Background: Pulmonary hypertension in children is progressive with wide variability in prognosis. This document provides an evidence-based clinical practice guideline for the management of children with progressive pulmonary hypertension despite optimal therapy. Methods: A multidisciplinary panel identified pertinent questions regarding the management of children with pulmonary hypertension that has progressed despite optimal therapy, conducted systematic reviews of the relevant literature, and applied the Grading of Recommendations, Assessment, Development and Evaluation approach to develop clinical recommendations. Results: After reviewing the research evidence, the panel considered the balance of desirable (benefits) and undesirable (harms and burdens) effects of the interventions in each proposed question. Valuation of our main outcomes was also considered, together with resources required, equity, acceptability, and feasibility. Recommendations were developed for or against interventional strategies specific to children with pulmonary hypertension that has progressed despite optimal therapy. Conclusions: Although there is a growing population of children with pulmonary hypertension, there is a striking lack of empirical evidence regarding management of those whose disease has progressed despite optimal pharmacotherapy. The panel formulated and provided the rationale for clinical recommendations for or against interventional strategies on the basis of this limited empirical evidence, coupled with expert opinion, to aid clinicians in the management of these complex pediatric patients. In addition, we identified important areas for future research.

The purpose of this review is to examine past and current literature regarding maternal and fetal outcomes in pregnancy in patients with pulmonary hypertension (PH). In this review we will outline the management of PH during and after pregnancy. Recent retrospective data has shown improvements in maternal and fetal outcomes in PH as well as successful management of PH and RV failure during pregnancy. With more data and experience, outcomes have improved, offering better guidance on the management of pregnancy in the PH patient. While it is important to recognize high-risk patients, low-risk patients may be able to safely carry and deliver a baby, representing a significant shift in the PH world. We hope to focus attention on the following aspects: comprehensive risk stratification, disease optimization, and careful planning through a multidisciplinary team approach.

SESSION TITLE: Chest Infections Case Report Posters 38 SESSION TYPE: Case Report Posters PRESENTED ON: 10/11/2023 12:00 pm - 12:45 pm INTRODUCTION: Legionnaire's disease was first described following an outbreak of severe pneumonia during the 1976 American Legion convention. Dwelling in water sources, Legionella pneumophila is the most common species causing disease, and can result in both community and healthcare associated pneumonias. CASE PRESENTATION: A 51-year-old male with a past medical history of prior tobacco use, hypertension, chronic kidney disease stage 5 not on hemodialysis, diabetes, obstructive sleep apnea, cocaine use, and diastolic heart failure presented to the Emergency Department with 4 days of fevers, progressive dyspnea, and hemoptysis. Initial vitals were notable for fever to 39.5° Celsius, heart rate of 101, blood pressure 137/79, and respiratory rate of 33 with oxygen saturation of 95% on room air. Exam was notable for respiratory distress, diffusely decreased breath sounds, with rhonchi and wheezing, lower extremity edema, and jugular venous distension. Labs revealed hyponatremia (Na 124), creatinine of 9.97, leukocytosis with neutrophilic predominance, and anemia. CT chest showed a consolidative opacity encompassing nearly the entire left lower lobe consistent with a lobar pneumonia. Cultures were obtained, and empiric ceftriaxone, azithromycin, and metronidazole were initiated. His respiratory distress and oxygen requirement rapidly worsened, resulting in medical intensive care unit (MICU) admission. In the MICU, urine legionella antigen returned positive. Levofloxacin was added to his antibiotic regimen. He had rapidly worsening hypoxia and infiltrates on imaging. This was complicated further by worsening hypertension and poor diuretic response. He was emergently intubated and continuous renal replacement therapy was started within 12 hours of admission. Bronchoscopy showed erythematous