High Pulmonary Arterial Hypertension Research Articles

Evaluation of serum uric acid level in systemic lupus erythematosus patients with normal and high pulmonary arterial hypertension

Evaluation of serum uric acid level in systemic lupus erythematosus patients with normal and high pulmonary arterial hypertension

Pulmonary Arterial Hypertension in Hyperthyroidism: Age, Ethnic, and Gender Disparities

Objective: Pulmonary arterial hypertension (PAH) affects 2.6% of adults and 36% of people with chronic obstructive pulmonary disease (COPD). Several case reports and small case series suggested a hyperthyroidism-PAH association.
 Design: Retrospective chart review.
 Methods: We undertook a retrospective chart review (1982–2018) to assess PAH prevalence in a multi-ethnic convenience sample of hyperthyroid adults with multiple etiologies. We calculated associations of pulmonary artery maximum systolic pressure (PSAPmax) with subject age, and maximum serum triiodothyronine (T3) and thyroxine (T4), free T3, and T4, minimum serum thyroid-stimulating hormone (TSH), and thyroid antibody titers, comparing PAH prevalence and the odds of being undiagnosed as to hyperthyroidism etiology by gender and ethnicity/race.
 Results: We found a high prevalence of PAH in hyperthyroid people, like that reported for people with COPD. We found no significant association between PSAPmax and any thyroid function test or thyroid antibody titer. As reported more recently in the general population, PSAPmax significantly correlated with age in hyperthyroid people. There was no significant disparity in the prevalence of PAH among White, non-Hispanic Black, and Latinx hyperthyroid people or between genders. The percentage of patients whose hyperthyroidism etiology was undiagnosed was high with significant disparity only between non-Hispanic Black and White people and between men and women. PAH was common in hyperthyroid subjects with any hyperthyroidism etiology.
 Conclusions: 2D-echocardiography should be performed in all hyperthyroid people because PAH is common, especially in older people because of their co-morbidities and poorer prognoses. Further research is needed regarding demographic disparities in being undiagnosed as to hyperthyroidism etiology.
 Principal Verdicts/Significance Statement: We reconfirmed the high PAH incidence in hyperthyroidism, previously reported, but profoundly under-recognized by physicians, to patients’ detriment. Further, we found that the shift in the general PAH population from younger to older individuals is mirrored in hyperthyroid people with PAH. This is concerning because older people have more co-morbidities and worse prognoses, necessitating early, effective intervention. PAH was present with diverse hyperthyroidism etiologies, suggesting that it is multicausal, resulting from autoimmunity, thyroid hormone excess, and goitrous upper airway obstruction and should be considered, regardless of etiology. Our observations that many subjects had no established hyperthyroidism etiology and that males and Blacks were likelier to be undiagnosed are concerning, warranting further study.

Atrial strain in patients with pulmonary arterial hypertension associated with congenital heart disease

Pulmonary arterial hypertension (PAH) has a major impact on mortality and morbidity on congenital heart disease (CHD) patients. Atrial strain in PAH patients has been related to clinical severity and adverse outcomes. The aim of this study was therefore to assess the prognostic role and compare bi-atrial function in patients with CHD-PAH, PAH from other causes (nPAH) and healthy controls. We included in this prospective cohort study 65 patients with CHD-PAH, 67 patients with nPAH and 65 healthy volunteers. Transthoracic echocardiography, clinical assessment, BNP measurement and 6MWT were performed at baseline. Classic echocardiographic measurements and atrial function studying the 3 different phases strain were measured in both. Atrial strain parameters are decreased in patients with CHD-PAH as compared to healthy volunteers, especially the right atrial (RA) reservoir (RASR 29,67% vs. 44,15%, P < 0,0001) and conduit phase (RASCD −15,85 vs. −28,52, P < 0,0001), but also left atrial (LA) reservoir and conduit phases. Active contractile phase seems preserved in both PAH group. Atrial function was comparable between CHD-PAH and nPAH patients. On multivariate analysis, BNP, pericardial effusion, RA ejection fraction, RASR and RASCD were independently associated with death or transplantation. RASR ≤ 30% or RASCD > −8% strain identified patients with a more than 3-fold-increased risk of death or transplant. Patients with CHD-PAH do not differ in atrial adaptation in comparison with npah. Impaired RASR and RASCD identify high risk PAH patients. RA conduit or reservoir function impairment represents a severity marker of PAH, including in patients with CHD-PAH suggesting the importance of RV diastolic dysfunction. This might be an early marker of poor prognosis (Fig. 1).

