Types Of Pulmonary Arterial Hypertension Research Articles

Hereditary pulmonary arterial hypertension burden in pediatrics: A single referral center experience.

Hereditary pulmonary arterial hypertension (HPAH) is a rare yet serious type of pulmonary arterial hypertension (PAH). The burden in the pediatric population remains high yet underreported. The objective of this study is to describe the distribution of mutations found on targeted PAH panel testing at a large pediatric referral center. Children with PAH panel administered by the John Welsh Cardiovascular Diagnostic Laboratory at Texas Children's Hospital and Baylor College of Medicine in Houston, Texas between October 2012 to August 2021 were included into this study. Medical records were retrospectively reviewed for clinical correlation. Sixty-six children with PAH underwent PAH genetic testing. Among those, 9 (14%) children were found to have pathogenic mutations, 16 (24%) children with variant of unknown significance and 41 (62%) children with polymorphism (classified as likely benign and benign). BMPR2 mutation was the most common pathogenic mutation, seen in 6 of the 9 children with detected mutations. Hemodynamic studies showed higher pulmonary vascular resistance among those with pathogenic mutations than those without (17.4 vs. 4.6 Wood units). All children with pathogenic mutations had severe PAH requiring triple therapy. There were tendencies for higher lung transplantation rate but lower mortality among those with pathogenic mutations. Abnormalities on genetic testing are not uncommon among children with PAH, although majority are of unclear significance. However, children with pathogenic mutations tended to present with more severe PAH requiring aggressive medical and surgical therapies. Genetic testing should be routinely considered due to consequences for treatment and prognostic implications. Larger scale population studies and registries are warranted to characterize the burden of HPAH in the pediatric population specifically.

Portopulmonary hypertension practice patterns after liver transplantation.

Portopulmonary hypertension (POPH) is a type of pulmonary arterial hypertension occurring exclusively in those with portal hypertensive liver disease. Liver transplantation (LT) can significantly improve outcomes. Current guidelines counsel against immediate adjustments to targeted therapy after LT and suggest routine echocardiography as sufficiently informative to guide therapeutic adjustments. Current practice patterns for adjusting targeted therapy after LT in POPH, and how they compare with guidelines, are not well established. To answer this question, we performed an institutional review board-approved, cross-sectional mixed-methods survey-based study of US POPH providers. Anonymized requests to complete the survey were sent through professional networks between January 20, 2022, and April 20, 2022. Responses were compared between cardiologists and pulmonologists using Fisher's exact tests, at a significance of 0.05. A total of 85 POPH physicians were included in the final analysis (66% pulmonologists and 34% cardiologists). Following LT, the majority of respondents routinely used a combination of standard cardiopulmonary assessment modalities to guide adjustment of targeted therapy following LT. Most respondents (69%) started by adjusting parenteral prostacyclins with small titrations and frequent reassessments within 3 months of LT, but some (19.7%) adjusted targeted therapy immediately after LT. Our results showed that the majority of respondents favored serial integrated cardiopulmonary testing (including routine right heart catheterization) to guide the adjustment of targeted therapy in POPH after LT, and almost one-fifth of respondents weaned therapy immediately after LT. Our study demonstrates heterogeneity in POPH practice patterns after LT, highlights differences between current practice patterns and the most recent guidelines, emphasizes the need for additional research, and supports a team-based approach to standardize care for these high-risk patients and optimize post-LT outcomes.

