Ryu, J H

Abstract Background Takayasu arteritis (TA) is a rare large-vessel vasculitis that can involve pulmonary arteries, potentially leading to pulmonary hypertension (PH). Noninvasive evaluation by echocardiography is often used, but its reliability in confirming and characterizing PH in TA is unclear. We investigated the role of invasive hemodynamic testing in TA patients with suspected PH. Methods We retrospectively identified 10 patients with TA meeting 2022 ACR criteria and suspected PH based on symptoms and/or echocardiography; all underwent echocardiography followed by right heart catheterization (RHC).PH was defined as mean pulmonary artery pressure (mPAP) >20 mmHg. PH was classified as pre-capillary (pulmonary artery wedge pressure [PAWP] ≤15 mmHg), post-capillary (PAWP >15 mmHg), or combined (PAWP >15 mmHg with elevated pulmonary vascular resistance). Echocardiographic parameters were collected where available, along with invasive hemodynamics, cardiac biomarkers (BNP/NT-proBNP), inflammatory markers (ESR, CRP), NYHA functional class, and outcomes. Results Median age was 44 years (range 18-58), and 90% were female. Based on invasive hemodynamics, pre-capillary PH was present in 5 patients, combined pre-/post-capillary PH in 3, and isolated post-capillary PH in 2. Median mPAP was 38 mmHg (IQR 30-55), median pulmonary vascular resistance 3.5 Wood units (IQR 2.3-8.7), and median PAWP 15 mmHg (IQR 8-24). Echocardiography frequently underestimated disease severity. Several patients with absent or low tricuspid regurgitation velocity (≤1.0 m/s), where measurable, demonstrated severe pre-capillary PH on RHC, including pulmonary vascular resistance >6 Wood units. Among patients with available data, NT-proBNP levels ranged from 59 to 51,968 pg/mL, and inflammatory markers varied widely (CRP <0.3 to 107.9 mg/L). Among patients with available NYHA data, most were class II-III. Conclusions In this TA cohort, RHC was essential to confirm and phenotype PH, which was present in the majority of those with suspected PH. Echocardiography alone often underestimated or misclassified PH in TA - in one case missing severe pre-capillary PH due to an absent TR signal, and in another failing to discern elevated left-heart filling pressure. Invasive assessment prevented missed diagnoses and misclassification, ensuring appropriate management of TA-associated PH This abstract is funded by: None

Abstract Background Tuberous sclerosis complex (TSC) is a multisystem genetic disorder frequently associated with lymphangioleiomyomatosis (LAM), a progressive cystic lung disease. The 2022 Updated International TSC Consensus guidelines recommend clinical assessment for LAM and chest CT in all females, and symptomatic males, 18 years or older. We aimed to evaluate pulmonary screening practices along with demographic, genetic and clinical characteristics of those with TSC-LAM in a large national TSC cohort. Methods We conducted a retrospective observational study using the TSC Alliance Natural History Database. Demographic, genetic, and clinical data were extracted. Screening rates for LAM were assessed, and clinical, genetic, and pulmonary characteristics of patients diagnosed with LAM were analyzed. Results Among 2,636 patients with TSC (1,301 females, 49%), molecular testing was performed in 1,591 (60%), identifying TSC1 mutations in 349 (21.9%) and TSC2 mutations in 978 (61.5%). Screening for LAM was reported by 312 patients (11.8%; 42 (13.5%) males), of whom 116 were diagnosed with LAM; 111 (95.7%) were female. Mean age at cohort characterization was 48 years (range 21-80, SD 12.9), and mean age at LAM diagnosis (available in 82 patients) was 33 years (range 14-69, SD 12.5). Among LAM patients, molecular testing was performed in 74 (64%), TSC1 mutations were present in 8 (6.9%), TSC2 in 47 (40.5%), and dual mutations in 2. Common clinical manifestations included renal angiomyolipomas (104, 89.7%), facial angiofibromas (90, 77.6%), epilepsy (70, 60.3%), and subependymal giant cell astrocytoma (27, 23.3%). Pulmonary function data were limited (mean FEV₁ 84.9% predicted, n = 43; mean DLCO 77.6% predicted, n = 27). Serum VEGF-D available in 10 patients, range 331-9,523 pg/mL). Chest CT was performed in 87 patients (75%) and biopsy in 4 (3%). Patient-reported respiratory complications included pneumothorax (14, 12.1%), chylothorax (3, 2.6%), and oxygen requirement (4, 3.4%). Treatments included mTOR inhibitors in 32 (27.6%) and lung transplantation in 1 patient. Conclusion Evaluation for LAM in patients with TSC appears to be underutilized in the U.S. LAM mainly affects women, is linked to TSC2 mutations, and is associated with high rates of renal and dermatologic manifestations. Although guidelines focus on females, LAM can occur in males, highlighting the need for awareness in all TSC patients. Limited lung function and biomarker data reveal gaps in evaluation, with some patients developing severe disease requiring oxygen or lung transplantation. These findings support standardized, genotype-informed surveillance for early detection and targeted care in TSC-related LAM. This abstract is funded by: None

Abstract Rationale Inflammatory bowel disease (IBD) is increasingly recognized as a systemic disorder, with extraintestinal manifestations (EIMs) involving multiple organ systems. Pulmonary involvement, particularly interstitial lung disease (ILD), remains an underrecognized manifestation of IBD. Its prevalence, clinical characteristics, and risk factors in IBD remain poorly defined. Methods We conducted a retrospective study of adults (≥18 years) with IBD who had at least one encounter in our health system between January 1, 2013 and December 31, 2023. IBD, and ILD cases were identified using ICD-9/ICD-10 codes, with ILD diagnoses confirmed by thoracic radiologists. Demographic, clinical, pulmonary, smoking, medication, and surgical data were abstracted. Associations between patient characteristics and ILD were evaluated using both a cohort design and a matched case-control design (1:3 ratio). Mortality was assessed using a Cox proportional hazards model with ILD as a time-dependent covariate. Results Among 875 patients with IBD, 109 (12%) had ILD. Radiographic patterns included nonspecific interstitial pneumonia (NSIP, 27%), indeterminate (26%), definite/probable UIP (24%), hypersensitivity pneumonitis (15%), and organizing pneumonia (8%). Pulmonary function testing demonstrated predominantly restrictive physiology and impaired diffusion capacity. In multivariable analysis, higher BMI (OR 1.04), bronchiectasis (OR 2.65), ex-smoking (OR 2.15), and use of adalimumab (OR 2.04) or infliximab (OR 2.14) were independently associated with ILD. The matched case-control design confirmed these findings and also identified older age (OR 1.04) as a significant factor. ILD was strongly associated with mortality (HR, 3.78; 95% CI, 2.50-5.72; p < 0.001). Conclusions ILD occurs in a meaningful subset of patients with IBD and is associated with older age, higher BMI, prior smoking, bronchiectasis, and TNF inhibitor use. ILD confers a markedly increased risk of death, highlighting the importance of early recognition and close monitoring in this population. This abstract is funded by: None