Abstract 15389: Insulin Like Growth Factor Binding Proteins 1 and 2 Are Prognostic Survival Markers in Intermediate Risk Pulmonary Arterial Hypertension

Introduction: Pulmonary arterial hypertension (PH) is an often fatal disease of the pre-capillary pulmonary vasculature. Recognizing high risk PH in ambulatory patients is important for optimization of therapy to improve outcomes. We previously identified insulin like growth factor binding proteins 1 and 2 (IGFBP1, IGFBP2) as prognostic markers in severe PH; here, we evaluated IGFBP1/2 as prognostic markers in PH with intermediate risk features. Methods: A multiplex ELISA assay measured serum IGFBP1/2 in the multicenter PH Biobank (N=2450), and independent validation cohorts (Johns Hopkins, N=145, Vanderbilt N= 128, 388 observations over time). IGFBP1/2 concentrations were compared to hemodynamics, six-minute walk (6MW), and WHO functional class using linear/logistic regression adjusted for age and sex. Time to death/transplant by IGFBP1/2 levels was assessed by Cox proportional hazard models. Analysis was repeated in subjects with low to intermediate risk features defined as WHO functional class 1-2, 6MW &gt;300 m, and NT-proBNP &lt;1500 pg/mL, based on the REVEAL and ERS risk scores. 1, 2 Results: In all cohorts, increased IGFBP1 and IGFBP2 were associated with lower cardiac output, higher mean pulmonary artery pressure and pulmonary vascular resistance (PVR, p&lt;0.05 for all). In each sub-analysis, a higher IGFBP1 and IGFBP2 was associated with lower cardiac output, lower systemic blood pressure, and higher PVR (p&lt;0.05 for all). Higher IGFBP1 and IGFBP2 were associated with shorter time to death/transplant in the overall cohort and each of the intermediate risk PH cohorts (Table 1), although underpowered in the Vanderbilt cohort. Conclusions: Identifying patients who will have adverse outcome in intermediate risk PH has proven challenging. These data suggest IGFBP1/2 are good prognostic markers in PH where functional class and exertional tolerance is preserved. IGFBP1/2 could further discriminate adverse outcomes in patients with low to intermediate risk PH.

Abstract 11386: Double Whammy Complicating Management of Pulmonary Hypertension

Introduction: When presented with challenging cardiac cases, in addition to obvious diagnoses, it is critical to maintain high level of suspicion about other subtle conditions. We describe one such case of pulmonary arterial hypertension (PAH) from severe mitral stenosis (MS) and another less obvious congenital cardiac condition that significantly impacted the clinical course. Case: 32-year-old immigrant male with known heart murmur presented with palpitations due to atrial fibrillation. His resting oxygen saturation was 95% in all extremities and he had no clubbing. He had pectus carinatum and scoliosis, prominent right ventricular lift, normal S1, loud S2, opening snap, rumbling diastolic murmur at the apex, and an ejection systolic murmur at the left upper sternal border. Echocardiogram revealed normal biventricular size and function, severely enlarged left atrium, rheumatic severe MS, moderate mitral regurgitation, a restrictive ventricular septal defect (VSD), and elevated right ventricular systolic pressure. Cardiac catheterization demonstrated mixed pre- and post-capillary PAH with mean pulmonary artery pressure of 80 mmHg, wedge pressure 30 mm Hg and pulmonary vascular resistance of 3.0 woods unit which was underestimated. Since pre-capillary component of the PAH could not be entirely explained by the small VSD, a congenital cardiac CT was performed revealing moderate sized patent ductus arteriosus (PDA). Further management decisions were complicated since MS was not amenable to percutaneous intervention and surgical risks were high given severe pre-capillary PAH- management of which with pulmonary vasodilators was itself high risk in the setting of severe MS and high wedge pressures. After optimal medical management, a multidisciplinary team carefully considered the risks and benefits of multiple interventions. Ultimately, the patient underwent surgical mitral valve replacement, fenestrated patch closure of the PDA, and then initiation of pulmonary vasodilators. The patient continues to do well on oral pulmonary vasodilator therapy 6 months after surgery. Conclusion: We describe an astute critical thought process of a multidisciplinary team utilized to manage a challenging case of mixed PAH from severe rheumatic MS and PDA.

