PAH In Patients Research Articles

Association of red cell distribution width with pulmonary arterial hypertension in patients with mixed connective tissue disease

BackgroundPulmonary arterial hypertension (PAH) is a severe complication of mixed connective tissue disease (MCTD) and contributes to increased morbidity and mortality. Still, the demographic characteristics and risk factors of PAH in MCTD remain poorly understood. This study explored risk factors for PAH development in MCTD.MethodsData from patients with MCTD and PAH hospitalized from May 2009 to December 2022 in a single center were collected and compared with patients with MCTD without PAH. The variables were analyzed by logistic regression to identify the factors associated with PAH in patients with MCTD. The receiver-operating characteristic (ROC) curve was used to assess the diagnostic value of the identified factors.ResultsFinally, 119 patients with MCTD were included; 46 had PAH. The mean age at PAH onset and diagnosis was 38.9 ± 13.4 and 39.9 ± 13.7 years, respectively. The median pulmonary arterial systolic pressure (PASP) was 67.0 mmHg. The median brain natriuretic peptide (BNP) level was 180.0 pg/ml at PAH diagnosis. Red cell distribution width (RDW) (OR: 2.128; 95% confidence interval: 1.497–3.026; P < 0.001) was associated with PAH in patients with MCTD. There was a positive correlation between RDW and PASP (r = 0.716, P < 0.001). At a cutoff of 15.2%, RDW had the best sensitivity (80.4%) and specificity (82.2%) for PAH.ConclusionRDW may serve as a sensitive index to predict PAH in patients with MCTD.

The prevalence of pulmonary arterial hypertension in patients with mixed connective tissue disease: a systematic review and meta-analysis.

The prevalence and outcome of mixed connective tissue disease-associated pulmonary arterial hypertension (MCTD-PAH) has not been well understood. Our aim was to review the current knowledge on the prevalence, severity, and mortality of MCTD-PAH. We also aimed to examine the prevalence trend of MCTD-PAH over the years. PubMed/Medline, Embase, Scopus and Web of Science electronic databases were searched for the published randomised controlled clinical trials (RCTs) and observational/original studies on PAH in patients with MCTD from January 1972 to December 2020. The results were pooled using random-effects meta-analysis based on DerSimonian and Laird method. A total of 983 patients from eight studies were included in the meta-analysis (K=8, n=983). Pooled prevalence of PAH in MCTD patients was 12.53% [95% CI 8.30-18.48%] with significant level statistical heterogeneity (tau2=0.30, tau=0.55, i2 83.3%, H=2.13 Q(df,7)=31.90, p=0.001). There was no association between PAH and female gender or age. The percentage of deaths in MCTD patients due to PAH varied and reached up to 81.8%. This is the first systematic review and meta-analysis investigating the prevalence of PAH in patients with MCTD and it revealed an overall prevalence of PAH in patients with MCTD of 12.53%. Our results showed trends of reduced prevalence of MCTD-PAH over last four decade, reconfirmed the lower prevalence rate in recent studies, but revealed an increased mortality rate. We also determined the low impact of the age, gender, and interstitial lung disease on MCTD-PAH.

STUDY OF SKIN CHANGES, HAND ABNORMALITIES AND PULMONARY MANIFESTATIONS IN DIFFUSE SCLERODERMA IN A TERTIARY CARE HOSPITAL OF EASTERN INDIA

