Pulmonary Hypertension Patients Research Articles

A Story of PA/BSA and Biomarkers to Diagnose Pulmonary Hypertension in Patients with Severe Aortic Valve Stenosis-The Rise of IGF-BP2 and GDF-15.

(1) Background: Currently, echocardiography is the primary non-invasive diagnostic method used to screen patients with severe aortic valve stenosis (AS) for pulmonary hypertension (PH) by estimating systolic pulmonary artery pressure (sPAP). Other radiological methods have been a focus of research in the past couple of years, as it was shown that by determining the pulmonary artery (PA) diameter, prognostic statements concerning overall mortality could be made in these patients. This study compared established and novel cardiovascular biomarkers with the PA/BSA value to detect PH in patients with severe AS. (2) Methods: The study cohort comprised 188 patients with severe AS undergoing transcatheter aortic valve replacement (TAVR), who were then divided into two groups based on PA/BSA values obtained through CT-angiography. The presence of PH was defined as a PA/BSA ≥ 16.6 mm/m2 (n = 81), and absence as a PA/BSA < 16.6 mm/m2 (n = 107). Blood samples were taken before TAVR to assess cardiovascular biomarkers used in this study, namely brain natriuretic peptide (BNP), cardiac troponin I (cTnI), high-sensitive troponin (hsTN), soluble suppression of tumorigenesis-2 (sST2), growth/differentiation factor 15 (GDF-15), heart-type fatty acid-binding protein (H-FABP), insulin-like growth factor binding protein 2 (IGF-BP2), and soluble urokinase-type plasminogen activator receptor (suPAR). (3) Results: Patients with a PA/BSA ≥ 16.6 mm/m2 showed significantly higher levels of BNP (p = <0.001), GDF-15 (p = 0.040), and H-FABP (p = 0.007). The other investigated cardiovascular biomarkers did not significantly differ between the two groups. To predict a PA/BSA ≥ 16.6 mm/m2, cut-off values for the biomarkers were calculated. Here, GDF-15 (p = 0.029; cut-off 1172.0 pg/mL) and BNP (p < 0.001; cut-off 2194.0 pg/mL) showed significant results. Consequently, analyses of combined biomarkers were performed, which yielded IGF-BP2 + BNP (AUC = 0.721; 95%CI = 0.585−0.857; p = 0.004) as the best result of the two-way analyses and GDF-15 + IGF-BP2 + BNP (AUC = 0.727; 95%CI = 0.590−0.864; p = 0.004) as the best result of the three-way analyses. No significant difference regarding the 1-year survival between patients with PA/BSA < 16.6 mm/m2 and patients with PA/BSA ≥ 16.6 mm/m2 was found (log-rank test: p = 0.452). (4) Conclusions: Although PA/BSA aims to reduce the bias of the PA value caused by different body compositions and sizes, it is still a controversial parameter for diagnosing PH. Combining the parameter with different cardiovascular biomarkers did not lead to a significant increase in the diagnostic precision for detecting PH in patients with severe AS.

PS-B04-5: AMELIORATIVE POTENTIAL OF COMBINATION OF VITAMIN D AND SILDENAFIL AGAINST MONOCROTALINE-INDUCED PULMONARY HYPERTENSION IN RATS VIA ACTIVATING ENOS

