scholarly journals Growth differentiation factor-15 levels in the blood around the pulmonary artery is associated with hospitalization for heart failure in patients with pulmonary arterial hypertension

2020 ◽  
Vol 10 (4) ◽  
pp. 204589402096294
Author(s):  
Wei-Ting Chang ◽  
Jhih-Yuan Shih ◽  
Yu-Wen Lin ◽  
Zhih-Cherng Chen ◽  
Jun-Neng Roan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Right Atrial ◽  
Heart Catheterization ◽  
Growth Differentiation Factor 15 ◽  
Arterial Blood ◽  
Differentiation Factor ◽  
Group I ◽  
Pulmonary Arterial

Despite no significant differences of growth differentiation factor-15 expressions in peripheral, right atrial, and right ventricular blood, in the pulmonary arterial blood, there was a significantly high level of growth differentiation factor-15 in Group I pulmonary arterial hypertension patients subsequently developing heart failure. During right heart catheterization, collecting pulmonary blood samples is suggested to measure growth differentiation factor-15.

Abstract 12455: Evaluation of N-Terminal Pro-B-type Natriuretic Peptide as a Therapeutic Response Biomarker in Group I Pulmonary Arterial Hypertension

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Aaron M Wolfson ◽  
Micheal L Maitland ◽  
Vasiliki Thomeas ◽  
Cherylanne Glassner ◽  
Mardi Gomberg-Maitland
Keyword(s):  
Heart Failure ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Roc Curve ◽  
Curve Analysis ◽  
Roc Curve Analysis ◽  
Goal Directed Therapy ◽  
Group I ◽  
Target Values ◽  
Pulmonary Arterial

Purpose: Goal directed management of left heart failure with an NT-proBNP target-based approach has some evidence of providing a survival benefit. To evaluate the potential utility of serial NT-proBNP measurements for goal-directed therapy in right heart failure we retrospectively assessed NT-proBNP as a predictor for survival in Group I pulmonary arterial hypertension (PAH) patients. Methods: We identified 103 Group I PAH patients from a pulmonary hypertension registry who had baseline elevated NT-proBNP prior to either the initiation or escalation of therapy and at least two serial NT-proBNP measurements. In a two-step process, we (1) estimated baseline NT-proBNP and slope (rate of change of NT-proBNP) with a linear mixed-effects model using all patient data and then (2) compared the power of serial versus single measurements in predicting survival with measured and model-derived values of baseline NT-proBNP with a Receiver Operative Characteristic (ROC) curve analysis . Survival was determined using the Kaplan-Meier methodology. Results: ROC curve analysis revealed significantly higher AUC for model-derived NT-proBNP values compared to the measured values (AUC: for baseline 0.74 vs 0.66, p= 0.009; for slope 0.78 vs 0.66, p= 0.02). Optimal cutpoints for prediction of survival on baseline NT-proBNP were 2012 (measured) vs. 1810 (model-derived) pg/mL. The optimal cutpoint for model-derived change in NT-proBNP was -0.004 log10pg/mL/month. Sensitivity, specificity, and negative predictive values for the three predictor variables were: 64%, 67%, 80% (measured baseline NT-proBNP), 61%, 80%, 81% (model-derived baseline NT-proBNP) and 73%, 57%, 85% (model-derived slope). Conclusions: In PAH patients, serial NT-proBNP measurements better predict survival than single measurements. This retrospective finding reveals that changes in NT-proBNP are associated with overall survival in PAH patients, and set initial target values for a pilot prospective study of NT-proBNP goal-directed therapy.

scholarly journals In Situ Expression of Bcl-2 in Pulmonary Artery Endothelial Cells Associates with Pulmonary Arterial Hypertension Relative to Heart Failure with Preserved Ejection Fraction

2016 ◽  
Vol 6 (4) ◽  
pp. 551-556 ◽  
Author(s):  
Raymond L. Benza ◽  
Gretchen Williams ◽  
Changgong Wu ◽  
Kelly J. Shields ◽  
Amresh Raina ◽  
...  
Keyword(s):  
Heart Failure ◽  
Endothelial Cells ◽  
Pulmonary Arterial Hypertension ◽  
Ejection Fraction ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
World Health ◽  
Heart Catheterization ◽  
Preserved Ejection Fraction ◽  
Pulmonary Arterial