Introduction: Scleroderma is a connective tissue disease characterized by brosis affecting the skin and internal organs.Joint involvement has been reported to occur in 46%- 97% of SSc patients. Bone and soft tissues may also be targeted; calcinosis and acro-osteolysis are thought to be the main characteristic ndings in SSc. Pulmonary disease in SSc falls into two major categories: interstitial lung disease (ILD) and pulmonary hypertension. Using PFTs, signicant pulmonary involvement is detectable in 25% of the patients with SSc within 3 years of initial diagnosis. The gold standard for determination of PAH in patients with SSc is right heart catheterization. The HRCT features of lung disease are ground-glass opacication predominant or admixed with reticular abnormalities in the majority of cases and little or no honeycombing. To study the demographic prole, Clini Aims and Objectives: cal Manifestations, Radiological abnormalities, Lung involvement and PAH. 35 newly diagnosed Sclederma patients Materials and Methods: attending Medicine and Rheumatology OPD of Medical College Kolkata were studied in this Cross-sectional observational study. Clinical Manifestations are noted and Radiological Investigations were recorded in structured Proforma. Data analysed using standard statistical methods. In Results and Analysis: our study, the study population had an F: M ratio of 10:1. majority of population (38%) having age group(30-40) yrs followed by less than 30 yrs &amp; 41yrs or more (31% each). In our study clinically hand abnormality was evident in 69% patients &amp; radiologically hand abnormality was evident in 74% patients. In our study population 29% patients have had acroosteolysis, 26% patients had erosion &amp; 19% patients had exion contracture. In our study we found all the patient with documented ILD had abnormal PFT. In our study group restrictive pattern in PFT was evident in 63% patients &amp; mixed pattern was evident in 23% patients. Twelve patients (35% of the total cohort) had pulmonary hypertension dened as PAs of 30 mm Hg or greater. In our study we found Out of 30 patients with documented ILD in HRCT 20 patients had PAH &amp; 10 patients had no PAH. Females are more affected than males. Majority Conclusion: of the patients affected are in the age group of 30-40 years.69% patients had clinically evident hand abnormality and 74% patients had radiologically evident hand abnormality.CXR showed ILD in 63% patients whereas86% patients had documented ILD in HRCT.Restrictive pattern of PFT abnormality is more than mixed pattern.57% patients had documented PAH in echocardiography.HRCT is more sensitive than chest radiography for detection of ILD.

Parámetros ecocardiográficos relacionados a hipertensión arterial pulmonar en pacientes con leucemia mieloide crónica en tratamiento con dasatinib

Introduction: The use of dasatinib in patients with CML has improved life expectancy and follow-up with transthoracic echocardiography (ECOTT) for early detection of PAH allows modifications to the treatment. Objective: To determine the echocardiographic parameters and echocardiographic probability for PAH in patients with CML treated with dasatinib. Methods: Correlation, cross-sectional, retrospective, single-center study; patients with CML treated with dasatinib were included. Spearman and Pearson correlation was used. Results: 16 patients were analyzed, mean age 53.5 years; 62.5% men, 37.5% women. The dasatinib dose was 50 mg / day in 18.7%, and 100 mg / day in 81.2%, mean pulmonary arterial pressure (mPAP) 26.3 mmHg, mean maximum tricuspid regurgitation velocity (VmxRT) 2.9 m / s, mean pulmonary artery systolic pressure (PSAP) 41 mmHg. 56.2% had right ventricular diastolic dysfunction (RVDD). 43% were categorized as low probability for PAH, 18.7% intermediate, and 37.5% as high. Relationship between PAPm and VmxRT with p = 0.012. Relationship between mPAP and RV diastolic function, with p = 0.002. Relationship between probability for PAH and mPAP, with p = 0.008. Conclusion: The echocardiographic parameters PAPm, VmxRT, PSAP, DDVD and echocardiographic probability for PAH are useful and necessary for the diagnosis of PAH. The determination of all these parameters should be carried out early and as a follow-up, since a considerable positive relationship was found for each one with the presence of PAH, which is not dependent on the treatment time or the dose of dasatinib.