and hyperemic airways. Serial bronchoscopic alveolar lavage (BAL) showed a progressively bloodier appearance, concerning for diffuse alveolar hemorrhage (DAH). The patient developed progressive acute respiratory distress syndrome (ARDS) with refractory hypoxemia, ultimately requiring veno-venous extracorporeal membrane oxygenation (VV-ECMO) on hospital day 3. Anticoagulation was initially deferred given ongoing hemoptysis and concern for DAH. Repeat BAL revealed no findings of DAH, and anticoagulation was initiated per ECMO protocol. He began to improve, was decannulated from ECMO hospital day 6, and extubated hospital day 22. On discharge, he required no oxygen, though remained newly dialysis dependent, likely as a result of poor preadmission renal function. DISCUSSION: This case demonstrates several typical features of legionellosis, including high fevers, hyponatremia, and diagnosis by legionella urinary antigen test, which has close to 100% specificity, and 56-99% sensitivity. Interestingly, up to 30% of patients with legionellosis may present with hemoptysis, but only six case reports have described legionella associated DAH. Legionellosis with ARDS requiring ECMO has also been described in the literature. However, this is the first report describing a patient with legionella associated DAH and ARDS requiring progression to ECMO. Consideration of anticoagulation to maintain ECMO circuit patency was impacted by concomitant DAH. CONCLUSIONS: Highlighting the rare association between legionellosis and DAH, this case also illustrates the uniquely difficult considerations in pursuing ECMO in the face of worsening ARDS. Higher-quality evidence is needed to help guide practice for critically ill patients with legionellosis and multiple severe complications with competing management, such as DAH and refractory ARDS requiring ECMO. REFERENCE #1: Naqvi A, Kapoor S, Pradhan M, Dicpinigaitis PV. Outcomes of severe Legionella pneumonia requiring extracorporeal membrane oxygenation (ECMO). J Crit Care. 2021 Feb;61:103-106. doi: 10.1016/j.jcrc.2020.10.017. Epub 2020 Oct 24. PMID: 33157304. REFERENCE #2: Ishikawa K, Nakamura T, Matsuo T, Kawai F, Murakami H, Aoki K, Nagasawa T, Uehara Y, Mori N. Clinical Presentation of Legionella pneumophila Serogroup 1-Associated Pneumonia and Diffuse Alveolar Hemorrhage: A Case Report and Literature Review. Am J Case Rep. 2022 Jul 12;23:e936309. doi: 10.12659/AJCR.936309. PMID: 35819928; PMCID: PMC9288852. REFERENCE #3: "Legionellosis." 2022 Sept 6. The World Health Organization. https://www.who.int/news-room/fact-sheets/detail/legionellosis. DISCLOSURES: No relevant relationships by Stephanie Hon Stock holder for publicly traded company relationship with BioNTech Please note: 2020 Added 03/29/2023 by Ann Whalen, source=Web Response, value=Own stock, less than $1,500

Focused cardiac ultrasound (FoCUS) is becoming standard practice in a wide spectrum of clinical settings. There is limited data evaluating the real-world use of FoCUS with artificial intelligence (AI). Our objective was to determine the accuracy of FoCUS AI-assisted left ventricular ejection fraction (LVEF) assessment and compare its accuracy between novice and experienced users. In this prospective, multicentre study, participants requiring a transthoracic echocardiogram (TTE) were recruited to have a FoCUS done by a novice or experienced user. The AI-assisted device calculated LVEF at the bedside, which was subsequently compared to TTE. 449 participants were enrolled with 424 studies included in the final analysis. The overall intraclass coefficient was 0.904, and 0.921 in the novice ( n = 208) and 0.845 in the experienced ( n = 216) cohorts. There was a significant bias of 0.73% towards TTE ( p = 0.005) with a level of agreement of 11.2%. Categorical grading of LVEF severity had excellent agreement to TTE (weighted kappa = 0.83). The area under the curve (AUC) was 0.98 for identifying an abnormal LVEF (<50%) with a sensitivity of 92.8%, specificity of 92.3%, negative predictive value (NPV) of 0.97 and a positive predictive value (PPV) of 0.83. In identifying severe dysfunction (<30%) the AUC was 0.99 with a sensitivity of 78.1%, specificity of 98.0%, NPV of 0.98 and PPV of 0.76. Here we report that FoCUS AI-assisted LVEF assessments provide highly reproducible LVEF estimations in comparison to formal TTE. This finding was consistent among senior and novice echocardiographers suggesting applicability in a variety of clinical settings.