Objective: The life expectancy in PAH is very less, and only symptomatic treatment is available. Patients with pulmonary hypertension are mostly diagnosed with co-existing vitamin D deficiency. In PAH, there is an increase in the level and expression of PDE 5 enzyme that results in increased degradation of cGMP but there is also a simultaneous decrease in the activation of cGMP due to a subsequent decrease in eNOS mediated nitric oxide synthesis. Thus, limiting the efficacy of sildenafil as monotherapy in the treatment of PAH. Furthermore, vitamin D deficiency is also associated with reduced expression of eNOS mediated NO synthesis, which further decreases cGMP synthesis thus increasing disease severity. Hence, this study was undertaken to study the combined effect of sildenafil and vitamin D therapy in monocrotaline-induced PAH in rats. Design and method: Rats were fed on a vitamin D deficient diet with exposure to filtered fluorescent light to induce vitamin D deficiency. PAH was induced by a single s.c. injection of MCT 50 mg/kg. Rats were divided into 6 groups: Control, MCT, MCT+Sildenafil, MCT+Vitamin D, MCT+Vitamin D+Sildenafil and MCT+L-NAME+Vitamin D+Sildenafil. Haemodynamic, echocardiographic, histopathological and biochemical parameters were analysed. The expression and level of eNOS was done using immunohistochemistry and western blot. Results: The effect of the vitamin D sildenafil combination group was significantly higher than the vitamin D and sildenafil treated alone groups. This protective effect of vitamin D sildenafil combination in PAH is attenuated when administered with L-NAME (20 mg/kg). Furthermore, the administration of MCT reduced the expression of eNOS, which was significantly reversed by the treatment with vitamin D sildenafil combination compared to vitamin D and sildenafil alone. Conclusion: The effect of vitamin D in the treatment of PAH is comparable to sildenafil alone and is further improved when given in combination with sildenafil. Moreover, if pulmonary hypertension is accompanied by vitamin D deficiency it results in increased disease severity of PAH. Thus, sildenafil when combined with vitamin D may exert a synergistic effect in amelioration of symptoms and disease severity in patients of pulmonary hypertension.

Frequency of hypothyroidism among patients of pulmonary hypertension.

Objective: To determine the frequency of hypothyroidism in patients with pulmonary hypertension. Study Design: Observational Cross-sectional study. Setting: Department of Medicine, Sandeman Provincial Hospital, Bolan University of Medical &amp; Health Sciences Quetta Pakistan. Period: March 2020 to March 2021. Material &amp; Methods: Pulmonary Hypertension was defined as mPASP of &gt;25 mm Hg at rest on transthoracic echocardiogram and hypothyroidism was labeled when TSH was high with low Free T4 and/or Free T3. Patients with congestive cardiac failure, pulmonary malignancy or pulmonary metastasis assessed by history and examination were excluded from the study. Using non-probability consecutive sampling, 186 patients of both genders, aged 20-65 years with pulmonary hypertension were included. Demographic information along with clinical variables noted, echocardiography was done and thyroid profile was sent for each patient. Results: Mean age was 41.2+11.2 years with 56 (30.1%) males and 130 (69.9%) females. The mean height, weight and BMI were 1.6+0.2 meters, 56.5+14.4 kilograms and 21.8+3.6 kg/m2 respectively. The mean mPASP was 40.2+7.1 mmHg. The mean serum TSH, free T3 and free T4 levels were 6.6+4.8 IU/L, 2.5+1.0 pmol/L and 1.1+0.4 pmol/L respectively. In our study, hypothyroidism was seen in 46 (24.7%) and was not significantly associated with age, gender, BMI or mPASP. Conclusion: Hypothyroidism was noted in about a quarter of the patients with pulmonary hypertension in this study.

Correlation between the surface of the regurgitant orifice of mitral insufficiency and pulmonary hypertension in patients with aortic stenosis at UHC Ibn Rochd Casablanca

Correlation between the surface of the regurgitant orifice of mitral insufficiency and pulmonary hypertension in patients with aortic stenosis at UHC Ibn Rochd Casablanca

Low-dose thrombolytic therapy versus unfractionated heparin in patients with intermediate-high risk pulmonary embolism.

Patients with intermediate-high risk pulmonary embolism (PE) who have acute right ventricular dysfunction and myocardial injury without overt hemodynamic compromise may be candidates for thrombolytic therapy (TT). In this study, we aimed to compare the clinical outcomes of low-dose prolonged TT and unfractionated heparin (UFH) in intermediate-high risk PE patients. This study enrolled 83 (female: 45 [54.2%], mean age: 70.07±10.7 years) retrospectively evaluated patients with the diagnosis of acute PE who were treated with low-dose and slow-infusion of TT or UFH. The primary outcomes of the study were de-fined as a combination of death from any cause and hemodynamic decompensation, and severe or life-threatening bleeding. Secondary endpoints were recurrent PE, pulmonary hypertension, and moderate bleeding. The initial management strategy of intermediate-high risk PE was TT in 41 (49.4%) patients and UFH in 42 (50.6%) cases. Low-dose prolonged TT was successful in all patients. While the frequency of hypotension decreased significantly after TT (22 vs. 0%, P<0.001), it did not decrease after UFH (2.4 vs. 7.1%, p=0.625). The proportion of hemodynamic decompensation was significantly lower in the TT group (0 vs. 11.9%, p=0.029). The rate of secondary endpoints was significantly higher in the UFH group (2.4 vs. 19%, P=0.016). Moreover, the prevalence of pulmonary hypertension was significantly higher in UFH group (0 vs. 19%, p=0.003). Prolonged TT regimen with low dose, slow infusion of tissue plasminogen activator was found to be associated with a lower risk of hemodynamic decompensation and pulmonary hypertension in patients with acute intermediate-high-risk PE compared to UFH.

