Ussavarungsi, Kamonpun

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

AbstractBackground and AimsTo determine the prevalence of metabolic syndrome (MetS) – a potential phenotypical risk for pulmonary hypertension (PH) – in patients with PH and by PH diagnostic group including group 1 pulmonary arterial hypertension (PAH); group 1.1 idiopathic PAH, groups 1.2 heritable PAH, 1.3 drug and toxin induced, 1.4 associated PAH, group 2 PH with left heart disease, group 3 PH associated with lung disease and/or hypoxemia, group 4 PH owing to chronic thrombotic and/or embolic disease, and group 5 PH from multifactorial mechanisms.MethodsWe conducted a retrospective chart review of patients referred to Mayo Clinic in Florida from January 1990 to October 2013 (N = 1287). Only patients whom PH was confirmed by right heart catheterization were included (N = 640). MetS was defined with at least three of the following: systemic hypertension, diabetes mellitus, hyperlipidemia and body mass index > 30.ResultsMetS was prevalent in 247 of 640 (39%) with PH: 13% in group 1.1 PAH, 12% in groups 1.2–1.4 PAH, 54% in group 2, 55% in group 3, 23% in group 4 and 24% in group 5. After adjusting for age, sex and race, diagnostic subgroup analysis revealed a higher prevalence of MetS in WHO Group 2 PH patients [adjusted odd ratios (OR): 2.58, P < 0.0001] and WHO group 3 PH (adjusted OR: 2.77, P < 0.0001) when compared to group 1 PH.ConclusionThe prevalence of MetS was observed in 39% of patients with PH; however, among PH patients, the prevalence was higher in group 2 and 3 PH.

A mosaic pattern of lung attenuation on chest computed tomography (CT) may be due to various etiologies. There is limited published data on CT results when used to evaluate pulmonary hypertension (PH). We retrospectively studied the frequency of mosaic pattern in patients with PH and the cause of the PH by diagnostic group, as well as the correlation between the mosaic pattern and the following: demographics, severity of the PH, main pulmonary artery (PA) size, PA/aorta (PA/Ao) ratio, pulmonary function tests (PFT), and ventilation perfusion scan results. Overall, 18% of the cohort had CT mosaic pattern (34/189). Mosaic pattern was present in 17/113 (15%) in Group 1 pulmonary arterial hypertension, 5/13 (28%) in Group 2 pulmonary venous hypertension and 8/50 (16%) in Group 3 PH. Conversely, Group 4 chronic thromboembolic PH was more prevalent in 4/8 (50%). Main PA size, PA/Ao ratio, and segmental perfusion defect were positively associated with mosaic pattern. In contrast, factors such as age, gender, body mass index, functional class, hemodynamic data, and PFT values were not associated with mosaic pattern. Mosaic pattern is not specific as an isolated finding for distinguishing the subtype of PH.

Pulmonary arterial hypertension (PAH) is a potentially life‐threatening complication of thalassemia. A sexagenarian with β‐thalassemia intermedia presented with new‐onset dyspnea and syncope. Right heart catheterization confirmed severe PAH. Her functional class IV symptoms and severely elevated mean pulmonary artery pressure prompted the initiation of continuous epoprostenol therapy. Clinical follow‐up documented significant improvement in functional class, 6‐minute walk distance, and right ventricular size and function as well as pulmonary arterial pressure on echocardiogram. At the patient's request, epoprostenol was down‐titrated and eventually discontinued. The patient was then safely transitioned to nifedipine therapy after verification of vasoresponsiveness.

Pulmonary hypertension (PH) has been found to have significant morbidity and mortality. The treatment of PH has advanced considerably with increasingly more effective and safer options. With an increasing effort to diagnose patients early, non-invasive techniques are often used to screen those patients likely to have PH. Computerized tomography (CT) chest scans are increasingly utilized in the evaluation of patients with exertional dyspnea, including those with suspected PH. The main role of the CT scan is to evaluate for any associated underlying diseases. There have been attempts to address the utility of CT to predict the presence of PH. This article reviews previously published investigations to summarize the relationship between pulmonary artery dimensions and PH to determine both the strength of the correlation and its discriminatory ability for use in clinical practice.

AbstractIntroductionThe prevalence of restless legs syndrome (RLS) varies from 5% to 24% in the general population and is associated with a variety of medical disorders. However, the association between RLS and pulmonary hypertension (PH) is unknown.ObjectivesTo determine the prevalence of RLS in PH patients.MethodsA cross‐sectional questionnaire was given to patients with PH who attended the Pulmonary Hypertension Association conference. We used the RLS Diagnostic Index questionnaire. Demographic data included age, gender, height, weight, body mass index (BMI), medication list, PH World Health Organization (WHO) diagnosis group and current WHO functional class.ResultsThe study included 128 PH patients. Most were females (86.8%) with a mean age of 49.68 years [standard deviation (SD) 14.24]. The mean BMI was 31.3 (SD 20.46). One hundred and twenty‐one patients (93.75%) were classified as WHO group 1 (pulmonary arterial hypertension). Three patients were identified in WHO group 3 (hypoxemic states), four patients in group 4 (chronic thromboemboli) and one patient in group 5 (2.3%, 3.1% and 0.8%, respectively). Definite RLS was found in 16 of 128 patients with PH resulting in a prevalence of 12.5%, possible RLS in 39 of 128 patients (30.46%) and no RLS in 73 (57.03%) patients.ConclusionThe prevalence of RLS is not increased in PH. There is a high prevalence of possible RLS in our study. The overall prevalence of combined definite and possible RLS is significant. Future research is needed to assess more patients with PH and the association or correlation with RLS.