Effects Of Pulmonary Arterial Hypertension Research Articles

Survival and response to pulmonary vasodilator therapies in patients with chronic obstructive pulmonary disease and pulmonary vascular phenotype

BackgroundThe aim of the study was to describe and investigate the effect of pulmonary arterial hypertension (PAH) therapies in a cohort of patients with severe precapillary pulmonary hypertension (PH) associated with chronic obstructive pulmonary disease (COPD; PH-COPD), and to assess factors predictive of treatment response and mortality. Material and methodsWe retrospectively included patients with severe incident PH-COPD who received PAH therapy and underwent RHC at diagnosis and on treatment. ResultsFrom 2015 to 2022, 35 severe PH-COPD patients, with clinical features of pulmonary vascular phenotype, were included. Seventeen (48.5%) patients were treated with combined PAH therapy. PAH therapy led to a significant improvement in hemodynamics (PVR -3.5 Wood Units (−39.3%); p < 0.0001), and in the simplified four-strata risk-assessment score, which improved by at least one category in 21 (60%) patients. This effect was more pronounced in patients on dual therapy. Kaplan-Meier estimated survival rates at 1, 3 and 5 years were 94%, 65% and 42% respectively. Univariate analysis showed a significant reduction in survival in patients with a higher simplified risk score at follow-up (Hazard ratio (HR) 2.88 [1.16–7.15]; p = 0.02). Hypoxemia <50 mmHg was correlated to mortality in multivariate analysis (HR 4.33 [1.08–17.42]; p = 0.04). ConclusionsOur study confirms the poor prognosis of patients with COPD and a pulmonary vascular phenotype and the potential interest of combined PAH therapy in this population, with good tolerability and greater clinical and hemodynamic improvement than monotherapy. Using the simplified risk score during follow-up could be of interest in this population.

The effect of peroxisome proliferator-activated receptor gamma (PPARγ) as a mediator of dietary fatty acids and thiazolidinedione in pulmonary arterial hypertension induced by cold stress of broilers

The objective of this experiment was to evaluate the effects of dietary fish oil and pioglitazone as peroxisome proliferators-activated receptor gamma (PPARγ) activating ligands on the reduction of cold-induced ascites in broiler chickens. A total of 480 one-day-old (Ross 308) male chicks were randomly allocated to four treatment groups with eight replicates of 15 birds each. The following treatments were used: 1) ambient temperature (negative control), with basal diet; 2) cold-induced ascites (positive control), with basal diet; 3) cold-induced ascites, with basal diet +10 mg/kg/day pioglitazone and 4) cold-induced ascites, with basal diet +1% of fish oil. When compared with the positive control, body weight gain was higher (P ≤ 0.05) for broilers fed diets containing fish oil and pioglitazone at 28, 42, and 0–42 d. Broilers under cold-induced ascites had the highest blood pressure at 21 and 42 d, while fish oil and pioglitazone treatment reduced the blood pressure (P ≤ 0.05). Red blood cells, white blood cells, hematocrit, erythrocyte osmotic fragility, bursa of Fabricius and spleen weights were improved (P ≤ 0.05) for chickens fed fish oil diets and pioglitazone compared to the cold-induced ascites (positive control). Exposure to cold temperature resulted in an increase in plasma T3 and T3/T4 ratio and decline in plasma T4 (P ≤ 0.05). In conclusion, PPARγ agonist pioglitazone and fish oil as source of omega-3 polyunsaturated fatty acid could be used as a strategy to reduce the negative effects of pulmonary arterial hypertension and ascites in broiler chickens.

Impression life with pulmonary hypertension: clinically relevant characteristics and quality of life among patients in Gansu, China.