Intersticijumske bolesti pluća i sekundarna plućna hipertenzija

Interstitial lung disease alone can have a poor prognosis, and when associated with pulmonary hypertension there is a significant reduction in survival rates. Since the incidence of pulmonary hypertension in patients with interstitial lung diseases is very high and the symptoms are similar and often unrecognized, our aim is to point out the significance of both coexisting diseases and to prompt clinicians to suspect pulmonary hypertension. Through a brief review of the pathohistological changes, diagnostic methods, and the clinical presentation of these diseases, the similarities and differences that can help in the management of these patients, are shown. The latest treatment guidelines, with a special focus on the impact of antifibrotic treatment (nintedanib and pirfenidone) on pulmonary hypertension, are presented.

Pulmonary Hypertension in a Group of Patients with Various Stages of Renal Disease

Background: The pathogenesis of pulmonary hypertension (PHT) associated with renal failure is complex. It includes metabolic and hormonal changes, high cardiac output due to arteriovenous fistula (AVF), anemia, and other factors. Objectives: The objective is to identify PHT frequency and associated factors in patients on hemodialysis (HD) compared to patients, not on HD. Methods: A cross-sectional study was conducted at Ibn Sena teaching hospital/Mosul and included 100 diabetic males with end-stage renal disease on HD (Group 1) compared to 96 diabetic males (of similar age) with chronic kidney disease but not on HD (Group 2) to assess the pulmonary artery pressure using Doppler echocardiogram. Patients with other causes of PHT such as heart failure and chronic lung disease were excluded from the study. Results: 42 (42%) of patients in Group 1 had PHT and 12 (12.5%) patients in Group 2. There were statistically significant differences between patients with and without PHT regarding ejection fraction (EF), but no significant differences regarding age, duration of dialysis, hemoglobin (Hb), and vascular access type in both groups. Conclusions: EF had a relationship with PHT, whereas the duration of dialysis, age of patients, Hb, and dialysis access type had no relationship to PHT. Recommendations: More studies are needed in our country regarding PHT in patients with variable stages of renal disease with larger sample sizes and different designs with the inclusion of data and parameters that were missing in our study such as duration of AVF creation.

Can Mean Platelet Volume (MPV) and Platelet Count be Used to Predict Survival in Pulmonary Hypertension Patients?

Can Mean Platelet Volume (MPV) and Platelet Count be Used to Predict Survival in Pulmonary Hypertension Patients?

Subcutaneous use of treprostinil in pediatric pulmonary hypertension patients: A report of three cases.

Treprostinil was approved by the United States Food and Drug Administration for use in the treatment of pulmonary arterial hypertension in 2002. Intravenous or subcutaneous treprostinil is used in pulmonary arterial hypertension patients in the functional classes of II-IV to alleviate exercise-related symptoms, or in cases where epoprostenol treatment should be reduced due to side effects. In this article, we describe three pediatric cases of pulmonary arterial hypertension in whom subcutaneous treprostinil was used.

Clinical characteristics of pulmonary hypertension patients who underwent right heart catheterization in Thailand: 5-year retrospective single-centre study.

Pulmonary arterial hypertension (PAH) is an uncommon and difficult-to-recognize condition. There is still limited evidence on Asian populations. This study aimed to clarify the clinical characteristics of pulmonary hypertension (PH) patients who underwent right heart catheterization (RHC). A single-centre retrospective observational analysis. An observational analysis of adult patients diagnosed with PH by RHC from 2015 to 2019; clinical characteristics and investigations were recorded and compared between PAH and non-PAH. The correlations between maximal tricuspid regurgitation velocity (TRVmax) and mean pulmonary arterial pressure (mPAP) were also estimated. From a total of 243 RHC patients, 79 PH patients were enrolled. The mean (SD) age was 56 (19) years. Dyspnea on exertion (DOE) was the most common clinical manifestation; 70 (89%). Most of them were in functional class II; 58 (73%). PAH was the most prevalent PH group; 46 (58%), followed by PH due to left heart disease; 26 (33%). In the PAH group, congenital heart disease-associated PAH was the most common aetiology; 25 (54%). Compared with the non-PAH group, PAH patients were younger and had fewer comorbidities, particularly atrial fibrillation. There were strong correlations between TRVmax and mPAP (r = 0.62, P < 0.01). PAH was the most prevalent among PH who underwent RHC. The most common presentation of PH patients was DOE. There were strong correlations between parameters from echocardiography and RHC (TRVmax and mPAP).

