mortar hospital). The study examined 1433 patients; 53% were men, 90.58% were White, and 68.2% were married. The mortality rate was 2.8%, 30-day readmission was 11.4%, and escalation back to brick-and-mortar hospitals was 8.7%. At the patient level, older age and male gender were significant predictors of 30-day mortality ( P -value <0.05), older age was a significant predictor of 30-day readmission ( P -value <0.05), and severity of illness was a significant predictor for readmission, mortality, and escalation back to the brick-and-mortar hospital ( P -value <0.01). Patients with COVID-19 were less likely to experience readmission, mortality, or escalations ( P -value <0.05). At the community level, the Gini Index and internet access were significant predictors of mortality ( P -value <0.05). Race and ethnicity did not significantly predict adverse outcomes ( P -value >0.05). This study showed promise in equitable treatment of diverse patient populations. The authors discuss and address health equity issues to approximate the vision of inclusive HaH delivery.

Pulmonary hypertension (PH) associated with chronic kidney disease (CKD) (PH-CKD) affects approximately 20%-40% of CKD patients and is associated with increased morbidity and mortality. PH and CKD are both pathophysiologically associated with nitric oxide (NO) deficiency. The NO pathway, an important therapeutic domain in pulmonary arterial hypertension (PAH), is an intriguing but unexplored target in PH-CKD. We sought to improve understanding of the clinical significance of the NO pathway in patients with PH-CKD by assessing the hemodynamic response to inhaled NO (iNO) during right heart catheterization (RHC). In this retrospective cohort study, patients with diagnosis codes of PH and stage IV/V CKD or end-stage renal disease and estimated glomerular filtration rate < 60 mL/min/body surface area who underwent RHC and hemodynamic drug study between July 2011 and June 2021 were eligible. Patients with mean pulmonary artery pressure (mPAP) > 20 mmHg and pulmonary vascular resistance (PVR) > 3 Wood units were included. The final cohort included 37 patients (45.9% female, mean age 72.5 ± 9.7 years). A total of 56.7% of the cohort (21/37) had precapillary PH, while 43.2% (16/37) had combined precapillary postcapillary PH (Cpc-PH). Median survival was 3.1 years after RHC. iNO was associated with a significant decrease in both mPAP and PVR. Hemodynamic changes in mPAP and PVR were similar in precapillary and Cpc-PH groups. Among a small subset ( n  = 14) who were subsequently treated with PAH-targeted therapy, treatment response was mixed and did not reveal significant benefit. Further studies are warranted to better define the potential role of PAH therapy in PH-CKD., Competing Interests: HMD has received research funding from Bayer Pharmaceuticals and has served on advisory boards and received consulting fees from Janssen. The other authors declare no conflict of interest., (© 2024 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Hospital at home is designed to offer patients hospital level care in the comfort of their own home. The process by which clinicians select eligible patients that are clinically and socially appropriate for this model of care requires labor-intensive manual chart reviews. We addressed this problem by providing a predictive model, web application, and data pipeline that produces an eligibility score based on a set of clinical and social factors that influence patients' success in the program. Providers used this predictive model to prioritize the order in which they perform chart reviews and patient screenings. Training performance area under the curve (AUC) was 0.77. Testing 'in production' had an AUC of 0.75. Admission criteria in training rapidly changed over the course of the study due to the novelty of the clinical model. The current algorithm successfully identified many inconsistencies in enrollment and has streamlined the process of patient identification., (©2022 AMIA - All rights reserved.)

BACKGROUND: Pulmonary arterial hypertension (PAH) is associated with a substantial clinical and economic burden. Inhaled prostacyclins are a well-established part of pharmacotherapy for PAH. There are differences between inhaled therapies in the burden imposed by administration frequency. Simpler and less time-consuming inhaled PAH therapies may improve both adherence and persistence and potentially affect outcomes. OBJECTIVE: To compare real-world health care resource use, costs, and treatment adherence and persistence in patients with PAH who initiated inhaled treprostinil or iloprost. METHODS: Adult patients with 1 inpatient or 2 outpatient medical claims separated by at least 30 days with a diagnosis of PAH were identified using International Classification of Diseases, Ninth Revision or Tenth Revision, Clinical Modification codes with a pharmacy claim for inhaled treprostinil or iloprost. Patients were required to be continuously enrolled in the health plan for 6 months prior to and 12 months after the index date. A proportion of days covered of 0.8 or more was considered adherent; persistence was no gap in therapy for at least 60 days. All-cause health care resource utilization and all-cause costs were assessed. RESULTS: 405 and 62 patients were included in the inhaled treprostinil and iloprost cohorts, respectively. Adherence (50.9% and 22.6%; P < 0.0001) and persistence (6 months, 65.2% vs 35.5%; 12 months, 46.7% vs 16.1%; log-rank P < 0.001) were significantly better with inhaled treprostinil. Post-index allcause inpatient admissions (39.3% vs 54.8%; P = 0.02) and post-index emergency department (ED) utilization (36.3% vs 50.0%; P = 0.04) were lower with inhaled treprostinil. Among patients who were persistent with therapy through 12 months, there was no significant difference between groups in mean (SD) all-cause total costs ($266,462 [137,324] vs $262,826 [112,452] for inhaled treprostinil vs iloprost, respectively; P = 0.98). CONCLUSIONS: The results suggest that inhaled treprostinil is less burdensome, is associated with greater adherence and persistence, and may reduce all-cause hospitalizations and ED visits. DISCLOSURES: This study was funded by the United Therapeutics Corporation to obtain data for this analysis and compose the manuscript. Dr Burger has served as clinical investigator in multicenter interventional trials sponsored by United Therapeutics but did not receive any direct compensation. Drs Wu and Morland and Mr Classi are employees of United Therapeutics Corporation and own stock/shares in the company.