Early and long-term results of ventricular septal defect repair in children with severe pulmonary hypertension and elevated pulmonary vascular resistance by the double or traditional patch technique.

In upper-income countries, infants undergo low-risk ventricular septal defect (VSD) repair. Children in low- and middle-income countries frequently present at older ages with elevated pulmonary vascular resistance (PVR) and pulmonary arterial hypertension (PAH). Expensive interventions for pulmonary hypertensive crisis are not available, and children are often denied an operation due to the mortality risk. We report our early and late experiences with these patients who underwent VSD closure by traditional patch (TP) or double patch (DP) techniques. We extracted data from patients with VSD and PAH who underwent VSD closure operations from 1996 to 2016. Information regarding cardiac catheterizations, operations, time in the intensive care unit and follow-up information was found. We identified 129 children and analysed the differences between the TP (89/129) and the DP (40/129) in unidirectional groups. After 2005, the patients were pretreated with sildenafil 3 months before catheterization. The TP group was younger (P < 0.001). Hospital mortality (2.5%, DP; 10.1%,TP) was not significantly different (P = 0.17) between the 2 groups despite significant differences in baseline PVR, PVR/systemic vascular resistance and the number of children with a saturation less than 90%. The long-term survival and regression of PAH were better in the DP group (survival over 97% vs 93% in the TP group). Moreover, 61% of children with DP and 75% of those with TP had normal to mild elevations in pulmonary artery pressures at the last follow-up examination (P = 0.046). The DP operation is a low-risk procedure. Moreover, the long-term outcome with the use of this technique in high-risk patients with VSD and high PVR and PAH is favourable with respect to survival and showed a decrease in PAH at the last follow-up.

Effects of YM155 on the proliferation and apoptosis of pulmonary artery smooth muscle cells in a rat model of high pulmonary blood flow-induced pulmonary arterial hypertension

ABSTRACT Introduction Proliferation and apoptosis of pulmonary artery smooth muscle cells (PASMCs) play an important role in the occurrence and development of pulmonary arterial hypertension (PAH). The purpose of this study was to investigate the effects of survivin inhibitor YM155 on the proliferation and apoptosis of PASMCs in rats with PAH induced by high pulmonary blood flow. Methods Thirty male Sprague-Dawley (SD) rats were randomly divided into control, model, and YM155 intervention groups. A rat model of PAH induced by high pulmonary blood flow was established, and it was confirmed by assessments of right-ventricular pressure (RVP) and right ventricular hypertrophy index (RVHI). Immunohistochemical staining and western blot analysis were used to detect the expression of survivin, and the proliferation and apoptosis of PASMCs. Lastly, the effects of in vivo treatment of YM155 were tested. Results The increased expression of survivin mRNA and protein were observed in the model group, accompanied by pulmonary arteriolar wall thickening, lumen stenosis, and perivascular inflammatory cell infiltration. Elevated expression of survivin and pulmonary vascular remodeling were significantly mitigated after YM155 treatment. Specifically, the YM155 intervention group had a significantly lower PASMC proliferation rate and a higher PASMC apoptotic rate. Conclusion YM155 suppressed PASMC proliferation and promoted PASMC apoptosis by inhibiting survivin expression and thereby reducing pulmonary vascular remodeling in high pulmonary blood flow-induced PAH in vivo.