The adverse effects of pulmonary arterial hypertension (PAH) on physical, emotional, and health-related quality of life (HRQoL) remain primarily unrecognized, especially in resource-limited settings. This study aims to characterize the HRQoL of patients with PAH in this area and also identify the potential role of clinically relevant characteristics, including the 6-min walk distance test (6MWD), WHO-Functional Classification (WHO-FC), and mental health in the occurrence of lowering quality of life. This was a cross-sectional observational study. Inpatients with PAH were chosen from a tertiary hospital located in Gansu province, China. All participants were interviewed face-by-face by using questionnaires, including items from the 36-Item Short Form Health Survey (SF-36), the self-rating anxiety scale, and the self-rating depression scale. Data on demographic and clinically relevant characteristics, including WHO-FC and 6MWD, were also collected by tracing medical recorders. Multiple linear regression analysis was used to determine the association between demographic, clinically relevant characteristics data, and physical component summary (PCS) or mental component summary (MCS) in SF-36. Of the 152 participants, SF-36 differed significantly from Chinese norms in all eight domains, with role-physical (21.55 ± 9.87) less than one-third of the norm (88.79 ± 28.49). Multiple linear regression results showed that the factors with the greatest impact on PCS were anxiety scores (β = -0.22, p = 0.001), followed by WHO-FC (β = -0.16, p = 0.014) and 6MWD (β = 0.15, p = 0.036). The factors with the greatest impact on MCS were WHO-FC (β = -0.30, p < 0.001), followed by anxiety (β = -0.23, p = 0.001) and depression scores (β = -0.16, p = 0.013). HRQoL was substantially reduced among PAH patients in the resource-limited area, mainly the physiological functions. WHO-FC and anxiety scores were independently associated with both PCS and MCS in SF-36. Clinicians should make reasonable rehabilitation programs and plans for patients according to their cardiac function grade and the severity of clinical symptoms. In addition, psychological interventions should also be taken, especially for those with anxiety symptoms, so as to improve their HRQoL.

Preparation of betaine injection and its therapeutic effect in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterised by elevated pulmonary pressure, right ventricular failure (RVF) and ultimately death. Aggressive treatment of RVF is considered an important therapeutic strategy to treat PAH. Previous studies have indicated that betaine may be may a promising therapeutic approach for PAH-induced RVF. Therefore, in this study, betaine solution for injection was prepared and characterised using various techniques. The therapeutic efficacy of three different methods of administration (intragastric, nebulised inhalation and intravenous injection) were comprehensively evaluated in terms of pharmacokinetics, tissue distribution and pharmacodynamics. The pharmacokinetic results demonstrated that betaine injection administered via nebulised inhalation significantly prolonged betaine's half-life and increased its internal circulation time compared to the intragastric and intravenous routes. Biodistribution experiments verified that the betaine formulation accumulated in the lung tissue when administered via inhalation. The results of the pharmacodynamic analysis further confirmed that right ventricular systolic pressure, mean pulmonary artery pressure and right ventricular hypertrophy index increased in the model group and that inhaled betaine suppressed these pathological changes to a level comparable to those observed in the control group. Taken together, these results indicate that betaine administered by inhalation is a promising strategy for the treatment of PAH-induced RVF.

Native T1 Mapping-Based Radiomics for Noninvasive Prediction of the Therapeutic Effect of Pulmonary Arterial Hypertension.

(1) Background: Novel markers for predicting the short-term therapeutic effect of pulmonary arterial hypertension (PAH) to assist in the prompt initiation of tailored treatment strategies are greatly needed and highly desirable. The aim of the study was to investigate the role of cardiac magnetic resonance (CMR) native T1 mapping radiomics in predicting the short-term therapeutic effect in PAH patients; (2) Methods: Fifty-five PAH patients who received targeted therapy were retrospectively included. Patients were subdivided into an effective group and an ineffective group by assessing the therapeutic effect after ≥3 months of treatment. All patients underwent CMR examinations prior to the beginning of the therapy. Radiomics features from native T1 mapping images were extracted. A radiomics model was constructed using the support vector machine (SVM) algorithm for predicting the therapeutic effect; (3) Results: The SVM radiomics model revealed favorable performance for predicting the therapeutic effect with areas under the receiver operating characteristic curve of 0.955 in the training cohort and 0.893 in the test cohort, respectively. With the optimal cutoff value, the radiomics model showed accuracies of 0.909 and 0.818 in the training and test cohorts, respectively; (4) Conclusions: The CMR native T1 mapping-based radiomics model holds promise for predicting the therapeutic effect in PAH patients.