Background: The American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax convened to update clinical practice guidelines for interstitial lung disease (ILD). Objective: To conduct a systematic review to evaluate existing ILD literature to determine whether patients with progressive pulmonary fibrosis (PPF) should be treated with the antifibrotic pirfenidone. Data Sources: A literature search was conducted across MEDLINE, EMBASE, and Cochrane databases through December 2020 for studies using pirfenidone to treat patients with PPF. Data Extraction: Mortality, disease progression, lung function, and adverse event data were extracted. Meta-analyses were performed when possible. The Grading of Recommendations, Assessment, Development and Evaluation Working Group approach was used to assess the quality of evidence. Synthesis: Two studies met inclusion criteria. Meta-analyses revealed that changes in forced vital capacity (FVC) percent predicted (mean difference [MD], 2.3%; 95% confidence interval [CI], 0.5-4.1%), the FVC in milliliters (MD, 100.0 ml; 95% CI, 98.1-101.9 ml), and the 6-minute-walk distance in meters (MD, 25.2 m; 95% CI, 8.3-42.1 m) all favored pirfenidone over placebo. The changes in the diffusing capacity of the lung for carbon monoxide (DLCO) in millimoles per kilopascal per minute (MD, 0.40 mmol/kPa/min; 95%, CI 0.10-0.70 mmol/kPa/min) and risk of DLCO declining more than 15% (relative risk [RR], 0.27; 95% CI, 0.08-0.95) also favored pirfenidone. The risks of gastrointestinal discomfort (RR, 1.83; 95% CI, 1.29-2.60) and photosensitivity (RR, 4.88; 95% CI, 1.09-21.83) were higher with pirfenidone. The quality of the evidence was low or very low according to the Grading of Recommendations, Assessment, Development and Evaluation criteria, depending on the outcome. Conclusions: Pirfenidone use in patients with PPF is associated with a statistically significant decrease in disease progression and with protection of lung function. However, there is very low certainty in the estimated effects because of limitations in the available evidence. Primary Source of Funding: Funded by the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax.

Background: This American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana de Tórax guideline updates prior idiopathic pulmonary fibrosis (IPF) guidelines and addresses the progression of pulmonary fibrosis in patients with interstitial lung diseases (ILDs) other than IPF. Methods: A committee was composed of multidisciplinary experts in ILD, methodologists, and patient representatives. 1) Update of IPF: Radiological and histopathological criteria for IPF were updated by consensus. Questions about transbronchial lung cryobiopsy, genomic classifier testing, antacid medication, and antireflux surgery were informed by systematic reviews and answered with evidence-based recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. 2) Progressive pulmonary fibrosis (PPF): PPF was defined, and then radiological and physiological criteria for PPF were determined by consensus. Questions about pirfenidone and nintedanib were informed by systematic reviews and answered with evidence-based recommendations using the GRADE approach. Results:1) Update of IPF: A conditional recommendation was made to regard transbronchial lung cryobiopsy as an acceptable alternative to surgical lung biopsy in centers with appropriate expertise. No recommendation was made for or against genomic classifier testing. Conditional recommendations were made against antacid medication and antireflux surgery for the treatment of IPF. 2) PPF: PPF was defined as at least two of three criteria (worsening symptoms, radiological progression, and physiological progression) occurring within the past year with no alternative explanation in a patient with an ILD other than IPF. A conditional recommendation was made for nintedanib, and additional research into pirfenidone was recommended. Conclusions: The conditional recommendations in this guideline are intended to provide the basis for rational, informed decisions by clinicians.