Metabolic Reprogramming of the Right Ventricle and Pulmonary Arteries in a Flow-Associated Pulmonary Arterial Hypertension Rat Model.

Pulmonary arterial hypertension (PAH) is a complex devastating disease relevant to remarkable metabolic dysregulation. Although various research studies on PAH from a metabolic perspective have been emerging, pathogenesis of PAH varies in different categories. Research on metabolic reprogramming in flow-associated PAH remains insufficient. An untargeted metabolomic profiling platform was used to evaluate the metabolic profile of pulmonary arteries (PAs) as well as the right ventricle (RV) in a flow-associated PAH rat model in the present work. A total of 79 PAs and 128 RV metabolites were significantly altered in PAH rats, among which 39 metabolites were assessed as shared dysregulated metabolites in PAs and the RV. Pathway analysis elucidated that, in PAs of PAH rats, pathways of phenylalanine, tyrosine, and tryptophan biosynthesis and linoleic acid metabolism were significantly altered, while in the RV, arginine biosynthesis and linoleic acid metabolism were altered dramatically. Further integrated analysis of shared dysregulated PA and RV metabolites demonstrated that the linoleic acid metabolism and the arachidonic acid (AA) metabolism were the key pathways involved in the pathogenesis of flow-associated PAH. Results obtained from the present work indicate that the PAH pathogenesis could be mediated by widespread metabolic reprogramming. In particular, the dysregulation of AA metabolism may considerably contribute to the development of high blood flow-associated PAH.

“A CROSS SECTIONAL, DESCRIPTIVE STUDY ON SYSTEMIC ILLNESSES AND CARDIAC FUNCTION ABNORMALITIES IN CHILDREN”

Background:There are wide number of diseases of almost every system in the body which can affect heart in a number of different ways including increasing demands on the heart ,ventricular dysfunction ,rhythm abnormalities ,valve abnormalities ,pulmonary pressures and lot more.Cardiac involvement in systemic diseases is usually silent or oligosymptomatic and includes different pathophysiological mechanisms such as myocardial inflammation, infarction ,subendocardial vasculitis,valvular disease and different patterns of fibrosis. Objective : To study association between systemic illnesses (hematological, endocrinal , renal) and cardiac function abnormalities as ventricular function,cardiac dimensions ,pulmonary artery pressure and pericardial effusion,for early diagnosis and treatment to decrease morbidity and mortality in patient with systemic illness. Design/Method:It was a cross sectional,descriptive study The present study was conducted in the Department of Pediatrics, LLRM Medical College,Meerut,Uttar Pradesh over a period of 1 year (June 2019-June 2020) Results: Cardiac findings in all three groups show ECG abnormalities and echocardiographic changes compared to general population. ECG abnormalities were prolonged PR interval and sinus tachycardia while echocardiographic changes mainly left ventricular(LV) dilatation and hypertrophy ,increased cardiac output ,ventricular dysfunction and pulmonary arterial hypertension(PAH),were noted in a significant proportion of patients. Conclusion:Systemic illnesses affect cardiac parameters in various ways including prolonged PR interval,cardiac dilatation,chamber hypertrophy ,high cardiac output,high cardiac index ,PAH and ventricular dysfunction.

TMEM16A Regulates Pulmonary Arterial Smooth Muscle Cells Proliferation via p38MAPK/ERK Pathway in High Pulmonary Blood Flow-Induced Pulmonary Arterial Hypertension