Portopulmonary hypertension in the current era of pulmonary hypertension management

Long-term outcomes in portopulmonary hypertension (PoPH) are poorly studied in the current era of pulmonary hypertension management. We analysed the effect of pulmonary arterial hypertension (PAH)-targeted therapies, survival and predictors of death in a large contemporary cohort of patients with PoPH. Data from patients with PoPH consecutively enrolled in the French Pulmonary Hypertension Registry between 2007 and 2017 were collected. The effect of initial treatment strategies on functional class, exercise capacity and cardiopulmonary haemodynamics were analysed. Survival and its association with PAH- and hepatic-related characteristics were also examined. Six hundred and thirty-seven patients (mean age 55 ± 10 years; 58% male) were included. Fifty-seven percent had mild cirrhosis, i.e. Child-Pugh stage A. The median model for end-stage liver disease (MELD) score was 11 (IQR 9-15). Most patients (n= 474; 74%) were initiated on monotherapy, either with a phosphodiesterase-5 inhibitor (n= 336) or with an endothelin-receptor antagonist (n= 128); 95 (15%) were initiated on double oral combination therapy and 5 (1%) on triple therapy. After a median treatment time of 4.5 months, there were significant improvements in functional class (p <0.001), 6-minute walk distance (6MWD) (p <0.0001) and pulmonary vascular resistance (p <0.0001). Overall survival rates were 84%, 69% and 51% at 1, 3 and 5 years, respectively. Baseline 6MWD, sex, age and MELD score or Child-Pugh stage were identified as independent prognostic factors. Survival from PoPH diagnosis was significantly better in the subgroup of patients who underwent liver transplantation (92%, 83% and 81% at 1, 3 and 5 years, respectively). Survival of patients with PoPH is strongly associated with the severity of liver disease. Patients who underwent liver transplantation had the best long-term outcomes. Portopulmonary hypertension is defined by the presence of pulmonary arterial hypertension in the context of chronic liver disease and is characterized by progressive shortness of breath and exercise limitation. The presence of severe pulmonary arterial hypertension in liver transplant candidates represents a contraindication for such a surgery; however, treatments targeting pulmonary arterial hypertension are efficacious, allowing for safe transplantation and conferring good survival outcomes in those who undergo liver transplantation.

Role of kallistatin in pediatric patients with pulmonary arterial hypertension.

Kallistatin, a serine proteinase inhibitor, exerts its effect by vascular repair, angiogenesis inhibition, strong vasodilation, inhibition of vascular endothelial growth factor (VEGF), antiinflammation, and anti-apoptosis. We hypothesized as to whether it has a protective role in pulmonary arterial hypertension (PAH). The study included 5 subgroups (78 patients; 44 male): Eisenmenger syndrome (n=16), PAH with left to right shunt (n=20), idiopathic PAH (n=7), patients with left to right shunt without PAH (n=19), and patients with innocent heart murmur (n=16). Physical examination, chest radiography, electrocardiography, and transthoracic echocardiography (TTE) were performed for each patient. PAH diagnosis was confirmed by catheterization. Serum kallistatin, tumor necrosis factor alpha (TNF-α), Interleukin-10 (IL-10) and N-terminal pro b-type natriuretic peptide (NT-proBNP) levels were studied for each patient. The lowest median kallistatin value was found in Eisenmenger syndrome: 1.19 (0.87-3.30) μg/ml. The highest value belonged to control group with innocent murmur: 2.89 (1.19-5.66) μg/ml. Serum levels of kallistatin were significantly lower in patients with PAH (p < 0.05). TNF-α values were increased and IL-10 values were decreased in pulmonary hypertension. However; no correlation was found between kallistatin levels and cytokines. Kallistatin may have a protective effect in pulmonary arterial hypertension by repairing vascular damage, inhibition of angiogenesis, strong vasodilator effect, inhibiting VEGF, and anti-inflammatory mechanism of action. To our knowledge, our study is the first one that shows the role of kallistatin in pulmonary hypertension. Kallistatin may represent a promising novel therapeutic approach for pulmonary hypertension in the near future.