Rationale: In 2018, a systematic review evaluating transbronchial lung cryobiopsy (TBLC) in patients with interstitial lung disease (ILD) was performed to inform American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociacion Latinoamericana del Tom clinical practice guidelines on the diagnosis of idiopathic pulmonary fibrosis. Objectives: To perform a new systematic review to inform updated guidelines. Methods: Medlin, Excerpta Medica Database, and the Cochrane Central Register of Controlled Trials (CCTR) were searched through June 2020. Studies that enrolled patients with ILD and reported the diagnostic yield or complication rates of TBLC were selected for inclusion. Data was extracted and then pooled across studies via meta-analysis. The quality of the evidence was appraised using the grading of recommendations, assessment, development, and evaluation approach. Results: Histopathologic diagnostic yield (number of procedures that yielded a histopathologic diagnosis divided by the total number of procedures performed) of TBLC was 80% (95% confidence interval [CI], 76-83%) in patients with ILD. TBLC was complicated by bleeding and pneumothorax in 30% (95% CI, 20-41%) and 8% (95% CI, 6-11%) of patients, respectively. Procedure-related mortality, severe bleeding, prolonged air leak, acute exacerbation, respiratory failure, and respiratory infection were rare. The quality of the evidence was very low owing to the uncontrolled study designs, lack of consecutive enrollment, and inconsistent results. Conclusions: Very low-quality evidence indicated that TBLC has a diagnostic yield of approximately 80% in patients with ILD, with manageable complications.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial pneumonia with impaired survival. Previous guidelines recommend antacid medication to improve respiratory outcomes in patients with IPF. Objectives: This systematic review was undertaken during the development of an American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax guideline. The clinical question was, "Should patients with IPF who have documented abnormal gastroesophageal reflux (GER) with or without symptoms of GER disease 1) be treated with antacid medication or 2) undergo antireflux surgery to improve respiratory outcomes?" Methods: Medline, Embase, the Cochrane Central Register of Controlled Trials, and the gray literature were searched through June 30, 2020. Studies that enrolled patients with IPF and 1) compared antacid medication to placebo or no medication or 2) compared antireflux surgery to no surgery were selected. Meta-analyses were performed when possible. Outcomes included disease progression, mortality, exacerbations, hospitalizations, lung function, respiratory symptoms, GER severity, and adverse effects/complications. Results: For antacid medication, when two studies were aggregated, there was no statistically significant effect on disease progression, defined as a 10% or more decline in FVC, more than 50-m decline in 6-minute walking distance, or death (risk ratio [RR], 0.88; 95% confidence interval [CI], 0.76-1.03). A separate study that could not be included in the meta-analysis found no statistically significant effect on disease progression when defined as a 5% or more decline in FVC or death (RR, 1.10; 95% CI, 1.00-1.21) and an increase in disease progression when defined as a 10% or more decline in FVC or death (RR, 1.28; 95% CI, 1.08-1.51). For antireflux surgery, there was also no statistically significant effect on disease progression (RR, 0.29; 95% CI, 0.06-1.26). Neither antacid medications nor antireflux surgery was associated with improvements in the other outcomes. Conclusions: There is insufficient evidence to conclude that antacid medication or antireflux surgery improves respiratory outcomes in patients with IPF, most of whom had not had abnormal GER confirmed. Well-designed and adequately powered prospective studies with objective evaluation for GER are critical to elucidate the role of antacid medication and antireflux surgery for respiratory outcomes in patients with IPF.

It is important to recognize and treat human immunodeficiency virus-associated pulmonary arterial hypertension (HIV-PAH) because of the associated morbidity and mortality. With the introduction of antiretroviral therapies (ART), improved survival has changed the focus of treatment management from immunodeficiency-related opportunistic infections to chronic cardiovascular complications, including HIV-PAH. The 2018 6th World Symposium of Pulmonary Hypertension recommended a revised definition of PAH that might result in a greater number of patients with HIV-PAH; however, the implication of this change is not yet clear. Here, we review the current literature on the diagnosis, management, and outcomes of patients with HIV-PAH.

