Computed tomography lung parenchymal descriptions in routine radiological reporting have diagnostic and prognostic utility in patients with idiopathic pulmonary arterial hypertension and pulmonary hypertension associated with lung disease

BackgroundPatients with pulmonary hypertension (PH) and lung disease may pose a diagnostic dilemma between idiopathic pulmonary arterial hypertension (IPAH) and PH associated with lung disease (PH-CLD). The prognostic impact of common CT parenchymal features is unknown.Methods660 IPAH and PH-CLD patients assessed between 2001–19 were included. Reports for all CT scans one year prior to diagnosis were analysed for common lung parenchymal patterns. Cox regression and Kaplan-Meier analysis was performed.ResultsAt univariate analysis of the whole cohort, centrilobular ground glass (CGG) changes (Hazard Ratio, HR 0.29) and ground glass opacification (GGO, HR 0.53) predicted improved survival while honeycombing (HR 2.79), emphysema (HR 2.09) and fibrosis (HR 2.38) predicted worse survival (p all <0.001). Fibrosis was an independent predictor after adjusting for baseline demographics, PH severity and DLco (HR 1.37, p<0.05). Patients with a clinical diagnosis of IPAH who had an absence of reported parenchymal lung disease (IPAH-noLD) demonstrated superior survival to patients diagnosed with either IPAH who had coexistent CT lung disease or PH-CLD (2-year survival of 85%, 60% and 46% respectively, p<0.05). CGG changes were present in 23.3% of IPAH-noLD and 5.8% of PH-CLD patients. There was no significant difference in survival between IPAH-noLD patients with or without CGG changes. PH-CLD patients with fibrosis had worse survival than those with emphysema.InterpretationRoutine clinical reports of CT lung parenchymal disease identify groups of patients IPAH and CLD-PH with significantly different prognoses. Isolated CGG changes are not uncommon in IPAH but are not associated with worse survival.

Clinical impact of subcutaneous treprostinil in trisomy 21 patient with pulmonary arterial hypertension associated with CHD

Subcutaneous treprostinil is commonly used to improve idiopathic pulmonary arterial hypertension in children. However, its effectiveness has not been reported in trisomy 21. We report the case of 9-year-old boy in trisomy 21 with CHD-pulmonary artery hypertension after surgical correction of CHD. Haemodynamics and exercise capacity dramatically improved with a transition from oral selexipag to subcutaneous treprostinil.

Prognostic Value of Follicle-Stimulating Hormone Levels in Predicting Survival in Men With Idiopathic Pulmonary Arterial Hypertension

The objective of the study was to assess the association between changes in plasma follicle-stimulating hormone (FSH) and the potential effect on idiopathic pulmonary arterial hypertension (IPAH) in male patients. A total of 116 male patients with IPAH and 53 healthy controls were included from XX Hospital. Plasma FSH concentration was assessed in all participants. Receiver operating characteristic curves were used to assess the mortality risk. Kaplan–Meier curve and Cox regression analyses were used to predict the value of FSH on the survival rate of male IPAH patients. The plasma FSH concentration in the IPAH group was significantly higher than that in the control group ( p = .017). Nonsurvivors had significantly higher levels of FSH than survivors ( p < .0001). FSH levels were positively correlated with World Health Organization Functional Class, mean pulmonary artery pressure, and pulmonary vascular resistance (PVR; p = .023, p < .0001, and p < .0001, respectively) and negatively correlated with 6-min walk distance (6MWD) and cardiac output (CO; p = .004 and p = .010). Cox regression model analysis showed that the levels of FSH were also the independent factors of mortality in male IPAH patients ( p < .0001). The IPAH patients with higher FSH levels had higher PVR, lower 6MWD, CO, and a lower survival rate ( p = .042, p = .003, p = .029, and p < .0001, respectively). Therefore, we identified that increased FSH levels were associated with disease severity in male patients with IPAH and independently predicted risk of disease and poor survival rate.

Algorithms for the diagnosis and treatment of idiopathic pulmonary arterial hypertension

