Impact of the COVID-19 pandemic on chronic disease management and patient reported outcomes in patients with pulmonary hypertension: The Pulmonary Hypertension Association Registry.

To better understand the impact of the COVID-19 pandemic on the care of patients with pulmonary hypertension, we conducted a retrospective cohort study evaluating health insurance status, healthcare access, disease severity, and patient reported outcomes in this population. Using the Pulmonary Hypertension Association Registry (PHAR), we defined and extracted a longitudinal cohort of pulmonary arterial hypertension (PAH) patients from the PHAR's inception in 2015 until March 2022. We used generalized estimating equations to model the impact of the COVID-19 pandemic on patient outcomes, adjusting for demographic confounders. We assessed whether insurance status modified these effects via covariate interactions. PAH patients were more likely to be on publicly-sponsored insurance during the COVID-19 pandemic compared with prior, and did not experience statistically significant delays in access to medications, increased emergency room visits or nights in the hospital, or worsening of mental health metrics. Patients on publicly-sponsored insurance had higher healthcare utilization and worse objective measures of disease severity compared with privately insured individuals irrespective of the COVID-19 pandemic. The relatively small impact of the COVID-19 pandemic on pulmonary hypertension-related outcomes was unexpected but may be due to pre-established access to high quality care at pulmonary hypertension comprehensive care centers. Irrespective of the COVID-19 pandemic, patients who were on publicly-sponsored insurance seemed to do worse, consistent with prior studies highlighting outcomes in this population. We speculate that previously established care relationships may lessen the impact of an acute event, such as a pandemic, on patients with chronic illness.

Gaps in the Care of Pulmonary Hypertension: A Cross-Sectional Patient Simulation Study Among Practicing Cardiologists and Pulmonologists.

Background Diagnosis of pulmonary hypertension (PH) is often delayed or missed, leading to disease progression and missed treatment opportunities. In this study, we measured variation in care provided by board-certified cardiologists and pulmonologists in simulated patients with potentially undiagnosed PH. Methods and Results In a cross-sectional study (https://www.clinicaltrials.gov, NCT04693793), 219 US practicing cardiologists and pulmonologists cared for simulated patients presenting with symptoms of chronic dyspnea and associated signs of potential PH. We scored the clinical quality-of-care decisions made in a clinical encounter against predetermined evidence-based criteria. Overall, quality-of-care scores ranged from 18% to 74%, averaging 43.2%±11.5%. PH, when present, was correctly suspected 49.1% of the time. Conversely, physicians incorrectly identified PH in 53.7% of non-PH cases. Physicians ordered 2-dimensional echocardiography in just 64.3% of cases overall. Physicians who ordered 2-dimensional echocardiography in the PH cases were significantly more likely to get the presumptive diagnosis (61.9% versus 30.7%; P<0.001). Ordering other diagnostic work-up items showed similar results for ventilation/perfusion scan (81.5% versus 51.4%; P=0.005) and high-resolution computed tomography (60.4% versus 43.2%; P=0.001). Physicians who correctly identified PH were significantly more likely to order confirmatory right heart catheterization or refer to PH center (67.3% versus 15.8%; P<0.001). Conclusions A wide range of care in the clinical practice among simulated patients presenting with possible PH was found, specifically in the evaluation and plan for definitive diagnosis of patients with PH. The delay or misdiagnosis of PH is likely attributed to a low clinical suspicion, nonspecific symptoms, and underuse of key diagnostic tests. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04693793.

Safety of macitentan for the treatment of pulmonary hypertension: Real-world experience from the OPsumit® USers Registry (OPUS) and OPsumit® Historical USers cohort (OrPHeUS).

