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Background: The characteristics of long-term survivors with idiopathic pulmonary fibrosis (IPF) have never been fully elucidated. We sought to illustrate the attenuated mortality and describe the characteristics of patients with IPF who survived at least 5 years beyond their initial presentation.Methods: Patients with IPF evaluated between 1997 and 2006 were identified through the clinic database. Patients who survived beyond 5 years from the time of their evaluation were compared with those who died or underwent lung transplantation within 5 years. Survival analyses were performed from the time of initial evaluation and contingent on annualized survival thereafter.Results: Eighty-seven patients who survived at least 5 years formed the comparator group to whom other patients were contrasted. These patients had a higher BMI, FVC % predicted, FEV1 % predicted, total lung capacity % predicted, and diffusing capacity of lung for carbon monoxide % predicted, but a lower FEV1/FVC ratio and lower mean pulmonary artery pressures. More than one-half of these patients had moderate or severe disease at the time of presentation. Our annualized contingent survival analyses revealed a progressively increasing median survival dependent on the duration of the disease.Conclusions: Although we were able to demonstrate differences in our 5-year survivors, rather than being a distinct group, these patients appear to exist within a continuum of improving survival dependent on prior disease duration. This progressively improving time-dependent prognosis mandates the serial reevaluation of an individual patient’s projected outcomes. The implementation of dynamic counseling is an important concept in more accurately predicting life expectancy for patients with IPF who are frequently haunted by the prospects of a dismal survival. [ABSTRACT FROM AUTHOR]

Background: Pulmonary hypertension (PH) is a common complication of sarcoidosis that is associated with increased mortality. The pathogenesis of PH in sarcoidosis is uncertain, and the role of pulmonary arterial hypertension (PAH)-specific therapies remains to be determined.Methods: We conducted a retrospective study of patients with sarcoidosis and PH at two referral centers. New York Heart Association (NYHA) functional class, exercise capacity, hemodynamic data, pulmonary function tests, and survival were collected and analyzed.Results: Twenty-two sarcoidosis patients treated with PAH-specific therapies were identified. After a median of 11 months of follow-up, NYHA class was improved in nine subjects. Mean 6-min walk distance (n = 18) increased by 59 m (p = 0.032). Patients with a higher FVC experienced a greater increment in exercise capacity. Among 12 patients with follow-up hemodynamic data, mean pulmonary artery pressure was reduced from 48.5 +/- 4.3 to 39.4 +/- 2.8 mm Hg (p = 0.008). The 1- and 3-year transplant-free survival rates were 90% and 74%, respectively.Conclusions: PAH-specific therapy may improve functional class, exercise capacity, and hemodynamics in PH associated with sarcoidosis. Prospective, controlled trials of PAH therapies for sarcoidosis are warranted to verify this apparent benefit. Mortality among the study population was high, highlighting the need for urgent evaluation at a lung transplant center. [ABSTRACT FROM AUTHOR]

Background: Current clinical guidelines support use of parenteral prostacyclin therapy for patients with pulmonary arterial hypertension (PAH) at intermediate risk. The objective of this study was to assess parenteral prostacyclin therapy use among patients at intermediate risk according to the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) 2.0 four-strata risk assessment model., Methods: This was a retrospective chart review and cross-sectional online survey of healthcare professionals (HCPs). Included patients were classified as intermediate-low or intermediate-high risk per COMPERA 2.0 between 2016 and 2020 (index visit), initiated on a parenteral prostacyclin any time following intermediate risk assessment, and had World Health Organization (WHO) Functional Class (FC), 6-minute walk distance (6MWD), and B-type natriuretic peptide/N-terminal pro B-type natriuretic peptide (BNP/NT-proBNP) assessments at index and first comprehensive follow-up visits (follow-up)., Results: A total of 139 HCPs (53% community-based, 47% Pulmonary Hypertension Care Center-based) participated in the survey and provided 350 patient records; among these, mean age (SD) was 54.1 (15.3) years and 52% were female. Median (IQR) time from parenteral prostacyclin initiation to follow-up was 3.0 months (2.0, 7.0). At parenteral prostacyclin initiation for the 280 patient records with available COMPERA 2.0 assessments, 62% of patients were intermediate-high risk, 33% were intermediate-low risk and 3% were low risk, improving to 38%, 53%, and 8%, respectively, at follow-up., Conclusions: Improvements were seen for the individual COMPERA 2.0 risk calculator parameters and for several other clinical parameters. Findings from this study substantiate recent guidelines suggesting earlier use of this treatment in intermediate-risk patients with PAH., Clinical Trial Number: Not applicable., Competing Interests: Declarations. Ethics approval and consent to participate: All participants provided informed consent prior to completing the survey and could withdraw at any time, and participants who completed the entire survey received a modest monetary incentive. The study protocol was submitted to the WCG Institutional Review Board for ethical approval and was determined to qualify for exemption status because sufficient protections were in place to protect the privacy of subjects and to maintain the confidentiality of data. The study and data accumulation were in conformity with all country, federal, or state laws, and the study adhered to the tenets of the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: O.A.S. is on the Speakers’ Bureau for United Therapeutics Corporation and is a consultant for Altavant Sciences Inc, Acceleron Pharma Inc, and Merck; she is also on an advisory board for Janssen Pharmaceuticals and received support from Ferrer for travel to meetings. A.V. is a consultant for United Therapeutics Corporation, Merck, and Janssen Pharmaceuticals; she is also on the Speakers’ Bureau for United Therapeutics Corporation, Janssen Pharmaceuticals, and Bayer. M.R.S. and M.B. are employees and shareholders of United Therapeutics Corporation., (© 2024. The Author(s).)

Background: The role of serotonin in pulmonary arterial hypertension has been extensively studied in recent decades, with preclinical data strongly indicating involvement in disease pathogenesis; however, clinical studies have yielded mixed results., Methods: ELEVATE-2 was a phase 2b dose-ranging, randomised, double-blind, placebo-controlled, multicentre trial investigating rodatristat ethyl as a treatment for patients with pulmonary arterial hypertension. The study was conducted at 64 sites across 16 countries in Europe and North America. Eligible participants were aged 18 years or older, had pulmonary arterial hypertension with WHO functional class II or III symptom severity, and had received a stable dose and regimen of one or more pulmonary arterial hypertension treatments for at least 12 weeks. Participants were randomly assigned 1:1:1 to receive two placebo tablets, one placebo and one rodatristat ethyl 300 mg tablet, or two rodatristat ethyl 300 mg tablets twice daily using an interactive response system. Participants, investigators, site personnel, and sponsors were masked to treatment allocation. Participants who completed the 24 week treatment period were invited to continue in an open-label extension. The primary endpoint was percent change in pulmonary vascular resistance (PVR) from baseline to week 24. Primary efficacy analyses were conducted on the intention-to-treat population and analyses of harms were conducted in the safety population, which included all patients who received any amount of the study drug. This trial is registered with ClinicalTrials.gov, NCT04712669, and is now complete., Findings: Between March 18, 2021 and Dec 13, 2022, 108 participants were enrolled and randomly assigned. 36 participants received placebo, 36 received rodatristat ethyl 300 mg, and 36 received rodatristat ethyl 600 mg twice daily. Overall, 85 (79%) of participants were female and 23 (21%) were male. The mean age was 52·8 years (SD 14·7) in the full analysis set. In the open-label extension phase, 62 (82%) of participants were female and 14 (18%) were male, and the mean age was 52·8 years (SD 14·7); this phase was terminated following sponsor review of unmasked main study results. Least-squares mean percent change in PVR from baseline to week 24 favoured placebo and was 5·8% (SE 18·1) for the placebo group, 63·1% (18·5) for the rodatristat ethyl 300 mg group, and 64·2% (18·0) for the rodatristat ethyl 600 mg group. Treatment-emergent adverse events (TEAE) were reported for 29 (81%) patients in the placebo group, 33 (92%) patients in the rodatristat ethyl 300 mg group, and all 36 (100%) patients in the rodatristat ethyl 600 mg group. TEAE leading to study discontinuation were reported for three (8%) patients in the placebo group, four (11%) patients in the rodatristat ethyl 300 mg group, and four (11%) in the rodatristat ethyl 600 mg group. There was one (3%) TEAE leading to death in the rodatristat ethyl 300 mg group., Interpretation: Our results indicate that reducing peripheral serotonin concentrations via rodatristat ethyl has a negative effect on pulmonary haemodynamics and cardiac function in patients with pulmonary arterial hypertension. This finding suggests that manipulating this pathway might not be a suitable option for pulmonary arterial hypertension therapy., Funding: Enzyvant Therapeutics (now Sumitomo Pharma America)., Competing Interests: Declaration of interests JD, RG, RJ, WK-K, MP, SW, and HN were all employees of Enzyvant at the time of the study. HML was Chief Medical Officer at Enzyvant at the time of the study. EP, GD, and TM were consultants at Enzyvant at the time of the study. OS received grants or contracts from Aerovate, AOP Orphan, Ferrer, Janssen, and MSD; received consulting fees from AOP Orphan, Enzyvant, Ferrer, Gossamer Bio, Janssen, Liquidia, MSD, and Respira Therapeutics; received honoraria from AOP Orphan, Ferrer, Janssen, and MSD; and has participated on the data monitoring committee or advisory boards for Enzyvant, Gossamer Bio, and Janssen. SS has received grants or contracts from United Therapeutics; received consulting fees for Keros, Liquidia, Merck, and Roivant; received honoraria from Actelion, Bayer, and United Therapeutics; participated on the drug safety monitoring board for the US National Institutes of Health K23 grants; acted as clinical trial endpoint adjudication committee member for a GSK-sponsored randomised controlled trial; and received research grant support from United Therapeutics. AS reports payments made to their institution for grants and contracts from Aerovate, AOP Orphan, Gossamer Bio, and Enzyvant; consulting fees from Liquidia and Merck; and support for meetings or travel from Enzyvant and Liquidia. MH received grants or contracts from Acceleron, AOP Orphan, Janssen, Merck, and Shou Ti; consulting fees from 35 Pharma, Aerovate, Altavant, AOP Orphan, Bayer, Chiesi, Ferrer, Janssen, Kerros, Merck, MorphogenIX, Shou Ti, and United Therapeutics; payment or honoraria from Janssen and Merck; and has participated in a drug safety monitoring board or committee for Acceleron, Altavant, Janssen, Merck, and United Therapeutics. DL received grants or contracts from Aerovate, Janssen, and Merck; acted as a consultant for Bayer, Janssen, and Merck; received honoraria from Janssen and Merck; received support for meetings or travel from Janssen and Merck; and participated as part of a data monitoring committee or advisory board for Insmed, Janssen, and Merck. JF, OAS, VM, and H-AG report no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Rationale: Quantitative interstitial abnormalities (QIAs) are a computed tomography (CT) measure of early parenchymal lung disease associated with worse clinical outcomes, including exercise capacity and symptoms. The presence of pulmonary vasculopathy in QIAs and its role in the QIA-outcome relationship is unknown. Objectives: To quantify radiographic pulmonary vasculopathy in QIAs and determine whether this vasculopathy mediates the QIA-outcome relationship. Methods: Ever-smokers with QIAs, outcomes, and pulmonary vascular mediator data were identified from the Genetic Epidemiology of COPD (COPDGene) study cohort. CT-based vascular mediators were right ventricle-to-left ventricle ratio, pulmonary artery-to-aorta ratio, and preacinar intraparenchymal arterial dilation (pulmonary artery volume, 5-20 mm 2 in cross-sectional area, normalized to total arterial volume). Outcomes were 6-minute walk distance and a modified Medical Council Research Council Dyspnea Scale score of 2 or higher. Adjusted causal mediation analyses were used to determine whether the pulmonary vasculature mediated the QIA effect on outcomes. Associations of preacinar arterial dilation with select plasma biomarkers of pulmonary vascular dysfunction were examined. Measurements and Main Results: Among 8,200 participants, QIA burden correlated positively with vascular damage measures, including preacinar arterial dilation. Preacinar arterial dilation mediated 79.6% of the detrimental impact of QIA on 6-minute walk distance (56.2-100%; P  < 0.001). Pulmonary artery-to-aorta ratio was a weak mediator, and right ventricle-to-left ventricle ratio was a suppressor. Similar results were observed in the relationship between QIA and modified Medical Council Research Council dyspnea score. Preacinar arterial dilation correlated with increased pulmonary vascular dysfunction biomarker levels, including angiopoietin-2 and N-terminal brain natriuretic peptide. Conclusions: Parenchymal QIAs deleteriously impact outcomes primarily through pulmonary vasculopathy. Preacinar arterial dilation may be a novel marker of pulmonary vasculopathy in QIAs.