Background. Pulmonary hypertension (PH) is a hemodynamic and pathophysiological condition characteri-zed by an increase in the average pressure in the pulmonary artery > 20 mm Hg and is evaluated according to the data of the right heart catheterization (RHC). In most cases, PH is not an independent disease but is a manifestation of other diseases. Idiopathic pulmonary arterial hypertension (IPAH) is a diagnosis that it is established by excluding all other causes of PH (damage to the left heart, connective tissue diseases, HIV infection, lung diseases, portal hypertension, congenital heart defects, a history of pulmonary thromboembolism, etc.). In IPAH, the etiology of the disease is unknown. Pathogenesis and symptoms of PH. Vasoconstriction, microthrombosis, and vascular remodeling are the three main pathophysiological elements in PH. Symptoms of PH are non-specific: shortness of breath, rapid fatigue, chest pain during physical exertion, and sometimes syncopal states are observed. Decompensated patients have signs of right-sided heart failure (edemas, ascites, bloating, pulsation of the jugular veins). Diagnosis. The diagnostic algorithm for РH consists of two stages. The first one is located outside the expert сenter, and the second one is located directly in the PH expert center. When this disease is suspected and there are typical symptoms and signs, all patients undergo an echocardiographic examination. Then, under certain conditions (for example, the absence of the underlying cause of PH), the patient is referred to the PH expert center, where it is possible to conduct RHC. Evaluating the prognosis. Evaluation of patients with IPAH is necessary to improve disease control and transition from a higher risk to a lower one. Prognosis assessment is comprehensive and is determined based on clinical status, symptom progression, syncope, results of a 6-minute walk test and NT-proBNP, results of examination methods (cardiopulmonary exercise test, echocardiography or MRI of the heart, hemodynamic assessment). Treatment. The main objectives of IPAH treatment are reducing the severity of symptoms, slowing the progression of the disease, improving the quality and increasing the life expectancy of patients. First of all, these are general measures (physical activity, prevention and management of pregnancy), prevention of infectious diseases, social and psychological assistance, monitoring compliance with the regime, recommendations for travel/journey, maintenance therapy (oral anticoagulants, diuretics, digoxin, oxygen therapy). Patients with a positive vasoreactive test are prescribed with calcium channel blockers. In all other patients, specific PH therapy may include prostaglandins (inhaled, intravenous, and subcutaneous forms), prostacyclin receptor antagonists, endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and soluble guanylate cyclase stimulants. Surgical treatment. One of the options for surgical treatment of IPAH is atrial septostomy — the creation of a perforation in the atrial septum. This leads to decompression of the right chambers of the heart and increases the preload on the left ventricle, which leads to an increase in cardiac output. In case of ineffectiveness of all the above methods of treatment and significant progression of the disease, patients are indicated for lung transplantation or heart — lung complex.

Genotypes and Phenotypes: A Review of Pulmonary Hypertension in Genetic Syndromes

There has been significant advancement in the understanding of the genetics of pulmonary hypertension (PH), particularly in those with heritable or idiopathic pulmonary arterial hypertension. In addition to genetic variants with a primarily pulmonary vascular disease phenotype, the prevalence of PH in other genetic syndromes is increasingly recognized. We will review the current knowledge of PH associated with multisystem genetic syndromes. There is high prevalence of coexisting cardiac and pulmonary disease, making it challenging to discern whether PH is secondary to these processes or underlying genetic makeup. There is a paucity of data on response to PH-targeted therapy and implications on overall prognosis.

Biological heterogeneity in idiopathic pulmonary arterial hypertension identified through unsupervised transcriptomic profiling of whole blood

Idiopathic pulmonary arterial hypertension (IPAH) is a rare but fatal disease diagnosed by right heart catheterisation and the exclusion of other forms of pulmonary arterial hypertension, producing a heterogeneous population with varied treatment response. Here we show unsupervised machine learning identification of three major patient subgroups that account for 92% of the cohort, each with unique whole blood transcriptomic and clinical feature signatures. These subgroups are associated with poor, moderate, and good prognosis. The poor prognosis subgroup is associated with upregulation of the ALAS2 and downregulation of several immunoglobulin genes, while the good prognosis subgroup is defined by upregulation of the bone morphogenetic protein signalling regulator NOG, and the C/C variant of HLA-DPA1/DPB1 (independently associated with survival). These findings independently validated provide evidence for the existence of 3 major subgroups (endophenotypes) within the IPAH classification, could improve risk stratification and provide molecular insights into the pathogenesis of IPAH.

Predictive value of chest HRCT for survival in idiopathic pulmonary arterial hypertension

Background Little attention has been paid to chest high resolution computed tomography (HRCT) findings in idiopathic pulmonary arterial hypertension (IPAH) patients so far, while a couple of small studies suggested that presence of centrilobular ground-glass opacifications (GGO) on lung scans could have a significant negative prognostic value. Therefore, the aims of the present study were: to assess frequency and clinical significance of GGO in IPAH, and to verify if it carries an add-on prognostic value in reference to multidimensional risk assessment tool recommended by the 2015 European pulmonary hypertension guidelines. Methods Chest HRCT scans of 110 IPAH patients were retrospectively analysed. Patients were divided into three groups: with panlobular (p)GGO, centrilobular (c)GGO, and normal lung pattern. Association of different GGO patterns with demographic, functional, haemodynamic, and biochemical parameters was tested. Survival analysis was also performed. Results GGO were found in 46% of the IPAH patients: pGGO in 24% and cGGO in 22%. Independent predictors of pGGO were: positive history of haemoptysis, higher number of low-risk factors, and lower cardiac output. Independent predictors of cGGO were: positive history of haemoptysis, younger age, higher right atrial pressure, and higher mixed venous blood oxygen saturation. CGGO had a negative prognostic value for outcome in a 2-year perspective. This effect was not seen in the longer term, probably due to short survival of cGGO patients. Conclusions Lung HRCT carries a significant independent prognostic information in IPAH, and in patients with cGGO present on the scans an early referral to lung transplantation centres should be considered.