Macitentan is an oral endothelin receptor antagonist for the management of pulmonary arterial hypertension (PAH). The OPsumit® USers Registry (OPUS) and the OPsumit® Historical USers cohort (OrPHeUS) medical chart review provide real-world data for patients newly initiating macitentan. This study aims to describe the characteristics, safety profile, and clinical outcomes of PAH patients newly treated with macitentan in the combined OPUS/OrPHeUS data set. OPUS was a prospective, multicenter, long-term, observational drug registry from April 2014 to June 2020. OrPHeUS was a retrospective, US, multicenter chart review: observation period October 2013 to March 2017. All analyses were descriptive. At registry closure in June 2020, the combined population consisted of 5654 patients, of whom 81.9% were diagnosed with PAH. For these 4626 patients, median duration of macitentan exposure observed was 14.5 (Q1 = 5.2, Q3 = 29.0) months; idiopathic PAH (54.8%) was the most common form of PAH; macitentan was initiated as monotherapy (37.9%), or as part of double (48.0%) or triple therapy (14.1%); discontinuation due to nonhepatic/hepatic adverse events occurred in 17.1%/0.3% of patients; 9.9% of patients experienced ≥1 hepatic adverse events; Kaplan-Meier estimates showed that at 1 year 59.9% (95% confidence interval: 58.3, 61.5) of patients were free from hospitalization and survival was 90.4% (89.3, 91.3). This analysis of real-world data from the combined OPUS and OrPHeUS populations demonstrated that macitentan is well tolerated in a large, diverse population of PAH patients, with overall and hepatic safety profiles consistent with previous macitentan clinical trials.

Hispanic Ethnicity and Social Determinants of Health in Pulmonary Arterial Hypertension: The Pulmonary Hypertension Association Registry.

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.

Clinical Differences and Outcomes between Methamphetamine-associated and Idiopathic Pulmonary Arterial Hypertension in the Pulmonary Hypertension Association Registry.

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.

Comparative effectiveness of oral prostacyclin pathway drugs on hospitalization in patients with pulmonary hypertension in the United States: a retrospective database analysis.

Two oral medications targeting the prostacyclin pathway are available to treat pulmonary arterial hypertension in the United States: oral treprostinil and selexipag. We compared real-world hospitalization in patients receiving these medications. A retrospective administrative claims study was conducted using the Optum® Clinformatics® Data Mart database. Patients with pulmonary hypertension were identified using diagnostic codes. Cohort inclusion required age ≥ 18 years, first oral treprostinil or selexipag prescription between 1 January 2015 and 30 September 2017 (index date), and continuous enrollment in the prior ≥6 months. Patients who switched index drug were excluded. Follow-up was from index date until the first of end of index drug exposure, end of continuous enrollment, death, or 31 December 2017. Multivariable Cox proportional hazard and Poisson regression were used to compare risk and rate, respectively, of hospitalization associated with oral treprostinil vs. selexipag, adjusting for potential confounders. The study cohort included 99 patients receiving oral treprostinil and 123 receiving selexipag. Mean age was 61 years, and most patients were females (71%). Compared with oral treprostinil, selexipag was associated with a 46% lower risk of all-cause hospitalization (hazard ratio 0.54, 95% confidence interval 0.31, 0.92; P = 0.02), a 47% lower risk of pulmonary hypertension-related hospitalization (hazard ratio 0.53, 95% confidence interval 0.31, 0.93; P = 0.03), a 42% lower all-cause hospitalization rate (rate ratio 0.58, 95% confidence interval 0.39, 0.87; P = 0.01), and a 46% lower pulmonary hypertension-related hospitalization rate (rate ratio 0.54, 95% confidence interval 0.35, 0.82; P = 0.004). This study suggests that selexipag is associated with lower hospitalization risk and rate than oral treprostinil.

Obesity in Pulmonary Arterial Hypertension (PAH): The Pulmonary Hypertension Association Registry (PHAR).