Objective: To explore clinical characteristics, risk profiles, and outcomes of patients with portopulmonary hypertension (PoPH) who have contraindications to liver transplant (LT)., Methods: From the largest US single-institution registry of patients with PoPH, we analyzed 160 patients who did not receive LT between 1988 to 2019. Pulmonary arterial hypertension (PAH)-pertinent characteristics, hemodynamic features, treatments, and risk stratification were compared at baseline, first follow-up visit, and censor/death time., Results: Median survival for the entire cohort was 27.5 months from the diagnosis of PoPH. Overall survival was 89%, 77%, 51%, and 38% at 6 months, 1 year, 3 years, and 5 years, respectively. Survival was significantly affected by the severity of liver disease (P<.001). Most patients received PAH-specific therapies (136 [85%]), predominantly monotherapy (123 [77%)]. With treatment, significant improvements were noted in World Health Organization functional class (P=.04), 6-minute walk distance (P<.001), right ventricular function (P<.001), pulmonary vascular resistance (P<.001), and Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL) Lite 2 score (P=.02) univariately. Per European Society of Cardiology risk stratification, no patient met full criteria for low risk at baseline or at follow-up. In a multivariate Cox risk model, 6-minute walk distance, right atrial pressure, pulmonary capillary wedge pressure, bilirubin level, and Model for End-Stage Liver Disease-sodium score of 15 or higher were associated with increased risk of death., Conclusion: Patients with PoPH who did not undergo LT had a poor prognosis. This persisted despite use of PAH-specific therapies and significant improvements in hemodynamics, echocardiography parameters of right ventricle function, 6-minute walk distance, and World Health Organization functional class., (Copyright © 2022 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Dual combination therapy with a phosphodiesterase-5 inhibitor (PDE5i) and endothelin receptor antagonist is recommended for most patients with intermediate-risk pulmonary arterial hypertension (PAH). The RESPITE and REPLACE studies suggest that switching from a PDE5i to a soluble guanylate cyclase (sGC) activator may provide clinical improvement in this situation. The optimal approach to escalation or transition of therapy in this or other scenarios is not well defined. We developed an expert consensus statement on the transition to sGC and other treatment escalations and transitions in PAH using a modified Delphi process. The Delphi process used a panel of 20 physicians with expertise in PAH. Panelists answered three questionnaires on the management of treatment escalations and transitions in PAH. The initial questionnaire included open-ended questions. Later questionnaires consolidated the responses into statements that panelists rated on a Likert scale from -5 ( strongly disagree ) to +5 ( strongly agree ) to determine consensus. The Delphi process produced several consensus recommendations. Escalation should be considered for patients who are at high risk or not achieving treatment goals, by adding an agent from a new class, switching from oral to parenteral prostacyclins, or increasing the dose. Switching to a new class or within a class should be considered if tolerability or other considerations unrelated to efficacy are affecting adherence. Switching from a PDE5i to an SGC activator may benefit patients with intermediate risk who are not improving on their present therapy. These consensus-based recommendations may be helpful to clinicians and beneficial for patients when evidence-based guidance is unavailable., Competing Interests: Franck F. Rahaghi reports consultation, research, and speakership honoraria from Bayer and Janssen, consultation and speakership from United Therapeutics, and consultation fees from Acceleron. Vijay P. Balasubramanian reports a research grant from United Therapeutics and serves on a speakers bureau for Bayer. Robert C. Bourge reports research grant support to my institution from United Therapeutics and Bayer, and service on a Scientific Advisory Board at United Therapeutics. Murali M. Chakinala reports grants or contracts from Actelion/Janssen, Bayer, Medtronic, NIH, Reata, Liquidia, Phase Bio, Complexa, United Therapeutics, Altavant, Trio Health Analytics, Reata, Acceleron, Arena, and Gossamer; consulting fees from Altavant, Vaderis Therapeutics, Aerovate, Reata, VWave, and Arena; honoraria from Bayer, Gilead, Simply Speaking, WebMD, and United Therapeutics; support for attending meetings and/or travel from Actelion/Janssen, United Therapeutics, Bayer, Acceleron, Reata, and Gilead; participation on a Data Safety Monitoring Board or Advisory Board for Actelion/Janssen, Express Scripts, Phase Bio, Altavant, Gossamer, United Therapeutics, Bayer, Acceleron, and Liquidia; and leadership or a fiduciary role in the Pulmonary Hypertension Association and the Cure HHT Global Research and Medical Advisory Board. Michael S. Eggert reports research contracts with United Therapeutics (BREEZE and ADVANCE Outcomes), Acceleron, and Actelion. Jean M. Elwing reports grants from Actelion, Acceleron, Reata, United Therapeutics, Liquidia, Phase Bio, Complexa, Gossamer Bio, Bayer, Arena, Eiger, Akros, Bellerophon, and Lung LLC and consulting fees from United Therapeutics, Acceleron, Liquidia, Altavant, Bayer, Gossamer Bio, Actelion, Bayer. Jeremy Feldman reports consulting and giving talks for Bayer, United Therapeutics, and Jansen. Christopher King reports personal fees from Actelion, personal fees from Genentech, United Therapeutics, and Boehringer Ingelheim; has served on advisory boards for and is on the Speakers’ Bureau of Actelion, Boehringer‐Ingelheim Pharmaceuticals, and United Therapeutics. James R. Klinger reports that his institution receives research funding from United Technologies, service on a Steering Committee and a Clinical Outcomes Committee for Bayer, and a leadership role in the Pulmonary Hypertension Association. Stephen C. Mathai reports personal fees from United Therapeutics; participation on a data safety monitoring board or