Pulmonary hypertension (PH) associated with chronic lung disease (CLD) is both common and underrecognised. The presence of PH in the setting of lung disease has been consistently shown to be associated with worse outcomes. Recent epidemiological studies have advanced understanding of the heterogeneity of this patient population and shown that defining both the specific type of CLD as well as the severity of PH ( i.e. deeper phenotyping) is necessary to inform natural history and prognosis. A systematic diagnostic approach to screening and confirmation of suspected PH in CLD is recommended. Numerous uncontrolled studies and one phase 3 randomised, controlled trial have suggested a benefit in treating PH in some patients with CLD, specifically those with fibrotic interstitial lung disease (ILD). However, other studies in diseases such as COPD-PH showed adverse outcomes with some therapies. Given the expanding list of approved pharmacological treatments for pulmonary arterial hypertension, developing a treatment algorithm for specific phenotypes of CLD-PH is required. This article will summarise existing data in COPD, ILD and other chronic lung diseases, and provide recommendations for classification of CLD-PH and approach to the diagnosis and management of these challenging patients., Competing Interests: Conflict of interest: O.A. Shlobin reports consultancy fees from United Therapeutics, Merck, Janssen and Aerami, payment or honoraria for lectures, presentations, manuscript writing or educational events from Ferrera and United Therapeutics, participation on a data safety monitoring board or advisory board with Janssen, and leadership roles with ACCP/Chest and World Symposium on Pulmonary Hypertension task force. Y. Adir reports consultancy fees and payment or honoraria for lectures, presentations, manuscript writing or educational events from MSD Israel and Bayer Israel, support for attending meetings from BI Israel and RAFA Israel, and participation on a data safety monitoring board or advisory board with MSD, GB and Acceleron. J.A. Barbera reports grants from Merck Sharp & Dome and Ferrer International, consultancy fees from Merck Sharp & Dome, Janssen-Cilag and Ferrer International, payment or honoraria for lectures, presentations, manuscript writing or educational events from Merck Sharp & Dome, Janssen-Cilag, Ferrer International and AOP Orphan, support for attending meetings from Merck Sharp & Dome and Janssen-Cilag, and a leadership role with the World Symposium on Pulmonary Hypertension task force. V. Cottin reports consultancy fees and payment or honoraria for lectures, presentations, or educational events from Ferrer/United Therapeutics. S. Harari reports consultancy fees from Roche-Boehringer Ingelheim, payment or honoraria for lectures, presentations, manuscript writing or educational events from Boehringer Ingelheim, participation on a data safety monitoring board or advisory board “Prise en charge pragmatique de la fibrose pulmonaire idiopathique en progression: essai randomisé PROGRESSION-IPF”, and leadership roles with the World Symposium on Pulmonary Hypertension task force, FERS of the ERS and officer of the society, and FATS of the ATS. E-M. Jutant reports consultancy fees from Chiesi, payment or honoraria for lectures, presentations, manuscript writing or educational events from Chiesi, GSK, MSD and AstraZeneca, support for attending meetings from Janssen and MSD, and a leadership role with the World Symposium on Pulmonary Hypertension task force. J. Pepke-Zaba reports grants from MSD, consultancy fees from MSD, Janssen, Gossamer and Ferrer, support for attending meetings from Janssen, and a leadership role with the World Symposium on Pulmonary Hypertension task force. H-A. Ghofrani reports consultancy fees from Gossamer Bio, Inc., Aerovate, Altavant, Bayer AG, Attgeno, Janssen/Actelion, MSD/Acceleron, Pfizer, Liquidia, Morphic and Keros, payment or honoraria for lectures, presentations, manuscript writing or educational events from Bayer AG, Janssen/Actelion, Gossamer Bio, Keros and MSD/Acceleron, participation on a data safety monitoring board or advisory board with Aerovate, Altavant, Attgeno, Janssen/Actelion, Insmed, MSD/Acceleron, Pfizer and Bayer AG, and the following financial (or non-financial) interests: the author's spouse is and employee of Liquidia. R. Channick reports consultancy fees from Bayer, Merck, Gossamer, Respira and Janssen, payment or honoraria for lectures, presentations, manuscript writing or educational events from Bayer and Janssen, and participation on a data safety monitoring board or advisory board with Altavant., (Copyright ©The authors 2024.)

The objective of this analysis was to compare clinician-based and formally calculated risk assessments by REVEAL Lite 2 and COMPERA 2.0 and to characterize parenteral prostacyclin utilization within 90 days of baseline in high-risk patients. A multisite, double-blind, retrospective chart review of patients with pulmonary arterial hypertension (PAH) was conducted with an index period of January 2014-March 2017. Patients were categorized into the "any PAH medication" or "prostacyclin-enriched" cohort based on latest PAH medication initiated within the index period. Clinicians classified the patient's 1-year mortality risk as "low," "intermediate," or "high" based on their clinical assessment. REVEAL Lite 2 and COMPERA 2.0 scores were independently calculated. Risk assessment congruency was evaluated. Parenteral prostacyclin use was evaluated within 90 days of baseline. Thirty-two clinicians participated and abstracted data for 299 patients with PAH. At baseline, mean patient age was 52 years, 6-min walk distance was 226 m, and most patients were WHO functional class II or III. Half of the patients (53%) were classified by clinician assessment as intermediate risk, while most were classified as high risk by REVEAL Lite 2 (59%) and intermediate-high risk by COMPERA 2.0 (52%). Parenteral prostascyclins were underutilized in high-risk patients, and not initiated in a timely fashion. Clinician-assessed risk category was incongruent with tool-based risk assessments in 40%-54% of patients with PAH, suggesting an underestimation of the patient's risk category by clinician gestalt. Additionally, there was a lack of timely prostacyclin initiation for patients with PAH stratified as high-risk by either tool., Competing Interests: Amresh Raina reports no potential conflict of interest with the study. Oksana A. Shlobin has served as a consultant to and on the speaker's bureau for United Therapeutics, Bayer, Merck, and Janssen; and has served as a consultant to Gossamer, Aerami, and Aerovate. Meredith Broderick, Benjamin Wu and Margaret R. Sketch are employees of United Therapeutics Corporation., (© 2024 The Author(s). Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