RATIONALE: Obesity is associated with pulmonary arterial hypertension (PAH), but its impact on outcomes such as health-related quality of life (HRQoL), hospitalizations and survival is not well understood. OBJECTIVES: To assess the effect of obesity on health-related quality of life (HRQoL), hospitalizations and survival in patients with PAH. METHODS: We performed a cohort study of adults with PAH from the Pulmonary Hypertension Association Registry, a prospective multicenter registry. Multivariate linear mixed effects regression was used to examine the relationship between weight categories and HRQoL using the Short Form-12 (SF-12) and emPHasis-10 (e10). We used multivariable negative binomial regression to estimate hospitalization incidence rate ratios (IRRs) and Cox regression to estimate hazard ratios (HRs) for transplant-free survival by weight status. RESULTS: 767 subjects were included: mean age of 57 years, 74% female, 33% overweight and 40% obese, with median follow-up duration of 527 days. Overweight and obese patients had higher baseline e10 scores (worse HRQoL), which persisted over time (p<0.001). The overweight and obese have a trend towards increased incidence of hospitalizations compared to normal weight (IRR 1.34, 95% confidence interval (95%CI) 0.94-1.92 and 1.33, 95%CI 0.93-1.89, respectively). Overweight and obese patients had lower risk of transplant or death as compared to normal weight patients (HR 0.45, 95%CI 0.25-0.80 and 0.39, 95%CI 0.22-0.70, respectively). CONCLUSIONS: In a large multicenter, prospective cohort of PAH, overweight and obese patients had worse disease-specific HRQoL despite better transplant-free survival compared to normal weight patients. Future interventions should address the specific needs of these patients.

Age-related differences in hemodynamics and functional status in pulmonary arterial hypertension: Baseline results from the Pulmonary Hypertension Association Registry.

BACKGROUND: The age of patients with pulmonary arterial hypertension (PAH) has increased, with registries now reporting mean ages of 50 to 65 years old. Limited data exist on age-related differences in hemodynamic and functional assessments in PAH. METHODS: Adults with PAH in the Pulmonary Hypertension Association Registry were divided into 3 groups (18-50, 51-65, and >65 years old). Analysis of variance and chi-square testing were used to assess for baseline differences. Linear regression was used to examine the association of age with continuous hemodynamic and functional variables. RESULTS: A total of 769 patients with mean age of 56 ± 16 years were included. Older patients had more connective tissue disease-associated PAH and less drug-associated PAH. In linear regression models, each year of increased age was associated with shorter 6-minute walk distance (-3.37 meters; 95% CI, -3.97 to -2.76), lower mean pulmonary arterial pressure (-0.21 mm Hg; 95% CI, -0.27 to -0.15), and lower pulmonary vascular resistance (-0.06 Wood units; 95% CI, -0.09 to -0.04). Pulmonary arterial compliance, cardiac index, right ventricular stroke work index, and percent predicted 6-minute walk distance were unrelated to age; resistance-compliance time was negatively related to age (-3 milliseconds per year; 95% CI, -4 to -2). CONCLUSIONS: Relative to their pulmonary vascular resistance, older patients have lower pulmonary artery compliance and worse right ventricular performance. Based on these findings, we suspect that age influences right ventricular loading conditions and the response of the right ventricle to increased afterload.

Safety and tolerability of transition from inhaled treprostinil to oral selexipag in pulmonary arterial hypertension: Results from the TRANSIT-1 study.

BACKGROUND: A long-term trial showed that the oral prostacyclin (PGl2) receptor (IP) agonist, selexipag, delayed disease progression in patients with pulmonary arterial hypertension (PAH). Transition to selexipag in patients treated with more burdensome inhaled therapies that target the prostacyclin pathway may be considered by patients and physicians. The Phase 3b, prospective, open-label TRANSIT-1 (Tolerability and Safety of the Transition From Inhaled Treprostinil to Oral Selexipag in Patients With Pulmonary Arterial Hypertension) study evaluated the safety and tolerability of transition from inhaled treprostinil to oral selexipag. METHODS: Patients receiving non-prostanoid oral PAH therapy and inhaled treprostinil at stable doses, in World Health Organization Functional Class II/III, with 6-minute walk distance ≥ 300 meters were enrolled. The 16-week main treatment period included downtitration of inhaled treprostinil over 8 weeks and parallel uptitration of selexipag over 12 weeks. Sustained treatment transition at Week 16 was defined as (1) receiving selexipag at Week 16; (2) no selexipag interruption(s) totaling ≥ 8 days; and (3) no inhaled treprostinil or other prostanoids after Week 8. Clinical parameters and patient-reported treatment satisfaction outcomes were assessed at Week 16. RESULTS: All 34 enrolled patients completed the study. At Week 16, 32 patients (94.1%) had stopped inhaled treprostinil and were receiving selexipag. Twenty-eight patients (82.4%) met all criteria for sustained treatment transition. During the study, 3 patients discontinued selexipag due to adverse events. Overall, most adverse events were typical of prostanoid therapies and started during the uptitration phase. In general, patients remained clinically stable throughout treatment and reported improved convenience. CONCLUSIONS: Transition to oral selexipag from inhaled treprostinil in PAH patients was successful and well tolerated in most patients, and associated with greater convenience. CLINICAL TRIAL NUMBER: NCT02471183.