Naples Prognostic Score and Clinical Outcomes in Pulmonary Arterial Hypertension Patients.

Pulmonary arterial hypertension (PAH) is a specific form of pulmonary hypertension characterized by an increased mean pulmonary arterial pressure. Risk stratification is crucial in managing PAH, using various clinical, laboratory, and imaging parameters. The Naples prognostic score (NPS), incorporating nutritional and inflammatory markers, has demonstrated prognostic value in other conditions but not in PAH. The goal of this study was to appraise the importance of NPS as a prognostic indicator for patients with PAH. This retrospective study involved 101 PAH patients. Echocardiographic, laboratory, and right heart catheterization data were collected. Statistical analyses compared variables between survivors and non-survivors, and multivariate logistic regression identified mortality risk factors. Among the 101 patients, 18 died within the follow-up period. The mortality group showed elevated levels of B-type natriuretic peptide (BNP) and significantly higher median NPS. Patients were categorized based on their NPS scores, revealing higher mortality in Group 2. Multivariate logistic regression identified age and BNP levels as independent predictors of mortality. The inclusion of NPS in the model further reinforced its association with mortality. The study suggests that NPS is linked to poor outcomes in PAH patients. NPS, a straightforward and easily calculated score, holds the potential to predict the clinical trajectory of PAH, offering advantages for risk assessment in this population.

The social and economic disadvantage in pulmonary hypertension: A work (still) in progress.

The social and economic disadvantage in pulmonary hypertension: A work (still) in progress.

Long-term impact of add-on sequential triple combination therapy in pulmonary arterial hypertension: real world experience.

Sequential triple combination therapy is recommended for pulmonary arterial hypertension (PAH) patients who are not at therapeutic goal on dual therapy, but long-term data on efficacy and safety is scarce. To assess the long-term impact of sequential triple combination therapy in patients with PAH who are not at goal on dual combination therapy. We performed a retrospective observational study in a racially/ethnically diverse cohort of consecutive PAH patients on a stable dual therapy regimen who remained in intermediate- or high-risk category and were subsequently initiated on sequential triple combination therapy. We studied interval change in functional, echocardiographic, and hemodynamic parameters, REVEAL 2.0 risk category and ERS/ESC 2022 simplified four-strata risk category. Multivariate logistic regression analysis was performed to identify independent predictors of successful risk reduction (achievement or maintenance of REVEAL 2.0 low-risk category). Kaplan-Meier survival curves were created to assess the effect of risk reduction on survival. Out of 414 PAH patients seen in our program, 55 patients received add-on sequential triple combination regimen and had follow-up hemodynamic data. The mean age was 57 years, with 85% women. The most common etiology of PAH was idiopathic/heritable (41.8%). Most patients were WHO functional class III (76.4%), and 34.5% of patients were in high-risk category (REVEAL 2.0). On a median follow-up of 68 weeks, there was a significant improvement in WHO Functional Class (p < 0.001), six-minute walk distance (35 m) with 61.8% of patients achieving low-risk status by REVEAL 2.0, and a 28% of patients' improvement in pulmonary vascular resistance. Female gender was identified as a strong predictor of successful risk reduction, whereas Hispanic ethnicity estimated right atrial pressure on echocardiogram and pericardial effusion predicted lower probability of risk reduction. Patients who achieved or maintained low-risk status had significantly improved survival. Add-on sequential triple combination therapy significantly increased functional, echocardiographic, and hemodynamic parameters with improvement in risk category and survival.