Multivisceral Transplant in a Patient With Portopulmonary Hypertension: A Case Report

Portopulmonary hypertension, a type of pulmonary arterial hypertension in the setting of cirrhotic or noncirrhotic portal hypertension, is associated with elevated morbidity and mortality during and after transplantation. Uncontrolled portopulmonary hypertension may prevent or delay listing for transplant candidates, and the prognosis without treatment and ultimately transplant is extremely poor. We present a 29-year-old White woman, who had a post-liver transplant at infancy due to biliary atresia. Later on, she developed extensive portal vein thrombosis and portopulmonary hypertension and underwent a multivisceral transplant (liver, stomach, pancreaticoduodenal complex, and small and large intestine). Preoperative mean pulmonary artery pressure was <30 mm Hg with a pulmonary vascular resistance of <300 dynes.s/cm5 on oral sildenafil and intravenous epoprostenol. Intraoperatively, management required comprehensive transfusion protocols, a careful balance between correcting blood loss and preventing thrombosis. Intravenous epoprostenol, sildenafil, milrinone, and inhaled nitric oxide were used to reduce elevated mean pulmonary artery pressure and right ventricular strain associated with vascular clamping, reperfusion, and massive fluid shifts. Nitric oxide and epoprostenol use unleashed antiplatelet effects on a patient already susceptible to coagulopathy. A multimodal and multidisciplinary approach continued throughout the surgery and in the postoperative period, which led to a successful outcome.

Características clínicas, evolución y tratamiento de hipertensión arterial pulmonar en un hospital peruano de referencia

Objective: To describe the clinical and epidemiological characteristics, evolution and treatment of patients with pulmonary arterial hypertension.Materials and methods: A descriptive study that included 47 patients with a primary diagnosis of pulmonary arterial hypertension. Results: The average age of the patients was 48 years and 91.49 % were females. The average follow-up was 39 months.The main types of pulmonary arterial hypertension were the one associated with congenital heart diseases (48.93 %), the one associated with connective tissue diseases (21.28 %) and idiopathic hypertension (17.02 %). Monotherapy (mainly with sildenafil) and sequential combination therapy (sildenafil plus bosentan) were used in 78.72 % and 21.28 % of the patients,respectively. During the follow-up, 70.21 % of the patients were hospitalized at least once and five patients died, resulting in a cumulative total mortality of 10.64 %. Conclusions: Pulmonary arterial hypertension predominantly affects young people and females. The main associated etiology is congenital heart disease. The most frequently used specific treatment is sildenafil monotherapy. The mortality rate was lower than that reported in other studies.

Treatment of Portopulmonary Hypertension (PoPH): A review

Portopulmonary Hypertension (PoPH) is a type of pulmonary arterial hypertension that uniquely afflicting patients with underlying liver disease and portal hypertension. The mainstay of treatment centers around the use of targeted pulmonary vasodilator therapy and evaluation for liver transplantation. This review article focuses on the role of targeted pulmonary vasodilator therapy and liver transplantation in the management of PoPH, with special emphasis on the expected hemodynamic and clinical effects of treatment. The relationship between PoPH and Hepatopulmonary Syndrome (HPS), another type of pulmonary vascular disease due to liver disease, is also reviewed.

The Heroic Chamber – an Outlook on the Right Ventricle in Eisenmenger Syndrome

Abstract Despite being at the extreme spectrum of congenital heart disease-associated pulmonary hypertension, patients with Eisenmenger syndrome have better outcomes compared to other types of pulmonary arterial hypertension, especially in the case of post-tricuspid shunts. This survival advantage seems to be at least partly due to significant resilience of the right ventricle and a relative resistance to failure. This paper aims to review the concept of right ventricular adaptive remodeling in Eisenmenger syndrome, its impact on prognosis and the role of multimodality imaging in the right ventricle's assessment in this setting.