This real-world study explored factors affecting persistence with macitentan and selexipag treatment from the perspective of 23 healthcare professionals (HCPs) and 134 patients with pulmonary arterial hypertension between 2019 and 2022. Continuous patient/HCP communication and education were key drivers of persistence, as were early discussion and management of side effects., (© 2024 Actelion Pharmaceuticals US, Inc. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Rationale: Little is known about hospitalization in other types of interstitial lung disease (ILD) besides idiopathic pulmonary fibrosis (IPF). Objectives: To determine the frequency of hospitalizations in various types of ILD and elucidate the association of hospitalization with outcomes. Methods: An analysis of the Pulmonary Fibrosis Foundation Patient Registry data was performed. Inpatient hospitalization rates and survival posthospitalization were compared for various types of ILD. Measurements and Main Results: Hospitalization rates were similar across ILD types: 40.6% of participants with IPF, 42.8% of participants with connective tissue disease-related ILD (CTD-ILD), 44.9% of participants with non-IPF idiopathic interstitial pneumonia (IIP), 46.5% of participants with chronic hypersensitivity pneumonitis (CHP), and 53.3% of participants with "other" ILD. All-cause hospitalization was not associated with decreased transplant-free survival (adjusted hazard ratio [AHR], 1.20; 95% confidence interval [CI] = 0.98, 1.46; P  = 0.0759) after adjusting for comorbidities and severity of illness; however, respiratory-related hospitalization was (AHR, 1.53; 95% CI = 1.23, 1.90; P  = 0.0001). Participants with CTD-ILD (HR, 0.43; 95% CI = 0.25, 0.75; P  = 0.0031) and non-IPF IIP (HR, 0.3; 95% CI = 0.15, 0.58; P  = 0.005) had a lower risk of death posthospitalization compared with those with IPF, whereas those with chronic hypersensitivity pneumonitis (HR, 0.67; 95% CI = 0.37, 1.20; P  = 0.1747) or other ILD (HR, 0.54; 95% CI = 0.19, 1.54; P  = 0.25) had a risk comparable with that for IPF. Conclusions: Rates of hospitalization are similar across ILD subtypes. The risk of death or transplant after posthospitalization is lower in patients with CTD-ILD and non-IPF IIP, compared with patients with IPF. In a mixed population of participants with ILD, all-cause hospitalizations were not associated with decreased transplant-free survival; however respiratory-related hospitalizations were.

Pulmonary hypertension (PH) due to interstitial lung disease (ILD), a commonly encountered complication of fibrotic ILDs, is associated with significant morbidity and mortality. Until recently, the studies of pulmonary vasodilator therapy in PH-ILD have been largely disappointing, with some even demonstrating the potential for harm. This paper is part of a series of Consensus Statements from the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative for Group 3 Pulmonary Hypertension, with prior publications covering pathogenesis, prevalence, clinical features, phenotyping, clinical trials, and impact of PH-ILD. It offers a comprehensive review of and a holistic approach to treatment of PH-ILD, including the management of underlying interstitial lung diseases, importance of treating the comorbidities, emphasis on importance of exercise and palliation of dyspnea, and review of the most up-to-date guidelines for referral for potential lung transplant work up. It also summarizes the prior, ongoing, and possibly future studies in treatment of the vascular derangement of this morbid condition., Competing Interests: Dr. Oksana A. Shlobin has consulted for United Therapeutics, Bayer, Altavant, Aerovate, Jenssen&Jenssen and Merck, and is on the speaker bureau for UT, Bayer, and J&J. Mr. Eric Shen is an employee of United Therapeutics Corporation and owns stocks/shares in the company. Dr. Lucilla Piccari has received research funding from and served as a speaker for Janssen and Ferrer, advised Janssen, Ferrer, and United Therapeutics as well as received support for attending congresses from Janssen, MSD, and Ferrer, all of which not related to this manuscript. Dr. John A. Scandurra is an employee of Aria CV Inc. and owns stocks/shares in the company. Dr. Paul M. Hassoun serves on a scientific advisory board for Merck, an activity unrelated to the current work. Dr. Stephen J. Wort received honoraria from Janssen, MSD, Bayer, and Acceleron for advisory boards, received honoraria from Janssen for educational activity, received unrestricted research grants from Janssen and Bayer, and travel grants, conference registration and accommodation from Actelion and GSK. Dr. Sylvia M. Nikkho is an employee of Bayer AG. Dr. Steven D. Nathan a consultant for United Therapeutics, Bellerophon, Third Pole, Roche, Boehringer‐Ingelheim, Merck, and Daewoong., (© 2024 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Pulmonary vascular dysfunction in the absence of pulmonary hypertension (PH) has been observed in patients with idiopathic pulmonary fibrosis (IPF). We describe the prevalence and etiology of elevated pulmonary vascular resistance (PVR) without PH among patients with IPF. Hemodynamic, echocardiographic, and functional respiratory imaging (FRI) data was compared between patients with IPF without PH with normal (<3 wood units) and elevated PVR (≥3 wood units). Mortality between these two groups were compared to patients with IPF and PH. Of 205 patients with IPF, there were 146 patients without PH, of whom 114 (78.1%) had a normal PVR and 32 (21.9%) who had a high PVR. Functional testing and hemodynamics were similar in the two groups, except for the cardiac index which was significantly lower in patients with a high PVR (2.3 vs. 2.6 L/min/m 2 ; p  = 0.004). Echocardiographic comparison demonstrated a higher tricuspid regurgitant velocity in those with a high PVR (3.4 vs 3.0 m/s; p  = 0.046). FRI revealed proportionately fewer large vessels as a proportion of the vasculature in the patients without PH and elevated PVRs. Among patients without PH, PVR was associated with increased mortality. In conclusion, patients with IPF without PH but a high PVR appear to be a distinct phenotype with a prognosis between those with and without PH, likely reflecting the continuum of vascular dysfunction. The basis for this unique hemodynamic profile could not be definitively discerned although FRI suggested an aberrant anatomical vascular response., Competing Interests: S. D. N. is a consultant for United Therapeutics, Roche, Bellerophon, and Merck. He is on the speaker bureau for United Therapeutics and Boehringer‐Ingelheim. O. A. S. is a consultant for United Therapeutics, Janssen, and Altavant, and serves on the speaker bureau of United Therapeutics, Bayer, and Janssen. B. R. L. is an employee of Fluidda, Inc. C. S. K. is a consultant for United Therapeutics, Actelion, Altavant, Merck, and Boehringer‐Ingelheim. The remaining authors declare no conflict of interest., (© 2024 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Connective tissue diseases (CTDs) can be associated with various forms of pulmonary hypertension, including pulmonary arterial hypertension (PAH), pulmonary veno-occlusive disease, pulmonary venous hypertension, interstitial lung disease-associated pulmonary hypertension, chronic thromboembolic pulmonary hypertension, and sometimes a combination of several processes. The prevalence of PAH varies among the different CTDs, with systemic sclerosis (SSc) having the highest at 8%-12%. The most recent European Society of Cardiology/European Respiratory Society guidelines recommend routine annual screening for PAH in SSc and CTDs with SSc features. As CTDs can be associated with a myriad of presentations of pulmonary hypertension, a thorough evaluation to include a right heart catheterization to clearly delineate the hemodynamic profile is essential in developing an appropriate treatment plan. Treatment strategies will depend on the predominant phenotype of pulmonary vasculopathy. In general, management approach to CTD-PAH mirrors that of idiopathic PAH. Despite this, outcomes of CTD-PAH are inferior to those of idiopathic PAH, with those of SSc-PAH being particularly poor. Reasons for this may include extrapulmonary manifestations of CTDs, including renal disease and gastrointestinal involvement, concurrent interstitial lung disease, and differences in the innate response of the right ventricle to increased pulmonary vascular resistance. Early referral for lung transplant evaluation of patients with CTD-PAH, particularly SSc-PAH, is recommended. It is hoped that in the near future, additional therapies may be added to the armamentarium of effective treatments for CTD-PAH. Ultimately, a better understanding of the pathogenesis of CTD-PAH will be required to develop targeted therapies for this morbid condition., Competing Interests: Christopher S. King—Speaker: United Therapeutics, Actelion, Altavant; Consulting—UT, Merck. Oksana A Shlobin—Speaker B: UT, Janssen; Consulting: UT, Janssen, Aerovate, Aerami, Renzyvant, Merck; Educational: Total CME, Medscape. Vikramjit Khangoora—Consulting: Janssen. Elana J. Bernstein—Consulting: Boehringer Ingelheim; Contracted research: Boehringer Ingelheim, Pfizer, Kadmon., (© 2023 The Authors. Pulmonary Circulation published by Wiley Periodicals LLC on behalf of the Pulmonary Vascular Research Institute.)