Haemoglobin Measurement from Eye Anterior Ciliary Arteries through Borescope Camera

Nowadays, smartphones are used as self-health monitoring devices for humans. Self-health monitoring devices help clinicians with big data for accurate diagnosis and guidance for treatment through repetitive measurement. Repetitive measurement of haemoglobin requires for pregnant women, pediatric, pulmonary hypertension and obstetric patients. Noninvasive haemoglobin measurement through conjunctiva leads to inaccurate measurement. The inaccuracy is due to a decrease in the density of goblet cells and acinar units in Meibomian glands in the human eye as age increases. Furthermore, conjunctivitis is a disease in the eye due to inflammation or infection at the conjunctiva. Conjunctivitis is in the form of lines in the eyelid and covers the white part of the eyeball. Moreover, small blood vessels in eye regions of conjunctiva inflammations are not visible to the human eye or standard camera. This paper proposes smartphone-based haemoglobin (SBH) measurement through a borescope camera from anterior ciliary arteries of the eye for the above problem. The proposed SBH method acquires images from the anterior ciliary arteries region of the eye through a smartphone attached with a high megapixel borescope camera. The anterior ciliary arteries are projected through transverse dyadic wavelet transform (TDyWT) and applied with delta segmentation to obtain blood cells from the ciliary arteries of the eye. Furthermore, the Gaussian regression algorithm measures haemoglobin (Hb) with more accuracy based on the person, eye arteries, red pixel statistical parameters obtained from the left and right eye, age, and weight. Furthermore, the experimental result of the proposed SBH method has an accuracy of 96% in haemoglobin measurement.

Fibrinogen-Aα THR312ALA Polymorphism is Associated to Chronic Thromboembolic Pulmonary Hypertension in Turkey.

Chronic thromboembolic pulmonary hypertension is a condition that occurs after mechanical obstruction of the pulmonary arteries by thrombus. Since the frequency and demographics of chronic thromboembolic pulmonary hypertension differ between countries, it is thought that genetic factors may play a role in its development. The aim of this study is to reveal the status of VKORC1, CYP2C9*3, CYP2C9*7, and fibrinogen-Aα THR312ALA gene polymorphisms in chronic thromboembolic pulmonary hypertension patients in Turkey. In this prospective cross-sectional study, a total of 46 chronic thromboembolic pulmonary hypertension patients and 106 healthy volunteers were included. Polymerase chain reaction-restriction fragment length polymorphism method was used to determine candidate gene polymorphisms for chronic thromboembolic pulmonary hypertension. The general population parameters of each locus were calculated, and the relationship between dominant, codominant, and recessive genotype models and chronic thromboembolic pulmonary hypertension was analyzed. For the fibrinogen-Aα gene, those with the THR/THR genotype were found to have a 13.51 (95% CI: 2.688-33.333) times less susceptibility rate to the disease than those with the ALA/THR genotype, the susceptibility of THR/ALA genotype to the disease was 5.026 (95% CI: 1.774-14.242) times more than those with ALA/ALA genotype. There was no difference between patient groups for VKORC1, CYP2C9*3 genes (P >.05). Since the CYP2C9*7 patient group was monomorphic for the ILE allele, the patient/control odds ratio and 95% CI could not be calculated. This study shows that there is an association between the fibrinogen-Aα gene ALA polymorphism at the amino acid position of 312 and the development of chronic thromboembolic pulmonary hypertension, but not between the CYP2C9 and VKORC1 gene polymorphisms.

Left Ventricular Fibrosis Assessment by Native T1, ECV, and LGE in Pulmonary Hypertension Patients.