advisory board from United Therapeutics, Actelion, and Bayer, and leadership or a fiduciary role in the PCORI Rare Disease Advisory Panel and the World Symposium on Pulmonary Hypertension. John Wesley McConnell reports consulting fees from Actelion, Bayer, Gossamer, Altavant, and Liquidia; honoraria from Actelion, Bayer, Simply Speaking, Impact PH, and Reata, and participation on a data safety monitoring board or advisory board for Actelion, Liquidia, Gossamer, and Altavant. Harold I. Palevsky reports honoraria for serving on scientific advisory boards for Acceleron, Actelion/Janssen, PhaseBio and United Therapeutics, and serving on a DSMB for United Therapeutics. Ricardo Restrepo‐Jaramillo reports serving on speaker's bureau for United Therapeutics, Bayer, and Actelion. Zeenat Safdar reports serving on a speakers bureau, consultation and advisory boards for Actelion, United Therapeutics, Boehringer Ingelheim, Bayer, and Roche. Jeffrey S. Sager reports personal fees from Bayer pharmaceuticals, grants and personal fees from United Therapeutics, grants and personal fees from Janssen (J and J), and grants from Reata outside the submitted work. Namita Sood reports a speaking fee from Bayer. Roxana Sulica reports research grants from Bayer, United Therapeutics, Complexa, and Reata, and serves on advisory boards for Actelion, Bayer, United Therapeutics, and Reata. R. James White reports research grants from United Therapeutics, Reata, Bayer, Merck, and Janssen and consulting fees from Merck and Bayer. Nicholas S. Hill reports honoraria from Axon Research for this study; grants to his institution from Actelion, Bayer, Gilead, and United Therapeutics; consulting fees from United Therapeutics; and participation in Data Safety Monitoring Boards for United Therapeutics and Pfizer. All authors had access to the Delphi questionnaire analysis and data and participated in the review, revision, and approval of the content of the manuscript for submission. Charles D. Burger reports no disclosures or conflicts of interest., (© 2022 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Inhaled treprostinil is an approved therapy for pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease in the United States. Studies have confirmed the robust benefits and safety of nebulized inhaled treprostinil, but it requires a time investment for nebulizer preparation, maintenance, and treatment. A small, portable treprostinil dry powder inhaler has been developed for the treatment of PAH. The primary objective of this study was to evaluate the safety and tolerability of treprostinil inhalation powder (TreT) in patients currently treated with treprostinil inhalation solution. Fifty-one patients on a stable dose of treprostinil inhalation solution enrolled and transitioned to TreT at a corresponding dose. Six-minute walk distance (6MWD), device preference and satisfaction (Preference Questionnaire for Inhaled Treprostinil Devices [PQ-ITD]), PAH Symptoms and Impact (PAH-SYMPACT®) questionnaire, and systemic exposure and pharmacokinetics for up to 5 h were assessed at baseline for treprostinil inhalation solution and at Week 3 for TreT. Adverse events (AEs) were consistent with studies of inhaled treprostinil in patients with PAH, and there were no study drug-related serious AEs. Statistically significant improvements occurred in 6MWD, PQ-ITD, and PAH-SYMPACT. Forty-nine patients completed the 3-week treatment phase and all elected to participate in an optional extension phase. These results demonstrate that, in patients with PAH, transition from treprostinil inhalation solution to TreT is safe, well-tolerated, and accompanied by statistically significant improvements in key clinical assessments and patient-reported outcomes with comparable systemic exposure between the two formulations at evaluated doses (trial registration: clinicaltrials.gov identifier: NCT03950739)., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: A.A.B. has received funding from Janssen, Bayer, and Actelion for research and honoraria from United Therapeutics Corporation, Bayer, Janssen, AstraZeneca, Intuitive, and Boehringer Ingelheim for lectures, presentations, or speakers' bureau. C.D.B. has no conflict of interest. C.D. is an employee of United Therapeutics Corporation. S.V.D. has no conflict of interest. M.S.E. reports ongoing industry‐sponsored research with Acceleron, Merck, and United Therapeutics Corporation. K.A.E. has received fees from United Therapeutics Corporation for serving on a speakers' bureau and advisory boards; from J&J Actelion for serving on advisory boards; and from Acceleron for consulting services; and institutional research funding from UT and J&J Actelion. M.R.F. has no conflict of interest. S.J. has received research funding from United Therapeutics Corporation and Bellerophon Therapeutics and honoraria from Actelion and Bayer for speakers programs. J.M. has received speaker fees from United Therapeutics Corporation. M.M. is an employee of United Therapeutics Corporation. J.M.J. has no conflict of interest. H.I.P. has received honoraria from Acceleron, United Therapeutics Corporation, and Actelion‐Janssen for serving on advisory boards. G.V.R. has no conflict of interest. R.R.J. has received fees from United Therapeutics Corporation, Bayer, and J&J Actelion for consulting, serving on a speakers' bureau, and research funding. S.S. has served as a consultant for United Therapeutics Corporation, Acceleron, Actelion, and Bayer Pharmaceuticals; as an advisor and speaker for United Therapeutics Corporation, Actelion, and Bayer; and as clinical trial site PI for United Therapeutics Corporation, Actelion, Merck, Liquidia Technologies, Altavant Sciences, and Gossamer Bio; and has received research grant support from ACCP CHEST and United Therapeutics Corporation. T.G.S. has served as an advisor for Bayer Pharmaceuticals and Liquidia Technologies and as clinical trial site PI for United Therapeutics Corporation, Actelion/J &J, Liquidia Technologies, Bayer Pharmaceuticals, and Regeneron Pharmaceuticals. S.M.S. has no conflict of interest. P.S. is an employee of United Therapeutics Corporation. L.A.S. has received consulting fees from Gossamer Bio and has served as clinical trial site PI for United Therapeutics Corporation, Gossamer Bio, INSMED, Actelion, Liquidia, Merck, and Altavant Sciences., (© 2022 United Therapeutics Corporation. United Therapeutics Corporation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Background: The pathophysiology of COVID-19 includes immune-mediated hyperinflammation, which could potentially lead to respiratory failure and death. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is among cytokines that contribute to the inflammatory processes. Lenzilumab, a GM-CSF neutralising monoclonal antibody, was investigated in the LIVE-AIR trial to assess its efficacy and safety in treating COVID-19 beyond available treatments., Methods: In LIVE-AIR, a phase 3, randomised, double-blind, placebo-controlled trial, hospitalised adult patients with COVID-19 pneumonia not requiring invasive mechanical ventilation were recruited from 29 sites in the USA and Brazil and were randomly assigned (1:1) to receive three intravenous doses of lenzilumab (600 mg per dose) or placebo delivered 8 h apart. All patients received standard supportive care, including the use of remdesivir and corticosteroids. Patients were stratified at randomisation by age and disease severity. The primary endpoint was survival without invasive mechanical ventilation to day 28 in the modified intention-to-treat population (mITT), comprising all randomised participants who received at least one dose of study drug under the documented supervision of the principal investigator or sub-investigator. Adverse events were assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT04351152, and is completed., Findings: Patients were enrolled from May 5, 2020, until Jan 27, 2021. 528 patients were screened, of whom 520 were randomly assigned and included in the intention-to-treat population. 479 of these patients (n=236, lenzilumab; n=243, placebo) were included in the mITT analysis for the primary outcome. Baseline demographics were similar between groups. 311 (65%) participants were males, mean age was 61 (SD 14) years at baseline, and median C-reactive protein concentration was 79 (IQR 41-137) mg/L. Steroids were administered to 449 (94%) patients and remdesivir to 347 (72%) patients; 331 (69%) patients received both treatments. Survival without invasive mechanical ventilation to day 28 was achieved in 198 (84%; 95% CI 79-89) participants in the lenzilumab group and in 190 (78%; 72-83) patients in the placebo group, and the likelihood of survival was greater with lenzilumab than placebo (hazard ratio 1·54; 95% CI 1·02-2·32; p=0·040). 68 (27%) of 255 patients in the lenzilumab group and 84 (33%) of 257 patients in the placebo group experienced at least one adverse event that was at least grade 3 in severity based on CTCAE criteria. The most common treatment-emergent adverse events of grade 3 or higher were related to respiratory disorders (26%) and cardiac disorders (6%) and none led to death., Interpretation: Lenzilumab significantly improved survival without invasive mechanical ventilation in hospitalised patients with COVID-19, with a safety profile similar to that of placebo. The added value of lenzilumab beyond other immunomodulators used to treat COVID-19 alongside steroids remains unknown., Funding: Humanigen., Competing Interests: Declaration of interests ZT has received research support from Humanigen and unrestricted education support from Gilead, ViiV, and Merck (all to the institution). CRL has received research support from Gilead, Pfizer, and NIAID (ACTIV-2–A5401). VMC and WSA are third-party agency consultants to Humanigen. CP is a paid consultant to Gilead. JB has received research support from Gilead and Humanigen. CFK has received research support grants (to the institution) from NIH, CDC, Gilead Sciences, and ViiV. VCM has received investigator-initiated research grants (to the institution) and consultation fees (both unrelated to the current work) from Eli Lilly, Bayer, Gilead Sciences, and ViiV. CD, DC, OA, and GC are employees of, or consultants to, Humanigen. ADB is supported by grants from NIAID (AI110173 and AI120698), Amfar (#109593), and Mayo Clinic (HH Sheikh Khalifa Bin Zayed Al-Nahyan Professorship of Infectious Diseases); he is a paid consultant for AbbVie and Flambeau Diagnostics, is a paid member of the DSMB for Corvus Pharmaceuticals, Equilium, and Excision Biotherapeutics, has received fees for speaking for Reach MD, owns equity for scientific advisory work in Zentalis and Nference, and is founder and President of Splissen Therapeutics. CDB and RO declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Once patients are diagnosed with pulmonary hypertension it is important to identify the correct diagnostic group as it will have implications on the disease state management. Pulmonary hypertension is increasingly diagnosed and treated in general medical practices; however, evidence-based guidelines recommend evaluation and treatment in pulmonary hypertension centers for accurate diagnosis and appropriate treatment recommendations. We conducted a retrospective cohort study of 509 random patients 18 years and older who were evaluated in our pulmonary hypertension clinic from January 2005 to December 2018. 68.4% ( n = 348) had their diagnostic group clarified or changed. Pulmonary hypertension was deemed an incorrect diagnosis in 12.4% ( n = 63). A total of 114 patients (22.4%) had been initiated on pulmonary hypertension specific treatment prior to presentation. Pulmonary hypertension specific medication was stopped in 57 (50.0%) cases. The estimated monthly saving of the stopped medication based on wholesale acquisition costs was USD 396,988.05-419,641.05, a monthly saving of USD 6964.70-7362.12 per patient. Evaluation outside of a pulmonary hypertension center may lead to misdiagnosis and inappropriate or inadequate treatment. Pulmonary arterial hypertension directed therapy improves median survival, but inappropriate therapy may cause harm; therefore, patients benefit from a specialized center with multiple resources to secure an accurate diagnosis and tailored treatment for their condition.