Efficacy and Safety of Long-Term Oral Bosentan in Different Types of Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis was conducted to identify if long-term bosentan is an effective and safe treatment for pulmonary arterial hypertension (PAH) regardless of type, including idiopathic PAH (IPAH), and PAH associated with congenital heart disease (APAH-CHD), connective tissue disease (APAH-CTD), and human immunodeficiency virus (APAH-HIV). All relevant observations were systematically searched by two independent investigators and obtained from three databases, including PubMed, EMBASE and the Cochrane Library, from the inception of each database to February 2020. Currently, long-term administration was defined as no less than 12months. A random-effects or fixed-effects model was selected according to outcomes of the heterogeneity test for meta-analysis, where standardized mean difference (SMD) with 95% confidence intervals (CIs) was used for continuous outcomes, in addition to the estimated effect (ES; 95% CI) for the synthesized survival rate. Furthermore, subgroup analysis was applied to analyze the differences of efficacy and survivals in each type of PAH cohort. Fifteen studies including a total of 659 subjects undergoing oral bosentan administration for at least 12months were pooled in this quantitative review. Meta-analysis and subgroup analysis indicated that significant clinical benefits existed, including an improved 6-min walk distance (6MWD) and functional class (FC), in patients with APAH-CHD (6MWD: SMD 0.72, 95% CI 0.52-0.93, p < 0.0001; functional benefits: 50.4%, 95% CI 43.7-57.1%), APAH-HIV (6MWD: SMD 0.83, 95% CI 0.36-1.30, p = 0.001; functional benefits: 80.4%), and IPAH (SMD 0.54, 95% CI 0.28-0.80, p < 0.0001; functional benefits: 61.4%, 95% CI 54.2-68.5%), but a non-significant change in APAH-CTD (6MWD: SMD 0.18, 95% CI - 0.60 to 0.95, p = 0.656; functional benefits: 27.5%). Furthermore, among the hemodynamic parameters, long-term bosentan led to a significant decrease in mean pulmonary artery pressure (SMD - 0.86, p < 0.0001) in APAH-CTD, and a decrease in pulmonary vascular resistance (SMD - 0.65, p < 0.0001) and elevated oxygen saturation (SMD 0.30, p = 0.006) in APAH-CHD. Importantly, in all pooled studies, the overall survival indicated 1-, 2-, and 3-year survival rates of 94.3%, 88.8%, and 81.7%, respectively, in all-cause PAH, and subgroup analysis demonstrated a relative decreasing trend in patients with HIV, from a 2-year survival of 89.8% to a 3-year survival of 66.1%. Adverse drug reactions were relatively mild. In this systematic review and meta-analysis, long-term administration of oral bosentan has been identified as a well-tolerated and effective agent in different types of PAH. In addition, we conclude that long-term oral bosentan should be considered for patients with CTD to achieve a satisfactory exercise capacity, and for those with APAH-HIV to improve survivals, where more attention on adverse events is required.

Idiopathic Pulmonary Arterial Hypertension and Pulmonary Arterial Hypertension Associated With Congenital Heart Disease in Chinese Children: Similarities, Differences, and Prognostic Factors.

Background: As the most common types of pulmonary arterial hypertension (PAH) in childhood, the similarities and differences in clinical characteristics and prognosis between idiopathic PAH (IPAH) and PAH associated with congenital heart disease (PAH-CHD) are not well-known. This study describes and compares clinical features of pediatric IPAH and PAH-CHD in a single center of China during an 11-year period and explores the prognostic factors.Methods: Twenty-five children with IPAH and 60 children with PAH-CHD, diagnosed in West China Second Hospital of Sichuan University from January 2008 to December 2018, were chosen as study objects. The follow-up deadline was June 2019, and the end-point was all-cause death. The baseline data, results of auxiliary examinations, treatment strategies, and follow-up outcomes were recorded and compared between IPAH and PAH-CHD patients to explore the similarities, differences, and prognostic factors.Results: The median diagnostic age for PAH-CHD patients was 2.3 years, which was younger than IPAH patients (7.3 years; p = 0.009). Sixty-eight percent of the IPAH patients presented with exercise-induced symptoms at initial diagnosis, whereas 58.3% of the PAH-CHD patients were asymptomatic (p < 0.001). Sixty percent of the IPAH patients were in World Health Organization-functional class (WHO-FC) III or IV, which was significantly worse than those of the PAH-CHD patients (p = 0.002). The incidence of ST-segment and T-wave (ST-T) change in children with IPAH (76.0%) was significantly higher than that (28.3%) in children with PAH-CHD (p < 0.001). Mean corpuscular volume (MCV), mean platelet volume (MPV), and platelet distribution width were larger in IPAH patients than those in PAH-CHD patients (p < 0.01). The 1-, 3-, and 5-year survival rates of IPAH and PAH-CHD patients were 53.5, 46.5, and 31.2% and 96.5, 93.1, and 77.6%, respectively (p < 0.05). WHO-FC III-IV [relative risk (RR) = 2.750, p = 0.008] and higher MPV (RR = 1.657, p = 0.006) predicted poor prognosis for pediatric PAH.Conclusion: We showed that there are more differences than similarities between IPAH and PAH-CHD patients in clinical characteristics. PAH-CHD patients have a better prognosis than IPAH patients. WHO-FC III-IV and higher MPV at initial diagnosis are independent risk factors for poor prognosis.