Pulmonary hypertension (PH) is a risk factor for mortality in patients with sarcoidosis. Severe PH in chronic lung disease has previously been defined as mean pulmonary arterial pressure (mPAP) ≥ 35 mmHg or mPAP 25 ≥ mmHg with cardiac index (CI) ≤ 2 L/min/m 2 . However, there is no clear definition denoting severity of sarcoidosis-associated PH (SAPH). We aimed to determine pulmonary hemodynamic cut-off values where transplant-free survival was worse among patients with SAPH. This was a retrospective cohort analysis of the Registry of SAPH database focusing on pulmonary hemodynamic predictors of transplant-free survival among patients with precapillary SAPH. Cox regression was performed to determine which pulmonary hemodynamic values predicted death or lung transplantation. Kaplan-Meier survival analysis was performed on statistically significant predictors to determine pulmonary hemodynamic cut-off values where transplant-free survival was decreased. Decreased transplant-free survival occurred among SAPH patients with mPAP ≥ 40 mmHg and SAPH patients with pulmonary vascular resistance (PVR) ≥ 5 Woods units (WU). Transplant-free survival was not decreased in patients who fulfilled prior criteria of severe PH in chronic lung disease. We identified new cut-offs with decreased transplant-free survival in the SAPH population. Neither cut-off of mPAP ≥ 40 mmHg nor PVR ≥ 5 WU has previously been shown to be associated with decreased transplant-free survival in SAPH. These values could suggest a new definition of severe SAPH. Our PVR findings are in line with the most recent European Society of Cardiology/European Respiratory Society guideline definition of severe PH in chronic lung disease., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S. J. W. has received honoraria for lectures and advisory boards from Janssen (previously known as Actelion), Bayer, MSD and GSK. He has received travel grants from Janssen and GSK. He has received research grants from Bayer and Janssen. RPB has grant support from Gilead, Bayer, Actelion, Genentech, aTyr, Novartis, and Bellephron for studies in sarcoidosis. O. A. S. consults for and is a speaker for Bayer, United Therapeutics, and Janssen & Janssen. She also consults for Altavant. L. C. P. declares personal fees from Janssen Pharmaceuticals, outside the submitted work. SB has received consultancy fees from aTy and Kinevant. S. D. N. is a consultant for Boehringer‐Ingelheim, Roche, United Therapeutics, Bellerophon, Third Pole, and Merck. He is on the speakers bureau for Boehringer‐Ingelheim and United Therapeutics. R. G. has received consultancy fees from Mallinckrodt. This research did not receive any specific grant from funding agencies in the public, commercial, or not‐for‐profit sectors. The remaining author declare no conflict of interest., (© 2023 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Rationale and Objectives: Lung transplantation is a potentially life-saving treatment option for patients with idiopathic pulmonary fibrosis (IPF); however, not all eligible candidates get referred and listed for transplantation. Amongst IPF patients within the Pulmonary Fibrosis Foundation Patient Registry (PFF-R), we sought to determine the proportion of patients who undergo lung transplant listing and the characteristics associated with transplant listing., Methods: An analysis of IPF patients with at least six months of follow-up data was performed. Patients with well-established contraindications to lung transplantation were excluded. Two complementary analyses were performed. The "prevalent" population included all patients with IPF at time of enrollment into the registry. The "incident severe" population included all patients with IPF who progressed to GAP Stage 3., Results: Of the 2003 patients in the PFF-R, 475 patients were included in the "prevalent" population. Of this group, only 42 (8.8%) were either listed for or underwent lung transplant. Univariable analysis of the "prevalent" population found age (per 10 year increase, OR 0.531, p = 0.0025), percent predicted FVC (OR 0.572, p=<0.0001), percent predicted DLCO (OR 0.606, p < 0.0001), 6-min walk distance (per 50 m, OR 0.831, p = 0.019), and oxygen use at rest (OR 5.157, p < 0.0001) were predictive of listing. On multivariable analysis, age (per 10 year increase, OR 0.558, p = 0.0088), percent predicted FVC (OR 0.728, p = 0.0161), and oxygen use at rest (OR 3.264, p = 0.0029) remained significant predictors for lung transplant listing. The "incident severe" group consisted of 176 patients (8.8%). 24 patients (13.6%) from this cohort were either listed for or received a transplant. Only age (per 10 year increase, OR 0.0286, p = 0.0465) was associated with transplant listing on univariable analysis in the Incident severe population., Conclusion: Only a small proportion of potentially eligible patients with IPF are listed for lung transplantation, even when seen at pulmonary fibrosis centers of excellence. Advanced age appears to be the primary factor associated with failure to be listed. Further refinement of future registry data is required to more clearly delineate exact reasons for low rates of listing., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Objective: Pulmonary artery compliance (PAC), estimated as stroke volume (SV) divided by pulmonary artery pulse pressure (PP), may be a predictor of survival in pulmonary arterial hypertension (PAH). Resistance-compliance (RC) time, the product of PAC and pulmonary vascular resistance, is reported to be a physiological constant. We investigated if differences in PAC and RC time exist between pulmonary hypertension (PH) subgroups and examined whether PAC is an independent predictor of transplant-free survival in PAH., Methods: This was a retrospective analysis of adult PAH (n=532) and chronic thromboembolic PH (CTEPH, n=84) patients enrolled in the US Pulmonary Hypertension Association Registry from 2015 to 2019. PAC and RC time were compared between PH subgroups (connective tissue disease-PAH (CTD-PAH), idiopathic/heritable-PAH (i/h-PAH), drug/toxin-PAH (d/t-PAH)). Cox proportional hazards models were constructed for transplant-free survival, adjusting for REVEAL 2.0 risk score., Results: There were no differences in estimated PAC between PAH subgroups, nor between PAH and CTEPH. RC time was shorter in CTEPH compared with PAH (median 0.55 (IQR 0.45-0.64) vs 0.62 (0.52-0.73) s, p<0.0001). RC time was shortest in CTD-PAH when compared with i/h-PAH and d/t-PAH ((0.59±0.18) vs (0.65±0.20) vs (0.73±0.25) s, p=0.0001). PAC was associated with transplant-free survival (HR 0.72, 95% CI 0.55 to 0.94, p=0.02) but was not an independent predictor of outcome after adjustment for REVEAL 2.0 score., Conclusion: PAC was similar between PH groups and was not an independent predictor of transplant-free survival in PAH. RC time was different between PH subgroups, challenging RC time constancy., Trial Registration Number: NCT04071327., Competing Interests: Competing interests: ARH: consultant for Bayer, Janssen, United Therapeutics, GossamerBio and Complexa. Holds stock in Tenax Therapeutics. MAS: research support from Novartis. Haemodyanamic core lab for Aadi. Consulting/scientific advisory board for Janssen, Acceleron, Liquidia, Bial, Impulse Dynamics. OAS: consultant and speaker for United Therapeutics, Johnson and Johnson, and Bayer. JSS: research grants from Janssen, PhaseBio, Reata, Bayer, United Therapeutics and Covance. Consultant for Janssen, Bayer and United Therapeutics. TDM: consultant for Actelion/Johnson and Johnson, United Therapeutic, SCIOS-Bial and TrioHealth. Advisory Boards for Altevant and Liquidia; MRL: dlinical trial participation with Gilead, Actelion/Janssen, Bayer, United Therapeutics, Altavant and Acceleron (all funds to the institution)., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Right heart (RH) structure and function are major determinants of symptoms and prognosis in pulmonary arterial hypertension (PAH). RH imaging provides detailed information, but evidence and guidelines on the use of RH imaging in treatment decisions are limited. We conducted a Delphi study to gather expert opinion on the role of RH imaging in decision-making for treatment escalation in PAH. A panel of 17 physicians with expertise in PAH and RH imaging used three surveys in a modified Delphi process to reach consensus on the role of RH imaging in PAH. Survey 1 used open-ended questions to gather information. Survey 2 contained Likert scale and other questions intended to identify consensus on topics identified in Survey 1. Survey 3 contained Likert scale questions derived from Survey 2 and summary information on the results of Survey 2. The Delphi panel reached consensus that RH imaging is likely to improve the current risk stratification algorithms and help differentiate risk levels in patients at intermediate risk. Tricuspid annular plane systolic excursion, right ventricular fractional area change, right atrial area, tricuspid regurgitation, inferior venae cavae diameter, and pericardial effusion should be part of routine echocardiography in PAH. Cardiac magnetic resonance imaging is valuable but limited by cost and access. A pattern of abnormal RH imaging results should prompt consideration of hemodynamic evaluation and possible treatment escalation. RH imaging is an important tool for decisions about treatment escalation in PAH, but systematically collected evidence is needed to clarify its role., Competing Interests: Paul Forfia has served on a speaker's bureau and consulted for Bayer, Janssen, and United Therapeutics. Raymond Benza has received consulting fees from Bayer, Janssen, United Therapeutics, Acceleron, CERENO, Abbott, and Gossamer; and advisory board fees from Acceleron. Michele D'Alto has received consulting fees from Janssen, MSD, Dompè, Ferrer, and AOP. Teresa De Marco has received research funding from Acceleron; and has served as a consultant for Action/Janssen, United Therapeutics, BIAL, Merck, NXT, Aerovate, and Pulnovo. Jean M. Elwing has served as a consultant for United Therapeutics, Altavant, Aerovate, Bayer, Gossamer Bio, Acceleron, Janssen, Liquid, and Insmed; and has participated in clinical research funded by Janssen, United Therapeutics, Liquidia, Phase Bio, Gossamer Bio, Bayer, Acceleron, Altavant, and Aerovate. Robert Frantz has received consulting fees from Altavant, Gossamer Bio, Insmed, Liquidia, ShouTi, and Tenax; serves on DSMB for IQVIA; and has received research grants from Bayer and United Therapeutics. Francois Haddad has received research funding from Janssen. Ronald Oudiz has received research funding, advisory board honoraria, and speaker fees from United Therapeutics. Ioana R. Preston has received research funding from Acceleron/Merck, Janssen, United Therapeutics, and PhaseBio; and consulting fees from Acceleron/Merck, Janssen, United Therapeutics, Aerovate, Gossamer Bio, and Respira. Stephan Rosenkranz has received fees for lectures and/or consultations from Abbott, Acceleron, Actelion, Aerovate, Altavant, AOP Orphan, AstraZeneca, Bayer, Boehringer Ingelheim, Edwards, Ferrer, Gossamer, Janssen, MSD, United Therapeutics, and Vifor; and his institution has received research grants from Actelion, AstraZeneca, Bayer, and Janssen. John Ryan has received consulting fees and payment or honoraria from lectures, presentations, speakers' bureaus, manuscript writing, or education events from Bayer, Merck, United Therapeutics, Kiniksa, and Janssen PH. Robert Schilz has received research funding from Acceleron/Merck, United Therapeutics, Respira, and Bellerophon; consulting fees from Janssen, United Therapeutics, and Acceleron; and currently serves on speakers' bureaus for Bayer, Janssen, and United Therapeutics. Oksana A. Shlobin has received consulting fees from United Therapeutics and Janssen; has received honoraria from Medscape, Total CME, and Bayer; and has participated in a Data Safety Monitoring Board or Advisory Board for Janssen and Altavant. Jean‐Luc Vachiery has received consulting fees from Acceleron, Actelion Pharmaceuticals (now Janssen), Altavant, Bayer HealthCare, Boehringer Ingelheim, GlaxoSmithKline, Gossamer Bio, MSD, Novartis, and Shouti. Carmine Dario Vizza has received consulting fees from Acceleron, Janssen, Altavant, Bayer HealthCare, Ferrer, GlaxoSmithKline, Gossamer Bio, and MSD. Anton Vonk Noordegraaf has served as a member of the scientific advisory board of Morphogen‐X, Ferrer, Gosamer Bio, and Johnson & Johnson. The institute of Anton Vonk Noordegraaf has received consulting fees from a speakers' bureau for Johnson & Johnson, MSD, Actelion, Bayer, and Ferrer. Margaret R. Sketch and Meredith Broderick are employees and shareholders of United Therapeutics Corporation. Vallerie McLaughlin has received research funding from Acceleron, Janssen, Sonovie, and United Therapeutics; and consulting fees from Acceleron, Aerovate, Altavant, Bayer, Caremark LLC, CiVi Biopharma Inc., Corvista, Gossamer Bio, Janssen, Merck, and United Therapeutics., (© 2023 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Background: The Distance-Oxygen-Gender-Age-Physiology (DO-GAP) index has been shown to improve prognostication in idiopathic pulmonary fibrosis (IPF) compared to the Gender-Age-Physiology (GAP) score. We sought to externally validate the DO-GAP index compared to the GAP index for baseline risk assessment in patients with IPF. Additionally, we evaluated the utility of serial change in the DO-GAP index in predicting survival., Methods: We performed an analysis of patients with IPF from the Pulmonary Fibrosis Foundation-Patient Registry (PFF-PR). Discrimination and calibration of the two models were assessed to predict transplant-free survival and IPF-related mortality. Joint longitudinal time-to-event modelling was utilised to individualise survival prediction based on DO-GAP index trajectory., Results: There were 516 patients with IPF from the PFF-PR with available demographics, pulmonary function tests, 6-min walk test data and outcomes included in this analysis. The DO-GAP index (C-statistic: 0.73) demonstrated improved discrimination in discerning transplant-free survival compared to the GAP index (C-statistic: 0.67). DO-GAP index calibration was adequate, and the model retained predictive accuracy to identify IPF-related mortality (C-statistic: 0.74). The DO-GAP index was similarly accurate in the subset of patients taking antifibrotic medications. Serial change in the DO-GAP index improved model discrimination (cross-validated area under the curve: 0.83) enabling the personalised prediction of disease trajectory in individual patients., Conclusion: The DO-GAP index is a simple, validated, multidimensional score that accurately predicts transplant-free survival in patients with IPF and can be adapted longitudinally in individual patients. The DO-GAP may also find use in studies of IPF to risk stratify patients and possibly as a clinical trial end-point., Competing Interests: Conflict of interest: C.S. King is a consultant for United Therapeutics, Actelion, Altavant and Boehringer Ingelheim, and serves on the advisory boards for Actelion, United Therapeutics, Merck and Boehringer Ingelheim. Conflict of interest: O.A. Shlobin is a consultant for United Therapeutics, Janssen, and Altavant, and serves on the speaker bureau of United Therapeutics, Bayer and Janssen. Conflict of interest: S.D. Nathan is a consultant for United Therapeutics, Roche, Bellerophon and Merck. He is on the speakers’ bureaus for United Therapeutics and Boehringer Ingelheim. Conflict of interest: A. Chandel, R.V. Ignacio, J. Pastre, V. Khangoora, S. Aryal, A. Nyguist, A. Singhal and K.R. Flaherty have no conflicts of interest to report., (Copyright ©The authors 2023.)