Background: Usual interstitial pneumonia (UIP) is the histopathologic hallmark of idiopathic pulmonary fibrosis (IPF), the prototypical interstitial lung disease (ILD). Diagnosis of IPF requires that a typical UIP pattern be identified by using high-resolution chest computed tomography or lung sampling. A genomic classifier for UIP has been developed to predict histopathologic UIP by using lung samples obtained through bronchoscopy. Objective: To perform a systematic review to evaluate genomic classifier testing in the detection of histopathologic UIP to inform new American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax guidelines. Data Sources: Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched through June 2020. Data Extraction: Data were extracted from studies that enrolled patients with ILD and reported the use of genomic classifier testing. Synthesis: Data were aggregated across studies via meta-analysis. The quality of the evidence was appraised by using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Results: Genomic classifier testing had a sensitivity of 68% (95% confidence interval [CI], 55-73%) and a specificity of 92% (95% CI, 81-95%) in predicting the UIP pattern in ILD. Confidence in an IPF diagnosis increased from 43% to 93% in one cohort and from 59% to 89% in another cohort. Agreement levels in categorical IPF and non-IPF diagnoses measured by using a concordance coefficient were 0.75 and 0.64 in the two cohorts. The quality of evidence was moderate for test characteristics and very low for both confidence and agreement. Conclusions: Genomic classifier testing predicts histopathologic UIP in patients with ILD with a specificity of 92% and improves diagnostic confidence; however, sensitivity is only 68%, and testing is not widely available.

Background The American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociaci & oacute;n Latinoamericana del T & oacute;rax convened to update clinical practice guidelines for interstitial lung disease (ILD).Objective To conduct a systematic review to evaluate existing ILD literature to determine whether patients with progressive pulmonary fibrosis (PPF) should be treated with the antifibrotic pirfenidone.Data Sources A literature search was conducted across MEDLINE, EMBASE, and Cochrane databases through December 2020 for studies using pirfenidone to treat patients with PPF.Data Extraction Mortality, disease progression, lung function, and adverse event data were extracted. Meta-analyses were performed when possible. The Grading of Recommendations, Assessment, Development and Evaluation Working Group approach was used to assess the quality of evidence.Synthesis Two studies met inclusion criteria. Meta-analyses revealed that changes in forced vital capacity (FVC) percent predicted (mean difference [MD], 2.3%; 95% confidence interval [CI], 0.5-4.1%), the FVC in milliliters (MD, 100.0 ml; 95% CI, 98.1-101.9 ml), and the 6-minute-walk distance in meters (MD, 25.2 m; 95% CI, 8.3-42.1 m) all favored pirfenidone over placebo. The changes in the diffusing capacity of the lung for carbon monoxide (DLCO) in millimoles per kilopascal per minute (MD, 0.40 mmol/kPa/min; 95%, CI 0.10-0.70 mmol/kPa/min) and risk of DLCO declining more than 15% (relative risk [RR], 0.27; 95% CI, 0.08-0.95) also favored pirfenidone. The risks of gastrointestinal discomfort (RR, 1.83; 95% CI, 1.29-2.60) and photosensitivity (RR, 4.88; 95% CI, 1.09-21.83) were higher with pirfenidone. The quality of the evidence was low or very low according to the Grading of Recommendations, Assessment, Development and Evaluation criteria, depending on the outcome.Conclusions Pirfenidone use in patients with PPF is associated with a statistically significant decrease in disease progression and with protection of lung function. However, there is very low certainty in the estimated effects because of limitations in the available evidence.Primary Source of Funding Funded by the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociaci & oacute;n Latinoamericana del T & oacute;rax.