The Effects of Pulmonary Arterial Hypertension on the Heart Work Dynamics: Gender Differences

Pulmonary arterial hypertension (PAH) is defined as hemodynamic disease with mean arterial pressure, according to the last guidelines

Inhibition of CHK 1 (Checkpoint Kinase 1) Elicits Therapeutic Effects in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a debilitating disease associated with progressive vascular remodeling of distal pulmonary arteries leading to elevation of pulmonary artery pressure, right ventricular hypertrophy, and death. Although presenting high levels of DNA damage that normally jeopardize their viability, pulmonary artery smooth muscle cells (PASMCs) from patients with PAH exhibit a cancer-like proproliferative and apoptosis-resistant phenotype accounting for vascular lumen obliteration. In cancer cells, overexpression of the serine/threonine-protein kinase CHK1 (checkpoint kinase 1) is exploited to counteract the excess of DNA damage insults they are exposed to. This study aimed to determine whether PAH-PASMCs have developed an orchestrated response mediated by CHK1 to overcome DNA damage, allowing cell survival and proliferation. Approach and Results: We demonstrated that CHK1 expression is markedly increased in isolated PASMCs and distal PAs from patients with PAH compared with controls, as well as in multiple complementary animal models recapitulating the disease, including monocrotaline rats and the simian immunodeficiency virus-infected macaques. Using a pharmacological and molecular loss of function approach, we showed that CHK1 promotes PAH-PASMCs proliferation and resistance to apoptosis. In addition, we found that inhibition of CHK1 induces downregulation of the DNA repair protein RAD 51 and severe DNA damage. In vivo, we provided evidence that pharmacological inhibition of CHK1 significantly reduces vascular remodeling and improves hemodynamic parameters in 2 experimental rat models of PAH. Our results show that CHK1 exerts a proproliferative function in PAH-PASMCs by mitigating DNA damage and suggest that CHK1 inhibition may, therefore, represent an attractive therapeutic option for patients with PAH.

Decreased Heart Rate Variability in Sickle Cell Anemia as Effect of Pulmonary Arterial Hypertension

Decreased heart rate variability (HRV) is associated with increased mortality risk in various diseases. The objective of this investigation:to study HRV in patients with sickle cell anemia (SCA) and to assess the effect of pulmonary arterial hypertension (PAH) on HRVin these patients. Materials and methods. HRV registration and Doppler echocardiographic assessment of systolic pulmonary arterialpressure (PAP) was carried out in 61 stable patients with SCA and 24 healthy subjects. Results. Low frequency power (LFP) and highfrequency power (HFP) were decreased in SCA patients compared to healthy subjects. Among SCA patients, PAH patients had lower LFP and HFP than patients without PAH. In SCA patients, systolic PAP showed significant negative correlation with LFP and HFP.Conclusion. HRV is significantly decreased in SCA patients, especially in those with PAH. HRV may be particularly useful in early detection of PAH patients who may have worse prognosis and higher mortality risk.

Bone Morphogenetic Protein 9 Is a Mechanistic Biomarker of Portopulmonary Hypertension.

BMP9 (bone morphogenetic protein 9) is a circulating endothelial quiescence factor with protective effects in pulmonary arterial hypertension (PAH). Loss-of-function mutations in BMP9, its receptors, and downstream effectors have been reported in heritable PAH. To determine how an acquired deficiency of BMP9 signaling might contribute to PAH. Plasma levels of BMP9 and antagonist soluble endoglin were measured in group 1 PAH, group 2 and 3 pulmonary hypertension (PH), and in patients with severe liver disease without PAH. BMP9 levels were markedly lower in portopulmonary hypertension (PoPH) versus healthy control subjects, or other etiologies of PAH or PH; distinguished PoPH from patients with liver disease without PAH; and were an independent predictor of transplant-free survival. BMP9 levels were decreased in mice with PH associated with CCl4-induced portal hypertension and liver cirrhosis, but were normal in other rodent models of PH. Administration of ALK1-Fc, a BMP9 ligand trap consisting of the activin receptor-like kinase-1 extracellular domain, exacerbated PH and pulmonary vascular remodeling in mice treated with hypoxia versus hypoxia alone. BMP9 is a sensitive and specific biomarker of PoPH, predicting transplant-free survival and the presence of PAH in liver disease. In rodent models, acquired deficiency of BMP9 signaling can predispose to or exacerbate PH, providing a possible mechanistic link between PoPH and heritable PAH. These findings describe a novel experimental model of severe PH that provides insight into the synergy between pulmonary vascular injury and diminished BMP9 signaling in the pathogenesis of PAH.