Pulmonary hypertension (PH) is a frequent complication of interstitial lung disease (ILD). Although PH has mostly been described in idiopathic pulmonary fibrosis, it can manifest in association with many other forms of ILD. Associated pathogenetic mechanisms are complex and incompletely understood but there is evidence of disruption of molecular and genetic pathways, with panvascular histopathologic changes, multiple pathophysiologic sequelae, and profound clinical ramifications. While there are some recognized clinical phenotypes such as combined pulmonary fibrosis and emphysema and some possible phenotypes such as connective tissue disease associated with ILD and PH, the identification of further phenotypes of PH in ILD has thus far proven elusive. This statement reviews the current evidence on the pathogenesis, recognized patterns, and useful diagnostic tools to detect phenotypes of PH in ILD. Distinct phenotypes warrant recognition if they are characterized through either a distinct presentation, clinical course, or treatment response. Furthermore, we propose a set of recommendations for future studies that might enable the recognition of new phenotypes., Competing Interests: Dr. Lucilla Piccari has received research funding from and served as a speaker for Janssen and Ferrer, advised Janssen, Ferrer and United Therapeutics as well as received support for attending congresses from Janssen, MSD and Ferrer, all of which not related to this manuscript. Prof Katerina Antoniou has a consultant role for Roche, Boehringer‐Ingelheim, GSK, honoraria for lecturing for Roche, Boehringer‐Ingelheim, GSK, Astra‐Zeneca, Chiesi & Menarini. Dr. Paul M. Hassoun serves on a scientific advisory board for Merck, an activity unrelated to the current work. Dr. Sylvia M. Nikkho is an employee of Bayer AG. Dr. Rajan Saggar has a Consulting and Advisory Role for United Therapeutics, Third Pole, Novartis, Acceleron, Aerovate, and Janssen. Dr. Oksana A. Shlobin has consulted for UT, Bayer, Altavant, Aerovate, Jenssen&Jenssen and Merck, and is on the speaker bureau for UT, Bayer, and JJ. Dr. Steven D. Nathan is a consultant for United Therapeutics, Bellerophon, Third Pole, Roche, Boehringer‐Ingelheim, Merck and Daewoong. Dr. Stephen John Wort received honoraria from Janssen, MSD, Bayer and Acceleron for advisory boards; received honoraria from Janssen for educational activity, received unrestricted research grants from Janssen and Bayer, and travel grants, conference registration, and accommodation from Actelion and GSK. The remaining authors declare no conflict of interest., (© 2023 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Background: Systemic sclerosis (SSc) is a rare, complex, connective tissue disorder. Interstitial lung disease (ILD) is common in SSc, occurring in 35-52% of patients and accounting for 20-40% of mortality. Evolution of therapeutic options has resulted in a lack of consensus on how to manage this condition. This Delphi study was initiated to develop consensus recommendations based on expert physician insights regarding screening, progression, treatment criteria, monitoring of response, and the role of recent therapeutic advances with antifibrotics and immunosuppressants in patients with SSc-ILD., Methods: A modified Delphi process was completed by pulmonologists (n = 13) and rheumatologists (n = 12) with expertise in the management of patients with SSc-ILD. Panelists rated their agreement with each statement on a Likert scale from - 5 (complete disagreement) to + 5 (complete agreement). Consensus was predefined as a mean Likert scale score of ≤  - 2.5 or ≥  + 2.5 with a standard deviation not crossing zero., Results: Panelists recommended that all patients with SSc be screened for ILD by chest auscultation, spirometry with diffusing capacity of the lungs for carbon monoxide, high-resolution computed tomography (HRCT), and/or autoantibody testing. Treatment decisions were influenced by baseline and changes in pulmonary function tests, extent of ILD on HRCT, duration and degree of dyspnea, presence of pulmonary hypertension, and potential contribution of reflux. Treatment success was defined as stabilization or improvement of signs or symptoms of ILD and functional status. Mycophenolate mofetil was identified as the initial treatment of choice. Experts considered nintedanib a therapeutic option in patients with progressive fibrotic ILD despite immunosuppressive therapy or patients contraindicated/unable to tolerate immunotherapy. Concomitant use of nintedanib with MMF/cyclophosphamide can be considered in patients with advanced disease at initial presentation, aggressive ILD, or significant disease progression. Although limited consensus was achieved on the use of tocilizumab, the experts considered it a therapeutic option for patients with early SSc and ILD with elevated acute-phase reactants., Conclusions: This modified Delphi study generated consensus recommendations for management of patients with SSc-ILD in a real-world setting. Findings from this study provide a management algorithm that will be helpful for treating patients with SSc-ILD and addresses a significant unmet need., (© 2023. The Author(s).)