Anticoagulation in pulmonary arterial hypertension: a decision analysis.

Systemic anticoagulation may be beneficial in pulmonary arterial hypertension, but there is no randomized clinical trial data to guide therapeutic decision making, and current guidelines do not account for patient preferences or quality of life. Decision analytic models to evaluate the potential risks and benefits of systemic anticoagulation in pulmonary arterial hypertension patients, focusing on the benefit in quality-adjusted life years, may be helpful in clarifying this uncertainty. We constructed a 31-state Markov decision analytic model to explore anticoagulation and no anticoagulation strategies. Modeled patient characteristics included gender, use of central catheter-based pulmonary arterial hypertension therapy, type of pulmonary arterial hypertension (idiopathic, idiopathic pulmonary arterial hypertension, or connective-tissue associated, connective tissue disease-pulmonary arterial hypertension), and use of oral contraceptive medication by females. Modeled events included mortality, thromboembolic complications, atrial fibrillation, stroke, and anticoagulation bleeding. Deterministic and probabilistic sensitivity analyses were performed. Anticoagulation was favored in all idiopathic pulmonary arterial hypertension cases, with a gain of 0.43–0.51 quality-adjusted life years, and detrimental in all connective tissue disease-pulmonary arterial hypertension cases, with a loss of 0.66–1.89 quality-adjusted life years. Anticoagulation would need to demonstrate a hazard ratio for pulmonary arterial hypertension mortality of 0.95 or better to be favored. In our model, idiopathic pulmonary arterial hypertension patients benefit from anticoagulation in terms of quality-adjusted life years, and connective tissue disease-pulmonary arterial hypertension patients were harmed, with a hazard ratio for pulmonary arterial hypertension mortality of 0.95 or better being required to favorably impact quality-adjusted life years. These results suggest that anticoagulation significantly improves quality adjusted life years and should be offered to all idiopathic pulmonary arterial hypertension patients. Shared decision models based on these results may help clarify therapeutic decision-making uncertainty in pulmonary arterial hypertension patients.

Machine learning-based microarray analyses indicate low-expression genes might collectively influence PAH disease.

Accurately predicting and testing the types of Pulmonary arterial hypertension (PAH) of each patient using cost-effective microarray-based expression data and machine learning algorithms could greatly help either identifying the most targeting medicine or adopting other therapeutic measures that could correct/restore defective genetic signaling at the early stage. Furthermore, the prediction model construction processes can also help identifying highly informative genes controlling PAH, leading to enhanced understanding of the disease etiology and molecular pathways. In this study, we used several different gene filtering methods based on microarray expression data obtained from a high-quality patient PAH dataset. Following that, we proposed a novel feature selection and refinement algorithm in conjunction with well-known machine learning methods to identify a small set of highly informative genes. Results indicated that clusters of small-expression genes could be extremely informative at predicting and differentiating different forms of PAH. Additionally, our proposed novel feature refinement algorithm could lead to significant enhancement in model performance. To summarize, integrated with state-of-the-art machine learning and novel feature refining algorithms, the most accurate models could provide near-perfect classification accuracies using very few (close to ten) low-expression genes.