Impact of preoperative pulmonary arterial hypertension on early and late outcomes in patients undergoing valve surgery for rheumatic heart disease.

Background and Aims:There is conflicting evidence on adverse effect of Pulmonary Arterial Hypertension (PAH) on outcomes after cardiac surgery for rheumatic heart disease (RHD). The authors studied Indian patients with RHD and preoperative PAH, who undergo cardiac surgery with a hypothesis that they have poor short and long-term outcomes.Methods:This was a retrospective observational study of 407 patients. The patients were divided in three groups based on PAH estimated on echocardiograph as; no or mild PAH (pulmonary artery systolic pressure (PASP) <30 mm of Hg); moderate PAH (PASP 31-55 mm of Hg) and severe PAH (PASP >55 mm of Hg). The primary endpoint was in-hospital mortality and major morbidities; while secondary endpoint was long-term survival.Results:In-hospital mortality was 24 (5.9%); and was not different in patients with severe, (9.1%), moderate (4.5%) or mild PAH (2.8%) (P = 0.09). Patients with severe PAH had higher incidence of prolonged ventilation (P = 0.007). Factors independently associated with mortality were; >2-packed cell transfusion, prolonged ventilation and acute kidney injury but not moderate and severe PAH. Patients with mitral stenosis (MS) and severe PAH had significantly higher mortality as compared to no or mild PAH (P = 0.03) on long-term follow-up [81.37% (mean duration 19.40 ± 14.10 months)], mortality was 8% and not statistically different (P = 0.25) across PAH categories.Conclusion:Moderate and severe PAH does not affect short and long term outcomes of patients undergoing valve surgery for RHD. Patients with MS with severe PAH had higher mortality compared to those with no PAH.

Cardioprotective effects of early and late aerobic exercise training in experimental pulmonary arterial hypertension

Clinical studies suggest that aerobic exercise can exert beneficial effects in pulmonary arterial hypertension (PAH), but the underlying mechanisms are largely unknown. We compared the impact of early or late aerobic exercise training on right ventricular function, remodeling and survival in experimental PAH. Male Wistar rats were submitted to normal cage activity (SED), exercise training in early (EarlyEX) and in late stage (LateEX) of PAH induced by monocrotaline (MCT, 60mg/kg). Both exercise interventions resulted in improved cardiac function despite persistent right pressure-overload, increased exercise tolerance and survival, with greater benefits in EarlyEX+MCT. This was accompanied by improvements in the markers of cardiac remodeling (SERCA2a), neurohumoral activation (lower endothelin-1, brain natriuretic peptide and preserved vascular endothelial growth factor mRNA), metabolism and mitochondrial oxidative stress in both exercise interventions. EarlyEX+MCT provided additional improvements in fibrosis, tumor necrosis factor-alpha/interleukin-10 and brain natriuretic peptide mRNA, and beta/alpha myosin heavy chain protein expression. The present study demonstrates important cardioprotective effects of aerobic exercise in experimental PAH, with greater benefits obtained when exercise training is initiated at an early stage of the disease.

Effect of pulmonary hypertension on outcome of pulmonary tuberculosis

ObjectivesPulmonary hypertension is a serious disorder with catastrophic outcomes. This study aimed to evaluate the effect of pulmonary arterial hypertension on the outcome among new cases of pulmonary tuberculosis. Novel modalities are available as therapeutic options, so early diagnosis of pulmonary arterial hypertension may be important. MethodsIn a cross-sectional study, 777 new cases of pulmonary tuberculosis were recruited in the National Research Institute of Tuberculosis and Lung Disease, Tehran, Iran. Pulmonary arterial pressure was measured by resting transthoracic echocardiography on the beginning of tuberculosis treatment. Echocardiography was performed by a cardiologist expert in the field. Patients with systolic pulmonary arterial pressure more than 35mmHg were defined as pulmonary hypertensive. The relationship between pulmonary arterial hypertension and mortality was assessed during six months of tuberculosis treatment. ResultsSeventy-four (9.5%) of 777 new cases of pulmonary tuberculosis had pulmonary arterial hypertension. Among them, 10 (13.5%) died during the treatment period. In comparison with 5% mortality among cases without pulmonary arterial hypertension, death was significantly associated with pulmonary hypertension (P=0.007). Logistic regression analysis showed that pulmonary arterial pressure more than 35mmHg is an independent predictor of death among tuberculosis patients. ConclusionAmong new cases of pulmonary tuberculosis, a significant association between mortality and pulmonary arterial pressure >35mmHg was found. Therapeutic intervention may change the outcome of these patients.