Objective: To evaluate the performance of an Electronic Health Record (EHR) integrated risk score for COVID-19 positive outpatients to predict 30-day risk of hospitalization., Patients and Methods: A retrospective observational study of 67 470 patients with COVID-19 confirmed by polymerase chain reaction (PCR) test between March 12, 2020 and February 8, 2021. Risk scores were calculated based on data in the chart at the time of the incident infection., Results: The Mayo Clinic COVID-19 risk score consisted of 13 components included age, sex, chronic lung disease, congenital heart disease, congestive heart failure, coronary artery disease, diabetes mellitus, end stage liver disease, end stage renal disease, hypertension, immune compromised, nursing home resident, and pregnant. Univariate analysis showed all components, except pregnancy, have significant ( P  < .001) association with admission. The Mayo Clinic COVID-19 risk score showed a Receiver Operating Characteristic Area Under Curve (AUC) of 0.837 for the prediction of admission for this large cohort of COVID-19 positive patients., Conclusion: The Mayo Clinic COVID-19 risk score is a simple score that is easily integrated into the EHR with excellent predictive performance for severe COVID-19. It can be leveraged to stratify risk for severe COVID-19 at initial contact, when considering therapeutics or in the allocation of vaccine supply.

Pulmonary hypertension is a complex condition but a relatively common manifestation of severe cardiopulmonary disease. By contrast, pulmonary arterial hypertension is uncommon and is more prevalent in young women. To better categorize patients and to guide clinical decision-making, 5 diagnostic groups and associated subgroups characterize the spectrum of disease. A multidisciplinary approach to evaluation and treatment is recommended by published guidelines and often entails referral to a designated pulmonary hypertension center. Several key publications during the last couple of years merit review. The PubMed database was searched for English-language studies and guidelines relating to pulmonary hypertension. The following terms were searched, alone and in combination: pulmonary hypertension, pulmonary arterial hypertension, portopulmonary hypertension, and chronic thromboembolic pulmonary hypertension. The focus was on those publications with new information on evaluation and management of pulmonary hypertension between January 1, 2019, and January 31, 2021. Of the subgroups, 2 were of particular interest for this review: portopulmonary hypertension and chronic thromboembolic pulmonary hypertension. Last, available data on the impact of the coronavirus disease 2019 pandemic and newer treatment agents in early trials were selectively reviewed. The review is therefore intended to serve as a practical, focused review of important topics germane to those clinicians caring for patients with pulmonary hypertension., (Copyright © 2021 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objectives: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are the most commonly prescribed antihypertensives, with prior studies identifying a possible association between long-term use and increased rates of lung cancer. This study evaluated this potential association in a large population using propensity matching., Methods: This was a population-based cohort study in a large healthcare system in three regions of the United States. Pairwise propensity score matching was performed using demographics and comorbidities. All of the adult patients in the healthcare system from January 1, 2000 to April 30, 2018 with at least 1 year of follow-up were included., Results: In total, 3,253,811 patients with a median age of 59 (range 18-103) years were included. The ACEI group had a higher freedom from lung cancer versus controls at 15 years (98.47%, 95% confidence interval [CI] 98.41-98.54) versus 98.26%, (95% CI 98.20-98.33), whereas ARBs had similar rates versus controls at all time points. For patients diagnosed as having lung cancer, median all-cause survival was significantly higher in the ACEI (34.7 months, 95% CI 32.8-36.6) and ARB (30.9 months, 95% CI 28.1-33.8) groups than the control group (20.6 months, 95% CI 20.1-21.1)., Conclusions: This study showed lower rates of lung cancer with ACEI use and no difference in risk with ARBs. In addition, use of these medications was found to be associated with increased survival in those diagnosed as having lung cancer. This study supports the continued use of these medications without concern for increasing the risk of lung cancer.