An Unfortunate Case of Dyspnea in Cryptogenic Cirrhosis

Portopulmonary hypertension is a type of pulmonary arterial hypertension associated with portal hypertension. It is a known complication of cirrhosis and can predict increased mortality after liver transplantation. A 35 year—old—female with suspected cirrhosis and acute dyspnea on exertion was transferred to our hospital for further management. Two weeks prior to transfer she had hematemesis; an upper endoscopy revealed medium—sized bleeding esophageal varices requiring banding. Cross—sectional imaging was concerning for a cirrhotic appearing liver. She had no past medical history and had an unknown family history as she was adopted. On admission she felt short of breath. Her physical exam was notable for scleral icterus, jugular venous distension to 10cm, right ventricular heave, and an abdominal fluid wave. Laboratory values included platelet 88x1000/uL (reference range 140—440), INR 1.4 (range 0.89—1.12), albumin 3.1g/dL (range 3.5—5.0), and total bilirubin 5.5mg/dL (range 0.1—1.2). She had an extensive laboratory workup for cirrhosis, of which the only remarkable finding was a positive anti—mitochondrial antibody at 73.8 units (range <20.0). She had an magnetic resonance imaging (MRI) liver which showed a cirrhotic—appearing liver with evidence of portal hypertension (Figure 1). A transjugular liver biopsy showed stage 4 fibrosis and areas of sinusoidal dilatation without signs of primary biliary cirrhosis. She had a hepatovenous pressure gradient (HVPG) of 11mmHg (reference range 0—5). Workup of her dyspnea included an echocardiogram which showed a dilated right ventricle (Figure 2) with an elevated right ventricular systolic pressure of 65mmHg (reference range 15—25). Subsequent right heart catheterization showed an elevated mean pulmonary artery pressure (mPAP) of 43mmHg (range 5—10) with a relatively normal pulmonary capillary wedge pressure of 12mmHg (range<10), indicative of pulmonary arterial hypertension. In the setting of cirrhosis a diagnosis of portopulmonary hypertension was made. Per consultation with pulmonology she was started on a prostacyclin analog and endothelin—receptor antagonist. Her case was discussed at the liver transplantation recipient review committee, but placed on hold pending improvements in her right—sided cardiac pressures. A diagnosis of pulmonary hypertension can be made via right heart catheterization indicating a mPAP >25mmHg. Per the 2013 AASLD liver transplant guidelines, a mPAP < 35mmHg is required for transplant.3052_A.tif Figure 1: MRI abdomen, T1—weighted; white arrow points to steatotic and echogenic liver consistent with cirrhosis; black arrow points to a recanalized paraumbilical vein, indicating portal hypertension3052_B.tif Figure 2: Transthoracic echocardiogram, short axis, showing dilated right atrium (RA) and right ventricle (RV)3052_C.tif Figure 3: Liver core biopsy, trichrome stain, blue area indicates fibrosis

P4538Simplified table for risk stratification in patients with different types of pulmonary arterial hypertension

P4538Simplified table for risk stratification in patients with different types of pulmonary arterial hypertension

The Effect of Epicardial Fat on the Right and Left Ventricular Function in Subjects with Various Etiological Types of Pulmonary Arterial Hypertension