We have previously reported that pulmonary artery endothelial cells (PAECs) can be harvested from the tips of discarded Swan-Ganz catheters after right heart catheterization (RHC). In this study, we tested the hypothesis that the existence of an antiapoptotic phenotype in PAECs obtained during RHC is a distinctive feature of pulmonary arterial hypertension (PAH; World Health Organization group 1) and might be used to differentiate PAH from other etiologies of pulmonary hypertension. Specifically, we developed a flow cytometry-based measure of Bcl-2 activity, referred to as the normalized endothelial Bcl-2 index (NEBI). We report that higher NEBI values are associated with PAH to the exclusion of heart failure with preserved ejection fraction (HFpEF) and that this simple diagnostic measurement is capable of differentiating PAH from HFpEF without presenting addition risk to the patient. If validated in a larger, multicenter study, the NEBI has the potential to assist physicians in the selection of appropriate therapeutic interventions in the common and dangerous scenario wherein patients present a clinical and hemodynamic phenotype that makes it difficult to confidently differentiate between PAH and HFpEF.

scholarly journals Right Ventricular and Right Atrial Function Are Less Compromised in Pulmonary Hypertension Secondary to Heart Failure With Preserved Ejection Fraction: A Comparison With Pulmonary Arterial Hypertension With Similar Pressure Overload

2021 ◽  
Author(s):  
Jessie van Wezenbeek ◽  
Azar Kianzad ◽  
Arno van de Bovenkamp ◽  
Jeroen Wessels ◽  
Sophia A. Mouratoglou ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Ejection Fraction ◽  
Arterial Hypertension ◽  
Vena Cava ◽  
Pressure Overload ◽  
Right Atrial ◽  
Preserved Ejection Fraction ◽  
Pulmonary Arterial

Background: Heart failure with preserved ejection fraction (HFpEF) is a prevalent disorder for which no effective treatment yet exists. Pulmonary hypertension (PH) and right atrial (RA) and ventricular (RV) dysfunction are frequently observed. The question remains whether the PH with the associated RV/RA dysfunction in HFpEF are markers of disease severity. Methods: To obtain insight in the relative importance of pressure-overload and left-to-right interaction, we compared RA and RV function in 3 groups: 1. HFpEF (n=13); 2. HFpEF-PH (n=33), and; 3. pulmonary arterial hypertension (PAH) matched to pulmonary artery pressures of HFpEF-PH (PH limited to mPAP ≥30 and ≤50 mmHg) (n=47). Patients underwent right heart catheterization and cardiac magnetic resonance imaging. Results: The right ventricle in HFpEF-PH was less dilated and hypertrophied than in PAH. In addition, RV ejection fraction was more preserved (HFpEF-PH: 52±11 versus PAH: 36±12%). RV filling patterns differed: vena cava backflow during RA contraction was observed in PAH only. In HFpEF-PH, RA pressure was elevated throughout the cardiac cycle (HFpEF-PH: 10 [8–14] versus PAH: 7 [5–10] mm Hg), while RA volume was smaller, reflecting excessive RA stiffness (HFpEF-PH: 0.14 [0.10–0.17] versus PAH: 0.08 [0.06–0.11] mm Hg/mL). RA stiffness was associated with an increased eccentricity index (HFpEF-PH: 1.3±0.2 versus PAH: 1.2±0.1) and interatrial pressure gradient (9 [5 to 12] versus 2 [−2 to 5] mm Hg). Conclusions: RV/RA function was less compromised in HFpEF-PH than in PAH, despite similar pressure-overload. Increased RA pressure and stiffness in HFpEF-PH were explained by left atrial/RA-interaction. Therefore, our results indicate that increased RA pressure is not a sign of overt RV failure but rather a reflection of HFpEF-severity.