Nerve growth factor receptor is involved in maintaining homeostasis of pulmonary arterial hypertension

Abstract Introduction Pulmonary arterial hypertension (PAH), characterized by vascular remodeling, is still disease with poor prognosis although many pulmonary vasodilators have been developed, and new mechanism of treatment for PAH is desired. Nerve growth factor receptor (Ngfr) is known to relate to inflammatory reaction and repair process in the damaged tissue. We have reported that Ngfr is associated to vascular remodeling in patients with acute coronary syndrome. However, it is unclear how Ngfr is involved in the pathogenesis of PAH. Purpose In this study, we investigated whether Ngfr relate to pathophysiology in PAH. Methods We estimated the frequency of Ngfr positive cells (% Ngfr+) in peripheral blood mononuclear cells obtained from PAH and non-PAH patients using flowcytometric analysis. In PAH patients, the hemodynamic parameters such as mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), and cardiac index (CI) were obtained by right heart catheterization, and evaluated for correlation with the % Ngfr+. Next, adult 8-week-old C57BL/6 (WT) mice and Ngfr knock out (KO) mice were exposed to chronic hypoxia (10% O2) or normoxia for 6 weeks. Then, mice were anesthetized and performed echocardiography and right heart catheterization. Then, mice were exsanguinated and blood sample was collected to evaluate the % Ngfr+ by flow cytometry. Right ventricular weight was measured and lung tissue was also collected for histological assessment and molecular pathway profiling. Results PAH (n=24) patients and non-PAH patients (n=17) were enrolled. The % Ngfr+ was significantly higher in PAH patients than that in non-PAH patients (0.056% versus 0.019%, p&amp;lt;0.0001). In PAH patients, the % Ngfr+ was correlated with severity of hemodynamic parameters such as mPAP (R=0.64 p&amp;lt;0.001), PVR (R=0.62 p&amp;lt;0.005), and CI (R=−0.48 p&amp;lt;0.05). In WT mice, chronic hypoxia significantly increased the right ventricular systolic pressure and induced vascular medial thickness and fibrosis around the pulmonary artery. Flow cytometry analysis revealed that the % Ngfr+ was significantly increased in the hypoxia compared to that in the normoxia. Under hypoxic conditions, the right ventricular systolic pressure was significantly increased in Ngfr KO mice compared to that in WT mice. In histological analysis, hypoxia-induced peripheral vascular fibrosis and medial thickness was more severe in Ngfr KO than that in WT mice. Conclusion Circulating Ngfr-positive cells are associated with severity of PAH in patients. In the hypoxia-induced PH model, gene deletion of Ngfr shows the progression of the pathogenesis of PAH. These results suggest that circulating Ngfr-positive cells have an important role in the pathogenesis of PAH and may be a novel target for PAH therapy. Funding Acknowledgement Type of funding source: None

Factors associated with pulmonary artery hypertension among premature infants with bronchopulmonary dysplasia in Vietnam

BackgroundPulmonary artery hypertension (PAH) is a common complication among premature infants with bronchopulmonary dysplasia (BPD). Factors associated with PAH among premature Vietnamese infants with BPD are unknown. The purpose of this study was to describe the epidemiological and clinical features of premature infants with BPD who had PAH and to identify the factors associated with PAH in these patients. MethodsThis descriptive study included 150 infants with BPD admitted to VNCH from August 2017 to July 2018.Clinical data were collected for all BPD patients. PAH screening was performed by echocardiography. ResultsPAH was more common among male BPD patients (71.9%). Median gestational age was 29 ± 2.1 weeks, 96.5% of cases were <32 gestational weeks of age. Median birth weight was 1100 ± 305.1 g. The prevalence of severe, moderate, mild PAH was 52.6%; 35.1%; 12.3%, respectively. Mean pulmonary pressure was 39.9 ± 7.8 mmHg, the majority had mild PAH (66.7%).The threshold level of N-terminal-pro-brain natriuretic peptide for PAH in BPD patients was 546 ng/L. Prematurity, low birth weight, severe BPD, long-lasting oxygen-dependence were significantly related to PAH (P < 0.05).PAH-associated factors were: no prenatal corticosteroid administration (OR, 2.1;95% CI,1.1–4.1;P = 0.04), oligohydramnios (OR,4.2; 95% CI,1.4–12.8; P = 0.01), inflammation of amniotic membrane (OR, 5.7; 95% CI,2.1–15.5; P = 0.001). ConclusionsPAH was common among premature infants with BPD. Prematurity, low birth weight, severe BPD, long-lasting oxygen-dependence were related to PAH in BPD patients.