Abstract Background: Little is known on the effect of epicardial fat in pulmonary arterial hypertension (PAH). Therefore, the present study sought to perform a comparative analysis on the influence of epicar-dial fat thickness (EFT) on the right and left ventricular function, between three different etiological varieties of pulmonary arterial hypertension: caused by congenital heart defects (atrial septum defects with left to right shunt), by systemic sclerosis, and by myocardial ischemia. Materials and Methods: This is a prospective observational study on 50 patients with documented PAH (systolic pulmonary artery pressure – PASP of &gt;35 mmHg). The thickness of the epicardial adipose tissue was evaluated by 2D cardiac ultrasound, on the free wall of the right ventricle, during end-diastole, in the long parasternal axis view. The patients were divided into three study groups: Group 1 – PAH determined by congenital heart defects with left to right shunts (atrial septum defects, n = 25); Group 2 – PAH induced by systemic sclerosis (n = 12); Group 3 – PAH induced by myocardial ischemia (n = 13). Results: The average age was 54.48 ± 10.78 years, 30% (n = 15) of subjects were males, with a mean body mass index of 24.65 ± 4.40 kg/m2, EFT was 9.15 ± 2.24 mm, and the PASP was 41.33 ± 5.11 mmHg. Patients in Group 3 were more likely to smoke (p = 0.025) and presented a significantly lower LVEF, compared to the other groups (Group 1: 60% ± 6 vs. Group 2: 60% ± 7 vs. Group 3: 48% ± 7, p &lt;0.0001). The largest EFT was found in Group 3 (11.08 ± 2.39 mm), followed by Group 2 (9.14 ± 2.03 mm), and Group 1 (8.16 ± 1.57 mm) (p = 0.0003). The linear regression analysis found no significant correlations between EFT and other echocardiographic parameters: PASP (r = −0.228, p = 0.118), LVEF (r = −0.265, p = 0.06), TAPSW (r = 0.015, p = 0.912), TEI (r = 0.085, p = 0.552), RVEDD (r = −0.195, p = 0.173), RA area (r = −178, p = 0.214), and LA diameter (r = 0.065, p = 0.650). Conclusions: Epicardial fat thickness was found to be significantly higher in patients with PAH induced by myocardial ischemia, followed by those with systemic sclerosis and congenital heart defects, respectively. EFT did not influence the echocardiographic parameters for left and right ventricular function in patients with pulmonary arterial hypertension of different etiologies.

The Changing Landscape of Pulmonary Arterial Hypertension in the Adult with Congenital Heart Disease.

Pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) is a common type of pulmonary arterial hypertension (PAH) and a frequent complication of congenital heart disease (CHD). PAH-CHD represents a heterogeneous patient population and it is important to distinguish between the underlying cardiac defects considering the prognostic and therapeutic implications. Improved interventional techniques have enabled repair or palliation of most cardiac defects, though a substantial number of patients remain at high risk for PAH after closure. Traditionally, the treatment and management of PAH-CHD patients has been limited to palliative and supportive care, and based on expert opinion rather than clinical trials. Recently, however, the availability of advanced PAH-specific treatment has opened up a new field for the clinical management of this condition. Nevertheless, there is limited evidence on the optimal therapeutic approach for PAH-CHD. Herein, we discuss the current and novel therapeutic options for PAH-CHD as well as highlight several challenges in the clinical management at present.

NADPH oxidase: its potential role in promotion of pulmonary arterial hypertension.

NADPH oxidases (NOXs) are a group of enzymes for superoxide anion (O2·- ) generation through transferring electrons from NADPH to molecular oxygen, which is rapidly converted into hydrogen peroxide (H2O2). There are seven members in NOX family, including NOX1 to NOX5, dual oxidase1, and dual oxidase 2. Recent studies have demonstrated that NOX subtypes may have different functions in different types of pulmonary arterial hypertension (PAH). The NOX-derived reactive oxygen species (ROS) are key factors that are involved in promoting the processes of pulmonary vascular remodeling, such as endothelial dysfunction, proliferation of pulmonary arterial smooth muscle cells (PASMCs), and cellular trans-differentiation, which are the basic pathologic characteristics of PAH. Inhibition of NOX shows beneficial effect on prevention of PAH development. Thus, NOX might be a potential target for PAH therapy. The main purpose of this review is to summarize recent findings on the role of NOX, particularly the NOX subtypes, in promotion of PAH development and to list recent progress regarding the NOX-based intervention for PAH.