L-arginine plasma levels and severity of idiopathic pulmonary arterial hypertension

VASA ◽  
2008 ◽  
Vol 37 (1) ◽  
pp. 61-67 ◽  
Author(s):  
Beyer ◽  
Kolditz ◽  
Ewert ◽  
Rubens ◽  
Opitz ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Plasma Levels ◽  
High Performance ◽  
Functional Class ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Right Atrial ◽  
Heart Catheterization ◽  
Pulmonary Arterial ◽  
Minute Walk

Background: Idiopathic pulmonary arterial hypertension (iPAH) is a rare disease of unknown aetiology characterized by a poor prognosis. Impairment of nitric oxide (NO) synthesis or NO-induced vasorelaxation has been suspected to play a role in the development of iPAH. This study was performed to investigate possible correlations between the plasma levels of the NO-related aminoacids L-arginine, L-citrulline and N-hydroxy-L-arginine (L-NHA) and the severity of iPAH. Methods: In twelve iPAH patients hemodynamics were measured by right heart catheterization, and plasma levels of L-arginine, L-citrulline and L-NHA were determined in blood samples from the pulmonary artery, peripheral artery and peripheral vein by high-performance liquid chromatography analysis. In eight of twelve patients a six minute walk test was performed. Results: Plasma levels of L-arginine strongly correlated to right atrial pressure, cardiac output, cardiac index, mixed-venous oxygen saturation, six minute walk data and NYHA functional class at all sites of blood sampling (p < 0.05). Conclusions: The results suggest a possible role of the NO precursor L-arginine in the pathogenesis of iPAH.

4972Upfront triple combination therapy with ambrisentan, tadalafil and subcutaneous treprostinil in incident patients with severe pulmonary arterial hypertension

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M D'Alto ◽  
E Romeo ◽  
P Argiento ◽  
R Badagliacca ◽  
S Papa ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Combination Therapy ◽  
Arterial Hypertension ◽  
Arterial Compliance ◽  
Right Atrial ◽  
Heart Catheterization ◽  
Triple Combination ◽  
Triple Combination Therapy ◽  
Pulmonary Arterial

Abstract Aim Current treatments strategies for high-risk patients with pulmonary arterial hypertension (PAH) are based on the use of parenteral prostanoids. The evidence to support triple upfront combination therapy remains largely based on expert consensus or small studies. Aim of this study was to evaluate the efficacy and safety of an upfront triple combination therapy with ambrisentan, tadalafil and subcutaneous (sc) treprostinil in patients with severe PAH. Methods This is a multi-center retrospective analysis of patients with newly diagnosed severe PAH treated with upfront triple combination therapy with ambrisentan, tadalafil and sc treprostinil between 2014 and 2018. Clinical evaluations, WHO functional class (FC), 6-min walk distance, biomarkers and right heart catheterization were collected from the patients' medical records at baseline and during the follow-up. Results Overall, 20 patients (mean age 44±15 years, 15 female) were included. Over a median follow-up of 12 months, all patients were still alive on triple combination therapy. At baseline 11 patients were in WHO-FC 3 and 9 patients in WHO-FC 4. At follow-up, WHO-FC (2.0±0.5 vs 3.5±0.5, p<0.001, improved in all: 2, 16, and 2 patients in FC 1, 2 and 3, respectively), exercise capacity (431±67 vs 152±130 m, p<0.001), NT-proBNP (423±260 vs 3492±1864 pg/ml; p<0.001), and haemodynamics (right atrial pressure 5±2 vs 13±3 mmHg, p<0.001; mean pulmonary artery pressure 42±5 vs 60±9 mmHg, p<0.001; cardiac index 3.5±0.8 vs 1.8±0.3 l/min/m2, p<0.001; pulmonary vascular resistance 5.5±1.3 vs 16.4±4.4 Wood units, p<0.001; pulmonary arterial compliance 2.5±0.9 vs 0.8±0.3 ml/mmHg, p<0.001) significantly improved compared with baseline. No patient discontinued the therapy due to serious adverse events. Conclusions Triple upfront combination therapy with ambrisentan, tadalafil and sc treprostinil is safe and offers clinical and heamodynamics benefits in incident patients with severe PAH.