The Black Lives Matter protests and COVID-19 pandemic have brought widening disparities experienced by disadvantaged communities of color to the forefront, generating much-needed acknowledgement of implicit biases across different professions, including medicine. Health disparities are magnified in rare diseases such as pulmonary arterial hypertension (PAH) and thus require proactive efforts toward equitable care. A key mechanism of health inequity and inequality in PAH is the lack of inclusivity in national registries and in randomized clinical trial (RCT) enrollment, which form the foundations of what is known about epidemiology and treatment algorithms and effectiveness in this field.Registries shed light on the demographics of a disease, including race, ethnicity, sex, age, geographic distribution, and socioeconomic status, which are intertwined and contribute to health disparities. Unfortunately, minority communities are often misrepresented in PAH registries. The REVEAL Registry, a multi-center US-based registry with 3,515 patients, has an overwhelming majority of white patients (72.8%), a trend reproduced in all major registries that report race and ethnicity: US National Institutes of Health registry (85.4%), Surveillance of Pulmonary Hypertension in America registry (81.5%), and the pulmonary hypertension registry of the United Kingdom and Ireland (87.7%).1Medrek S.K. Sahay S. Ethnicity in pulmonary arterial hypertension: possibilities for novel phenotypes in the age of personalized medicine.Chest. 2018; 153: 310-320Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar Although Black patients are reasonably represented in REVEAL Registry compared with the expected prevalence based on the 2019 US census data (12.2% vs 13.4%), there is a noticeable underrepresentation of Hispanic (8.9% vs 18.5%) and Asian/Pacific Islander (3.3% vs 6.1%) patients.1Medrek S.K. Sahay S. Ethnicity in pulmonary arterial hypertension: possibilities for novel phenotypes in the age of personalized medicine.Chest. 2018; 153: 310-320Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar Differences between registry and census demographics are magnified on an international scale because most demographic data come from registries in the United States and Europe, with limited data from Asia, Central and South America, and Africa. Still, this imperfect demographic information from registries remains the only data we have to characterize our PAH population.A closer look at the details of pivotal RCTs reveals a shocking discordance between registry demographics and trial enrollment (Fig 1), which further challenges the internal and external validity of evidence-based treatment guidelines, contributes to unequal access to novel therapies, and ultimately may affect outcomes. All too often, racial and ethnic minorities are underrepresented in white-dominated clinical trials (89.2% white patients in AMBITION,2Galie N. Barbera J.A. Frost A.E. et al.Initial use of ambrisentan + tadalafil in pulmonary arterial hypertension..N Engl J Med. 2015; 373: 834-844Crossref PubMed Scopus (701) Google Scholar 85.2% in SUPER,3Galie N. Ghofrani H.A. Torbicki A. et al.Sildenafil citrate therapy for pulmonary arterial hypertension..N Engl J Med. 2005; 353: 2148-2157Crossref PubMed Scopus (2020) Google Scholar 84.9% in ARIES-2,4Galie N. Olschewski H. Oudiz R.J. et al.Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2..Circulation. 2008; 117: 3010-3019Crossref PubMed Scopus (862) Google Scholar and 83.6% in SC-TRE5Simonneau B. Barst R.J. Galie N. et al.Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial..Am J Respir Crit Care Med. 2002; 165: 800-804Crossref PubMed Scopus (1221) Google Scholar); the percentage of Black patients was as low as 0% (ARIES-24Galie N. Olschewski H. Oudiz R.J. et al.Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2..Circulation. 2008; 117: 3010-3019Crossref PubMed Scopus (862) Google Scholar) to an unimpressive maximum of 15% (Study 3516Channick R.N. Simonneau G. Sitbon O. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study..Lancet. 2001; 358: 1119-1123Abstract Full Text Full Text PDF PubMed Scopus (1401) Google Scholar).1Medrek S.K. Sahay S. Ethnicity in pulmonary arterial hypertension: possibilities for novel phenotypes in the age of personalized medicine.Chest. 