Determination of the effects of pulmonary arterial hypertension and therapy on the cardiovascular system of rats by impedance cardiography.

AimTo evaluate the effects of bosentan, sildenafil, and combined therapy on the cardiovascular system using impedance cardiography (ICG) in rats with monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH).MethodsSeventy male Wistar-albino rats were randomized into five groups. A single dose of MCT was given to all rats, except to the control group. After 4 weeks, bosentan, sildenafil, and combined treatment was started and lasted for 3 weeks. The last group that developed PAH did not receive any medication. Echocardiographic evaluation was performed to determine the PAH development. Thoracic fluid content index (TFCI), stroke volume index (SI), heart rate (HR), cardiac index (CI), and myocardial contractility index (IC) were determined. All procedures were performed at the baseline and after 4 and 7 weeks.ResultsEchocardiographic parameters showed that the all MCT-injected rats developed PAH. There were no significant inter- and intra-group differences in TFCI, SI, and IC (P > 0.05), but at the 7th week, CI value in the sildenafil-treated PAH rats was significantly higher than in other groups and HR of PAH rats with combined therapy was significantly lower than in other groups.ConclusionPAH did not have an effect on LV function of rats, or if it did, the effect was compensated by physiological processes. Also, sildenafil treatment deteriorated the LV cardiac index.

Novel mechanisms of sildenafil in pulmonary hypertension involving cytokines/chemokines, MAP kinases and Akt.

Pulmonary arterial hypertension (PH) is associated with high mortality due to right ventricular failure and hypoxia, therefore to understand the mechanism by which pulmonary vascular remodeling initiates these processes is very important. We used a well-characterized monocrotaline (MCT)-induced rat PH model, and analyzed lung morphology, expression of cytokines, mitogen-activated protein kinase (MAPK) phosphorylation, and phosphatidylinositol 3-kinase-Akt (PI-3k-Akt) pathway and nuclear factor (NF)-κB activation in order to elucidate the mechanisms by which sildenafil's protective effect in PH is exerted. Besides its protective effect on lung morphology, sildenafil suppressed multiple cytokines involved in neutrophil and mononuclear cells recruitment including cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2α/β, tissue inhibitor of metalloproteinase (TIMP)-1, interleukin (IL)-1α, lipopolysaccharide induced CXC chemokine (LIX), monokine induced by gamma interferon (MIG), macrophage inflammatory protein (MIP)-1α, and MIP-3α. NF-κB activation and phosphorylation were also attenuated by sildenafil. Furthermore, sildenafil reduced extracellular signal-regulated kinase (ERK)1/2 and p38 MAPK activation while enhanced activation of the cytoprotective Akt pathway in PH. These data suggest a beneficial effect of sildenafil on inflammatory and kinase signaling mechanisms that substantially contribute to its protective effects, and may have potential implications in designing future therapeutic strategies in the treatment of pulmonary hypertension.

Use of pulmonary arterial hypertension-specific therapy in overweight or obese patients with obstructive sleep apnea and pulmonary hypertension.