Little is known about the effect of wearing a facemask on the physiological and perceptual responses to exercise in patients with pulmonary arterial hypertension (PAH). We performed a single-center retrospective study to evaluate whether facemask wearing impacted distanced covered, rating of perceived exertion (RPE), and arterial oxygen saturation (SpO 2 ) during a 6-minute walk test (6MWT) in PAH patients. Forty-five patients being treated for group 1 PAH and who performed a 6MWT before and after implementation of a facemask mandate were included in the analysis. Each included patient performed a 6MWT without (test 1) and with (test 2) a facemask between October 1, 2019, and October 31, 2020. At both time points, all patients also underwent a submaximal cardiopulmonary exercise test, echocardiogram, and blood laboratory tests, with a Registry to Evaluate Early and Long-Term PAH Disease Management Lite 2.0 score calculated. The two 6MWTs were performed 81±51 days apart, and all patients were clinically stable at both testing timepoints. Six-minute walk test distance was not different between test 1 and test 2 (405±108 m vs 400±103 m, P =.81). Similarly, both end-test RPE and lowest SpO 2 during the 6MWT were not different in test 1 and test 2 (RPE: 2.5±1.7 vs 2.5±2.1, P =.91; SpO 2 nadir: 92.8±3.4% vs 93.3±3.3%, P =.55). Our findings show that wearing a facemask has no discernable impact on the arterial oxygen saturation and perceptual responses to exercise or exercise capacity in patients with moderate-to-severe PAH. This study reinforces the evidence that wearing a facemask is safe in PAH patients, even during exercise., (© 2021 THE AUTHORS.)

Compared to idiopathic pulmonary arterial hypertension (IPAH), patients with portopulmonary hypertension (POPH) have worse survival. Health disparities may contribute to these differences but have not been studied. We sought to compare socioeconomic factors in patients with POPH and IPAH and to determine whether socioeconomic status and/or POPH diagnosis were associated with treatment and health-care utilization. We performed a cross-sectional study of adults enrolled in the Pulmonary Hypertension Association Registry. Patients with IPAH (n = 344) and POPH (n = 57) were compared. Compared with IPAH, patients with POPH were less likely to be college graduates (19.6% vs. 34.9%, p = 0.02) and more likely to be unemployed (54.7% vs. 30.5%, p < 0.001) and have an annual household income below poverty level (45.7% vs. 19.0%, p < 0.001). Patients with POPH had similar functional class, quality of life, 6-min walk distance, and mean pulmonary arterial pressure with a higher cardiac index. Compared with IPAH, patients with POPH were less likely to receive combination therapy (46.4% vs. 62.2%, p = 0.03) and endothelin receptor antagonists (28.6% vs. 55.1%, p < 0.001) at enrollment with similar treatment at follow-up. Patients with POPH had more emergency department visits (1.7 ± 2.1 vs. 0.9 ± 1.2, p = 0.009) and hospitalizations in the six months preceding enrollment (1.5 ± 2.1 vs. 0.8 ± 1.1, p = 0.02). Both POPH diagnosis and lower education level were independently associated with a higher number of emergency department visits. Compared to IPAH, patients with POPH have lower socioeconomic status, are less likely to receive initial combination therapy and endothelin receptor antagonists but have similar treatment at follow-up, and have increased health-care utilization., (© The Author(s) 2021.)

Rationale: Single-center studies demonstrated that methamphetamine use is associated with pulmonary arterial hypertension (Meth-APAH). We used the Pulmonary Hypertension Association Registry to evaluate the national distribution of Meth-APAH and to compare its impact on patient-reported and clinical outcomes relative to idiopathic PAH. Objectives: To determine if patients with Meth-APAH differ from those with idiopathic PAH in demographics, regional distribution in the United States, hemodynamics, health-related quality of life, PAH-specific treatment, and health care use. Methods: The Pulmonary Hypertension Association Registry is a U.S.-based prospective cohort of patients new to care at a Pulmonary Hypertension Care Center. The registry collects baseline demographics, clinical parameters, and repeated measures of health-related quality of life, World Health Organization functional class, 6-minute walk distance, therapy, and health care use. Repeated measures of functional class, health-related quality of life, type of therapy, emergency department visits, and hospitalizations were compared using generalized estimating equations. Results: Of 541 participants included, 118 had Meth-APAH; 83% of Meth-APAH arose in the western United States. The Meth-APAH group was younger and had a poorer socioeconomic status and lower cardiac index than the idiopathic PAH group, despite no difference in mean pulmonary artery pressure or pulmonary vascular resistance. The Meth-APAH group had a more advanced functional class in longitudinal models (0.22 points greater; 95% confidence interval [CI], 0.07 to 0.37) and worse PAH-specific (emPHasis-10) health-related quality of life (-5.4; 95% CI, -8.1 to -2.8). There was no difference in dual combination therapy; however, participants with Meth-APAH were less likely to be initiated on triple therapy (odds ratio [OR], 0.43; 95% CI, 0.24 to 0.77) or parenteral therapy (OR, 0.10; 95% CI, 0.04 to 0.24). Participants with Meth-APAH were more likely to seek care in the emergency department (incidence rate ratio, 2.30; 95% CI, 1.71 to 3.11) and more likely to be hospitalized (incidence rate ratio, 1.42; 95% CI, 1.10 to 1.83). Conclusions: Meth-APAH represents a unique clinical phenotype of PAH, most common in the western United States. It accounts for a notable proportion of PAH in expert centers. Assessment for methamphetamine use is necessary in patients with PAH.

