Moss, John E.

Abstract Rationale Pulmonary hypertension (PH) develops in up to 50% of patients with advanced interstitial lung disease (ILD) and is associated with increased morbidity, mortality, and impaired quality of life. Early recognition is essential, as available therapy for ILD-PH has been shown to improve outcomes. Identifying physiologic markers of PH may facilitate earlier referral for right heart catheterization (RHC) and initiation of targeted treatment. Thus, this study aimed to (1) compare functional parameters between ILD patients with and without RHC-confirmed PH, and (2) assess the applicability of previously proposed ILD-PH screening criteria. Methods We retrospectively analyzed ILD transplant candidates with available pre-transplant pulmonary function tests (FVC%, DLCO%), echocardiographic right-ventricular systolic pressure (RVSP), six-minute walk distance (6MWD) with oxygen requirement, and RHC data. PH was defined according to the 2022 ESC/ERS criteria. Functional parameters were compared between patients with and without PH. Among those without a prior PH diagnosis, screening thresholds derived from previously published tools were applied (RVSP ≥ 35 mmHg, DLCO < 40%, FVC/DLCO > 1.6, 6MWD < 350 m, or oxygen use during 6MWD). Results Of 107 ILD patients evaluated, 90 had complete RHC data (48 ILD-PH, 42 ILD without PH). Group comparisons are summarized in Table 1. Patients with PH had lower DLCO% (median 18.5 [11.5-26.7] vs 26.5 [20.0-34.7], p = 0.08), higher FVC/DLCO ratios (2.68 [2.1-3.4] vs 1.7 [1.4-2.6], p = 0.08), and higher RVSP (55 [39.7-63.2] vs 39.5 [29-48] mmHg, p = 0.002). Oxygen requirement during 6MWD was more frequent in ILD-PH (79.2% vs 61.9%, p = 0.08). Among patients with PH, 38 (79.16%) had no formal diagnosis prior to pre-transplant RHC. Of these cases, all (100%) met ≥3 screening criteria, most commonly DLCO < 40% (n = 38, 100%), FVC/DLCO > 1.6 (n = 37, 97.3%), and 6MWD < 350 m (n = 33, 86.8%). Additionally, 32 patients (84.21%) met ≥4 criteria and 8 (21.05%) met all five criteria. Conclusion In ILD transplant candidates, patients with PH had worse functional profiles when compared to those without PH, and nearly 80% of PH cases were previously undiagnosed. Systematic application of validated PH screening tools in ILD populations may facilitate earlier recognition, potentially improving patient outcomes. This abstract is funded by: None

Abstract Introduction Pulmonary arterial hypertension (PAH) is a progressive and deadly disease characterized by pulmonary vascular remodeling and eventual right heart failure. A mainstay of treatment for PAH is prostacyclin therapy which can be delivered via continuous subcutaneous (SQ) or intravenous (IV) infusion. Infusion site reactions are a common occurrence with SQ Treprostinil resulting in discontinuation in approximately 10% of patients. Given that switching from SQ to IV prostacyclin therapy contains risks associated with long-term central venous access such as blood stream infections and deep venous thrombosis, the development of better strategies to improve SQ Treprostinil tolerability are needed. Case Report We report two patients with PAH who developed delayed infusion site reactions to SQ Treprostinil. Both patients were female, in their 30s, with severe group 1 PAH (mean pulmonary artery pressures of 44 and 81 mmHg on right heat catheterization at diagnosis), who had been on SQ Treprostinil for approximately 6 years on a dose around 60 ng/kg/min. Within two weeks of starting a new SQ infusion site, each patient developed a raised, hyperemic site reaction in the area of the infusion catheter draining yellow fluid (Figure 1). Skin patch testing was done from an ampule of preservative-free Treprostinil demonstrating a type 1 hypersensitivity reaction. There was no skin reaction to the Tegaderm dressing alone. Dupilumab 300 mg weekly SQ injections were started for these type 1 hypersensitivity reactions with resolution of the site reactions and pain. Because of this, both patients were able to remain on their SQ Treprostinil infusions. Discussion Infusion site reactions to SQ Treprostinil are common and can necessitate discontinuation of the medication. SQ Treprostinil infusion site reactions typically occur within 48 hours of establishing a new SQ infusion site and are thought to be a local vasodilatory reaction to the Treprostinil itself. These reactions can be minimized by analgesic pain medication and by increasing the Treprostinil infusion concentration. Here we describe two infusion site reactions that occurred two weeks after establishing a new site and were consistent with a type 1 hypersensitivity reaction. These reactions were successfully treated with Dupilumab which allowed the patients to remain on SQ Treprostinil. This abstract is funded by: None