Cardiac magnetic resonance imaging (MRI) is emerging as an alternative to right heart catheterization for the evaluation of pulmonary hypertension (PH) patients. The aim of this study was to compare cardiac MRI-derived left ventricle fibrosis indices between pre-capillary PH (PrePH) and isolated post-capillary PH (IpcPH) patients and assess their associations with measures of ventricle function. Global and segmental late gadolinium enhancement (LGE), longitudinal relaxation time (native T1) maps, and extracellular volume fraction (ECV) were compared among healthy controls (N = 25; 37% female; 52 ± 13 years), PH patients (N = 48; 60% female; 60 ± 14 years), and PH subgroups (PrePH: N = 29; 65% female; 55 ± 12 years, IpcPH: N = 19; 53% female; 66 ± 13 years). Cardiac cine measured ejection fraction, end diastolic, and end systolic volumes and were assessed for correlations with fibrosis. LGE mural location was qualitatively assessed on a segmental basis for all subjects. PrePH patients had elevated (apical-, mid-antero-, and mid-infero) septal left ventricle native T1 values (1080 ± 74 ms, 1077 ± 39 ms, and 1082 ± 47 ms) compared to IpcPH patients (1028 ± 53 ms, 1046 ± 36 ms, 1051 ± 44 ms) (p < 0.05). PrePH had a higher amount of insertional point LGE (69%) and LGE patterns characteristic of non-vascular fibrosis (77%) compared to IpcPH (37% and 46%, respectively) (p < 0.05; p < 0.05). Assessment of global LGE, native T1, and ECV burdens did not show a statistically significant difference between PrePH (1.9 ± 2.7%, 1056.2 ± 36.3 ms, 31.2 ± 3.7%) and IpcPH (2.7 ± 2.7%, 1042.4 ± 28.1 ms, 30.7 ± 4.7%) (p = 0.102; p = 0.229 p = 0.756). Global native T1 and ECV were higher in patients (1050.9 ± 33.8 and 31.0 ± 4.1%) than controls (28.2 ± 3.7% and 1012.9 ± 29.4 ms) (p < 0.05). Cardiac MRI-based tissue characterization may augment understanding of cardiac involvement and become a tool to facilitate PH patient classification.

CircNFXL1 Modulates the Kv2.1 Channel Function in Hypoxic Human Pulmonary Artery Smooth Muscle Cells via Sponging miR-29b-2-5p as a Competitive Endogenous RNA.

Pulmonary arterial hypertension is characterized by abnormal pulmonary vasoconstriction and vascular remodeling caused by the dysregulation of K + channels in PA smooth muscle cells (PASMCs). However, how the K + channels are dysregulated is still unclear. Circular RNAs (circRNAs) are noncoding RNAs with a closed-loop structure capable of sponging microRNAs (miRs), thus regulating gene expression at the post-transcriptional level. Our previous studies have demonstrated the importance of one novel circRNA (hsa_circNFXL1_009, circNFXL1) in pulmonary arterial hypertension patients, playing as a critical regulator for K + channel activation in hypoxic human PASMCs (hPASMCs). Here, we explore the mechanisms underlying circNFXL1-regulated K + channel expression and functions in hypoxic hPASMCs. In cultured hPASMCs, the reduction of Kv current induced by hypoxia was significantly recovered by delivering exogenous circNFXL1. Moreover, luciferase, quantitative reverse transcription-quantitative polymerase chain reaction, western blot, and mutagenesis studies confirmed that circNFXL1 reversed hypoxia-induced inhibitory effects on the Kv2.1 channel via sponging hsa-miR-29b-2-5p (miR-29b-2). Furthermore, we found that circNFXL1 reversed the miR-29b-induced Kv2.1 channel dysfunction at the whole-cell and single-channel level in HEK cells using a patch-clamp. Finally, calcium imaging revealed that hypoxia also triggered a substantial rise in the cytosolic calcium concentration ([Ca2 + ]cyt) in hPASMCs, and this hypoxia-induced elevation of [Ca2 + ]cyt was reduced by circNFXL1 through miR-29b-2. These data suggested that circNFXL1-mediated regulation of the Kv2.1 channel activation and the related intracellular calcium concentration may contribute to the effects of hypoxic pulmonary vasoconstriction.

Development and validation of a risk nomogram model for predicting pulmonary hypertension in patients with stage 3–5 chronic kidney disease

