Burger, Charles

ABSTRACT Pulmonary hypertension (PH) comprises a heterogeneous group of disorders characterized by elevated pressure in the pulmonary arteries. Despite advances in awareness, utilization of non‐invasive screening with echocardiography, increasing number of targeted therapies, and evolving clinical guidelines emphasizing referral to PH specialty centers, barriers to timely diagnosis and treatment persist. Key challenges span patient‐related and system‐level domains that hinder the effective diagnosis, management, and treatment of PH, particularly pulmonary arterial hypertension (PAH). In this article, the obstacles to PH care are examined and actionable recommendations are proposed. By integrating patient‐related and system‐level perspectives, this review provides a framework to bridge persistent gaps in PH care delivery in the United States.

Abstract Rationale Pulmonary arterial hypertension (PAH) is associated with significant morbidity and mortality. The extent of medication nonadherence in PAH is uncertain and may be linked to adverse outcomes. There has been a lack of multicenter, registry-based studies assessing medication nonadherence and patient-centered outcomes in PAH. Objectives To determine the prevalence of self-reported nonadherence in Pulmonary Hypertension Association Registry (PHAR) participants with PAH or chronic thromboembolic pulmonary hypertension and the relationship of nonadherence with several patient-centered outcomes (mortality, hospitalization rates, emergency department visits, and health-related quality of life). Methods Self-reported PAH medication nonadherence was captured at PHAR enrollment and during follow-up visits. Predictors of nonadherence were modeled using generalized estimating equations assuming a binary distribution. Outcomes associated with nonadherence were modeled using generalized estimating equations with a Poisson distribution. Results A total of 1,543 patients were included, of whom 1,092 (70.8%) were female and 1,340 (86.8%) had PAH. The overall rate of any self-reported nonadherence was 6.1% (95% confidence interval [CI], 5.3–6.9). Predictors of nonadherence included self-reported male sex at birth (odds ratio [OR], 1.4; 95% CI, 1.0–1.9; P = 0.02), poverty (OR, 1.6; 95% CI, 1.2–2.3; P = 0.01), not being married or partnered (OR, 1.5; 95% CI, 1.1–1.9; P = 0.01), having Medicaid or no health insurance (OR, 2.1; 95% CI, 1.5–2.9; P < 0.001), and having completed high school but not having a college degree (OR, 1.7; 95% CI, 1.1–2.9; P < 0.001). PHAR participants who reported any nonadherence had 50.0% more emergency department visits (P < 0.001), 13.3% more hospital admissions (P = 0.03), and 61.9% more days hospitalized (P = 0.01). No relationship was observed between nonadherence and the type or number of PAH therapies or all-cause mortality. Participants reporting nonadherence had worse mean Short Form-12 scores (P < 0.001) and worse emPHasis-10 scores (P = 0.02). Conclusions The rate of self-reported nonadherence in PHAR registrants was low but was associated with male sex and several social determinants of health. Although the complexity or type of PAH regimen did not appear to influence nonadherence, nonadherence was associated with numerous adverse patient-centered outcomes, including greater healthcare use and worse health-related quality of life. Because of limitations in the structure of the gathered data, relationships between exposure and outcomes were not temporally definitive; these observations warrant additional prospective studies.

AbstractSelexipag is an oral selective agonist of the prostacyclin receptor approved to treat adults with pulmonary arterial hypertension (PAH). Selexipag is initiated at a dose of 200 μg twice daily (bid) and usually titrated up by 200 μg bid weekly (per label) or more slowly (e.g., every other week in real‐world clinical practice) to the highest tolerated individualized dose (ID) ranging from 200 to 1600 µg bid. In the Phase 3 GRIPHON trial, selexipag delayed disease progression and reduced risk of PAH‐related hospitalization compared with placebo; the effect was consistent across three prespecified ID groups: low (200–400 µg bid), medium (600–1000 µg bid), and high (1200–1600 µg bid). This study evaluated patient outcomes across selexipag dose ranges in real‐world practice. Data were analyzed from 1186 US adult patients with PAH on selexipag from the Komodo closed‐claims database (2015‒2022). Of these, 634 (53.5%) patients completed titration and reached their selexipag ID (43.8% high ID, 29.8% medium ID, 26.3% low ID). Subsequently, 72.4% of patients in the low ID group had dose adjustments compared with 61.9% (medium ID) and 34.5% (high ID; standardized mean difference 0.63). There were no significant differences in patient outcomes, i,e, persistence (time to discontinuation) and risk of all‐cause and PAH‐related hospitalization across ID groups. The findings in this diverse, real‐world population of patients with PAH reinforced an individualized approach to the dosing scheme to maximize benefit‐risk and achieve the highest tolerated dose with selexipag similar to findings from the GRIPHON trial and other studies.

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

Pulmonary arterial hypertension (PAH) is a devastating disease with significant morbidity and mortality. There are many psychosocial and financial implications of this disease; however, little is known how this affects the treatment of PAH patients. A questionnaire-based prospective cohort study was performed on 106 PAH patients from a Pulmonary Hypertension Center and the Pulmonary Hypertension Association national conference in 2018. The demographic, treatment, psychosocial, employment, financial impact on treatment data was obtained. The majority of patients had cardiopulmonary symptoms despite treatment. The symptoms affected their social and work lives, with about one in three applying for disability because of their PAH. The majority of PAH patients had insurance coverage, but still noted a significant financial burden of the disease, with nearly a half who needed financial assistance to pay for their PAH medications. Thirty (28.3%; 95% CI, 20.6–37.5%) patients mentioned they changed their medication regimen, with some skipping doses outright (28 [26.4%; 95% CI, 19–35.6%]) in order to save money. PAH continues to cause significant psychosocial and financial burden on patients despite advances in medications. This impact ranged from dissatisfaction with quality of life, to unemployment, to altering their medication regimen to save money.

Pulmonary arterial hypertension (PAH) is a progressive disease that requires validated biomarkers of disease severity. While PAH is defined hemodynamically by right heart catheterization (RHC), brain natriuretic peptide (BNP) is recommended by guidelines to assess disease status. Retrospectively collected data in 138 group 1 PAH patients were examined for the correlation of BNP levels to simultaneously obtained right heart catheterization (RHC). Patients were mostly Caucasian women, with functional class III symptoms, mean BNP of 406 ± 443 pg/mL, and an average right atrial pressure (RAP) of 9.9 ± 5.7 mm Hg and mean pulmonary artery pressure (mPAP) of 47.3 ± 14.7 mm Hg. Significant correlation was demonstrated between BNP and RAP (p = 0.021) and mPAP (p = 0.003). Additional correlation was seen with right heart size on echocardiography: right atrial (RAE; p = 0.04) and right ventricular enlargement (p = 0.03). An increased BNP level was an independent predictor of mortality (p < 0.0001), along with RAP (p = 0.039) and RAE (p = 0.018). Simultaneous collection of BNP at the time of RHC confirmed the correlation of BNP with right heart hemodynamics. The current results reinforce the use of BNP level as a continuous variable to assess disease severity in group 1 PAH.