scholarly journals Growth/differentiation factor 15 causes TGFβ-activated kinase 1-dependent muscle atrophy in pulmonary arterial hypertension

Thorax ◽  
2018 ◽  
Vol 74 (2) ◽  
pp. 164-176 ◽  
Author(s):  
Benjamin E Garfield ◽  
Alexi Crosby ◽  
Dongmin Shao ◽  
Peiran Yang ◽  
Cai Read ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Muscle Atrophy ◽  
Fibre Diameter ◽  
Muscle Loss ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
Pulmonary Arterial

IntroductionSkeletal muscle dysfunction is a clinically important complication of pulmonary arterial hypertension (PAH). Growth/differentiation factor 15 (GDF-15), a prognostic marker in PAH, has been associated with muscle loss in other conditions. We aimed to define the associations of GDF-15 and muscle wasting in PAH, to assess its utility as a biomarker of muscle loss and to investigate its downstream signalling pathway as a therapeutic target.MethodsGDF-15 levels and measures of muscle size and strength were analysed in the monocrotaline (MCT) rat, Sugen/hypoxia mouse and in 30 patients with PAH. In C2C12 myotubes the downstream targets of GDF-15 were identified. The pathway elucidated was then antagonised in vivo.ResultsCirculating GDF-15 levels correlated with tibialis anterior (TA) muscle fibre diameter in the MCT rat (Pearson r=−0.61, p=0.003). In patients with PAH, plasma GDF-15 levels of <564 pg/L predicted those with preserved muscle strength with a sensitivity and specificity of ≥80%. In vitro GDF-15 stimulated an increase in phosphorylation of TGFβ-activated kinase 1 (TAK1). Antagonising TAK1, with 5(Z)-7-oxozeaenol, in vitro and in vivo led to an increase in fibre diameter and a reduction in mRNA expression of atrogin-1 in both C2C12 cells and in the TA of animals who continued to grow. Circulating GDF-15 levels were also reduced in those animals which responded to treatment.ConclusionsCirculating GDF-15 is a biomarker of muscle loss in PAH that is responsive to treatment. TAK1 inhibition shows promise as a method by which muscle atrophy may be directly prevented in PAH.Trial registration numberNCT01847716; Results.

scholarly journals Increased Expression of Growth Differentiation Factor-15 in Systemic Sclerosis-Associated Pulmonary Arterial Hypertension

CHEST Journal ◽  
2011 ◽  
Vol 139 (5) ◽  
pp. 994-1002 ◽  
Author(s):  
Christina A. Meadows ◽  
Michael G. Risbano ◽  
Li Zhang ◽  
Mark W. Geraci ◽  
Rubin M. Tuder ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
Pulmonary Arterial

CARDIORESPIRATORY SYNDROME OF OBESITY (PICKWICKIAN SYNDROME) IN CHILDREN

PEDIATRICS ◽  
1961 ◽  
Vol 27 (2) ◽  
pp. 237-245
Author(s):  
Glen G. Cayler ◽  
James Mays ◽  
Harris D. Riley
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Weight Reduction ◽  
Practical Importance ◽  
Right Atrial ◽  
Oxygen Administration ◽  
Pulmonary Arterial ◽  
Pickwickian Syndrome

The clinical, pulmonary and hemodynamic findings in two boys with the Pickwickian syndrome are presented. In contrast to adults with this syndrome, all four children thus far reported have been mentally retarded. Both of our cases were cyanotic, lethargic and in congestive heart failure at the time of admission. They both exhibited polycythemia, cardiac enlargement, electrocardiographic evidence of right atrial and right ventricular hypertrophy, decreased pulmonary function without evidence of obstructive pulmonary disease and pulmonary arterial hypertension. Symptoms of cardiorespiratory disease subsided following weight reduction. The pathophysiologic mechanisms of alveolar hypoventilation, pulmonary arterial hypertension, and congestive heart failure in patients with this disease complex are discussed. The clinical recognition of this syndrome is of practical importance because: 1) it is a preventable disease, 2) the changes are reversible following weight reduction and 3) because of the dangers of oxygen administration.

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