The relationship between endothelial progenitor cells and pulmonary arterial hypertension in children with congenital heart disease

BackgroundPulmonary arterial hypertension (PAH) caused by congenital heart disease (CHD) is very common in clinics. Some studies have shown that PAH is related to the number of endothelial progenitor cells (EPCs), but there is no report on the relationship between PAH and the number of EPCs in children with CHD.MethodsIn this study, a total of 173 cases with CHD (from 0 to 6 years old) were collected. According to the mean pulmonary arterial pressure (mPAP) measured by right heart catheterization, these cases were divided into PAH groups (including high PAH group, mPAP> 25 mmHg, n = 32, and the middle PAH group, 20 mmHg ≤ mPAP≤25 mmHg, n = 30) and non-PAH group (mPAP< 20 mmHg, n = 111). Peripheral blood was taken for flow cytometry, and the number of EPCs (CD133+/KDR+ cells) was counted. The number of EPCs /μL of peripheral blood was calculated using the following formula: EPCs /μL = WBC /L × lymphocytes % × EPCs % × 10− 6.ResultsThe median EPCs of the non-PAH group, middle PAH group and high PAH group is 1.86/μL, 1.30 /μL and 0.98/μL, respectively. The mPAP decreases steadily as the level of EPCs increases (P < 0.05). After adjustment of gender, age and BMI, the number of EPCs was significantly associated with a decreased risk of high PAH (OR = 0.37, 95% CI: 0.16–0.87, P < 0.05). However, EPCs was not significantly associated with middle PAH (P > 0.05).ConclusionThe findings revealed that the EPCs and high PAH in patients with CHD correlate significantly and EPCs may become an effective treatment for PAH in patients with CHD. EPCs may be a protective factor of high PAH for children with CHD.

Early pulmonary arterial hypertension immediately after closure of a ventricular or complete atrioventricular septal defect beyond 6 months of age

BackgroundPulmonary arterial hypertension (PAH) is virtually absent after closure of ventricular septal defect (VSD) in the first six months of life. However the prevalence of PAH in patients, who underwent VSD closure later, is not clear. The aim of this study was to analyse the prevalence of PAH after a successful VSD closure after the age of 6months and whether there are risk factors for developing PAH. MethodsEchocardiographic and right heart catheter data of patients with VSD or complete atrioventricular septal defect, who underwent VSD closure after the age of 6months in our institution between 01/2005 and 06/2014, were retrospectively analyzed. PAH was defined as mean pulmonary arterial pressure (mPAP) of ≥25mmHg or tricuspid regurgitation jet velocity of ≥3.5m/s. ResultsIn 228 patients (median age at shunt closure 4.0years, range 0.5–69) and 174 complete follow-up data (median follow-up 3.7years, range 0.5–39.4), 9 patients needed pulmonary vasodilator therapy after shunt closure, 4 of them temporarily for up to 79months. Three patients are still on vasodilator treatment 1, 2.6 and 6years after surgery, other two were lost to follow-up. Another 6 patients with preoperatively borderline hemodynamics due to elevated mPAP and pulmonary vascular resistance, recovered well without signs of postoperative PAH. ConclusionWith the current practice for safe late VSD closure, PAH is very rare at least in the first years of follow-up. In most patients with perioperative PAH, this condition appears to be transient and shows good response on pulmonary vasodilator treatment.

Early Detection of PAH in Patients With Systemic Connective Tissue Disease

Early Detection of PAH in Patients With Systemic Connective Tissue Disease

Human immunodeficiency virus-associated pulmonary arterial hypertension: considerations for pulmonary vascular diseases in the developing world.