Objective: Pulmonary arterial hypertension (PAH) is a complex disease of the small pulmonary arteries that is mainly characterized by vascular remodeling. It has been demonstrated that excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs) plays a pivotal role in vascular remodeling during PAH. The present study was undertaken to explore the role of TMEM16A in regulating PASMCs proliferation in high pulmonary blood flow-induced PAH. Methods: Aortocaval shunt surgery was undertaken to establish an animal model. Pulmonary artery pressure and pulmonary vascular structure remodeling (PVSR) were tested. Immunohistochemical staining and Western blot were performed to investigate the expression of TMEM16A. The proliferation of PASMCs was tested by the MTT assay. After treating PASMCs with TMEM16A-siRNA, the expression of proliferating cell nuclear antigen (PCNA), phosphorylated p38 mitogen-activated protein kinase (p-p38MAPK), and phosphorylated extracellular signal-regulated kinase (p-ERK) signaling in PASMCs were tested. Results: PAH and PVSR developed 11 weeks postoperation. Elevated expression of TMEM16A accompanied by high expression of PCNA in pulmonary arteries of the shunt group was observed. The increased proliferation of PASMCs and increased expression of TMEM16A and PCNA, along with activated p-p38MAPK and p-ERK signaling in PASMCs of the shunt group, were all attenuated by siRNA-specific TMEM16A knockdown. Conclusion: TMEM16A regulates PASMCs proliferation in high pulmonary blood flow-induced PAH, and the p38MAPK/ERK signaling pathway is probably involved.

TMEM16A regulates the cell cycle of pulmonary artery smooth muscle cells in high-flow-induced pulmonary arterial hypertension rat model.

High-flow-induced pulmonary arterial hypertension (PAH) has attained global notoriety, the mechanism of which remains elusive. The present study investigated the regulation of Anoctamin-1, also known as transmembrane member 16A (TMEM16A), in the cell cycle progression of pulmonary artery smooth muscle cells (PASMCs) from a PAH rat model induced by high pulmonary blood flow. A total of 30 Sprague-Dawley rats were randomly assigned into control, sham and shunt groups. A rat model of high pulmonary blood flow-induced PAH was established by surgery using abdominal aorta-inferior vena cava fistula. Right ventricular pressure, right ventricular hypertrophy index and pulmonary arteriole structural remodeling were assessed 11 weeks following operation. The cell cycle statuses of PASMCs was assessed via flow cytometry, whereas western blot analysis was performed to measure the expression of cyclin D1, CDK2, p27KIP and cyclin E in primary PASMCs isolated from rats. The expression of cyclin E and cyclin D1 was revealed to be increased in the shunt group compared with the control group, which was accompanied with an increased expression of TMEM16A in the shunt group. Changes in the ratio of PASMCs in the G0/G1, S and G2/M phases of cycle induced by PAH were reversed by TMEM16A knockdown. The expression of cyclin E and cyclin D1 in the shunt group was significantly higher compared with the control group in vitro, which was reversed by TMEM16A-siRNA transfection. In conclusion, TMEM16A may be involved in high pulmonary blood flow-induced PAH by regulating PASMC cell cycle progression.

Evaluation of serum uric acid level in systemic lupus erythematosus patients with normal and high pulmonary arterial hypertension.

Background: Systemic lupus erythematosus (SLE) is a life-threatening multisystem inflammatory condition affected any organ system. Considering the role of uric acid as a pro-inflammatory compound in high pulmonary arterial pressure, serum levels of uric acid and its relation to severity and duration of the disease were assessed in SLE patients.Methods: As a cross-sectional study, 75 patients with SLE were enrolled in Imam Khomeini Hospital and Sahand Clinic. Serum uric acid level was measured by pars azmoon kit. Pearson correlation coefficient and T-test were used for statistical analysis of data.Results: The mean duration of SLE was 56.44 ± 40.57 months. High serum uric acid was observed in 13.3% of patients with SLE. Moreover, 8% of these patients had high pulmonary arterial pressure. Serum uric acid in patients with high pulmonary artery pressure was significantly higher than patients with normal pulmonary artery pressure (P < 0.01). Furthermore, a significant relation was seen between severity of SLE disease with serum uric acid level and pulmonary artery systolic pressure (P < 0.05). However, there was no significant correlation between serum uric acid level and duration of the disease (p = 0.90, r = 0.016).Conclusion: According to these results, a significantly increased level of serum uric acid was observed in patients with pulmonary arterial pressure. Hence, serum uric acid level could be a prognostic marker of pulmonary arterial pressure in SLE patients which correlates with disease severity. It also would help to reduce clinical demands for echocardiography in patients with normal uric acid levels.

