Kristin B. Highland

Pulmonary arterial hypertension (PAH) is a chronic and progressive disease with substantial physiological and psychosocial burden. Effective patient education is essential for self‐management and improved outcomes, yet access to reliable information remains limited by brief clinic visits and variable‐quality external resources. Although video‐assisted learning has been used in other chronic diseases, patient perceptions of video education in PAH have not been studied. To address this gap, we developed the SMART‐PAH Library, a web‐based learning management platform featuring 12 concise, expert‐developed videos on key aspects of PAH management. This qualitative pilot explored patient perceptions, feasibility, and perceived impact of the SMART‐PAH library. After completing the SMART‐PAH course, 13 PAH patients participated in semi‐structured virtual interviews exploring user experience, unmet educational needs, and the impact of the content on knowledge and self‐management. Transcripts were analyzed iteratively by multiple reviewers using an inductive grounded theory‐informed approach until thematic saturation was reached. Transcript analysis identified four domains in which patients sought support from a PAH‐focused educational platform: emotional, physical, educational, and structural. Patients valued credible, relatable content, practical disease‐management guidance, and education on under‐addressed topics such as sexual health and palliative care. The platform helped address barriers including limited specialist access, financial complexity, and provider trust through accessible, repeatable reinforcement of clinical guidance. The SMART‐PAH video library was perceived as a feasible and impactful approach to PAH education. Video‐assisted learning can complement traditional PAH care by addressing informational gaps and supporting self‐management. Larger studies are needed to evaluate effects on mental health, patient knowledge, and outcomes.

Sotatercept, a first‐in‐class activin signaling inhibitor, improves pulmonary vascular hemodynamics and clinical outcomes in pulmonary arterial hypertension (PAH). However, despite reductions in mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR), cardiac output (CO) does not generally increase, and some patients experience a decline in CO, a finding of unclear clinical significance. We sought to characterize the heterogeneity of CO responses to sotatercept in PAH and to determine whether incorporating oxygen delivery (DO ₂ ) provides additional insight into the physiological significance of these changes. We retrospectively analyzed PAH patients who underwent right heart catheterization before and during sotatercept therapy (median 7.3 months, IQR 4.8, 9.3). Hemodynamic, echocardiographic, hematologic, and clinical parameters were collected, including functional class, 6‐min walk distance (6MWD) and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP). Patients were dichotomized by CO response (decreased vs. maintained), and DO ₂ was calculated at each catheterization. A total of 56 patients were included. While most demonstrated reductions in PVR and mPAP, 63% experienced decreased CO. Improvements in 6MWD and NT‐proBNP were similar between groups, and hemoglobin increased comparably. However, among patients with decreased CO, 63% had a concomitant decline in DO ₂ accompanied by worsening 6MWD and a reduced NT‐proBNP response. In this real‐world cohort, over half of sotatercept‐treated PAH patients experienced reduced CO despite overall hemodynamic and clinical improvement. Concomitant reductions in DO ₂ identify a subgroup with worse functional outcomes. These findings suggest that DO ₂ adds additional information beyond CO alone when assessing the physiological response to sotatercept.

Introduction: Racial/ethnic minority populations in the US have a high burden of pulmonary arterial hypertension (PAH). Objective: To evaluate demographics, disease characteristics, prescribing patterns, hospitalization, and survival in racial/ethnic groups in the SPHERE registry. Methods: SPHERE was a US, multicenter, prospective, observational registry of adults prescribed selexipag in clinical practice (November 2016–March 2020). Follow-up was ≤ 18 months, with data collected at routine quarterly visits. Results: There were 759 patients with PAH: 549 (72.3%) non-Hispanic White; 117 (15.4%) Black/African American; 45 (5.9%) Hispanic; and 48 (6.3%) other/unknown race/ethnicity. Overall, 50.6% of participants had idiopathic and 27.0% had connective tissue disorder-associated PAH. Median age at diagnosis in non-Hispanic White, Black/African American, and Hispanic groups was 57, 56, and 43 years, and at selexipag initiation was 62, 60, and 51 years, respectively. Hispanic participants had less severe symptoms at enrollment: 40.0% had World Health Organization functional class III versus 53.4% and 50.4% of non-Hispanic White and Black/African American participants, respectively. Comorbidities were high, with some differences between groups. No notable differences existed between groups in selexipag dose or PAH-specific therapy; overall, 30.8% received monotherapy, 55.6% dual therapy, and 8.4% triple therapy before selexipag initiation. Discontinuations resulting from selexipag-related adverse events in any group were few (2.2%–7.7%). All-cause hospitalization and survival were similar across groups. Conclusion: Selexipag was prescribed as part of combination therapy for PAH regardless of differing demographics and clinical characteristics across racial/ethnic groups, with no differences in selexipag discontinuation, hospitalization, and survival.