Pulmonary hypertension is broadly recognized as a group of disorders that share the common characteristic of an elevated mean pulmonary arterial pressure (≥25 mm Hg). Pulmonary arterial hypertension (PAH; Group 1) is a subset of the pulmonary hypertension disorders that is also characterized by pulmonary arterial remodeling, the formation of plexiform lesions, and poor clinical outcomes. When present, pulmonary hypertension is associated with a worse overall prognosis. Clinical evaluation of patients with human immunodeficiency virus (HIV) has indicated that there is a high prevalence of PAH in patients with HIV suggesting a relationship between HIV infection and the pathogenesis of PAH. Human immunodeficiency virus is a member of the genus Lentivirus of the family Retroviridae. The primary target of HIV is the immune system; destruction of lymphocytes (mainly CD4+ T cells) by the virus induces severe damage to the host immune function, which increases patient risk for developing opportunistic infections. AIDS is a clinical syndrome representing the final stage of HIV infection and is often characterized by a CD4+ T cell count <200 cells/μL. Even in the contemporary era of immune-modulating therapies, the prevalence of HIV infection continues to grow worldwide, devastating the health of individuals, communities, regions, and entire countries.1 Two major types of the virus are reported: HIV type 1 (HIV-1) is related to viruses originally endemic to West African primates and is primarily responsible for the AIDS pandemic, whereas HIV type 2 (HIV-2) is comparatively less virulent. HIV infection promotes a range of cardiovascular diseases,2,3 and is an independent risk factor for the development of pulmonary vascular diseases, including severe PAH, the latter of which is the subject of this review. In 1987, Kim and Factor4 published the first case report of a 40-year-old homosexual man with hemophilia and AIDS, …

Relevance of partitioning DLCO to detect pulmonary hypertension in systemic sclerosis.

We investigated whether partitioning DLCO into membrane conductance for CO (DmCO) and pulmonary capillary blood volume (Vcap) was helpful in suspecting precapillary pulmonary (arterial) hypertension (P(A)H) in systemic sclerosis (SSc) patients with or without interstitial lung disease (ILD). We included 63 SSc patients with isolated PAH (n=6), isolated ILD (n=19), association of both (n=12) or without PAH and ILD (n=26). Partitioning of DLCO was performed by the combined DLNO/DLCO method. DLCO, DmCO and Vcap were equally reduced in patients with isolated PAH and patients with isolated ILD but Vcap/alveolar volume (VA) ratio was significantly lower in the isolated PAH group. In patients without ILD, DLCO, DmCO, Vcap and Vcap/VA ratio were reduced in patients with isolated PAH when compared to patients without PAH and both Vcap/VA and DLCO had the highest AUC to detect PAH. In patients with ILD, Vcap had the highest AUC and performed better than DLCO to detect PH in this subgroup. In conclusion, Vcap/VA was lower in PAH than in ILD in SSC whereas DLCO was not different. Vcap/VA ratio and DLCO had similar high performance to detect PAH in patients without ILD. Vcap had better AUC than DLCO, DmCO and FVC/DLCO ratio to detect PH in SSC patients with ILD. These results suggest that partitioning of DLCO might be of interest to detect P(A)H in SSC patients with or without ILD.

Long-term survival of patients with repaired Congenital Heart Disease associated Pulmonary Arterial Hypertension (CHD-PAH) in the modern management era

Purpose: To explore long-term survival and prognostic factors for patients developed into pulmonary arterial hypertension after or before correction of their congenital heart diseases. Methods: This study retrospectively included congenital heart disease associated pulmonary arterial hypertension (CHD-PAH) patients who underwent correction for pure shunt previously, all of which consecutively visited Shanghai pulmonary hospital between August 1, 2006 and July 31, 2012. Patients diagnosed as idiopathic pulmonary arterial hypertension (IPAH) and Eisenmenger's syndrome during the corresponding period in the same center were taken as control groups. Analyses of type of defects, gender, age at surgery, WHO functional class, hemodynamic parameters, as well as biomarkers were made to illustrate their influence on the overall survival. Results: One hundred and forty-eight repaired CHD-PAH patients while 377 IPAH patients and 103 patients with Eisenmenger's syndrome were enrolled. All the three groups have female predominance in gender distribution. Compared with other two control groups, the patients with repaired CHD-PAH patients had younger age at diagnosis and higher mean right atrial pressure. The pulmonary arterial mean pressure of repaired CHD-PAH patients was higher than that of IPAH patients, but lower than that of patients with Eisenmenger's syndrome. Repaired CHD-PAH patients had higher cardiac indexes than IPAH patients, but lower than patients with Eisenmenger's syndrome. One-year, three-year and five-year survival for repaired CHD-PAH patients are 94.5%, 79.0% and 74.0%, respectively. There is no significant statistical difference in survival between three groups. Multivariate Cox regression analysis found that WHO-FC and SvO2 are two independent prognostic factor (P = 0.009 and 0.030) in PAH patients after correction for CHD, while the original shunt type, type of operation, age at PAH have no significant influence on their prognosis. Conclusions: PAH in patients underwent correction of simple shunt congenital heart disease is independent of the original CHD, the disease for this subgroup is somehow similar to IPAH, including pathophysiological changes, disease development as well as prognosis.