ObjectivesThe occurrence of pulmonary arterial hypertension (PAH) can greatly affect the prognosis of patients with chronic kidney disease (CKD). We aimed to construct a nomogram to predict the probability of PAH development in patients with stage 3–5 CKD to guide early intervention and to improve prognosis.MethodsFrom August 2018 to December 2021, we collected the data of 1258 patients with stage 3–5 CKD hospitalized at the Affiliated Hospital of Xuzhou Medical University as a training set and 389 patients hospitalized at Zhongda Hospital as a validation set. These patients were divided into PAH and N-PAH groups with pulmonary arterial systolic pressure ≥ 35 mmHg as the cutoff. The results of univariate and multivariate logistic regression analyses were used to establish the nomogram. Then, areas under the receiver operating characteristic curve (AUC-ROCs), a calibration plot, and decision curve analysis (DCA) were used to validate the nomogram.ResultsThe nomogram included nine variables: age, diabetes mellitus, hemoglobin, platelet count, serum creatinine, left ventricular end-diastolic diameter, left atrial diameter, main pulmonary artery diameter and left ventricular ejection fraction. The AUC-ROCs of the training set and validation set were 0.801 (95% confidence interval (CI) 0.771–0.830) and 0.760 (95% CI 0.699–0.818), respectively, which showed good discriminative ability of the nomogram. The calibration diagram showed good agreement between the predicted and observed results. DCA also demonstrated that the nomogram could be clinically useful.ConclusionThe evaluation of the nomogram model for predicting PAH in patients with CKD based on risk factors showed its ideal efficacy. Thus, the nomogram can be used to screen for patients at high risk for PAH and has guiding value for the subsequent formulation of prevention strategies and clinical treatment.

Corosolic acid ameliorates vascular remodeling in pulmonary arterial hypertension via the downregulation of STAT3 signaling

Pulmonary arterial hypertension (PAH) is a progressive and fatal disease that is characterized by vascular remodeling of the pulmonary artery. PAH remodeling is primarily caused by the excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs). Therefore, an inhibitory mechanism is expected as a target for the treatment of PAH. Corosolic acid (CRA) is a pentacyclic triterpenoid extracted from the leaves of Banaba (Lagerstroemia speciosa) that exerts anti-diabetic, anti-inflammatory, and anti-tumor effects. In the present study, the effects of CRA on PAH remodeling were examined using PASMCs from idiopathic pulmonary arterial hypertension (IPAH) patients and monocrotaline (MCT)-induced pulmonary hypertensive (PH) rats. CRA inhibited the excessive proliferation of IPAH-PASMCs in a concentration-dependent manner (IC50 = 14.1 μM). It also reduced the migration of IPAH-PASMCs. The CRA treatment downregulated the expression of signal transducer and activator of transcription 3 (STAT3) in IPAH-PASMCs. In MCT-PH rats, the administration of CRA (1 mg/kg/day) attenuated increases in right ventricular systolic pressure, pulmonary vascular remodeling, and right ventricular hypertrophy. CRA also decreased the expression of STAT3 in pulmonary arterial smooth muscles from MCT-PH rats. In conclusion, the anti-proliferative and anti-migratory effects of CRA in PASMCs ameliorated PAH remodeling by downregulating STAT3 signaling pathways.

Heterogeneity of phenotypic manifestations of cystic fibrosis in children and predictors of the disease severity

The aim of the study was to investigate the heterogeneity of phenotypic manifestations of cystic fibrosis (CF) in children depending on the CFTR gene mutation and to determine predictors of the disease severity for the personalization of treatment and prevention of complications. Materials and methods. Fifty-nine children with CF, aged 1 to 18 years (mean age was 12.0 (8.5; 15.0) years), were examined. All patients underwent general clinical, genetic, laboratory and microbiological examination. Instrumental methods of examination included spirometry, chest X-ray and computed tomography, ultrasound densitometry. According to the functional effects of CFTR mutations, the patients were divided into two groups. The group with “severe” genotypes (n = 40) included patients with two class I and/or II mutations, and the group with “mild” genotypes (n = 10) included patients with at least one class IV or V mutation. Mutations were not identified in 9 patients. Results. Analysis of the spectrum of genetic variants in the CFTR gene showed that 10 patients (20.0 %) were identified with the “mild” genotype, and 40 patients (80.0 %) with the “severe” genotype. The most common mutation was F508del predominantly in the compound heterozygous state (42.4 %). It was found that patients with the “mild” genotype were characterized by a more favorable course of the disease than patients with the “severe” genotype. No statistically significant phenotypic features of the CF course in children depending on the F508del mutation status (F508del/F508del or F508del/nonF508del) were found, except for earlier formation of pulmonary hypertension in patients with the homozygous condition (47.1% vs 16.0 %, P &lt; 0.05). Conclusions. Examination of the relationship between CFTR genotype and phenotype has revealed associations between CFTR mutations and lesion severity of both the digestive and bronchopulmonary systems. Identification of disease severity predictors can provide a more accurate prediction of the disease course, that will determine the patient management and prevent the development of complications.