Rationale: There is a noticeable underrepresentation of minorities in clinical trials and registries in pulmonary arterial hypertension (PAH). Prior studies evaluating the association between Hispanic ethnicity and clinical outcomes in patients with PAH have not assessed the socioeconomic profile of Hispanic individuals or the significance of social determinants of health in clinical outcomes. Objectives: To determine the association between Hispanic ethnicity, social determinants of health, and clinical outcomes in PAH. Methods: This was a prospective cohort study of adult participants with PAH enrolled in the Pulmonary Hypertension Association Registry, a multicenter U.S.-based registry of patients treated at pulmonary hypertension care centers. Participants were classified as Hispanics and non-Hispanic White individuals, based on self-reported ethnicity. A comparison of baseline clinical and sociodemographic characteristics between groups was performed as well using absolute standardized differences (ASD). The primary outcome of the study was to assess transplant-free survival between Hispanics and non-Hispanic White individuals. A Cox proportional hazards model was used for the multivariable analysis after adjusting for age, sex, PAH etiology, annual income, education level, and health insurance. Results: A total of 683 individuals were included, 98 (14.3%) of Hispanic ethnicity. Hispanic patients had impaired access to health care (31.6% vs. 12.9% Medicaid/uninsured; ASD, 0.35), lower education level (72.6% vs. 94.0% high school graduates or higher; ASD, 0.60), and lower annual income (32.0% vs. 17.4% with income <20,000 U.S. dollars; ASD, 0.47), compared with non-Hispanic White individuals. Hispanic patients had a higher frequency of emergency room visits and a higher number of hospitalizations, despite having similar disease severity (incidence rate ratio, 1.452; 95% confidence interval [CI], 1.326-1.590; and 1.428; 95% CI, 1.292-1.577, respectively). Although the unadjusted analysis showed a lower transplant/death hazard ratio for Hispanics (hazard ratio, 0.47; 95% CI, 0.24-0.94; P  = 0.032), there was no association between Hispanic ethnicity and outcome in the multivariable model after adjusting for social determinants of health and other covariates (HR, 0.76; 95% CI, 0.35-1.62; P  = 0.474). Conclusions: Hispanic ethnicity was not associated with differences in survival after adjusting for social determinants of health and other factors. Social determinants of health are important to consider when assessing the association between ethnicity and outcomes in PAH.

Pulmonary hypertension (PH) has been linked to worse outcomes in chronic lung diseases. The presence of PH in the setting of underlying Interstitial Lung Disease (ILD) is strongly associated with decreased exercise and functional capacity, an increased risk of hospitalizations and death. Examining the scope of this issue and its impact on patients is the first step in trying to define a roadmap to facilitate and encourage future research in this area. The aim of our working group is to strengthen the communities understanding of PH due to lung diseases and to improve the care and quality of life of affected patients. This introductory statement provides a broad overview and lays the foundation for further in-depth papers on specific topics pertaining to PH-ILD., Competing Interests: Dr. Nikkho is an employee of Bayer AG; Dr. Richter received funding from the JLU‐CAREER program (German Research Foundation, DFG, 413584448) and from the Collaborative Research Center (SFB) 1213—Pulmonary Hypertension and Cor Pulmonale, grant number SFB1213/1, project B08 (German Research Foundation, Bonn, Germany); Eric Shen is an employee of United Therapeutics Corporation; Dr. Abman serves as a scientific advisor to Oak Hill Bio and NHLBI grants HL68702, HL145679 and UHL151458 not related to this manuscript; Dr. Antoniou has no conflict of interest.; Dr. Chung has no conflict of interest as it pertains to this paper; Peter Fernandes is an employee of Bellerophon Pharma; Dr. Hassoun serves on a scientific advisory board for Merck, an activity unrelated to the current work; Howard M. Lazarus is an employee of Altavant Sciences; Dr. Olschewski received funding from Actelion, Algorithm Sciences, AOP, Astra Zeneca, Bayer, Boehringer, Chiesi, GSK, Janssen, Menarini, MSD, Novartis, Ludwig Boltzmann Society, Ferrer, MedUpdate, and Mondial not related to this work; Dr. Piccari has received research funding from and served as a speaker for Janssen as well as received support for attending congresses from Janssen, MSD and Ferrer, not related to this manuscript; Dr. Psotka has no conflict of interest; Dr. Saggar has a Consulting and Advisory Role for United Therapeutics, Third Pole, Novartis, Acceleron, Aerovate, and Janssen; Dr. Shlobin has consulted for UT, Bayer, ALtavant, Aerovate, Jenssen & Jenssen, and Merck, and is on the speaker bureau for UT, Bayer, and J&J; Dr. Stockbridge has no conflict of interest; Dr. Vizza has no conflict of interest regarding this topic; Dr. Vitulo has no conflicts of interest to disclose; Dr. S. John Wort received honoraria from Janssen, MSD, Bayer and Acceleron for advisory boards; received honoraria from Janssen for educational activity, received unrestricted research grants from Janssen and Bayer, and travel grants, conference registration and accommodation from Actelion and GSK; Dr. Nathan is a consultant for United Therapeutics, Bellerophon, Third Pole, Roche, Boehringer‐Ingelheim, Merck and Daewoong., (© 2022 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Background: The use of veno-arterial extracorporeal membrane oxygenation (VA ECMO) for cardiogenic shock in pregnant and postpartum patients remains limited by concerns of bleeding, hemolysis, and fetal risks. This case series examines the underlying characteristics and management strategies for this high-risk population., Methods: All pregnant and post-partum patients who underwent VA ECMO in the cardiovascular intensive care unit between January 1, 2016 and November 1, 2019, were included in this retrospective study. Management of maternal and fetal O 2 delivery, left ventricular (LV) unloading, anticoagulation, and ECMO circuit characteristics were evaluated., Results: Five patients required veno-arterial ECMO for restoration of systemic perfusion. Three patients developed peripartum cardiomyopathy, one septic cardiomyopathy, and one acute right ventricular (RV) failure. The median age was 30.6 years, with median gestational age in pregnant patients of 31 weeks. Maternal and fetal survival to discharge was 80%. Bleeding was the primary complication, with two patients requiring blood transfusions; one requiring interventional radiology (IR) embolization and the other requiring surgical intervention to control bleeding. One patient was successfully delivered on VA ECMO. No fetal complications were directly attributed to VA ECMO., Conclusions: VA ECMO can be employed successfully in obstetric patients with cardiogenic shock with appropriate patient selection. Further research is needed to determine if VA ECMO provides a survival advantage over traditional management strategies in this vulnerable population.

Background: Pulmonary hypertension (PH) is a common complication of interstitial lung disease (ILD) and is associated with worse outcomes and increased mortality. Evaluation of PH is recommended in lung transplant candidates, but there are currently no standardized screening approaches. Trials have identified therapies that are effective in this setting, providing another rationale to routinely screen patients with ILD for PH., Research Question: What screening strategies for identifying PH in patients with ILD are supported by expert consensus?, Study Design and Methods: The study convened a panel of 16 pulmonologists with expertise in PH and ILD, and used a modified Delphi consensus process with three surveys to identify PH screening strategies. Survey 1 consisted primarily of open-ended questions. Surveys 2 and 3 were developed from responses to survey 1 and contained statements about PH screening that panelists rated from -5 (strongly disagree) to 5 (strongly agree)., Results: Panelists reached consensus on several triggers for suspicion of PH including the following: symptoms, clinical signs, findings on chest CT scan or other imaging, abnormalities in pulse oximetry, elevations in brain natriuretic peptide (BNP) or N-terminal pro-brain natriuretic peptide (NT-proBNP), and unexplained worsening in pulmonary function tests or 6-min walk distance. Echocardiography and BNP/NT-proBNP were identified as screening tools for PH. Right heart catheterization was deemed essential for confirming PH., Interpretation: Many patients with ILD may benefit from early evaluation of PH now that an approved therapy is available. Protocols to evaluate patients with ILD often overlap with evaluations for pulmonary hypertension-interstitial lung disease and can be used to assess the risk of PH. Because standardized approaches are lacking, this consensus statement is intended to aid physicians in the identification of patients with ILD and possible PH, and provide guidance for timely right heart catheterization., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors declare no funding or conflicts of interest.