FRI0279 Anemic hypoxia is associated with pulmonary arterial hypertension in patients with systemic lupus erythematosus

BackgroundPulmonary arterial hypertension (PAH) is a serious and often fatal complication of systemic lupus erythematosus (SLE), but its pathogenesis is still unclear. Hypoxia-induced pulmonary vascular remodelling has been suggested to...

Pulmonary Lymphoid Neogenesis in Idiopathic Pulmonary Arterial Hypertension

Patients with idiopathic pulmonary arterial hypertension (IPAH) present circulating autoantibodies against vascular wall components. Pathogenic antibodies may be generated in tertiary (ectopic) lymphoid tissues (tLTs). To assess the frequency of tLTs in IPAH lungs, as compared with control subjects and flow-induced PAH in patients with Eisenmenger syndrome, and to identify local mechanisms responsible for their formation, perpetuation, and function. tLT composition and structure were studied by multiple immunostainings. Cytokine/chemokine and growth factor expression was quantified by real-time polymerase chain reaction and localized by immunofluorescence. The systemic mark of pulmonary lymphoid neogenesis was investigated by flow cytometry analyses of circulating lymphocytes. As opposed to lungs from control subjects and patients with Eisenmenger syndrome, IPAH lungs contained perivascular tLTs, comprising B- and T-cell areas with high endothelial venules and dendritic cells. Lymphocyte survival factors, such as IL-7 and platelet-derived growth factor-A, were expressed in tLTs as well as the lymphorganogenic cytokines/chemokines, lymphotoxin-α/-β, CCL19, CCL20, CCL21, and CXCL13, which might explain the depletion of circulating CCR6(+) and CXCR5(+) lymphocytes. tLTs were connected with remodeled vessels via an ER-TR7(+) stromal network and supplied by lymphatic channels. The presence of germinal center centroblasts, follicular dendritic cells, activation-induced cytidine deaminase, and IL-21(+)PD1(+) follicular helper T cells in tLTs together with CD138(+) plasma cell accumulation around remodeled vessels in areas of immunoglobulin deposition argued for local immunoglobulin class switching and ongoing production. We highlight the main features of lymphoid neogenesis specifically in the lungs of patients with IPAH, providing new evidence of immunological mechanisms in this severe condition.

S97 BMPR2 R899X knock-in mice developed age-related pulmonary hypertension

BackgroundHeterozygous germline mutations in the gene encoding the bone morphogenetic protein type II receptor (BMPR2) underlie the majority (>70%) of cases of heritable pulmonary arterial hypertension (hPAH) and a variable...

Effects of uremic sera on renal tubular P-aminohippurate transport.

The effects of uremic sera from patients with different kidney disorders on PAH uptake by isolated renal tubules of the rabbit were investigated. These sera were found to depress PAH uptake when compared to normal control sera. The inhibitory effect of the uremic sera was markedly reduced by hemodialysis or peritoneal dialysis of the patient or in vitro dialysis of the sera. The inhibiting effect was also noted in peritoneal dialysate. The in vitro inhibition of PAH transport demonstrated in this study indicates a mechanism that may explain poor extraction of PAH in patients with renal insufficiency and makes difficult the interpretation of certain renal function studies on them.