Objective: To report the Mayo Clinic experience with coronavirus disease 2019 (COVID-19) related to patient outcomes., Methods: We conducted a retrospective chart review of patients with COVID-19 diagnosed between March 1, 2020, and July 31, 2020, at any of the Mayo Clinic sites. We abstracted pertinent comorbid conditions such as age, sex, body mass index, Charlson Comorbidity Index variables, and treatments received. Factors associated with hospitalization and mortality were assessed in univariate and multivariate models., Results: A total of 7891 patients with confirmed COVID-19 infection with research authorization on file received care across the Mayo Clinic sites during the study period. Of these, 7217 patients were adults 18 years or older who were analyzed further. A total of 897 (11.4%) patients required hospitalization, and 354 (4.9%) received care in the intensive care unit (ICU). All hospitalized patients were reviewed by a COVID-19 Treatment Review Panel, and 77.5% (695 of 897) of inpatients received a COVID-19-directed therapy. Overall mortality was 1.2% (94 of 7891), with 7.1% (64 of 897) mortality in hospitalized patients and 11.3% (40 of 354) in patients requiring ICU care., Conclusion: Mayo Clinic outcomes of patients with COVID-19 infection in the ICU, hospital, and community compare favorably with those reported nationally. This likely reflects the impact of interprofessional multidisciplinary team evaluation, effective leveraging of clinical trials and available treatments, deployment of remote monitoring tools, and maintenance of adequate operating capacity to not require surge adjustments. These best practices can help guide other health care systems with the continuing response to the COVID-19 pandemic., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the design, implementation, and utilization of electronic health record (EHR)-based digital health surveillance strategies used to manage the coronavirus disease 2019 (COVID-19) pandemic and to ensure delivery of high-quality clinical care, such as case identification, remote monitoring, telemedicine services, and recruitment to clinical trials at Mayo Clinic., Methods: The design and implementation work described in this report was performed at Mayo Clinic, a large multistate integrated health care system with more than 1.5 million annual patient visits that uses the Epic EHR system. Rule-based live registries were designed in the EHR system to classify patients who currently test positive for COVID-19, patients who test positive but have recovered from COVID-19, patients who are thought to have COVID-19 but do not yet meet clinical diagnostic criteria, patients who test negative for COVID-19, and patients who exceed a risk score for serious complications from COVID-19., Results: By use of registries, custom dashboards and operational reports were developed to provide a daily high-level summary for clinical practice use and up-to-date information to manage individual patients affected by COVID-19, including support of case identification, contact isolation, and other care management tasks., Conclusion: We developed and implemented a systematic approach to the use of EHR patient registries to manage the COVID-19 pandemic that proved feasible and useful in a large multistate group clinical practice. The key to harnessing the potential of digital surveillance tools to promote patient-centered care during the COVID-19 pandemic was to use the registry data, reports, and dashboards as informatics tools to inform decision-making ., (© 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc.)

Rationale: Patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) typically undergo frequent clinical evaluation. The incidence and outcomes of coronavirus disease (COVID-19) and its impact on routine management for patients with pulmonary vascular disease is currently unknown. Objectives: To assess the cumulative incidence and outcomes of recognized COVID-19 for patients with PAH/CTEPH followed at accredited pulmonary hypertension centers, and to evaluate the pandemic's impact on clinic operations at these centers. Methods: A survey was e-mailed to program directors of centers accredited by the Pulmonary Hypertension Association. Descriptive analyses and linear regression were used to analyze results. Results: Seventy-seven center directors were successfully e-mailed a survey, and 58 responded (75%). The cumulative incidence of COVID-19 recognized in individuals with PAH/CTEPH was 2.9 cases per 1,000 patients, similar to the general U.S. population. In patients with PAH/CTEPH for whom COVID-19 was recognized, 30% were hospitalized and 12% died. These outcomes appear worse than the general population. A large impact on clinic operations was observed including fewer clinic visits and substantially increased use of telehealth. A majority of centers curtailed diagnostic testing and a minority limited new starts of medical therapy. Most centers did not use experimental therapies in patients with PAH/CTEPH diagnosed with COVID-19. Conclusions: The cumulative incidence of COVID-19 recognized in patients with PAH/CTEPH appears similar to the broader population, although outcomes may be worse. Although the total number of patients with PAH/CTEPH recognized to have COVID-19 was small, the impact of COVID-19 on broader clinic operations, testing, and treatment was substantial.