Purpose of Review: Despite improvements in available medical therapies, pulmonary arterial hypertension (PAH) remains a progressive, ultimately fatal disorder. Lung transplantation is a viable treatment option for PAH patients with advanced disease., Recent Findings: Recent guidelines from the International Society of Heart and Lung Transplantation (ISHLT) have updated recommendations regarding time of referral and listing for lung transplantation in PAH. The new guidelines emphasize earlier referral for transplant evaluation to ensure adequate time for proper evaluation and listing. They also incorporate objective risk stratification criteria to assist in decision-making regarding timing of referral and listing. With regards to the transplant procedure, bilateral lung transplantation has largely supplanted heart-lung transplantation as the procedure of choice for transplantation for advanced PAH. Exceptions to this include patients with PAH because of congenital heart disease and those with concurrent LV dysfunction. Use of mechanical support via venoarterial ECMO initiated before transplantation and continued into the early postoperative period is emerging as a standard of care and may help to reduce early posttransplant mortality in this population. There has been increased recognition of the importance of WHO Group 3 pulmonary hypertension. Many of the lessons learned from PAH may be applied when transplanting patients with severe WHO Group 3 pulmonary hypertension., Summary: Patients with PAH present unique challenges with regards to transplantation that require a therapeutic approach distinct from other lung disorders. Lung transplantations for PAH are high-risk endeavors best performed at centers with expertise in management of both PAH and extracorporeal support., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Sarcoidosis associated pulmonary hypertension (SAPH) is a leading contributor to sarcoidosis-related mortality. The 6-min walk test (6MWT) is widely used in assessment of cardiorespiratory conditions. A reduced 6-min walk distance (6MWD) has been associated with increased mortality in SAPH. We examined patients from the Registry of Sarcoidosis Associated Pulmonary Hypertension (ReSAPH) who had performed 6MWT at enrollment to identify variables that affect 6MWD, and the prognostic value of 6MWT variables regarding death or lung transplantation., Material and Methods: ReSAPH patients with available 6MWT were included. Variables analyzed using pre-defined cutoffs included 6MWD, initial and end of test Borg dyspnea score, oxygen saturation, and heart rate at beginning, end, and after 1-min recovery, absolute change in oxygen saturation, modified distance-saturation product (mDSP), and the heart rate recovery at 1-min (HRR)., Findings: 174 patients met inclusion criteria; 48 patients died and 8 underwent lung transplantation. Patients with 6MWD<300 m had a higher chance of dying or undergoing transplantation compared to those with 6MWD>300 m (p = 0.012). No associations with outcome were observed with mDSP cutoff 200 m%, desaturation≥5% and oxygen saturation<88% at end of 6MWT, or multiple HRR cutoffs (13,14,16). 6MWD correlated with initial Borg score, (p = 0.001), DLCO% (p = 0.0001) and sPAP (p = 0.031) on multivariate analysis. These variables were significant for both pre- and post-capillary PH subgroups. 6MWD also correlated with fatigue assessment scale (FAS) (p = 0.015)., Conclusion: Of the parameters evaluated, 6MWD had the greatest prognostic value in SAPH which correlated with other physiologic and hemodynamic variables. 6MWT captures the multidimensional effects of sarcoidosis., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Pulmonary hypertension (PH) because of chronic lung disease is categorized as Group 3 PH in the most recent classification system. Prevalence of these diseases is increasing over time, creating a growing need for effective therapeutic options. Recent approval of the first pulmonary arterial hypertension therapy for the treatment of Group 3 PH related to interstitial lung disease represents an encouraging advancement. This review focuses on molecular mechanisms contributing to pulmonary vasculopathy in chronic hypoxia, the pathology and epidemiology of Group 3 PH, the right ventricular dysfunction observed in this population and clinical trial data that inform the use of pulmonary vasodilators in Group 3 PH.

Despite numerous therapeutic advances in pulmonary arterial hypertension, patients continue to suffer high morbidity and mortality, particularly considering a median age of 50 years. This article explores whether early, robust reduction of right ventricular afterload would facilitate substantial improvement in right ventricular function and thus whether afterload reduction should be a treatment goal for pulmonary arterial hypertension. The earliest clinical studies of prostanoid treatment in pulmonary arterial hypertension demonstrated an important link between lowering mean pulmonary arterial pressure (or pulmonary vascular resistance) and improved survival. Subsequent studies of oral monotherapy or sequential combination therapy demonstrated smaller reductions in mean pulmonary arterial pressure and pulmonary vascular resistance. More recently, retrospective reports of initial aggressive prostanoid treatment or initial combination oral and parenteral therapy have shown marked afterload reduction along with significant improvements in right ventricular function. Some data suggest that reaching threshold levels for pressure or resistance (components of right ventricular afterload) may be key to interrupting the self-perpetuating injury of pulmonary vascular disease in pulmonary arterial hypertension and could translate into improved long-term clinical outcomes. Based on these clues, the authors postulate that improved clinical outcomes might be achieved by targeting significant afterload reduction with initial oral combination therapy and early parenteral prostanoids.

Background: Riociguat is effective in delaying the time to clinical worsening (TCW) in patients with groups 1 and 4 pulmonary hypertension., Research Question: Is riociguat more effective than placebo in prolonging TCW in sarcoidosis-associated pulmonary hypertension (SAPH)?, Study Design and Methods: This was a double-blind placebo-controlled trial. Patients with SAPH confirmed by right heart catheterization were randomized 1:1 to riociguat or placebo. Patients underwent 6-min walk distance (6MWD) and spirometry testing every 8 weeks. The primary end point was TCW, which was defined by the time to the first of the following: (1) all-cause mortality, (2) need for hospitalization because of worsening cardiopulmonary status attributable to progression of disease, (3) > 50 m decrease in the 6MWD test, or (4) worsening of World Health Organization functional class., Results: A total of 16 patients were randomized to riociguat (n = 8) or placebo (n = 8). No difference was found in pulmonary artery mean, pulmonary vascular resistance, initial 6MWD, or FVC between the two groups. Five of eight patients who received placebo met TCW criteria, whereas none of the patients who received riociguat experienced a qualifying event. By log-rank analysis, patients who received riociguat were in the study for a significantly longer period (χ 2  = 6.259; P = .0124). The 6MWD decreased in the placebo group (median, -55.9 m; range, -176.8 to 60 m), but rose in the riociguat group (median, +42.7 m; range, -7.5 to +91.4 m; P = .0149), with a placebo-corrected difference of 94 m (P < .01). Four of eight patients who received riociguat, but only 1 of 8 patients who received placebo, showed a > 30-m improvement in 6MWD (P > .05). No significant adverse events associated with riociguat occurred., Interpretation: Over the 1 year of the study, riociguat was effective in preventing clinical worsening and improving exercise capacity in patients with SAPH., Trial Registry: ClinicalTrials.gov; No.: NCT02625558; URL: www.clinicaltrials.gov., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Introduction: Echocardiographic measurement of the right ventricular systolic pressure (RVSP) is commonly used for estimating systolic pulmonary artery pressure (PASP) measured during right heart catheterization (RHC) in patients suspected for pulmonary hypertension (PH). Generally, there seems to be a strong correlation. However, this has been reported as less robust in sarcoidosis. We aim to investigate the correlation between RVSP and RHC measurements using real world data and analyzed factors influencing the relationship between RVSP and PASP in sarcoidosis., Methods & Results: Data of patients with and without sarcoidosis associated PH who had both a measurable echocardiographic RVSP and invasive PASP were collected from the RESAPH registry, PULSAR study and Cincinnati Sarcoidosis Clinic database (n=173, 60.1% female, mean age 56.0±9.5 years). Among them, 124 had PH confirmed by RHC. There was a strong correlation between RVSP and PASP (r=0.640). This correlation was significant in both male and female, white or non-white, forced vital capacity (FVC) >60%, and presence of fibrosis (p<0.001). However, it was less robust in patients with FVC of 50% or less. RVSP was considered inaccurate if the difference with PASP was > 10mmHg. Inaccurate echocardiographic estimation of the invasive PASP occurred in 50.8%, with overestimation mostly in patients without PH, and underestimation in patients with severe PH. An RVSP>50mmHg was associated with worse survival., Conclusions: In this real world multicenter cohort of sarcoidosis patients, we found a significant correlation between RVSP as determined by echocardiography and invasive PASP. Over- or underestimation of PASP occurred frequently. Therefore, echocardiographic RVSP measurement alone to screen for PH in sarcoidosis should be used with caution., (Copyright: © 2021 SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES.)

Rationale: Interpreting the radiologic data in conjunction with an objective clinical score could help to harmonize idiopathic pulmonary fibrosis (IPF) diagnosis and improve accuracy. Objectives: We sought to establish and validate a multivariable objective scoring model based on clinical parameters by stratifying the risk of patients having IPF diagnosed versus having other forms of interstitial lung disease (ILD) diagnosis. Methods: A clinical score was derived from review of patients evaluated at the Inova Fairfax ILD Program and validated in three distinct cohorts. On the basis of known IPF clinical characteristics, a multivariable model was created and assessed by using receiver operating characteristic curves. Results: There were 844 patients with ILD with either IPF ( n = 347, 41%) or non-IPF ILD ( n = 497, 59%) diagnosis. On the basis of calculated odds ratios, a score was assigned to each of the following clinical parameters: age, sex, smoking history, race or ethnicity, ILD family history, exposures, presence of connective tissue disease signs or symptoms, and velcro crackles. The final Fairfax IPF Clinical Score (FICS) ranged from 1 to 25. The clinical diagnostic score system was accurate in predicting IPF, as measured by the area under the curve (0.88) in the derivation cohort, with similar areas under the curve of 0.91, 0.81, and 0.71 being demonstrated in the respective validation cohorts. Conclusions: The FICS appears to be an accurate tool for estimating the pretest probability of IPF in patients with ILD. How the FICS performs in conjunction with the various high-resolution computed tomographic patterns remains to be determined. This model could ultimately be useful for increasing the degree of confidence in the final diagnosis and could help to obviate the need for lung biopsy in cases with non-usual interstitial pneumonia patterns on high-resolution computed tomographic images.