Pulmonary hypertension (PH) in overweight or obese patients with obstructive sleep apnea (OSA) may be multifactorial. The effect of pulmonary artery hypertension (PAH)-specific drugs on PH and exercise capacity in such patients is unknown. We performed a retrospective review of overweight or obese patients with OSA and PH who were treated with PAH-specific therapy in our PH clinic. We identified 9 female and 2 male patients. The mean age ± SD was 54.9 ± 9.3 years. The mean pulmonary artery pressure at the time of diagnosis of PH was 39.8 ± 16.1 mmHg. The right atrial pressure was 11.1 ± 4.5 mmHg, the pulmonary artery wedge pressure was 14.1 ± 2.9 mmHg, the cardiac index was 2.6 ± 0.5 L/min/m(2), and the pulmonary vascular resistance index was 10.6 ± 7.1 Wood units/m(2). The indications for use of PAH-specific therapy were dyspnea in association with right heart failure (n = 4), persistent PH despite compliance with nocturnal positive airway pressure (PAP) therapy (n = 4), or inability to tolerate PAP therapy (n = 3). PH was treated with an endothelin receptor antagonist (n = 8) or a phosphodiesterase-5 inhibitor (n = 3). The 6-minute walk distance (6MWD) improved significantly, from 234 ± 49.7 to 258 ± 54.6 m (24 m [95% confidence interval (CI): 6.5-341.5 m]; P = 0.014) over a period of 4.4 ± 1.8 months (n = 8) and from 241.7 ± 48.5 to 289.9 ± 91 m (48 m [95% CI: 5.5-90.8 m]; P = 0.033) in those with a longer follow-up period of 12.1 ± 6.4 months (n = 7). The systolic pulmonary artery pressure dropped significantly, from 64 ± 25.2 to 42 ± 10.4 mmHg (22 mmHg [95% CI: 4-40 mmHg]; P = 0.024) over a period of 6.1 ± 4.1 months (n = 7). In conclusion, PAH-specific therapy resulted in significant improvement in both PH and 6MWD.

Effect of PAH specific therapy on pulmonary hemodynamics and six-minute walk distance in portopulmonary hypertension: a systematic review and meta-analysis.

Background. Little is known about the effect of pulmonary arterial hypertension (PAH) specific therapy on pulmonary hemodynamics and exercise capacity in patients with portopulmonary hypertension (PoPH) because such patients are usually excluded from randomized clinical trials (RCT) of such therapy. Methods. We searched PUBMED using the terms “(Therapy/Broad (filter)) AND (portopulmonary hypertension).” We included studies that met the following criteria: ≥5 patients, AND PoPH confirmed by right heart catheterization (RHC), AND follow-up RHC data, AND/OR baseline and follow-up 6MWD available. Results. 12 studies met our inclusion criteria. None was a RCT. The baseline mPAP was 48.6 ± 4.4 mmHg, cardiac output (CO) 5.6 ± 0.9 L/min, and pulmonary vascular resistance (PVR) 668.6 ± 219.1 dynes.sec/cm5. The baseline 6MWD was 348.2 ± 35.6 meters. The use of PAH specific therapy improved mPAP by 7.54 mmHg (95% CI 10.2 to 4.9), CO by 1.77 L/min (95% CI 1.1 to 2.4), and PVR by 253 dynes.sec/cm5 (95% CI 291.4 to 214.6) (n = 135) and 6MWD by 61.8 meters (95% CI 47.5 to 76) (n = 122). Conclusions. The use of PAH specific therapy in PoPH results in significant improvement in both pulmonary hemodynamics and 6MWD.

Cardiovascular Modeling in Pulmonary Arterial Hypertension: Focus on Mechanisms and Treatment of Right Heart Failure Using the CircAdapt Model

In recent years, increased understanding of cardiovascular system dynamics has led to the development of mathematical models of the heart and circulation. Models that enable realistic simulation of ventricular mechanics and interactions under a range of conditions have the potential to provide an ideal method with which to investigate the effects of pulmonary arterial hypertension and its treatment on cardiac mechanics and hemodynamics. Such mathematical models have the potential to contribute to a personalized, patient-specific treatment approach and allow more objective diagnostic decision-making, patient monitoring, and assessment of treatment outcome. This review discusses the development of mathematical models of the heart and circulation, with particular reference to the closed-loop CircAdapt model, and how the model performs under both normal and pathophysiological (pulmonary hypertensive) conditions.

E0553 Effect of pulmonary hypertension on the prognosis of patients with cardiac resynchronisation therapy

IntroductionThere was a little of information about the effect of pulmonary artery hypertension to the clinical prognosis in patients with cardiac resynchronisation therapy (CRT). We aimed to investigate the effect...