This chapter describes two major pulmonary complications of systemic sclerosis (SSc, scleroderma) and mixed connective tissue disease (MCTD), namely interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). For each of these serious disease manifestations, the epidemiology, pathobiology, diagnosis, and management are discussed. Given the serious nature of the pulmonary manifestations of these rare systemic diseases, close collaboration and a multidisciplinary approach by pulmonologists and rheumatologists, together with other specialists, is recommended for diagnosis and optimal disease management.

Certain diseases may involve organ systems that cross the boundaries of specialties. For instance, a patient with scleroderma can develop interstitial lung disease, or a patient with relapsing polychondritis can have the clinical manifestation of subglottic stenosis. This book represents a collaboration between specialties, helping clinicians recognize the implications of disease both within their own specialty and in the overlapping specialty. Here, leading experts from the fields of rheumatology and pulmonology provide a masterclass in the care of patients with systemic illnesses that involve the immune system and the lungs. Key Features: Provides an evidence-based clinical approach to the patient with pulmonary manifestations of rheumatic disease Details cutting-edge research with input from the world’s leading experts Discusses possible future directions for research and advancement

Background: Interstitial lung disease (ILD) is a significant cause of morbidity and mortality in patients with systemic sclerosis (SSc). To date, clinical practice guidelines regarding treatment for patients with SSc-ILD are primarily consensus based. Methods: An international expert guideline committee composed of 24 individuals with expertise in rheumatology, SSc, pulmonology, ILD, or methodology, and with personal experience with SSc-ILD, discussed systematic reviews of the published evidence assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Predetermined conflict-of-interest management strategies were applied, and recommendations were made for or against specific treatment interventions exclusively by the nonconflicted panelists. The confidence in effect estimates, importance of outcomes studied, balance of desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention, and implications for health equity were all considered in making the recommendations. This was in accordance with the American Thoracic Society guideline development process, which is in compliance with the Institute of Medicine standards for trustworthy guidelines. Results: For treatment of patients with SSc-ILD, the committee: 1) recommends the use of mycophenolate; 2) recommends further research into the safety and efficacy of (a) pirfenidone and (b) the combination of pirfenidone plus mycophenolate; and 3) suggests the use of (a) cyclophosphamide, (b) rituximab, (c) tocilizumab, (d) nintedanib, and (e) the combination of nintedanib plus mycophenolate. Conclusions: The recommendations herein provide an evidence-based clinical practice guideline for the treatment of patients with SSc-ILD and are intended to serve as the basis for informed and shared decision making by clinicians and patients.

Connective tissue diseases are a multisystem disorder that can cause impairments in quality of life, shorten life expectancy, and increase the risk of mortality at a younger age. These patients have an increased risk for the development of pulmonary hypertension through several mechanisms including pulmonary arterial hypertension and pulmonary hypertension associated with interstitial lung disease. This review aims to discuss the various presentations of connective tissue disease associated with pulmonary hypertension associated with interstitial lung disease, demographics, and survival. It gives an overview of accepted mechanisms of disease pathogenesis, discusses advances in diagnostics, and treatment options. Despite a deeper understanding of disease pathogenesis, treatment for this remains limited to prevention of disease progression. The identification of the primary disease driver requires careful evaluation of the disease phenotype and is a potential target for treatment and prevention of death.

Rationale: The prognosis of pulmonary arterial hypertension is poor, especially amongst patients with connective tissue disease related pulmonary arterial hypertension. Right ventricular contractility is known to be decreased in scleroderma related pulmonary arterial hypertension. However, it is not known whether intrinsic right ventricular dysfunction is seen in a general CTD population. Objectives: In this study of a large cohort of patients with pulmonary arterial hypertension with multi-year follow-up, we sought to examine the association of measurements of right ventricular function with survival in connective tissue disease associated pulmonary arterial hypertension. Methods: Clinical characteristics of a deidentified cohort of 845 patients with pulmonary arterial hypertension were compared between patients with and without connective tissue disease. The Kaplan-Meier method was used to examine the survival of patients over more than 4 years. The association between right ventricular stroke work index and mortality was examined in patients with connective tissue disease associated pulmonary arterial hypertension. Measurements and Main Results: Significant differences in the 6-min walk distance, Borg dyspnea index, right ventricular stroke work index, and pulmonary artery pulsatility index were identified between patients with and without connective tissue disease associated pulmonary arterial hypertension. Patients with connective tissue disease had a lower right ventricular stroke work index, which was associated with decreased survival in this group; this association approached significance when adjusting for age and renal function. Conclusions: Right ventricular dysfunction as measured by right ventricular stroke work index is associated with decreased survival in patients with connective tissue disease associated pulmonary arterial hypertension despite similar pulmonary vascular resistance. These findings are suggestive of intrinsic right ventricular function in connective tissue disease associated pulmonary arterial hypertension that has a negative impact on the long-term survival of these individuals.