Tens of thousands of patients with advanced lung diseases may be eligible to be considered as potential candidates for lung transplant around the world each year. The timing of referral, evaluation, determination of candidacy, and listing of candidates continues to pose challenges and even ethical dilemmas. To address these challenges, the International Society for Heart and Lung Transplantation appointed an international group of members to review the literature, to consider recent advances in the management of advanced lung diseases, and to update prior consensus documents on the selection of lung transplant candidates. The purpose of this updated consensus document is to assist providers throughout the world who are caring for patients with pulmonary disease to identify potential candidates for lung transplant, to optimize the timing of the referral of these patients to lung transplant centers, and to provide transplant centers with a framework for evaluating and selecting candidates. In addition to addressing general considerations and providing disease specific recommendations for referral and listing, this updated consensus document includes an ethical framework, a recognition of the variability in acceptance of risk between transplant centers, and establishes a system to account for how a combination of risk factors may be taken into consideration in candidate selection for lung transplantation., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Patients with connective tissue disease (CTD) present unique surgical, perioperative, operative, and postoperative challenges related to the often underlying severe pulmonary hypertension and right ventricular dysfunction. The International Society for Heart and Lung Transplantation-supported consensus document on lung transplantation in patients with CTD standardization addresses the surgical challenges and relevant cardiac involvement in the perioperative, operative, and postoperative management in patients with CTD., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, morbid, potentially curable subtype of pulmonary hypertension that negatively impacts health-related quality of life (HRQoL). Little is known about differences in HRQoL and hospitalization between CTEPH patients and idiopathic pulmonary arterial hypertension (IPAH) patients. Using multivariable linear regression and mixed effects models, we examined differences in HRQoL assessed by emPHasis-10 (E10) and SF-12 between CTEPH and IPAH patients in the Pulmonary Hypertension Association Registry, a prospective multicenter cohort of patients newly evaluated at a Pulmonary Hypertension Care Center. Multivariable negative binomial regression models were used to estimate incidence rate ratios (IRR) for hospitalization amongst the two groups. We included 461 IPAH patients and 169 CTEPH patients. Twenty-one percent of CTEPH patients underwent pulmonary thromboendarterectomy (PTE) before the end of follow-up. At baseline, patients with CTEPH had significantly worse HRQoL (higher E10 scores) (ß 2.83, SE 1.11, p = 0.01); however, differences did not persist over time. CTEPH patients had higher rates of hospitalization (excluding the hospitalization for PTE) compared to IPAH patients after adjusting for age, sex, body mass index, WHO functional class and six-minute walk distance (IRR 1.66, 95%CI 1.04-2.65, p = 0.03). CTEPH patients who underwent PTE had improved HRQoL as compared to those who were medically managed, but patients who underwent PTE were younger, had higher cardiac outputs and greater six-minute walk distances. In this large, prospective, multicenter cohort, CTEPH patients had significantly worse baseline HRQoL and higher rates of hospitalizations than those with IPAH. CTEPH patients who underwent PTE had significant improvements in HRQoL., (© The Author(s) 2021.)

Introduction: Limited evidence exists regarding use of inhaled nitric oxide (iNO) in spontaneously breathing patients. We evaluated the effectiveness of continuous iNO via high-flow nasal cannula (HFNC) in COVID-19 respiratory failure., Methods: We performed a multicenter cohort study of patients with respiratory failure from COVID-19 managed with HFNC. Patients were stratified by administration of iNO via HFNC. Regression analysis was used to compare the need for mechanical ventilation and secondary endpoints including hospital mortality, length of stay, acute kidney injury, need for renal replacement therapy, and need for extracorporeal life support., Results: A total of 272 patients were identified and 66 (24.3%) of these patients received iNO via HFNC for a median of 88 h (interquartile range: 44, 135). After 12 h of iNO, supplemental oxygen requirement was unchanged or increased in 52.7% of patients. Twenty-nine (43.9%) patients treated with iNO compared to 79 (38.3%) patients without iNO therapy required endotracheal intubation ( P  = .47). After multivariable adjustment, there was no difference in need for mechanical ventilation between groups (odds ratio: 1.53; 95% confidence interval [CI]: 0.74-3.17), however, iNO administration was associated with longer hospital length of stay (incidence rate ratio: 1.41; 95% CI: 1.31-1.51). No difference was found for mortality, acute kidney injury, need for renal replacement therapy, or need for extracorporeal life support., Conclusion: In patients with COVID-19 respiratory failure, iNO delivered via HFNC did not reduce oxygen requirements in the majority of patients or improve clinical outcomes. Given the observed association with increased length of stay, judicious selection of those likely to benefit from this therapy is warranted., Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

The diagnosis and management of pulmonary arterial hypertension (PAH) includes several advances, such as a broader recognition of extrapulmonary vascular organ system involvement, validated point-of-care clinical assessment tools, and focus on the early initiation of multiple pharmacotherapeutics in appropriate patients. Indeed, a principal goal in PAH today is an early diagnosis for prompt initiation of treatment to achieve a minimal symptom burden; optimize the patient's biochemical, hemodynamic, and functional profile; and limit adverse events. To accomplish this end, clinicians must be familiar with novel risk factors and the revised hemodynamic definition for PAH. Fresh insights into the role of developmental biology (i.e., perinatal health) may also be useful for predicting incident PAH in early adulthood. Emergent or underused approaches to PAH management include a novel TGF-β ligand trap pharmacotherapy, remote pulmonary arterial pressure monitoring, next-generation imaging using inert gas-based magnetic resonance and other technologies, right atrial pacing, and pulmonary arterial denervation. These and other PAH state of the art advances are summarized here for the wider pulmonary medicine community.

It has been suggested pleural effusions may develop in right heart failure in the absence of left heart disease. The incidence and prognostic significance of pleural effusions in pulmonary arterial hypertension is uncertain. Patients with pulmonary arterial hypertension followed at our tertiary care center were reviewed. Survival was examined based on the subsequent development of a pleural effusion. A total of 191 patients with pulmonary arterial hypertension met the inclusion criteria. The prevalence of pleural effusions on initial assessment was 7.3%. Among patients without a pleural effusion on initial imaging and at least one follow-up computerized tomography ( N  = 142), pleural effusion developed in 27.5% ( N  = 39) of patients. No alternative etiology of the effusion was identified in 19 (48.7%) cases and effusions deemed related to pulmonary arterial hypertension occurred at an incident rate of 38.6 cases per 1000 person-years. Of these, 14 (73.7%) were bilateral, 3 (15.8%) were right-sided, and 2 (10.5%) were left-sided. Effusion size was trace or small in 18 patients (94.7%). Development of a new pleural effusion was associated with attenuated survival in unadjusted survival analysis (HR: 3.80; 95% CI: 1.55-9.31), multivariate analysis (HR: 5.13; 95% CI: 1.86-14.16), and after the multivariate model was adjusted for concomitant pericardial effusion (HR: 4.86; 95% CI: 1.51-15.71). Negative impact on survival remained unchanged when effusions more likely related to an alternative cause were removed from analysis. In conclusion, pleural effusions can complicate pulmonary arterial hypertension in the absence of left heart disease. These effusions are frequently small in size, bilateral in location, and their presence is associated with decreased survival. Attenuated survival appears independent of the risk associated with a new pericardial effusion., (© The Author(s) 2021.)

Background: Aberrations in the coagulation system have been implicated in the pathogenesis of interstitial lung disease (ILD). Anticoagulants have been proposed as a potential therapy in ILD; however, a randomized controlled trial examining warfarin as a treatment for IPF was terminated early due to increased death rates. This has led some to speculate that warfarin specifically may be harmful in ILD, and use of direct oral anticoagulants (DOACs) could result in superior outcomes., Research Question: The goal of this study was to delineate the relationship between anticoagulation and outcomes in patients with ILD through an analysis of the Pulmonary Fibrosis Foundation Patient Registry., Study Design and Methods: An analysis of all patients in the Pulmonary Fibrosis Foundation Patient Registry was performed. Patients were stratified into three groups: no anticoagulation, DOAC use, or warfarin use. Survival was analyzed by using both Kaplan-Meier curves and Cox proportional hazards models., Results: Of 1,911 patients included in the analysis, 174 (9.1%) were given anticoagulants; 93 (4.9%) received DOACs, and 81 (4.2%) received warfarin. There was a twofold increased risk of death or transplant for patients receiving DOACS; for warfarin, the risk was over two and half times greater. DOACs were not associated with an increased risk of mortality following adjustment for confounding variables. However, even after adjustment, patients given the anticoagulant warfarin remained at increased risk of mortality. In patients with IPF, warfarin was associated with reduced transplant-free survival, but DOACs were not. There was no statistically significant difference in survival between those receiving warfarin and those receiving a DOAC., Interpretation: The need for anticoagulation is associated with an increased risk for death or transplant in patients with ILD, in both the IPF and non-IPF population. Further research is required to determine if warfarin and DOACs present varying safety profiles in patients with ILD., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

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.