Abstract Rationale: Since the initial descriptions of pulmonary arterial hypertension (PAH), there has been a significant increase in PAH diagnoses among the geriatric population. Studies suggest that older PAH patients exhibit unique hemodynamic profiles and treatment responses. We hypothesized that patients ≥80 years old would have a unique clinical profile and worse outcomes. Methods: The Pulmonary Hypertension Association Registry (PHAR) is a prospective cohort of PAH and chronic thromboembolic pulmonary hypertension (CTEPH) patients new to care at a Pulmonary Hypertension Care Center in the US. Individuals <18 years of age and those with CTEPH were excluded. Clinical data, quality of life measures, and functional capacity were recorded at time of enrollment and at follow up visits. Octogenarians were defined as those ≥80 years old and non-octogenarians as <80 years old. Associations between age subgroups with the change in six-minute walk distance (6MWD), and worsened WHO functional class (WHO FC) at the next visit, and time to all-cause mortality were assessed using linear, binomial, and Cox regression, respectively. Results: The study sample included 87 PAH octogenarian patients and 2,583 non-octogenarian patients at enrollment. The Table shows that octogenarian PAH patients were of similar sex and race distribution as others, but had lower body mass index. Octogenarians were more likely to have idiopathic or CTD-related PAH, and differed from younger patients in terms of several sociodemographic variables. PAH treatment, WHO FC, quality of life, and hemodynamic also differed between the groups. Octogenarians had a lower change in 6MWD (-26m, 95%CI -52 – -2, p = 0.066) and worse WHO FC (2.0, 95%CI 1.1 – 3.8, p = 0.038) over time compared to other adults after adjustment for sex, BMI, PAH etiology, annual income, marital status, right atrial pressure, mean pulmonary artery pressure, and PAH treatment. Octogenarians had an increased risk of death compared to younger adults (hazard ratio 1.7, 95%CI 1.1 – 2.6, p = 0.022) after adjustment for covariates. Conclusions: While the eldest PAH patients may have some comparable features to younger patients, they are different in a variety of socioeconomic variables, disease type, hemodynamics, and number of PAH therapies. The eldest PAH patients demonstrate worse exercise and functional capacity with time and a 70% increased risk of death compared to younger patients. Further studies are needed to better characterize PAH in the elderly, as this may lead to more effective treatments and enhanced quality of life.

Background. The current model for end-stage liver disease (MELD) exception policies for portopulmonary hypertension (POPH) require serial right heart catheterizations (RHCs) every 3 mo to maintain exception points. RHC is necessary for the initial diagnosis of POPH, but the utility of serial catheterizations has not been studied. In patients with POPH MELD exceptions, we sought to compare noninvasive and invasive hemodynamics and determine the sensitivity of echocardiography for the detection of hemodynamically severe POPH that would preclude liver transplant. Methods. We performed a single-center retrospective cohort study of patients with POPH MELD exceptions who underwent liver transplant from December 2008 to January 2024. Results were validated at an external center. Echocardiograms and RHCs performed within 1 mo were compared. Pearson correlation coefficient and Bland-Altman plots assessed the association between echocardiogram and RHC variables. We examined varied echocardiographic parameters to optimize sensitivity for the detection of hemodynamically severe POPH. Results. Twenty-two individuals underwent 60 follow-up RHCs with paired echocardiograms. Right ventricular systolic pressure (RVSP) and cardiac index estimated with echocardiogram were not strongly correlated with RHC measurements at follow-up (RVSP and RHC pulmonary artery systolic pressure: R = 0.30, P = 0.02; cardiac index: R = 0.17, P = 0.21). However, echocardiograms with RVSP ≥48 mm Hg had 100% sensitivity for detecting hemodynamically severe POPH, with 100% negative predictive value. In external validation of 13 paired echocardiograms and RHCs, our algorithm had 64% specificity and 100% negative predictive value. Conclusions. Although echocardiogram and RHC hemodynamic estimates were not strongly correlated, these results could potentially negate the current requirement for repeat RHC every 3 mo to maintain POPH MELD exception.

Objectives Palliative Medicine involvement in MICU patients have improved length of stay and mortality, but with varying effects on specific patient decision outcomes, such as, advance care planning. These studies have utilized Palliative Medicine later in the hospital or ICU course, with some evidence showing that earlier involvement resulted in better results. The purpose of this study was to evaluate the benefits of early (within 24 hours) palliative care consultation in medical ICU (MICU) patients to clinical and satisfaction outcomes. Methods An unblinded randomized study performed in the MICU in one academic hospital in the USA. Ninety-one adult patients admitted to MICU received a Palliative care medicine consultation within 24 hours as the intervention. Measurements and results Ninety-one patients admitted to the MICU underwent randomization with 50 patients randomly assigned to receive Palliative Medicine consultation and 41 patients randomly assigned to receive standard-of-care based on predefined criteria. The median satisfaction score was 23 points higher for the patients in the intervention group (P < .001). The median length of MICU stay was 5 days shorter in the intervention group compared to the control group (95% CI; 1 day to 18 days, P = .018). Advance care planning was completed in the hospital for 34% of patients in the intervention arm and 12% of patients in the controls arm (absolute risk difference 22%, 95% CI 4% to 37%, P = .016). Conclusion Early Palliative Medicine consultation within 24 hours of MICU admission showed significant benefits to patients by improving satisfaction and decreasing length of stay. This study provides evidence that Palliative Medicine involvement earlier in the course of severe disease is important. Further studies in other types of intensive care units (neurological and Cardiovascular) are necessary to determine their impact.

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.

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.

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.