Psychometric Validation of the Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Questionnaire: Results of the SYMPHONY Trial.

BACKGROUND: Disease-specific patient-reported outcome (PRO) instruments are important in assessing the impact of disease and treatment. The Pulmonary Arterial Hypertension-Symptoms and Impact Questionnaire is the first instrument for quantifying pulmonary arterial hypertension (PAH) symptoms and impacts developed according to the 2009 US Food and Drug Administration PRO guidance; previous qualitative research in patients with PAH supported its initial content validity. METHODS: Content finalization and psychometric validation were conducted by using data from A Study of Macitentan in Pulmonary Arterial Hypertension to Validate the PAH-SYMPACT (SYMPHONY), a single-arm, 16-week trial with macitentan 10 mg in US patients with PAH. Item performance, Rasch analysis, and factor analyses were used to select the final item content of the PRO and to define its domain structure. Internal consistency, test-retest reliability, known-group and construct validity, sensitivity to change, and influence of oxygen on item performance were evaluated. RESULTS: Data from 278 patients (79% female; mean age: 60 years) were analyzed. Following removal of redundant/misfitting items, the final questionnaire has 11 symptom items across two domains (cardiopulmonary and cardiovascular symptoms) and 11 impact items across two domains (physical and cognitive/emotional impacts). Differential item function analysis confirmed that PRO scoring is unaffected by oxygen use. For all four domains, internal consistency reliability was high (Cronbach's alpha > 0.80), and scores were highly reproducible in stable patients (intraclass correlation coefficient: 0.84-0.94). Correlations with the Cambridge Pulmonary Hypertension Outcome Review questionnaire and the 36-item Medical Outcomes Study Short Form Survey were moderate to high ([r] = 0.34-0.80). The questionnaire differentiated well between patients with varying disease severity levels and was sensitive to improvements in clinician- and patient-reported disease severity. CONCLUSIONS: The Pulmonary Arterial Hypertension-Symptoms and Impact Questionnaire is a brief, disease-specific PRO instrument possessing good psychometric properties that can be administered in clinical practice and clinical studies. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01841762; URL: www.clinicaltrials.gov.

Effects of yoga on patients in an adolescent mental health hospital and the relationship between those effects and the patients' sensory-processing patterns.

PROBLEM: This study investigated the effects of yoga as a sensory regulation tool in reducing adolescent distress in an acute care psychiatric hospital. METHODS: This was a descriptive, correlational pre-intervention/post-intervention design conducted in a mental health hospital over 5 months from mid-January to mid-June 2012. The population consisted of a convenience sample of 75 adolescent mental health unit inpatients and partial-hospitalization patients 12-18 years of age who participated in two or more yoga sessions. Patient charts provided Diagnostic and Statistical Manual of Mental Disorders-IV Axes I-V diagnosis, gender, and age. Dependent variables were pulse and Subjective Units of Disturbance Scale scores, which were recorded before and after each yoga class. The Adult/Adolescent Sensory Profile provided a measure of patient sensory-processing preference levels that were related to the pulse and Subjective Units of Disturbance Scale results. FINDINGS: Yoga sessions significantly improved patient pulse and self-reported distress ratings regardless of gender or sensory profile levels. CONCLUSIONS: This article contributes to research on the therapeutic effects of yoga as a sensory regulation intervention in the treatment of psychiatrically hospitalized adolescents. Yoga has the potential to help adolescents in an acute care psychiatric hospital learn to soothe themselves, to regulate their emotions, and to find relief from emotional distress while hospitalized.