Multidisciplinary Perioperative Management of Pulmonary Arterial Hypertension in Patients Undergoing Noncardiac Surgery.

To describe the effect of implementing a contemporary perioperative pulmonary hypertension (PH)-targeted protocol in patients with pulmonary arterial hypertension (PAH) undergoing noncardiac surgery (NCS). The data of consecutive patients with PAH diagnosed by right heart catheterization who underwent NCS between January 1, 2006 and February 9, 2016 were reviewed. Patient demographics, etiology of PAH, clinical features, diagnostic data, utilization of PH-specific medications, and trend of perioperative complications rate were recorded during the study period. In the base cohort of 375 patients, 37 had NCS. The mean age at surgery was 62 years. Most patients were women (78%) classified in group 1 PAH. At the time of the surgery, 86% were New York Heart Association functional class III/IV and 97% had American Society of Anesthesiologists classifications 3 and 4. A larger proportion of patients displayed lower PAH risk scores between 2006 and 2011 (P = 0.045). Conversely, a higher percentage of patients exhibited moderately high to very high PAH risk scores between 2012 and 2016 (P = 0.003). Perioperative and anesthetic-related morbidity was 27%, and no difference was observed between either period (P = 0.944). Most of the complications (70%) were related to general anesthesia. Two deaths (5%) occurred in our study group, both during the 2006-2011 period. The combination of a multidisciplinary perioperative approach, utilization of novel pulmonary vascular disease-targeted therapy, adequate perioperative optimization, and thoughtful selection of anesthetic technique seems to be a potential strategy to at least maintain similar perioperative outcomes among higher- and lower-risk patients with PAH undergoing NCS.

Red blood cell distribution width as a related factor of pulmonary arterial hypertension in patients with systemic sclerosis.

The aim of this study was to investigate the utility of red blood cell distribution width (RDW) as a simple and readily available marker of occurrence of pulmonary arterial hypertension (PAH) in patients with systemic sclerosis (SSc). One hundred and forty-five consecutive patients with SSc were recruited to the single-center cross-sectional study. Demographic characteristics, hematological parameters, Modified Rodnan Skin Score, and World Health Organization functional classification were determined. Diagnosis of PAH was based on screening by echocardiography and was confirmed by right heart catheterization. Interstitial lung disease (ILD) was diagnosed based on chest high-resolution computed tomography findings. There were no significant differences in gender, age, or disease duration between limited and diffused SSc groups. PAH was detected in 28 of lcSSc (33.3%) and 14 of dcSSc (23.0%) subjects. Patients with higher RDW values were more likely to be men with high anti-u1RNP titers and PAH. A significant correlation was found between RDW and high-sensitivity C-reactive protein (p = 0.375, p < 0.01) and the diffusing capacity of the lungs for carbon monoxide (ρ = - 0.396, p < 0.01). The SSc-PAH group had significantly higher RDW values compared to the SSc group without pulmonary disease (15.7 ± 2.2 and 13.7 ± 1.0, p < 0.001). The mean RDW in the SSc-PAH-ILD group was significantly higher than that in the SSc-ILD group (16.3 ± 2.2% and 14.0 ± 1.5%, p < 0.001). Besides the recognized risk factors, high RDW was an independent predictor of PAH in patients with SSc (OR = 3.314 [95%CI 1.038-10.580], p < 0.05). RDW may be a related factor for identifying the pulmonary arterial hypertension in SSc patients.

Pregnancy outcome in women with Eisenmenger's syndrome: a case series from west China.