2018; 153: 310-320Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar It was not until the INCREASE trial7Waxman A. Restrepo-Jaramillo R. Thenappan T. et al.Inhaled treprostinil in pulmonary hypertension due to interstitial lung disease..N Engl J Med. 2021; 384: 325-334Crossref PubMed Scopus (98) Google Scholar in 2021 that Black patients were relatively “overrepresented” (21.8%). From the limited data available, Black patients constituted 2% to 7% in RCTs compared with 12.2% registered in the REVEAL Registry.1Medrek S.K. Sahay S. Ethnicity in pulmonary arterial hypertension: possibilities for novel phenotypes in the age of personalized medicine.Chest. 2018; 153: 310-320Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar,8Hill N.S. Preston I.R. Roberts K.E. Patients with pulmonary arterial hypertension in clinical trials: who are they?.Proc Am Thorac Soc. 2008; 5: 603-609Crossref PubMed Scopus (11) Google Scholar Some RCTs do not even report or perform subgroup analyses based on racial, ethnic, or socioeconomic status (eg, GRIPHON, the largest PAH RCT ever undertaken). Furthermore, current PAH treatment guidelines are largely derived from the United States, Europe, and Australia, countries that monopolize RCTs. In the United States, there are approximately 133 PAH clinical trials underway, whereas in China and India there are only 13.9Sastry B.K. McGoon M.D. Gibbs J.S. Clinical trials for pulmonary hypertension in the developing world: pulmonary vascular disease: the global perspective.Chest. 2010; 137: 62S-68SAbstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar Even in multinational PAH trials, there is a glaring omission of African countries. Among the recent RCTs, CHEST (riociguat),10Ghofrani G.A. D’Armini A.M. Grimminger F. et al.Riociguat for the treatment of chronic thromboembolic pulmonary hypertension..N Engl J Med. 2013; 369: 319-329Crossref PubMed Scopus (899) Google Scholar PATENT (riociguat),11Ghofrani H.A. Galie N. Grimminger F. et al.Riociguat for the treatment of pulmonary arterial hypertension..N Engl J Med. 2013; 369: 330-340Crossref PubMed Scopus (914) Google Scholar SERAPHIN (macitentan),12Pulido T. Adzerikho I. Channick R.N. et al.Macitentan and morbidity and mortality in pulmonary arterial hypertension..N Engl J Med. 2013; 369: 809-818Crossref PubMed Scopus (930) Google Scholar AMBITION (ambrisentan and tadalafil),2Galie N. Barbera J.A. Frost A.E. et al.Initial use of ambrisentan + tadalafil in pulmonary arterial hypertension..N Engl J Med. 2015; 373: 834-844Crossref PubMed Scopus (701) Google Scholar and GRIPHON (selexipag),13Sitbon O. Channick R.N. Chin K.M. et al.Selexipag for the treatment of pulmonary arterial hypertension..Engl J Med. 2015; 373: 2522-2533Crossref PubMed Scopus (552) Google Scholar South Africa was the only African country included (and that too, only in SERAPHIN); the above-mentioned INCREASE trial (inhaled treprostinil)7Waxman A. Restrepo-Jaramillo R. Thenappan T. et al.Inhaled treprostinil in pulmonary hypertension due to interstitial lung disease..N Engl J Med. 2021; 384: 325-334Crossref PubMed Scopus (98) Google Scholar was conducted entirely in the United States.As such, what is the generalizability of our treatment guidelines? Once referred to a PAH center, patients of diverse backgrounds are treated based on data from RCTs that do not represent that same diversity. Some argue we should be race-blind because the concept of race may not necessarily reflect genetic ancestry. However, it is imperative to consider potential differences in individual response to therapy. For example, Evans et al14Treiber F.A. Jackson R.W. Davis H. et al.Racial differences in endothelin-1 at rest and in response to acute stress in adolescent males..Hypertension. 2000; 35: 722-725Crossref PubMed Scopus (76) Google Scholar and Treiber et al15Gabler N.B. French B. Strom B.L. et al.Race and sex differences in response to endothelin receptor antagonists for pulmonary arterial hypertension..Chest. 2012; 141: 20-26Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar reported that Black patients have increased levels of circulating endothelin-1, and in a pool analysis of six RCTs, Gabler et al16Evans R.R. Phillips B.G. Singh G. Bauman J.L. Gulati A. Racial and gender differences in endothelin-1..Am J Cardiol. 