Proinflammatory high-density lipoprotein results from oxidized lipid mediators in the pathogenesis of both idiopathic and associated types of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterized by abnormal elaboration of vasoactive peptides, endothelial cell dysfunction, vascular remodeling, and inflammation, which collectively contribute to its pathogenesis. We investigated the potential for high-density lipoprotein (HDL) dysfunction (i.e., proinflammatory effects) and abnormal plasma eicosanoid levels to contribute to the pathobiology of PAH and assessed ex vivo the effect of treatment with apolipoprotein A-I mimetic peptide 4F on the observed HDL dysfunction. We determined the "inflammatory indices" HII and LII for HDL and low-density lipoprotein (LDL), respectively, in subjects with idiopathic PAH (IPAH) and associated PAH (APAH) by an in vitro monocyte chemotaxis assay. The 4F was added ex vivo, and repeat LII and HII values were obtained versus a sham treatment. We further determined eicosanoid levels in plasma and HDL fractions from patients with IPAH and APAH relative to controls. The LIIs were significantly higher for IPAH and APAH patients than for controls. Incubation of plasma with 4F before isolation of LDL and HDL significantly reduced the LII values, compared with sham-treated LDL, for IPAH and APAH. The increased LII values reflected increased states of LDL oxidation and thereby increased proinflammatory effects in both cohorts. The HIIs for both PAH cohorts reflected a "dysfunctional HDL phenotype," that is, proinflammatory HDL effects. In contrast to "normal HDL function," the determined HIIs were significantly increased for the IPAH and APAH cohorts. Ex vivo 4F treatment significantly improved the HDL function versus the sham treatment. Although there was a significant "salutary effect" of 4F treatment, this did not entirely normalize the HII. Significantly increased levels for both IPAH and APAH versus controls were evident for the eicosanoids 9-HODE, 13-HODE, 5-HETE, 12-HETE, and 15-HETE, while no statistical differences were evident for comparisons of IPAH and APAH for the determined plasma eicosanoid levels in the HDL fractions. Our study has further implicated the putative role of "oxidant stress" and inflammation in the pathobiology of PAH. Our data suggest the influences on the "dysfunctional HDL phenotype" of increased oxidized fatty acids, which are paradoxically proinflammatory. We speculate that therapies that target either the "inflammatory milieu" or the "dysfunctional HDL phenotype," such as apoA-I mimetic peptides, may be valuable avenues of further research in pulmonary vascular diseases.

Intravenous clonidine administration and its ability to reduce pulmonary arterial pressure in patients undergoing heart surgery

ObjectiveEvaluate the ability of clonidine to reduce pulmonary arterial pressure in patients with pulmonary hypertension undergoing heart surgery, either by reducing the pressure values from the direct measurement of pulmonary arterial pressure or by reducing or eliminating the need for intraoperative dobutamine and nitroprusside. MethodRandomized, double-blind, placebo-controlled, comparative study conducted in 30 patients with pulmonary arterial hypertension type 2 undergoing cardiac surgery. Mean pulmonary arterial pressure and dosage of dobutamine and sodium nitroprusside were assessed four times: before intravenous administration of clonidine (2μg/kg) or placebo (T0), 30min after tested treatment and before cardiopulmonary bypass (T1), immediately after CPB (T2), 10min after protamine injection (T3). ResultsThere were no significant differences regarding mean pulmonary arterial pressure at any time of evaluation. There was no significant difference between groups regarding other variables, such as mean systemic arterial pressure, heart rate, total dose of dobutamine, total dose of sodium nitroprusside, and need for fentanyl. ConclusionData analysis from patients included in this study allows us to conclude that intravenous clonidine (2μg/kg) was not able to reduce the mean pulmonary arterial pressure in patients with pulmonary hypertension in group 2 (pulmonary venous hypertension), undergoing heart surgery, or reduce or eliminate the need for intraoperative administration of dobutamine and sodium nitroprusside.