BackgroundEisenmenger’s syndrome (ES) consists of pulmonary hypertension with a reversed or bidirectional shunt at the atrioventricular, or aortopulmonary level.The cardiovascular changes that occur during the pregnancy contribute to the high maternal morbidity and mortality in patients with ES. This study is to assess maternal and fetal outcomes in patients with ES.MethodsThis study is a retrospective analysis of 11 pregnancies in women with ES who delivered at a tertiary care center in west China between 2010 and 2014. Cases were divided into group I (maternal survival) and group II (maternal death). Clinical data were noted and analyzed.ResultsAll ES patients presented with severe pulmonary arterial hypertension (PAH). Four maternal deaths were recorded (maternal mortality of 36%). Only one pregnancy continued to term. Ventricular septal defect diameter in group II was larger than that in group I (2.93 ± 0.76 cm vs. 1.90 ± 0.54 cm, p < 0.05). Arterial oxygen saturation and pre-delivery arterial oxygen tension during oxygen inhalation were significantly lower in group II (p < 0.05). Pulmonary arterial blood pressure (PABP) in both groups were high while ejection fractions (EF) were significantly lower in group II (p < 0.05). The incidence of pre-delivery heart failure in group II was substantially higher than in survivors (100 vs.14.3%, p < 0.05). Fetal complications were exceptionally high: preterm delivery (88%), small for gestational age (83%), fetal mortality (27%) and neonatal mortality (25%).ConclusionsIn west China,the perinatal outcome of pregnant women with ES is poor, especially when complicated with high pulmonary arterial hypertension (PAH). Pregnancy remains strongly contraindicated in ES. Effective contraception is essential, and the option of terminating pregnancy in the first trimester should be presented to pregnant women with ES.

Evaluation of Tricuspid Regurgitant Jet Velocity in Thalassemia Patients with Splenectomy

Background: β-thalassemia is an inherited disorder of β-globin biosynthesis. Dysfunction in hemoglobin chain production, ineffective erythropoiesis, and hemolysis occur in β-thalassemia. Pulmonary arterial hypertension (PAH) is increasingly detected in patients with β-thalassemia, and splenectomy which decreases the need for blood transfusion increases the pulmonary artery pressure (PAP). Objectives: This study aimed to assess the PAP in patients with β-thalassemia (male or female and major or intermedia) who had undergone splenectomy. Methods: A total of 137 patients suffering from β-thalassemia were evaluated during the study. All subjects were referred for cardiac evaluation. Clinical history, presence of cardiac symptoms, and previous splenectomy were noted. Standard M-mode, 2D, and Doppler echocardiographic examinations were performed for all subjects. Patients with a tricuspid regurgitant jet velocity (TRV) ≥ 2.5 m/s were considered at risk for PAH. Results: Average age of the patients was 21.15 ± 6.68 years. No significant difference was observed in the PAP between the 2 groups of thalassemia major and intermedia and also the 2 sex groups. Indeed, 6.6% of the patients had an increased PAP. The significant finding of the study was that the patients who had had splenectomy were significantly at an increased risk of PAH (P = 0.046). Conclusions: The etiology of PAH in thalassemia is multifactorial such as inflammatory mediators. Also, the absence of the spleen plays an important role in developing a high TRV and PAH.

Pulmonary Arterial Hypertension in Patients with Primary Sjögren’s Syndrome

Introduction. Primary Sjögren's syndrome (pSS) is an autoimmune epithelitis. Pulmonary arterial hypertension (PAH) is an important and severe complication, which is encountered in many collagen tissue disorders. Early diagnostic strategies are required to define it at the asymptomatic stage. Doppler echocardiography is an important, noninvasive screening test for PAH diagnosis. Objective. The aim of this present study is to define the frequency of PAH in patients with pSS and to reveal correlations with laboratory and clinical findings. Material and Methods. A total of 47 patients, who were diagnosed with pSS according to American-European Study Group criteria were enrolled in the study. After all patients were evaluated clinically and by laboratory tests, Doppler echocardiography was performed in the cardiology outpatient clinic. Systolic pulmonary artery pressure (SPAP) >30 mm Hg values, which were measured at the resting state, were accepted as significant for PAH. Results. Forty-seven patients with pSS were included in the study. The mean age of patients was 48 years and the mean disease duration was 5.3 years. PAH was defined in 11 of the 47 patients (23.4%). The SPAP value was over 35 mm Hg in 5 out of 11 patients, whereas six patients had SPAP measuring 30–35 mm Hg. While pulmonary hypertension was related with earlier age and shorter duration of disease (P = 0.04), there was no statistically significant correlation between SPAP increase and clinical findings (P > 0.05). Conclusion. We have defined high PAH frequency in patients with pSS. Since there are different data in the literature, it is obvious that large scale, multicentre studies are required.