1996; 78: 486-488Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar showed that Black patients had a blunted response to treatment with endothelin receptor antagonists.1Medrek S.K. Sahay S. Ethnicity in pulmonary arterial hypertension: possibilities for novel phenotypes in the age of personalized medicine.Chest. 2018; 153: 310-320Abstract Full Text Full Text PDF PubMed Scopus (15) Google ScholarThus, equitable RCT enrollment is critical to understanding whether PAH outcomes are different depending on the patient population. Given the challenges of categorizing patients and inconsistent demographic reporting, it is easy to appreciate why there are conflicting data regarding the role of race/ethnicity in outcomes. Parikh et al17Parikh K.S. Stackhouse K.A. Hart S.A. Bashore T.M. Krasuski R.A. Health insurance and racial disparities in pulmonary hypertension outcomes.Am J Manag Care. 2017; 23: 474-480PubMed Google Scholar showed that, despite a similar prevalence of PAH in Black (6.6%) and white (6.8%) patients, Black patients had an increased risk of death when adjusted for baseline differences in age and functional class (hazards ratio, 2.06; P = .012); however, the difference disappeared when adjusted for insurance status.17Parikh K.S. Stackhouse K.A. Hart S.A. Bashore T.M. Krasuski R.A. Health insurance and racial disparities in pulmonary hypertension outcomes.Am J Manag Care. 2017; 23: 474-480PubMed Google Scholar In PAHQuERI, a 3-year observational registry, employment status predicted 3-year mortality (P < .0001).18Talwar A. Garcia J.G.N. Tsai H. et al.Health disparities in patients with pulmonary arterial hypertension: a blueprint for action—an official American Thoracic Society statement.Am J Respir Crit Care Med. 2017; 196: e32-e47Crossref PubMed Scopus (22) Google Scholar However, certain races constitute a higher proportion of lower-income groups, which can affect employment and insurance status. In REVEAL Registry, Blacks and Hispanics were in the two lowest income categories at higher frequency (15.98% and 10.20%, respectively), and patients with an income

RATIONALE:Pulmonary Arterial Hypertension (PAH), a rare complication of HHT is associated with poor outcome. There are no trials to date that have investigated whether pulmonary vasodilator therapy improves hemodynamics or survival in this disease. OBJECTIVE:To determine whether pulmonary vasodilator therapy improves survival, exercise capacity, or hemodynamics in HHT patients with pre-capillary PH. METHODS:We performed a before-and-after observational study on a multicenter cohort of subjects with HHT-PAH who received intravenous prostanoid therapy. We then conducted a systematic review, searching Medline and EMBASE through December 2019. Studies that enrolled HHT-PAH subjects and reported treatment outcomes were selected. PROSPERO #158179. RESULTS:Twenty-one articles were selected. Studies were before-and-after observational studies, case reports, and case series. Among all subjects with HHT-PAH, both mPAP (65 ± 19 pre-treatment vs 51 ± 16 mmHg post-treatment p = 0.04) and PVR (12 ± 6 pre-treatment vs 8 ± 4 WU post-treatment p = 0.01) improved with treatment. The mPAP improved with either oral (57 ± 17 pre-treatment versus 44 ± 13 mmHg post-treatment, p = 0.03) or intravenous (80 ± 15 pre-treatment versus 64 ± 16 mmHg post-treatment, p = 0.017) therapy. PVR also improved with either oral (10 ± 4 pre-treatment versus 6 ± 3 WU post-treatment, p = 0.004) or intravenous (17 ± 5 pre-treatment versus 10 ± 4 WU post-treatment, p = 0.04) therapy. Survival among HHT-PAH patients who received oral or intravenous therapy was not different (p = 0.2). Unadjusted survival among HHT-PAH patients was longer than that of IPAH patients (p = 0.008). There was no difference in side effects among HHT-PAH patient who received oral or intravenous therapy (p = 0.1). CONCLUSION:Pulmonary vasodilator therapy is effective in improving hemodynamics of subjects with HHT-PAH and was not associated with increased risk of side effects.

Pulmonary tumor thrombotic microangiopathy is a rare entity, often diagnosed postmortem. We describe a patient with signs and symptoms of pulmonary hypertension secondary to metastatic cholangiocarcinoma with invasion of the myocardium and pulmonary vasculature, and highlight the diagnostic challenges and therapeutic limitations of this disease. (Level of Difficulty: Intermediate.).