Pulmonary hypertension related to congenital heart disease: a call for action

Pulmonary arterial hypertension related to congenital heart disease (PAH-CHD) is a common type of pulmonary arterial hypertension (PAH). Despite this, little emphasis has been given to this group of patients until recently, when compared with idiopathic PAH. This is largely because of the complexity and the wide range of underlying cardiac anatomy and physiology, with a multitude of adaptive mechanisms not fully understood. Pulmonary arterial hypertension related to congenital heart disease is, therefore, best diagnosed and managed in centres specializing in both CHD and PAH, to avoid common pitfalls and old practices and to provide state-of-the-art care. We discuss the optimal management of PAH-CHD patients in a series of actions to be taken in order to optimize short- and long-term outcome, based on current knowledge of the condition and the advent of targeted advanced therapies.

Pro-Inflammatory HDL Result from Altered HDL Oxidized Lipid Mediators in Both Idiopathic and Associated Types of Pulmonary Arterial Hypertension

Purpose We have previously demonstrated pro-inflammatory HDL in vitro which improved with addition of apolipoprotein-A1 mimetic peptide in patients with both idiopathic (IPAH) and associated type (APAH) pulmonary arterial hypertension, [ J Heart Lung Transplant 2011; 30(4): S106-107 ]. We now evaluate alterations in HDL eicosanoid mediators that may contribute to pro-inflammatory HDL. Methods and Materials Plasma from either healthy controls (N=21) or patients with either IPAH (N=17) or APAH (N=11) was fractionated using fast performance liquid chromatography. HDL fractions from each group were analyzed for eicosanoid levels by ELISA. Results [table 1] Conclusions 1. IPAH & APAH are associated with significant increases in “oxidant stress”. 2. Significant alterations in plasma HDL-associated eicosanoid levels, likely contributed to pro-inflammatory HDL in both IPAH & APAH, in particular, increased 13- & 9-HODE. 3. Alterations in eicosanoid production may also contribute to a decreased endothelial prostacyclin synthase activity in PAH. 5-HETE 12-HETE 15-HETE 9-HODE 13-HODE CONTROL 1.65±0.29 0.30±0.04 0.24±0.05 1.05±0.14 1.13±0.23 IPAH† 65.81±8.31 13.06±1.62 10.72±1.92 24.19±7.69 29.38±3.12 APAH† 67.12±8.36 13.72±1.94 12.16±2.22 24.89±7.08 31.10±2.69 (Mean±SD); †p

Echocardiographic Predictors of Outcome in Eisenmenger Syndrome

Eisenmenger syndrome differs significantly from other types of pulmonary arterial hypertension in its physiology and prognosis. We sought to assess the relationship between the echocardiographic characteristics of patients with Eisenmenger syndrome and mortality. Clinical and echocardiographic variables were assessed in 181 consecutive patients with Eisenmenger syndrome, excluding those with complex congenital heart disease. Patients' mean age was 39.1 ± 12.8 years, 59 (32.6%) were male, 122 (67.4%) were in functional class III or higher, and 74 (40.9%) were on advanced therapies. Mean oxygen saturation at rest was 85.1 ± 7.8%, and median B-type natriuretic peptide was 55.4 ng/L. Over a median follow-up of 16.4 months, 19 patients died; the strongest predictors of mortality were tricuspid annular plane systolic excursion and peak systolic velocity, myocardial performance (expressed as total isovolumic time and ratio of systolic to diastolic duration), and elevated central venous pressure (expressed as right atrial [RA] area, RA pressure, and ratio of RA to left atrial area), even after we accounted for advanced therapies. A composite score based on the strongest echocardiographic predictors of outcome, including 1 point for each of the following: tricuspid annular plane systolic excursion <15 mm, ratio of right ventricular effective systolic to diastolic duration ≥ 1.5, RA area ≥ 25 cm², ratio of RA to left atrial area ≥ 1.5, was highly predictive of clinical outcome (area under the curve 0.90 ± 0.01), with no improvement when B-type natriuretic peptide and resting saturations were added into the model. Echocardiographic parameters of right ventricular function and RA area predict mortality in Eisenmenger patients. A new composite echocardiographic score, described herewith, may be incorporated into the noninvasive, periodic assessment of these patients.