Mesenchymal stem cell prevention of vascular remodeling in high flow-induced pulmonary hypertension through a paracrine mechanism

Pulmonary arterial hypertension (PAH) is characterized by functional and structural changes in the pulmonary vasculature, and despite the drug treatment that made significant progress, the prognosis of patients with advanced PH remains extremely poor. In the present study, we investigated the early effect of bone marrow mesenchymal stem cells (BMSCs) on experimental high blood flow-induced PAH model rats and discussed the mechanism. BMSCs were isolated, cultured from bone marrow of Sprague–Dawley (SD) rat. The animal model of PAH was created by surgical methods to produce a left-to-right shunt. Following the successful establishment of the PAH model, rats were randomly assigned to three groups (n=20 in each group): sham group (control), PAH group, and BMSC group (received a sublingual vein injection of 1–5×106 BMSCs). Two weeks after the administration, BMSCs significantly reduced the vascular remodeling, improved the hemodynamic data, and deceased the right ventricle weight ratio to left ventricular plus septal weight (RV/LV+S) (P<0.05). Real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry analysis results indicated that the inflammation factors such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) were reduced (P<0.05); the expression of matrix metallo proteinase-9 (MMP-9) was lower (P<0.05); vascular endothelial growth factor (VEGF) was higher in BMSC group than those in PAH group (P<0.05). ConclusionSublingual vein injection of BMSCs for 2weeks, significantly improved the lung and heart injury caused by left-to-right shunt-induced PAH; decreased pulmonary vascular remodeling and inflammation; and enhanced angiogenesis.

Accuracy of Doppler-Derived Estimation of Pulmonary Vascular Resistance in Congenital Heart Disease: An Index of Operability

Pulmonary vascular resistance (PVR) is a critical and essential parameter during the assessment and selection of modality of treatment in patients with congenital heart disease (CHD) accompanied by pulmonary arterial hypertension (PAH). Cardiac catheterization is the "gold standard" but is an invasive method for PVR measurement. A noninvasive and reliable method for estimation of PVR in children has been a major challenge and most desirable during past decades, especially for those who need repeated measurements. In a prospective study and among consecutive patients who were referred for cardiac catheterizations, PVR was calculated as the ratio of the transpulmonary pressure gradient (∆P) to the amount of the pulmonary flow (QP) accordingly for 20 patients with CHD and high PAH. Subsequently and noninvasively, PVR was assessed for these patients by a Doppler echocardiography-derived index defined as the ratio of the tricuspid regurgitation velocity (TRV(m/s)) to the velocity time integral (VTI(cm)) of the right-ventricular outflow tract (RVOT). There was a good correlation between PVR measured at catheterization (PVR(cath)) and TRV/VTI(m) ratio; the mean of three measurements of VTI (VTI(m)) with R (2) = 0.53 (p = 0.008). In addition, a TRV/VTI(m) value of 0.2 provided a sensitivity of 71.4% and a specificity of 100% for PVR >6 Woods units (WU) as well as sensitivity of 90% and specificity of 90% for a PVR equal to 8 WU. PVR value between 6 and 8 WU by catheterization has been considered as a cut-off point for intervention in children with left-to-right shunts and PAH. In conclusion, Doppler-derived TRV/VTI(m) ratio is a reliable index that may be helpful as a supplementary diagnostic tool for the selection of modality of treatment and follow-up of patients with PAH and increased PVR.