Portopulmonary hypertension (POPH), pulmonary arterial hypertension (PAH) that develops in the setting of portal hypertension, affects 5%-6% of patients with liver disease and is associated with significant morbidity and mortality. A mean pulmonary arterial pressure (mPAP) threshold of 35 mm Hg is used to stratify perioperative risk and liver transplant eligibility in treated POPH patients but does not take into account the specific factors that contribute to the pressure elevation., Methods: In this case series, we describe the characteristics and posttransplant outcomes of patients with treated POPH and an mPAP ≥35 mm Hg and pulmonary vascular resistance (PVR) <250 dynes-s-cm -5 at or just before liver transplantation (LT). We also describe the effect of PAH therapy on pulmonary hemodynamics in patients with POPH., Results: Sixteen patients were included. All patients were on PAH therapy at the time of LT. PAH therapy resulted in a decrease of mPAP (median 18.4%; interquartile range [IQR] 8.9%-27.0%) with a reduction in PVR (median 50.5%; IQR, 45.4%-70.7%), and an increase in both cardiac output (CO) (median 28.1%; IQR 5.7%-63.8%) and PAWP (median 50.0%; IQR 16.7%-108.3%) before LT. One year posttransplant survival was 69% (11/16); however, only 1 death was attributed to POPH. At 1-year posttransplant, 63.6% (7/11) of patients were weaned off all PAH therapy with clinical and echocardiographic resolution of POPH., Conclusions: In treated POPH patients with an mPAP ≥35 mm Hg and PVR < 250 dynes-s-cm -5 before LT, 1-year posttransplant survival was 69% and the majority of patients were able to discontinue PAH therapy., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Objective: To assess the efficacy and safety of lenzilumab in patients with severe coronavirus disease 2019 (COVID-19) pneumonia., Methods: Hospitalized patients with COVID-19 pneumonia and risk factors for poor outcomes were treated with lenzilumab 600 mg intravenously for three doses through an emergency single-use investigational new drug application. Patient characteristics, clinical and laboratory outcomes, and adverse events were recorded. We also identified a cohort of patients matched to the lenzilumab patients for age, sex, and disease severity. Study dates were March 13, 2020, to June 18, 2020. All patients were followed through hospital discharge or death., Results: Twelve patients were treated with lenzilumab; 27 patients comprised the matched control cohort (untreated). Clinical improvement, defined as improvement of at least 2 points on the 8-point ordinal clinical endpoints scale, was observed in 11 of 12 (91.7%) patients treated with lenzilumab and 22 of 27 (81.5%) untreated patients. The time to clinical improvement was significantly shorter for the lenzilumab-treated group compared with the untreated cohort with a median of 5 days versus 11 days (P=.006). Similarly, the proportion of patients with acute respiratory distress syndrome (oxygen saturation/fraction of inspired oxygen<315 mm Hg) was significantly reduced over time when treated with lenzilumab compared with untreated (P<.001). Significant improvement in inflammatory markers (C-reactive protein and interleukin 6) and markers of disease severity (absolute lymphocyte count) were observed in patients who received lenzilumab, but not in untreated patients. Cytokine analysis showed a reduction in inflammatory myeloid cells 2 days after lenzilumab treatment. There were no treatment-emergent adverse events attributable to lenzilumab., Conclusion: In high-risk COVID-19 patients with severe pneumonia, granulocyte-macrophage colony-stimulating factor neutralization with lenzilumab was safe and associated with faster improvement in clinical outcomes, including oxygenation, and greater reductions in inflammatory markers compared with a matched control cohort of patients hospitalized with severe COVID-19 pneumonia. A randomized, placebo-controlled clinical trial to validate these findings is ongoing (NCT04351152)., (Copyright © 2020. Published by Elsevier Inc.)

A bstract: Pulmonary arterial hypertension (PAH) is a devastating disease with significant morbidity and mortality. There are many psychosocial and financial implications of this disease; however, little is known how this affects the treatment of PAH patients. A questionnaire-based prospective cohort study was performed on 106 PAH patients from a Pulmonary Hypertension Center and the Pulmonary Hypertension Association national conference in 2018. The demographic, treatment, psychosocial, employment, financial impact on treatment data was obtained. The majority of patients had cardiopulmonary symptoms despite treatment. The symptoms affected their social and work lives, with about one in three applying for disability because of their PAH. The majority of PAH patients had insurance coverage, but still noted a significant financial burden of the disease, with nearly a half who needed financial assistance to pay for their PAH medications. Thirty (28.3%; 95% CI, 20.6-37.5%) patients mentioned they changed their medication regimen, with some skipping doses outright (28 [26.4%; 95% CI, 19-35.6%]) in order to save money. PAH continues to cause significant psychosocial and financial burden on patients despite advances in medications. This impact ranged from dissatisfaction with quality of life, to unemployment, to altering their medication regimen to save money., Competing Interests: The authors declare no conflict of interest.

Background: Ambrisentan has shown effectiveness in the treatment of Group 1 pulmonary arterial hypertension (PAH). Although portopulmonary hypertension (PoPH) is a subset of Group 1 PAH, few clinical trials have been testing PAH therapies in patients with PoPH. The objective of this study is to evaluate the efficacy and safety of ambrisentan in PoPH., Methods: This study is a prospective, multicenter, open-label trial in which treatment-naive patients with PoPH with Child-Pugh class A/B were administered with ambrisentan for 24 weeks, followed by a long-term extension (24-28 weeks). The primary end-points were change in pulmonary vascular resistance (PVR) and 6-minutes walk distance (6MWD) at 24 weeks, whereas secondary end-points included safety, World Health Organization (WHO) functional class (FC) and echocardiographic assessments., Results: Of the 31 patients, 23 finished 24 weeks of ambrisentan therapy and 19 finished the extension. PVR decreased significantly (mean ± SD) (7.1 ± 5 vs 3.8 ± 1.8 Wood units, p < 0.001), whereas 6MWD remained unchanged (314 ± 94 vs 336 ± 108 m). Other hemodynamic parameters such as right atrial pressure (13 ± 8 vs 9 ± 4 mm Hg, p < 0.05), mean pulmonary arterial pressure (46 ± 13 vs. 38 ± 8 mm Hg, p < 0.01), cardiac index (2.6 ± 0.6 vs. 3.5 ± 0.7 liter/min/m 2 , p < 0.001) showed improvement, whereas pulmonary capillary wedge pressure remained unchanged. Of the 22 patients with WHO FC assessments at baseline and 24 weeks, WHO FC improved significantly (p = 0.005). Most frequent drug-related adverse events were edema (38.7%) and headache (22.5%). One episode of leg edema resulted into the permanent discontinuation of ambrisentan., Conclusions: Ambrisentan monotherapy in PoPH improves hemodynamics and FC at 24 weeks; however, it did not show any improvement in 6MWD. These preliminary outcomes should be interpreted with caution (Clinicaltrials.Gov:NCT01224210)., (Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)